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Time-resolved Förster-resonance-energy-transfer DNA assay on an active CMOS microarray
Schwartz, David Eric; Gong, Ping; Shepard, Kenneth L.
We present an active oligonucleotide microarray platform for time-resolved Förster resonance energy transfer (TR-FRET) assays. In these assays, immobilized probe is labeled with a donor fluorophore and analyte target is labeled with a fluorescence quencher. Changes in the fluorescence decay lifetime of the donor are measured to determine the extent of hybridization. In this work, we demonstrate that TR-FRET assays have reduced sensitivity to variances in probe surface density compared with standard fluorescence-based microarray assays. Use of an active array substrate, fabricated in a standard complementary metal-oxide-semiconductor (CMOS) process, provides the additional benefits of reduced system complexity and cost. The array consists of 4096 independent single-photon avalanche diode (SPAD) pixel sites and features on-chip time-to-digital conversion. We demonstrate the functionality of our system by measuring a DNA target concentration series using TR-FRET with semiconductor quantum dot donors. PMID:18515059
A 256 pixel magnetoresistive biosensor microarray in 0.18μm CMOS
Hall, Drew A.; Gaster, Richard S.; Makinwa, Kofi; Wang, Shan X.; Murmann, Boris
Magnetic nanotechnologies have shown significant potential in several areas of nanomedicine such as imaging, therapeutics, and early disease detection. Giant magnetoresistive spin-valve (GMR SV) sensors coupled with magnetic nanotags (MNTs) possess great promise as ultra-sensitive biosensors for diagnostics. We report an integrated sensor interface for an array of 256 GMR SV biosensors designed in 0.18 μm CMOS. Arranged like an imager, each of the 16 column level readout channels contains an analog front- end and a compact ΣΔ modulator (0.054 mm2) with 84 dB of dynamic range and an input referred noise of 49 nT/√Hz. Performance is demonstrated through detection of an ovarian cancer biomarker, secretory leukocyte peptidase inhibitor (SLPI), spiked at concentrations as low as 10 fM. This system is designed as a replacement for optical protein microarrays while also providing real-time kinetics monitoring. PMID:24761029
Microarrays Made Simple: "DNA Chips" Paper Activity
ERIC Educational Resources Information Center
Barnard, Betsy
DNA microarray technology is revolutionizing biological science. DNA microarrays (also called DNA chips) allow simultaneous screening of many genes for changes in expression between different cells. Now researchers can obtain information about genes in days or weeks that used to take months or years. The paper activity described in this article…
CMOS Active Pixel Sensor Technology and Reliability Characterization Methodology
NASA Technical Reports Server (NTRS)
Chen, Yuan; Guertin, Steven M.; Pain, Bedabrata; Kayaii, Sammy
This paper describes the technology, design features and reliability characterization methodology of a CMOS Active Pixel Sensor. Both overall chip reliability and pixel reliability are projected for the imagers.
ERIC Educational Resources Information Center
Plomin, Robert; Schalkwyk, Leonard C.
Microarrays are revolutionizing genetics by making it possible to genotype hundreds of thousands of DNA markers and to assess the expression (RNA transcripts) of all of the genes in the genome. Microarrays are slides the size of a postage stamp that contain millions of DNA sequences to which single-stranded DNA or RNA can hybridize. This…
CMOS Active-Pixel Image Sensor With Simple Floating Gates
NASA Technical Reports Server (NTRS)
Fossum, Eric R.; Nakamura, Junichi; Kemeny, Sabrina E.
Experimental complementary metal-oxide/semiconductor (CMOS) active-pixel image sensor integrated circuit features simple floating-gate structure, with metal-oxide/semiconductor field-effect transistor (MOSFET) as active circuit element in each pixel. Provides flexibility of readout modes, no kTC noise, and relatively simple structure suitable for high-density arrays. Features desirable for "smart sensor" applications.
CMOS Monolithic Active Pixel Sensors (MAPS): Developments and future outlook
NASA Astrophysics Data System (ADS)
Turchetta, R.; Fant, A.; Gasiorek, P.; Esbrand, C.; Griffiths, J. A.; Metaxas, M. G.; Royle, G. J.; Speller, R.; Venanzi, C.; van der Stelt, P. F.; Verheij, H.; Li, G.; Theodoridis, S.; Georgiou, H.; Cavouras, D.; Hall, G.; Noy, M.; Jones, J.; Leaver, J.; Machin, D.; Greenwood, S.; Khaleeq, M.; Schulerud, H.; Østby, J. M.; Triantis, F.; Asimidis, A.; Bolanakis, D.; Manthos, N.; Longo, R.; Bergamaschi, A.
Re-invented in the early 1990s, on both sides of the Atlantic, Monolithic Active Pixel Sensors (MAPS) in a CMOS technology are today the most sold solid-state imaging devices, overtaking the traditional technology of Charge-Coupled Devices (CCD). The slow uptake of CMOS MAPS started with low-end applications, for example web-cams, and is slowly pervading the high-end applications, for example in prosumer digital cameras. Higher specifications are required for scientific applications: very low noise, high speed, high dynamic range, large format and radiation hardness are some of these requirements. This paper will present a brief overview of the CMOS Image Sensor technology and of the requirements for scientific applications. As an example, a sensor for X-ray imaging will be presented. This sensor was developed within a European FP6 Consortium, intelligent imaging sensors (I-ImaS).
Thin Film on CMOS Active Pixel Sensor for Space Applications
Schulze Spuentrup, Jan Dirk; Burghartz, Joachim N.; Graf, Heinz-Gerd; Harendt, Christine; Hutter, Franz; Nicke, Markus; Schmidt, Uwe; Schubert, Markus; Sterzel, Juergen
A 664 × 664 element Active Pixel image Sensor (APS) with integrated analog signal processing, full frame synchronous shutter and random access for applications in star sensors is presented and discussed. A thick vertical diode array in Thin Film on CMOS (TFC) technology is explored to achieve radiation hardness and maximum fill factor.
Monolithic active pixel sensors (MAPS) in a VLSI CMOS technology
NASA Astrophysics Data System (ADS)
Turchetta, R.; French, M.; Manolopoulos, S.; Tyndel, M.; Allport, P.; Bates, R.; O'Shea, V.; Hall, G.; Raymond, M.
Monolithic Active Pixel Sensors (MAPS) designed in a standard VLSI CMOS technology have recently been proposed as a compact pixel detector for the detection of high-energy charged particle in vertex/tracking applications. MAPS, also named CMOS sensors, are already extensively used in visible light applications. With respect to other competing imaging technologies, CMOS sensors have several potential advantages in terms of low cost, low power, lower noise at higher speed, random access of pixels which allows windowing of region of interest, ability to integrate several functions on the same chip. This brings altogether to the concept of 'camera-on-a-chip'. In this paper, we review the use of CMOS sensors for particle physics and we analyse their performances in term of the efficiency (fill factor), signal generation, noise, readout speed and sensor area. In most of high-energy physics applications, data reduction is needed in the sensor at an early stage of the data processing before transfer of the data to tape. Because of the large number of pixels, data reduction is needed on the sensor itself or just outside. This brings in stringent requirements on the temporal noise as well as to the sensor uniformity, expressed as a Fixed Pattern Noise (FPN). A pixel architecture with an additional transistor is proposed. This architecture, coupled to correlated double sampling of the signal will allow cancellation of the two dominant noise sources, namely the reset or kTC noise and the FPN. A prototype has been designed in a standard 0.25 μm CMOS technology. It has also a structure for electrical calibration of the sensor. The prototype is functional and detailed tests are under way.
CMOS VLSI Active-Pixel Sensor for Tracking
NASA Technical Reports Server (NTRS)
Pain, Bedabrata; Sun, Chao; Yang, Guang; Heynssens, Julie
An architecture for a proposed active-pixel sensor (APS) and a design to implement the architecture in a complementary metal oxide semiconductor (CMOS) very-large-scale integrated (VLSI) circuit provide for some advanced features that are expected to be especially desirable for tracking pointlike features of stars. The architecture would also make this APS suitable for robotic- vision and general pointing and tracking applications. CMOS imagers in general are well suited for pointing and tracking because they can be configured for random access to selected pixels and to provide readout from windows of interest within their fields of view. However, until now, the architectures of CMOS imagers have not supported multiwindow operation or low-noise data collection. Moreover, smearing and motion artifacts in collected images have made prior CMOS imagers unsuitable for tracking applications. The proposed CMOS imager (see figure) would include an array of 1,024 by 1,024 pixels containing high-performance photodiode-based APS circuitry. The pixel pitch would be 9 m. The operations of the pixel circuits would be sequenced and otherwise controlled by an on-chip timing and control block, which would enable the collection of image data, during a single frame period, from either the full frame (that is, all 1,024 1,024 pixels) or from within as many as 8 different arbitrarily placed windows as large as 8 by 8 pixels each. A typical prior CMOS APS operates in a row-at-a-time ( grolling-shutter h) readout mode, which gives rise to exposure skew. In contrast, the proposed APS would operate in a sample-first/readlater mode, suppressing rolling-shutter effects. In this mode, the analog readout signals from the pixels corresponding to the windows of the interest (which windows, in the star-tracking application, would presumably contain guide stars) would be sampled rapidly by routing them through a programmable diagonal switch array to an on-chip parallel analog memory array. The
A 128 x 128 CMOS Active Pixel Image Sensor for Highly Integrated Imaging Systems
NASA Technical Reports Server (NTRS)
Mendis, Sunetra K.; Kemeny, Sabrina E.; Fossum, Eric R.
A new CMOS-based image sensor that is intrinsically compatible with on-chip CMOS circuitry is reported. The new CMOS active pixel image sensor achieves low noise, high sensitivity, X-Y addressability, and has simple timing requirements. The image sensor was fabricated using a 2 micrometer p-well CMOS process, and consists of a 128 x 128 array of 40 micrometer x 40 micrometer pixels. The CMOS image sensor technology enables highly integrated smart image sensors, and makes the design, incorporation and fabrication of such sensors widely accessible to the integrated circuit community.
A CMOS active pixel sensor for retinal stimulation
NASA Astrophysics Data System (ADS)
Prydderch, Mark L.; French, Marcus J.; Mathieson, Keith; Adams, Christopher; Gunning, Deborah; Laudanski, Jonathan; Morrison, James D.; Moodie, Alan R.; Sinclair, James
Degenerative photoreceptor diseases, such as age-related macular degeneration and retinitis pigmentosa, are the most common causes of blindness in the western world. A potential cure is to use a microelectronic retinal prosthesis to provide electrical stimulation to the remaining healthy retinal cells. We describe a prototype CMOS Active Pixel Sensor capable of detecting a visual scene and translating it into a train of electrical pulses for stimulation of the retina. The sensor consists of a 10 x 10 array of 100 micron square pixels fabricated on a 0.35 micron CMOS process. Light incident upon each pixel is converted into output current pulse trains with a frequency related to the light intensity. These outputs are connected to a biocompatible microelectrode array for contact to the retinal cells. The flexible design allows experimentation with signal amplitudes and frequencies in order to determine the most appropriate stimulus for the retina. Neural processing in the retina can be studied by using the sensor in conjunction with a Field Programmable Gate Array (FPGA) programmed to behave as a neural network. The sensor has been integrated into a test system designed for studying retinal response. We present the most recent results obtained from this sensor.
Proof of principle study of the use of a CMOS active pixel sensor for proton radiography
Seco, Joao; Depauw, Nicolas
Purpose: Proof of principle study of the use of a CMOS active pixel sensor (APS) in producing proton radiographic images using the proton beam at the Massachusetts General Hospital (MGH). Methods: A CMOS APS, previously tested for use in s-ray radiation therapy applications, was used for proton beam radiographic imaging at the MGH. Two different setups were used as a proof of principle that CMOS can be used as proton imaging device: (i) a pen with two metal screws to assess spatial resolution of the CMOS and (ii) a phantom with lung tissue, bone tissue, and water to assess tissue contrast of the CMOS. The sensor was then traversed by a double scattered monoenergetic proton beam at 117 MeV, and the energy deposition inside the detector was recorded to assess its energy response. Conventional x-ray images with similar setup at voltages of 70 kVp and proton images using commercial Gafchromic EBT 2 and Kodak X-Omat V films were also taken for comparison purposes. Results: Images were successfully acquired and compared to x-ray kVp and proton EBT2/X-Omat film images. The spatial resolution of the CMOS detector image is subjectively comparable to the EBT2 and Kodak X-Omat V film images obtained at the same object-detector distance. X-rays have apparent higher spatial resolution than the CMOS. However, further studies with different commercial films using proton beam irradiation demonstrate that the distance of the detector to the object is important to the amount of proton scatter contributing to the proton image. Proton images obtained with films at different distances from the source indicate that proton scatter significantly affects the CMOS image quality. Conclusion: Proton radiographic images were successfully acquired at MGH using a CMOS active pixel sensor detector. The CMOS demonstrated spatial resolution subjectively comparable to films at the same object-detector distance. Further work will be done in order to establish the spatial and energy resolution of the
Development of radiation hard CMOS active pixel sensors for HL-LHC
NASA Astrophysics Data System (ADS)
Pernegger, Heinz
New pixel detectors, based on commercial high voltage and/or high resistivity full CMOS processes, hold promise as next-generation active pixel sensors for inner and intermediate layers of the upgraded ATLAS tracker. The use of commercial CMOS processes allow cost-effective detector construction and simpler hybridisation techniques. The paper gives an overview of the results obtained on AMS-produced CMOS sensors coupled to the ATLAS Pixel FE-I4 readout chips. The SOI (silicon-on-insulator) produced sensors by XFAB hold great promise as radiation hard SOI-CMOS sensors due to their combination of partially depleted SOI transistors reducing back-gate effects. The test results include pre-/post-irradiation comparison, measurements of charge collection regions as well as test beam results.
Integrated imaging sensor systems with CMOS active pixel sensor technology
NASA Technical Reports Server (NTRS)
Yang, G.; Cunningham, T.; Ortiz, M.; Heynssens, J.; Sun, C.; Hancock, B.; Seshadri, S.; Wrigley, C.; McCarty, K.; Pain, B.
This paper discusses common approaches to CMOS APS technology, as well as specific results on the five-wire programmable digital camera-on-a-chip developed at JPL. The paper also reports recent research in the design, operation, and performance of APS imagers for several imager applications.
Low Power Camera-on-a-Chip Using CMOS Active Pixel Sensor Technology
NASA Technical Reports Server (NTRS)
Fossum, E. R.
A second generation image sensor technology has been developed at the NASA Jet Propulsion Laboratory as a result of the continuing need to miniaturize space science imaging instruments. Implemented using standard CMOS, the active pixel sensor (APS) technology permits the integration of the detector array with on-chip timing, control and signal chain electronics, including analog-to-digital conversion.
Passive radiation detection using optically active CMOS sensors
NASA Astrophysics Data System (ADS)
Dosiek, Luke; Schalk, Patrick D.
Recently, there have been a number of small-scale and hobbyist successes in employing commodity CMOS-based camera sensors for radiation detection. For example, several smartphone applications initially developed for use in areas near the Fukushima nuclear disaster are capable of detecting radiation using a cell phone camera, provided opaque tape is placed over the lens. In all current useful implementations, it is required that the sensor not be exposed to visible light. We seek to build a system that does not have this restriction. While building such a system would require sophisticated signal processing, it would nevertheless provide great benefits. In addition to fulfilling their primary function of image capture, cameras would also be able to detect unknown radiation sources even when the danger is considered to be low or non-existent. By experimentally profiling the image artifacts generated by gamma ray and β particle impacts, algorithms are developed to identify the unique features of radiation exposure, while discarding optical interaction and thermal noise effects. Preliminary results focus on achieving this goal in a laboratory setting, without regard to integration time or computational complexity. However, future work will seek to address these additional issues.
Enzyme family-specific and activity-based screening of chemical libraries using enzyme microarrays.
Funeriu, Daniel P; Eppinger, Jörg; Denizot, Lucile; Miyake, Masato; Miyake, Jun
The potential of protein microarrays in high-throughput screening (HTS) still remains largely unfulfilled, essentially because of the difficulty of extracting meaningful, quantitative data from such experiments. In the particular case of enzyme microarrays, low-molecular-weight fluorescent affinity labels (FALs) can function as ideally suited activity probes of the microarrayed enzymes. FALs form covalent bonds with enzymes in an activity-dependent manner and therefore can be used to characterize enzyme activity at each enzyme's address, as predetermined by the microarraying process. Relying on this principle, we introduce herein thematic enzyme microarrays (TEMA). In a kinetic setup we used TEMAs to determine the full set of kinetic constants and the reaction mechanism between the microarrayed enzymes (the theme of the microarray) and a family-wide FAL. Based on this kinetic understanding, in an HTS setup we established the practical and theoretical methodology for quantitative, multiplexed determination of the inhibition profile of compounds from a chemical library against each microarrayed enzyme. Finally, in a validation setup, K(i)(app) values and inhibitor profiles were confirmed and refined. PMID:15821728
Analysis of noise characteristics for the active pixels in CMOS image sensors for X-ray imaging
NASA Astrophysics Data System (ADS)
Kim, Young Soo; Cho, Gyuseong; Bae, Jun-Hyung
CMOS image sensors have poorer performance compared to conventional charge coupled devices (CCDs). Since CMOS Active Pixel Sensors (APSs) in general have higher temporal noise, higher dark current, smaller full well charge capacitance, and lower spectral response, they cannot provide the same wide dynamic range and superior signal to noise ratio as CCDs. In view of electronic noise, the main source for the CMOS APS is the pixel, along with other signal processing blocks such as row and column decoder, analog signal processor (ASP), analog-to-digital converter (ADC), and timing and control logic circuitry. Therefore, it is important and necessary to characterize noise of the active pixels in CMOS APSs, and we performed experimental measurements and comparisons with theoretical estimations. To derive noise source of the pixels, we designed and fabricated four types of CMOS active pixels, and each pixel is composed of a photodiode and three MOS transistors. The size of these pixels is 100 μm×100 μm. The test chip was fabricated using ETRI 0.8 μm (2P/2M) standard CMOS process. It was found that the dominant noise in CMOS active pixels is shot noise during integration under normal operating conditions. And, it was also seen that epitaxial type pixels have similar noise level compared to non-epitaxial type, and the noise of diffusion type pixel is larger than for a well type pixel on the same substrate type.
Which Members of the Microbial Communities Are Active? Microarrays
NASA Astrophysics Data System (ADS)
Morris, Brandon E. L.
only at the early stages of understanding the microbial processes that occur in petroliferous formations and the surrounding subterranean environment. Important first steps in characterising the microbiology of oilfield systems involve identifying the microbial community structure and determining how population diversity changes are affected by the overall geochemical and biological parameters of the system. This is relatively easy to do today by using general 16S rRNA primers for PCR and building clone libraries. For example, previous studies using molecular methods characterised many dominant prokaryotes in petroleum reservoirs (Orphan et al., 2000) and in two Alaskan North Slope oil facilities (Duncan et al., 2009; Pham et al., 2009). However, the problem is that more traditional molecular biology approaches, such as 16S clone libraries, fail to detect large portions of the community perhaps missing up to half of the biodiversity (see Hong et al., 2009) and require significant laboratory time to construct large libraries necessary to increase the probability of detecting the majority of even bacterial biodiversity. In the energy sector, the overarching desire would be to quickly assess the extent of in situ hydrocarbon biodegradation or to disrupt detrimental processes such as biofouling, and in these cases it may not be necessary to identify specific microbial species. Rather, it would be more critical to evaluate metabolic processes or monitor gene products that are implicated in the specific activity of interest. Research goals such as these are well suited for a tailored application of microarray technology.
Performance of a novel wafer scale CMOS active pixel sensor for bio-medical imaging.
Esposito, M; Anaxagoras, T; Konstantinidis, A C; Zheng, Y; Speller, R D; Evans, P M; Allinson, N M; Wells, K
Recently CMOS active pixels sensors (APSs) have become a valuable alternative to amorphous silicon and selenium flat panel imagers (FPIs) in bio-medical imaging applications. CMOS APSs can now be scaled up to the standard 20 cm diameter wafer size by means of a reticle stitching block process. However, despite wafer scale CMOS APS being monolithic, sources of non-uniformity of response and regional variations can persist representing a significant challenge for wafer scale sensor response. Non-uniformity of stitched sensors can arise from a number of factors related to the manufacturing process, including variation of amplification, variation between readout components, wafer defects and process variations across the wafer due to manufacturing processes. This paper reports on an investigation into the spatial non-uniformity and regional variations of a wafer scale stitched CMOS APS. For the first time a per-pixel analysis of the electro-optical performance of a wafer CMOS APS is presented, to address inhomogeneity issues arising from the stitching techniques used to manufacture wafer scale sensors. A complete model of the signal generation in the pixel array has been provided and proved capable of accounting for noise and gain variations across the pixel array. This novel analysis leads to readout noise and conversion gain being evaluated at pixel level, stitching block level and in regions of interest, resulting in a coefficient of variation ⩽1.9%. The uniformity of the image quality performance has been further investigated in a typical x-ray application, i.e. mammography, showing a uniformity in terms of CNR among the highest when compared with mammography detectors commonly used in clinical practice. Finally, in order to compare the detection capability of this novel APS with the technology currently used (i.e. FPIs), theoretical evaluation of the detection quantum efficiency (DQE) at zero-frequency has been performed, resulting in a higher DQE for this
Performance of a novel wafer scale CMOS active pixel sensor for bio-medical imaging
NASA Astrophysics Data System (ADS)
Esposito, M.; Anaxagoras, T.; Konstantinidis, A. C.; Zheng, Y.; Speller, R. D.; Evans, P. M.; Allinson, N. M.; Wells, K.
Recently CMOS active pixels sensors (APSs) have become a valuable alternative to amorphous silicon and selenium flat panel imagers (FPIs) in bio-medical imaging applications. CMOS APSs can now be scaled up to the standard 20 cm diameter wafer size by means of a reticle stitching block process. However, despite wafer scale CMOS APS being monolithic, sources of non-uniformity of response and regional variations can persist representing a significant challenge for wafer scale sensor response. Non-uniformity of stitched sensors can arise from a number of factors related to the manufacturing process, including variation of amplification, variation between readout components, wafer defects and process variations across the wafer due to manufacturing processes. This paper reports on an investigation into the spatial non-uniformity and regional variations of a wafer scale stitched CMOS APS. For the first time a per-pixel analysis of the electro-optical performance of a wafer CMOS APS is presented, to address inhomogeneity issues arising from the stitching techniques used to manufacture wafer scale sensors. A complete model of the signal generation in the pixel array has been provided and proved capable of accounting for noise and gain variations across the pixel array. This novel analysis leads to readout noise and conversion gain being evaluated at pixel level, stitching block level and in regions of interest, resulting in a coefficient of variation ⩽1.9%. The uniformity of the image quality performance has been further investigated in a typical x-ray application, i.e. mammography, showing a uniformity in terms of CNR among the highest when compared with mammography detectors commonly used in clinical practice. Finally, in order to compare the detection capability of this novel APS with the technology currently used (i.e. FPIs), theoretical evaluation of the detection quantum efficiency (DQE) at zero-frequency has been performed, resulting in a higher DQE for this
CMOS Active Pixel Sensors as energy-range detectors for proton Computed Tomography
NASA Astrophysics Data System (ADS)
Esposito, M.; Anaxagoras, T.; Evans, P. M.; Green, S.; Manolopoulos, S.; Nieto-Camero, J.; Parker, D. J.; Poludniowski, G.; Price, T.; Waltham, C.; Allinson, N. M.
Since the first proof of concept in the early 70s, a number of technologies has been proposed to perform proton CT (pCT), as a means of mapping tissue stopping power for accurate treatment planning in proton therapy. Previous prototypes of energy-range detectors for pCT have been mainly based on the use of scintillator-based calorimeters, to measure proton residual energy after passing through the patient. However, such an approach is limited by the need for only a single proton passing through the energy-range detector in a read-out cycle. A novel approach to this problem could be the use of pixelated detectors, where the independent read-out of each pixel allows to measure simultaneously the residual energy of a number of protons in the same read-out cycle, facilitating a faster and more efficient pCT scan. This paper investigates the suitability of CMOS Active Pixel Sensors (APSs) to track individual protons as they go through a number of CMOS layers, forming an energy-range telescope. Measurements performed at the iThemba Laboratories will be presented and analysed in terms of correlation, to confirm capability of proton tracking for CMOS APSs.
CMOS Active Pixel Sensor Star Tracker with Regional Electronic Shutter
NASA Technical Reports Server (NTRS)
Yadid-Pecht, Orly; Pain, Bedabrata; Staller, Craig; Clark, Christopher; Fossum, Eric
The guidance system in a spacecraft determines spacecraft attitude by matching an observed star field to a star catalog....An APS(active pixel sensor)-based system can reduce mass and power consumption and radiation effects compared to a CCD(charge-coupled device)-based system...This paper reports an APS (active pixel sensor) with locally variable times, achieved through individual pixel reset (IPR).
Assessing design activity in complex CMOS circuit design
NASA Astrophysics Data System (ADS)
Biswas, Gautam; Goldman, Susan R.; Fisher, Doug; Bhuva, Bharat; Glewwe, Grant
This chapter characterizes human problem solving in digital circuit design. We analyze protocols of designers with varying degrees of training, identifying problem solving strategies used by these designers, discuss activity patterns that differentiate designers, and propose these as a tentative basis for assessing expertise in digital design. Throughout, we argue that a comprehensive model of human design should integrate a variety of strategies, which heretofore have been proposed as individually sufficient models of human design problem solving. We close by describing an automated tool for design and its assessment.
Peptide microarrays for the profiling of cytotoxic T-lymphocyte activity using minimum numbers of cells
Hoff, Antje; Bagû, Ana-Cristina; André, Thomas; Roth, Günter; Wiesmüller, Karl-Heinz; Gückel, Brigitte
The identification of epitopes that elicit cytotoxic T-lymphocyte activity is a prerequisite for the development of cancer-specific immunotherapies. However, especially the parallel characterization of several epitopes is limited by the availability of T cells. Microarrays have enabled an unprecedented miniaturization and parallelization in biological assays. Here, we developed peptide microarrays for the detection of CTL activity. MHC class I-binding peptide epitopes were pipetted onto polymer-coated glass slides. Target cells, loaded with the cell-impermeant dye calcein, were incubated on these arrays, followed by incubation with antigen-expanded CTLs. Cytotoxic activity was detected by release of calcein and detachment of target cells. With only 200,000 cells per microarray, CTLs could be detected at a frequency of 0.5% corresponding to 1,000 antigen-specific T cells. Target cells and CTLs only settled on peptide spots enabling a clear separation of individual epitopes. Even though no physical boundaries were present between the individual spots, peptide loading only occurred locally and cytolytic activity was confined to the spots carrying the specific epitope. The peptide microarrays provide a robust platform that implements the whole process from antigen presentation to the detection of CTL activity in a miniaturized format. The method surpasses all established methods in the minimum numbers of cells required. With antigen uptake occurring on the microarray, further applications are foreseen in the testing of antigen precursors that require uptake and processing prior to presentation. PMID:20512327
Wide tuning-range CMOS VCO based on a tunable active inductor
NASA Astrophysics Data System (ADS)
Babaei Kia, Hojjat; Khari A'ain, Abu; Grout, Ian
In this paper, a wide tuning-range CMOS voltage-controlled oscillator (VCO) with high output power using an active inductor circuit is presented. In this VCO design, the coarse frequency is achieved by tuning the integrated active inductor. The circuit has been simulated using a 0.18-µm CMOS fabrication process and presents output frequency range from 100 MHz to 2.5 GHz, resulting in a tuning range of 96%. The phase noise is -85 dBc/Hz at a 1 MHz frequency offset. The output power is from -3 dBm at 2.55 GHz to +14 dBm at 167 MHz. The active inductor power dissipation is 6.5 mW and the total power consumption is 16.27 mW when operating on a 1.8 V supply voltage. By comparing this active inductor architecture VCO with general VCO topology, the result shows that this topology, which employs the proposed active inductor, produces a better performance.
Application-specific architectures of CMOS monolithic active pixel sensors
NASA Astrophysics Data System (ADS)
Szelezniak, Michal; Besson, Auguste; Claus, Gilles; Colledani, Claude; Degerli, Yavuz; Deptuch, Grzegorz; Deveaux, Michael; Dorokhov, Andrei; Dulinski, Wojciech; Fourches, Nicolas; Goffe, Mathieu; Grandjean, Damien; Guilloux, Fabrice; Heini, Sebastien; Himmi, Abdelkader; Hu, Christine; Jaaskelainen, Kimmo; Li, Yan; Lutz, Pierre; Orsini, Fabienne; Pellicioli, Michel; Shabetai, Alexandre; Valin, Isabelle; Winter, Marc
Several development directions intended to adapt and optimize monolithic active pixel sensors for specific applications are presented in this work. The first example, compatible with the STAR microvertex upgrade, is based on a simple two-transistor pixel circuitry. It is suited for a long integration time, room-temperature operation and minimum power dissipation. In another approach for this application, a specific readout method is proposed, allowing optimization of the integration time independently of the full frame-readout time. The circuit consists of an in-pixel front-end voltage amplifier, with a gain on the order of five, followed by two analog memory cells. The extended version of this scheme, based on the implementation of more memory cells per pixel, is the solution considered for the outer layers of a microvertex detector at the international linear collider. For the two innermost layers, a circuit allowing fast frame scans together with on-line, on-chip data sparsification is proposed. The first results of this prototype demonstrate that the fixed pattern dispersion is reduced below a noise level of 15 e -, allowing the use of a single comparator or a low-resolution ADC per pixel column. A common element for most of the mentioned readout schemes is a low-noise, low power consumption, layout efficient in-pixel amplifier. A review of possible solutions for this element together with some experimental results is presented.
A CMOS Active Pixel Sensor for Charged Particle Detection
Matis, Howard S.; Bieser, Fred; Kleinfelder, Stuart; Rai, Gulshan; Retiere, Fabrice; Ritter, Hans George; Singh, Kunal; Wurzel, Samuel E.; Wieman, Howard; Yamamoto, Eugene
Active Pixel Sensor (APS) technology has shown promise for next-generation vertex detectors. This paper discusses the design and testing of two generations of APS chips. Both are arrays of 128 by 128 pixels, each 20 by 20 {micro}m. Each array is divided into sub-arrays in which different sensor structures (4 in the first version and 16 in the second) and/or readout circuits are employed. Measurements of several of these structures under Fe{sup 55} exposure are reported. The sensors have also been irradiated by 55 MeV protons to test for radiation damage. The radiation increased the noise and reduced the signal. The noise can be explained by shot noise from the increased leakage current and the reduction in signal is due to charge being trapped in the epi layer. Nevertheless, the radiation effect is small for the expected exposures at RHIC and RHIC II. Finally, we describe our concept for mechanically supporting a thin silicon wafer in an actual detector.
Prototype Active Silicon Sensor in 150 nm HR-CMOS technology for ATLAS Inner Detector Upgrade
NASA Astrophysics Data System (ADS)
Rymaszewski, P.; Barbero, M.; Breugnon, P.; Godiot, S.; Gonella, L.; Hemperek, T.; Hirono, T.; Hügging, F.; Krüger, H.; Liu, J.; Pangaud, P.; Peric, I.; Rozanov, A.; Wang, A.; Wermes, N.
The LHC Phase-II upgrade will lead to a significant increase in luminosity, which in turn will bring new challenges for the operation of inner tracking detectors. A possible solution is to use active silicon sensors, taking advantage of commercial CMOS technologies. Currently ATLAS R&D programme is qualifying a few commercial technologies in terms of suitability for this task. In this paper a prototype designed in one of them (LFoundry 150 nm process) will be discussed. The chip architecture will be described, including different pixel types incorporated into the design, followed by simulation and measurement results.
Development of CMOS Active Pixel Image Sensors for Low Cost Commercial Applications
NASA Technical Reports Server (NTRS)
Fossum, E.; Gee, R.; Kemeny, S.; Kim, Q.; Mendis, S.; Nakamura, J.; Nixon, R.; Ortiz, M.; Pain, B.; Zhou, Z.; Ackland, B.; Dickinson, A.; Eid, E.; Inglis, D.
This paper describes ongoing research and development of CMOS active pixel image sensors for low cost commercial applications. A number of sensor designs have been fabricated and tested in both p-well and n-well technologies. Major elements in the development of the sensor include on-chip analog signal processing circuits for the reduction of fixed pattern noise, on-chip timing and control circuits and on-chip analog-to-digital conversion (ADC). Recent results and continuing efforts in these areas will be presented.
Depleted Monolithic Active Pixel Sensors (DMAPS) implemented in LF-150 nm CMOS technology
NASA Astrophysics Data System (ADS)
Kishishita, T.; Hemperek, T.; Krüger, H.; Wermes, N.
We present the recent development of Depleted Monolithic Active Pixel Sensors (DMAPS), implemented with an LFoundry (LF) 150 nm CMOS process. MAPS detectors based on an epi-layer have been matured in recent years and have attractive features in terms of reducing material budget and handling cost compared to conventional hybrid pixel detectors. However, the obtained signal is relatively small (~1000 e-) due to the thin epi-layer, and charge collection time is relatively slow, e.g., in the order of 100 ns, because charges are mainly collected by diffusion. Modern commercial CMOS technology, however, offers advanced process options to overcome such difficulties and enable truly monolithic devices as an alternative to hybrid pixel sensors and charge coupled devices. Unlike in the case of the standard MAPS technologies with epi-layers, the LF process provides a high-resistivity substrate that enables large signal and fast charge collection by drift in a ~50 μm thick depleted layer. Since this process also enables the use of deep n- and p-wells to isolate the collection electrode from the thin active device layer, PMOS and NMOS transistors are available for the readout electronics in each pixel cell. In order to evaluate the sensor and transistor characteristics, several collection electrodes variants and readout architectures have been implemented. In this report, we focus on its design aspect of the LF-DMAPS prototype chip.
Photon small-field measurements with a CMOS active pixel sensor.
Spang, F Jiménez; Rosenberg, I; Hedin, E; Royle, G
In this work the dosimetric performance of CMOS active pixel sensors for the measurement of small photon beams is presented. The detector used consisted of an array of 520 × 520 pixels on a 25 µm pitch. Dosimetric parameters measured with this sensor were compared with data collected with an ionization chamber, a film detector and GEANT4 Monte Carlo simulations. The sensor performance for beam profiles measurements was evaluated for field sizes of 0.5 × 0.5 cm(2). The high spatial resolution achieved with this sensor allowed the accurate measurement of profiles, beam penumbrae and field size under lateral electronic disequilibrium. Field size and penumbrae agreed within 5.4% and 2.2% respectively with film measurements. Agreements with ionization chambers better than 1.0% were obtained when measuring tissue-phantom ratios. Output factor measurements were in good agreement with ionization chamber and Monte Carlo simulation. The data obtained from this imaging sensor can be easily analyzed to extract dosimetric information. The results presented in this work are promising for the development and implementation of CMOS active pixel sensors for dosimetry applications. PMID:25985207
Photon small-field measurements with a CMOS active pixel sensor
NASA Astrophysics Data System (ADS)
Jiménez Spang, F.; Rosenberg, I.; Hedin, E.; Royle, G.
In this work the dosimetric performance of CMOS active pixel sensors for the measurement of small photon beams is presented. The detector used consisted of an array of 520 × 520 pixels on a 25 µm pitch. Dosimetric parameters measured with this sensor were compared with data collected with an ionization chamber, a film detector and GEANT4 Monte Carlo simulations. The sensor performance for beam profiles measurements was evaluated for field sizes of 0.5 × 0.5 cm2. The high spatial resolution achieved with this sensor allowed the accurate measurement of profiles, beam penumbrae and field size under lateral electronic disequilibrium. Field size and penumbrae agreed within 5.4% and 2.2% respectively with film measurements. Agreements with ionization chambers better than 1.0% were obtained when measuring tissue-phantom ratios. Output factor measurements were in good agreement with ionization chamber and Monte Carlo simulation. The data obtained from this imaging sensor can be easily analyzed to extract dosimetric information. The results presented in this work are promising for the development and implementation of CMOS active pixel sensors for dosimetry applications.
Comparison of RNA-Seq and Microarray in Transcriptome Profiling of Activated T Cells
Zhao, Shanrong; Fung-Leung, Wai-Ping; Bittner, Anton; Ngo, Karen; Liu, Xuejun
To demonstrate the benefits of RNA-Seq over microarray in transcriptome profiling, both RNA-Seq and microarray analyses were performed on RNA samples from a human T cell activation experiment. In contrast to other reports, our analyses focused on the difference, rather than similarity, between RNA-Seq and microarray technologies in transcriptome profiling. A comparison of data sets derived from RNA-Seq and Affymetrix platforms using the same set of samples showed a high correlation between gene expression profiles generated by the two platforms. However, it also demonstrated that RNA-Seq was superior in detecting low abundance transcripts, differentiating biologically critical isoforms, and allowing the identification of genetic variants. RNA-Seq also demonstrated a broader dynamic range than microarray, which allowed for the detection of more differentially expressed genes with higher fold-change. Analysis of the two datasets also showed the benefit derived from avoidance of technical issues inherent to microarray probe performance such as cross-hybridization, non-specific hybridization and limited detection range of individual probes. Because RNA-Seq does not rely on a pre-designed complement sequence detection probe, it is devoid of issues associated with probe redundancy and annotation, which simplified interpretation of the data. Despite the superior benefits of RNA-Seq, microarrays are still the more common choice of researchers when conducting transcriptional profiling experiments. This is likely because RNA-Seq sequencing technology is new to most researchers, more expensive than microarray, data storage is more challenging and analysis is more complex. We expect that once these barriers are overcome, the RNA-Seq platform will become the predominant tool for transcriptome analysis. PMID:24454679
Use of a multiplexed CMOS microarray to optimize and compare oligonucleotide binding to DNA probes synthesized or immobilized on individual electrodes.
Maurer, Karl; Yazvenko, Nina; Wilmoth, Jodi; Cooper, John; Lyon, Wanda; Danley, David
The CombiMatrix microarray with 12,544 electrodes supports in situ electrochemical synthesis of user-defined DNA probes. As an alternative, we immobilized commercially synthesized DNA probes on individual electrodes coated with electropolymerized polypyrrole (Ppy). Hybridization was measured using a biotinylated target oligonucleotide and either Cy5-streptavidin and fluorescence detection or horseradish peroxidase-streptavidin and enzyme-enhanced electrochemical detection. Detection efficiencies were optimized by varying the deposition of the Ppy, the terminal groups on the DNA probes, and other factors that impacted fluorescence quenching and electrical conductivity. Optimized results were compared against those obtained using a microarray with the same DNA sequences synthesized in situ. Immobilized probes produced higher fluorescence signals, possibly by providing a greater stand off between the Cy5 on the target oligonucleotide and the quenching effects of the Ppy and the platinum electrode. PMID:22163607
Use of a Multiplexed CMOS Microarray to Optimize and Compare Oligonucleotide Binding to DNA Probes Synthesized or Immobilized on Individual Electrodes
Maurer, Karl; Yazvenko, Nina; Wilmoth, Jodi; Cooper, John; Lyon, Wanda; Danley, David
The CombiMatrix microarray with 12,544 electrodes supports in situ electrochemical synthesis of user-defined DNA probes. As an alternative, we immobilized commercially synthesized DNA probes on individual electrodes coated with electropolymerized polypyrrole (Ppy). Hybridization was measured using a biotinylated target oligonucleotide and either Cy5-streptavidin and fluorescence detection or horseradish peroxidase-streptavidin and enzyme-enhanced electrochemical detection. Detection efficiencies were optimized by varying the deposition of the Ppy, the terminal groups on the DNA probes, and other factors that impacted fluorescence quenching and electrical conductivity. Optimized results were compared against those obtained using a microarray with the same DNA sequences synthesized in situ. Immobilized probes produced higher fluorescence signals, possibly by providing a greater stand off between the Cy5 on the target oligonucleotide and the quenching effects of the Ppy and the platinum electrode. PMID:22163607
Full colour RGB OLEDs on CMOS for active-matrix OLED microdisplays
NASA Astrophysics Data System (ADS)
Kreye, D.; Toerker, M.; Vogel, U.; Amelung, J.
Microdisplays are used in various optical devices such as headsets, viewfinders and helmet-mounted displays. The use of organic light emitting diodes (OLEDs) in a microdisplay on silicone substrate provides the opportunity of lower power consumption and higher optical performance compared to other near-to-eye display technologies. Highly efficient, low-voltage, top emitting OLEDs are well suitable for the integration into a CMOSprocess. By reducing the operating voltage for the OLEDs below 5V, the costs for the CMOS process can be reduced significantly, because a standard process without high-voltage option can be used. Various OLED stacks on silicone substrate are presented, suitable for full colour (RGB) applications. Red and green emitting phosphorescent OLEDs and blue emitting fluorescent OLEDs all with doped charge transport layers were prepared on a two metal layer CMOS test substrate without active transistor area. Afterwards, the different test displays were measured and compared with respect to their performance (current, luminance, voltage, luminance dependence on viewing angle, optical outcoupling etc.)
12-inch-wafer-scale CMOS active-pixel sensor for digital mammography
NASA Astrophysics Data System (ADS)
Heo, Sung Kyn; Kosonen, Jari; Hwang, Sung Ha; Kim, Tae Woo; Yun, Seungman; Kim, Ho Kyung
This paper describes the development of an active-pixel sensor (APS) panel, which has a field-of-view of 23.1×17.1 cm and features 70-μm-sized pixels arranged in a 3300×2442 array format, for digital mammographic applications. The APS panel was realized on 12-inch wafers based on the standard complementary metal-oxide-semiconductor (CMOS) technology without physical tiling processes of several small-area sensor arrays. Electrical performance of the developed panel is described in terms of dark current, full-well capacity and leakage current map. For mammographic imaging, the optimized CsI:Tl scintillator is experimentally determined by being combined with the developed panel and analyzing im aging characteristics, such as modulation-transfer function, noise-power spectrum, detective quantum efficiency, image l ag, and contrast-detail analysis by using the CDMAM 3.4 phantom. With these results, we suggest that the developed CMOS-based detector can be used for conventional and advanced digital mammographic applications.
A CMOS Energy Harvesting and Imaging (EHI) Active Pixel Sensor (APS) Imager for Retinal Prosthesis.
Ay, S U
A CMOS image sensor capable of imaging and energy harvesting on same focal plane is presented for retinal prosthesis. The energy harvesting and imaging (EHI) active pixel sensor (APS) imager was designed, fabricated, and tested in a standard 0.5 μm CMOS process. It has 54 × 50 array of 21 × 21 μm(2) EHI pixels, 10-bit supply boosted (SB) SAR ADC, and charge pump circuits consuming only 14.25 μW from 1.2 V and running at 7.4 frames per second. The supply boosting technique (SBT) is used in an analog signal chain of the EHI imager. Harvested solar energy on focal plane is stored on an off-chip capacitor with the help of a charge pump circuit with better than 70% efficiency. Energy harvesting efficiency of the EHI pixel was measured at different light levels. It was 9.4% while producing 0.41 V open circuit voltage. The EHI imager delivers 3.35 μW of power was delivered to a resistive load at maximum power point operation. The measured pixel array figure of merit (FoM) was 1.32 pW/frame/pixel while imager figure of merit (iFoM) including whole chip power consumption was 696 fJ/pixel/code for the EHI imager. PMID:23852551
Evaluation of quantum dot immunofluorescence and a digital CMOS imaging system as an alternative to conventional organic fluorescence dyes and laser scanning for quantifying protein microarrays.
Jain, Aarti; Taghavian, Omid; Vallejo, Derek; Dotsey, Emmanuel; Schwartz, Dan; Bell, Florian G; Greef, Chad; Davies, D Huw; Grudzien, Jennipher; Lee, Abraham P; Felgner, Philip L; Liang, Li
Organic fluorescent dyes are widely used for the visualization of bound antibody in a variety of immunofluorescence assays. However, the detection equipment is often expensive, fragile, and hard to deploy widely. Quantum dots (Qdot) are nanocrystals made of semiconductor materials that emit light at different wavelengths according to the size of the crystal, with increased brightness and stability. Here, we have evaluated a small benchtop "personal" optical imager (ArrayCAM) developed for quantification of protein arrays probed by Qdot-based indirect immunofluorescence. The aim was to determine if the Qdot imager system provides equivalent data to the conventional organic dye-labeled antibody/laser scanner system. To do this, duplicate proteome microarrays of Vaccinia virus, Brucella melitensis and Plasmodium falciparum were probed with identical samples of immune sera, and IgG, IgA, and IgM profiles visualized using biotinylated secondary antibodies followed by a tertiary reagent of streptavidin coupled to either P3 (an organic cyanine dye typically used for microarrays) or Q800 (Qdot). The data show excellent correlation for all samples tested (R > 0.8) with no significant change of antibody reactivity profiles. We conclude that Qdot detection provides data equivalent to that obtained using conventional organic dye detection. The portable imager offers an economical, more robust, and deployable alternative to conventional laser array scanners. PMID:26842269
Active inductor based fully integrated CMOS transmit/ receive switch for 2.4 GHz RF transceiver.
Bhuiyan, Mohammad A S; Zijie, Yeoh; Yu, Jae S; Reaz, Mamun B I; Kamal, Noorfazila; Chang, Tae G
Modern Radio Frequency (RF) transceivers cannot be imagined without high-performance (Transmit/Receive) T/R switch. Available T/R switches suffer mainly due to the lack of good trade-off among the performance parameters, where high isolation and low insertion loss are very essential. In this study, a T/R switch with high isolation and low insertion loss performance has been designed by using Silterra 0.13µm CMOS process for 2.4GHz ISM band RF transceivers. Transistor aspect ratio optimization, proper gate bias resistance, resistive body floating and active inductor-based parallel resonance techniques have been implemented to achieve better trade-off. The proposed T/R switch exhibits 0.85dB insertion loss and 45.17dB isolation in both transmit and receive modes. Moreover, it shows very competitive values of power handling capability (P1dB) and linearity (IIP3) which are 11.35dBm and 19.60dBm, respectively. Due to avoiding bulky inductor and capacitor, the proposed active inductor-based T/R switch became highly compact occupying only 0.003mm2 of silicon space; which will further trim down the total cost of the transceiver. Therefore, the proposed active inductor-based T/R switch in 0.13µm CMOS process will be highly useful for the electronic industries where low-power, high-performance and compactness of devices are the crucial concerns. PMID:27254443
The Peptide Microarray-Based Resonance Light Scattering Assay for Sensitively Detecting Intracellular Kinase Activity.
Li, Tao; Liu, Xia; Liu, Dianjun; Wang, Zhenxin
The peptide microarray technology is a robust, reliable, and efficient technique for large-scale determination of enzyme activities, and high-throughput profiling of substrate/inhibitor specificities of enzymes. Here, the activities of cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) in different cell lysates have been detected by a peptide microarray-based resonance light scattering (RLS) assay with gold nanoparticle (GNP) probes. Highly sensitive detection of PKA activity in 0.1 μg total cell proteins of SHG-44 (human glioma cell) cell lysate (corresponding to 200 cells) is achieved by a selected peptide substrate. The experimental results also demonstrate that the RLS assay can be employed to evaluate the chemical regulation of intracellular kinase activity. PMID:26490469
A 512×512 CMOS Monolithic Active Pixel Sensor with integrated ADCs for space science
NASA Astrophysics Data System (ADS)
Prydderch, M. L.; Waltham, N. J.; Turchetta, R.; French, M. J.; Holt, R.; Marshall, A.; Burt, D.; Bell, R.; Pool, P.; Eyles, C.; Mapson-Menard, H.
In the last few years, CMOS sensors have become widely used for consumer applications, but little has been done for scientific instruments. In this paper we present the design and experimental characterisation of a Monolithic Active Pixel Sensor (MAPS) intended for a space science application. The sensor incorporates a 525×525 array of pixels on a 25 μm pitch. Each pixel contains a detector together with three transistors that are used for pixel reset, pixel selection and charge-to-voltage conversion. The detector consists of four n-well/p-substrate diodes combining optimum charge collection and low noise performance. The array readout is column-parallel with adjustable gain column amplifiers and a 10-bit single slope ADC. Data conversion takes place simultaneously for all the 525 pixels in one row. The ADC slope can be adjusted in order to give the best dynamic range for a given brightness of a scene. The digitised data are output on a 10-bit bus at 3 MHz. An on-chip state machine generates all of the control signals needed for the readout. All of the bias currents and voltages are generated on chip by a DAC that is programmable through an I 2C compatible interface. The sensor was designed and fabricated on a standard 0.5 μm CMOS technology. The overall die size is 16.7 mm×19.9 mm including the associated readout electronics and bond pads. Preliminary test results show that the full-scale design works well, meeting the Star Tracker requirements with less than 1-bit noise, good linearity and good optical performance.
Improved Design of Active Pixel CMOS Sensors for Charged Particle Detection
Deptuch, Grzegorz
The Department of Energy (DOE) nuclear physics program requires developments in detector instrumentation electronics with improved energy, position and timing resolution, sensitivity, rate capability, stability, dynamic range, and background suppression. The current Phase-I project was focused on analysis of standard-CMOS photogate Active Pixel Sensors (APS) as an efficient solution to this challenge. The advantages of the CMOS APS over traditional hybrid approaches (i.e., separate detection regions bump-bonded to readout circuits) include greatly reduced cost, low power and the potential for vastly larger pixel counts and densities. However, challenges remain in terms of the signal-to-noise ratio (SNR) and readout speed (currently on the order of milliseconds), which is the major problem for this technology. Recent work has shown that the long readout time for photogate APS is due to the presence of (interface) traps at the semiconductor-oxide interface. This Phase-I work yielded useful results in two areas: (a) Advanced three-dimensional (3D) physics-based simulation models and simulation-based analysis of the impact of interface trap density on the transient charge collection characteristics of existing APS structures; and (b) Preliminary analysis of the feasibility of an improved photogate pixel structure (i.e., new APS design) with an induced electric field under the charge collecting electrode to enhance charge collection. Significant effort was dedicated in Phase-I to the critical task of implementing accurate interface trap models in CFDRC's NanoTCAD 3D semiconductor device-physics simulator. This resulted in validation of the new NanoTCAD models and simulation results against experimental (published) data, within the margin of uncertainty associated with obtaining device geometry, material properties, and experimentation details. Analyses of the new, proposed photogate APS design demonstrated several promising trends.
Radiation-hard Active Pixel Sensors for HL-LHC Detector Upgrades based on HV-CMOS Technology
NASA Astrophysics Data System (ADS)
Miucci, A.; Gonella, L.; Hemperek, T.; Hügging, F.; Krüger, H.; Obermann, T.; Wermes, N.; Garcia-Sciveres, M.; Backhaus, M.; Capeans, M.; Feigl, S.; Nessi, M.; Pernegger, H.; Ristic, B.; Gonzalez-Sevilla, S.; Ferrere, D.; Iacobucci, G.; La Rosa, A.; Muenstermann, D.; George, M.; Große-Knetter, J.; Quadt, A.; Rieger, J.; Weingarten, J.; Bates, R.; Blue, A.; Buttar, C.; Hynds, D.; Kreidl, C.; Peric, I.; Breugnon, P.; Pangaud, P.; Godiot-Basolo, S.; Fougeron, D.; Bompard, F.; Clemens, J. C.; Liu, J.; Barbero, M.; Rozanov, A.; HV-CMOS Collaboration
Luminosity upgrades are discussed for the LHC (HL-LHC) which would make updates to the detectors necessary, requiring in particular new, even more radiation-hard and granular, sensors for the inner detector region. A proposal for the next generation of inner detectors is based on HV-CMOS: a new family of silicon sensors based on commercial high-voltage CMOS technology, which enables the fabrication of part of the pixel electronics inside the silicon substrate itself. The main advantages of this technology with respect to the standard silicon sensor technology are: low material budget, fast charge collection time, high radiation tolerance, low cost and operation at room temperature. A traditional readout chip is still needed to receive and organize the data from the active sensor and to handle high-level functionality such as trigger management. HV-CMOS has been designed to be compatible with both pixel and strip readout. In this paper an overview of HV2FEI4, a HV-CMOS prototype in 180 nm AMS technology, will be given. Preliminary results after neutron and X-ray irradiation are shown.
Characterization of Depleted Monolithic Active Pixel detectors implemented with a high-resistive CMOS technology
NASA Astrophysics Data System (ADS)
Kishishita, T.; Hemperek, T.; Rymaszewski, P.; Hirono, T.; Krüger, H.; Wermes, N.
We present the recent development of DMAPS (Depleted Monolithic Active Pixel Sensor), implemented with a Toshiba 130 nm CMOS process. Unlike in the case of standard MAPS technologies which are based on an epi-layer, this process provides a high-resistive substrate that enables larger signal and faster charge collection by drift in a 50 - 300 μm thick depleted layer. Since this process also enables the use of deep n-wells to isolate the collection electrodes from the thin active device layer, NMOS and PMOS transistors are available for the readout electronics in each pixel cell. In order to characterize the technology, we implemented a simple three transistor readout with a variety of pixel pitches and input FET sizes. This layout variety gives us a clue on sensor characteristics for future optimization, such as the input detector capacitance or leakage current. In the initial measurement, the radiation spectra were obtained from 55Fe with an energy resolution of 770 eV (FWHM) and 90Sr with the MVP of 4165 e-.
Physical characterization and performance comparison of active- and passive-pixel CMOS detectors for mammography.
Elbakri, I A; McIntosh, B J; Rickey, D W
We investigated the physical characteristics of two complementary metal oxide semiconductor (CMOS) mammography detectors. The detectors featured 14-bit image acquisition, 50 microm detector element (del) size and an active area of 5 cm x 5 cm. One detector was a passive-pixel sensor (PPS) with signal amplification performed by an array of amplifiers connected to dels via data lines. The other detector was an active-pixel sensor (APS) with signal amplification performed at each del. Passive-pixel designs have higher read noise due to data line capacitance, and the APS represents an attempt to improve the noise performance of this technology. We evaluated the detectors' resolution by measuring the modulation transfer function (MTF) using a tilted edge. We measured the noise power spectra (NPS) and detective quantum efficiencies (DQE) using mammographic beam conditions specified by the IEC 62220-1-2 standard. Our measurements showed the APS to have much higher gain, slightly higher MTF, and higher NPS. The MTF of both sensors approached 10% near the Nyquist limit. DQE values near dc frequency were in the range of 55-67%, with the APS sensor DQE lower than the PPS DQE for all frequencies. Our results show that lower read noise specifications in this case do not translate into gains in the imaging performance of the sensor. We postulate that the lower fill factor of the APS is a possible cause for this result. PMID:19242050
Characterisation of a CMOS active pixel sensor for use in the TEAM microscope
NASA Astrophysics Data System (ADS)
Battaglia, Marco; Contarato, Devis; Denes, Peter; Doering, Dionisio; Duden, Thomas; Krieger, Brad; Giubilato, Piero; Gnani, Dario; Radmilovic, Velimir
A 1M- and a 4M-pixel monolithic CMOS active pixel sensor with 9.5×9.5 μm2 pixels have been developed for direct imaging in transmission electron microscopy as part of the TEAM project. We present the design and a full characterisation of the detector. Data collected with electron beams at various energies of interest in electron microscopy are used to determine the detector response. Data are compared to predictions of simulation. The line spread function measured with 80 and 300 keV electrons is (12.1±0.7) and (7.4±0.6) μm, respectively, in good agreement with our simulation. We measure the detection quantum efficiency to be 0.78±0.04 at 80 keV and 0.74±0.03 at 300 keV. Using a new imaging technique, based on single electron reconstruction, the line spread function for 80 and 300 keV electrons becomes (6.7±0.3) and (2.4±0.2) μm, respectively. The radiation tolerance of the pixels has been tested up to 5 Mrad and the detector is still functional with a decrease of dynamic range by ≃30%, corresponding to a reduction in full-well depth from ˜39 to ˜27 primary 300 keV electrons, due to leakage current increase, but identical line spread function performance.
Pitch dependence of the tolerance of CMOS monolithic active pixel sensors to non-ionizing radiation
NASA Astrophysics Data System (ADS)
Doering, D.; Deveaux, M.; Domachowski, M.; Fröhlich, I.; Koziel, M.; Müntz, C.; Scharrer, P.; Stroth, J.
CMOS monolithic active pixel sensors (MAPS) have demonstrated excellent performance as tracking detectors for charged particles. They provide an outstanding spatial resolution (a few μm), a detection efficiency of ≳ 99.9 %, very low material budget (0.05 %X0) and good radiation tolerance (≳ 1 Mrad, ≳1013neq /cm2) (Deveaux et al. [1]). This makes them an interesting technology for various applications in heavy ion and particle physics. Their tolerance to bulk damage was recently improved by using high-resistivity (∼ 1 kΩ cm) epitaxial layers as sensitive volume (Deveaux et al. [1], Dorokhov et al. [2]). The radiation tolerance of conventional MAPS is known to depend on the pixel pitch. This is as a higher pitch extends the distance, which signal electrons have to travel by thermal diffusion before being collected. Increased diffusion paths turn into a higher probability of loosing signal charge due to recombination. Provided that a similar effect exists in MAPS with high-resistivity epitaxial layer, it could be used to extend their radiation tolerance further. We addressed this question with MIMOSA-18AHR prototypes, which were provided by the IPHC Strasbourg and irradiated with reactor neutrons. We report about the results of this study and provide evidences that MAPS with 10 μm pixel pitch tolerate doses of ≳ 3 ×1014neq /cm2.
Radiation-hard active CMOS pixel sensors for HL-LHC detector upgrades
NASA Astrophysics Data System (ADS)
Backhaus, Malte
The luminosity of the Large Hadron Collider (LHC) will be increased during the Long Shutdown of 2022 and 2023 (LS3) in order to increase the sensitivity of its experiments. A completely new inner detector for the ATLAS experiment needs to be developed to withstand the extremely harsh environment of the upgraded, so-called High-Luminosity LHC (HL-LHC). High radiation hardness as well as granularity is mandatory to cope with the requirements in terms of radiation damage as well as particle occupancy. A new silicon detector concept that uses commercial high voltage and/or high resistivity full complementary metal-oxide-semiconductor (CMOS) processes as active sensor for pixel and/or strip layers has risen high attention, because it potentially provides high radiation hardness and granularity and at the same time reduced price due to the commercial processing and possibly relaxed requirements for the hybridization technique. Results on the first prototypes characterized in a variety of laboratory as well as test beam environments are presented.
The Dexela 2923 CMOS X-ray detector: A flat panel detector based on CMOS active pixel sensors for medical imaging applications
NASA Astrophysics Data System (ADS)
Konstantinidis, Anastasios C.; Szafraniec, Magdalena B.; Speller, Robert D.; Olivo, Alessandro
Complementary metal-oxide-semiconductors (CMOS) active pixel sensors (APS) have been introduced recently in many scientific applications. This work reports on the performance (in terms of signal and noise transfer) of an X-ray detector that uses a novel CMOS APS which was developed for medical X-ray imaging applications. For a full evaluation of the detector's performance, electro-optical and X-ray characterizations were carried out. The former included measuring read noise, full well capacity and dynamic range. The latter, which included measuring X-ray sensitivity, presampling modulation transfer function (pMTF), noise power spectrum (NPS) and the resulting detective quantum efficiency (DQE), was assessed under three beam qualities (28 kV, 50 kV (RQA3) and 70 kV (RQA5) using W/Al) all in accordance with the IEC standard. The detector features an in-pixel option for switching the full well capacity between two distinct modes, high full well (HFW) and low full well (LFW). Two structured CsI:Tl scintillators of different thickness (a "thin" one for high resolution and a thicker one for high light efficiency) were optically coupled to the sensor array to optimize the performance of the system for different medical applications. The electro-optical performance evaluation of the sensor results in relatively high read noise (∼360 e-), high full well capacity (∼1.5×106 e-) and wide dynamic range (∼73 dB) under HFW mode operation. When the LFW mode is used, the read noise is lower (∼165) at the expense of a reduced full well capacity (∼0.5×106 e-) and dynamic range (∼69 dB). The maximum DQE values at low frequencies (i.e. 0.5 lp/mm) are high for both HFW (0.69 for 28 kV, 0.71 for 50 kV and 0.75 for 70 kV) and LFW (0.69 for 28 kV and 0.7 for 50 kV) modes. The X-ray performance of the studied detector compares well to that of other mammography and general radiography systems, obtained under similar experimental conditions. This demonstrates the suitability
Fourier analysis of the imaging characteristics of a CMOS active pixel detector for mammography by using a linearization method
NASA Astrophysics Data System (ADS)
Han, Jong Chul; Yun, Seungman; Youn, Hanbean; Kam, Soohwa; Cho, Seungryong; Achterkirchen, Thorsten G.; Kim, Ho Kyung
Active pixel design using the complementary metal-oxide-semiconductor (CMOS) process is a compelling solution for use in X-ray imaging detectors because of its excellent electronic noise characteristics. We have investigated the imaging performance of a CMOS active pixel photodiode array coupled to a granular phosphor through a fiber-optic faceplate for mammographic applications. The imaging performance included the modulation-transfer function (MTF), noise-power spectrum (NPS), and detective quantum efficiency (DQE). Because we observed a nonlinear detector response at low exposures, we used the linearization method for the analysis of the DQE. The linearization method uses the images obtained at detector input, which are converted from those obtained at detector output by using the inverse of the detector response. Compared to the conventional method, the linearization method provided almost the same MTF and a slightly lower normalized NPS. However, the difference between the DQE results obtained by using the two methods was significant. We claim that the conventional DQE analysis of a detector having a nonlinear response characteristic can yield wrong results. Under the standard mammographic imaging condition, we obtained a DQE performance that was competitive with the performances of conventional flat-panel mammography detectors. We believe that the CMOS detector investigated in this study can be successfully used for mammography.
Measurements on HV-CMOS active sensors after irradiation to HL-LHC fluences
NASA Astrophysics Data System (ADS)
Ristic, B.
During the long shutdown (LS) 3 beginning 2022 the LHC will be upgraded for higher luminosities pushing the limits especially for the inner tracking detectors of the LHC experiments. In order to cope with the increased particle rate and radiation levels the ATLAS Inner Detector will be completely replaced by a purely silicon based one. Novel sensors based on HV-CMOS processes prove to be good candidates in terms of spatial resolution and radiation hardness. In this paper measurements conducted on prototypes built in the AMS H18 HV-CMOS process and irradiated to fluences of up to 2·1016 neq cm-2 are presented.
Large area CMOS active pixel sensor x-ray imager for digital breast tomosynthesis: Analysis, modeling, and characterization
Zhao, Chumin; Kanicki, Jerzy; Konstantinidis, Anastasios C.; Patel, Tushita
Purpose: Large area x-ray imagers based on complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology have been proposed for various medical imaging applications including digital breast tomosynthesis (DBT). The low electronic noise (50–300 e{sup −}) of CMOS APS x-ray imagers provides a possible route to shrink the pixel pitch to smaller than 75 μm for microcalcification detection and possible reduction of the DBT mean glandular dose (MGD). Methods: In this study, imaging performance of a large area (29 × 23 cm{sup 2}) CMOS APS x-ray imager [Dexela 2923 MAM (PerkinElmer, London)] with a pixel pitch of 75 μm was characterized and modeled. The authors developed a cascaded system model for CMOS APS x-ray imagers using both a broadband x-ray radiation and monochromatic synchrotron radiation. The experimental data including modulation transfer function, noise power spectrum, and detective quantum efficiency (DQE) were theoretically described using the proposed cascaded system model with satisfactory consistency to experimental results. Both high full well and low full well (LFW) modes of the Dexela 2923 MAM CMOS APS x-ray imager were characterized and modeled. The cascaded system analysis results were further used to extract the contrast-to-noise ratio (CNR) for microcalcifications with sizes of 165–400 μm at various MGDs. The impact of electronic noise on CNR was also evaluated. Results: The LFW mode shows better DQE at low air kerma (K{sub a} < 10 μGy) and should be used for DBT. At current DBT applications, air kerma (K{sub a} ∼ 10 μGy, broadband radiation of 28 kVp), DQE of more than 0.7 and ∼0.3 was achieved using the LFW mode at spatial frequency of 0.5 line pairs per millimeter (lp/mm) and Nyquist frequency ∼6.7 lp/mm, respectively. It is shown that microcalcifications of 165–400 μm in size can be resolved using a MGD range of 0.3–1 mGy, respectively. In comparison to a General Electric GEN2 prototype DBT system (at
CMOS Active-Pixel Image Sensor With Intensity-Driven Readout
NASA Technical Reports Server (NTRS)
Langenbacher, Harry T.; Fossum, Eric R.; Kemeny, Sabrina
Proposed complementary metal oxide/semiconductor (CMOS) integrated-circuit image sensor automatically provides readouts from pixels in order of decreasing illumination intensity. Sensor operated in integration mode. Particularly useful in number of image-sensing tasks, including diffractive laser range-finding, three-dimensional imaging, event-driven readout of sparse sensor arrays, and star tracking.
A high frequency active voltage doubler in standard CMOS using offset-controlled comparators for inductive power transmission.
Lee, Hyung-Min; Ghovanloo, Maysam
In this paper, we present a fully integrated active voltage doubler in CMOS technology using offset-controlled high speed comparators for extending the range of inductive power transmission to implantable microelectronic devices (IMD) and radio-frequency identification (RFID) tags. This active voltage doubler provides considerably higher power conversion efficiency (PCE) and lower dropout voltage compared to its passive counterpart and requires lower input voltage than active rectifiers, leading to reliable and efficient operation with weakly coupled inductive links. The offset-controlled functions in the comparators compensate for turn-on and turn-off delays to not only maximize the forward charging current to the load but also minimize the back current, optimizing PCE in the high frequency (HF) band. We fabricated the active voltage doubler in a 0.5-μm 3M2P std . CMOS process, occupying 0.144 mm(2) of chip area. With 1.46 V peak AC input at 13.56 MHz, the active voltage doubler provides 2.4 V DC output across a 1 kΩ load, achieving the highest PCE = 79% ever reported at this frequency. In addition, the built-in start-up circuit ensures a reliable operation at lower voltages. PMID:23853321
A High Frequency Active Voltage Doubler in Standard CMOS Using Offset-Controlled Comparators for Inductive Power Transmission
Lee, Hyung-Min; Ghovanloo, Maysam
In this paper, we present a fully integrated active voltage doubler in CMOS technology using offset-controlled high speed comparators for extending the range of inductive power transmission to implantable microelectronic devices (IMD) and radio-frequency identification (RFID) tags. This active voltage doubler provides considerably higher power conversion efficiency (PCE) and lower dropout voltage compared to its passive counterpart and requires lower input voltage than active rectifiers, leading to reliable and efficient operation with weakly coupled inductive links. The offset-controlled functions in the comparators compensate for turn-on and turn-off delays to not only maximize the forward charging current to the load but also minimize the back current, optimizing PCE in the high frequency (HF) band. We fabricated the active voltage doubler in a 0.5-μm 3M2P std. CMOS process, occupying 0.144 mm2 of chip area. With 1.46 V peak AC input at 13.56 MHz, the active voltage doubler provides 2.4 V DC output across a 1 kΩ load, achieving the highest PCE = 79% ever reported at this frequency. In addition, the built-in start-up circuit ensures a reliable operation at lower voltages. PMID:23853321
Accelerated life testing effects on CMOS microcircuit characteristics
NASA Technical Reports Server (NTRS)
Accelerated life tests were performed on CMOS microcircuits to predict their long term reliability. The consistency of the CMOS microcircuit activation energy between the range of 125 C to 200 C and the range 200 C to 250 C was determined. Results indicate CMOS complexity and the amount of moisture detected inside the devices after testing influences time to failure of tested CMOS devices.
Non-linear responsivity characterisation of a CMOS Active Pixel Sensor for high resolution imaging of the Jovian system
NASA Astrophysics Data System (ADS)
Soman, M.; Stefanov, K.; Weatherill, D.; Holland, A.; Gow, J.; Leese, M.
The Jovian system is the subject of study for the Jupiter Icy Moon Explorer (JUICE), an ESA mission which is planned to launch in 2022. The scientific payload is designed for both characterisation of the magnetosphere and radiation environment local to the spacecraft, as well as remote characterisation of Jupiter and its satellites. A key instrument on JUICE is the high resolution and wide angle camera, JANUS, whose main science goals include detailed characterisation and study phases of three of the Galilean satellites, Ganymede, Callisto and Europa, as well as studies of other moons, the ring system, and irregular satellites. The CIS115 is a CMOS Active Pixel Sensor from e2v technologies selected for the JANUS camera. It is fabricated using 0.18 μ m CMOS imaging sensor process, with an imaging area of 2000 × 1504 pixels, each 7 μ m square. A 4T pixel architecture allows for efficient correlated double sampling, improving the readout noise to better than 8 electrons rms, whilst the sensor is operated in a rolling shutter mode, sampling at up to 10 Mpixel/s at each of the four parallel outputs.A primary parameter to characterise for an imaging device is the relationship that converts the sensor's voltage output back to the corresponding number of electrons that were detected in a pixel, known as the Charge to Voltage Factor (CVF). In modern CMOS sensors with small feature sizes, the CVF is known to be non-linear with signal level, therefore a signal-dependent measurement of the CIS115's CVF has been undertaken and is presented here. The CVF is well modelled as a quadratic function leading to a measurement of the maximum charge handling capacity of the CIS115 to be 3.4 × 104 electrons. If the CIS115's response is assumed linear, its CVF is 21.1 electrons per mV (1/47.5 μ V per electron).
A New Versatile Microarray-based Method for High Throughput Screening of Carbohydrate-active Enzymes*
Vidal-Melgosa, Silvia; Pedersen, Henriette L.; Schückel, Julia; Arnal, Grégory; Dumon, Claire; Amby, Daniel B.; Monrad, Rune Nygaard; Westereng, Bjørge; Willats, William G. T.
Carbohydrate-active enzymes have multiple biological roles and industrial applications. Advances in genome and transcriptome sequencing together with associated bioinformatics tools have identified vast numbers of putative carbohydrate-degrading and -modifying enzymes including glycoside hydrolases and lytic polysaccharide monooxygenases. However, there is a paucity of methods for rapidly screening the activities of these enzymes. By combining the multiplexing capacity of carbohydrate microarrays with the specificity of molecular probes, we have developed a sensitive, high throughput, and versatile semiquantitative enzyme screening technique that requires low amounts of enzyme and substrate. The method can be used to assess the activities of single enzymes, enzyme mixtures, and crude culture broths against single substrates, substrate mixtures, and biomass samples. Moreover, we show that the technique can be used to analyze both endo-acting and exo-acting glycoside hydrolases, polysaccharide lyases, carbohydrate esterases, and lytic polysaccharide monooxygenases. We demonstrate the potential of the technique by identifying the substrate specificities of purified uncharacterized enzymes and by screening enzyme activities from fungal culture broths. PMID:25657012
A new versatile microarray-based method for high throughput screening of carbohydrate-active enzymes.
Vidal-Melgosa, Silvia; Pedersen, Henriette L; Schückel, Julia; Arnal, Grégory; Dumon, Claire; Amby, Daniel B; Monrad, Rune Nygaard; Westereng, Bjørge; Willats, William G T
Carbohydrate-active enzymes have multiple biological roles and industrial applications. Advances in genome and transcriptome sequencing together with associated bioinformatics tools have identified vast numbers of putative carbohydrate-degrading and -modifying enzymes including glycoside hydrolases and lytic polysaccharide monooxygenases. However, there is a paucity of methods for rapidly screening the activities of these enzymes. By combining the multiplexing capacity of carbohydrate microarrays with the specificity of molecular probes, we have developed a sensitive, high throughput, and versatile semiquantitative enzyme screening technique that requires low amounts of enzyme and substrate. The method can be used to assess the activities of single enzymes, enzyme mixtures, and crude culture broths against single substrates, substrate mixtures, and biomass samples. Moreover, we show that the technique can be used to analyze both endo-acting and exo-acting glycoside hydrolases, polysaccharide lyases, carbohydrate esterases, and lytic polysaccharide monooxygenases. We demonstrate the potential of the technique by identifying the substrate specificities of purified uncharacterized enzymes and by screening enzyme activities from fungal culture broths. PMID:25657012
Performance of CMOS imager as sensing element for a Real-time Active Pixel Dosimeter for Interventional Radiology procedures
NASA Astrophysics Data System (ADS)
Magalotti, D.; Bissi, L.; Conti, E.; Paolucci, M.; Placidi, P.; Scorzoni, A.; Servoli, L.
Staff members applying Interventional Radiology procedures are exposed to ionizing radiation, which can induce detrimental effects to the human body, and requires an improvement of radiation protection. This paper is focused on the study of the sensor element for a wireless real-time dosimeter to be worn by the medical staff during the interventional radiology procedures, in the framework of the Real-Time Active PIxel Dosimetry (RAPID) INFN project. We characterize a CMOS imager to be used as detection element for the photons scattered by the patient body. The CMOS imager has been first characterized in laboratory using fluorescence X-ray sources, then a PMMA phantom has been used to diffuse the X-ray photons from an angiography system. Different operating conditions have been used to test the detector response in realistic situations, by varying the X-ray tube parameters (continuous/pulsed mode, tube voltage and current, pulse parameters), the sensor parameters (gain, integration time) and the relative distance between sensor and phantom. The sensor response has been compared with measurements performed using passive dosimeters (TLD) and also with a certified beam, in an accredited calibration centre, in order to obtain an absolute calibration. The results are very encouraging, with dose and dose rate measurement uncertainties below the 10% level even for the most demanding Interventional Radiology protocols.
Integrated X-ray and charged particle active pixel CMOS sensor arrays using an epitaxial silicon sensitive region
Kleinfelder, Stuart; Bichsel, Hans; Bieser, Fred; Matis, Howard S.; Rai, Gulshan; Retiere, Fabrice; Weiman, Howard; Yamamoto, Eugene
Integrated CMOS Active Pixel Sensor (APS) arrays have been fabricated and tested using X-ray and electron sources. The 128 by 128 pixel arrays, designed in a standard 0.25 micron process, use a {approx}10 micron epitaxial silicon layer as a deep detection region. The epitaxial layer has a much greater thickness than the surface features used by standard CMOS APS, leading to stronger signals and potentially better signal-to-noise ratio (SNR). On the other hand, minority carriers confined within the epitaxial region may diffuse to neighboring pixels, blur images and reduce peak signal intensity. But for low-rate, sparse-event images, centroid analysis of this diffusion may be used to increase position resolution. Careful trade-offs involving pixel size and sense-node area verses capacitance must be made to optimize overall performance. The prototype sensor arrays, therefore, include a range of different pixel designs, including different APS circuits and a range of different epitaxial layer contact structures. The fabricated arrays were tested with 1.5 GeV electrons and Fe-55 X-ray sources, yielding a measured noise of 13 electrons RMS and an SNR for single Fe-55 X-rays of greater than 38.
Identification of Biologically Active, HIV TAR RNA-Binding Small Molecules Using Small Molecule Microarrays
Identifying small molecules that selectively bind to structured RNA motifs remains an important challenge in developing potent and specific therapeutics. Most strategies to find RNA-binding molecules have identified highly charged compounds or aminoglycosides that commonly have modest selectivity. Here we demonstrate a strategy to screen a large unbiased library of druglike small molecules in a microarray format against an RNA target. This approach has enabled the identification of a novel chemotype that selectively targets the HIV transactivation response (TAR) RNA hairpin in a manner not dependent on cationic charge. Thienopyridine 4 binds to and stabilizes the TAR hairpin with a Kd of 2.4 μM. Structure–activity relationships demonstrate that this compound achieves activity through hydrophobic and aromatic substituents on a heterocyclic core, rather than cationic groups typically required. Selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) analysis was performed on a 365-nucleotide sequence derived from the 5′ untranslated region (UTR) of the HIV-1 genome to determine global structural changes in the presence of the molecule. Importantly, the interaction of compound 4 can be mapped to the TAR hairpin without broadly disrupting any other structured elements of the 5′ UTR. Cell-based anti-HIV assays indicated that 4 inhibits HIV-induced cytopathicity in T lymphocytes with an EC50 of 28 μM, while cytotoxicity was not observed at concentrations approaching 1 mM. PMID:24820959
Characterizing the Activation of the Wnt Signaling Pathway in Hilar Cholangiocarcinoma Using a Tissue Microarray Approach
Chen, W.; Huang, L.; Liang, J.; Cai, J.; Lei, Y.; Lai, J.; Liang, L.; Zhang, K.
Hilar cholangiocarcinoma (HCCA) is an invasive hepatic malignancy that is difficult to biopsy; therefore, novel markers of HCCA prognosis are needed. Here, the level of canonical Wnt activation in patients with HCCA, intrahepatic cholangiocarcinoma (IHCC), and congenital choledochal cysts (CCC) was compared to understand the role of Wnt signaling in HCCA. Pathology specimens from HCCA (n=129), IHCC (n=31), and CCC (n=45) patients were used to construct tissue microarrays. Wnt2, Wnt3, β-catenin, TCF4, c-Myc, and cyclin D1 were detected by immunohistochemistry. Parallel correlation analysis was used to analyze differences in protein levels between the HCCA, IHCC, and CCC groups. Univariate and multivariate analyses were used to determine independent predictors of successful resection and prognosis in the HCCA group. The protein levels of Wnt2, β-catenin, TCF4, c-Myc, and cyclin D1 were significantly higher in HCCA compared to IHHC or CCC. Wnt signaling activation (Wnt2+, Wnt3+, nuclear β-catenin+, nuclear TCF4+) was significantly greater in HCCA tissues than CCC tissues. Univariable analyses indicated that expression of cyclin D1 as well as Wnt signaling activation, and partial Wnt activation (Wnt2+ or Wnt3+ and nuclear β-catenin+ or nuclear TCF4+) predicted successful resection, but only cyclin D1 expression remained significant in multivariable analyses. Only partial Wnt activation was an independent predictor of survival time. Proteins in the canonical Wnt signaling pathway were present at higher levels in HCCA and correlated with tumor resecility and patient prognosis. These results suggest that Wnt pathway analysis may be a useful marker for clinical outcome in HCCA. PMID:26972709
T Cell Dynamic Activation and Functional Analysis in Nanoliter Droplet Microarray
Sarkar, Saheli; Motwani, Vinny; Sabhachandani, Pooja; Cohen, Noa; Konry, Tania
Objective Characterization of the heterogeneity in immune reactions requires assessing dynamic single cell responses as well as interactions between the various immune cell subsets. Maturation and activation of effector cells is regulated by cell contact-dependent and soluble factor-mediated paracrine signalling. Currently there are few methods available that allow dynamic investigation of both processes simultaneously without physically constraining non-adherent cells and eliminating crosstalk from neighboring cell pairs. We describe here a microfluidic droplet microarray platform that permits rapid functional analysis of single cell responses and co-encapsulation of heterotypic cell pairs, thereby allowing us to evaluate the dynamic activation state of primary T cells. Methods The microfluidic droplet platform enables generation and docking of monodisperse nanoliter volume (0.523 nl) droplets, with the capacity of monitoring a thousand droplets per experiment. Single human T cells were encapsulated in droplets and stimulated on-chip with the calcium ionophore ionomycin. T cells were also co-encapsulated with dendritic cells activated by ovalbumin peptide, followed by dynamic calcium signal monitoring. Results Ionomycin-stimulated cells depicted fluctuation in calcium signalling compared to control. Both cell populations demonstrated marked heterogeneity in responses. Calcium signalling was observed in T cells immediately following contact with DCs, suggesting an early activation signal. T cells further showed non-contact mediated increase in calcium level, although this response was delayed compared to contact-mediated signals. Conclusions Our results suggest that this nanoliter droplet array-based microfluidic platform is a promising technique for assessment of heterogeneity in various types of cellular responses, detection of early/delayed signalling events and live cell phenotyping of immune cells. PMID:26613065
A CMOS active pixel sensor system for laboratory- based x-ray diffraction studies of biological tissue.
Bohndiek, Sarah E; Cook, Emily J; Arvanitis, Costas D; Olivo, Alessandro; Royle, Gary J; Clark, Andy T; Prydderch, Mark L; Turchetta, Renato; Speller, Robert D
X-ray diffraction studies give material-specific information about biological tissue. Ideally, a large area, low noise, wide dynamic range digital x-ray detector is required for laboratory-based x-ray diffraction studies. The goal of this work is to introduce a novel imaging technology, the CMOS active pixel sensor (APS) that has the potential to fulfil all these requirements, and demonstrate its feasibility for coherent scatter imaging. A prototype CMOS APS has been included in an x-ray diffraction demonstration system. An industrial x-ray source with appropriate beam filtration is used to perform angle dispersive x-ray diffraction (ADXRD). Optimization of the experimental set-up is detailed including collimator options and detector operating parameters. Scatter signatures are measured for 11 different materials, covering three medical applications: breast cancer diagnosis, kidney stone identification and bone mineral density calculations. Scatter signatures are also recorded for three mixed samples of known composition. Results are verified using two independent models for predicting the APS scatter signature: (1) a linear systems model of the APS and (2) a linear superposition integral combining known monochromatic scatter signatures with the input polychromatic spectrum used in this case. Cross validation of experimental, modelled and literature results proves that APS are able to record biologically relevant scatter signatures. Coherent scatter signatures are sensitive to multiple materials present in a sample and provide a means to quantify composition. In the future, production of a bespoke APS imager for x-ray diffraction studies could enable simultaneous collection of the transmitted beam and scattered radiation in a laboratory-based coherent scatter system, making clinical transfer of the technique attainable. PMID:18199908
Advanced monolithic active pixel sensors for tracking, vertexing and calorimetry with full CMOS capability
NASA Astrophysics Data System (ADS)
Stanitzki, M.; SPiDeR Collaboration, www. spider. ac. uk
We present test results from the "TPAC" and "F ORTIS" sensors produced using the 180 nm CMOS INMAPS process. The TPAC sensor has a 50 μm pixel size with advanced in-pixel electronics. Although TPAC was developed for digital electromagnetic calorimetry, the technology can be readily extended to tracking and vertexing applications where highly granular pixels with in-pixel intelligence are required. By way of example, a variant of the TPAC sensor has been proposed for the Super B vertex detector. The F ORTIS sensor is a prototype with several pixel variants to study the performance of a four transistors (4T) architecture and is the first sensor of this type tested for particle physics applications. TPAC and F ORTIS sensors have been fabricated with some of the processing innovations available in INMAPS such as deep p-wells and high-resistivity epitaxial layers. The performance of these sensor variants has been measured both in the laboratory and at test beams and results showing significant improvements due to these innovations are presented. We have recently manufactured the "C HERWELL" sensor, building on the experience with both TPAC and F ORTIS and making use of the 4T approach. C HERWELL is designed for tracking and vertexing and has an integrated ADC and targets very low-noise performance. The principal features of C HERWELL are described.
A 0.18-µm CMOS Array Sensor for Integrated Time-Resolved Fluorescence Detection
Huang, Ta-chien D.; Sorgenfrei, Sebastian; Gong, Ping; Levicky, Rastislav; Shepard, Kenneth L.
This paper describes the design of an active, integrated CMOS sensor array for fluorescence applications which enables time-gated, time-resolved fluorescence spectroscopy. The 64-by-64 array is sensitive to photon densities as low as 8.8 × 106 photons/cm2 with 64-point averaging and, through a differential pixel design, has a measured impulse response of better than 800 ps. Applications include both active microarrays and high-frame-rate imagers for fluorescence lifetime imaging microscopy. PMID:20436922
NASA Astrophysics Data System (ADS)
Turchetta, R.; Guerrini, N.; Sedgwick, I.
CMOS image sensors, also known as CMOS Active Pixel Sensors (APS) or Monolithic Active Pixel Sensors (MAPS), are today the dominant imaging devices. They are omnipresent in our daily life, as image sensors in cellular phones, web cams, digital cameras, ... In these applications, the pixels can be very small, in the micron range, and the sensors themselves tend to be limited in size. However, many scientific applications, like particle or X-ray detection, require large format, often with large pixels, as well as other specific performance, like low noise, radiation hardness or very fast readout. The sensors are also required to be sensitive to a broad spectrum of radiation: photons from the silicon cut-off in the IR down to UV and X- and gamma-rays through the visible spectrum as well as charged particles. This requirement calls for modifications to the substrate to be introduced to provide optimized sensitivity. This paper will review existing CMOS image sensors, whose size can be as large as a single CMOS wafer, and analyse the technical requirements and specific challenges of large format CMOS image sensors.
Synchrotron based planar imaging and digital tomosynthesis of breast and biopsy phantoms using a CMOS active pixel sensor.
Szafraniec, Magdalena B; Konstantinidis, Anastasios C; Tromba, Giuliana; Dreossi, Diego; Vecchio, Sara; Rigon, Luigi; Sodini, Nicola; Naday, Steve; Gunn, Spencer; McArthur, Alan; Olivo, Alessandro
The SYRMEP (SYnchrotron Radiation for MEdical Physics) beamline at Elettra is performing the first mammography study on human patients using free-space propagation phase contrast imaging. The stricter spatial resolution requirements of this method currently force the use of conventional films or specialized computed radiography (CR) systems. This also prevents the implementation of three-dimensional (3D) approaches. This paper explores the use of an X-ray detector based on complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology as a possible alternative, for acquisitions both in planar and tomosynthesis geometry. Results indicate higher quality of the images acquired with the synchrotron set-up in both geometries. This improvement can be partly ascribed to the use of parallel, collimated and monochromatic synchrotron radiation (resulting in scatter rejection, no penumbra-induced blurring and optimized X-ray energy), and partly to phase contrast effects. Even though the pixel size of the used detector is still too large - and thus suboptimal - for free-space propagation phase contrast imaging, a degree of phase-induced edge enhancement can clearly be observed in the images. PMID:25498332
NASA Astrophysics Data System (ADS)
Ricard-Blum, S.
Proteins are key actors in the life of the cell, involved in many physiological and pathological processes. Since variations in the expression of messenger RNA are not systematically correlated with variations in the protein levels, the latter better reflect the way a cell functions. Protein microarrays thus supply complementary information to DNA chips. They are used in particular to analyse protein expression profiles, to detect proteins within complex biological media, and to study protein-protein interactions, which give information about the functions of those proteins [3-9]. They have the same advantages as DNA microarrays for high-throughput analysis, miniaturisation, and the possibility of automation. Section 18.1 gives a brief overview of proteins. Following this, Sect. 18.2 describes how protein microarrays can be made on flat supports, explaining how proteins can be produced and immobilised on a solid support, and discussing the different kinds of substrate and detection method. Section 18.3 discusses the particular format of protein microarrays in suspension. The diversity of protein microarrays and their applications are then reported in Sect. 18.4, with applications to therapeutics (protein-drug interactions) and diagnostics. The prospects for future developments of protein microarrays are then outlined in the conclusion. The bibliography provides an extensive list of reviews and detailed references for those readers who wish to go further in this area. Indeed, the aim of the present chapter is not to give an exhaustive or detailed analysis of the state of the art, but rather to provide the reader with the basic elements needed to understand how proteins are designed and used.
Characterization of imaging performance of a large-area CMOS active-pixel detector for low-energy X-ray imaging
NASA Astrophysics Data System (ADS)
Hwy Lim, Chang; Yun, Seungman; Chul Han, Jong; Kim, Ho Kyung; Farrier, Michael G.; Graeve Achterkirchen, Thorsten; McDonald, Mike; Cunningham, Ian A.
We report the imaging characteristics of the recently developed large-area complementary metal-oxide-semiconductor (CMOS) active-pixel detector for low-energy digital X-ray imaging applications. The detector consists of a scintillator to convert X-ray into light and a photodiode pixel array made by the CMOS fabrication process to convert light into charge signals. Between two layers, we introduce a fiber-optic faceplate (FOP) to avoid direct absorption of X-ray photons in the photodiode array. A single pixel is composed of a photodiode and three transistors, and the pixel pitch is 96 μm. The imaging characteristics of the detector have been investigated in terms of modulation-transfer function (MTF), noise-power spectrum (NPS), and detective quantum efficiency (DQE). From the measured results, the MTF at the Nyquist frequency is about 20% and the DQE around zero-spatial frequency is about 40%. Simple cascaded linear-systems analysis has showed that the FOP prevents direct absorption of X-ray photons within the CMOS photodiode array, leading to a lower NPS and consequently improved DQE especially at high spatial frequencies.
50 μm pixel pitch wafer-scale CMOS active pixel sensor x-ray detector for digital breast tomosynthesis
NASA Astrophysics Data System (ADS)
Zhao, C.; Konstantinidis, A. C.; Zheng, Y.; Anaxagoras, T.; Speller, R. D.; Kanicki, J.
Wafer-scale CMOS active pixel sensors (APSs) have been developed recently for x-ray imaging applications. The small pixel pitch and low noise are very promising properties for medical imaging applications such as digital breast tomosynthesis (DBT). In this work, we evaluated experimentally and through modeling the imaging properties of a 50 μm pixel pitch CMOS APS x-ray detector named DynAMITe (Dynamic Range Adjustable for Medical Imaging Technology). A modified cascaded system model was developed for CMOS APS x-ray detectors by taking into account the device nonlinear signal and noise properties. The imaging properties such as modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) were extracted from both measurements and the nonlinear cascaded system analysis. The results show that the DynAMITe x-ray detector achieves a high spatial resolution of 10 mm-1 and a DQE of around 0.5 at spatial frequencies <1 mm-1. In addition, the modeling results were used to calculate the image signal-to-noise ratio (SNRi) of microcalcifications at various mean glandular dose (MGD). For an average breast (5 cm thickness, 50% glandular fraction), 165 μm microcalcifications can be distinguished at a MGD of 27% lower than the clinical value (~1.3 mGy). To detect 100 μm microcalcifications, further optimizations of the CMOS APS x-ray detector, image aquisition geometry and image reconstruction techniques should be considered.
50 μm pixel pitch wafer-scale CMOS active pixel sensor x-ray detector for digital breast tomosynthesis.
Zhao, C; Konstantinidis, A C; Zheng, Y; Anaxagoras, T; Speller, R D; Kanicki, J
Wafer-scale CMOS active pixel sensors (APSs) have been developed recently for x-ray imaging applications. The small pixel pitch and low noise are very promising properties for medical imaging applications such as digital breast tomosynthesis (DBT). In this work, we evaluated experimentally and through modeling the imaging properties of a 50 μm pixel pitch CMOS APS x-ray detector named DynAMITe (Dynamic Range Adjustable for Medical Imaging Technology). A modified cascaded system model was developed for CMOS APS x-ray detectors by taking into account the device nonlinear signal and noise properties. The imaging properties such as modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) were extracted from both measurements and the nonlinear cascaded system analysis. The results show that the DynAMITe x-ray detector achieves a high spatial resolution of 10 mm(-1) and a DQE of around 0.5 at spatial frequencies <1 mm(-1). In addition, the modeling results were used to calculate the image signal-to-noise ratio (SNRi) of microcalcifications at various mean glandular dose (MGD). For an average breast (5 cm thickness, 50% glandular fraction), 165 μm microcalcifications can be distinguished at a MGD of 27% lower than the clinical value (~1.3 mGy). To detect 100 μm microcalcifications, further optimizations of the CMOS APS x-ray detector, image aquisition geometry and image reconstruction techniques should be considered. PMID:26540090
c-mos and cdc2 Cooperate in the Translational Activation of Fibroblast Growth Factor Receptor-1 during Xenopus Oocyte Maturation
Culp, Patricia A.; Musci, Thomas J.
During oocyte maturation in Xenopus, previously quiescent maternal mRNAs are translationally activated at specific times. We hypothesized that the translational recruitment of individual messages is triggered by particular cellular events and investigated the potential for known effectors of the meiotic cell cycle to activate the translation of the FGF receptor-1 (XFGFR) maternal mRNA. We found that both c-mos and cdc2 activate the translation of XFGFR. However, although oocytes matured by injection of recombinant cdc2/cyclin B translate normal levels of XFGFR protein, c-mos depletion reduces the level of XFGFR protein induced by cdc2/cyclin B injection. In oocytes blocked for cdc2 activity, injection of mos RNA induced low levels of XFGFR protein, independent of MAPK activity. Through the use of injected reporter RNAs, we show that the XFGFR 3′ untranslated region inhibitory element is completely derepressed by cdc2 alone. In addition, we identified a new inhibitory element through which both mos and cdc2 activate translation. We found that cdc2 derepresses translation in the absence of polyadenylation, whereas mos requires poly(A) extension to activate XFGFR translation. Our results demonstrate that mos and cdc2, in addition to functioning as key regulators of the meiotic cell cycle, cooperate in the translational activation of a specific maternal mRNA during oocyte maturation. PMID:10564256
First tests of CHERWELL, a Monolithic Active Pixel Sensor: A CMOS Image Sensor (CIS) using 180 nm technology
NASA Astrophysics Data System (ADS)
Mylroie-Smith, James; Kolya, Scott; Velthuis, Jaap; Bevan, Adrian; Inguglia, Gianluca; Headspith, Jon; Lazarus, Ian; Lemon, Roy; Crooks, Jamie; Turchetta, Renato; Wilson, Fergus
The Cherwell is a 4T CMOS sensor in 180 nm technology developed for the detection of charged particles. Here, the different test structures on the sensor will be described and first results from tests on the reference pixel variant are shown. The sensors were shown to have a noise of 12 e- and a signal to noise up to 150 in 55Fe.
Anderson, Sharon
Over the last half century, knowledge about genetics, genetic testing, and its complexity has flourished. Completion of the Human Genome Project provided a foundation upon which the accuracy of genetics, genomics, and integration of bioinformatics knowledge and testing has grown exponentially. What is lagging, however, are efforts to reach and engage nurses about this rapidly changing field. The purpose of this article is to familiarize nurses with several frequently ordered genetic tests including chromosomes and fluorescence in situ hybridization followed by a comprehensive review of chromosome microarray. It shares the complexity of microarray including how testing is performed and results analyzed. A case report demonstrates how this technology is applied in clinical practice and reveals benefits and limitations of this scientific and bioinformatics genetic technology. Clinical implications for maternal-child nurses across practice levels are discussed. PMID:27276104
Using a customized DNA microarray for expression profiling of the estrogen-responsive genes to evaluate estrogen activity among natural estrogens and industrial chemicals.
Terasaka, Shunichi; Aita, Yukie; Inoue, Akio; Hayashi, Shinichi; Nishigaki, Michiko; Aoyagi, Kazuhiko; Sasaki, Hiroki; Wada-Kiyama, Yuko; Sakuma, Yasuo; Akaba, Shuichi; Tanaka, Junko; Sone, Hideko; Yonemoto, Junzo; Tanji, Masao; Kiyama, Ryoiti
We developed a DNA microarray to evaluate the estrogen activity of natural estrogens and industrial chemicals. Using MCF-7 cells, we conducted a comprehensive analysis of estrogen-responsive genes among approximately 20,000 human genes. On the basis of reproducible and reliable responses of the genes to estrogen, we selected 172 genes to be used for developing a customized DNA microarray. Using this DNA microarray, we examined estrogen activity among natural estrogens (17beta-estradiol, estriol, estrone, genistein), industrial chemicals (diethylstilbestrol, bisphenol A, nonylphenol, methoxychlor), and dioxin. We obtained results identical to those for other bioassays that are used for detecting estrogen activity. On the basis of statistical correlations analysis, these bioassays have shown more sensitivity for dioxin and methoxychlor. PMID:15159206
Development of CMOS Active Pixel Image Sensors for Low Cost Commercial Applications
NASA Technical Reports Server (NTRS)
Gee, R.; Kemeny, S.; Kim, Q.; Mendis, S.; Nakamura, J.; Nixon, R.; Ortiz, M.; Pain, B.; Staller, C.; Zhou, Z; Fossum, E.
JPL, under sponsorship from the NASA Office of Advanced Concepts and Technology, has been developing a second-generation solid-state image sensor technology. Charge-coupled devices (CCD) are a well-established first generation image sensor technology. For both commercial and NASA applications, CCDs have numerous shortcomings. In response, the active pixel sensor (APS) technology has been under research. The major advantages of APS technology are the ability to integrate on-chip timing, control, signal-processing and analog-to-digital converter functions, reduced sensitivity to radiation effects, low power operation, and random access readout.
Optical and electrical characterization of a back-thinned CMOS active pixel sensor
NASA Astrophysics Data System (ADS)
Blue, Andrew; Clark, A.; Houston, S.; Laing, A.; Maneuski, D.; Prydderch, M.; Turchetta, R.; O'Shea, V.
This work will report on the first work on the characterization of a back-thinned Vanilla-a 512×512 (25 μm squared) active pixel sensor (APS). Characterization of the detectors was carried out through the analysis of photon transfer curves to yield a measurement of full well capacity, noise levels, gain constants and linearity. Spectral characterization of the sensors was also performed in the visible and UV regions. A full comparison against non-back-thinned front illuminated Vanilla sensors is included. Such measurements suggest that the Vanilla APS will be suitable for a wide range of applications, including particle physics and biomedical imaging.
The Nanoelectronics Research Initiative and Beyond CMOS Research Activities in the US
NASA Astrophysics Data System (ADS)
Bourianoff, George I.
The six leading Semiconductor Companies in the US have joined forces with Federal and State government to form the Nanoelectronics Research Initiative in 2005. The goal is to find new information processing paradigms, systems and devices which will extend Moore's Law functional scaling into the indefinite future. The research activities are guided by 5 central research vectors which define the scope and content of the program and are listed below. *Computational state variables other than electronic charge *Non-equilibrium systems out of equilibrium with the thermal environment *Novel information transport mechanisms *Nanoscale thermal management *Directed self assembly of complex heterostructures The current NRI research effort consists of 56 projects at 25 universities and 3 research centers in a coherent program where each project is aligned with one or more of the research vectors. During the past two years, significant progress has been made in a number of areas including spin wave, generation, detection and characterization, room temperature DMS materials, femptosecond magnetic domain switching characterization, improved MQCA structures, multiferroic and, magnetoelectric materials and devices, non-conformational metal insulator phase transitions in VO2 and ferromagnetic ring nanodevices. A brief discussion and references will be provided.
Low nickel germanide contact resistances by carrier activation enhancement techniques for germanium CMOS application
NASA Astrophysics Data System (ADS)
Miyoshi, Hidenori; Ueno, Tetsuji; Hirota, Yoshihiro; Yamanaka, Junji; Arimoto, Keisuke; Nakagawa, Kiyokazu; Kaitsuka, Takanobu
We fabricated and studied nickel germanide (NiGe) contacts on both n- and p-type germanium (Ge) substrates by applying the carrier activation enhancement (CAE) technique. We achieved a high electron concentration of 8.6 × 1019 cm-3 using a P/Sb co-implant and a record-high hole concentration of 8.4 × 1020 cm-3 using a Ge preamorphization implant and a boron implant. We used the circular transfer length method and two-dimensional DC simulation to determine the specific contact resistivity (ρc). Using the CAE technique, we obtained low ρc values of 6.4 × 10-7 Ω cm2 for the NiGe/n+-Ge contact and 4.0 × 10-8 Ω cm2 for the NiGe/p+-Ge contact. Theoretical calculation of ρc shows that, to achieve a ρc of 1 × 10-8 Ω cm2 as required by the International Technology Roadmap for Semiconductors for the year 2015, contacts on p+-Ge need contact process optimization, while contacts on n+-Ge need further CAE improvement and/or Schottky barrier height reduction.
Analysis of Escherichia coli RNase E and RNase III activity in vivo using tiling microarrays
Stead, Mark B.; Marshburn, Sarah; Mohanty, Bijoy K.; Mitra, Joydeep; Castillo, Lourdes Peňa; Ray, Debashish; van Bakel, Harm; Hughes, Timothy R.; Kushner, Sidney R.
Tiling microarrays have proven to be a valuable tool for gaining insights into the transcriptomes of microbial organisms grown under various nutritional or stress conditions. Here, we describe the use of such an array, constructed at the level of 20 nt resolution for the Escherichia coli MG1655 genome, to observe genome-wide changes in the steady-state RNA levels in mutants defective in either RNase E or RNase III. The array data were validated by comparison to previously published results for a variety of specific transcripts as well as independent northern analysis of additional mRNAs and sRNAs. In the absence of RNase E, 60% of the annotated coding sequences showed either increases or decreases in their steady-state levels. In contrast, only 12% of the coding sequences were affected in the absence of RNase III. Unexpectedly, many coding sequences showed decreased abundance in the RNase E mutant, while more than half of the annotated sRNAs showed changes in abundance. Furthermore, the steady-state levels of many transcripts showed overlapping effects of both ribonucleases. Data are also presented demonstrating how the arrays were used to identify potential new genes, RNase III cleavage sites and the direct or indirect control of specific biological pathways. PMID:21149258
Pathway modeling of microarray data: A case study of pathway activity changes in the testis following in utero exposure to dibutyl phthalate (DBP)
Ovacik, Meric A.; Sen, Banalata; Euling, Susan Y.; Gaido, Kevin W.; Ierapetritou, Marianthi G.; Androulakis, Ioannis P.
Pathway activity level analysis, the approach pursued in this study, focuses on all genes that are known to be members of metabolic and signaling pathways as defined by the KEGG database. The pathway activity level analysis entails singular value decomposition (SVD) of the expression data of the genes constituting a given pathway. We explore an extension of the pathway activity methodology for application to time-course microarray data. We show that pathway analysis enhances our ability to detect biologically relevant changes in pathway activity using synthetic data. As a case study, we apply the pathway activity level formulation coupled with significance analysis to microarray data from two different rat testes exposed in utero to Dibutyl Phthalate (DBP). In utero DBP exposure in the rat results in developmental toxicity of a number of male reproductive organs, including the testes. One well-characterized mode of action for DBP and the male reproductive developmental effects is the repression of expression of genes involved in cholesterol transport, steroid biosynthesis and testosterone synthesis that lead to a decreased fetal testicular testosterone. Previous analyses of DBP testes microarray data focused on either individual gene expression changes or changes in the expression of specific genes that are hypothesized, or known, to be important in testicular development and testosterone synthesis. However, a pathway analysis may inform whether there are additional affected pathways that could inform additional modes of action linked to DBP developmental toxicity. We show that Pathway activity analysis may be considered for a more comprehensive analysis of microarray data.
Microarray analysis of active cardiac remodeling genes in a familial hypertrophic cardiomyopathy mouse model rescued by a phospholamban knockout
Rajan, Sudarsan; Pena, James R.; Jegga, Anil G.; Aronow, Bruce J.; Wolska, Beata M.
Familial hypertrophic cardiomyopathy (FHC) is a disease characterized by ventricular hypertrophy, fibrosis, and aberrant systolic and/or diastolic function. Our laboratories have previously developed two mouse models that affect cardiac performance. One mouse model encodes an FHC-associated mutation in α-tropomyosin: Glu → Gly at amino acid 180, designated as Tm180. These mice display a phenotype that is characteristic of FHC, including severe cardiac hypertrophy with fibrosis and impaired physiological performance. The other model was a gene knockout of phospholamban (PLN KO), a regulator of calcium uptake in the sarcoplasmic reticulum of cardiomyocytes; these hearts exhibit hypercontractility with no pathological abnormalities. Previous work in our laboratories shows that when mice were genetically crossed between the PLN KO and Tm180, the progeny (PLN KO/Tm180) display a rescued hypertrophic phenotype with improved morphology and cardiac function. To understand the changes in gene expression that occur in these models undergoing cardiac remodeling (Tm180, PLN KO, PLN KO/Tm180, and nontransgenic control mice), we conducted microarray analyses of left ventricular tissue at 4 and 12 mo of age. Expression profiling reveals that 1,187 genes changed expression in direct response to the three genetic models. With these 1,187 genes, 11 clusters emerged showing normalization of transcript expression in the PLN KO/Tm180 hearts. In addition, 62 transcripts are highly involved in suppression of the hypertrophic phenotype. Confirmation of the microarray analysis was conducted by quantitative RT-PCR. These results provide insight into genes that alter expression during cardiac remodeling and are active during modulation of the cardiomyopathic phenotype. PMID:23800848
Riza, Nabeel A; La Torre, Juan Pablo; Amin, M Junaid
Proposed and experimentally demonstrated is the CAOS-CMOS camera design that combines the coded access optical sensor (CAOS) imager platform with the CMOS multi-pixel optical sensor. The unique CAOS-CMOS camera engages the classic CMOS sensor light staring mode with the time-frequency-space agile pixel CAOS imager mode within one programmable optical unit to realize a high dynamic range imager for extreme light contrast conditions. The experimentally demonstrated CAOS-CMOS camera is built using a digital micromirror device, a silicon point-photo-detector with a variable gain amplifier, and a silicon CMOS sensor with a maximum rated 51.3 dB dynamic range. White light imaging of three different brightness simultaneously viewed targets, that is not possible by the CMOS sensor, is achieved by the CAOS-CMOS camera demonstrating an 82.06 dB dynamic range. Applications for the camera include industrial machine vision, welding, laser analysis, automotive, night vision, surveillance and multispectral military systems. PMID:27410361
NASA Astrophysics Data System (ADS)
Nguyen, C.; Gidrol, X.
Genomics has revolutionised biological and biomedical research. This revolution was predictable on the basis of its two driving forces: the ever increasing availability of genome sequences and the development of new technology able to exploit them. Up until now, technical limitations meant that molecular biology could only analyse one or two parameters per experiment, providing relatively little information compared with the great complexity of the systems under investigation. This gene by gene approach is inadequate to understand biological systems containing several thousand genes. It is essential to have an overall view of the DNA, RNA, and relevant proteins. A simple inventory of the genome is not sufficient to understand the functions of the genes, or indeed the way that cells and organisms work. For this purpose, functional studies based on whole genomes are needed. Among these new large-scale methods of molecular analysis, DNA microarrays provide a way of studying the genome and the transcriptome. The idea of integrating a large amount of data derived from a support with very small area has led biologists to call these chips, borrowing the term from the microelectronics industry. At the beginning of the 1990s, the development of DNA chips on nylon membranes [1, 2], then on glass [3] and silicon [4] supports, made it possible for the first time to carry out simultaneous measurements of the equilibrium concentration of all the messenger RNA (mRNA) or transcribed RNA in a cell. These microarrays offer a wide range of applications, in both fundamental and clinical research, providing a method for genome-wide characterisation of changes occurring within a cell or tissue, as for example in polymorphism studies, detection of mutations, and quantitative assays of gene copies. With regard to the transcriptome, it provides a way of characterising differentially expressed genes, profiling given biological states, and identifying regulatory channels.
Application of a Novel Functional Gene Microarray to Probe the Functional Ecology of Ammonia Oxidation in Nitrifying Activated Sludge
Short, Michael D.; Abell, Guy C. J.; Bodrossy, Levente; van den Akker, Ben
We report on the first study trialling a newly-developed, functional gene microarray (FGA) for characterising bacterial and archaeal ammonia oxidisers in activated sludge. Mixed liquor (ML) and media biofilm samples from a full-scale integrated fixed-film activated sludge (IFAS) plant were analysed with the FGA to profile the diversity and relative abundance of ammonia-oxidising archaea and bacteria (AOA and AOB respectively). FGA analyses of AOA and AOB communities revealed ubiquitous distribution of AOA across all samples – an important finding for these newly-discovered and poorly characterised organisms. Results also revealed striking differences in the functional ecology of attached versus suspended communities within the IFAS reactor. Quantitative assessment of AOB and AOA functional gene abundance revealed a dominance of AOB in the ML and approximately equal distribution of AOA and AOB in the media-attached biofilm. Subsequent correlations of functional gene abundance data with key water quality parameters suggested an important functional role for media-attached AOB in particular for IFAS reactor nitrification performance and indicate possible functional redundancy in some IFAS ammonia oxidiser communities. Results from this investigation demonstrate the capacity of the FGA to resolve subtle ecological shifts in key microbial communities in nitrifying activated sludge and indicate its value as a tool for better understanding the linkages between the ecology and performance of these engineered systems. PMID:24155925
Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study
Background This study undertakes a systematic and comprehensive analysis of brain gene expression profiles of immune/inflammation-related genes in aging and Alzheimer's disease (AD). Methods In a well-powered microarray study of young (20 to 59 years), aged (60 to 99 years), and AD (74 to 95 years) cases, gene responses were assessed in the hippocampus, entorhinal cortex, superior frontal gyrus, and post-central gyrus. Results Several novel concepts emerge. First, immune/inflammation-related genes showed major changes in gene expression over the course of cognitively normal aging, with the extent of gene response far greater in aging than in AD. Of the 759 immune-related probesets interrogated on the microarray, approximately 40% were significantly altered in the SFG, PCG and HC with increasing age, with the majority upregulated (64 to 86%). In contrast, far fewer immune/inflammation genes were significantly changed in the transition to AD (approximately 6% of immune-related probesets), with gene responses primarily restricted to the SFG and HC. Second, relatively few significant changes in immune/inflammation genes were detected in the EC either in aging or AD, although many genes in the EC showed similar trends in responses as in the other brain regions. Third, immune/inflammation genes undergo gender-specific patterns of response in aging and AD, with the most pronounced differences emerging in aging. Finally, there was widespread upregulation of genes reflecting activation of microglia and perivascular macrophages in the aging brain, coupled with a downregulation of select factors (TOLLIP, fractalkine) that when present curtail microglial/macrophage activation. Notably, essentially all pathways of the innate immune system were upregulated in aging, including numerous complement components, genes involved in toll-like receptor signaling and inflammasome signaling, as well as genes coding for immunoglobulin (Fc) receptors and human leukocyte antigens I
Microarray profiling of L1-overexpressing endothelial cells reveals STAT3 activation via IL-6/IL-6Rα axis
Magrini, Elena; Cavallaro, Ugo; Bianchi, Fabrizio
We recently identified a novel role for the L1 transmembrane glycoprotein (also known as L1CAM or CD171) in the regulation of tumor angiogenesis and vessels stabilization. L1 overexpression in cultured endothelial cells of the lung (luECs) exerted a pleiotropic effect in that it regulated proliferation, migration, tubulogenesis, vascular permeability, and endothelial-to-mesenchymal transition (EndMT). In addition, we provided strong evidence that antibody-mediated targeting of L1 may be an effective strategy for vessel normalization with the potential to increase efficacy of chemotherapeutic agents. High-throughput microarray expression profile revealed that L1 modulates the expression of hundreds of genes mainly involved in cell cycle regulation, DNA replication, cellular assembly, migration, development and organization. By using a 'pathway-oriented' analysis strategy we were able to identify a network of 105 genes modulated by L1 through the predicted activation of five transcription factors: STAT1, STAT2, STAT3, IRF7, and ATF4. Indeed, L1 overexpression resulted in the strong induction of STAT3 phosphorylation which was abolished by antibody-mediated neutralization of IL-6Rα. These results indicated that L1 promoted STAT3 activation via the IL-6/IL-6Rα axis. PMID:26484199
NASA Astrophysics Data System (ADS)
Ehrler, F.; Blanco, R.; Leys, R.; Perić, I.
High-voltage CMOS (HVCMOS) pixel sensors are depleted active pixel sensors implemented in standard commercial CMOS processes. The sensor element is the n-well/p-substrate diode. The sensor electronics are entirely placed inside the n-well which is at the same time used as the charge collection electrode. High voltage is used to deplete the part of the substrate around the n-well. HVCMOS sensors allow implementation of complex in-pixel electronics. This, together with fast signal collection, allows a good time resolution, which is required for particle tracking in high energy physics. HVCMOS sensors will be used in Mu3e experiment at PSI and are considered as an option for both ATLAS and CLIC (CERN). Radiation tolerance and time walk compensation have been tested and results are presented.
Empirical electro-optical and x-ray performance evaluation of CMOS active pixels sensor for low dose, high resolution x-ray medical imaging.
Arvanitis, C D; Bohndiek, S E; Royle, G; Blue, A; Liang, H X; Clark, A; Prydderch, M; Turchetta, R; Speller, R
Monolithic complementary metal oxide semiconductor (CMOS) active pixel sensors with high performance have gained attention in the last few years in many scientific and space applications. In order to evaluate the increasing capabilities of this technology, in particular where low dose high resolution x-ray medical imaging is required, critical electro-optical and physical x-ray performance evaluation was determined. The electro-optical performance includes read noise, full well capacity, interacting quantum efficiency, and pixels cross talk. The x-ray performance, including x-ray sensitivity, modulation transfer function, noise power spectrum, and detection quantum efficiency, has been evaluated in the mammographic energy range. The sensor is a 525 x 525 standard three transistor CMOS active pixel sensor array with more than 75% fill factor and 25 x 25 microm pixel pitch. Reading at 10 f/s, it is found that the sensor has 114 electrons total additive noise, 10(5) electrons full well capacity with shot noise limited operation, and 34% interacting quantum efficiency at 530 nm. Two different structured CsI:Tl phosphors with thickness 95 and 115 microm, respectively, have been optically coupled via a fiber optic plate to the array resulting in two different system configurations. The sensitivity of the two different system configurations was 43 and 47 electrons per x-ray incident on the sensor. The MTF at 10% of the two different system configurations was 9.5 and 9 cycles/mm with detective quantum efficiency of 0.45 and 0.48, respectively, close to zero frequency at approximately 0.44 microC/kg (1.72 mR) detector entrance exposure. The detector was quantum limited at low spatial frequencies and its performance was comparable with high resolution a: Si and charge coupled device based x-ray imagers. The detector also demonstrates almost an order of magnitude lower noise than active matrix flat panel imagers. The results suggest that CMOS active pixel sensors when coupled
Empirical electro-optical and x-ray performance evaluation of CMOS active pixels sensor for low dose, high resolution x-ray medical imaging
Arvanitis, C. D.; Bohndiek, S. E.; Royle, G.; Blue, A.; Liang, H. X.; Clark, A.; Prydderch, M.; Turchetta, R.; Speller, R.
Monolithic complementary metal oxide semiconductor (CMOS) active pixel sensors with high performance have gained attention in the last few years in many scientific and space applications. In order to evaluate the increasing capabilities of this technology, in particular where low dose high resolution x-ray medical imaging is required, critical electro-optical and physical x-ray performance evaluation was determined. The electro-optical performance includes read noise, full well capacity, interacting quantum efficiency, and pixels cross talk. The x-ray performance, including x-ray sensitivity, modulation transfer function, noise power spectrum, and detection quantum efficiency, has been evaluated in the mammographic energy range. The sensor is a 525x525 standard three transistor CMOS active pixel sensor array with more than 75% fill factor and 25x25 {mu}m pixel pitch. Reading at 10 f/s, it is found that the sensor has 114 electrons total additive noise, 10{sup 5} electrons full well capacity with shot noise limited operation, and 34% interacting quantum efficiency at 530 nm. Two different structured CsI:Tl phosphors with thickness 95 and 115 {mu}m, respectively, have been optically coupled via a fiber optic plate to the array resulting in two different system configurations. The sensitivity of the two different system configurations was 43 and 47 electrons per x-ray incident on the sensor. The MTF at 10% of the two different system configurations was 9.5 and 9 cycles/mm with detective quantum efficiency of 0.45 and 0.48, respectively, close to zero frequency at {approx}0.44 {mu}C/kg (1.72 mR) detector entrance exposure. The detector was quantum limited at low spatial frequencies and its performance was comparable with high resolution a:Si and charge coupled device based x-ray imagers. The detector also demonstrates almost an order of magnitude lower noise than active matrix flat panel imagers. The results suggest that CMOS active pixel sensors when coupled to
Angel-Syrett, Heather; Collett, Jim; Ellington, Andrew D.
In vitro selection can yield specific, high-affinity aptamers. We and others have devised methods for the automated selection of aptamers, and have begun to use these reagents for the construction of arrays. Arrayed aptamers have proven to be almost as sensitive as their solution phase counterparts, and when ganged together can provide both specific and general diagnostic signals for proteins and other analytes. We describe here technical details regarding the production and processing of aptamer microarrays, including blocking, washing, drying, and scanning. We will also discuss the challenges involved in developing standardized and reproducible methods for binding and quantitating protein targets. While signals from fluorescent analytes or sandwiches are typically captured, it has proven possible for immobilized aptamers to be uniquely coupled to amplification methods not available to protein reagents, thus allowing for protein-binding signals to be greatly amplified. Into the future, many of the biosensor methods described in this book can potentially be adapted to array formats, thus further expanding the utility of and applications for aptamer arrays.
A cell-based microarray to investigate combinatorial effects of microparticle-encapsulated adjuvants on dendritic cell activation
Acharya, Abhinav P.; Carstens, Matthew R.; Lewis, Jamal S.; Dolgova, Natalia; Xia, C. Q.; Clare-Salzler, Michael J.
Experimental vaccine adjuvants are being designed to target specific toll-like receptors (TLRs) alone or in combination, expressed by antigen presenting cells, notably dendritic cells (DCs). There is a need for high-content screening (HCS) platforms to explore how DC activation is affected by adjuvant combinations. Presented is a cell-based microarray approach, "immunoarray", exposing DCs to a large number of adjuvant combinations. Microparticles encapsulating TLR ligands are printed onto arrays in a range of doses for each ligand, in all possible dose combinations. Dendritic cells are then co-localized with physisorbed microparticles on the immunoarray, adherent to isolated islands surrounded by a non-fouling background, and DC activation is quantified. Delivery of individual TLR ligands was capable of eliciting high levels of specific DC activation markers. For example, either TLR9 ligand, CpG, or TLR3 ligand, poly I:C, was capable of inducing among the highest 10% expression levels of CD86. In contrast, MHC-II expression in response to TLR4 agonist MPLA was among the highest, whereas either MPLA or poly I:C, was capable of producing among the highest levels of CCR7 expression, as well as inflammatory cytokine IL-12. However, in order to produce robust responses across all activation markers, adjuvant combinations were required, and combinations were more represented among the high responders. The immunoarray also enables investigation of interactions between adjuvants, and each TLR ligand suggested antagonism to other ligands, for various markers. Altogether, this work demonstrates feasibility of the immunoarray platform to screen microparticle-encapsulated adjuvant combinations for the development of improved and personalized vaccines. PMID:26985393
Activity Based High-Throughput Screening for Novel O-GlcNAc Transferase Substrates Using a Dynamic Peptide Microarray.
Shi, Jie; Sharif, Suhela; Ruijtenbeek, Rob; Pieters, Roland J
O-GlcNAcylation is a reversible and dynamic protein post-translational modification in mammalian cells. The O-GlcNAc cycle is catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). O-GlcNAcylation plays important role in many vital cellular events including transcription, cell cycle regulation, stress response and protein degradation, and altered O-GlcNAcylation has long been implicated in cancer, diabetes and neurodegenerative diseases. Recently, numerous approaches have been developed to identify OGT substrates and study their function, but there is still a strong demand for highly efficient techniques. Here we demonstrated the utility of the peptide microarray approach to discover novel OGT substrates and study its specificity. Interestingly, the protein RBL-2, which is a key regulator of entry into cell division and may function as a tumor suppressor, was identified as a substrate for three isoforms of OGT. Using peptide Ala scanning, we found Ser 420 is one possible O-GlcNAc site in RBL-2. Moreover, substitution of Ser 420, on its own, inhibited OGT activity, raising the possibility of mechanism-based development for selective OGT inhibitors. This approach will prove useful for both discovery of novel OGT substrates and studying OGT specificity. PMID:26960196
Activity Based High-Throughput Screening for Novel O-GlcNAc Transferase Substrates Using a Dynamic Peptide Microarray
Shi, Jie; Sharif, Suhela; Ruijtenbeek, Rob; Pieters, Roland J.
O-GlcNAcylation is a reversible and dynamic protein post-translational modification in mammalian cells. The O-GlcNAc cycle is catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). O-GlcNAcylation plays important role in many vital cellular events including transcription, cell cycle regulation, stress response and protein degradation, and altered O-GlcNAcylation has long been implicated in cancer, diabetes and neurodegenerative diseases. Recently, numerous approaches have been developed to identify OGT substrates and study their function, but there is still a strong demand for highly efficient techniques. Here we demonstrated the utility of the peptide microarray approach to discover novel OGT substrates and study its specificity. Interestingly, the protein RBL-2, which is a key regulator of entry into cell division and may function as a tumor suppressor, was identified as a substrate for three isoforms of OGT. Using peptide Ala scanning, we found Ser 420 is one possible O-GlcNAc site in RBL-2. Moreover, substitution of Ser 420, on its own, inhibited OGT activity, raising the possibility of mechanism-based development for selective OGT inhibitors. This approach will prove useful for both discovery of novel OGT substrates and studying OGT specificity. PMID:26960196
Pathway modeling of microarray data: a case study of pathway activity changes in the testis following in utero exposure to dibutyl phthalate (DBP).
Ovacik, Meric A; Sen, Banalata; Euling, Susan Y; Gaido, Kevin W; Ierapetritou, Marianthi G; Androulakis, Ioannis P
Pathway activity level analysis, the approach pursued in this study, focuses on all genes that are known to be members of metabolic and signaling pathways as defined by the KEGG database. The pathway activity level analysis entails singular value decomposition (SVD) of the expression data of the genes constituting a given pathway. We explore an extension of the pathway activity methodology for application to time-course microarray data. We show that pathway analysis enhances our ability to detect biologically relevant changes in pathway activity using synthetic data. As a case study, we apply the pathway activity level formulation coupled with significance analysis to microarray data from two different rat testes exposed in utero to Dibutyl Phthalate (DBP). In utero DBP exposure in the rat results in developmental toxicity of a number of male reproductive organs, including the testes. One well-characterized mode of action for DBP and the male reproductive developmental effects is the repression of expression of genes involved in cholesterol transport, steroid biosynthesis and testosterone synthesis that lead to a decreased fetal testicular testosterone. Previous analyses of DBP testes microarray data focused on either individual gene expression changes or changes in the expression of specific genes that are hypothesized, or known, to be important in testicular development and testosterone synthesis. However, a pathway analysis may inform whether there are additional affected pathways that could inform additional modes of action linked to DBP developmental toxicity. We show that Pathway activity analysis may be considered for a more comprehensive analysis of microarray data. PMID:20850466
Discovery of Pituitary Adenylate Cyclase-Activating Polypeptide-Regulated Genes through Microarray Analyses in Cell Culture and In Vivo
Eiden, Lee E.; Samal, Babru; Gerdin, Matthew J.; Mustafa, Tomris; Vaudry, David; Stroth, Nikolas
Pituitary adenylate cyclase-activating polypeptide (PACAP) is an evolutionarily well conserved neuropeptide with multiple functions in the nervous, endocrine, and immune systems. PACAP provides neuroprotection from ischemia and toxin exposure, is anti-inflammatory in gastric inflammatory disease and sepsis, controls proliferative signaling pathways involved in neural cell transformation, and modulates glucohomeostasis. PACAP-based, disease-targeted therapeutics might thus be both effective and benign, enhancing homeostatic responses to behavioral, metabolic, oncogenic, and inflammatory stressors. PACAP signal transduction employs synergistic regulation of calcium and cyclic adenosine monophosphate (cAMP), and noncanonical activation of both calcium- and cAMP-dependent processes. Pharmacological activation of PACAP signaling should consequently have highly specific effects even in vivo. Here, a combined cellular biochemical, pharmacologic, transcriptomic, and bioinformatic approach to understanding PACAP signal transduction by identifying PACAP target genes with oligonucleotide- and cDNA-based microarray is described. Calcium- and cAMP-dependent PACAP signaling pathways for regulation of genes encoding proteins required for neuritogenesis, changes in cell morphology, and cell survival have been traced in PC12 cells. Pharmacological experiments have linked gene expression to cell physiological responses in this system, in which gene silencing can also be employed to confirm the functional significance of induction of specific transcripts. Differential transcriptional responses to metabolic, ischemic, and other stressors in wild type compared to PACAP-deficient mice establish in principle which PACAP-responsive transcripts in culture are PACAP-dependent in vivo. Bioinformatic approaches aid in creating a pipeline for identifying neuropeptide-regulated genes, validating their cellular functions, and defining their expression in the context of neuropeptide signaling
Performance of capacitively coupled active pixel sensors in 180 nm HV-CMOS technology after irradiation to HL-LHC fluences
NASA Astrophysics Data System (ADS)
Feigl, S.
In this ATLAS upgrade R&D project, we explore the concept of using a deep-submicron HV-CMOS process to produce a drop-in replacement for traditional radiation-hard silicon sensors. Such active sensors contain simple circuits, e.g. amplifiers and discriminators, but still require a traditional (pixel or strip) readout chip. This approach yields most advantages of MAPS (improved resolution, reduced cost and material budget, etc.), without the complication of full integration on a single chip. After outlining the basic design of the HV2FEI4 test ASIC, results after irradiation with X-rays to 862 Mrad and neutrons up to 1016(1 MeV neq)/cm2 will be presented. Finally, a brief outlook on further development plans is given.
Angiogenesis Interactome and Time Course Microarray Data Reveal the Distinct Activation Patterns in Endothelial Cells
Chu, Liang-Hui; Lee, Esak; Bader, Joel S.; Popel, Aleksander S.
Angiogenesis involves stimulation of endothelial cells (EC) by various cytokines and growth factors, but the signaling mechanisms are not completely understood. Combining dynamic gene expression time-course data for stimulated EC with protein-protein interactions associated with angiogenesis (the "angiome") could reveal how different stimuli result in different patterns of network activation and could implicate signaling intermediates as points for control or intervention. We constructed the protein-protein interaction networks of positive and negative regulation of angiogenesis comprising 367 and 245 proteins, respectively. We used five published gene expression datasets derived from in vitro assays using different types of blood endothelial cells stimulated by VEGFA (vascular endothelial growth factor A). We used the Short Time-series Expression Miner (STEM) to identify significant temporal gene expression profiles. The statistically significant patterns between 2D fibronectin and 3D type I collagen substrates for telomerase-immortalized EC (TIME) show that different substrates could influence the temporal gene activation patterns in the same cell line. We investigated the different activation patterns among 18 transmembrane tyrosine kinase receptors, and experimentally measured the protein level of the tyrosine-kinase receptors VEGFR1, VEGFR2 and VEGFR3 in human umbilical vein EC (HUVEC) and human microvascular EC (MEC). The results show that VEGFR1–VEGFR2 levels are more closely coupled than VEGFR1–VEGFR3 or VEGFR2–VEGFR3 in HUVEC and MEC. This computational methodology can be extended to investigate other molecules or biological processes such as cell cycle. PMID:25329517
Active Fail-Safe Micro-Array Flow Control for Advanced Embedded Propulsion Systems
NASA Technical Reports Server (NTRS)
Anderson, Bernhard H.; Mace, James L.; Mani, Mori
The primary objective of this research effort was to develop and analytically demonstrate enhanced first generation active "fail-safe" hybrid flow-control techniques to simultaneously manage the boundary layer on the vehicle fore-body and to control the secondary flow generated within modern serpentine or embedded inlet S-duct configurations. The enhanced first-generation technique focused on both micro-vanes and micro-ramps highly-integrated with micro -jets to provide nonlinear augmentation for the "strength' or effectiveness of highly-integrated flow control systems. The study focused on the micro -jet mass flow ratio (Wjet/Waip) range from 0.10 to 0.30 percent and jet total pressure ratios (Pjet/Po) from 1.0 to 3.0. The engine bleed airflow range under study represents about a 10 fold decrease in micro -jet airflow than previously required. Therefore, by pre-conditioning, or injecting a very small amount of high-pressure jet flow into the vortex generated by the micro-vane and/or micro-ramp, active flow control is achieved and substantial augmentation of the controlling flow is realized.
Cytokines in cerebrospinal fluid of neurosyphilis patients: Identification of Urokinase plasminogen activator using antibody microarrays.
Lu, Ping; Zheng, Dao-Cheng; Fang, Chang; Huang, Jin-Mei; Ke, Wu-Jian; Wang, Liu-Yuan; Zeng, Wei-Ying; Zheng, He-Ping; Yang, Bin
Little is known regarding protein responses to syphilis infection in cerebrospinal fluid (CSF) of patients presenting with neurosyphilis. Protein and antibody arrays offer a new opportunity to gain insights into global protein expression profiles in these patients. Here we obtained CSF samples from 46 syphilis patients, 25 of which diagnosed as having central nervous system involvement based on clinical and laboratory findings. The CSF samples were then analyzed using a RayBioH L-Series 507 Antibody Array system designed to simultaneously analyze 507 specific cytokines. The results indicated that 41 molecules showed higher levels in patients with neurosyphilis in comparison with patients without neural involvement. For validation by single target ELISA, we selected five of them (MIP-1a, I-TAC/CXCL11, Urokinase plasminogen activator [uPA], and Oncostatin M) because they have previously been found to be involved in central nervous system (CNS) disorders. The ELISA tests confirmed that uPA levels were significantly higher in the CSF of neurosyphilis patients (109.1±7.88pg/ml) versus patients without CNS involvement (63.86±4.53pg/ml, p<0.0001). There was also a clear correlation between CSF uPA levels and CSF protein levels (p=0.0128) as well as CSF-VDRL titers (p=0.0074) used to diagnose neurosyphilis. No significant difference between the two groups of patients, however, was found in uPA levels in the serum, suggesting specific activation of the inflammatory system in the CNS but not the periphery in neurosyphilis patients. We conclude that measurements of uPA levels in CSF may be an additional parameter for diagnosing neurosyphilis. PMID:27049560
High responsivity CMOS imager pixel implemented in SOI technology
NASA Technical Reports Server (NTRS)
Zheng, X.; Wrigley, C.; Yang, G.; Pain, B.
Availability of mature sub-micron CMOS technology and the advent of the new low noise active pixel sensor (APS) concept have enabled the development of low power, miniature, single-chip, CMOS digital imagers in the decade of the 1990's.
Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR)
Holtrup, Frank; Bauer, Andrea; Fellenberg, Kurt; Hilger, Ralf A; Wink, Michael; Hoheisel, Jörg D
BACKGROUND AND PURPOSE Pancreatic cancer is one of the leading cancer-related causes of death due to high chemo-resistance and fast metastasation. Nemorosone, a polycyclic polyprenylated acylphloroglucinol, has recently been identified as a promising anticancer agent. Here, we examine its growth-inhibitory effects on pancreatic cancer cells. Based on transcription profiling, a molecular mode of action is proposed. EXPERIMENTAL APPROACH Nemorosone cytotoxicity was assessed by the resazurin proliferation assay on pancreatic cancer cells and fibroblasts. Apoptosis was determined by Annexin V/propidium iodide staining as well as cytochrome c and caspase activation assays. Staining with the voltage-dependent dye JC-1 and fluorescence microscopy were used to detect effects on mitochondrial membrane potential. Total RNA was isolated from treated cell lines and subjected to microarray analysis, subsequent pathway identification and modelling. Gene expression data were validated by quantitative polymerase chain reaction and siRNA-mediated gene knock-down. KEY RESULTS Nemorosone significantly inhibited cancer cell growth, induced cytochrome c release and subsequent caspase-dependent apoptosis, rapidly abolished mitochondrial membrane potential and elevated cytosolic calcium levels, while fibroblasts were largely unaffected. Expression profiling revealed 336 genes to be affected by nemorosone. A total of 75 genes were altered in all three cell lines, many of which were within the unfolded protein response (UPR) network. DNA damage inducible transcript 3 was identified as a key regulator in UPR-mediated cell death. CONCLUSIONS AND IMPLICATIONS Nemorosone could be a lead compound for the development of novel anticancer drugs amplifying the already elevated UPR level in solid tumours, thus driving them into apoptosis. This study forms the basis for further investigations identifying nemorosone's direct molecular target(s). PMID:21091652
NASA Technical Reports Server (NTRS)
Bandera, Cesar (Inventor); Scott, Peter (Inventor); Sridhar, Ramalingam (Inventor); Xia, Shu (Inventor)
A foveal image sensor integrated circuit comprising a plurality of CMOS active pixel sensors arranged both within and about a central fovea region of the chip. The pixels in the central fovea region have a smaller size than the pixels arranged in peripheral rings about the central region. A new photocharge normalization scheme and associated circuitry normalizes the output signals from the different size pixels in the array. The pixels are assembled into a multi-resolution rectilinear foveal image sensor chip using a novel access scheme to reduce the number of analog RAM cells needed. Localized spatial resolution declines monotonically with offset from the imager's optical axis, analogous to biological foveal vision.
Ion traps fabricated in a CMOS foundry
Mehta, K. K.; Ram, R. J.; Eltony, A. M.; Chuang, I. L.; Bruzewicz, C. D.; Sage, J. M. Chiaverini, J.
We demonstrate trapping in a surface-electrode ion trap fabricated in a 90-nm CMOS (complementary metal-oxide-semiconductor) foundry process utilizing the top metal layer of the process for the trap electrodes. The process includes doped active regions and metal interconnect layers, allowing for co-fabrication of standard CMOS circuitry as well as devices for optical control and measurement. With one of the interconnect layers defining a ground plane between the trap electrode layer and the p-type doped silicon substrate, ion loading is robust and trapping is stable. We measure a motional heating rate comparable to those seen in surface-electrode traps of similar size. This demonstration of scalable quantum computing hardware utilizing a commercial CMOS process opens the door to integration and co-fabrication of electronics and photonics for large-scale quantum processing in trapped-ion arrays.
Microarrays, Integrated Analytical Systems
NASA Astrophysics Data System (ADS)
Combinatorial chemistry is used to find materials that form sensor microarrays. This book discusses the fundamentals, and then proceeds to the many applications of microarrays, from measuring gene expression (DNA microarrays) to protein-protein interactions, peptide chemistry, carbodhydrate chemistry, electrochemical detection, and microfluidics.
Implantable CMOS Biomedical Devices
Ohta, Jun; Tokuda, Takashi; Sasagawa, Kiyotaka; Noda, Toshihiko
The results of recent research on our implantable CMOS biomedical devices are reviewed. Topics include retinal prosthesis devices and deep-brain implantation devices for small animals. Fundamental device structures and characteristics as well as in vivo experiments are presented. PMID:22291554
Evaluation of MOBILE-based gate-level pipelining augmenting CMOS with RTDs
NASA Astrophysics Data System (ADS)
Nuñez, Juan; Avedillo, María J.; Quintana, José M.
The incorporation of Resonant Tunnel Diodes (RTDs) into III/V transistor technologies has shown an improved circuit performance: higher circuit speed, reduced component count, and/or lowered power consumption. Currently, the incorporation of these devices into CMOS technologies (RTD-CMOS) is an area of active research. Although some works have focused the evaluation of the advantages of this incorporation, additional work in this direction is required. We compare RTD-CMOS and pure CMOS realizations of a network of logic gates which can be operated in a gate-level pipeline. Significant lower average power is obtained for RTD-CMOS implementations.
Analysis and Enhancement of Low-Light-Level Performance of Photodiode-Type CMOS Active Pixel Images Operated with Sub-Threshold Reset
NASA Technical Reports Server (NTRS)
Pain, Bedabrata; Yang, Guang; Ortiz, Monico; Wrigley, Christopher; Hancock, Bruce; Cunningham, Thomas
Noise in photodiode-type CMOS active pixel sensors (APS) is primarily due to the reset (kTC) noise at the sense node, since it is difficult to implement in-pixel correlated double sampling for a 2-D array. Signal integrated on the photodiode sense node (SENSE) is calculated by measuring difference between the voltage on the column bus (COL) - before and after the reset (RST) is pulsed. Lower than kTC noise can be achieved with photodiode-type pixels by employing "softreset" technique. Soft-reset refers to resetting with both drain and gate of the n-channel reset transistor kept at the same potential, causing the sense node to be reset using sub-threshold MOSFET current. However, lowering of noise is achieved only at the expense higher image lag and low-light-level non-linearity. In this paper, we present an analysis to explain the noise behavior, show evidence of degraded performance under low-light levels, and describe new pixels that eliminate non-linearity and lag without compromising noise.
Peptide Microarrays for Real-Time Kinetic Profiling of Tyrosine Phosphatase Activity of Recombinant Phosphatases and Phosphatases in Lysates of Cells or Tissue Samples.
Hovestad-Bijl, Liesbeth; van Ameijde, Jeroen; Pijnenburg, Dirk; Hilhorst, Riet; Liskamp, Rob; Ruijtenbeek, Rob
A high-throughput method for the determination of the kinetics of protein tyrosine phosphatase (PTP) activity in a microarray format is presented, allowing real-time monitoring of the dephosphorylation of a 3-nitro-phosphotyrosine residue. The 3-nitro-phosphotyrosine residue is incorporated in potential PTP substrates. The peptide substrates are immobilized onto a porous surface in discrete spots. After dephosphorylation by a PTP, a 3-nitrotyrosine residue is formed that can be detected by a specific, sequence-independent antibody. The rate of dephosphorylation can be measured simultaneously on 12 microarrays, each comprising three concentrations of 48 clinically relevant peptides, using 1.0-5.0 μg of protein from a cell or tissue lysate or 0.1-2.0 μg of purified phosphatase. The data obtained compare well with solution phase assays involving the corresponding unmodified phosphotyrosine substrates. This technology, characterized by high-throughput (12 assays in less than 2 h), multiplexing and low sample requirements, facilitates convenient and unbiased investigation of the enzymatic activity of the PTP enzyme family, for instance by profiling of PTP substrate specificities, evaluation of PTP inhibitors and pinpointing changes in PTP activity in biological samples related to diseases. PMID:27514800
All-CMOS night vision viewer with integrated microdisplay
NASA Astrophysics Data System (ADS)
Goosen, Marius E.; Venter, Petrus J.; du Plessis, Monuko; Faure, Nicolaas M.; Janse van Rensburg, Christo; Rademeyer, Pieter
The unrivalled integration potential of CMOS has made it the dominant technology for digital integrated circuits. With the advent of visible light emission from silicon through hot carrier electroluminescence, several applications arose, all of which rely upon the advantages of mature CMOS technologies for a competitive edge in a very active and attractive market. In this paper we present a low-cost night vision viewer which employs only standard CMOS technologies. A commercial CMOS imager is utilized for near infrared image capturing with a 128x96 pixel all-CMOS microdisplay implemented to convey the image to the user. The display is implemented in a standard 0.35 μm CMOS process, with no process alterations or post processing. The display features a 25 μm pixel pitch and a 3.2 mm x 2.4 mm active area, which through magnification presents the virtual image to the user equivalent of a 19-inch display viewed from a distance of 3 meters. This work represents the first application of a CMOS microdisplay in a low-cost consumer product.
NASA Astrophysics Data System (ADS)
Waltham, Nick
The charge-coupled device (CCD) has been developed primarily as a compact image sensor for consumer and industrial markets, but is now also the preeminent visible and ultraviolet wavelength image sensor in many fields of scientific research including space-science and both Earth and planetary remote sensing. Today"s scientific or science-grade CCD will strive to maximise pixel count, focal plane coverage, photon detection efficiency over the broadest spectral range and signal dynamic range whilst maintaining the lowest possible readout noise. The relatively recent emergence of complementary metal oxide semiconductor (CMOS) image sensor technology is arguably the most important development in solid-state imaging since the invention of the CCD. CMOS technology enables the integration on a single silicon chip of a large array of photodiode pixels alongside all of the ancillary electronics needed to address the array and digitise the resulting analogue video signal. Compared to the CCD, CMOS promises a more compact, lower mass, lower power and potentially more radiation tolerant camera.
Walker, Josef; Flower, Darren; Rigley, Kevin
Microarrays are fast becoming routine tools for the high-throughput analysis of gene expression in a wide range of biologic systems, including hematology. Although a number of approaches can be taken when implementing microarray-based studies, all are capable of providing important insights into biologic function. Although some technical issues have not been resolved, microarrays will continue to make a significant impact on hematologically important research. PMID:11753074
CMOS monolithic pixel sensors research and development at LBNL
NASA Astrophysics Data System (ADS)
Contarato, D.; Bussat, J.-M.; Denes, P.; Greiner, L.; Kim, T.; Stezelberger, T.; Wieman, H.; Battaglia, M.; Hooberman, B.; Tompkins, L.
This paper summarizes the recent progress in the design and characterization of CMOS pixel sensors at LBNL. Results of lab tests, beam tests and radiation hardness tests carried out at LBNL on a test structure with pixels of various sizes are reported. The first results of the characterization of back-thinned CMOS pixel sensors are also reported, and future plans and activities are discussed.
CMOS Image Sensors: Electronic Camera On A Chip
NASA Technical Reports Server (NTRS)
Fossum, E. R.
Recent advancements in CMOS image sensor technology are reviewed, including both passive pixel sensors and active pixel sensors. On- chip analog to digital converters and on-chip timing and control circuits permit realization of an electronic camera-on-a-chip. Highly miniaturized imaging systems based on CMOS image sensor technology are emerging as a competitor to charge-coupled devices for low cost uses.
Lee, Norman H; Saeed, Alexander I
Gene expression microarrays are being used widely to address a myriad of complex biological questions. To gather meaningful expression data, it is crucial to have a firm understanding of the steps involved in the application of microarrays. The available microarray platforms are discussed along with their advantages and disadvantages. Additional considerations include study design, quality control and systematic assessment of microarray performance, RNA-labeling strategies, sample allocation, signal amplification schemes, defining the number of appropriate biological replicates, data normalization, statistical approaches to identify differentially regulated genes, and clustering algorithms for data visualization. In this chapter, the underlying principles regarding microarrays are reviewed, to serve as a guide when navigating through this powerful technology. PMID:17332646
Microarrays--status and prospects.
Venkatasubbarao, Srivatsa
Microarrays have become an extremely important research tool for life science researchers and are also beginning to be used in diagnostic, treatment and monitoring applications. This article provides a detailed description of microarrays prepared by in situ synthesis, deposition using microspotting methods, nonplanar bead arrays, flow-through microarrays, optical fiber bundle arrays and nanobarcodes. The problems and challenges in the development of microarrays, development of standards and diagnostic microarrays are described. Tables summarizing the vendor list of various derivatized microarray surfaces, commercially sold premade microarrays, bead arrays and unique microarray products in development are also included. PMID:15542153
Regenerative switching CMOS system
Welch, J.D.
Complementary Metal Oxide Semiconductor (CMOS) Schottky barrier Field Effect Transistor systems, which are a series combination of N and P-Channel MOSFETS, in which Source Schottky barrier junctions of the N and P-Channel Schottky barrier MOSFETS are electrically interconnected, (rather than the Drains as in conventional diffused junction CMOS), which Schottky barrier MOSFET system demonstrates Regenerative Inverting Switching Characteristics in use are disclosed. Both the N and P-Channel Schottky barrier MOSFET devices are unique in that they provide operational Drain Current vs. Drain to Source voltage as a function of Gate voltage only where the polarities of the Drain voltage and Gate voltage are opposite, referenced to the Source as a common terminal, and where the polarity of the voltage applied to the Gate is appropriate to cause Channel inversion. Experimentally derived results which demonstrate and verify the operation of N and P-Channel Schottky barrier MOSFETS actually fabricated on P and N-type Silicon respectively, by a common procedure using vacuum deposited Chromium as a Schottky barrier forming metal, are also provided. 14 figs.
Regenerative switching CMOS system
Welch, James D.
Complementary Metal Oxide Semiconductor (CMOS) Schottky barrier Field Effect Transistor systems, which are a seriesed combination of N and P-Channel MOSFETS, in which Source Schottky barrier junctions of the N and P-Channel Schottky barrier MOSFETS are electically interconnected, (rather than the Drains as in conventional diffused junction CMOS), which Schottky barrier MOSFET system demonstrates Regenerative Inverting Switching Characteristics in use are disclosed. Both the N and P-Channel Schottky barrier MOSFET devices are unique in that they provide operational Drain Current vs. Drain to Source voltage as a function of Gate voltage only where the polarities of the Drain voltage and Gate voltage are opposite, referenced to the Source as a common terminal, and where the polarity of the voltage applied to the Gate is appropriate to cause Channel inversion. Experimentally derived results which demonstrate and verify the operation of N and P-Channel Schottky barrier MOSFETS actually fabricated on P and N-type Silicon respectively, by a common procedure using vacuum deposited Chromium as a Schottky barrier forming metal, are also provided.
Microarray Analysis in Glioblastomas.
Bhawe, Kaumudi M; Aghi, Manish K
Microarray analysis in glioblastomas is done using either cell lines or patient samples as starting material. A survey of the current literature points to transcript-based microarrays and immunohistochemistry (IHC)-based tissue microarrays as being the preferred methods of choice in cancers of neurological origin. Microarray analysis may be carried out for various purposes including the following: i. To correlate gene expression signatures of glioblastoma cell lines or tumors with response to chemotherapy (DeLay et al., Clin Cancer Res 18(10):2930-2942, 2012). ii. To correlate gene expression patterns with biological features like proliferation or invasiveness of the glioblastoma cells (Jiang et al., PLoS One 8(6):e66008, 2013). iii. To discover new tumor classificatory systems based on gene expression signature, and to correlate therapeutic response and prognosis with these signatures (Huse et al., Annu Rev Med 64(1):59-70, 2013; Verhaak et al., Cancer Cell 17(1):98-110, 2010). While investigators can sometimes use archived tumor gene expression data available from repositories such as the NCBI Gene Expression Omnibus to answer their questions, new arrays must often be run to adequately answer specific questions. Here, we provide a detailed description of microarray methodologies, how to select the appropriate methodology for a given question, and analytical strategies that can be used. Experimental methodology for protein microarrays is outside the scope of this chapter, but basic sample preparation techniques for transcript-based microarrays are included here. PMID:26113463
Microarray-integrated optoelectrofluidic immunoassay system.
Han, Dongsik; Park, Je-Kyun
A microarray-based analytical platform has been utilized as a powerful tool in biological assay fields. However, an analyte depletion problem due to the slow mass transport based on molecular diffusion causes low reaction efficiency, resulting in a limitation for practical applications. This paper presents a novel method to improve the efficiency of microarray-based immunoassay via an optically induced electrokinetic phenomenon by integrating an optoelectrofluidic device with a conventional glass slide-based microarray format. A sample droplet was loaded between the microarray slide and the optoelectrofluidic device on which a photoconductive layer was deposited. Under the application of an AC voltage, optically induced AC electroosmotic flows caused by a microarray-patterned light actively enhanced the mass transport of target molecules at the multiple assay spots of the microarray simultaneously, which reduced tedious reaction time from more than 30 min to 10 min. Based on this enhancing effect, a heterogeneous immunoassay with a tiny volume of sample (5 μl) was successfully performed in the microarray-integrated optoelectrofluidic system using immunoglobulin G (IgG) and anti-IgG, resulting in improved efficiency compared to the static environment. Furthermore, the application of multiplex assays was also demonstrated by multiple protein detection. PMID:27190571
OLED-on-CMOS integration for optoelectronic sensor applications
NASA Astrophysics Data System (ADS)
Vogel, Uwe; Kreye, Daniel; Reckziegel, Sven; Törker, Michael; Grillberger, Christiane; Amelung, Jörg
Highly-efficient, low-voltage organic light emitting diodes (OLEDs) are well suitable for post-processing integration onto the top metal layer of CMOS devices. This has been proven for OLED microdisplays so far. Moreover, OLEDon- CMOS technology may also be excellently suitable for various optoelectronic sensor applications by combining highly efficient emitters, use of low-cost materials and cost-effective manufacturing together with silicon-inherent photodetectors and CMOS circuitry. The use of OLEDs on CMOS substrates requires a top-emitting, low-voltage and highly efficient OLED structure. By reducing the operating voltage for the OLED below 5V, the costs for the CMOS process can be reduced, because a process without high-voltage option can be used. Red, orange, white, green and blue OLED-stacks with doped charge transport layers were prepared on different dualmetal layer CMOS test substrates without active transistor area. Afterwards, the different devices were measured and compared with respect to their performance (current, luminance, voltage, luminance dependence on viewing angle, optical outcoupling etc.). Low operating voltages of 2.4V at 100cd/m2 for the red p-i-n type phosphorescent emitting OLED stack, 2.5V at 100cd/m2 for the orange phosphorescent emitting OLED stack and 3.2V at 100cd/m2 for the white fluorescent emitting OLED have been achieved here. Therefore, those OLED stacks are suitable for use in a CMOS process even within a regular 5V process option. Moreover, the operating voltage achieved so far is expected to be reduced further when using different top electrode materials. Integrating such OLEDs on a CMOS-substrate provide a preferable choice for silicon-based optical microsystems targeted towards optoelectronic sensor applications, as there are integrated light barriers, optocouplers, or lab-onchip devices.
Optimisation algorithms for microarray biclustering.
Perrin, Dimitri; Duhamel, Christophe
In providing simultaneous information on expression profiles for thousands of genes, microarray technologies have, in recent years, been largely used to investigate mechanisms of gene expression. Clustering and classification of such data can, indeed, highlight patterns and provide insight on biological processes. A common approach is to consider genes and samples of microarray datasets as nodes in a bipartite graphs, where edges are weighted e.g. based on the expression levels. In this paper, using a previously-evaluated weighting scheme, we focus on search algorithms and evaluate, in the context of biclustering, several variations of Genetic Algorithms. We also introduce a new heuristic "Propagate", which consists in recursively evaluating neighbour solutions with one more or one less active conditions. The results obtained on three well-known datasets show that, for a given weighting scheme, optimal or near-optimal solutions can be identified. PMID:24109756
Dynamic of active microorganisms inhabiting a bioleaching industrial heap of low‐grade copper sulfide ore monitored by real‐time PCR and oligonucleotide prokaryotic acidophile microarray
Remonsellez, Francisco; Galleguillos, Felipe; Moreno‐Paz, Mercedes; Parro, Víctor; Acosta, Mauricio; Demergasso, Cecilia
Summary The bioleaching of metal sulfide has developed into a very important industrial process and understanding the microbial dynamic is key to advancing commercial bioleaching operations. Here we report the first quantitative description of the dynamic of active communities in an industrial bioleaching heap. Acidithiobacillus ferrooxidans was the most abundant during the first part of the leaching cycle, while the abundance of Leptospirillum ferriphilum and Ferroplasma acidiphilum increased with age of the heap. Acidithiobacillus thiooxidans kept constant throughout the leaching cycle, and Firmicutes group showed a low and a patchy distribution in the heap. The Acidiphilium‐like bacteria reached their highest abundance corresponding to the amount of autotrophs. The active microorganisms in the leaching system were determined using two RNA‐based sensitive techniques. In most cases, the 16S rRNA copy numbers of At. ferrooxidans, L. ferriphilum, At. thiooxidans and F. acidiphilum, was concomitant with the DNA copy numbers, whereas Acidiphilium‐like bacteria and some Firmicutes members did not show a clear correlation between 16S rRNA accumulation and DNA copy numbers. However, the prokaryotic acidophile microarray (PAM) analysis showed active members of Alphaproteobacteria in all samples and of Sulfobacillus genus in older ones. Also, new active groups such as Actinobacteria and Acidobacterium genus were detected by PAM. The results suggest that changes during the leaching cycle in chemical and physical conditions, such as pH and Fe3+/Fe2+ ion rate, are primary factors shaping the microbial dynamic in the heap. PMID:21255296
Evaluation of Surface Chemistries for Antibody Microarrays
Seurynck-Servoss, Shannon L.; White, Amanda M.; Baird, Cheryl L.; Rodland, Karin D.; Zangar, Richard C.
Antibody microarrays are an emerging technology that promises to be a powerful tool for the detection of disease biomarkers. The current technology for protein microarrays has been primarily derived from DNA microarrays and is not fully characterized for use with proteins. For example, there are a myriad of surface chemistries that are commercially available for antibody microarrays, but no rigorous studies that compare these different surfaces. Therefore, we have used an enzyme-linked immunosorbent assay (ELISA) microarray platform to analyze 16 different commercially available slide types. Full standard curves were generated for 24 different assays. We found that this approach provides a rigorous and quantitative system for comparing the different slide types based on spot size and morphology, slide noise, spot background, lower limit of detection, and reproducibility. These studies demonstrate that the properties of the slide surface affect the activity of immobilized antibodies and the quality of data produced. Although many slide types can produce useful data, glass slides coated with poly-L-lysine or aminosilane, with or without activation with a crosslinker, consistently produce superior results in the ELISA microarray analyses we performed.
Nanotechnologies in protein microarrays.
Krizkova, Sona; Heger, Zbynek; Zalewska, Marta; Moulick, Amitava; Adam, Vojtech; Kizek, Rene
Protein microarray technology became an important research tool for study and detection of proteins, protein-protein interactions and a number of other applications. The utilization of nanoparticle-based materials and nanotechnology-based techniques for immobilization allows us not only to extend the surface for biomolecule immobilization resulting in enhanced substrate binding properties, decreased background signals and enhanced reporter systems for more sensitive assays. Generally in contemporarily developed microarray systems, multiple nanotechnology-based techniques are combined. In this review, applications of nanoparticles and nanotechnologies in creating protein microarrays, proteins immobilization and detection are summarized. We anticipate that advanced nanotechnologies can be exploited to expand promising fields of proteins identification, monitoring of protein-protein or drug-protein interactions, or proteins structures. PMID:26039143
High-performance monolithic CMOS detectors for space applications
NASA Astrophysics Data System (ADS)
Saint-Pe, Olivier; Tulet, Michel; Davancens, Robert; Larnaudie, Franck; Vignon, Bruno; Magnan, Pierre; Farre, Jean A.; Corbiere, Franck; Martin-Gonthier, Philippe
During the last 10 years, research about CMOS image sensors (also called APS - Active Pixel Sensors) has been intensively carried out, in order to offer an alternative to CCDs as image sensors. This is particularly the case for space applications as CMOS image sensors feature characteristics which are obviously of interest for flight hardware: parallel or semi-parallel architecture, on chip control and processing electronics, low power dissipation, high level of radiation tolerance... Many image sensor companies, institutes and laboratories have demonstrated the compatibility of CMOS image sensors with consumer applications: micro-cameras, video-conferencing, digital- still cameras. And recent designs have shown that APS is getting closer to the CCD in terms of performance level. However, he large majority of the existing products do not offer the specific features which are required for many space applications. ASTRIUM and SUPAERO/CIMI have decided to work together in view of developing CMOS image sensors dedicated to space business. After a brief presentation of the team organization for space image sensor design and production, the latest results of a high performances 512 X 512 pixels CMOS device characterization are presented with emphasis on the achieved electro-optical performance. Finally, the on going and short-term coming activities of the team are discussed.
Design and Fabrication of Vertically-Integrated CMOS Image Sensors
Skorka, Orit; Joseph, Dileepan
Technologies to fabricate integrated circuits (IC) with 3D structures are an emerging trend in IC design. They are based on vertical stacking of active components to form heterogeneous microsystems. Electronic image sensors will benefit from these technologies because they allow increased pixel-level data processing and device optimization. This paper covers general principles in the design of vertically-integrated (VI) CMOS image sensors that are fabricated by flip-chip bonding. These sensors are composed of a CMOS die and a photodetector die. As a specific example, the paper presents a VI-CMOS image sensor that was designed at the University of Alberta, and fabricated with the help of CMC Microsystems and Micralyne Inc. To realize prototypes, CMOS dies with logarithmic active pixels were prepared in a commercial process, and photodetector dies with metal-semiconductor-metal devices were prepared in a custom process using hydrogenated amorphous silicon. The paper also describes a digital camera that was developed to test the prototype. In this camera, scenes captured by the image sensor are read using an FPGA board, and sent in real time to a PC over USB for data processing and display. Experimental results show that the VI-CMOS prototype has a higher dynamic range and a lower dark limit than conventional electronic image sensors. PMID:22163860
Study of antimutagenic and antioxidant activities of gallic acid and 1,2,3,4,6-pentagalloylglucose from Pistacia lentiscus. Confirmation by microarray expression profiling.
Abdelwahed, Afef; Bouhlel, Ines; Skandrani, Ines; Valenti, Kita; Kadri, Malika; Guiraud, Pascal; Steiman, Régine; Mariotte, Anne-Marie; Ghedira, Kamel; Laporte, François; Dijoux-Franca, Marie-Geneviève; Chekir-Ghedira, Leila
In vitro antioxidant and antimutagenic activities of two polyphenols isolated from the fruits of Pistacia lentiscus was assessed. Antioxidant activity was determined by the ability of each compound to scavenge the free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH*), to inhibit xanthine oxidase and to inhibit the lipid peroxidation induced by H(2)O(2) in K562 cell line. Antimutagenic activity was assayed with SOS chromotest using Escherichia coli PQ37 as tester strain and Comet assay using K562 cell line. 1,2,3,4,6-Pentagalloylglucose was found to be more effective to scavenge DPPH* radical and protect against lipid peroxidation. Moreover, these two compounds induced an inhibitory activity against nifuroxazide and aflatoxin B1 mutagenicity. The protective effect exhibited by these molecules was also determined by analysis of gene expression as response to an oxidative stress. For this purpose, we used a cDNA-microarray containing 82 genes related to cell defense, essentially represented by antioxidant and DNA repair proteins. We found that 1,2,3,4,6-pentagalloylglucose induced a decrease in the expression of 11 transcripts related to antioxidant enzymes family (GPX1, TXN, AOE372, SHC1 and SEPW1) and DNA repair (POLD1, APEX, POLD2, MPG, PARP and XRCC5). The use of Gallic acid, induced expression of TXN, TXNRD1, AOE372, GSS (antioxidant enzymes) and LIG4, POLD2, MPG, GADD45A, PCNA, RPA2, DDIT3, HMOX2, XPA, TDG, ERCC1 and GTF2H1 (DNA repair) as well as the repression of GPX1, SEPW1, POLD1 and SHC1 gene expression. PMID:17129579
Microarray analysis of tick-infested skin in resistant and susceptible cattle confirms the role of inflammatory pathways in immune activation and larval rejection.
Carvalho, Wanessa Araújo; Domingues, Robert; de Azevedo Prata, Marcia Cristina; da Silva, Marcos Vinícius G B; de Oliveira, Guilherme Corrêa; Guimarães, Simone Eliza Facioni; Machado, Marco Antônio
Tick bites promote activation of an inflammatory process that is influenced by bovine genetic composition and its history of previous exposure. Taurine and indicine breeds are known to differ on its immune response development against Rhipicephalus microplus. Nevertheless, further investigation about the complex molecular pathways involved in the development of immune response to tick infestation in cattle presenting the same genetic background is mandatory. The aim of this work was to access the early immune response triggered by R. microplus larvae attachment in previously selected resistant and susceptible animals in a bovine F2 population derived from Gyr (Bos indicus)×Holstein (Bos taurus) crosses. Microarray data analysis of RNA samples from tick infested skin was used to evaluate the gene expression at 0, 24 and 48h after R. microplus larvae attachment. Our experimental design allowed us to deeply explore the immune response related to R. microplus infestation avoiding the innate differences between these breeds. The differentially expressed genes found reveal networks and pathways that suggest a key role of lipid metabolism in inflammation control and impairment of tick infestation in resistant animals. Acute phase response also seems to be impaired in susceptible animals. These results provide new insights about early immune response against ticks and raise the possibility of using immunomodulation processes to improve and develop novel tools for tick control. PMID:25108850
Microarrays for Undergraduate Classes
ERIC Educational Resources Information Center
Hancock, Dale; Nguyen, Lisa L.; Denyer, Gareth S.; Johnston, Jill M.
A microarray experiment is presented that, in six laboratory sessions, takes undergraduate students from the tissue sample right through to data analysis. The model chosen, the murine erythroleukemia cell line, can be easily cultured in sufficient quantities for class use. Large changes in gene expression can be induced in these cells by…
Studying cellular processes and detecting disease with protein microarrays
Zangar, Richard C.; Varnum, Susan M.; Bollinger, Nikki
Protein microarrays are a rapidly developing analytic tool with diverse applications in biomedical research. These applications include profiling of disease markers or autoimmune responses, understanding molecular pathways, protein modifications and protein activities. One factor that is driving this expanding usage is the wide variety of experimental formats that protein microarrays can take. In this review, we provide a short, conceptual overview of the different approaches for protein microarray. We then examine some of the most significant applications of these microarrays to date, with an emphasis on how global protein analyses can be used to facilitate biomedical research.
Improved Space Object Observation Techniques Using CMOS Detectors
NASA Astrophysics Data System (ADS)
Schildknecht, T.; Hinze, A.; Schlatter, P.; Silha, J.; Peltonen, J.; Santti, T.; Flohrer, T.
CMOS-sensors, or in general Active Pixel Sensors (APS), are rapidly replacing CCDs in the consumer camera market. Due to significant technological advances during the past years these devices start to compete with CCDs also for demanding scientific imaging applications, in particular in the astronomy community. CMOS detectors offer a series of inherent advantages compared to CCDs, due to the structure of their basic pixel cells, which each contain their own amplifier and readout electronics. The most prominent advantages for space object observations are the extremely fast and flexible readout capabilities, feasibility for electronic shuttering and precise epoch registration, and the potential to perform image processing operations on-chip and in real-time. Presently applied and proposed optical observation strategies for space debris surveys and space surveillance applications had to be analyzed. The major design drivers were identified and potential benefits from using available and future CMOS sensors were assessed. The major challenges and design drivers for ground-based and space-based optical observation strategies have been analyzed. CMOS detector characteristics were critically evaluated and compared with the established CCD technology, especially with respect to the above mentioned observations. Similarly, the desirable on-chip processing functionalities which would further enhance the object detection and image segmentation were identified. Finally, the characteristics of a particular CMOS sensor available at the Zimmerwald observatory were analyzed by performing laboratory test measurements.
Microarray Analysis of Genes Involved with Shell Strength in Layer Shell Gland at the Early Stage of Active Calcification
Liu, Zhangguo; Zheng, Qi; Zhang, Xueyu; Lu, Lizhi
The objective of this study was to get a comprehensive understanding of how genes in chicken shell gland modulate eggshell strength at the early stage of active calcification. Four 32-week old of purebred Xianju hens with consistent high or low shell breakage strength were grouped into two pairs. Using Affymetrix Chicken Array, a whole-transcriptome analysis was performed on hen's shell gland at 9 h post oviposition. Gene ontology enrichment analysis for differentially expressed (DE) transcripts was performed using the web-based GOEAST, and the validation of DE-transcripts was tested by qRT-PCR. 1,195 DE-transcripts, corresponding to 941 unique genes were identified in hens with strong eggshell compared to weak shell hens. According to gene ontology annotations, there are 77 DE-transcripts encoding ion transporters and secreted extracellular matrix proteins, and at least 26 DE-transcripts related to carbohydrate metabolism or post-translation glycosylation modification; furthermore, there are 88 signaling DE-transcripts. GO term enrichment analysis suggests that some DE-transcripts mediate reproductive hormones or neurotransmitters to affect eggshell quality through a complex suite of biophysical processes. These results reveal some candidate genes involved with eggshell strength at the early stage of active calcification which may facilitate our understanding of regulating mechanisms of eggshell quality. PMID:25049830
CMOS Integrated Carbon Nanotube Sensor
Perez, M. S.; Lerner, B.; Boselli, A.; Lamagna, A.; Obregon, P. D. Pareja; Julian, P. M.; Mandolesi, P. S.; Buffa, F. A.
Recently carbon nanotubes (CNTs) have been gaining their importance as sensors for gases, temperature and chemicals. Advances in fabrication processes simplify the formation of CNT sensor on silicon substrate. We have integrated single wall carbon nanotubes (SWCNTs) with complementary metal oxide semiconductor process (CMOS) to produce a chip sensor system. The sensor prototype was designed and fabricated using a 0.30 um CMOS process. The main advantage is that the device has a voltage amplifier so the electrical measure can be taken and amplified inside the sensor. When the conductance of the SWCNTs varies in response to media changes, this is observed as a variation in the output tension accordingly.
Advancing microarray assembly with acoustic dispensing technology.
Wong, E Y; Diamond, S L
In the assembly of microarrays and microarray-based chemical assays and enzymatic bioassays, most approaches use pins for contact spotting. Acoustic dispensing is a technology capable of nanoliter transfers by using acoustic energy to eject liquid sample from an open source well. Although typically used for well plate transfers, when applied to microarraying, it avoids the drawbacks of undesired physical contact with the sample; difficulty in assembling multicomponent reactions on a chip by readdressing, a rigid mode of printing that lacks patterning capabilities; and time-consuming wash steps. We demonstrated the utility of acoustic dispensing by delivering human cathepsin L in a drop-on-drop fashion into individual 50-nanoliter, prespotted reaction volumes to activate enzyme reactions at targeted positions on a microarray. We generated variable-sized spots ranging from 200 to 750 microm (and higher) and handled the transfer of fluorescent bead suspensions with increasing source well concentrations of 0.1 to 10 x 10(8) beads/mL in a linear fashion. There are no tips that can clog, and liquid dispensing CVs are generally below 5%. This platform expands the toolbox for generating analytical arrays and meets needs associated with spatially addressed assembly of multicomponent microarrays on the nanoliter scale. PMID:19035650
A Synthetic Kinome Microarray Data Generator
Maleki, Farhad; Kusalik, Anthony
Cellular pathways involve the phosphorylation and dephosphorylation of proteins. Peptide microarrays called kinome arrays facilitate the measurement of the phosphorylation activity of hundreds of proteins in a single experiment. Analyzing the data from kinome microarrays is a multi-step process. Typically, various techniques are possible for a particular step, and it is necessary to compare and evaluate them. Such evaluations require data for which correct analysis results are known. Unfortunately, such kinome data is not readily available in the community. Further, there are no established techniques for creating artificial kinome datasets with known results and with the same characteristics as real kinome datasets. In this paper, a methodology for generating synthetic kinome array data is proposed. The methodology relies on actual intensity measurements from kinome microarray experiments and preserves their subtle characteristics. The utility of the methodology is demonstrated by evaluating methods for eliminating heterogeneous variance in kinome microarray data. Phosphorylation intensities from kinome microarrays often exhibit such heterogeneous variance and its presence can negatively impact downstream statistical techniques that rely on homogeneity of variance. It is shown that using the output from the proposed synthetic data generator, it is possible to critically compare two variance stabilization methods.
Microarrays under the microscope.
Wildsmith, S E; Elcock, F J
Microarray technology is a rapidly advancing area, which is gaining popularity in many biological disciplines from drug target identification to predictive toxicology. Over the past few years, there has been a dramatic increase in the number of methods and techniques available for carrying out this form of gene expression analysis. The techniques and associated peripherals, such as slide types, deposition methods, robotics, and scanning equipment, are undergoing constant improvement, helping to drive the technology forward in terms of robustness and ease of use. These rapid developments, combined with the number of options available and the associated hyperbole, can prove daunting for the new user. This review aims to guide the researcher through the various steps of conducting microarray experiments, from initial strategy to analysing the data, with critical examination of the benefits and disadvantages along the way. PMID:11212888
Navigating Public Microarray Databases
Bähler, Jürg
With the ever-escalating amount of data being produced by genome-wide microarray studies, it is of increasing importance that these data are captured in public databases so that researchers can use this information to complement and enhance their own studies. Many groups have set up databases of expression data, ranging from large repositories, which are designed to comprehensively capture all published data, through to more specialized databases. The public repositories, such as ArrayExpress at the European Bioinformatics Institute contain complete datasets in raw format in addition to processed data, whilst the specialist databases tend to provide downstream analysis of normalized data from more focused studies and data sources. Here we provide a guide to the use of these public microarray resources. PMID:18629145
Navigating public microarray databases.
Penkett, Christopher J; Bähler, Jürg
With the ever-escalating amount of data being produced by genome-wide microarray studies, it is of increasing importance that these data are captured in public databases so that researchers can use this information to complement and enhance their own studies. Many groups have set up databases of expression data, ranging from large repositories, which are designed to comprehensively capture all published data, through to more specialized databases. The public repositories, such as ArrayExpress at the European Bioinformatics Institute contain complete datasets in raw format in addition to processed data, whilst the specialist databases tend to provide downstream analysis of normalized data from more focused studies and data sources. Here we provide a guide to the use of these public microarray resources. PMID:18629145
Photoelectrochemical synthesis of DNA microarrays
Chow, Brian Y.; Emig, Christopher J.; Jacobson, Joseph M.
Optical addressing of semiconductor electrodes represents a powerful technology that enables the independent and parallel control of a very large number of electrical phenomena at the solid-electrolyte interface. To date, it has been used in a wide range of applications including electrophoretic manipulation, biomolecule sensing, and stimulating networks of neurons. Here, we have adapted this approach for the parallel addressing of redox reactions, and report the construction of a DNA microarray synthesis platform based on semiconductor photoelectrochemistry (PEC). An amorphous silicon photoconductor is activated by an optical projection system to create virtual electrodes capable of electrochemically generating protons; these PEC-generated protons then cleave the acid-labile dimethoxytrityl protecting groups of DNA phosphoramidite synthesis reagents with the requisite spatial selectivity to generate DNA microarrays. Furthermore, a thin-film porous glass dramatically increases the amount of DNA synthesized per chip by over an order of magnitude versus uncoated glass. This platform demonstrates that PEC can be used toward combinatorial bio-polymer and small molecule synthesis. PMID:19706433
A novel colour-sensitive CMOS detector
NASA Astrophysics Data System (ADS)
Langfelder, G.; Longoni, A.; Zaraga, F.
A novel colour-sensitive semiconductor detector is proposed. The device (named Transverse Field Detector (TFD)) can be used to measure the colour of the incident light without any colour filter. The device is completely compatible with standard CMOS processes and is suitable to be integrated in a pixel array for imaging purposes. The working principle is based on the capability of this device to collect at different superficial junctions the carriers, generated at different depths, by means of suitable transverse electric fields. The transverse components of the electric field are generated inside the depleted region by a suitable bias of the superficial junctions. Thanks to the differences in the light absorption coefficients at different wavelengths, the device performs colour separation. Among the advantages of this approach are the capability of an active tuning of the pixel colour response, which can be obtained just by changing the biasing values of collecting junctions, and foreseen higher colour fidelity, thanks to the easy extension to four colour pixels. First test structures of three colours TFD pixels were designed and built in a standard CMOS 90 nm technology. Operative principles of the device and first experimental results are presented.
Fully CMOS analog and digital SiPMs
NASA Astrophysics Data System (ADS)
Zou, Yu; Villa, Federica; Bronzi, Danilo; Tisa, Simone; Tosi, Alberto; Zappa, Franco
Silicon Photomultipliers (SiPMs) are emerging single photon detectors used in many applications requiring large active area, photon-number resolving capability and immunity to magnetic fields. We present three families of analog SiPM fabricated in a reliable and cost-effective fully standard planar CMOS technology with a total photosensitive area of 1×1 mm2. These three families have different active areas with fill-factors (21%, 58.3%, 73.7%) comparable to those of commercial SiPM, which are developed in vertical (current flow) custom technologies. The peak photon detection efficiency in the near-UV tops at 38% (fill-factor included) comparable to commercial custom-process ones and dark count rate density is just a little higher than the best-in-class commercial analog SiPMs. Thanks to the CMOS processing, these new SiPMs can be integrated together with active components and electronics both within the microcell and on-chip, in order to act at the microcell level or to perform global pre-processing. We also report CMOS digital SiPMs in the same standard CMOS technology, based on microcells with digitalized processing, all integrated on-chip. This CMOS digital SiPMs has four 32×1 cells (128 microcells), each consisting of SPAD, active quenching circuit with adjustable dead time, digital control (to switch off noisy SPADs and readout position of detected photons), and fast trigger output signal. The achieved 20% fill-factor is still very good.
Planar CMOS analog SiPMs: design, modeling, and characterization
NASA Astrophysics Data System (ADS)
Zou, Yu; Villa, Federica; Bronzi, Danilo; Tisa, Simone; Tosi, Alberto; Zappa, Franco
Silicon photomultipliers (SiPMs) are large area detectors consisting of an array of single-photon-sensitive microcells, which make SiPMs extremely attractive to substitute the photomultiplier tubes in many applications. We present the design, fabrication, and characterization of analog SiPMs in standard planar 0.35 μm CMOS technology, with about 1 mm × 1 mm total area and different kinds of microcells, based on single-photon avalanche diodes with 30 μm diameter reaching 21.0% fill-factor (FF), 50 μm diameter (FF = 58.3%) or 50 μm square active area with rounded corner of 5 μm radius (FF = 73.7%). We also developed the electrical SPICE model for CMOS SiPMs. Our CMOS SiPMs have 25 V breakdown voltage, in line with most commercial SiPMs and higher gain (8.8 × 106, 13.2 × 106, and 15.0 × 106, respectively). Although dark count rate density is slightly higher than state-of-the-art analog SiPMs, the proposed standard CMOS processing opens the feasibility of integration with active electronics, for switching hot pixels off, drastically reducing the overall dark count rate, or for further on-chip processing.
Tiling Microarray Analysis Tools
Nix, Davis Austin
TiMAT is a package of 23 command line Java applications for use in the analysis of Affymetrix tiled genomic microarray data. TiMAT enables: 1) Rebuilding the genome annotation for entire tiled arrays (repeat filtering, chromosomal coordinate assignment). 2) Post processing of oligo intensity values (quantile normalization, median scaling, PMMM transformation), 3) Significance testing (Wilcoxon rank sum and signed rank tests, intensity difference and ratio tests) and Interval refinement (filtering based on multiple statistics, overlap comparisons), 4) Data visualization (detailed thumbnail/zoomed view with Interval Plots and data export to Affymetrix's Integrated Genome Browser) and Data reports (spreadsheet summaries and detailed profiles)
The use of microarrays in microbial ecology
Andersen, G.L.; He, Z.; DeSantis, T.Z.; Brodie, E.L.; Zhou, J.
Microarrays have proven to be a useful and high-throughput method to provide targeted DNA sequence information for up to many thousands of specific genetic regions in a single test. A microarray consists of multiple DNA oligonucleotide probes that, under high stringency conditions, hybridize only to specific complementary nucleic acid sequences (targets). A fluorescent signal indicates the presence and, in many cases, the abundance of genetic regions of interest. In this chapter we will look at how microarrays are used in microbial ecology, especially with the recent increase in microbial community DNA sequence data. Of particular interest to microbial ecologists, phylogenetic microarrays are used for the analysis of phylotypes in a community and functional gene arrays are used for the analysis of functional genes, and, by inference, phylotypes in environmental samples. A phylogenetic microarray that has been developed by the Andersen laboratory, the PhyloChip, will be discussed as an example of a microarray that targets the known diversity within the 16S rRNA gene to determine microbial community composition. Using multiple, confirmatory probes to increase the confidence of detection and a mismatch probe for every perfect match probe to minimize the effect of cross-hybridization by non-target regions, the PhyloChip is able to simultaneously identify any of thousands of taxa present in an environmental sample. The PhyloChip is shown to reveal greater diversity within a community than rRNA gene sequencing due to the placement of the entire gene product on the microarray compared with the analysis of up to thousands of individual molecules by traditional sequencing methods. A functional gene array that has been developed by the Zhou laboratory, the GeoChip, will be discussed as an example of a microarray that dynamically identifies functional activities of multiple members within a community. The recent version of GeoChip contains more than 24,000 50mer
CMOS output buffer wave shaper
NASA Technical Reports Server (NTRS)
Albertson, L.; Whitaker, S.; Merrell, R.
As the switching speeds and densities of Digital CMOS integrated circuits continue to increase, output switching noise becomes more of a problem. A design technique which aids in the reduction of switching noise is reported. The output driver stage is analyzed through the use of an equivalent RLC circuit. The results of the analysis are used in the design of an output driver stage. A test circuit based on these techniques is being submitted to MOSIS for fabrication.
Compressive Sensing DNA Microarrays
Compressive sensing microarrays (CSMs) are DNA-based sensors that operate using group testing and compressive sensing (CS) principles. In contrast to conventional DNA microarrays, in which each genetic sensor is designed to respond to a single target, in a CSM, each sensor responds to a set of targets. We study the problem of designing CSMs that simultaneously account for both the constraints from CS theory and the biochemistry of probe-target DNA hybridization. An appropriate cross-hybridization model is proposed for CSMs, and several methods are developed for probe design and CS signal recovery based on the new model. Lab experiments suggest that in order to achieve accurate hybridization profiling, consensus probe sequences are required to have sequence homology of at least 80% with all targets to be detected. Furthermore, out-of-equilibrium datasets are usually as accurate as those obtained from equilibrium conditions. Consequently, one can use CSMs in applications in which only short hybridization times are allowed. PMID:19158952
Fabrication of CMOS image sensors
NASA Astrophysics Data System (ADS)
Malinovich, Yacov; Koltin, Ephie; Choen, David; Shkuri, Moshe; Ben-Simon, Meir
In order to provide its customers with sub-micron CMOS fabrication solutions for imaging applications, Tower Semiconductor initiated a project to characterize the optical parameters of Tower's 0.5-micron process. A special characterization test chip was processed using the TS50 process. The results confirmed a high quality process for optical applications. Perhaps the most important result is the process' very low dark current, of 30-50 pA/cm2, using the entire window of process. This very low dark current characteristic was confirmed for a variety of pixel architectures. Additionally, we have succeeded to reduce and virtually eliminate the white spots on large sensor arrays. As a foundry Tower needs to support fabrication of many different imaging products. Therefore we have developed a fabrication methodology that is adjusted to the special needs of optical applications. In order to establish in-line process monitoring of the optical parameters, Tower places a scribe line optical test chip that enables wafer level measurements of the most important parameters, ensuring the optical quality and repeatability of the process. We have developed complementary capabilities like in house deposition of color filter and fabrication of very large are dice using sub-micron CMOS technologies. Shellcase and Tower are currently developing a new CMOS image sensor optical package.
CMOS imager for pointing and tracking applications
NASA Technical Reports Server (NTRS)
Pain, Bedabrata (Inventor); Sun, Chao (Inventor); Yang, Guang (Inventor); Heynssens, Julie B. (Inventor)
Systems and techniques to realize pointing and tracking applications with CMOS imaging devices. In general, in one implementation, the technique includes: sampling multiple rows and multiple columns of an active pixel sensor array into a memory array (e.g., an on-chip memory array), and reading out the multiple rows and multiple columns sampled in the memory array to provide image data with reduced motion artifact. Various operation modes may be provided, including TDS, CDS, CQS, a tracking mode to read out multiple windows, and/or a mode employing a sample-first-read-later readout scheme. The tracking mode can take advantage of a diagonal switch array. The diagonal switch array, the active pixel sensor array and the memory array can be integrated onto a single imager chip with a controller. This imager device can be part of a larger imaging system for both space-based applications and terrestrial applications.
Virulence Characterization of Salmonella enterica by a New Microarray: Detection and Evaluation of the Cytolethal Distending Toxin Gene Activity in the Unusual Host S. Typhimurium
Figueiredo, Rui; Card, Roderick; Nunes, Carla; AbuOun, Manal; Bagnall, Mary C.; Nunez, Javier; Mendonça, Nuno; Anjum, Muna F.; da Silva, Gabriela Jorge
Salmonella enterica is a zoonotic foodborne pathogen that causes acute gastroenteritis in humans. We assessed the virulence potential of one-hundred and six Salmonella strains isolated from food animals and products. A high through-put virulence genes microarray demonstrated Salmonella Pathogenicity Islands (SPI) and adherence genes were highly conserved, while prophages and virulence plasmid genes were variably present. Isolates were grouped by serotype, and virulence plasmids separated S. Typhimurium in two clusters. Atypical microarray results lead to whole genome sequencing (WGS) of S. Infantis Sal147, which identified deletion of thirty-eight SPI-1 genes. Sal147 was unable to invade HeLa cells and showed reduced mortality in Galleria mellonella infection model, in comparison to a SPI-1 harbouring S. Infantis. Microarray and WGS of S. Typhimurium Sal199, established for the first time in S. Typhimurium presence of cdtB and other Typhi-related genes. Characterization of Sal199 showed cdtB genes were upstream of transposase IS911, and co-expressed with other Typhi-related genes. Cell cycle arrest, cytoplasmic distension, and nuclear enlargement were detected in HeLa cells infected by Sal199, but not with S. Typhimurium LT2. Increased mortality of Galleria was detected on infection with Sal199 compared to LT2. Thus, Salmonella isolates were rapidly characterized using a high through-put microarray; helping to identify unusual virulence features which were corroborated by further characterisation. This work demonstrates that the use of suitable screening methods for Salmonella virulence can help assess the potential risk associated with certain Salmonella to humans. Incorporation of such methodology into surveillance could help reduce the risk of emergence of epidemic Salmonella strains. PMID:26244504
CMOS downsizing toward sub-10 nm
NASA Astrophysics Data System (ADS)
Iwai, Hiroshi
Recently, CMOS downsizing has been accelerated very aggressively in both production and research level, and even transistor operation of a 6 nm gate length p-channel MOSFET was reported in a conference. However, many serious problems are expected for implementing such small-geometry MOSFETs into large scale integrated circuits, and it is still questionable whether we can successfully introduce sub-10 nm CMOS LSIs into the market or not. In this paper, limitation and its possible causes for the downscaling of CMOS towards sub-10 nm are discussed with consideration of past CMOS predictions for the limitation.
INDEP approach for leakage reduction in nanoscale CMOS circuits
NASA Astrophysics Data System (ADS)
Sharma, Vijay Kumar; Pattanaik, Manisha; Raj, Balwinder
Complementary metal oxide semiconductor (CMOS) technology scaling for improving speed and functionality turns leakage power one of the major concerns for nanoscale circuits design. The minimization of leakage power is a rising challenge for the design of the existing and future nanoscale CMOS circuits. This paper presents a novel, input-dependent, transistor-level, low leakage and reliable INput DEPendent (INDEP) approach for nanoscale CMOS circuits. INDEP approach is based on Boolean logic calculations for the input signals of the extra inserted transistors within the logic circuit. The gate terminals of extra inserted transistors depend on the primary input combinations of the logic circuits. The appropriate selection of input gate voltages of INDEP transistors are reducing the leakage current efficiently along with rail to rail output voltage swing. The important characteristic of INDEP approach is that it works well in both active as well as standby modes of the circuits. This approach overcomes the limitations created by the prevalent current leakage reduction techniques. The simulation results indicate that INDEP approach mitigates 41.6% and 35% leakage power for 1-bit full adder and ISCAS-85 c17 benchmark circuit, respectively, at 32 nm bulk CMOS technology node.
Analysis of pixel circuits in CMOS image sensors
NASA Astrophysics Data System (ADS)
Mei, Zou; Chen, Nan; Yao, Li-bin
CMOS image sensors (CIS) have lower power consumption, lower cost and smaller size than CCD image sensors. However, generally CCDs have higher performance than CIS mainly due to lower noise. The pixel circuit used in CIS is the first part of the signal processing circuit and connected to photodiode directly, so its performance will greatly affect the CIS or even the whole imaging system. To achieve high performance, CMOS image sensors need advanced pixel circuits. There are many pixel circuits used in CIS, such as passive pixel sensor (PPS), 3T and 4T active pixel sensor (APS), capacitive transimpedance amplifier (CTIA), and passive pixel sensor (PPS). At first, the main performance parameters of each pixel structure including the noise, injection efficiency, sensitivity, power consumption, and stability of bias voltage are analyzed. Through the theoretical analysis of those pixel circuits, it is concluded that CTIA pixel circuit has good noise performance, high injection efficiency, stable photodiode bias, and high sensitivity with small integrator capacitor. Furthermore, the APS and CTIA pixel circuits are simulated in a standard 0.18-μm CMOS process and using a n-well/p-sub photodiode by SPICE and the simulation result confirms the theoretical analysis result. It shows the possibility that CMOS image sensors can be extended to a wide range of applications requiring high performance.
High-content analysis of single cells directly assembled on CMOS sensor based on color imaging.
Tanaka, Tsuyoshi; Saeki, Tatsuya; Sunaga, Yoshihiko; Matsunaga, Tadashi
A complementary metal oxide semiconductor (CMOS) image sensor was applied to high-content analysis of single cells which were assembled closely or directly onto the CMOS sensor surface. The direct assembling of cell groups on CMOS sensor surface allows large-field (6.66 mm×5.32 mm in entire active area of CMOS sensor) imaging within a second. Trypan blue-stained and non-stained cells in the same field area on the CMOS sensor were successfully distinguished as white- and blue-colored images under white LED light irradiation. Furthermore, the chemiluminescent signals of each cell were successfully visualized as blue-colored images on CMOS sensor only when HeLa cells were placed directly on the micro-lens array of the CMOS sensor. Our proposed approach will be a promising technique for real-time and high-content analysis of single cells in a large-field area based on color imaging. PMID:20728336
The Genopolis Microarray Database
Splendiani, Andrea; Brandizi, Marco; Even, Gael; Beretta, Ottavio; Pavelka, Norman; Pelizzola, Mattia; Mayhaus, Manuel; Foti, Maria; Mauri, Giancarlo; Ricciardi-Castagnoli, Paola
Background Gene expression databases are key resources for microarray data management and analysis and the importance of a proper annotation of their content is well understood. Public repositories as well as microarray database systems that can be implemented by single laboratories exist. However, there is not yet a tool that can easily support a collaborative environment where different users with different rights of access to data can interact to define a common highly coherent content. The scope of the Genopolis database is to provide a resource that allows different groups performing microarray experiments related to a common subject to create a common coherent knowledge base and to analyse it. The Genopolis database has been implemented as a dedicated system for the scientific community studying dendritic and macrophage cells functions and host-parasite interactions. Results The Genopolis Database system allows the community to build an object based MIAME compliant annotation of their experiments and to store images, raw and processed data from the Affymetrix GeneChip® platform. It supports dynamical definition of controlled vocabularies and provides automated and supervised steps to control the coherence of data and annotations. It allows a precise control of the visibility of the database content to different sub groups in the community and facilitates exports of its content to public repositories. It provides an interactive users interface for data analysis: this allows users to visualize data matrices based on functional lists and sample characterization, and to navigate to other data matrices defined by similarity of expression values as well as functional characterizations of genes involved. A collaborative environment is also provided for the definition and sharing of functional annotation by users. Conclusion The Genopolis Database supports a community in building a common coherent knowledge base and analyse it. This fills a gap between a local
DNA Microarray-Based Diagnostics.
Marzancola, Mahsa Gharibi; Sedighi, Abootaleb; Li, Paul C H
The DNA microarray technology is currently a useful biomedical tool which has been developed for a variety of diagnostic applications. However, the development pathway has not been smooth and the technology has faced some challenges. The reliability of the microarray data and also the clinical utility of the results in the early days were criticized. These criticisms added to the severe competition from other techniques, such as next-generation sequencing (NGS), impacting the growth of microarray-based tests in the molecular diagnostic market.Thanks to the advances in the underlying technologies as well as the tremendous effort offered by the research community and commercial vendors, these challenges have mostly been addressed. Nowadays, the microarray platform has achieved sufficient standardization and method validation as well as efficient probe printing, liquid handling and signal visualization. Integration of various steps of the microarray assay into a harmonized and miniaturized handheld lab-on-a-chip (LOC) device has been a goal for the microarray community. In this respect, notable progress has been achieved in coupling the DNA microarray with the liquid manipulation microsystem as well as the supporting subsystem that will generate the stand-alone LOC device.In this chapter, we discuss the major challenges that microarray technology has faced in its almost two decades of development and also describe the solutions to overcome the challenges. In addition, we review the advancements of the technology, especially the progress toward developing the LOC devices for DNA diagnostic applications. PMID:26614075
Yarmush, Martin L.; King, Kevin R.
Living cells are remarkably complex. To unravel this complexity, living-cell assays have been developed that allow delivery of experimental stimuli and measurement of the resulting cellular responses. High-throughput adaptations of these assays, known as living-cell microarrays, which are based on microtiter plates, high-density spotting, microfabrication, and microfluidics technologies, are being developed for two general applications: (a) to screen large-scale chemical and genomic libraries and (b) to systematically investigate the local cellular microenvironment. These emerging experimental platforms offer exciting opportunities to rapidly identify genetic determinants of disease, to discover modulators of cellular function, and to probe the complex and dynamic relationships between cells and their local environment. PMID:19413510
Tiling Microarray Analysis Tools
TiMAT is a package of 23 command line Java applications for use in the analysis of Affymetrix tiled genomic microarray data. TiMAT enables: 1) Rebuilding the genome annotation for entire tiled arrays (repeat filtering, chromosomal coordinate assignment). 2) Post processing of oligo intensity values (quantile normalization, median scaling, PMMM transformation), 3) Significance testing (Wilcoxon rank sum and signed rank tests, intensity difference and ratio tests) and Interval refinement (filtering based on multiple statistics, overlap comparisons),more » 4) Data visualization (detailed thumbnail/zoomed view with Interval Plots and data export to Affymetrix's Integrated Genome Browser) and Data reports (spreadsheet summaries and detailed profiles)« less
CMOS digital pixel sensors: technology and applications
NASA Astrophysics Data System (ADS)
Skorka, Orit; Joseph, Dileepan
CMOS active pixel sensor technology, which is widely used these days for digital imaging, is based on analog pixels. Transition to digital pixel sensors can boost signal-to-noise ratios and enhance image quality, but can increase pixel area to dimensions that are impractical for the high-volume market of consumer electronic devices. There are two main approaches to digital pixel design. The first uses digitization methods that largely rely on photodetector properties and so are unique to imaging. The second is based on adaptation of a classical analog-to-digital converter (ADC) for in-pixel data conversion. Imaging systems for medical, industrial, and security applications are emerging lower-volume markets that can benefit from these in-pixel ADCs. With these applications, larger pixels are typically acceptable, and imaging may be done in invisible spectral bands.
Contact CMOS imaging of gaseous oxygen sensor array
Daivasagaya, Daisy S.; Yao, Lei; Yi Yung, Ka; Hajj-Hassan, Mohamad; Cheung, Maurice C.; Chodavarapu, Vamsy P.; Bright, Frank V.
We describe a compact luminescent gaseous oxygen (O2) sensor microsystem based on the direct integration of sensor elements with a polymeric optical filter and placed on a low power complementary metal-oxide semiconductor (CMOS) imager integrated circuit (IC). The sensor operates on the measurement of excited-state emission intensity of O2-sensitive luminophore molecules tris(4,7-diphenyl-1,10-phenanthroline) ruthenium(II) ([Ru(dpp)3]2+) encapsulated within sol–gel derived xerogel thin films. The polymeric optical filter is made with polydimethylsiloxane (PDMS) that is mixed with a dye (Sudan-II). The PDMS membrane surface is molded to incorporate arrays of trapezoidal microstructures that serve to focus the optical sensor signals on to the imager pixels. The molded PDMS membrane is then attached with the PDMS color filter. The xerogel sensor arrays are contact printed on top of the PDMS trapezoidal lens-like microstructures. The CMOS imager uses a 32 × 32 (1024 elements) array of active pixel sensors and each pixel includes a high-gain phototransistor to convert the detected optical signals into electrical currents. Correlated double sampling circuit, pixel address, digital control and signal integration circuits are also implemented on-chip. The CMOS imager data is read out as a serial coded signal. The CMOS imager consumes a static power of 320 µW and an average dynamic power of 625 µW when operating at 100 Hz sampling frequency and 1.8 V DC. This CMOS sensor system provides a useful platform for the development of miniaturized optical chemical gas sensors. PMID:24493909
Results of the 2015 testbeam of a 180 nm AMS High-Voltage CMOS sensor prototype
NASA Astrophysics Data System (ADS)
Benoit, M.; Bilbao de Mendizabal, J.; Casse, G.; Chen, H.; Chen, K.; Di Bello, F. A.; Ferrere, D.; Golling, T.; Gonzalez-Sevilla, S.; Iacobucci, G.; Lanni, F.; Liu, H.; Meloni, F.; Meng, L.; Miucci, A.; Muenstermann, D.; Nessi, M.; Perić, I.; Rimoldi, M.; Ristic, B.; Barrero Pinto, M. Vicente; Vossebeld, J.; Weber, M.; Wu, W.; Xu, L.
Active pixel sensors based on the High-Voltage CMOS technology are being investigated as a viable option for the future pixel tracker of the ATLAS experiment at the High-Luminosity LHC. This paper reports on the testbeam measurements performed at the H8 beamline of the CERN Super Proton Synchrotron on a High-Voltage CMOS sensor prototype produced in 180 nm AMS technology. Results in terms of tracking efficiency and timing performance, for different threshold and bias conditions, are shown.
Deciphering the glycosaminoglycan code with the help of microarrays.
de Paz, Jose L; Seeberger, Peter H
Carbohydrate microarrays have become a powerful tool to elucidate the biological role of complex sugars. Microarrays are particularly useful for the study of glycosaminoglycans (GAGs), a key class of carbohydrates. The high-throughput chip format enables rapid screening of large numbers of potential GAG sequences produced via a complex biosynthesis while consuming very little sample. Here, we briefly highlight the most recent advances involving GAG microarrays built with synthetic or naturally derived oligosaccharides. These chips are powerful tools for characterizing GAG-protein interactions and determining structure-activity relationships for specific sequences. Thereby, they contribute to decoding the information contained in specific GAG sequences. PMID:18563243
Nanosecond monolithic CMOS readout cell
Souchkov, Vitali V.
A pulse shaper is implemented in monolithic CMOS with a delay unit formed of a unity gain buffer. The shaper is formed of a difference amplifier having one input connected directly to an input signal and a second input connected to a delayed input signal through the buffer. An elementary cell is based on the pulse shaper and a timing circuit which gates the output of an integrator connected to the pulse shaper output. A detector readout system is formed of a plurality of elementary cells, each connected to a pixel of a pixel array, or to a microstrip of a plurality of microstrips, or to a detector segment.
Microarray platform for omics analysis
NASA Astrophysics Data System (ADS)
Mecklenburg, Michael; Xie, Bin
Microarray technology has revolutionized genetic analysis. However, limitations in genome analysis has lead to renewed interest in establishing 'omic' strategies. As we enter the post-genomic era, new microarray technologies are needed to address these new classes of 'omic' targets, such as proteins, as well as lipids and carbohydrates. We have developed a microarray platform that combines self- assembling monolayers with the biotin-streptavidin system to provide a robust, versatile immobilization scheme. A hydrophobic film is patterned on the surface creating an array of tension wells that eliminates evaporation effects thereby reducing the shear stress to which biomolecules are exposed to during immobilization. The streptavidin linker layer makes it possible to adapt and/or develop microarray based assays using virtually any class of biomolecules including: carbohydrates, peptides, antibodies, receptors, as well as them ore traditional DNA based arrays. Our microarray technology is designed to furnish seamless compatibility across the various 'omic' platforms by providing a common blueprint for fabricating and analyzing arrays. The prototype microarray uses a microscope slide footprint patterned with 2 by 96 flat wells. Data on the microarray platform will be presented.
Accelerated life testing effects on CMOS microcircuit characteristics, phase 1
NASA Technical Reports Server (NTRS)
Maximow, B.
An accelerated life test of sufficient duration to generate a minimum of 50% cumulative failures in lots of CMOS devices was conducted to provide a basis for determining the consistency of activation energy at 250 C. An investigation was made to determine whether any thresholds were exceeded during the high temperature testing, which could trigger failure mechanisms unique to that temperature. The usefulness of the 250 C temperature test as a predictor of long term reliability was evaluated.
Chemistry of Natural Glycan Microarray
Song, Xuezheng; Heimburg-Molinaro, Jamie; Cummings, Richard D.; Smith, David F.
Glycan microarrays have become indispensable tools for studying protein-glycan interactions. Along with chemo-enzymatic synthesis, glycans isolated from natural sources have played important roles in array development and will continue to be a major source of glycans. N- and O-glycans from glycoproteins, and glycans from glycosphingolipids can be released from corresponding glycoconjugates with relatively mature methods, although isolation of large numbers and quantities of glycans are still very challenging. Glycosylphosphatidylinositol (GPI)-anchors and glycosaminoglycans (GAGs) are less represented on current glycan microarrays. Glycan microarray development has been greatly facilitated by bifunctional fluorescent linkers, which can be applied in a "Shotgun Glycomics" approach to incorporate isolated natural glycans. Glycan presentation on microarrays may affect glycan binding by GBPs, often through multivalent recognition by the GBP. PMID:24487062
Microarray Analysis of Microbial Weathering
NASA Astrophysics Data System (ADS)
Olsson-Francis, K.; van Houdt, R.; Leys, N.; Mergeay, M.; Cockell, C. S.
Microarray analysis of the heavy metal resistant bacterium, Cupriavidus metallidurans CH34 was used to investigate the genes involved in the weathering. The results demonstrated that large porin and membrane transporter genes were unregulated.
Low-cost uncooled infrared detector arrays in standard CMOS
NASA Astrophysics Data System (ADS)
Eminoglu, Selim; Tanrikulu, M. Y.; Akin, Tayfun
This paper reports the development of a low-cost 128 x 128 uncooled infrared focal plane array (FPA) based on suspended and thermally isolated CMOS p+-active/n-well diodes. The FPA is fabricated using a standard 0.35 μm CMOS process followed by simple post-CMOS bulk micromachining that does not require any critical lithography or complicated deposition steps; and therefore, the cost of the uncooled FPA is almost equal to the cost of the CMOS chip. The post-CMOS fabrication steps include an RIE etching to reach the bulk silicon and an anisotropic silicon etching to obtain thermally isolated pixels. During the RIE etching, CMOS metal layers are used as masking layers, and therefore, narrow openings such as 2 μm can be defined between the support arms. This approach allows achieving small pixel size of 40 μm x 40 μm with a fill factor of 44%. The FPA is scanned at 30 fps by monolithically integrated multi-channel parallel readout circuitry which is composed of low-noise differential transconductance amplifiers, switched capacitor (SC) integrators, sample-and-hold circuits, and various other circuit blocks for reducing the effects of variations in detector voltage and operating temperature. The fabricated detector has a temperature coefficient of -2 mV/K, a thermal conductance value of 1.8 x 10-7 W/K, and a thermal time constant value of 36 msec, providing a measured DC responsivity (R) of 4970 V/W under continuous bias. Measured detector noise is 0.69 μV in 8 kHz bandwidth at 30 fps scanning rate, resulting a measured detectivity (D*) of 9.7 x 108 cm√HzW. Contribution of the 1/f noise component is found to be negligible due to the single crystal nature of the silicon n-well and its low value at low bias levels. The noise of the readout circuit is measured as 0.76 μV, resulting in an expected NETD value of 1 K when scanned at 30 fps using f=1 optics. This NETD value can be decreased below 350 mK by decreasing the electrical bandwidth with the help of increased
A Human Platelet Receptor Protein Microarray Identifies the High Affinity Immunoglobulin E Receptor Subunit α (FcεR1α) as an Activating Platelet Endothelium Aggregation Receptor 1 (PEAR1) Ligand*
Sun, Yi; Vandenbriele, Christophe; Kauskot, Alexandre; Verhamme, Peter; Hoylaerts, Marc F.; Wright, Gavin J.
Genome-wide association studies to identify loci responsible for platelet function and cardiovascular disease susceptibility have repeatedly identified polymorphisms linked to a gene encoding platelet endothelium aggregation receptor 1 (PEAR1), an "orphan" cell surface receptor that is activated to stabilize platelet aggregates. To investigate how PEAR1 signaling is initiated, we sought to identify its extracellular ligand by creating a protein microarray representing the secretome and receptor repertoire of the human platelet. Using an avid soluble recombinant PEAR1 protein and a systematic screening assay designed to detect extracellular interactions, we identified the high affinity immunoglobulin E (IgE) receptor subunit α (FcεR1α) as a PEAR1 ligand. FcεR1α and PEAR1 directly interacted through their membrane-proximal Ig-like and 13th epidermal growth factor domains with a relatively strong affinity (KD ∼ 30 nm). Precomplexing FcεR1α with IgE potently inhibited the FcεR1α-PEAR1 interaction, and this was relieved by the anti-IgE therapeutic omalizumab. Oligomerized FcεR1α potentiated platelet aggregation and led to PEAR1 phosphorylation, an effect that was also inhibited by IgE. These findings demonstrate how a protein microarray resource can be used to gain important insight into the function of platelet receptors and provide a mechanistic basis for the initiation of PEAR1 signaling in platelet aggregation. PMID:25713122
A fully integrated CMOS inverse sine circuit for computational systems
NASA Astrophysics Data System (ADS)
Seon, Jong-Kug
An inverse trigonometric function generator using CMOS technology is presented and implemented. The development and synthesis of inverse trigonometric functional circuits based on the simple approximation equations are also introduced. The proposed inverse sine function generator has the infinite input range and can be used in many measurement and instrumentation systems. The nonlinearity of less than 2.8% for the entire input range of 0.5 Vp-p with a small-signal bandwidth of 3.2 MHz is achieved. The chip implemented in 0.25 μm CMOS process operates from a single 1.8 V supply. The measured power consumption and the active chip area of the inverse sine function circuit are 350 μW and 0.15 mm2, respectively.
Monolithic CMOS-MEMS integration for high-g accelerometers
NASA Astrophysics Data System (ADS)
Narasimhan, Vinayak; Li, Holden; Tan, Chuan Seng
This paper highlights work-in-progress towards the conceptualization, simulation, fabrication and initial testing of a silicon-germanium (SiGe) integrated CMOS-MEMS high-g accelerometer for military, munition, fuze and shock measurement applications. Developed on IMEC's SiGe MEMS platform, the MEMS offers a dynamic range of 5,000 g and a bandwidth of 12 kHz. The low noise readout circuit adopts a chopper-stabilization technique implementing the CMOS through the TSMC 0.18 µm process. The device structure employs a fully differential split comb-drive set up with two sets of stators and a rotor all driven separately. Dummy structures acting as protective over-range stops were designed to protect the active components when under impacts well above the designed dynamic range.
Carbon Nanotube Integration with a CMOS Process
Perez, Maximiliano S.; Lerner, Betiana; Resasco, Daniel E.; Pareja Obregon, Pablo D.; Julian, Pedro M.; Mandolesi, Pablo S.; Buffa, Fabian A.; Boselli, Alfredo; Lamagna, Alberto
This work shows the integration of a sensor based on carbon nanotubes using CMOS technology. A chip sensor (CS) was designed and manufactured using a 0.30 μm CMOS process, leaving a free window on the passivation layer that allowed the deposition of SWCNTs over the electrodes. We successfully investigated with the CS the effect of humidity and temperature on the electrical transport properties of SWCNTs. The possibility of a large scale integration of SWCNTs with CMOS process opens a new route in the design of more efficient, low cost sensors with high reproducibility in their manufacture. PMID:22319330
Improved Space Object Orbit Determination Using CMOS Detectors
NASA Astrophysics Data System (ADS)
Schildknecht, T.; Peltonen, J.; Sännti, T.; Silha, J.; Flohrer, T.
CMOS-sensors, or in general Active Pixel Sensors (APS), are rapidly replacing CCDs in the consumer camera market. Due to significant technological advances during the past years these devices start to compete with CCDs also for demanding scientific imaging applications, in particular in the astronomy community. CMOS detectors offer a series of inherent advantages compared to CCDs, due to the structure of their basic pixel cells, which each contains their own amplifier and readout electronics. The most prominent advantages for space object observations are the extremely fast and flexible readout capabilities, feasibility for electronic shuttering and precise epoch registration, and the potential to perform image processing operations on-chip and in real-time. The major challenges and design drivers for ground-based and space-based optical observation strategies have been analyzed. CMOS detector characteristics were critically evaluated and compared with the established CCD technology, especially with respect to the above mentioned observations. Similarly, the desirable on-chip processing functionalities which would further enhance the object detection and image segmentation were identified. Finally, we simulated several observation scenarios for ground- and space-based sensor by assuming different observation and sensor properties. We will introduce the analyzed end-to-end simulations of the ground- and space-based strategies in order to investigate the orbit determination accuracy and its sensitivity which may result from different values for the frame-rate, pixel scale, astrometric and epoch registration accuracies. Two cases were simulated, a survey using a ground-based sensor to observe objects in LEO for surveillance applications, and a statistical survey with a space-based sensor orbiting in LEO observing small-size debris in LEO. The ground-based LEO survey uses a dynamical fence close to the Earth shadow a few hours after sunset. For the space-based scenario
A new CMOS-based digital imaging detector for applications in mammography
NASA Astrophysics Data System (ADS)
Baysal, Mehmet A.; Toker, Emre
We have developed a CMOS-based x-ray imaging detector in the same form factor of a standard film cassette (18 cm × 24 cm) for Small Field-of-view Digital Mammography (SFDM) applications. This SFDM cassette is based on our three-side buttable, 25 mm × 50 mm, 48μm active-pixel CMOS sensor modules and utilizes a 150μm columnar CsI(Tl) scintillator. For imaging up to 100 mm × 100 mm field-of-view, a number of CMOS sensor modules need to be tiled and electronically synchronized together. By using fiber-optic communication, acquired images from the SFDM cassette can be transferred, processed and displayed on a review station within approximately 5 seconds of exposure, greatly enhancing patient flow. We present the physical performance of this CMOS-based SFDM cassette, using established objective criteria such as the Modulation Transfer Function (MTF), Detective Quantum Efficiency (DQE), and more subjective criteria, by evaluating images from a phantom study and the clinical studies of our collaborators. Driven by the strong demand from the computer industry, CMOS technology is one of the lowest cost, and the most readily accessible technologies available for digital mammography today. Recent popular use of CMOS imagers in high-end consumer cameras have also resulted in significant advances in the imaging performance of CMOS sensors against rivaling CCD sensors. The SFDM cassette can be employed in various mammography applications, including spot imaging, stereotactic biopsy imaging, core biopsy and surgical biopsy specimen radiography. This study demonstrates that all the image quality requirements for demanding mammography applications can be addressed with CMOS technology.
First result on biased CMOS MAPs-on-diamond devices
NASA Astrophysics Data System (ADS)
Kanxheri, K.; Citroni, M.; Fanetti, S.; Lagomarsino, S.; Morozzi, A.; Parrini, G.; Passeri, D.; Sciortino, S.; Servoli, L.
Recently a new type of device, the MAPS-on-diamond, obtained bonding a thinned to 25 μm CMOS Monolithic Active Pixel Sensor to a standard 500 μm pCVD diamond substrate, has been proposed and fabricated, allowing a highly segmented readout (10×10 μm pixel size) of the signal produced in the diamond substrate. The bonding between the two materials has been obtained using a new laser technique to deliver the needed energy at the interface. A biasing scheme has been adopted to polarize the diamond substrate to allow the charge transport inside the diamond without disrupting the functionalities of the CMOS Monolithic Active Pixel Sensor. The main concept of this class of devices is the capability of the charges generated in the diamond by ionizing radiation to cross the silicon-diamond interface and to be collected by the MAPS photodiodes. In this work we demonstrate that such passage occurs and measure its overall efficiency. This study has been carried out first calibrating the CMOS MAPS with monochromatic X-rays, and then testing the device with charged particles (electrons) either with and without biasing the diamond substrate, to compare the amount of signal collected.
CMOS-sensors for energy-resolved X-ray imaging
NASA Astrophysics Data System (ADS)
Doering, D.; Amar-Youcef, S.; Baudot, J.; Deveaux, M.; Dulinski, W.; Kachel, M.; Linnik, B.; Müntz, C.; Stroth, Joachim
Due to their low noise, CMOS Monolithic Active Pixel Sensors are suited to sense X-rays with a few keV quantum energy, which is of interest for high resolution X-ray imaging. Moreover, the good energy resolution of the silicon sensors might be used to measure this quantum energy. Combining both features with the good spatial resolution of CMOS sensors opens the potential to build ``color sensitive" X-ray cameras. Taking such colored images is hampered by the need to operate the CMOS sensors in a single photon counting mode, which restricts the photon flux capability of the sensors. More importantly, the charge sharing between the pixels smears the potentially good energy resolution of the sensors. Based on our experience with CMOS sensors for charged particle tracking, we studied techniques to overcome the latter by means of an offline processing of the data obtained from a CMOS sensor prototype. We found that the energy resolution of the pixels can be recovered at the expense of reduced quantum efficiency. We will introduce the results of our study and discuss the feasibility of taking colored X-ray pictures with CMOS sensors.
Biosensing with integrated CMOS nanopores
NASA Astrophysics Data System (ADS)
Uddin, Ashfaque; Yemenicioglu, Sukru; Chen, Chin-Hsuan; Corgliano, Ellie; Milaninia, Kaveh; Xia, Fan; Plaxco, Kevin; Theogarajan, Luke
This paper outlines our recent efforts in using solid-state nanopores as a biosensing platform. Traditionally biosensors concentrate mainly on the detection platform and not on signal processing. This decoupling can lead to inferior sensors and is exacerbated in nanoscale devices, where device noise is large and large dynamic range is required. This paper outlines a novel platform that integrates the nano, micro and macroscales in a closely coupled manner that mitigates many of these problems. We discuss our initial results of DNA translocation through the nanopore. We also briefly discuss the use of molecular recognition properties of aptamers with the versatility of the nanopore detector to design a new class of biosensors in a CMOS compatible platform.
The Stanford Tissue Microarray Database.
Marinelli, Robert J; Montgomery, Kelli; Liu, Chih Long; Shah, Nigam H; Prapong, Wijan; Nitzberg, Michael; Zachariah, Zachariah K; Sherlock, Gavin J; Natkunam, Yasodha; West, Robert B; van de Rijn, Matt; Brown, Patrick O; Ball, Catherine A
The Stanford Tissue Microarray Database (TMAD; http://tma.stanford.edu) is a public resource for disseminating annotated tissue images and associated expression data. Stanford University pathologists, researchers and their collaborators worldwide use TMAD for designing, viewing, scoring and analyzing their tissue microarrays. The use of tissue microarrays allows hundreds of human tissue cores to be simultaneously probed by antibodies to detect protein abundance (Immunohistochemistry; IHC), or by labeled nucleic acids (in situ hybridization; ISH) to detect transcript abundance. TMAD archives multi-wavelength fluorescence and bright-field images of tissue microarrays for scoring and analysis. As of July 2007, TMAD contained 205 161 images archiving 349 distinct probes on 1488 tissue microarray slides. Of these, 31 306 images for 68 probes on 125 slides have been released to the public. To date, 12 publications have been based on these raw public data. TMAD incorporates the NCI Thesaurus ontology for searching tissues in the cancer domain. Image processing researchers can extract images and scores for training and testing classification algorithms. The production server uses the Apache HTTP Server, Oracle Database and Perl application code. Source code is available to interested researchers under a no-cost license. PMID:17989087
Comparing Bacterial DNA Microarray Fingerprints
Willse, Alan R.; Chandler, Darrell P.; White, Amanda M.; Protic, Miroslava; Daly, Don S.; Wunschel, Sharon C.
Detecting subtle genetic differences between microorganisms is an important problem in molecular epidemiology and microbial forensics. In a typical investigation, gel electrophoresis is used to compare randomly amplified DNA fragments between microbial strains, where the patterns of DNA fragment sizes are proxies for a microbe's genotype. The limited genomic sample captured on a gel is often insufficient to discriminate nearly identical strains. This paper examines the application of microarray technology to DNA fingerprinting as a high-resolution alternative to gel-based methods. The so-called universal microarray, which uses short oligonucleotide probes that do not target specific genes or species, is intended to be applicable to all microorganisms because it does not require prior knowledge of genomic sequence. In principle, closely related strains can be distinguished if the number of probes on the microarray is sufficiently large, i.e., if the genome is sufficiently sampled. In practice, we confront noisy data, imperfectly matched hybridizations, and a high-dimensional inference problem. We describe the statistical problems of microarray fingerprinting, outline similarities with and differences from more conventional microarray applications, and illustrate the statistical fingerprinting problem for 10 closely related strains from three Bacillus species, and 3 strains from non-Bacillus species.
Profiling In Situ Microbial Community Structure with an Amplification Microarray
Knickerbocker, Christopher; Bryant, Lexi; Golova, Julia; Wiles, Cory; Williams, Kenneth H.; Peacock, Aaron D.; Long, Philip E.
The objectives of this study were to unify amplification, labeling, and microarray hybridization chemistries within a single, closed microfluidic chamber (an amplification microarray) and verify technology performance on a series of groundwater samples from an in situ field experiment designed to compare U(VI) mobility under conditions of various alkalinities (as HCO3−) during stimulated microbial activity accompanying acetate amendment. Analytical limits of detection were between 2 and 200 cell equivalents of purified DNA. Amplification microarray signatures were well correlated with 16S rRNA-targeted quantitative PCR results and hybridization microarray signatures. The succession of the microbial community was evident with and consistent between the two microarray platforms. Amplification microarray analysis of acetate-treated groundwater showed elevated levels of iron-reducing bacteria (Flexibacter, Geobacter, Rhodoferax, and Shewanella) relative to the average background profile, as expected. Identical molecular signatures were evident in the transect treated with acetate plus NaHCO3, but at much lower signal intensities and with a much more rapid decline (to nondetection). Azoarcus, Thaurea, and Methylobacterium were responsive in the acetate-only transect but not in the presence of bicarbonate. Observed differences in microbial community composition or response to bicarbonate amendment likely had an effect on measured rates of U reduction, with higher rates probable in the part of the field experiment that was amended with bicarbonate. The simplification in microarray-based work flow is a significant technological advance toward entirely closed-amplicon microarray-based tests and is generally extensible to any number of environmental monitoring applications. PMID:23160129
Fully depleted, thick, monolithic CMOS pixels with high quantum efficiency
NASA Astrophysics Data System (ADS)
Clarke, A.; Stefanov, K.; Johnston, N.; Holland, A.
The Centre for Electronic Imaging (CEI) has an active programme of evaluating and designing Complementary Metal-Oxide Semiconductor (CMOS) image sensors with high quantum efficiency, for applications in near-infrared and X-ray photon detection. This paper describes the performance characterisation of CMOS devices made on a high resistivity 50 μ m thick p-type substrate with a particular focus on determining the depletion depth and the quantum efficiency. The test devices contain 8 × 8 pixel arrays using CCD-style charge collection, which are manufactured in a low voltage CMOS process by ESPROS Photonics Corporation (EPC). Measurements include determining under which operating conditions the devices become fully depleted. By projecting a spot using a microscope optic and a LED and biasing the devices over a range of voltages, the depletion depth will change, causing the amount of charge collected in the projected spot to change. We determine if the device is fully depleted by measuring the signal collected from the projected spot. The analysis of spot size and shape is still under development.
CMOS-liquid-crystal-based image transceiver device
NASA Astrophysics Data System (ADS)
Efron, Uzi; Davidov, Isak; Sinelnikov, Vladimir; Levin, Ilya
A CMOS-Liquid Crystal-Based Image Transceiver Device (ITD) is under development at the Holon Institute of Technology. The device combines both functions of imaginary and display in a single array structure. This unique structure allows the combination of see-through, aiming, imaging and the displaying of a superposed image to be combined in a single, compact, head mounted display. The CMOS-based pixel elements are designed to provide image sensor part of the pixel is based on an n-well photodiode and a three-transistors readout circuit. The imaging function is based on a back- illuminated sensor configuration. In order to provide a high imager fill-factor, two pixel configuration are proposed: 1) A p++/p-/p-well silicon structure using twin- well CMOS process; 2) an n-well processed silicon structure with a micro-lens array. The display portion of the IT device is to be fabricate don a silicon-based reflective, active matrix driver, using nematic liquid crystal material. The reflective display pixel electrode is driven by an n-MOS transistor, formed in the corresponding pixel region on the silicon substrate. The timing, sequencing and control of the IT device array are designed in a pipeline array processing scheme. A preliminary prototype system and device design have been performed and the first test device is currently being tested. Details of the device design as well as its smart goggle applications are presented.
CMOS/LCOS-based image transceiver device: II
NASA Astrophysics Data System (ADS)
Efron, Uzi; Davidov, Isak; Sinelnikov, Vladimir; Friesem, Asher A.
A CMOS-liquid crystal-based image transceiver device (ITD) is under development at the Holon Institute of Technology. The device combines both functions of imaging and display in a single array configuration. This unique structure allows the combination of see-through, aiming, imaging and the displaying of a superposed image to be combined in a single, compact, head mounted display. The CMOS-based pixel elements are designed to provide efficient imaging in the visible range as well as driver capabilities for the overlying liquid crystal modulator. The image sensor part of the pixel is based on an n-well photodiode and a three-transistor readout circuit. The imaging function is based on a back- illuminated sensor configuration. In order to provide a high imager fill-factor, two pixel configurations are proposed: 1) A p++/p-/p-well silicon structure using twin- well CMOS process; 2) An n-well processed silicon structure with a micro-lens array. The display portion of the IT device is to be fabricated on a silicon-based reflective, active matrix driver, using nematic liquid crystal material, in LCOS technology. The timing, sequencing and control of the IT device array are designed in a pipeline array processing scheme. A preliminary prototype system and device design have been performed and the first test device is currently undergoing testing. Details of the device design as well as its Smart Goggle applications are presented.
Characterization of a CMOS detector for limited-view mammography
NASA Astrophysics Data System (ADS)
Elbakri, Idris A.
Sensors based on complementary metal oxide semiconductors (CMOS) technology have recently been considered for mammography applications. CMOS offers the advantages of lower cost and relative ease of fabrications. We report on the evaluation of a CMOS imager (C9730DK, Hamamatsu Corporation) with 14-bit digitization and 50-micron detector element (del) resolution. The imager has an active area of 5 x 5 cm and uses 160-micron layer of needle-crystal CsI (55 mg/cc) to convert x-rays to light. The detector is suitable for spot and specimen imaging and image-guided biopsy. To evaluate resolution performance, we measured the modulation transfer function (MTF) using the slanted edge method. We also measured the normalized noise power spectrum (NNPS) using Fourier analysis of uniform images. The MTF and NNPS were used to determine the detective quantum efficiency (DQE) of the detector. The detector was characterized using a molybdenum target/molybdenum filter mammography x-ray source operated at 28 kVp with 44mm of PMMA added to mimic clinical beam quality (HVL = 0.62 mm Al). Our analysis showed that the imager had a linear response. The MTF was 28% at 5 lp/mm and 8% at 10 lp/mm. The product of the NNPS and exposure showed that the detector was quantum limited. The DQE near 0 lp/mm was in the 55-60% range. The DQE and MTF performance of the CMOS detector are comparable to published values for other digital mammography detectors.
Characteristic attributes in cancer microarrays.
Sarkar, I N; Planet, P J; Bael, T E; Stanley, S E; Siddall, M; DeSalle, R; Figurski, D H
Rapid advances in genome sequencing and gene expression microarray technologies are providing unprecedented opportunities to identify specific genes involved in complex biological processes, such as development, signal transduction, and disease. The vast amount of data generated by these technologies has presented new challenges in bioinformatics. To help organize and interpret microarray data, new and efficient computational methods are needed to: (1) distinguish accurately between different biological or clinical categories (e.g., malignant vs. benign), and (2) identify specific genes that play a role in determining those categories. Here we present a novel and simple method that exhaustively scans microarray data for unambiguous gene expression patterns. Such patterns of data can be used as the basis for classification into biological or clinical categories. The method, termed the Characteristic Attribute Organization System (CAOS), is derived from fundamental precepts in systematic biology. In CAOS we define two types of characteristic attributes ('pure' and 'private') that may exist in gene expression microarray data. We also consider additional attributes ('compound') that are composed of expression states of more than one gene that are not characteristic on their own. CAOS was tested on three well-known cancer DNA microarray data sets for its ability to classify new microarray samples. We found CAOS to be a highly accurate and robust class prediction technique. In addition, CAOS identified specific genes, not emphasized in other analyses, that may be crucial to the biology of certain types of cancer. The success of CAOS in this study has significant implications for basic research and the future development of reliable methods for clinical diagnostic tools. PMID:12474425
Microarrayed Materials for Stem Cells
Mei, Ying
Stem cells hold remarkable promise for applications in disease modeling, cancer therapy and regenerative medicine. Despite the significant progress made during the last decade, designing materials to control stem cell fate remains challenging. As an alternative, materials microarray technology has received great attention because it allows for high throughput materials synthesis and screening at a reasonable cost. Here, we discuss recent developments in materials microarray technology and their applications in stem cell engineering. Future opportunities in the field will also be reviewed. PMID:24311967
Immunoprofiling Using NAPPA Protein Microarrays
Sibani, Sahar; LaBaer, Joshua
Protein microarrays provide an efficient method to immunoprofile patients in an effort to rapidly identify disease immunosignatures. The validity of using autoantibodies in diagnosis has been demonstrated in type 1 diabetes, rheumatoid arthritis, and systemic lupus, and is now being strongly considered in cancer. Several types of protein microarrays exist including antibody and antigen arrays. In this chapter, we describe the immunoprofiling application for one type of antigen array called NAPPA (nucleic acids programmable protein array). We provide a guideline for setting up the screening study and designing protein arrays to maximize the likelihood of obtaining quality data. PMID:21370064
Flexible packaging and integration of CMOS IC with elastomeric microfluidics
NASA Astrophysics Data System (ADS)
Zhang, Bowei; Dong, Quan; Korman, Can E.; Li, Zhenyu; Zaghloul, Mona E.
We have demonstrated flexible packaging and integration of CMOS IC chips with PDMS microfluidics. Microfluidic channels are used to deliver both liquid samples and liquid metals to the CMOS die. The liquid metals are used to realize electrical interconnects to the CMOS chip. As a demonstration we integrated a CMOS magnetic sensor die and matched PDMS microfluidic channels in a flexible package. The packaged system is fully functional under 3cm bending radius. The flexible integration of CMOS ICs with microfluidics enables previously unavailable flexible CMOS electronic systems with fluidic manipulation capabilities, which hold great potential for wearable health monitoring, point-of-care diagnostics and environmental sensing.
Microarray Analysis Reveals Increased Transcriptional Repression and Reduced Metabolic Activity but Not Major Changes in the Core Apoptotic Machinery during Maturation of Sympathetic Neurons
Raba, Mikk; Palgi, Jaan; Lehtivaara, Maria; Arumäe, Urmas
Postnatal maturation of the neurons whose main phenotype and basic synaptic contacts are already established includes neuronal growth, refinement of synaptic contacts, final steps of differentiation, programmed cell death period (PCD) etc. In the sympathetic neurons, postnatal maturation includes permanent end of the PCD that occurs with the same time schedule in vivo and in vitro suggesting that the process could be genetically determined. Also many other changes in the neuronal maturation could be permanent and thus based on stable changes in the genome expression. However, postnatal maturation of the neurons is poorly studied. Here we compared the gene expression profiles of immature and mature sympathetic neurons using Affymetrix microarray assay. We found 1310 significantly up-regulated and 1151 significantly down-regulated genes in the mature neurons. Gene ontology analysis reveals up-regulation of genes related to neuronal differentiation, chromatin and epigenetic changes, extracellular factors and their receptors, and cell adhesion, whereas many down-regulated genes were related to metabolic and biosynthetic processes. We show that termination of PCD is not related to major changes in the expression of classical genes for apoptosis or cell survival. Our dataset is deposited to the ArrayExpress database and is a valuable source to select candidate genes in the studies of neuronal maturation. As an example, we studied the changes in the expression of selected genes Igf2bp3, Coro1A, Zfp57, Dcx, and Apaf1 in the young and mature sympathetic ganglia by quantitative PCR and show that these were strongly downregulated in the mature ganglia. PMID:27013977
Construction and validation of a Bovine Innate Immune Microarray
Donaldson, Laurelea; Vuocolo, Tony; Gray, Christian; Strandberg, Ylva; Reverter, Antonio; McWilliam, Sean; Wang, YongHong; Byrne, Keren; Tellam, Ross
Background Microarray transcript profiling has the potential to illuminate the molecular processes that are involved in the responses of cattle to disease challenges. This knowledge may allow the development of strategies that exploit these genes to enhance resistance to disease in an individual or animal population. Results The Bovine Innate Immune Microarray developed in this study consists of 1480 characterised genes identified by literature searches, 31 positive and negative control elements and 5376 cDNAs derived from subtracted and normalised libraries. The cDNA libraries were produced from 'challenged' bovine epithelial and leukocyte cells. The microarray was found to have a limit of detection of 1 pg/μg of total RNA and a mean slide-to-slide correlation co-efficient of 0.88. The profiles of differentially expressed genes from Concanavalin A (ConA) stimulated bovine peripheral blood lymphocytes were determined. Three distinct profiles highlighted 19 genes that were rapidly up-regulated within 30 minutes and returned to basal levels by 24 h; 76 genes that were up-regulated between 2–8 hours and sustained high levels of expression until 24 h and 10 genes that were down-regulated. Quantitative real-time RT-PCR on selected genes was used to confirm the results from the microarray analysis. The results indicate that there is a dynamic process involving gene activation and regulatory mechanisms re-establishing homeostasis in the ConA activated lymphocytes. The Bovine Innate Immune Microarray was also used to determine the cross-species hybridisation capabilities of an ovine PBL sample. Conclusion The Bovine Innate Immune Microarray has been developed which contains a set of well-characterised genes and anonymous cDNAs from a number of different bovine cell types. The microarray can be used to determine the gene expression profiles underlying innate immune responses in cattle and sheep. PMID:16176586
Microfluidic microarray systems and methods thereof
West, Jay A. A.; Hukari, Kyle W.; Hux, Gary A.
Disclosed are systems that include a manifold in fluid communication with a microfluidic chip having a microarray, an illuminator, and a detector in optical communication with the microarray. Methods for using these systems for biological detection are also disclosed.
Microarray analysis: Uses and Limitations
Technology Transfer Automated Retrieval System (TEKTRAN)
The use of microarray technology has exploded in resent years. All areas of biological research have found application for this powerful platform. From human disease studies to microbial detection systems, a plethora of uses for this technology are currently in place with new uses being developed ...
Microarray Developed on Plastic Substrates.
Bañuls, María-José; Morais, Sergi B; Tortajada-Genaro, Luis A; Maquieira, Ángel
There is a huge potential interest to use synthetic polymers as versatile solid supports for analytical microarraying. Chemical modification of polycarbonate (PC) for covalent immobilization of probes, micro-printing of protein or nucleic acid probes, development of indirect immunoassay, and development of hybridization protocols are described and discussed. PMID:26614067
The Microarray Revolution: Perspectives from Educators
ERIC Educational Resources Information Center
Brewster, Jay L.; Beason, K. Beth; Eckdahl, Todd T.; Evans, Irene M.
In recent years, microarray analysis has become a key experimental tool, enabling the analysis of genome-wide patterns of gene expression. This review approaches the microarray revolution with a focus upon four topics: 1) the early development of this technology and its application to cancer diagnostics; 2) a primer of microarray research,…
Nanopore-CMOS Interfaces for DNA Sequencing.
Magierowski, Sebastian; Huang, Yiyun; Wang, Chengjie; Ghafar-Zadeh, Ebrahim
DNA sequencers based on nanopore sensors present an opportunity for a significant break from the template-based incumbents of the last forty years. Key advantages ushered by nanopore technology include a simplified chemistry and the ability to interface to CMOS technology. The latter opportunity offers substantial promise for improvement in sequencing speed, size and cost. This paper reviews existing and emerging means of interfacing nanopores to CMOS technology with an emphasis on massively-arrayed structures. It presents this in the context of incumbent DNA sequencing techniques, reviews and quantifies nanopore characteristics and models and presents CMOS circuit methods for the amplification of low-current nanopore signals in such interfaces. PMID:27509529
Characterization and reliability of CMOS microstructures
NASA Astrophysics Data System (ADS)
Fedder, Gary K.; Blanton, Ronald D. S.
This paper provides an overview of high-aspect-ratio CMOS micromachining, focusing on materials characterization, reliability, and fault analysis. Composite microstrutural beam widths and gaps down to 1.2 micrometers are etched out of conventional CMOS dielectric, aluminum, and gate-polysilicon thin films using post-CMOS dry etching for both structural sidewall definition and for release from the substrate. Differences in stress between the multiple metal and dielectric layers cause vertical stress gradients and curl, while misalignment between layers causes lateral stress gradients and curl. Cracking is induced in a resonant fatigue structures at 620 MPa of repetitive stress after over 50 million cycles. Beams have withstood over 1.3 billion cycles at 124 MPa stress levels induced by electrostatic actuation. Failures due to process defects are classified according to the geometrical features of the defective structures. Relative probability of occurrence of each defect type is extracted from the process simulation results.
High-temperature Complementary Metal Oxide Semiconductors (CMOS)
NASA Technical Reports Server (NTRS)
Mcbrayer, J. D.
The results of an investigation into the possibility of using complementary metal oxide semiconductor (CMOS) technology for high temperature electronics are presented. A CMOS test chip was specifically developed as the test bed. This test chip incorporates CMOS transistors that have no gate protection diodes; these diodes are the major cause of leakage in commercial devices.
Low power, CMOS digital autocorrelator spectrometer for spaceborne applications
NASA Technical Reports Server (NTRS)
Chandra, Kumar; Wilson, William J.
A 128-channel digital autocorrelator spectrometer using four 32 channel low power CMOS correlator chips was built and tested. The CMOS correlator chip uses a 2-bit multiplication algorithm and a full-custom CMOS VLSI design to achieve low DC power consumption. The digital autocorrelator spectrometer has a 20 MHz band width, and the total DC power requirement is 6 Watts.
Resistor Extends Life Of Battery In Clocked CMOS Circuit
NASA Technical Reports Server (NTRS)
Wells, George H., Jr.
Addition of fixed resistor between battery and clocked complementary metal oxide/semiconductor (CMOS) circuit reduces current drawn from battery. Basic idea to minimize current drawn from battery by operating CMOS circuit at lowest possible current consistent with use of simple, fixed off-the-shelf components. Prolongs lives of batteries in such low-power CMOS circuits as watches and calculators.
Deposition of titanium dioxide nanoparticles on the membrane of a CMOS-MEMS resonator
NASA Astrophysics Data System (ADS)
Ahmed, A. Y.; Dennis, J. O.; Khir, M. H. Md; Saad, M. N. Mohamad
A CMOS-MEMS resonator is optimized as a highly sensitive gas sensor. The principle of detection is based on change in resonant frequency of the resonator due to adsorption/absorption of trace gases onto the active material on the resonator membrane. The resonator was successfully fabricated using 0.35 μm CMOS technology and post-CMOS micromachining process. The post-CMOS process is used to etch the silicon substrate and silicon oxide to release the suspended structures of the devices. Preliminary trials of nanocrystalline Titania paste (TiO2) was screen-printed on three aluminum plates of sizes 2mm × 2 mm. One of the samples was analysed as prepared while the other two samples were sintered at 300°C and 550°C, respectively. Physical observation indicated a change of the color for heated samples as compared to the unheated one. EDX results indicates a carbon (C) peak with average weight % of 18.816 in the as prepared sample and absence of the peaks for the samples sintered at 300°C and 550°C. EDX results also show that the TiO2 used consists of a uniform distribution of spherical shaped nanoparticles with a diameter of about 13.49 to 48.42 nm. Finally, the Titania paste was successfully deposit on the membrane of the CMOS-MEMS resonator for use as the gas sensitive membrane of the sensor.
Biclustering of time series microarray data.
Meng, Jia; Huang, Yufei
Clustering is a popular data exploration technique widely used in microarray data analysis. In this chapter, we review ideas and algorithms of bicluster and its applications in time series microarray analysis. We introduce first the concept and importance of biclustering and its different variations. We then focus our discussion on the popular iterative signature algorithm (ISA) for searching biclusters in microarray dataset. Next, we discuss in detail the enrichment constraint time-dependent ISA (ECTDISA) for identifying biologically meaningful temporal transcription modules from time series microarray dataset. In the end, we provide an example of ECTDISA application to time series microarray data of Kaposi's Sarcoma-associated Herpesvirus (KSHV) infection. PMID:22130875
Transcriptional analysis of the innate immune response using the avian innate immunity microarray
Technology Transfer Automated Retrieval System (TEKTRAN)
The avian innate immunity microarray (AIIM) is a genomics tool designed to study the transcriptional activity of the avian immune response (Cytogenet. Genome Res. 117:139-145, 2007). It is an avian cDNA microarray representing 4,959 avian genes spotted in triplicate. The AIIM contains 25 avian int...
End-of-fabrication CMOS process monitor
NASA Technical Reports Server (NTRS)
Buehler, M. G.; Allen, R. A.; Blaes, B. R.; Hannaman, D. J.; Lieneweg, U.; Lin, Y.-S.; Sayah, H. R.
A set of test 'modules' for verifying the quality of a complementary metal oxide semiconductor (CMOS) process at the end of the wafer fabrication is documented. By electrical testing of specific structures, over thirty parameters are collected characterizing interconnects, dielectrics, contacts, transistors, and inverters. Each test module contains a specification of its purpose, the layout of the test structure, the test procedures, the data reduction algorithms, and exemplary results obtained from 3-, 2-, or 1.6-micrometer CMOS/bulk processes. The document is intended to establish standard process qualification procedures for Application Specific Integrated Circuits (ASIC's).
Production of biomolecule microarrays through laser induced forward transfer
NASA Astrophysics Data System (ADS)
Fernandez-Pradas, Juan Marcos; Serra, Pere; Colina, Monica; Morenza, Jose-Luis
Biomolecule microarrays are a kind of biosensors that consist in patterns of different biological molecules immobilized on a solid substrate and capable to bind specifically to their complementary targets. In particular, DNA and protein microarrays have been revealed to be very efficient devices for genen and protein identification, what has converted them in powerful tools for many applications, like clinical diagnose, drug discovery analysis, genomics and proteomics. The production of these devices requires the manipulation of tiny amounts of a liquid solution containing biomolecules without damaging them. In this work laser induced forward transfer (LIFT) has been used for spotting a biomolecule in order to check the viability of this technique for the production of microarrays. A pulsed Nd:YAG laser beam (355 nm wavelength) has been used to transfer droplets of a biomolecule containing solution onto a solid slide. Optical microscopy of the transferred material has been carried out to investigate the morphological characteristics of the droplets obtained under different irradiation conditions. Afterwards, a DNA microarray has been spotted. The viability of the transference has been tested by checking the biological activity of the biomolecule in front of its specific complementary target. This has revealed that, indeed, the LIFT technique is adequate for the production of DNA microarrays.
The Current Status of DNA Microarrays
NASA Astrophysics Data System (ADS)
Shi, Leming; Perkins, Roger G.; Tong, Weida
DNA microarray technology that allows simultaneous assay of thousands of genes in a single experiment has steadily advanced to become a mainstream method used in research, and has reached a stage that envisions its use in medical applications and personalized medicine. Many different strategies have been developed for manufacturing DNA microarrays. In this chapter, we discuss the manufacturing characteristics of seven microarray platforms that were used in a recently completed large study by the MicroArray Quality Control (MAQC) consortium, which evaluated the concordance of results across these platforms. The platforms can be grouped into three categories: (1) in situ synthesis of oligonucleotide probes on microarrays (Affymetrix GeneChip® arrays based on photolithography synthesis and Agilent's arrays based on inkjet synthesis); (2) spotting of presynthesized oligonucleotide probes on microarrays (GE Healthcare's CodeLink system, Applied Biosystems' Genome Survey Microarrays, and the custom microarrays printed with Operon's oligonucleotide set); and (3) deposition of presynthesized oligonucleotide probes on bead-based microarrays (Illumina's BeadChip microarrays). We conclude this chapter with our views on the challenges and opportunities toward acceptance of DNA microarray data in clinical and regulatory settings.
The Current Status of DNA Microarrays
NASA Astrophysics Data System (ADS)
Shi, Leming; Perkins, Roger G.; Tong, Weida
DNA microarray technology that allows simultaneous assay of thousands of genes in a single experiment has steadily advanced to become a mainstream method used in research, and has reached a stage that envisions its use in medical applications and personalized medicine. Many different strategies have been developed for manufacturing DNA microarrays. In this chapter, we discuss the manu facturing characteristics of seven microarray platforms that were used in a recently completed large study by the MicroArray Quality Control (MAQC) consortium, which evaluated the concordance of results across these platforms. The platforms can be grouped into three categories: (1) in situ synthesis of oligonucleotide probes on microarrays (Affymetrix GeneChip® arrays based on photolithography synthesis and Agilent's arrays based on inkjet synthesis); (2) spotting of presynthe-sized oligonucleotide probes on microarrays (GE Healthcare's CodeLink system, Applied Biosystems' Genome Survey Microarrays, and the custom microarrays printed with Operon's oligonucleotide set); and (3) deposition of presynthesized oligonucleotide probes on bead-based microarrays (Illumina's BeadChip microar-rays). We conclude this chapter with our views on the challenges and opportunities toward acceptance of DNA microarray data in clinical and regulatory settings.
Tissue microarrays: applications in genomic research.
Watanabe, Aprill; Cornelison, Robert; Hostetter, Galen
The widespread application of tissue microarrays in cancer research and the clinical pathology laboratory demonstrates a versatile and portable technology. The rapid integration of tissue microarrays into biomarker discovery and validation processes reflects the forward thinking of researchers who have pioneered the high-density tissue microarray. The precise arrangement of hundreds of archival clinical tissue samples into a composite tissue microarray block is now a proven method for the efficient and standardized analysis of molecular markers. With applications in cancer research, tissue microarrays are a valuable tool in validating candidate markers discovered in highly sensitive genome-wide microarray experiments. With applications in clinical pathology, tissue microarrays are used widely in immunohistochemistry quality control and quality assurance. The timeline of a biomarker implicated in prostate neoplasia, which was identified by complementary DNA expression profiling, validated by tissue microarrays and is now used as a prognostic immunohistochemistry marker, is reviewed. The tissue microarray format provides opportunities for digital imaging acquisition, image processing and database integration. Advances in digital imaging help to alleviate previous bottlenecks in the research pipeline, permit computer image scoring and convey telepathology opportunities for remote image analysis. The tissue microarray industry now includes public and private sectors with varying degrees of research utility and offers a range of potential tissue microarray applications in basic research, prognostic oncology and drug discovery. PMID:15833047
Microarray analysis in pulmonary hypertension
Hoffmann, Julia; Wilhelm, Jochen; Olschewski, Andrea
Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions. They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles. Combined, they provide important information on development, progression and the end-stage disease. In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance. PMID:27076594
Phenotypic MicroRNA Microarrays
Kwon, Yong-Jun; Heo, Jin Yeong; Kim, Hi Chul; Kim, Jin Yeop; Liuzzi, Michel; Soloveva, Veronica
Microarray technology has become a very popular approach in cases where multiple experiments need to be conducted repeatedly or done with a variety of samples. In our lab, we are applying our high density spots microarray approach to microscopy visualization of the effects of transiently introduced siRNA or cDNA on cellular morphology or phenotype. In this publication, we are discussing the possibility of using this micro-scale high throughput process to study the role of microRNAs in the biology of selected cellular models. After reverse-transfection of microRNAs and siRNA, the cellular phenotype generated by microRNAs regulated NF-κB expression comparably to the siRNA. The ability to print microRNA molecules for reverse transfection into cells is opening up the wide horizon for the phenotypic high content screening of microRNA libraries using cellular disease models.
Microarray analysis in pulmonary hypertension.
Hoffmann, Julia; Wilhelm, Jochen; Olschewski, Andrea; Kwapiszewska, Grazyna
Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions. They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles. Combined, they provide important information on development, progression and the end-stage disease. In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance. PMID:27076594
Self-Assembling Protein Microarrays
NASA Astrophysics Data System (ADS)
Ramachandran, Niroshan; Hainsworth, Eugenie; Bhullar, Bhupinder; Eisenstein, Samuel; Rosen, Benjamin; Lau, Albert Y.; C. Walter, Johannes; LaBaer, Joshua
Protein microarrays provide a powerful tool for the study of protein function. However, they are not widely used, in part because of the challenges in producing proteins to spot on the arrays. We generated protein microarrays by printing complementary DNAs onto glass slides and then translating target proteins with mammalian reticulocyte lysate. Epitope tags fused to the proteins allowed them to be immobilized in situ. This obviated the need to purify proteins, avoided protein stability problems during storage, and captured sufficient protein for functional studies. We used the technology to map pairwise interactions among 29 human DNA replication initiation proteins, recapitulate the regulation of Cdt1 binding to select replication proteins, and map its geminin-binding domain.
A novel CMOS sensor with in-pixel auto-zeroed discrimination for charged particle tracking
NASA Astrophysics Data System (ADS)
Degerli, Y.; Guilloux, F.; Orsini, F.
With the aim of developing fast and granular Monolithic Active Pixels Sensors (MAPS) as new charged particle tracking detectors for high energy physics experiments, a new rolling shutter binary pixel architecture concept (RSBPix) with in-pixel correlated double sampling, amplification and discrimination is presented. The discriminator features auto-zeroing in order to compensate process-related transistor mismatches. In order to validate the pixel, a first monolithic CMOS sensor prototype, including a pixel array of 96 × 64 pixels, has been designed and fabricated in the Tower-Jazz 0.18 μm CMOS Image Sensor (CIS) process. Results of laboratory tests are presented.
Enzyme Microarrays Assembled by Acoustic Dispensing Technology
Wong, E. Y.; Diamond, S. L.
Miniaturizing bioassays to the nanoliter scale for high-throughput screening reduces the consumption of reagents that are expensive or difficult to handle. Utilizing acoustic dispensing technology, nanodroplets containing 10 µM ATP (3 µCi/µL 32P) and reaction buffer in 10% glycerol were positionally dispensed to the surface of glass slides to form 40 nL compartments (100 droplets/slide) for Pim1 (Proviral integration site 1) kinase reactions. The reactions were activated by dispensing 4 nL of various levels of a pyridocarbazolo-cyclopentadienyl ruthenium-complex Pim1 inhibitor, followed by dispensing 4 nL of a Pim1 kinase and peptide substrate solution to achieve final concentrations of 150 nM enzyme and 10 µM substrate. The microarray was incubated at 30°C (97% Rh) for 1.5 hr. The spots were then blotted to phosphocellulose membranes to capture phosphorylated substrate. Using phosphor imaging to quantify the washed membranes, the assay showed that, for doses of inhibitor from 0.75 µM to 3 µM, Pim1 was increasingly inhibited. Signal-to-background ratios were as high as 165 and average coefficients of variation (CVs) for the assay were ~20%. CVs for dispensing typical working buffers were under 5%. Thus, microarrays assembled by acoustic dispensing are promising as cost-effective tools that can be used in protein assay development. PMID:18616925
Enzyme microarrays assembled by acoustic dispensing technology.
Wong, E Y; Diamond, S L
Miniaturizing bioassays to the nanoliter scale for high-throughput screening reduces the consumption of reagents that are expensive or difficult to handle. Through the use of acoustic dispensing technology, nanodroplets containing 10 microM ATP (3 microCi/microL (32)P) and reaction buffer in 10% glycerol were positionally dispensed to the surface of glass slides to form 40-nL compartments (100 droplets/slide) for Pim1 (proviral integration site 1) kinase reactions. The reactions were activated by dispensing 4 nL of various levels of a pyridocarbazolo-cyclopentadienyl ruthenium complex Pim1 inhibitor, followed by dispensing 4 nL of a Pim1 kinase and peptide substrate solution to achieve final concentrations of 150 nM enzyme and 10 microM substrate. The microarray was incubated at 30 degrees C (97% R(h)) for 1.5 h. The spots were then blotted to phosphocellulose membranes to capture phosphorylated substrate. With phosphor imaging to quantify the washed membranes, the assay showed that, for doses of inhibitor from 0.75 to 3 microM, Pim1 was increasingly inhibited. Signal-to-background ratios were as high as 165, and average coefficients of variation for the assay were approximately 20%. Coefficients of variation for dispensing typical working buffers were under 5%. Thus, microarrays assembled by acoustic dispensing are promising as cost-effective tools that can be used in protein assay development. PMID:18616925
Radiation Tolerance of 65nm CMOS Transistors
Krohn, M.; Bentele, B.; Christian, D. C.; Cumalat, J. P.; Deptuch, G.; Fahim, F.; Hoff, J.; Shenai, A.; Wagner, S. R.
We report on the effects of ionizing radiation on 65 nm CMOS transistors held at approximately -20°C during irradiation. The pattern of damage observed after a total dose of 1 Grad is similar to damage reported in room temperature exposures, but we observe less damage than was observed at room temperature.
SEU hardening of CMOS memory circuit
NASA Technical Reports Server (NTRS)
Whitaker, S.; Canaris, J.; Liu, K.
This paper reports a design technique to harden CMOS memory circuits against Single Event Upset (SEU) in the space environment. A RAM cell and Flip Flop design are presented to demonstrate the method. The Flip Flop was used in the control circuitry for a Reed Solomon encoder designed for the Space Station.
Low energy CMOS for space applications
NASA Technical Reports Server (NTRS)
Panwar, Ramesh; Alkalaj, Leon
The current focus of NASA's space flight programs reflects a new thrust towards smaller, less costly, and more frequent space missions, when compared to missions such as Galileo, Magellan, or Cassini. Recently, the concept of a microspacecraft was proposed. In this concept, a small, compact spacecraft that weighs tens of kilograms performs focused scientific objectives such as imaging. Similarly, a Mars Lander micro-rover project is under study that will allow miniature robots weighing less than seven kilograms to explore the Martian surface. To bring the microspacecraft and microrover ideas to fruition, one will have to leverage compact 3D multi-chip module-based multiprocessors (MCM) technologies. Low energy CMOS will become increasingly important because of the thermodynamic considerations in cooling compact 3D MCM implementations and also from considerations of the power budget for space applications. In this paper, we show how the operating voltage is related to the threshold voltage of the CMOS transistors for accomplishing a task in VLSI with minimal energy. We also derive expressions for the noise margins at the optimal operating point. We then look at a low voltage CMOS (LVCMOS) technology developed at Stanford University which improves the power consumption over conventional CMOS by a couple of orders of magnitude and consider the suitability of the technology for space applications by characterizing its SEU immunity.
Low power SEU immune CMOS memory circuits
NASA Technical Reports Server (NTRS)
Liu, M. N.; Whitaker, Sterling
The authors report a design improvement for CMOS static memory circuits hardened against single event upset (SEU) using a recently proposed logic/circuit design technique. This improvement drastically reduces static power consumption, reduces the number of transistors required in a D flip-flop design, and eliminates the possibility of capturing an upset state in the slave section during a clock transition.
Fully CMOS-compatible titanium nitride nanoantennas
NASA Astrophysics Data System (ADS)
Briggs, Justin A.; Naik, Gururaj V.; Petach, Trevor A.; Baum, Brian K.; Goldhaber-Gordon, David; Dionne, Jennifer A.
CMOS-compatible fabrication of plasmonic materials and devices will accelerate the development of integrated nanophotonics for information processing applications. Using low-temperature plasma-enhanced atomic layer deposition (PEALD), we develop a recipe for fully CMOS-compatible titanium nitride (TiN) that is plasmonic in the visible and near infrared. Films are grown on silicon, silicon dioxide, and epitaxially on magnesium oxide substrates. By optimizing the plasma exposure per growth cycle during PEALD, carbon and oxygen contamination are reduced, lowering undesirable loss. We use electron beam lithography to pattern TiN nanopillars with varying diameters on silicon in large-area arrays. In the first reported single-particle measurements on plasmonic TiN, we demonstrate size-tunable darkfield scattering spectroscopy in the visible and near infrared regimes. The optical properties of this CMOS-compatible material, combined with its high melting temperature and mechanical durability, comprise a step towards fully CMOS-integrated nanophotonic information processing.
NASA Technical Reports Server (NTRS)
Bobin, V.; Whitaker, S.
This paper reports a design technique to make Complex CMOS Gates fail-safe for a class of faults. Two classes of faults are defined. The fail-safe design presented has limited fault-tolerance capability. Multiple faults are also covered.
CMOS preamplifiers for detectors large and small
O`Connor, P.
We describe four CMOS preamplifiers developed for multiwire proportional chambers (MWPC) and silicon drift detectors (SDD) covering a capacitance range from 150 pF to 0.15 pF. Circuit techniques to optimize noise performance, particularly in the low-capacitance regime, are discussed.
Low energy CMOS for space applications
NASA Astrophysics Data System (ADS)
Panwar, Ramesh; Alkalaj, Leon
The current focus of NASA's space flight programs reflects a new thrust towards smaller, less costly, and more frequent space missions, when compared to missions such as Galileo, Magellan, or Cassini. Recently, the concept of a microspacecraft was proposed. In this concept, a small, compact spacecraft that weighs tens of kilograms performs focused scientific objectives such as imaging. Similarly, a Mars Lander micro-rover project is under study that will allow miniature robots weighing less than seven kilograms to explore the Martian surface. To bring the microspacecraft and microrover ideas to fruition, one will have to leverage compact 3D multi-chip module-based multiprocessors (MCM) technologies. Low energy CMOS will become increasingly important because of the thermodynamic considerations in cooling compact 3D MCM implementations and also from considerations of the power budget for space applications. In this paper, we show how the operating voltage is related to the threshold voltage of the CMOS transistors for accomplishing a task in VLSI with minimal energy. We also derive expressions for the noise margins at the optimal operating point. We then look at a low voltage CMOS (LVCMOS) technology developed at Stanford University which improves the power consumption over conventional CMOS by a couple of orders of magnitude and consider the suitability of the technology for space applications by characterizing its SEU immunity.
Low-Power SOI CMOS Transceiver
NASA Technical Reports Server (NTRS)
Fujikawa, Gene (Technical Monitor); Cheruiyot, K.; Cothern, J.; Huang, D.; Singh, S.; Zencir, E.; Dogan, N.
The work aims at developing a low-power Silicon on Insulator Complementary Metal Oxide Semiconductor (SOI CMOS) Transceiver for deep-space communications. RF Receiver must accomplish the following tasks: (a) Select the desired radio channel and reject other radio signals, (b) Amplify the desired radio signal and translate them back to baseband, and (c) Detect and decode the information with Low BER. In order to minimize cost and achieve high level of integration, receiver architecture should use least number of external filters and passive components. It should also consume least amount of power to minimize battery cost, size, and weight. One of the most stringent requirements for deep-space communication is the low-power operation. Our study identified that two candidate architectures listed in the following meet these requirements: (1) Low-IF receiver, (2) Sub-sampling receiver. The low-IF receiver uses minimum number of external components. Compared to Zero-IF (Direct conversion) architecture, it has less severe offset and flicker noise problems. The Sub-sampling receiver amplifies the RF signal and samples it using track-and-hold Subsampling mixer. These architectures provide low-power solution for the short- range communications missions on Mars. Accomplishments to date include: (1) System-level design and simulation of a Double-Differential PSK receiver, (2) Implementation of Honeywell SOI CMOS process design kit (PDK) in Cadence design tools, (3) Design of test circuits to investigate relationships between layout techniques, geometry, and low-frequency noise in SOI CMOS, (4) Model development and verification of on-chip spiral inductors in SOI CMOS process, (5) Design/implementation of low-power low-noise amplifier (LNA) and mixer for low-IF receiver, and (6) Design/implementation of high-gain LNA for sub-sampling receiver. Our initial results show that substantial improvement in power consumption is achieved using SOI CMOS as compared to standard CMOS
SOI CMOS Imager with Suppression of Cross-Talk
NASA Technical Reports Server (NTRS)
Pain, Bedabrata; Zheng, Xingyu; Cunningham, Thomas J.; Seshadri, Suresh; Sun, Chao
A monolithic silicon-on-insulator (SOI) complementary metal oxide/semiconductor (CMOS) image-detecting integrated circuit of the active-pixel-sensor type, now undergoing development, is designed to operate at visible and near-infrared wavelengths and to offer a combination of high quantum efficiency and low diffusion and capacitive cross-talk among pixels. The imager is designed to be especially suitable for astronomical and astrophysical applications. The imager design could also readily be adapted to general scientific, biological, medical, and spectroscopic applications. One of the conditions needed to ensure both high quantum efficiency and low diffusion cross-talk is a relatively high reverse bias potential (between about 20 and about 50 V) on the photodiode in each pixel. Heretofore, a major obstacle to realization of this condition in a monolithic integrated circuit has been posed by the fact that the required high reverse bias on the photodiode is incompatible with metal oxide/semiconductor field-effect transistors (MOSFETs) in the CMOS pixel readout circuitry. In the imager now being developed, the SOI structure is utilized to overcome this obstacle: The handle wafer is retained and the photodiode is formed in the handle wafer. The MOSFETs are formed on the SOI layer, which is separated from the handle wafer by a buried oxide layer. The electrical isolation provided by the buried oxide layer makes it possible to bias the MOSFETs at CMOS-compatible potentials (between 0 and 3 V), while biasing the photodiode at the required higher potential, and enables independent optimization of the sensory and readout portions of the imager.
Changes in hepatic gene expression related to innate immunity, growth and iron metabolism in GH-transgenic amago salmon (Oncorhynchus masou) by cDNA subtraction and microarray analysis, and serum lysozyme activity.
Mori, Tsukasa; Hiraka, Ikuei; Kurata, Youichi; Kawachi, Hiroko; Mano, Nobuhiro; Devlin, Robert H; Nagoya, Hiroyuki; Araki, Kazuo
Growth hormone (GH) transgenic amago salmon (Oncorhynchus masou) were generated with a construct containing the sockeye salmon GH1 gene fused to the metallothionein-B (MT-B) promoter from the same species. This transgene directed significant growth enhancement with transgenic fish reaching approximately four to five times greater weight than control salmon in F(2) and F(3) generations. This drastic growth enhancement by GH transgene is well known in fish species compared with mammals, however, such fish can show morphological abnormalities and physiological disorders like other GH transgenic animals. GH is known to have many acute effects, but currently there are no data describing the chronic effects of over-expression of GH on various hepatic genes in GH transgenic fish. Hepatic gene expression is anticipated to play very important roles in many physiological functions and growth performance of transgenic and control salmon. To examine these effects, we performed subtractive hybridization (using cDNA generated from liver RNA) in both directions to identify genes both increased and decreased in transgenic salmon relative to controls (576 clones were isolated and sequenced in total). Heme oxygenase, vitelline envelope protein, Acyl-coA binding protein, NADH dehydrogenase, mannose binding lectin-associated serine protease, hemopexin-like protein, leucyte-derived chemotaxin2 (LECT2), and many other genes were obtained in higher clone frequencies suggesting enhanced expression. In contrast, complement C3-1, lectin, rabin, alcohol dehydrogenase, Tc1-like transposase, Delta6-desaturase, and pentraxin genes were obtained in lower frequencies. Microarray analysis was also performed to obtain quantitative expression data for these subtracted cDNA clones. Analysis of fish across seasons was also conducted using both F(2) and F(3) salmon. Results of the microarray data essentially corresponded with those of the subtraction data when both F(2) and F(3) fish were completely
Further developments on a novel color sensitive CMOS detector
NASA Astrophysics Data System (ADS)
Langfelder, G.; Longoni, A.; Zaraga, F.
The Transverse Field Detector (TFD) is a recently proposed Silicon pixel device designed to perform color imaging without the use of color filters. The color detection principle is based on the dependence of the Silicon absorption coefficient from the wavelength and relies on the generation of a suitable transverse electric field configuration, within the semiconductor active layer, to drive photocarriers generated at different depths towards different collecting electrodes. Each electrode has in this way a different spectral response with respect to the incoming wavelength. Pixels with three or four different spectral responses can be implemented within ~ 6 μm of pixel dimension. Thanks to the compatibility with standard triple well CMOS processes, the TFD can be used in an Active Pixel Sensor exploiting a dedicated readout topology, based on a single transistor charge amplifier. The overall APS electronics includes five transistors (5T) and a feedback capacitance, with a resulting overall fill factor around 50%. In this work the three colors and four colors TFD pixel simulations and implementations in a 90 nm standard CMOS triple well technology are described. Details on the design of a TFD APS mini matrix are provided and preliminary experimental results on four colors pixels are presented.
Amorphous selenium direct detection CMOS digital x-ray imager with 25 micron pixel pitch
NASA Astrophysics Data System (ADS)
Scott, Christopher C.; Abbaszadeh, Shiva; Ghanbarzadeh, Sina; Allan, Gary; Farrier, Michael; Cunningham, Ian A.; Karim, Karim S.
We have developed a high resolution amorphous selenium (a-Se) direct detection imager using a large-area compatible back-end fabrication process on top of a CMOS active pixel sensor having 25 micron pixel pitch. Integration of a-Se with CMOS technology requires overcoming CMOS/a-Se interfacial strain, which initiates nucleation of crystalline selenium and results in high detector dark currents. A CMOS-compatible polyimide buffer layer was used to planarize the backplane and provide a low stress and thermally stable surface for a-Se. The buffer layer inhibits crystallization and provides detector stability that is not only a performance factor but also critical for favorable long term cost-benefit considerations in the application of CMOS digital x-ray imagers in medical practice. The detector structure is comprised of a polyimide (PI) buffer layer, the a-Se layer, and a gold (Au) top electrode. The PI layer is applied by spin-coating and is patterned using dry etching to open the backplane bond pads for wire bonding. Thermal evaporation is used to deposit the a-Se and Au layers, and the detector is operated in hole collection mode (i.e. a positive bias on the Au top electrode). High resolution a-Se diagnostic systems typically use 70 to 100 μm pixel pitch and have a pre-sampling modulation transfer function (MTF) that is significantly limited by the pixel aperture. Our results confirm that, for a densely integrated 25 μm pixel pitch CMOS array, the MTF approaches the fundamental material limit, i.e. where the MTF begins to be limited by the a-Se material properties and not the pixel aperture. Preliminary images demonstrating high spatial resolution have been obtained from a frst prototype imager.
Fabrication and Characterization of a CMOS-MEMS Humidity Sensor.
Dennis, John-Ojur; Ahmed, Abdelaziz-Yousif; Khir, Mohd-Haris
This paper reports on the fabrication and characterization of a Complementary Metal Oxide Semiconductor-Microelectromechanical System (CMOS-MEMS) device with embedded microheater operated at relatively elevated temperatures (40 °C to 80 °C) for the purpose of relative humidity measurement. The sensing principle is based on the change in amplitude of the device due to adsorption or desorption of humidity on the active material layer of titanium dioxide (TiO2) nanoparticles deposited on the moving plate, which results in changes in the mass of the device. The sensor has been designed and fabricated through a standard 0.35 µm CMOS process technology and post-CMOS micromachining technique has been successfully implemented to release the MEMS structures. The sensor is operated in the dynamic mode using electrothermal actuation and the output signal measured using a piezoresistive (PZR) sensor connected in a Wheatstone bridge circuit. The output voltage of the humidity sensor increases from 0.585 mV to 30.580 mV as the humidity increases from 35% RH to 95% RH. The output voltage is found to be linear from 0.585 mV to 3.250 mV as the humidity increased from 35% RH to 60% RH, with sensitivity of 0.107 mV/% RH; and again linear from 3.250 mV to 30.580 mV as the humidity level increases from 60% RH to 95% RH, with higher sensitivity of 0.781 mV/% RH. On the other hand, the sensitivity of the humidity sensor increases linearly from 0.102 mV/% RH to 0.501 mV/% RH with increase in the temperature from 40 °C to 80 °C and a maximum hysteresis of 0.87% RH is found at a relative humidity of 80%. The sensitivity is also frequency dependent, increasing from 0.500 mV/% RH at 2 Hz to reach a maximum value of 1.634 mV/% RH at a frequency of 12 Hz, then decreasing to 1.110 mV/% RH at a frequency of 20 Hz. Finally, the CMOS-MEMS humidity sensor showed comparable response, recovery, and repeatability of measurements in three cycles as compared to a standard sensor that directly
Fabrication and Characterization of a CMOS-MEMS Humidity Sensor
Dennis, John-Ojur; Ahmed, Abdelaziz-Yousif; Khir, Mohd-Haris
This paper reports on the fabrication and characterization of a Complementary Metal Oxide Semiconductor-Microelectromechanical System (CMOS-MEMS) device with embedded microheater operated at relatively elevated temperatures (40 °C to 80 °C) for the purpose of relative humidity measurement. The sensing principle is based on the change in amplitude of the device due to adsorption or desorption of humidity on the active material layer of titanium dioxide (TiO2) nanoparticles deposited on the moving plate, which results in changes in the mass of the device. The sensor has been designed and fabricated through a standard 0.35 µm CMOS process technology and post-CMOS micromachining technique has been successfully implemented to release the MEMS structures. The sensor is operated in the dynamic mode using electrothermal actuation and the output signal measured using a piezoresistive (PZR) sensor connected in a Wheatstone bridge circuit. The output voltage of the humidity sensor increases from 0.585 mV to 30.580 mV as the humidity increases from 35% RH to 95% RH. The output voltage is found to be linear from 0.585 mV to 3.250 mV as the humidity increased from 35% RH to 60% RH, with sensitivity of 0.107 mV/% RH; and again linear from 3.250 mV to 30.580 mV as the humidity level increases from 60% RH to 95% RH, with higher sensitivity of 0.781 mV/% RH. On the other hand, the sensitivity of the humidity sensor increases linearly from 0.102 mV/% RH to 0.501 mV/% RH with increase in the temperature from 40 °C to 80 °C and a maximum hysteresis of 0.87% RH is found at a relative humidity of 80%. The sensitivity is also frequency dependent, increasing from 0.500 mV/% RH at 2 Hz to reach a maximum value of 1.634 mV/% RH at a frequency of 12 Hz, then decreasing to 1.110 mV/% RH at a frequency of 20 Hz. Finally, the CMOS-MEMS humidity sensor showed comparable response, recovery, and repeatability of measurements in three cycles as compared to a standard sensor that directly
Integrated Amplification Microarrays for Infectious Disease Diagnostics
Chandler, Darrell P.; Bryant, Lexi; Griesemer, Sara B.; Gu, Rui; Knickerbocker, Christopher; Kukhtin, Alexander; Parker, Jennifer; Zimmerman, Cynthia; George, Kirsten St.; Cooney, Christopher G.
This overview describes microarray-based tests that combine solution-phase amplification chemistry and microarray hybridization within a single microfluidic chamber. The integrated biochemical approach improves microarray workflow for diagnostic applications by reducing the number of steps and minimizing the potential for sample or amplicon cross-contamination. Examples described herein illustrate a basic, integrated approach for DNA and RNA genomes, and a simple consumable architecture for incorporating wash steps while retaining an entirely closed system. It is anticipated that integrated microarray biochemistry will provide an opportunity to significantly reduce the complexity and cost of microarray consumables, equipment, and workflow, which in turn will enable a broader spectrum of users to exploit the intrinsic multiplexing power of microarrays for infectious disease diagnostics.
Over the past several years microarray technology has evolved into a critical component of any discovery based program. Since 1999, the Association of Biomolecular Resource Facilities (ABRF) Microarray Research Group (MARG) has conducted biennial surveys designed to generate a pr...
Living Cell Microarrays: An Overview of Concepts.
Jonczyk, Rebecca; Kurth, Tracy; Lavrentieva, Antonina; Walter, Johanna-Gabriela; Scheper, Thomas; Stahl, Frank
Living cell microarrays are a highly efficient cellular screening system. Due to the low number of cells required per spot, cell microarrays enable the use of primary and stem cells and provide resolution close to the single-cell level. Apart from a variety of conventional static designs, microfluidic microarray systems have also been established. An alternative format is a microarray consisting of three-dimensional cell constructs ranging from cell spheroids to cells encapsulated in hydrogel. These systems provide an in vivo-like microenvironment and are preferably used for the investigation of cellular physiology, cytotoxicity, and drug screening. Thus, many different high-tech microarray platforms are currently available. Disadvantages of many systems include their high cost, the requirement of specialized equipment for their manufacture, and the poor comparability of results between different platforms. In this article, we provide an overview of static, microfluidic, and 3D cell microarrays. In addition, we describe a simple method for the printing of living cell microarrays on modified microscope glass slides using standard DNA microarray equipment available in most laboratories. Applications in research and diagnostics are discussed, e.g., the selective and sensitive detection of biomarkers. Finally, we highlight current limitations and the future prospects of living cell microarrays. PMID:27600077
Living Cell Microarrays: An Overview of Concepts
Jonczyk, Rebecca; Kurth, Tracy; Lavrentieva, Antonina; Walter, Johanna-Gabriela; Scheper, Thomas; Stahl, Frank
Living cell microarrays are a highly efficient cellular screening system. Due to the low number of cells required per spot, cell microarrays enable the use of primary and stem cells and provide resolution close to the single-cell level. Apart from a variety of conventional static designs, microfluidic microarray systems have also been established. An alternative format is a microarray consisting of three-dimensional cell constructs ranging from cell spheroids to cells encapsulated in hydrogel. These systems provide an in vivo-like microenvironment and are preferably used for the investigation of cellular physiology, cytotoxicity, and drug screening. Thus, many different high-tech microarray platforms are currently available. Disadvantages of many systems include their high cost, the requirement of specialized equipment for their manufacture, and the poor comparability of results between different platforms. In this article, we provide an overview of static, microfluidic, and 3D cell microarrays. In addition, we describe a simple method for the printing of living cell microarrays on modified microscope glass slides using standard DNA microarray equipment available in most laboratories. Applications in research and diagnostics are discussed, e.g., the selective and sensitive detection of biomarkers. Finally, we highlight current limitations and the future prospects of living cell microarrays. PMID:27600077
Clustering Short Time-Series Microarray
NASA Astrophysics Data System (ADS)
Ping, Loh Wei; Hasan, Yahya Abu
Most microarray analyses are carried out on static gene expressions. However, the dynamical study of microarrays has lately gained more attention. Most researches on time-series microarray emphasize on the bioscience and medical aspects but few from the numerical aspect. This study attempts to analyze short time-series microarray mathematically using STEM clustering tool which formally preprocess data followed by clustering. We next introduce the Circular Mould Distance (CMD) algorithm with combinations of both preprocessing and clustering analysis. Both methods are subsequently compared in terms of efficiencies.
Protein microarrays as tools for functional proteomics.
LaBaer, Joshua; Ramachandran, Niroshan
Protein microarrays present an innovative and versatile approach to study protein abundance and function at an unprecedented scale. Given the chemical and structural complexity of the proteome, the development of protein microarrays has been challenging. Despite these challenges there has been a marked increase in the use of protein microarrays to map interactions of proteins with various other molecules, and to identify potential disease biomarkers, especially in the area of cancer biology. In this review, we discuss some of the promising advances made in the development and use of protein microarrays. PMID:15701447
Graphene/Si CMOS Hybrid Hall Integrated Circuits
Huang, Le; Xu, Huilong; Zhang, Zhiyong; Chen, Chengying; Jiang, Jianhua; Ma, Xiaomeng; Chen, Bingyan; Li, Zishen; Zhong, Hua; Peng, Lian-Mao
Graphene/silicon CMOS hybrid integrated circuits (ICs) should provide powerful functions which combines the ultra-high carrier mobility of graphene and the sophisticated functions of silicon CMOS ICs. But it is difficult to integrate these two kinds of heterogeneous devices on a single chip. In this work a low temperature process is developed for integrating graphene devices onto silicon CMOS ICs for the first time, and a high performance graphene/CMOS hybrid Hall IC is demonstrated. Signal amplifying/process ICs are manufactured via commercial 0.18 um silicon CMOS technology, and graphene Hall elements (GHEs) are fabricated on top of the passivation layer of the CMOS chip via a low-temperature micro-fabrication process. The sensitivity of the GHE on CMOS chip is further improved by integrating the GHE with the CMOS amplifier on the Si chip. This work not only paves the way to fabricate graphene/Si CMOS Hall ICs with much higher performance than that of conventional Hall ICs, but also provides a general method for scalable integration of graphene devices with silicon CMOS ICs via a low-temperature process. PMID:24998222
Versatile High Resolution Oligosaccharide Microarrays for Plant Glycobiology and Cell Wall Research*
Pedersen, Henriette L.; Fangel, Jonatan U.; McCleary, Barry; Ruzanski, Christian; Rydahl, Maja G.; Ralet, Marie-Christine; Farkas, Vladimir; von Schantz, Laura; Marcus, Susan E.; Andersen, Mathias C. F.; Field, Rob; Ohlin, Mats; Knox, J. Paul; Clausen, Mads H.; Willats, William G. T.
Microarrays are powerful tools for high throughput analysis, and hundreds or thousands of molecular interactions can be assessed simultaneously using very small amounts of analytes. Nucleotide microarrays are well established in plant research, but carbohydrate microarrays are much less established, and one reason for this is a lack of suitable glycans with which to populate arrays. Polysaccharide microarrays are relatively easy to produce because of the ease of immobilizing large polymers noncovalently onto a variety of microarray surfaces, but they lack analytical resolution because polysaccharides often contain multiple distinct carbohydrate substructures. Microarrays of defined oligosaccharides potentially overcome this problem but are harder to produce because oligosaccharides usually require coupling prior to immobilization. We have assembled a library of well characterized plant oligosaccharides produced either by partial hydrolysis from polysaccharides or by de novo chemical synthesis. Once coupled to protein, these neoglycoconjugates are versatile reagents that can be printed as microarrays onto a variety of slide types and membranes. We show that these microarrays are suitable for the high throughput characterization of the recognition capabilities of monoclonal antibodies, carbohydrate-binding modules, and other oligosaccharide-binding proteins of biological significance and also that they have potential for the characterization of carbohydrate-active enzymes. PMID:22988248
Over the past several years, the field of microarrays has grown and evolved drastically. In its continued efforts to track this evolution, the ABRF-MARG has once again conducted a survey of international microarray facilities and individual microarray users. The goal of the surve...
2008 Microarray Research Group (MARG Survey): Sensing the State of Microarray Technology
Over the past several years, the field of microarrays has grown and evolved drastically. In its continued efforts to track this evolution and transformation, the ABRF-MARG has once again conducted a survey of international microarray facilities and individual microarray users. Th...
Gene-set activity toolbox (GAT): A platform for microarray-based cancer diagnosis using an integrative gene-set analysis approach.
Engchuan, Worrawat; Meechai, Asawin; Tongsima, Sissades; Doungpan, Narumol; Chan, Jonathan H
Cancer is a complex disease that cannot be diagnosed reliably using only single gene expression analysis. Using gene-set analysis on high throughput gene expression profiling controlled by various environmental factors is a commonly adopted technique used by the cancer research community. This work develops a comprehensive gene expression analysis tool (gene-set activity toolbox: (GAT)) that is implemented with data retriever, traditional data pre-processing, several gene-set analysis methods, network visualization and data mining tools. The gene-set analysis methods are used to identify subsets of phenotype-relevant genes that will be used to build a classification model. To evaluate GAT performance, we performed a cross-dataset validation study on three common cancers namely colorectal, breast and lung cancers. The results show that GAT can be used to build a reasonable disease diagnostic model and the predicted markers have biological relevance. GAT can be accessed from http://gat.sit.kmutt.ac.th where GAT's java library for gene-set analysis, simple classification and a database with three cancer benchmark datasets can be downloaded. PMID:27102089
A portable optical waveguide resonance light-scattering scanner for microarray detection.
Xing, Xuefeng; Liu, Wanyao; Li, Tao; Xing, Shu; Fu, Xueqi; Wu, Dongyang; Liu, Dianjun; Wang, Zhenxin
In the present work, a portable and low-cost planar waveguide based resonance light scattering (RLS) scanner (termed as: PW-RLS scanner) has been developed for microarray detection. The PW-RLS scanner employs a 2 × 4 white light emitting diode array (WLEDA) as the excitation light source, a folded optical path with a complementary metal oxide semiconductor (CMOS) as the signal/image acquisition device and stepper motors with gear drives as the mechanical drive system. The biological binding/recognizing events on the microarray can be detected with an evanescent waveguide-directed illumination and light-scattering label (e.g., nanoparticles) while the microarray slide acts as an evanescent waveguide substrate. The performance of the as-developed PW-RLS scanner has been evaluated by analyzing type 2 diabetes mellitus (T2DM) risk genes. Highly selective and sensitive (less than 1% allele frequency at the attomole-level) T2DM risk gene detection is achieved using single-stranded DNA functionalized gold nanoparticles (ssDNA-GNPs) as detection probes. Additionally, the successful simultaneous analysis of 15 T2DM patient genotypes suggests that the device has great potential for the realization of a personalized diagnostic test for a given disease or patient follow-up. PMID:26567521
Ultralow-Loss CMOS Copper Plasmonic Waveguides.
Fedyanin, Dmitry Yu; Yakubovsky, Dmitry I; Kirtaev, Roman V; Volkov, Valentyn S
Surface plasmon polaritons can give a unique opportunity to manipulate light at a scale well below the diffraction limit reducing the size of optical components down to that of nanoelectronic circuits. At the same time, plasmonics is mostly based on noble metals, which are not compatible with microelectronics manufacturing technologies. This prevents plasmonic components from integration with both silicon photonics and silicon microelectronics. Here, we demonstrate ultralow-loss copper plasmonic waveguides fabricated in a simple complementary metal-oxide semiconductor (CMOS) compatible process, which can outperform gold plasmonic waveguides simultaneously providing long (>40 μm) propagation length and deep subwavelength (∼λ(2)/50, where λ is the free-space wavelength) mode confinement in the telecommunication spectral range. These results create the backbone for the development of a CMOS plasmonic platform and its integration in future electronic chips. PMID:26654281
Noise in a CMOS digital pixel sensor
NASA Astrophysics Data System (ADS)
Chi, Zhang; Suying, Yao; Jiangtao, Xu
Based on the study of noise performance in CMOS digital pixel sensor (DPS), a mathematical model of noise is established with the pulse-width-modulation (PWM) principle. Compared with traditional CMOS image sensors, the integration time is different and A/D conversion is implemented in each PWM DPS pixel. Then, the quantitative calculating formula of system noise is derived. It is found that dark current shot noise is the dominant noise source in low light region while photodiode shot noise becomes significantly important in the bright region. In this model, photodiode shot noise does not vary with luminance, but dark current shot noise does. According to increasing photodiode capacitance and the comparator's reference voltage or optimizing the mismatch in the comparator, the total noise can be reduced. These results serve as a guideline for the design of PWM DPS.
Spectrum acquisition of detonation based on CMOS
NASA Astrophysics Data System (ADS)
Li, Yan; Bai, Yonglin; Wang, Bo; Liu, Baiyu; Xue, Yingdong; Zhang, Wei; Gou, Yongsheng; Bai, Xiaohong; Qin, Junjun; Xian, Ouyang
The detection of high-speed dynamic spectrum is the main method to acquire transient information. In order to obtain the large amount spectral data in real-time during the process of detonation, a CMOS-based system with high-speed spectrum data acquisition is designed. The hardware platform of the system is based on FPGA, and the unique characteristic of CMOS image sensors in the rolling shutter model is used simultaneously. Using FPGA as the master control chip of the system, not only provides the time sequence for CIS, but also controls the storage and transmission of the spectral data. In the experiment of spectral data acquisition, the acquired information is transmitted to the host computer through the CameraLink bus. The dynamic spectral curve is obtained after the subsequent processing. The experimental results demonstrate that this system is feasible in the acquisition and storage of high-speed dynamic spectrum information during the process of detonation.
IR CMOS: infrared enhanced silicon imaging
NASA Astrophysics Data System (ADS)
Pralle, M. U.; Carey, J. E.; Haddad, Homayoon; Vineis, C.; Sickler, J.; Li, X.; Jiang, J.; Sahebi, F.; Palsule, C.; McKee, J.
SiOnyx has developed visible and infrared CMOS image sensors leveraging a proprietary ultrafast laser semiconductor process technology. This technology demonstrates 10 fold improvements in infrared sensitivity over incumbent imaging technology while maintaining complete compatibility with standard CMOS image sensor process flows. Furthermore, these sensitivity enhancements are achieved on a focal plane with state of the art noise performance of 2 electrons/pixel. By capturing light in the visible regime as well as infrared light from the night glow, this sensor technology provides imaging in daytime through twilight and into nighttime conditions. The measured 10x quantum efficiency at the critical 1064 nm laser node enables see spot imaging capabilities in a variety of ambient conditions. The spectral sensitivity is from 400 to 1200 nm.
Cmos spdt switch for wlan applications
NASA Astrophysics Data System (ADS)
Bhuiyan, M. A. S.; Reaz, M. B. I.; Rahman, L. F.; Minhad, K. N.
WLAN has become an essential part of our today's life. The advancement of CMOS technology let the researchers contribute low power, size and cost effective WLAN devices. This paper proposes a single pole double through transmit/receive (T/R) switch for WLAN applications in 0.13 μm CMOS technology. The proposed switch exhibit 1.36 dB insertion loss, 25.3 dB isolation and 24.3 dBm power handling capacity. Moreover, it only dissipates 786.7 nW power per cycle. The switch utilizes only transistor aspect ratio optimization and resistive body floating technique to achieve such desired performance. In this design the use of bulky inductor and capacitor is avoided to evade imposition of unwanted nonlinearities to the communication signal.
CMOS Camera Array With Onboard Memory
NASA Technical Reports Server (NTRS)
Gat, Nahum
A compact CMOS (complementary metal oxide semiconductor) camera system has been developed with high resolution (1.3 Megapixels), a USB (universal serial bus) 2.0 interface, and an onboard memory. Exposure times, and other operating parameters, are sent from a control PC via the USB port. Data from the camera can be received via the USB port and the interface allows for simple control and data capture through a laptop computer.
CMOS-array design-automation techniques
NASA Technical Reports Server (NTRS)
Feller, A.; Lombardt, T.
Thirty four page report discusses design of 4,096-bit complementary metal oxide semiconductor (CMOS) read-only memory (ROM). CMOSROM is either mask or laser programable. Report is divided into six sections; section one describes background of ROM chips; section two presents design goals for chip; section three discusses chip implementation and chip statistics; conclusions and recommendations are given in sections four thru six.
Advanced CMOS Radiation Effects Testing Analysis
NASA Technical Reports Server (NTRS)
Pellish, Jonathan Allen; Marshall, Paul W.; Rodbell, Kenneth P.; Gordon, Michael S.; LaBel, Kenneth A.; Schwank, James R.; Dodds, Nathaniel A.; Castaneda, Carlos M.; Berg, Melanie D.; Kim, Hak S.; Phan, Anthony M.; Seidleck, Christina M.
Presentation at the annual NASA Electronic Parts and Packaging (NEPP) Program Electronic Technology Workshop (ETW). The material includes an update of progress in this NEPP task area over the past year, which includes testing, evaluation, and analysis of radiation effects data on the IBM 32 nm silicon-on-insulator (SOI) complementary metal oxide semiconductor (CMOS) process. The testing was conducted using test vehicles supplied by directly by IBM.
Advanced CMOS Radiation Effects Testing and Analysis
NASA Technical Reports Server (NTRS)
Pellish, J. A.; Marshall, P. W.; Rodbell, K. P.; Gordon, M. S.; LaBel, K. A.; Schwank, J. R.; Dodds, N. A.; Castaneda, C. M.; Berg, M. D.; Kim, H. S.; Phan, A. M.; Seidleck, C. M.
Presentation at the annual NASA Electronic Parts and Packaging (NEPP) Program Electronic Technology Workshop (ETW). The material includes an update of progress in this NEPP task area over the past year, which includes testing, evaluation, and analysis of radiation effects data on the IBM 32 nm silicon-on-insulator (SOI) complementary metal oxide semiconductor (CMOS) process. The testing was conducted using test vehicles supplied by directly by IBM.
Radiation effects on scientific CMOS image sensor
NASA Astrophysics Data System (ADS)
Yuanfu, Zhao; Liyan, Liu; Xiaohui, Liu; Xiaofeng, Jin; Xiang, Li
A systemic solution for radiation hardened design is presented. Besides, a series of experiments have been carried out on the samples, and then the photoelectric response characteristic and spectral characteristic before and after the experiments have been comprehensively analyzed. The performance of the CMOS image sensor with the radiation hardened design technique realized total-dose resilience up to 300 krad(Si) and resilience to single-event latch up for LET up to 110 MeV·cm2/mg.
Radiation characteristics of scintillator coupled CMOS APS for radiography conditions
NASA Astrophysics Data System (ADS)
Kim, Kwang Hyun; Kim, Soongpyung; Kang, Dong-Won; Kim, Dong-Kie
Under industrial radiography conditions, we analyzed short-term radiation characteristics of scintillator coupled CMOS APS (hereinafter SC CMOS APS). By means of experimentation, the contribution of the transmitted X-ray through the scintillator to the properties of the CMOS APS and the afterimage, generated in the acquired image even at low dose condition, were investigated. To see the transmitted X-ray effects on the CMOS APS, Fein focus™ X-ray machine, two scintillators of Lanex™ Fine and Regular, and two CMOS APS array of RadEye™ were used under the conditions of 50 kV p/1 mAs and 100 kV p/1 mAs. By measuring the transmitted X-ray on signal and Noise Power Spectrum, we analytically examined the generation mechanism of the afterimage, based on dark signal or dark current increase in the sensor, and explained the afterimage in the SC CMOS APS.
Disc-based microarrays: principles and analytical applications.
Morais, Sergi; Puchades, Rosa; Maquieira, Ángel
The idea of using disk drives to monitor molecular biorecognition events on regular optical discs has received considerable attention during the last decade. CDs, DVDs, Blu-ray discs and other new optical discs are universal and versatile supports with the potential for development of protein and DNA microarrays. Besides, standard disk drives incorporated in personal computers can be used as compact and affordable optical reading devices. Consequently, a CD technology, resulting from the audio-video industry, has been used to develop analytical applications in health care, environmental monitoring, food safety and quality assurance. The review presents and critically evaluates the current state of the art of disc-based microarrays with illustrative examples, including past, current and future developments. Special mention is made of the analytical developments that use either chemically activated or raw standard CDs where proteins, oligonucleotides, peptides, haptens or other biological probes are immobilized. The discs are also used to perform the assays and must maintain their readability with standard optical drives. The concept and principle of evolving disc-based microarrays and the evolution of disk drives as optical detectors are also described. The review concludes with the most relevant uses ordered chronologically to provide an overview of the progress of CD technology applications in the life sciences. Also, it provides a selection of important references to the current literature. Graphical Abstract High density disc-based microarrays. PMID:26922341
Carboxymethyl cellulose film as a substrate for microarray fabrication.
Shlyapnikov, Yuri M; Shlyapnikova, Elena A; Morozov, Victor N
Magnetic beads (MB) are widely used for quick and highly sensitive signal detection in microarray-based assays. However, this technique imposes stringent requirements for smoothness and adhesive properties of the surface, which most common substrates do not satisfy. We report here a new type of substrate for microarrays with a low adhesion to MB-thermally cross-linked carboxymethyl cellulose (CMC) film. This substrate can be readily fabricated on a conventional glass slide. A highly cross-linked CMC film (∼1 cross-link per monomer unit) possesses a surface smooth on a nanometer scale and a low adhesion to protein-coated MB, which partly originates from electrostatic repulsion of MB from negatively charged CMC surface. The efficiency of the CMC substrate is demonstrated hereby in fabrication of microarrays for the detection of three bacterial toxins: cholera toxin, staphylococcal enterotoxin A, and toxic shock syndrome toxin. The assay employing a primary antibodies arrayed on a CMC surface and detection of the bound bacterial toxins with a biotinylated secondary antibodies and streptavidin-coated MB resulted in a limits of detection as low as 0.1 ng/mL. The CMC-based microarrays demonstrated very high storage stability; their activity did not change after one year storage at room temperature. PMID:24446727
CMOS-controlled rapidly tunable photodetectors
NASA Astrophysics Data System (ADS)
Chen, Ray
With rapidly increasing data bandwidth demands, wavelength-division-multiplexing (WDM) optical access networks seem unavoidable in the near future. To operate WDM optical networks in an efficient scheme, wavelength reconfigurability and scalability of the network are crucial. Unfortunately, most of the existing wavelength tunable technologies are neither rapidly tunable nor spectrally programmable. This dissertation presents a tunable photodetector that is designed for dynamic-wavelength allocation WDM network environments. The wavelength tuning mechanism is completely different from existing technologies. The spectrum of this detector is programmable through low-voltage digital patterns. Since the wavelength selection is achieved by electronic means, the device wavelength reconfiguration time is as fast as the electronic switching time. In this dissertation work, we have demonstrated a tunable detector that is hybridly integrated with its customized CMOS driver and receiver with nanosecond wavelength reconfiguration time. In addition to its nanosecond wavelength reconfiguration time, the spectrum of this detector is digitally programmable, which means that it can adapt to system changes without re-fabrication. We have theoretically developed and experimentally demonstrated two device operating algorithms based on the same orthogonal device-optics basis. Both the rapid wavelength tuning time and the scalability make this novel device very viable for new reconfigurable WDM networks. By taking advantage of CMOS circuit design, this detector concept can be further extended for simultaneous multiple wavelength detection. We have developed one possible chip architecture and have designed a CMOS tunable optical demux for simultaneous controllable two-wavelength detection.
Efficient design of CMOS TSC checkers
NASA Technical Reports Server (NTRS)
Biddappa, Anita; Shamanna, Manjunath K.; Maki, Gary; Whitaker, Sterling
This paper considers the design of an efficient, robustly testable, CMOS Totally Self-Checking (TSC) Checker for k-out-of-2k codes. Most existing implementations use primitive gates and assume the single stuck-at fault model. The self-testing property has been found to fail for CMOS TSC checkers under the stuck-open fault model due to timing skews and arbitrary delays in the circuit. A new four level design using CMOS primitive gates (NAND, NOR, INVERTERS) is presented. This design retains its properties under the stuck-open fault model. Additionally, this method offers an impressive reduction (greater than 70 percent) in gate count, gate inputs, and test set size when compared to the existing method. This implementation is easily realizable and is based on Anderson's technique. A thorough comparative study has been made on the proposed implementation and Kundu's implementation and the results indicate that the proposed one is better than Kundu's in all respects for k-out-of-2k codes.
Quantitative optical metrology with CMOS cameras
NASA Astrophysics Data System (ADS)
Furlong, Cosme; Kolenovic, Ervin; Ferguson, Curtis F.
Recent advances in laser technology, optical sensing, and computer processing of data, have lead to the development of advanced quantitative optical metrology techniques for high accuracy measurements of absolute shapes and deformations of objects. These techniques provide noninvasive, remote, and full field of view information about the objects of interest. The information obtained relates to changes in shape and/or size of the objects, characterizes anomalies, and provides tools to enhance fabrication processes. Factors that influence selection and applicability of an optical technique include the required sensitivity, accuracy, and precision that are necessary for a particular application. In this paper, sensitivity, accuracy, and precision characteristics in quantitative optical metrology techniques, and specifically in optoelectronic holography (OEH) based on CMOS cameras, are discussed. Sensitivity, accuracy, and precision are investigated with the aid of National Institute of Standards and Technology (NIST) traceable gauges, demonstrating the applicability of CMOS cameras in quantitative optical metrology techniques. It is shown that the advanced nature of CMOS technology can be applied to challenging engineering applications, including the study of rapidly evolving phenomena occurring in MEMS and micromechatronics.
Accelerated life testing effects on CMOS microcircuit characteristics
NASA Technical Reports Server (NTRS)
The 250 C, 200C and 125C accelerated tests are described. The wear-out distributions from the 250 and 200 C tests were used to estimate the activation energy between the two test temperatures. The duration of the 125 C test was not sufficient to bring the test devices into the wear-out region. It was estimated that, for the most complex of the three devices types, the activation energy between 200 C and 125 C should be at least as high as that between 250 C and 200 C. The practicality of the use of high temperature for the accelerated life tests from the point of view of durability of equipment is assessed. Guidlines for the development of accelerated life-test conditions are proposed. The use of the silicon nitride overcoat to improve the high temperature accelerated life-test characteristics of CMOS microcircuits is described.
Correct CMOS IC defect models for quality testing
NASA Technical Reports Server (NTRS)
Soden, Jerry M.; Hawkins, Charles F.
Leading edge, high reliability, and low escape CMOS IC test practices have now virtually removed the stuck-at fault model and replaced it with more defect-orientated models. Quiescent power supply current testing (I(sub DDQ)) combined with strategic use of high speed test patterns is the recommended approach to zero defect and high reliability testing goals. This paper reviews the reasons for the change in CMOS IC test practices and outlines an improved CMOS IC test methodology.
A Standard CMOS Humidity Sensor without Post-Processing
Nizhnik, Oleg; Higuchi, Kohei; Maenaka, Kazusuke
A 2 μW power dissipation, voltage-output, humidity sensor accurate to 5% relative humidity was developed using the LFoundry 0.15 μm CMOS technology without post-processing. The sensor consists of a woven lateral array of electrodes implemented in CMOS top metal, a Intervia Photodielectric 8023–10 humidity-sensitive layer, and a CMOS capacitance to voltage converter. PMID:22163949
Behavior of faulty double BJT BiCMOS logic gates
NASA Technical Reports Server (NTRS)
Menon, Sankaran M.; Malaiya, Yashwant K.; Jayasumana, Anura P.
Logic Behavior of a Double BJT BiCMOS device under transistor level shorts and opens is examined. In addition to delay faults, faults that cause the gate to exhibit sequential behavior were observed. Several faults can be detected only by monitoring the current. The faulty behavior of Bipolar (TTL) and CMOS logic families is compared with BiCMOS, to bring out the testability differences.
Functional assessment of time course microarray data
Nueda, María José; Sebastián, Patricia; Tarazona, Sonia; García-García, Francisco; Dopazo, Joaquín; Ferrer, Alberto; Conesa, Ana
Motivation Time-course microarray experiments study the progress of gene expression along time across one or several experimental conditions. Most developed analysis methods focus on the clustering or the differential expression analysis of genes and do not integrate functional information. The assessment of the functional aspects of time-course transcriptomics data requires the use of approaches that exploit the activation dynamics of the functional categories to where genes are annotated. Methods We present three novel methodologies for the functional assessment of time-course microarray data. i) maSigFun derives from the maSigPro method, a regression-based strategy to model time-dependent expression patterns and identify genes with differences across series. maSigFun fits a regression model for groups of genes labeled by a functional class and selects those categories which have a significant model. ii) PCA-maSigFun fits a PCA model of each functional class-defined expression matrix to extract orthogonal patterns of expression change, which are then assessed for their fit to a time-dependent regression model. iii) ASCA-functional uses the ASCA model to rank genes according to their correlation to principal time expression patterns and assess functional enrichment on a GSA fashion. We used simulated and experimental datasets to study these novel approaches. Results were compared to alternative methodologies. Results Synthetic and experimental data showed that the different methods are able to capture different aspects of the relationship between genes, functions and co-expression that are biologically meaningful. The methods should not be considered as competitive but they provide different insights into the molecular and functional dynamic events taking place within the biological system under study. PMID:19534758
Clinical Utility of Microarrays: Current Status, Existing Challenges and Future Outlook
Li, Xinmin; Quigg, Richard J; Zhou, Jian; Gu, Weikuan; Nagesh Rao, P; Reed, Elaine F
Microarray-based clinical tests have become powerful tools in the diagnosis and treatment of diseases. In contrast to traditional DNA-based tests that largely focus on single genes associated with rare conditions, microarray-based tests are ideal for the study of diseases with underlying complex genetic causes. Several microarray based tests have been translated into clinical practice such as MammaPrint and AmpliChip CYP450. Additional cancer-related microarray-based tests are either in the process of FDA review or under active development, including Tissue of Tumor Origin and AmpliChip p53. All diagnostic microarray testing is ordered by physicians and tested by a Clinical Laboratories Improvement Amendment-certified (CLIA) reference laboratory. Recently, companies offering consumer based microarray testing have emerged. Individuals can order tests online and service providers deliver the results directly to the clients via a password-protected secure website. Navigenics, 23andMe and deCODE Genetics represent pioneering companies in this field. Although the progress of these microarray-based tests is extremely encouraging with the potential to revolutionize the recognition and treatment of common diseases, these tests are still in their infancy and face technical, clinical and marketing challenges. In this article, we review microarray-based tests which are currently approved or under review by the FDA, as well as the consumer-based testing. We also provide a summary of the challenges and strategic solutions in the development and clinical use of the microarray-based tests. Finally, we present a brief outlook for the future of microarray-based clinical applications. PMID:19506735
Protein-Based Microarray for the Detection of Pathogenic Bacteria
Technology Transfer Automated Retrieval System (TEKTRAN)
Microarrays have been used for gene expression and protein interaction studies, but recently, multianalyte diagnostic assays have employed the microarray platform. We developed a microarray immunoassay for bacteria, with biotinylated capture antibodies on streptavidin slides. To complete the fluor...
Interferometric comparison of the performance of a CMOS and sCMOS detector
NASA Astrophysics Data System (ADS)
Flores-Moreno, J. M.; De la Torre I., Manuel H.; Hernández-Montes, M. S.; Pérez-López, Carlos; Mendoza S., Fernando
We present an analysis of the imaging performance of two state-of-the-art sensors widely used in the nondestructive- testing area (NDT). The analysis is based on the quantification of the signal-to-noise (SNR) ratio from an optical phase image. The calculation of the SNR is based on the relation of the median (average) and standard deviation measurements over specific areas of interest in the phase images of both sensors. This retrieved phase is coming from the vibrational behavior of a large object by means of an out-of-plane holographic interferometer. The SNR is used as a figure-of-merit to evaluate and compare the performance of the CMOS and scientific CMOS (sCMOS) camera as part of the experimental set-up. One of the cameras has a high speed CMOS sensor while the other has a high resolution sCMOS sensor. The object under study is a metallically framed table with a Formica cover with an observable area of 1.1 m2. The vibration induced to the sample is performed by a linear step motor with an attached tip in the motion stage. Each camera is used once at the time to record the deformation keeping the same experimental conditions for each case. These measurements may complement the conventional procedures or technical information commonly used to evaluate a camerás performance such as: quantum efficiency, spatial resolution and others. Results present post processed images from both cameras, but showing a smoother and easy to unwrap optical phase coming from those recorded with the sCMOS camera.
Tissue Microarrays in Clinical Oncology
Voduc, David; Kenney, Challayne; Nielsen, Torsten O.
The tissue microarray is a recently-implemented, high-throughput technology for the analysis of molecular markers in oncology. This research tool permits the rapid assessment of a biomarker in thousands of tumor samples, using commonly available laboratory assays such as immunohistochemistry and in-situ hybridization. Although introduced less than a decade ago, the TMA has proven to be invaluable in the study of tumor biology, the development of diagnostic tests, and the investigation of oncological biomarkers. This review describes the impact of TMA-based research in clinical oncology and its potential future applications. Technical aspects of TMA construction, and the advantages and disadvantages inherent to this technology are also discussed. PMID:18314063
DNA Microarrays for Identifying Fishes
Nölte, M.; Weber, H.; Silkenbeumer, N.; Hjörleifsdottir, S.; Hreggvidsson, G. O.; Marteinsson, V.; Kappel, K.; Planes, S.; Tinti, F.; Magoulas, A.; Garcia Vazquez, E.; Turan, C.; Hervet, C.; Campo Falgueras, D.; Antoniou, A.; Landi, M.; Blohm, D.
In many cases marine organisms and especially their diverse developmental stages are difficult to identify by morphological characters. DNA-based identification methods offer an analytically powerful addition or even an alternative. In this study, a DNA microarray has been developed to be able to investigate its potential as a tool for the identification of fish species from European seas based on mitochondrial 16S rDNA sequences. Eleven commercially important fish species were selected for a first prototype. Oligonucleotide probes were designed based on the 16S rDNA sequences obtained from 230 individuals of 27 fish species. In addition, more than 1200 sequences of 380 species served as sequence background against which the specificity of the probes was tested in silico. Single target hybridisations with Cy5-labelled, PCR-amplified 16S rDNA fragments from each of the 11 species on microarrays containing the complete set of probes confirmed their suitability. True-positive, fluorescence signals obtained were at least one order of magnitude stronger than false-positive cross-hybridisations. Single nontarget hybridisations resulted in cross-hybridisation signals at approximately 27% of the cases tested, but all of them were at least one order of magnitude lower than true-positive signals. This study demonstrates that the 16S rDNA gene is suitable for designing oligonucleotide probes, which can be used to differentiate 11 fish species. These data are a solid basis for the second step to create a "Fish Chip" for approximately 50 fish species relevant in marine environmental and fisheries research, as well as control of fisheries products. PMID:18270778
Current-mode CMOS hybrid image sensor
NASA Astrophysics Data System (ADS)
Benyhesan, Mohammad Kassim
Digital imaging is growing rapidly making Complimentary Metal-Oxide-Semi conductor (CMOS) image sensor-based cameras indispensable in many modern life devices like cell phones, surveillance devices, personal computers, and tablets. For various purposes wireless portable image systems are widely deployed in many indoor and outdoor places such as hospitals, urban areas, streets, highways, forests, mountains, and towers. However, the increased demand on high-resolution image sensors and improved processing features is expected to increase the power consumption of the CMOS sensor-based camera systems. Increased power consumption translates into a reduced battery life-time. The increased power consumption might not be a problem if there is access to a nearby charging station. On the other hand, the problem arises if the image sensor is located in widely spread areas, unfavorable to human intervention, and difficult to reach. Given the limitation of energy sources available for wireless CMOS image sensor, an energy harvesting technique presents a viable solution to extend the sensor life-time. Energy can be harvested from the sun light or the artificial light surrounding the sensor itself. In this thesis, we propose a current-mode CMOS hybrid image sensor capable of energy harvesting and image capture. The proposed sensor is based on a hybrid pixel that can be programmed to perform the task of an image sensor and the task of a solar cell to harvest energy. The basic idea is to design a pixel that can be configured to exploit its internal photodiode to perform two functions: image sensing and energy harvesting. As a proof of concept a 40 x 40 array of hybrid pixels has been designed and fabricated in a standard 0.5 microm CMOS process. Measurement results show that up to 39 microW of power can be harvested from the array under 130 Klux condition with an energy efficiency of 220 nJ /pixel /frame. The proposed image sensor is a current-mode image sensor which has several
X-ray characterization of CMOS imaging detector with high resolution for fluoroscopic imaging application
NASA Astrophysics Data System (ADS)
Cha, Bo Kyung; Kim, Cho Rong; Jeon, Seongchae; Kim, Ryun Kyung; Seo, Chang-Woo; Yang, Keedong; Heo, Duchang; Lee, Tae-Bum; Shin, Min-Seok; Kim, Jong-Boo; Kwon, Oh-Kyung
This paper introduces complementary metal-oxide semiconductor (CMOS) active pixel sensor (APS)-based X-ray imaging detectors with high spatial resolution for medical imaging application. In this study, our proposed X-ray CMOS imaging sensor has been fabricated by using a 0.35 μm 1 Poly 4 Metal CMOS process. The pixel size is 100 μm×100 μm and the pixel array format is 24×96 pixels, which provide a field-of-view (FOV) of 9.6 mm×2.4 mm. The 14.3-bit extend counting analog-to digital converter (ADC) with built-in binning mode was used to reduce the area and simultaneously improve the image resolution. Both thallium-doped CsI (CsI:Tl) and Gd2O2S:Tb scintillator screens were used as converters for incident X-rays to visible light photons. The optical property and X-ray imaging characterization such as X-ray to light response as a function of incident X-ray exposure dose, spatial resolution and X-ray images of objects were measured under different X-ray energy conditions. The measured results suggest that our developed CMOS-based X-ray imaging detector has the potential for fluoroscopic imaging and cone-beam computed tomography (CBCT) imaging applications.
Single-Photon Avalanche Diodes (SPAD) in CMOS 0.35 μm technology
NASA Astrophysics Data System (ADS)
Pellion, D.; Jradi, K.; Brochard, N.; Prêle, D.; Ginhac, D.
Some decades ago single photon detection used to be the terrain of photomultiplier tube (PMT), thanks to its characteristics of sensitivity and speed. However, PMT has several disadvantages such as low quantum efficiency, overall dimensions, and cost, making them unsuitable for compact design of integrated systems. So, the past decade has seen a dramatic increase in interest in new integrated single-photon detectors called Single-Photon Avalanche Diodes (SPAD) or Geiger-mode APD. SPAD are working in avalanche mode above the breakdown level. When an incident photon is captured, a very fast avalanche is triggered, generating an easily detectable current pulse. This paper discusses SPAD detectors fabricated in a standard CMOS technology featuring both single-photon sensitivity, and excellent timing resolution, while guaranteeing a high integration. In this work, we investigate the design of SPAD detectors using the AMS 0.35 μm CMOS Opto technology. Indeed, such standard CMOS technology allows producing large surface (few mm2) of single photon sensitive detectors. Moreover, SPAD in CMOS technologies could be associated to electronic readout such as active quenching, digital to analog converter, memories and any specific processing required to build efficient calorimeters1
A Guided Materials Screening Approach for Developing Quantitative Sol-gel Derived Protein Microarrays
Helka, Blake-Joseph; Brennan, John D.
Microarrays have found use in the development of high-throughput assays for new materials and discovery of small-molecule drug leads. Herein we describe a guided material screening approach to identify sol-gel based materials that are suitable for producing three-dimensional protein microarrays. The approach first identifies materials that can be printed as microarrays, narrows down the number of materials by identifying those that are compatible with a given enzyme assay, and then hones in on optimal materials based on retention of maximum enzyme activity. This approach is applied to develop microarrays suitable for two different enzyme assays, one using acetylcholinesterase and the other using a set of four key kinases involved in cancer. In each case, it was possible to produce microarrays that could be used for quantitative small-molecule screening assays and production of dose-dependent inhibitor response curves. Importantly, the ability to screen many materials produced information on the types of materials that best suited both microarray production and retention of enzyme activity. The materials data provide insight into basic material requirements necessary for tailoring optimal, high-density sol-gel derived microarrays. PMID:24022739
Envelope tracking CMOS power amplifier with high-speed CMOS envelope amplifier for mobile handsets
NASA Astrophysics Data System (ADS)
Yoshida, Eiji; Sakai, Yasufumi; Oishi, Kazuaki; Yamazaki, Hiroshi; Mori, Toshihiko; Yamaura, Shinji; Suto, Kazuo; Tanaka, Tetsu
A high-efficiency CMOS power amplifier (PA) based on envelope tracking (ET) has been reported for a wideband code division multiple access (W-CDMA) and long term evolution (LTE) application. By adopting a high-speed CMOS envelope amplifier with current direction sensing, a 5% improvement in total power-added efficiency (PAE) and a 11 dB decrease in adjacent channel leakage ratio (ACLR) are achieved with a W-CDMA signal. Moreover, the proposed PA achieves a PAE of 25.4% for a 10 MHz LTE signal at an output power (Pout) of 25.6 dBm and a gain of 24 dB.
MARS: Microarray analysis, retrieval, and storage system
Maurer, Michael; Molidor, Robert; Sturn, Alexander; Hartler, Juergen; Hackl, Hubert; Stocker, Gernot; Prokesch, Andreas; Scheideler, Marcel; Trajanoski, Zlatko
Background Microarray analysis has become a widely used technique for the study of gene-expression patterns on a genomic scale. As more and more laboratories are adopting microarray technology, there is a need for powerful and easy to use microarray databases facilitating array fabrication, labeling, hybridization, and data analysis. The wealth of data generated by this high throughput approach renders adequate database and analysis tools crucial for the pursuit of insights into the transcriptomic behavior of cells. Results MARS (Microarray Analysis and Retrieval System) provides a comprehensive MIAME supportive suite for storing, retrieving, and analyzing multi color microarray data. The system comprises a laboratory information management system (LIMS), a quality control management, as well as a sophisticated user management system. MARS is fully integrated into an analytical pipeline of microarray image analysis, normalization, gene expression clustering, and mapping of gene expression data onto biological pathways. The incorporation of ontologies and the use of MAGE-ML enables an export of studies stored in MARS to public repositories and other databases accepting these documents. Conclusion We have developed an integrated system tailored to serve the specific needs of microarray based research projects using a unique fusion of Web based and standalone applications connected to the latest J2EE application server technology. The presented system is freely available for academic and non-profit institutions. More information can be found at . PMID:15836795
Microarray analysis of gene expression profiles in ripening pineapple fruits
Background Pineapple (Ananas comosus) is a tropical fruit crop of significant commercial importance. Although the physiological changes that occur during pineapple fruit development have been well characterized, little is known about the molecular events that occur during the fruit ripening process. Understanding the molecular basis of pineapple fruit ripening will aid the development of new varieties via molecular breeding or genetic modification. In this study we developed a 9277 element pineapple microarray and used it to profile gene expression changes that occur during pineapple fruit ripening. Results Microarray analyses identified 271 unique cDNAs differentially expressed at least 1.5-fold between the mature green and mature yellow stages of pineapple fruit ripening. Among these 271 sequences, 184 share significant homology with genes encoding proteins of known function, 53 share homology with genes encoding proteins of unknown function and 34 share no significant homology with any database accession. Of the 237 pineapple sequences with homologs, 160 were up-regulated and 77 were down-regulated during pineapple fruit ripening. DAVID Functional Annotation Cluster (FAC) analysis of all 237 sequences with homologs revealed confident enrichment scores for redox activity, organic acid metabolism, metalloenzyme activity, glycolysis, vitamin C biosynthesis, antioxidant activity and cysteine peptidase activity, indicating the functional significance and importance of these processes and pathways during pineapple fruit development. Quantitative real-time PCR analysis validated the microarray expression results for nine out of ten genes tested. Conclusions This is the first report of a microarray based gene expression study undertaken in pineapple. Our bioinformatic analyses of the transcript profiles have identified a number of genes, processes and pathways with putative involvement in the pineapple fruit ripening process. This study extends our knowledge of the
Microactuateur electrothermique bistable: Etude d'implementation avec une technologie standard CMOS
NASA Astrophysics Data System (ADS)
Ressejac, Isabelle
up to a hundred times higher than its thickness. This natural deflection results from the relaxation of internal stresses inside the thin films which are part of the microactuator. These internal stresses are intrinsics to the host CMOS process. We have developed a model of the microactuator's initial deflection using mechanical properties of thin films and dimensions of the structure. Actuation experiments were performed in order to characterize the deflection of the microactuator with respect to the heating of the bilayers (separately and together). We have developed a thermal actuation analytical model for an n-layers multimorph structure, which takes into account the initial deflection resulting from the relaxation of stresses as well as the deflection due to the temperature increase during the electrothermal activation of the bilayers. (Abstract shortened by UMI.)
Faint-meteor survey with a large-format CMOS sensor
NASA Astrophysics Data System (ADS)
Watanabe, J.; Enomoto, T.; Terai, T.; Kasuga, T.; Miyazaki, S.; Oota, K.; Muraoka, F.; Onishi, T.; Yamasaki, T.; Mito, H.; Aoki, T.; Soyano, T.; Tarusawa, K.; Matsunaga, N.; Sako, S.; Kobayashi, N.; Doi, M.
performed during the active period of the Geminid meteor shower. We could take valuable data on December 12 and 13. The result will be given in this presentation, together with the future potential of the large format CMOS sensor.
CMOS APS detector characterization for quantitative X-ray imaging
NASA Astrophysics Data System (ADS)
Endrizzi, Marco; Oliva, Piernicola; Golosio, Bruno; Delogu, Pasquale
An X-ray Imaging detector based on CMOS Active Pixel Sensor and structured scintillator is characterized for quantitative X-ray imaging in the energy range 11-30 keV. Linearity, dark noise, spatial resolution and flat-field correction are the characteristics of the detector subject of investigation. The detector response, in terms of mean Analog-to-Digital Unit and noise, is modeled as a function of the energy and intensity of the X-rays. The model is directly tested using monochromatic X-ray beams and it is also indirectly validated by means of polychromatic X-ray-tube spectra. Such a characterization is suitable for quantitative X-ray imaging and the model can be used in simulation studies that take into account the actual performance of the detector.
Interferometric metrology of wafer nanotopography for advanced CMOS process integration
NASA Astrophysics Data System (ADS)
Valley, John F.; Koliopoulos, Chris L.; Tang, Shouhong
According to industry standards (SEMI M43, Guide for Reporting Wafer Nanotopography), Nanotopography is the non- planar deviation of the whole front wafer surface within a spatial wavelength range of approximately 0.2 to 20 mm and within the fixed quality area (FQA). The need for precision metrology of wafer nanotopography is being actively addressed by interferometric technology. In this paper we present an approach to mapping the whole wafer front surface nanotopography using an engineered coherence interferometer. The interferometer acquires a whole wafer raw topography map. The raw map is then filtered to remove the long spatial wavelength, high amplitude shape contributions and reveal the nanotopography in the filtered map. Filtered maps can be quantitatively analyzed in a variety of ways to enable statistical process control (SPC) of nanotopography parameters. The importance of tracking these parameters for CMOS gate level processes at 180-nm critical dimension, and below, is examined.
Intrinsic signal imaging of brain function using a small implantable CMOS imaging device
NASA Astrophysics Data System (ADS)
Haruta, Makito; Sunaga, Yoshinori; Yamaguchi, Takahiro; Takehara, Hironari; Noda, Toshihiko; Sasagawa, Kiyotaka; Tokuda, Takashi; Ohta, Jun
A brain functional imaging technique over a long period is important to understand brain functions related to animal behavior. We have developed a small implantable CMOS imaging device for measuring brain activity in freely moving animals. This device is composed of a CMOS image sensor chip and LEDs for illumination. In this study, we demonstrated intrinsic signal imaging of blood flow using the device with a green LED light source at a peak wavelength of 535 nm, which corresponds to one of the absorption spectral peaks of blood cells. Brain activity increases regional blood flow. The device light weight of about 0.02 g makes it possible to stably measure brain activity through blood flow over a long period. The device has successfully measured the intrinsic signal related to sensory stimulation on the primary somatosensory cortex.
CMOS cassette for digital upgrade of film-based mammography systems
NASA Astrophysics Data System (ADS)
Baysal, Mehmet A.; Toker, Emre
While full-field digital mammography (FFDM) technology is gaining clinical acceptance, the overwhelming majority (96%) of the installed base of mammography systems are conventional film-screen (FSM) systems. A high performance, and economical digital cassette based product to conveniently upgrade FSM systems to FFDM would accelerate the adoption of FFDM, and make the clinical and technical advantages of FFDM available to a larger population of women. The planned FFDM cassette is based on our commercial Digital Radiography (DR) cassette for 10 cm x 10 cm field-of-view spot imaging and specimen radiography, utilizing a 150 micron columnar CsI(Tl) scintillator and 48 micron active-pixel CMOS sensor modules. Unlike a Computer Radiography (CR) cassette, which requires an external digitizer, our DR cassette transfers acquired images to a display workstation within approximately 5 seconds of exposure, greatly enhancing patient flow. We will present the physical performance of our prototype system against other FFDM systems in clinical use today, using established objective criteria such as the Modulation Transfer Function (MTF), Detective Quantum Efficiency (DQE), and subjective criteria, such as a contrast-detail (CD-MAM) observer performance study. Driven by the strong demand from the computer industry, CMOS technology is one of the lowest cost, and the most readily accessible technologies available for FFDM today. Recent popular use of CMOS imagers in high-end consumer cameras have also resulted in significant advances in the imaging performance of CMOS sensors against rivaling CCD sensors. This study promises to take advantage of these unique features to develop the first CMOS based FFDM upgrade cassette.
Microarray-Based Phospho-Proteomic Profiling of Complex Biological Systems.
Goodwin, C Rory; Woodard, Crystal L; Zhou, Xin; Pan, Jianbo; Olivi, Alessandro; Xia, Shuli; Bettegowda, Chetan; Sciubba, Daniel M; Pevsner, Jonathan; Zhu, Heng; Laterra, John
Protein microarray technology has been successfully used for identifying substrates of purified activated kinases. We used protein microarrays to globally interrogate the effects of PTEN and Akt activity on the phospho-kinome of in vitro and in vivo glioma models and validated results in clinical pathological specimens. Whole cell lysates extracted from tumor samples can be applied to human kinome chip microarrays to profile the global kinase phosphorylation patterns in a high-throughput manner and identify novel substrates inherent to the tumor cell and the interactions with tumor microenvironment. Our findings identify a novel microarray-based method for assessing intracellular signaling events applicable to human oncogenesis and other pathophysiologic states. PMID:27084428
Microarray-Based Phospho-Proteomic Profiling of Complex Biological Systems12
Goodwin, C. Rory; Woodard, Crystal L.; Zhou, Xin; Pan, Jianbo; Olivi, Alessandro; Xia, Shuli; Bettegowda, Chetan; Sciubba, Daniel M.; Pevsner, Jonathan; Zhu, Heng; Laterra, John
Protein microarray technology has been successfully used for identifying substrates of purified activated kinases. We used protein microarrays to globally interrogate the effects of PTEN and Akt activity on the phospho-kinome of in vitro and in vivo glioma models and validated results in clinical pathological specimens. Whole cell lysates extracted from tumor samples can be applied to human kinome chip microarrays to profile the global kinase phosphorylation patterns in a high-throughput manner and identify novel substrates inherent to the tumor cell and the interactions with tumor microenvironment. Our findings identify a novel microarray-based method for assessing intracellular signaling events applicable to human oncogenesis and other pathophysiologic states. PMID:27084428
Detection of antibodies against avian influenza virus by protein microarray using nucleoprotein expressed in insect cells
ZHAO, Yuhui; WANG, Xiurong; CHEN, Pucheng; ZENG, Xianying; BAO, Hongmei; WANG, Yunhe; XU, Xiaolong; JIANG, Yongping; CHEN, Hualan; LI, Guangxing
Avian influenza (AI) is an infectious disease caused by avian influenza viruses (AIVs) which belong to the influenza virus A group. AI causes tremendous economic losses in poultry industry and pose great threatens to human health. Active serologic surveillance is necessary to prevent and control the spread of AI. In this study, a protein microarray using nucleoprotein (NP) of H5N1 AIV expressed in insect cells was developed to detect antibodies against AIV NP protein. The protein microarray was used to test Newcastle disease virus (NDV), infectious bursal disease virus (IBDV), AIV positive and negative sera. The results indicated that the protein microarray could hybridize specifically with antibodies against AIV with strong signals and without cross-hybridization. Moreover, 76 field serum samples were detected by microarray, enzyme-linked immunosorbent assay (ELISA) and hemagglutination inhibition test (HI). The positive rate was 92.1% (70/76), 93.4% (71/76) and 89.4% (68/76) by protein microarray, ELISA and HI test, respectively. Compared with ELISA, the microarray showed 100% (20/20) agreement ratio in chicken and 98.2% (55/56) in ornamental bird. In conclusion, this method provides an alternative serological diagnosis for influenza antibody screening and will provide a basis for the development of protein microarrays that can be used to respectively detect antibodies of different AIV subtypes and other pathogens. PMID:25650059
Detection of antibodies against avian influenza virus by protein microarray using nucleoprotein expressed in insect cells.
Zhao, Yuhui; Wang, Xiurong; Chen, Pucheng; Zeng, Xianying; Bao, Hongmei; Wang, Yunhe; Xu, Xiaolong; Jiang, Yongping; Chen, Hualan; Li, Guangxing
Avian influenza (AI) is an infectious disease caused by avian influenza viruses (AIVs) which belong to the influenza virus A group. AI causes tremendous economic losses in poultry industry and pose great threatens to human health. Active serologic surveillance is necessary to prevent and control the spread of AI. In this study, a protein microarray using nucleoprotein (NP) of H5N1 AIV expressed in insect cells was developed to detect antibodies against AIV NP protein. The protein microarray was used to test Newcastle disease virus (NDV), infectious bursal disease virus (IBDV), AIV positive and negative sera. The results indicated that the protein microarray could hybridize specifically with antibodies against AIV with strong signals and without cross-hybridization. Moreover, 76 field serum samples were detected by microarray, enzyme-linked immunosorbent assay (ELISA) and hemagglutination inhibition test (HI). The positive rate was 92.1% (70/76), 93.4% (71/76) and 89.4% (68/76) by protein microarray, ELISA and HI test, respectively. Compared with ELISA, the microarray showed 100% (20/20) agreement ratio in chicken and 98.2% (55/56) in ornamental bird. In conclusion, this method provides an alternative serological diagnosis for influenza antibody screening and will provide a basis for the development of protein microarrays that can be used to respectively detect antibodies of different AIV subtypes and other pathogens. PMID:25650059
DNA Microarrays in Herbal Drug Research
Chavan, Preeti; Joshi, Kalpana; Patwardhan, Bhushan
Natural products are gaining increased applications in drug discovery and development. Being chemically diverse they are able to modulate several targets simultaneously in a complex system. Analysis of gene expression becomes necessary for better understanding of molecular mechanisms. Conventional strategies for expression profiling are optimized for single gene analysis. DNA microarrays serve as suitable high throughput tool for simultaneous analysis of multiple genes. Major practical applicability of DNA microarrays remains in DNA mutation and polymorphism analysis. This review highlights applications of DNA microarrays in pharmacodynamics, pharmacogenomics, toxicogenomics and quality control of herbal drugs and extracts. PMID:17173108
Progress in the application of DNA microarrays.
Lobenhofer, E K; Bushel, P R; Afshari, C A; Hamadeh, H K
Microarray technology has been applied to a variety of different fields to address fundamental research questions. The use of microarrays, or DNA chips, to study the gene expression profiles of biologic samples began in 1995. Since that time, the fundamental concepts behind the chip, the technology required for making and using these chips, and the multitude of statistical tools for analyzing the data have been extensively reviewed. For this reason, the focus of this review will be not on the technology itself but on the application of microarrays as a research tool and the future challenges of the field. PMID:11673116
Lab-on-CMOS Integration of Microfluidics and Electrochemical Sensors
Huang, Yue; Mason, Andrew J.
This paper introduces a CMOS-microfluidics integration scheme for electrochemical microsystems. A CMOS chip was embedded into a micro-machined silicon carrier. By leveling the CMOS chip and carrier surface to within 100 nm, an expanded obstacle-free surface suitable for photolithography was achieved. Thin film metal planar interconnects were microfabricated to bridge CMOS pads to the perimeter of the carrier, leaving a flat and smooth surface for integrating microfluidic structures. A model device containing SU-8 microfluidic mixers and detection channels crossing over microelectrodes on a CMOS integrated circuit was constructed using the chip-carrier assembly scheme. Functional integrity of microfluidic structures and on-CMOS electrodes was verified by a simultaneous sample dilution and electrochemical detection experiment within multi-channel microfluidics. This lab-on-CMOS integration process is capable of high packing density, is suitable for wafer-level batch production, and opens new opportunities to combine the performance benefits of on-CMOS sensors with lab-on-chip platforms. PMID:23939616
High-performance VGA-resolution digital color CMOS imager
NASA Astrophysics Data System (ADS)
Agwani, Suhail; Domer, Steve; Rubacha, Ray; Stanley, Scott
This paper discusses the performance of a new VGA resolution color CMOS imager developed by Motorola on a 0.5micrometers /3.3V CMOS process. This fully integrated, high performance imager has on chip timing, control, and analog signal processing chain for digital imaging applications. The picture elements are based on 7.8micrometers active CMOS pixels that use pinned photodiodes for higher quantum efficiency and low noise performance. The image processing engine includes a bank of programmable gain amplifiers, line rate clamping for dark offset removal, real time auto white balancing, per column gain and offset calibration, and a 10 bit pipelined RSD analog to digital converter with a programmable input range. Post ADC signal processing includes features such as bad pixel replacement based on user defined thresholds levels, 10 to 8 bit companding and 5 tap FIR filtering. The sensor can be programmed via a standard I2C interface that runs on 3.3V clocks. Programmable features include variable frame rates using a constant frequency master clock, electronic exposure control, continuous or single frame capture, progressive or interlace scanning modes. Each pixel is individually addressable allowing region of interest imaging and image subsampling. The sensor operates with master clock frequencies of up to 13.5MHz resulting in 30FPS. A total programmable gain of 27dB is available. The sensor power dissipation is 400mW at full speed of operation. The low noise design yields a measured 'system on a chip' dynamic range of 50dB thus giving over 8 true bits of resolution. Extremely high conversion gain result in an excellent peak sensitivity of 22V/(mu) J/cm2 or 3.3V/lux-sec. This monolithic image capture and processing engine represent a compete imaging solution making it a true 'camera on a chip'. Yet in its operation it remains extremely easy to use requiring only one clock and a 3.3V power supply. Given the available features and performance levels, this sensor will be
CMOS-compatible RF MEMS switch
NASA Astrophysics Data System (ADS)
Lakamraju, Narendra V.; Kim, Bruce; Phillips, Stephen M.
Mobile technologies have relied on RF switches for a long time. Though the basic function of the switch has remained the same, the way they have been made has changed in the recent past. In the past few years work has been done to use MEMS technologies in designing and fabricating an RF switch that would in many ways replace the electronic and mechanical switches that have been used for so long. The work that is described here is an attempt to design and fabricate an RF MEMS switch that can handle higher RF power and have CMOS compatible operating voltages.
Vertical Isolation for Photodiodes in CMOS Imagers
NASA Technical Reports Server (NTRS)
Pain, Bedabrata
In a proposed improvement in complementary metal oxide/semi conduct - or (CMOS) image detectors, two additional implants in each pixel would effect vertical isolation between the metal oxide/semiconductor field-effect transistors (MOSFETs) and the photodiode of the pixel. This improvement is expected to enable separate optimization of the designs of the photodiode and the MOSFETs so as to optimize their performances independently of each other. The purpose to be served by enabling this separate optimization is to eliminate or vastly reduce diffusion cross-talk, thereby increasing sensitivity, effective spatial resolution, and color fidelity while reducing noise.
Monolithic CMOS imaging x-ray spectrometers
NASA Astrophysics Data System (ADS)
Kenter, Almus; Kraft, Ralph; Gauron, Thomas; Murray, Stephen S.
The Smithsonian Astrophysical Observatory (SAO) in collaboration with SRI/Sarnoff is developing monolithic CMOS detectors optimized for x-ray astronomy. The goal of this multi-year program is to produce CMOS x-ray imaging spectrometers that are Fano noise limited over the 0.1-10keV energy band while incorporating the many benefits of CMOS technology. These benefits include: low power consumption, radiation "hardness", high levels of integration, and very high read rates. Small format test devices from a previous wafer fabrication run (2011-2012) have recently been back-thinned and tested for response below 1keV. These devices perform as expected in regards to dark current, read noise, spectral response and Quantum Efficiency (QE). We demonstrate that running these devices at rates ~> 1Mpix/second eliminates the need for cooling as shot noise from any dark current is greatly mitigated. The test devices were fabricated on 15μm, high resistivity custom (~30kΩ-cm) epitaxial silicon and have a 16 by 192 pixel format. They incorporate 16μm pitch, 6 Transistor Pinned Photo Diode (6TPPD) pixels which have ~40μV/electron sensitivity and a highly parallel analog CDS signal chain. Newer, improved, lower noise detectors have just been fabricated (October 2013). These new detectors are fabricated on 9μm epitaxial silicon and have a 1k by 1k format. They incorporate similar 16μm pitch, 6TPPD pixels but have ~ 50% higher sensitivity and much (3×) lower read noise. These new detectors have undergone preliminary testing for functionality in Front Illuminated (FI) form and are presently being prepared for back thinning and packaging. Monolithic CMOS devices such as these, would be ideal candidate detectors for the focal planes of Solar, planetary and other space-borne x-ray astronomy missions. The high through-put, low noise and excellent low energy response, provide high dynamic range and good time resolution; bright, time varying x-ray features could be temporally and
AMIC@: All MIcroarray Clusterings @ once
Geraci, Filippo; Pellegrini, Marco; Renda, M. Elena
The AMIC@ Web Server offers a light-weight multi-method clustering engine for microarray gene-expression data. AMIC@ is a highly interactive tool that stresses user-friendliness and robustness by adopting AJAX technology, thus allowing an effective interleaved execution of different clustering algorithms and inspection of results. Among the salient features AMIC@ offers, there are: (i) automatic file format detection, (ii) suggestions on the number of clusters using a variant of the stability-based method of Tibshirani et al. (iii) intuitive visual inspection of the data via heatmaps and (iv) measurements of the clustering quality using cluster homogeneity. Large data sets can be processed efficiently by selecting algorithms (such as FPF-SB and k-Boost), specifically designed for this purpose. In case of very large data sets, the user can opt for a batch-mode use of the system by means of the Clustering wizard that runs all algorithms at once and delivers the results via email. AMIC@ is freely available and open to all users with no login requirement at the following URL http://bioalgo.iit.cnr.it/amica. PMID:18477631
AMIC@: All MIcroarray Clusterings @ once.
Geraci, Filippo; Pellegrini, Marco; Renda, M Elena
The AMIC@ Web Server offers a light-weight multi-method clustering engine for microarray gene-expression data. AMIC@ is a highly interactive tool that stresses user-friendliness and robustness by adopting AJAX technology, thus allowing an effective interleaved execution of different clustering algorithms and inspection of results. Among the salient features AMIC@ offers, there are: (i) automatic file format detection, (ii) suggestions on the number of clusters using a variant of the stability-based method of Tibshirani et al. (iii) intuitive visual inspection of the data via heatmaps and (iv) measurements of the clustering quality using cluster homogeneity. Large data sets can be processed efficiently by selecting algorithms (such as FPF-SB and k-Boost), specifically designed for this purpose. In case of very large data sets, the user can opt for a batch-mode use of the system by means of the Clustering wizard that runs all algorithms at once and delivers the results via email. AMIC@ is freely available and open to all users with no login requirement at the following URL http://bioalgo.iit.cnr.it/amica. PMID:18477631
Integrating Microarray Data and GRNs.
Koumakis, L; Potamias, G; Tsiknakis, M; Zervakis, M; Moustakis, V
With the completion of the Human Genome Project and the emergence of high-throughput technologies, a vast amount of molecular and biological data are being produced. Two of the most important and significant data sources come from microarray gene-expression experiments and respective databanks (e,g., Gene Expression Omnibus-GEO (http://www.ncbi.nlm.nih.gov/geo)), and from molecular pathways and Gene Regulatory Networks (GRNs) stored and curated in public (e.g., Kyoto Encyclopedia of Genes and Genomes-KEGG (http://www.genome.jp/kegg/pathway.html), Reactome (http://www.reactome.org/ReactomeGWT/entrypoint.html)) as well as in commercial repositories (e.g., Ingenuity IPA (http://www.ingenuity.com/products/ipa)). The association of these two sources aims to give new insight in disease understanding and reveal new molecular targets in the treatment of specific phenotypes.Three major research lines and respective efforts that try to utilize and combine data from both of these sources could be identified, namely: (1) de novo reconstruction of GRNs, (2) identification of Gene-signatures, and (3) identification of differentially expressed GRN functional paths (i.e., sub-GRN paths that distinguish between different phenotypes). In this chapter, we give an overview of the existing methods that support the different types of gene-expression and GRN integration with a focus on methodologies that aim to identify phenotype-discriminant GRNs or subnetworks, and we also present our methodology. PMID:26134183
DNA microarrays in prostate cancer.
Ho, Shuk-Mei; Lau, Kin-Mang
DNA microarray technology provides a means to examine large numbers of molecular changes related to a biological process in a high throughput manner. This review discusses plausible utilities of this technology in prostate cancer research, including definition of prostate cancer predisposition, global profiling of gene expression patterns associated with cancer initiation and progression, identification of new diagnostic and prognostic markers, and discovery of novel patient classification schemes. The technology, at present, has only been explored in a limited fashion in prostate cancer research. Some hurdles to be overcome are the high cost of the technology, insufficient sample size and repeated experiments, and the inadequate use of bioinformatics. With the completion of the Human Genome Project and the advance of several highly complementary technologies, such as laser capture microdissection, unbiased RNA amplification, customized functional arrays (eg, single-nucleotide polymorphism chips), and amenable bioinformatics software, this technology will become widely used by investigators in the field. The large amount of novel, unbiased hypotheses and insights generated by this technology is expected to have a significant impact on the diagnosis, treatment, and prevention of prostate cancer. Finally, this review emphasizes existing, but currently underutilized, data-mining tools, such as multivariate statistical analyses, neural networking, and machine learning techniques, to stimulate wider usage. PMID:12084220
Real-time, multiplexed electrochemical DNA detection using an active complementary metal-oxide-semiconductor biosensor array with integrated sensor electronics.
Levine, Peter M; Gong, Ping; Levicky, Rastislav; Shepard, Kenneth L
Optical biosensing based on fluorescence detection has arguably become the standard technique for quantifying extents of hybridization between surface-immobilized probes and fluorophore-labeled analyte targets in DNA microarrays. However, electrochemical detection techniques are emerging which could eliminate the need for physically bulky optical instrumentation, enabling the design of portable devices for point-of-care applications. Unlike fluorescence detection, which can function well using a passive substrate (one without integrated electronics), multiplexed electrochemical detection requires an electronically active substrate to analyze each array site and benefits from the addition of integrated electronic instrumentation to further reduce platform size and eliminate the electromagnetic interference that can result from bringing non-amplified signals off chip. We report on an active electrochemical biosensor array, constructed with a standard complementary metal-oxide-semiconductor (CMOS) technology, to perform quantitative DNA hybridization detection on chip using targets conjugated with ferrocene redox labels. A 4 x 4 array of gold working electrodes and integrated potentiostat electronics, consisting of control amplifiers and current-input analog-to-digital converters, on a custom-designed 5 mm x 3 mm CMOS chip drive redox reactions using cyclic voltammetry, sense DNA binding, and transmit digital data off chip for analysis. We demonstrate multiplexed and specific detection of DNA targets as well as real-time monitoring of hybridization, a task that is difficult, if not impossible, with traditional fluorescence-based microarrays. PMID:19054661
Quality Visualization of Microarray Datasets Using Circos
Koch, Martin; Wiese, Michael
Quality control and normalization is considered the most important step in the analysis of microarray data. At present there are various methods available for quality assessments of microarray datasets. However there seems to be no standard visualization routine, which also depicts individual microarray quality. Here we present a convenient method for visualizing the results of standard quality control tests using Circos plots. In these plots various quality measurements are drawn in a circular fashion, thus allowing for visualization of the quality and all outliers of each distinct array within a microarray dataset. The proposed method is intended for use with the Affymetrix Human Genome platform (i.e., GPL 96, GPL570 and GPL571). Circos quality measurement plots are a convenient way for the initial quality estimate of Affymetrix datasets that are stored in publicly available databases.
Microarray: an approach for current drug targets.
Gomase, Virendra S; Tagore, Somnath; Kale, Karbhari V
Microarrays are a powerful tool has multiple applications both in clinical and cellular and molecular biology arenas. Early assessment of the probable biological importance of drug targets, pharmacogenomics, toxicogenomics and single nucleotide polymorphisms (SNPs). A list of new drug candidates along with proposed targets for intervention is described. Recent advances in the knowledge of microarrays analysis of organisms and the availability of the genomics sequences provide a wide range of novel targets for drug design. This review gives different process of microarray technologies; methods for comparative gene expression study, applications of microarrays in medicine and pharmacogenomics and current drug targets in research, which are relevant to common diseases as they relate to clinical and future perspectives. PMID:18336225
Theoretical performance analysis for CMOS based high resolution detectors.
Jain, Amit; Bednarek, Daniel R; Rudin, Stephen
High resolution imaging capabilities are essential for accurately guiding successful endovascular interventional procedures. Present x-ray imaging detectors are not always adequate due to their inherent limitations. The newly-developed high-resolution micro-angiographic fluoroscope (MAF-CCD) detector has demonstrated excellent clinical image quality; however, further improvement in performance and physical design may be possible using CMOS sensors. We have thus calculated the theoretical performance of two proposed CMOS detectors which may be used as a successor to the MAF. The proposed detectors have a 300 μm thick HL-type CsI phosphor, a 50 μm-pixel CMOS sensor with and without a variable gain light image intensifier (LII), and are designated MAF-CMOS-LII and MAF-CMOS, respectively. For the performance evaluation, linear cascade modeling was used. The detector imaging chains were divided into individual stages characterized by one of the basic processes (quantum gain, binomial selection, stochastic and deterministic blurring, additive noise). Ranges of readout noise and exposure were used to calculate the detectors' MTF and DQE. The MAF-CMOS showed slightly better MTF than the MAF-CMOS-LII, but the MAF-CMOS-LII showed far better DQE, especially for lower exposures. The proposed detectors can have improved MTF and DQE compared with the present high resolution MAF detector. The performance of the MAF-CMOS is excellent for the angiography exposure range; however it is limited at fluoroscopic levels due to additive instrumentation noise. The MAF-CMOS-LII, having the advantage of the variable LII gain, can overcome the noise limitation and hence may perform exceptionally for the full range of required exposures; however, it is more complex and hence more expensive. PMID:24353390
A CMOS high speed imaging system design based on FPGA
NASA Astrophysics Data System (ADS)
Tang, Hong; Wang, Huawei; Cao, Jianzhong; Qiao, Mingrui
CMOS sensors have more advantages than traditional CCD sensors. The imaging system based on CMOS has become a hot spot in research and development. In order to achieve the real-time data acquisition and high-speed transmission, we design a high-speed CMOS imaging system on account of FPGA. The core control chip of this system is XC6SL75T and we take advantages of CameraLink interface and AM41V4 CMOS image sensors to transmit and acquire image data. AM41V4 is a 4 Megapixel High speed 500 frames per second CMOS image sensor with global shutter and 4/3" optical format. The sensor uses column parallel A/D converters to digitize the images. The CameraLink interface adopts DS90CR287 and it can convert 28 bits of LVCMOS/LVTTL data into four LVDS data stream. The reflected light of objects is photographed by the CMOS detectors. CMOS sensors convert the light to electronic signals and then send them to FPGA. FPGA processes data it received and transmits them to upper computer which has acquisition cards through CameraLink interface configured as full models. Then PC will store, visualize and process images later. The structure and principle of the system are both explained in this paper and this paper introduces the hardware and software design of the system. FPGA introduces the driven clock of CMOS. The data in CMOS is converted to LVDS signals and then transmitted to the data acquisition cards. After simulation, the paper presents a row transfer timing sequence of CMOS. The system realized real-time image acquisition and external controls.
Application of DNA microarray for screening metagenome library clones.
Park, Soo-Je; Chae, Jong-Chan; Rhee, Sung-Keun
Sequence-based screening tools of a metagenome library can expedite metagenome researches considering tremendous metagenome diversities. Several critical disadvantages of activity-based screening of metagenome libraries could be overcome by sequence-based screening approaches. DNA microarray technology widely used for monitoring environmental genes can be employed for screening environmental fosmid and BAC clones harboring target genes due to its high throughput nature. DNAs of fosmid clones are extracted and spotted on a glass slide and fluorescence-labeled probes are hybridized to the microarray. Specific hybridization signals can be obtained only for the fosmid clones that contain the target gene with high sensitivity (10 ng/μL of fosmid clone DNA) and quantitativeness. PMID:20830574
Contributions to Statistical Problems Related to Microarray Data
ERIC Educational Resources Information Center
Hong, Feng
Microarray is a high throughput technology to measure the gene expression. Analysis of microarray data brings many interesting and challenging problems. This thesis consists three studies related to microarray data. First, we propose a Bayesian model for microarray data and use Bayes Factors to identify differentially expressed genes. Second, we…
A CMOS Neural Interface for a Multichannel Vestibular Prosthesis.
Hageman, Kristin N; Kalayjian, Zaven K; Tejada, Francisco; Chiang, Bryce; Rahman, Mehdi A; Fridman, Gene Y; Dai, Chenkai; Pouliquen, Philippe O; Georgiou, Julio; Della Santina, Charles C; Andreou, Andreas G
We present a high-voltage CMOS neural-interface chip for a multichannel vestibular prosthesis (MVP) that measures head motion and modulates vestibular nerve activity to restore vision- and posture-stabilizing reflexes. This application specific integrated circuit neural interface (ASIC-NI) chip was designed to work with a commercially available microcontroller, which controls the ASIC-NI via a fast parallel interface to deliver biphasic stimulation pulses with 9-bit programmable current amplitude via 16 stimulation channels. The chip was fabricated in the ONSemi C5 0.5 micron, high-voltage CMOS process and can accommodate compliance voltages up to 12 V, stimulating vestibular nerve branches using biphasic current pulses up to 1.45±0.06 mA with durations as short as 10 μs/phase. The ASIC-NI includes a dedicated digital-to-analog converter for each channel, enabling it to perform complex multipolar stimulation. The ASIC-NI replaces discrete components that cover nearly half of the 2nd generation MVP (MVP2) printed circuit board, reducing the MVP system size by 48% and power consumption by 17%. Physiological tests of the ASIC-based MVP system (MVP2A) in a rhesus monkey produced reflexive eye movement responses to prosthetic stimulation similar to those observed when using the MVP2. Sinusoidal modulation of stimulus pulse rate from 68-130 pulses per second at frequencies from 0.1 to 5 Hz elicited appropriately-directed slow phase eye velocities ranging in amplitude from 1.9-16.7 °/s for the MVP2 and 2.0-14.2 °/s for the MVP2A. The eye velocities evoked by MVP2 and MVP2A showed no significant difference ( t-test, p=0.34), suggesting that the MVP2A achieves performance at least as good as the larger MVP2. PMID:25974945
High-Q CMOS-integrated photonic crystal microcavity devices
Mehta, Karan K.; Orcutt, Jason S.; Tehar-Zahav, Ofer; Sternberg, Zvi; Bafrali, Reha; Meade, Roy; Ram, Rajeev J.
Integrated optical resonators are necessary or beneficial in realizations of various functions in scaled photonic platforms, including filtering, modulation, and detection in classical communication systems, optical sensing, as well as addressing and control of solid state emitters for quantum technologies. Although photonic crystal (PhC) microresonators can be advantageous to the more commonly used microring devices due to the former's low mode volumes, fabrication of PhC cavities has typically relied on electron-beam lithography, which precludes integration with large-scale and reproducible CMOS fabrication. Here, we demonstrate wavelength-scale polycrystalline silicon (pSi) PhC microresonators with Qs up to 60,000 fabricated within a bulk CMOS process. Quasi-1D resonators in lateral p-i-n structures allow for resonant defect-state photodetection in all-silicon devices, exhibiting voltage-dependent quantum efficiencies in the range of a few 10 s of %, few-GHz bandwidths, and low dark currents, in devices with loaded Qs in the range of 4,300–9,300; one device, for example, exhibited a loaded Q of 4,300, 25% quantum efficiency (corresponding to a responsivity of 0.31 A/W), 3 GHz bandwidth, and 30 nA dark current at a reverse bias of 30 V. This work demonstrates the possibility for practical integration of PhC microresonators with active electro-optic capability into large-scale silicon photonic systems. PMID:24518161
A CMOS Neural Interface for a Multichannel Vestibular Prosthesis
Hageman, Kristin N.; Kalayjian, Zaven K.; Tejada, Francisco; Chiang, Bryce; Rahman, Mehdi A.; Fridman, Gene Y.; Dai, Chenkai; Pouliquen, Philippe O.; Georgiou, Julio; Della Santina, Charles C.; Andreou, Andreas G.
We present a high-voltage CMOS neural-interface chip for a multichannel vestibular prosthesis (MVP) that measures head motion and modulates vestibular nerve activity to restore vision- and posture-stabilizing reflexes. This application specific integrated circuit neural interface (ASIC-NI) chip was designed to work with a commercially available microcontroller, which controls the ASIC-NI via a fast parallel interface to deliver biphasic stimulation pulses with 9-bit programmable current amplitude via 16 stimulation channels. The chip was fabricated in the ONSemi C5 0.5 micron, high-voltage CMOS process and can accommodate compliance voltages up to 12 V, stimulating vestibular nerve branches using biphasic current pulses up to 1.45 ± 0.06 mA with durations as short as 10 µs/phase. The ASIC-NI includes a dedicated digital-to-analog converter for each channel, enabling it to perform complex multipolar stimulation. The ASIC-NI replaces discrete components that cover nearly half of the 2nd generation MVP (MVP2) printed circuit board, reducing the MVP system size by 48% and power consumption by 17%. Physiological tests of the ASIC-based MVP system (MVP2A) in a rhesus monkey produced reflexive eye movement responses to prosthetic stimulation similar to those observed when using the MVP2. Sinusoidal modulation of stimulus pulse rate from 68–130 pulses per second at frequencies from 0.1 to 5 Hz elicited appropriately-directed slow phase eye velocities ranging in amplitude from 1.9–16.7°/s for the MVP2 and 2.0–14.2°/s for the MVP2A. The eye velocities evoked by MVP2 and MVP2A showed no significant difference (t-test, p = 0.034), suggesting that the MVP2A achieves performance at least as good as the larger MVP2. PMID:25974945
Packaging commercial CMOS chips for lab on a chip integration.
Datta-Chaudhuri, Timir; Abshire, Pamela; Smela, Elisabeth
Combining integrated circuitry with microfluidics enables lab-on-a-chip (LOC) devices to perform sensing, freeing them from benchtop equipment. However, this integration is challenging with small chips, as is briefly reviewed with reference to key metrics for package comparison. In this paper we present a simple packaging method for including mm-sized, foundry-fabricated dies containing complementary metal oxide semiconductor (CMOS) circuits within LOCs. The chip is embedded in an epoxy handle wafer to yield a level, large-area surface, allowing subsequent photolithographic post-processing and microfluidic integration. Electrical connection off-chip is provided by thin film metal traces passivated with parylene-C. The parylene is patterned to selectively expose the active sensing area of the chip, allowing direct interaction with a fluidic environment. The method accommodates any die size and automatically levels the die and handle wafer surfaces. Functionality was demonstrated by packaging two different types of CMOS sensor ICs, a bioamplifier chip with an array of surface electrodes connected to internal amplifiers for recording extracellular electrical signals and a capacitance sensor chip for monitoring cell adhesion and viability. Cells were cultured on the surface of both types of chips, and data were acquired using a PC. Long term culture (weeks) showed the packaging materials to be biocompatible. Package lifetime was demonstrated by exposure to fluids over a longer duration (months), and the package was robust enough to allow repeated sterilization and re-use. The ease of fabrication and good performance of this packaging method should allow wide adoption, thereby spurring advances in miniaturized sensing systems. PMID:24682025
The Impact of Photobleaching on Microarray Analysis
von der Haar, Marcel; Preuß, John-Alexander; von der Haar, Kathrin; Lindner, Patrick; Scheper, Thomas; Stahl, Frank
DNA-Microarrays have become a potent technology for high-throughput analysis of genetic regulation. However, the wide dynamic range of signal intensities of fluorophore-based microarrays exceeds the dynamic range of a single array scan by far, thus limiting the key benefit of microarray technology: parallelization. The implementation of multi-scan techniques represents a promising approach to overcome these limitations. These techniques are, in turn, limited by the fluorophores' susceptibility to photobleaching when exposed to the scanner's laser light. In this paper the photobleaching characteristics of cyanine-3 and cyanine-5 as part of solid state DNA microarrays are studied. The effects of initial fluorophore intensity as well as laser scanner dependent variables such as the photomultiplier tube's voltage on bleaching and imaging are investigated. The resulting data is used to develop a model capable of simulating the expected degree of signal intensity reduction caused by photobleaching for each fluorophore individually, allowing for the removal of photobleaching-induced, systematic bias in multi-scan procedures. Single-scan applications also benefit as they rely on pre-scans to determine the optimal scanner settings. These findings constitute a step towards standardization of microarray experiments and analysis and may help to increase the lab-to-lab comparability of microarray experiment results. PMID:26378589
Challenges of nickel silicidation in CMOS technologies
Breil, Nicolas; Lavoie, Christian; Ozcan, Ahmet; Baumann, Frieder; Klymko, Nancy; Nummy, Karen; Sun, Bing; Jordan-Sweet, Jean; Yu, Jian; Zhu, Frank; Narasimha, Shreesh; Chudzik, Michael
In our paper, we review some of the key challenges associated with the Ni silicidation process in the most recent CMOS technologies. The introduction of new materials (e.g.SiGe), and of non-planar architectures bring some important changes that require fundamental investigation from a material engineering perspective. Following a discussion of the device architecture and silicide evolution through the last CMOS generations, we focus our study on a very peculiar defect, termed NiSi-Fangs. We describe a mechanism for the defect formation, and present a detailed material analysis that supports this mechanism. We highlight some of the possible metal enrichment processes of the nickel monosilicide such as oxidation or various RIE (Reactive Ion Etching) plasma process, leading to a metal source available for defect formation. Furthermore, we investigate the NiSi formation and re-formation silicidation differences between Si and SiGe materials, and between (1 0 0) and (1 1 1) orientations. Finally, we show that the thermal budgets post silicidation can lead to the formation of NiSi-Fangs if the structure and the processes are not optimized. Beyond the understanding of the defect and the discussion on the engineering solutions used to prevent its formation, the interest of this investigation also lies in the fundamental learning within the Ni–Pt–Si–Ge system and some additional perspective on Ni-based contacts to advanced microelectronic devices.
Modulated CMOS camera for fluorescence lifetime microscopy.
Chen, Hongtao; Holst, Gerhard; Gratton, Enrico
Widefield frequency-domain fluorescence lifetime imaging microscopy (FD-FLIM) is a fast and accurate method to measure the fluorescence lifetime of entire images. However, the complexity and high costs involved in construction of such a system limit the extensive use of this technique. PCO AG recently released the first luminescence lifetime imaging camera based on a high frequency modulated CMOS image sensor, QMFLIM2. Here we tested and provide operational procedures to calibrate the camera and to improve the accuracy using corrections necessary for image analysis. With its flexible input/output options, we are able to use a modulated laser diode or a 20 MHz pulsed white supercontinuum laser as the light source. The output of the camera consists of a stack of modulated images that can be analyzed by the SimFCS software using the phasor approach. The nonuniform system response across the image sensor must be calibrated at the pixel level. This pixel calibration is crucial and needed for every camera settings, e.g. modulation frequency and exposure time. A significant dependency of the modulation signal on the intensity was also observed and hence an additional calibration is needed for each pixel depending on the pixel intensity level. These corrections are important not only for the fundamental frequency, but also for the higher harmonics when using the pulsed supercontinuum laser. With these post data acquisition corrections, the PCO CMOS-FLIM camera can be used for various biomedical applications requiring a large frame and high speed acquisition. PMID:26500051
Biclustering of microarray data with MOSPO based on crowding distance
Liu, Junwan; Li, Zhoujun; Hu, Xiaohua; Chen, Yiming
Background High-throughput microarray technologies have generated and accumulated massive amounts of gene expression datasets that contain expression levels of thousands of genes under hundreds of different experimental conditions. The microarray datasets are usually presented in 2D matrices, where rows represent genes and columns represent experimental conditions. The analysis of such datasets can discover local structures composed by sets of genes that show coherent expression patterns under subsets of experimental conditions. It leads to the development of sophisticated algorithms capable of extracting novel and useful knowledge from a biomedical point of view. In the medical domain, these patterns are useful for understanding various diseases, and aid in more accurate diagnosis, prognosis, treatment planning, as well as drug discovery. Results In this work we present the CMOPSOB (Crowding distance based Multi-objective Particle Swarm Optimization Biclustering), a novel clustering approach for microarray datasets to cluster genes and conditions highly related in sub-portions of the microarray data. The objective of biclustering is to find sub-matrices, i.e. maximal subgroups of genes and subgroups of conditions where the genes exhibit highly correlated activities over a subset of conditions. Since these objectives are mutually conflicting, they become suitable candidates for multi-objective modelling. Our approach CMOPSOB is based on a heuristic search technique, multi-objective particle swarm optimization, which simulates the movements of a flock of birds which aim to find food. In the meantime, the nearest neighbour search strategies based on crowding distance and ϵ-dominance can rapidly converge to the Pareto front and guarantee diversity of solutions. We compare the potential of this methodology with other biclustering algorithms by analyzing two common and public datasets of gene expression profiles. In all cases our method can find localized structures
A Liposome-Based Approach to the Integrated Multi-Component Antigen Microarrays
Wang, Denong
This report describes an experimental procedure for constructing integrated lipid, carbohydrate, and protein microarrays. In essence, it prints liposomes on nitrocellulose-coated micro-glass slides, a biochip substrate for spotting protein and carbohydrate microarrays, and the substances that can form liposomes (homo-liposomes) or can be incorporated into liposomes (hetero-liposomes) are suitable for microarray construction using existing microarray spotting devices. Importantly, this technology allows simultaneous detection of serum antibody activities among the three major classes of antigens, i.e., lipids, carbohydrates, and proteins. The potential of this technology is illustrated by its use in revealing a broad-spectrum of pre-existing anti-lipid antibodies in blood circulation and monitoring the epitope spreading of autoantibody reactivities among protein, carbohydrate, and lipid antigens in experimental autoimmune encephalomyelitis (EAE).
Imaging combined autoimmune and infectious disease microarrays
NASA Astrophysics Data System (ADS)
Ewart, Tom; Raha, Sandeep; Kus, Dorothy; Tarnopolsky, Mark
Bacterial and viral pathogens are implicated in many severe autoimmune diseases, acting through such mechanisms as molecular mimicry, and superantigen activation of T-cells. For example, Helicobacter pylori, well known cause of stomach ulcers and cancers, is also identified in ischaemic heart disease (mimicry of heat shock protein 65), autoimmune pancreatitis, systemic sclerosis, autoimmune thyroiditis (HLA DRB1*0301 allele susceptibility), and Crohn's disease. Successful antibiotic eradication of H.pylori often accompanies their remission. Yet current diagnostic devices, and test-limiting cost containment, impede recognition of the linkage, delaying both diagnosis and therapeutic intervention until the chronic debilitating stage. We designed a 15 minute low cost 39 antigen microarray assay, combining autoimmune, viral and bacterial antigens1. This enables point-of-care serodiagnosis and cost-effective narrowly targeted concurrent antibiotic and monoclonal anti-T-cell and anti-cytokine immunotherapy. Arrays of 26 pathogen and 13 autoimmune antigens with IgG and IgM dilution series were printed in triplicate on epoxysilane covalent binding slides with Teflon well masks. Sera diluted 1:20 were incubated 10 minutes, washed off, anti-IgG-Cy3 (green) and anti-IgM-Dy647 (red) were incubated for 5 minutes, washed off and the slide was read in an ArrayWoRx(e) scanning CCD imager (Applied Precision, Issaquah, WA). As a preliminary model for the combined infectious disease-autoimmune diagnostic microarray we surveyed 98 unidentified, outdated sera that were discarded after Hepatitis B antibody testing. In these, significant IgG or IgM autoantibody levels were found: dsDNA 5, ssDNA 11, Ro 2, RNP 7, SSB 4, gliadin 2, thyroglobulin 13 cases. Since control sera showed no autoantibodies, the high frequency of anti-DNA and anti-thyroglobulin antibodies found in infected sera lend increased support for linkage of infection to subsequent autoimmune disease. Expansion of the antigen
New technologies for fabricating biological microarrays
NASA Astrophysics Data System (ADS)
Larson, Bradley James
This dissertation contains the description of two technologies that we have developed to reduce the cost and improve the quality of spotted biological microarrays. The first is a device, called a fluid microplotter, that uses ultrasonics to deposit spots with diameters of less than 5 microns. It consists of a dispenser, composed of a micropipette fastened to a piece of PZT piezoelectric, attached to a precision positioning system. A gentle pumping of fluid to the surface occurs when the micropipette is driven at specific frequencies. Spots or continuous lines can be deposited in this manner. The small fluid features conserve expensive and limited-quantity biological reagents. We characterize the performance of the microplotter in depositing fluid and examine the theoretical underpinnings of its operation. We present an analytical expression for the diameter of a deposited spot as a function of droplet volume and wettability of a surface and compare it with experimental results. We also examine the resonant properties of the piezoelectric element used to drive the dispenser and relate that to the frequencies at which pumping occurs. Finally, we propose a mechanism to explain the pumping behavior within the microplotter dispenser. The second technology we present is a process that uses a cold plasma and a subsequent in vacuo vapor-phase reaction to terminate a variety of oxide surfaces with epoxide chemical groups. These epoxide groups can react with amine-containing biomolecules to form strong covalent linkages between the biomolecules and the treated surface. The use of a plasma activation step followed by an in vacuo vapor-phase reaction allows for the precise control of surface functional groups, rather than the mixture of functionalities normally produced. This process modifies a range of different oxide surfaces, is fast, consumes a minimal amount of reagents, and produces attachment densities for bound biomolecules that are comparable to or better than
Chromosomal Microarray versus Karyotyping for Prenatal Diagnosis
Wapner, Ronald J.; Martin, Christa Lese; Levy, Brynn; Ballif, Blake C.; Eng, Christine M.; Zachary, Julia M.; Savage, Melissa; Platt, Lawrence D.; Saltzman, Daniel; Grobman, William A.; Klugman, Susan; Scholl, Thomas; Simpson, Joe Leigh; McCall, Kimberly; Aggarwal, Vimla S.; Bunke, Brian; Nahum, Odelia; Patel, Ankita; Lamb, Allen N.; Thom, Elizabeth A.; Beaudet, Arthur L.; Ledbetter, David H.; Shaffer, Lisa G.; Jackson, Laird
Background Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis. Methods Samples from women undergoing prenatal diagnosis at 29 centers were sent to a central karyotyping laboratory. Each sample was split in two; standard karyotyping was performed on one portion and the other was sent to one of four laboratories for chromosomal microarray. Results We enrolled a total of 4406 women. Indications for prenatal diagnosis were advanced maternal age (46.6%), abnormal result on Down's syndrome screening (18.8%), structural anomalies on ultrasonography (25.2%), and other indications (9.4%). In 4340 (98.8%) of the fetal samples, microarray analysis was successful; 87.9% of samples could be used without tissue culture. Microarray analysis of the 4282 nonmosaic samples identified all the aneuploidies and unbalanced rearrangements identified on karyotyping but did not identify balanced translocations and fetal triploidy. In samples with a normal karyotype, microarray analysis revealed clinically relevant deletions or duplications in 6.0% with a structural anomaly and in 1.7% of those whose indications were advanced maternal age or positive screening results. Conclusions In the context of prenatal diagnostic testing, chromosomal microarray analysis identified additional, clinically significant cytogenetic information as compared with karyotyping and was equally efficacious in identifying aneuploidies and unbalanced rearrangements but did not identify balanced translocations and triploidies. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01279733.) PMID:23215555
Glycan profiling of endometrial cancers using lectin microarray.
Nishijima, Yoshihiro; Toyoda, Masashi; Yamazaki-Inoue, Mayu; Sugiyama, Taro; Miyazawa, Masaki; Muramatsu, Toshinari; Nakamura, Kyoko; Narimatsu, Hisashi; Umezawa, Akihiro; Mikami, Mikio
Cell surface glycans change during the process of malignant transformation. To characterize and distinguish endometrial cancer and endometrium, we performed glycan profiling using an emerging modern technology, lectin microarray analysis. The three cell lines, two from endometrial cancers [well-differentiated type (G1) and poorly differentiated type (G3)] and one from normal endometrium, were successfully categorized into three independent groups by 45 lectins. Furthermore, in cancer cells, a clear difference between G1 and G3 type was observed for the glycans recognized with six lectins, Ulex europaeus agglutinin I (UEA-I), Sambucus sieboldiana agglutinin (SSA), Sambucus nigra agglutinin (SNA), Trichosanthes japonica agglutinin I (TJA-I), Amaranthus caudatus agglutinin (ACA), and Bauhinia purpurea lectin (BPL). The lectin microarray analysis using G3 type tissues demonstrated that stage I and stage III or IV were distinguished depending on signal pattern of three lectins, Dolichos biflorus agglutinin (DBA), BPL, and ACA. In addition, the analysis of the glycans on the ovarian cancer cells showed that only anticancer drug-sensitive cell lines had almost no activities to specific three lectins. Glycan profiling by the lectin microarray may be used to assess the characteristics of tumors and potentially to predict the success of chemotherapy treatment. PMID:22957961
Beyond microarrays: Finding key transcription factors controlling signal transduction pathways
Kel, Alexdander; Voss, Nico; Jauregui, Ruy; Kel-Margoulis, Olga; Wingender, Edgar
Background Massive gene expression changes in different cellular states measured by microarrays, in fact, reflect just an "echo" of real molecular processes in the cells. Transcription factors constitute a class of the regulatory molecules that typically require posttranscriptional modifications or ligand binding in order to exert their function. Therefore, such important functional changes of transcription factors are not directly visible in the microarray experiments. Results We developed a novel approach to find key transcription factors that may explain concerted expression changes of specific components of the signal transduction network. The approach aims at revealing evidence of positive feedback loops in the signal transduction circuits through activation of pathway-specific transcription factors. We demonstrate that promoters of genes encoding components of many known signal transduction pathways are enriched by binding sites of those transcription factors that are endpoints of the considered pathways. Application of the approach to the microarray gene expression data on TNF-alpha stimulated primary human endothelial cells helped to reveal novel key transcription factors potentially involved in the regulation of the signal transduction pathways of the cells. Conclusion We developed a novel computational approach for revealing key transcription factors by knowledge-based analysis of gene expression data with the help of databases on gene regulatory networks (TRANSFAC® and TRANSPATH®). The corresponding software and databases are available at . PMID:17118134
PALM and STORM: Into large fields and high-throughput microscopy with sCMOS detectors.
Almada, Pedro; Culley, Siân; Henriques, Ricardo
Single Molecule Localization Microscopy (SMLM) techniques such as Photo-Activation Localization Microscopy (PALM) and Stochastic Optical Reconstruction Microscopy (STORM) enable fluorescence microscopy super-resolution: the overcoming of the resolution barrier imposed by the diffraction of light. These techniques are based on acquiring hundreds or thousands of images of single molecules, locating them and reconstructing a higher-resolution image from the high-precision localizations. These methods generally imply a considerable trade-off between imaging speed and resolution, limiting their applicability to high-throughput workflows. Recent advancements in scientific Complementary Metal-Oxide Semiconductor (sCMOS) camera sensors and localization algorithms reduce the temporal requirements for SMLM, pushing it toward high-throughput microscopy. Here we outline the decisions researchers face when considering how to adapt hardware on a new system for sCMOS sensors with high-throughput in mind. PMID:26079924
Gate-leakage-tolerant circuits in deep sub-100-nm CMOS technologies
NASA Astrophysics Data System (ADS)
Kang, Sung-Mo; Yang, Ge; Wang, Zhongda
The leakage power consumption in deep sub-100nm CMOS systems is projected to become a significant part of the total power dissipation. Although the dual Vt CMOS process helps reduce the subthreshold leakage current, the gate leakage problem poses a significant design challenge. We introduce gate leakage tolerant circuits. We describe two new circuit techniques to suppress gate leakage currents in dual Vt Domino circuits. In standby mode, proposed circuits generate low inputs and low outputs for all Domino stages to suppress gate leakage currents in the NMOS logic tree. Simulation results using 45nm BSIM4 SPICE models for 32-bit adders show that adders using the two proposed circuits can reduce the standby gate leakage by 66% and 90%, respectively. Proposed adders have 7% active power overhead to achieve the same speed as single Vt domino adder and the area penalty is minimal with careful layout.
Radiation hardness of two CMOS prototypes for the ATLAS HL-LHC upgrade project.
NASA Astrophysics Data System (ADS)
Huffman, B. T.; Affolder, A.; Arndt, K.; Bates, R.; Benoit, M.; Di Bello, F.; Blue, A.; Bortoletto, D.; Buckland, M.; Buttar, C.; Caragiulo, P.; Das, D.; Dopke, J.; Dragone, A.; Ehrler, F.; Fadeyev, V.; Galloway, Z.; Grabas, H.; Gregor, I. M.; Grenier, P.; Grillo, A.; Hoeferkamp, M.; Hommels, L. B. A.; John, J.; Kanisauskas, K.; Kenney, C.; Kramberger, J.; Liang, Z.; Mandić, I.; Maneuski, D.; Martinez-Mckinney, F.; McMahon, S.; Meng, L.; Mikuž, M.; Muenstermann, D.; Nickerson, R.; Perić, I.; Phillips, P.; Plackett, R.; Rubbo, F.; Segal, J.; Seidel, S.; Seiden, A.; Shipsey, I.; Song, W.; Stanitzki, M.; Su, D.; Tamma, C.; Turchetta, R.; Vigani, L.; Volk, J.; Wang, R.; Warren, M.; Wilson, F.; Worm, S.; Xiu, Q.; Zhang, J.; Zhu, H.
The LHC luminosity upgrade, known as the High Luminosity LHC (HL-LHC), will require the replacement of the existing silicon strip tracker and the transistion radiation tracker. Although a baseline design for this tracker exists the ATLAS collaboration and other non-ATLAS groups are exploring the feasibility of using CMOS Monolithic Active Pixel Sensors (MAPS) which would be arranged in a strip-like fashion and would take advantage of the service and support structure already being developed for the upgrade. Two test devices made with the AMS H35 process (a High voltage or HV CMOS process) have been subjected to various radiation environments and have performed well. The results of these tests are presented in this paper.
Experimental characterization of peripheral photocurrent in CMOS photodiodes down to 65 nm technology
NASA Astrophysics Data System (ADS)
Blanco-Filgueira, B.; López, P.; Roldán, J. B.
In this work, an in-depth experimental characterization of submicron CMOS p-n+ junction photodiodes operating under uniform illumination in the visible range is performed. The experimental measurements are used to validate a previous two-dimensional analytical model for the photoresponse estimation of these structures, which pays special attention to the lateral collection and was verified by means of device simulations. To do so, square p-n+ junction photodiodes with different sizes down to an active area of 0.56 μm wide have been fabricated in 180 and 65 nm technological nodes and characterized under blue, green and red light sources. As a result, the importance of the lateral collection in the overall response for small photodiodes that was previously theoretically reported is confirmed. The experimentally validated two-dimensional analytical model is a powerful tool that can be employed for the design of CMOS imagers and related electronics circuits.
Analysis of neuronal cells of dissociated primary culture on high-density CMOS electrode array.
Matsuda, Eiko; Mita, Takeshi; Hubert, Julien; Bakkum, Douglas; Frey, Urs; Hierlemann, Andreas; Takahashi, Hirokazu; Ikegami, Takashi
Spontaneous development of neuronal cells was recorded around 4-34 days in vitro (DIV) with high-density CMOS array, which enables detailed study of the spatio-temporal activity of neuronal culture. We used the CMOS array to characterize the evolution of the inter-spike interval (ISI) distribution from putative single neurons, and estimate the network structure based on transfer entropy analysis, where each node corresponds to a single neuron. We observed that the ISI distributions gradually obeyed the power law with maturation of the network. The amount of information transferred between neurons increased at the early stage of development, but decreased as the network matured. These results suggest that both ISI and transfer entropy were very useful for characterizing the dynamic development of cultured neural cells over a few weeks. PMID:24109870
Heterogeneous CMOS/memristor hardware neural networks for real-time target classification
NASA Astrophysics Data System (ADS)
Merkel, Cory; Kudithipudi, Dhireesha; Ptucha, Ray
The advent of nanoscale metal-insulator-metal (MIM) structures with memristive properties has given birth to a new generation of hardware neural networks based on CMOS/memristor integration (CMHNNs). The advantage of the CMHNN paradigm compared to a pure CMOS approach lies in the multi-faceted functionality of memristive devices: They can efficiently store neural network configurations (weights and activation function parameters) via non-volatile, quasi-analog resistance states. They also provide high-density interconnects between neurons when integrated into 2-D and 3-D crossbar architectures. In this work, we explore the combination of CMHNN classifiers with manifold learning to reduce the dimensionality of CMHNN inputs. This allows the size of the CMHNN to be reduced significantly (by ≍ 97%). We tested the proposed system using the Caltech101 database and were able to achieve classification accuracies within ≍ 1:5% of those produced by a traditional support vector machine.
Ink-Jet Printed CMOS Electronics from Oxide Semiconductors.
Garlapati, Suresh Kumar; Baby, Tessy Theres; Dehm, Simone; Hammad, Mohammed; Chakravadhanula, Venkata Sai Kiran; Kruk, Robert; Hahn, Horst; Dasgupta, Subho
Complementary metal oxide semiconductor (CMOS) technology with high transconductance and signal gain is mandatory for practicable digital/analog logic electronics. However, high performance all-oxide CMOS logics are scarcely reported in the literature; specifically, not at all for solution-processed/printed transistors. As a major step toward solution-processed all-oxide electronics, here it is shown that using a highly efficient electrolyte-gating approach one can obtain printed and low-voltage operated oxide CMOS logics with high signal gain (≈21 at a supply voltage of only 1.5 V) and low static power dissipation. PMID:25867029
Lower-Dark-Current, Higher-Blue-Response CMOS Imagers
NASA Technical Reports Server (NTRS)
Pain, Bedabrata; Cunningham, Thomas; Hancock, Bruce
Several improved designs for complementary metal oxide/semiconductor (CMOS) integrated-circuit image detectors have been developed, primarily to reduce dark currents (leakage currents) and secondarily to increase responses to blue light and increase signal-handling capacities, relative to those of prior CMOS imagers. The main conclusion that can be drawn from a study of the causes of dark currents in prior CMOS imagers is that dark currents could be reduced by relocating p/n junctions away from Si/SiO2 interfaces. In addition to reflecting this conclusion, the improved designs include several other features to counteract dark-current mechanisms and enhance performance.
Quantifying the Antibody Binding on Protein Microarrays using Microarray Nonlinear Calibration
Yu, Xiaobo; Wallstrom, Garrick; Magee, Dewey Mitchell; Qiu, Ji; Mendoza, D. Eliseo A.; Wang, Jie; Bian, Xiaofang; Graves, Morgan; LaBaer, Joshua
To address the issue of quantification for antibody assays with protein microarrays, we firstly developed a Microarray Nonlinear Calibration (MiNC) method that applies in the quantification of antibody binding to the surface of microarray spots. We found that MiNC significantly increased the linear dynamic range and reduced assay variations. A serological analysis of guinea pig Mycobacterium tuberculosis models showed that a larger number of putative antigen targets were identified with MiNC, which is consistent with the improved assay performance of protein microarrays. We expect that our cumulative results will provide scientists with a new appreciation of antibody assays with protein microarrays. Our MiNC method has the potential to be employed in biomedical research with multiplex antibody assays which need quantitation, including the discovery of antibody biomarkers, clinical diagnostics with multi-antibody signatures and construction of immune mathematical models. PMID:23662896
Alternative Post-Processing on a CMOS Chip to Fabricate a Planar Microelectrode Array
López-Huerta, Francisco; Herrera-May, Agustín L.; Estrada-López, Johan J.; Zuñiga-Islas, Carlos; Cervantes-Sanchez, Blanca; Soto, Enrique; Soto-Cruz, Blanca S.
We present an alternative post-processing on a CMOS chip to release a planar microelectrode array (pMEA) integrated with its signal readout circuit, which can be used for monitoring the neuronal activity of vestibular ganglion neurons in newborn Wistar strain rats. This chip is fabricated through a 0.6 μm CMOS standard process and it has 12 pMEA through a 4 × 3 electrodes matrix. The alternative CMOS post-process includes the development of masks to protect the readout circuit and the power supply pads. A wet etching process eliminates the aluminum located on the surface of the p+-type silicon. This silicon is used as transducer for recording the neuronal activity and as interface between the readout circuit and neurons. The readout circuit is composed of an amplifier and tunable bandpass filter, which is placed on a 0.015 mm2 silicon area. The tunable bandpass filter has a bandwidth of 98 kHz and a common mode rejection ratio (CMRR) of 87 dB. These characteristics of the readout circuit are appropriate for neuronal recording applications. PMID:22346681
CMOS focal-plane-array for analysis of enzymatic reaction in system-on-chip spectrophotometer
NASA Astrophysics Data System (ADS)
Wang, Dong; Ha, Chanki; Park, Chan B.; Joo, Youngjoong
A CMOS focal-plane-array is designed for the high-throughput analysis of enzymatic reaction in on-chip spectrophotometer system. One of potential applications of the presented prototype system is to perform enzymatic analysis of biocompounds contained in blood. This function normally requires an expensive diode-array spectrophotometer, but it is possible to perform high throughput analysis with low budget if the spectrophotometer system is scaled down to a chip. The CMOS active pixel sensor array can cover a layer of polydimethylsiloxane (PDMS) forming the microfluidic channels and the substrate solution for enzymatic reaction can be injected into the channels by capillary force. Under room light, the underneath CMOS active pixel sensor with 40 x 40 pixels detect the gray levels of the fluid"s color. Inside the image sensor chip (size: 3mm x 3mm), the pixels of the same column share the same sample and hold circuits. The analog signals from 40 columns are multiplexed into one input feeding an on-chip 8 bits dual-slope analog to digital converter. The color change can be displayed on the external monitor by using a data acquisition card and personal computer.
Lee, Myoyong; Xiang, Charlie C.; Trent, Jeffrey M.; Bittner, Michael L.
Microarray fabrication using pre-synthesized long oligonucleotide is becoming increasingly important, but a study of large-scale array productions is not published yet. We addressed the issue of fabricating oligonucleotide microarrays by spotting commercial, pre-synthesized 65-mers with 5′ amines representing 7500 murine genes. Amine-modified oligonucleotides were immobilized on glass slides having aldehyde groups via transient Schiff base formation followed by reduction to produce a covalent conjugate. When RNA derived from the same source was used for Cy3 and Cy5 labeling and hybridized to the same array, signal intensities spanning three orders of magnitude were observed, and the coefficient of variation between the two channels for all spots was 8–10%. To ascertain the reproducibility of ratio determination of these arrays, two triplicate hybridizations (with fluorochrome reversal) comparing RNAs from a fibroblast (NIH3T3) and a breast cancer (JC) cell line were carried out. The 95% confidence interval for all spots in the six hybridizations was 0.60 – 1.66. This level of reproducibility allows use of the full range of pattern finding and discriminant analysis typically applied to cDNA microarrays. Further comparative testing was carried out with oligonucleotide microarrays, cDNA microarrays and RT-PCR assays to examine the comparability of results across these different methodologies. PMID:17617369
Latchup in CMOS devices from heavy ions
NASA Technical Reports Server (NTRS)
Soliman, K.; Nichols, D. K.
It is noted that complementary metal oxide semiconductor (CMOS) microcircuits are inherently latchup prone. The four-layer n-p-n-p structures formed from the parasitic pnp and npn transistors make up a silicon controlled rectifier. If properly biased, this rectifier may be triggered 'ON' by electrical transients, ionizing radiation, or a single heavy ion. This latchup phenomenon might lead to a loss of functionality or device burnout. Results are presented from tests on 19 different device types from six manufacturers which investigate their latchup sensitivity with argon and krypton beams. The parasitic npnp paths are identified in general, and a qualitative rationale is given for latchup susceptibility, along with a latchup cross section for each type of device. Also presented is the correlation between bit-flip sensitivity and latchup susceptibility.
CMOS image sensor with contour enhancement
NASA Astrophysics Data System (ADS)
Meng, Liya; Lai, Xiaofeng; Chen, Kun; Yuan, Xianghui
Imitating the signal acquisition and processing of vertebrate retina, a CMOS image sensor with bionic pre-processing circuit is designed. Integration of signal-process circuit on-chip can reduce the requirement of bandwidth and precision of the subsequent interface circuit, and simplify the design of the computer-vision system. This signal pre-processing circuit consists of adaptive photoreceptor, spatial filtering resistive network and Op-Amp calculation circuit. The adaptive photoreceptor unit with a dynamic range of approximately 100 dB has a good self-adaptability for the transient changes in light intensity instead of intensity level itself. Spatial low-pass filtering resistive network used to mimic the function of horizontal cell, is composed of the horizontal resistor (HRES) circuit and OTA (Operational Transconductance Amplifier) circuit. HRES circuit, imitating dendrite of the neuron cell, comprises of two series MOS transistors operated in weak inversion region. Appending two diode-connected n-channel transistors to a simple transconductance amplifier forms the OTA Op-Amp circuit, which provides stable bias voltage for the gate of MOS transistors in HRES circuit, while serves as an OTA voltage follower to provide input voltage for the network nodes. The Op-Amp calculation circuit with a simple two-stage Op-Amp achieves the image contour enhancing. By adjusting the bias voltage of the resistive network, the smoothing effect can be tuned to change the effect of image's contour enhancement. Simulations of cell circuit and 16×16 2D circuit array are implemented using CSMC 0.5μm DPTM CMOS process.
Use of a bacterial antimicrobial resistance gene microarray for the identification of resistant Staphylococcus aureus.
Garneau, P; Labrecque, O; Maynard, C; Messier, S; Masson, L; Archambault, M; Harel, J
As diagnostic and surveillance activities are vital to determine measures needed to control antimicrobial resistance (AMR), new and rapid laboratory methods are necessary to facilitate this important effort. DNA microarray technology allows the detection of a large number of genes in a single reaction. This technology is simple, specific and high-throughput. We have developed a bacterial antimicrobial resistance gene DNA microarray that will allow rapid antimicrobial resistance gene screening for all Gram-positive and Gram-negative bacteria. A prototype microarray was designed using a 70-mer based oligonucleotide set targeting AMR genes of Gram-negative and Gram-positive bacteria. In the present version, the microarray consists of 182 oligonucleotides corresponding to 166 different acquired AMR gene targets, covering most of the resistance genes found in both Gram-negative and -positive bacteria. A test study was performed on a collection of Staphylococcus aureus isolates from milk samples from dairy farms in Québec, Canada. The reproducibility of the hybridizations was determined, and the microarray results were compared with those obtained by phenotypic resistance tests (either MIC or Kirby-Bauer). The microarray genotyping demonstrated a correlation between penicillin, tetracycline and erythromycin resistance phenotypes with the corresponding acquired resistance genes. The hybridizations showed that the 38 antimicrobial resistant S. aureus isolates possessed at least one AMR gene. PMID:21083822
A microarray system for Y chromosomal and mitochondrial single nucleotide polymorphism analysis in chimpanzee populations.
Andrés, Olga; Rönn, Ann-Charlotte; Bonhomme, Maxime; Kellermann, Thomas; Crouau-Roy, Brigitte; Doxiadis, Gaby; Verschoor, Ernst J; Goossens, Benoît; Domingo-Roura, Xavier; Bruford, Michael W; Bosch, Montserrat; Syvänen, Ann-Christine
Chimpanzee populations are diminishing as a consequence of human activities, and as a result this species is now endangered. In the context of conservation programmes, genetic data can add vital information, for instance on the genetic diversity and structure of threatened populations. Single nucleotide polymorphisms (SNP) are biallelic markers that are widely used in human molecular studies and can be implemented in efficient microarray systems. This technology offers the potential of robust, multiplexed SNP genotyping at low reagent cost in other organisms than humans, but it is not commonly used yet in wild population studies. Here, we describe the characterization of new SNPs in Y-chromosomal intronic regions in chimpanzees and also identify SNPs from mitochondrial genes, with the aim of developing a microarray system that permits the simultaneous study of both paternal and maternal lineages. Our system consists of 42 SNPs for the Y chromosome and 45 SNPs for the mitochondrial genome. We demonstrate the applicability of this microarray in a captive population where genotypes accurately reflected its large pedigree. Two wild-living populations were also analysed and the results show that the microarray will be a useful tool alongside microsatellite markers, since it supplies complementary information about population structure and ecology. SNP genotyping using microarray technology, therefore, is a promising approach and may become an essential tool in conservation genetics to help in the management and study of captive and wild-living populations. Moreover, microarrays that combine SNPs from different genomic regions could replace microsatellite typing in the future. PMID:21585830
Accelerated life testing effects on CMOS microcircuit characteristics
NASA Technical Reports Server (NTRS)
This report covers the time period from May 1976 to December 1979 and encompasses the three phases of accelerated testing: Phase 1, the 250 C testing; Phase 2, the 200 C testing; and Phase 3, the 125 C testing. The duration of the test in Phase 1 and Phase 2 was sufficient to take the devices into the wear out region. The wear out distributions were used to estimate the activation energy between the 250 C and the 200 C test temperatures. The duration of the 125 C test, 20,000 hours, was not sufficient to bring the test devices into the wear out region; consequently the third data point at 125 C for determining the consistency of activation energy could not be obtained. It was estimated that, for the most complex of the three device types, the activation energy between 200 C and 125 C should be at least as high as that between 250 C and 200 C. The practicality of the use of high temperature for the accelerated life tests from the point of view of durability of equipment was assessed. Guidelines for the development of accelerated life test conditions were proposed. The use of the silicon nitride overcoat to improve the high temperature accelerated life test characteristics of CMOS microcircuits was explored in Phase 4 of this study and is attached as an appendix to this report.
Long synthetic oligonucleotides for microarray expression measurement
NASA Astrophysics Data System (ADS)
Li, Jiong; Wang, Hong; Liu, Heping; Zhang, M.; Zhang, Chunxiu; Lu, Zu-Hong; Gao, Xiang; Kong, Dong
There are generally two kinds of DNA microarray used for genomic-scale gene expression profiling of mRNA: cDNA and DNA chip, but both of them suffer from some drawbacks. To meet more requirements, another oligonucleotide microarray with long was produced. This type of microarray had the advantages of low cost, minimal Cross-hybridization, flexible and easy to make, which is most fit for small laboratories with special purposes. In this paper, we devised different probes with different probe lengths, GC contents and gene positions to optimization the probe design. Experiments showed 70 mer probes are suitable for both sufficient sensitivity and reasonable costs. Higher G-C content produces stronger signal intensity thus better sensitivity and probes designed at 3 untranslated region of gene within the range of 300 pb should be best for both sensitivity and specificity.
Protein microarrays for parasite antigen discovery.
Driguez, Patrick; Doolan, Denise L; Molina, Douglas M; Loukas, Alex; Trieu, Angela; Felgner, Phil L; McManus, Donald P
The host serological profile to a parasitic infection, such as schistosomiasis, can be used to define potential vaccine and diagnostic targets. Determining the host antibody response using traditional approaches is hindered by the large number of putative antigens in any parasite proteome. Parasite protein microarrays offer the potential for a high-throughput host antibody screen to simplify this task. In order to construct the array, parasite proteins are selected from available genomic sequence and protein databases using bioinformatic tools. Selected open reading frames are PCR amplified, incorporated into a vector for cell-free protein expression, and printed robotically onto glass slides. The protein microarrays can be probed with antisera from infected/immune animals or humans and the antibody reactivity measured with fluorophore labeled antibodies on a confocal laser microarray scanner to identify potential targets for diagnosis or therapeutic or prophylactic intervention. PMID:25388117
Applications of protein microarrays for biomarker discovery
Ramachandran, Niroshan; Srivastava, Sanjeeva; LaBaer, Joshua
The search for new biomarkers for diagnosis, prognosis and therapeutic monitoring of diseases continues in earnest despite dwindling success at finding novel reliable markers. Some of the current markers in clinical use do not provide optimal sensitivity and specificity, with the prostate cancer antigen (PSA) being one of many such examples. The emergence of proteomic techniques and systems approaches to study disease pathophysiology has rekindled the quest for new biomarkers. In particular the use of protein microarrays has surged as a powerful tool for large scale testing of biological samples. Approximately half the reports on protein microarrays have been published in the last two years especially in the area of biomarker discovery. In this review, we will discuss the application of protein microarray technologies that offer unique opportunities to find novel biomarkers. PMID:21136793
A safety monitoring system for taxi based on CMOS imager
NASA Astrophysics Data System (ADS)
Liu, Zhi
CMOS image sensors now become increasingly competitive with respect to their CCD counterparts, while adding advantages such as no blooming, simpler driving requirements and the potential of on-chip integration of sensor, analogue circuitry, and digital processing functions. A safety monitoring system for taxi based on cmos imager that can record field situation when unusual circumstance happened is described in this paper. The monitoring system is based on a CMOS imager (OV7120), which can output digital image data through parallel pixel data port. The system consists of a CMOS image sensor, a large capacity NAND FLASH ROM, a USB interface chip and a micro controller (AT90S8515). The structure of whole system and the test data is discussed and analyzed in detail.
Tests of commercial colour CMOS cameras for astronomical applications
NASA Astrophysics Data System (ADS)
Pokhvala, S. M.; Reshetnyk, V. M.; Zhilyaev, B. E.
We present some results of testing commercial colour CMOS cameras for astronomical applications. Colour CMOS sensors allow to perform photometry in three filters simultaneously that gives a great advantage compared with monochrome CCD detectors. The Bayer BGR colour system realized in colour CMOS sensors is close to the astronomical Johnson BVR system. The basic camera characteristics: read noise (e^{-}/pix), thermal noise (e^{-}/pix/sec) and electronic gain (e^{-}/ADU) for the commercial digital camera Canon 5D MarkIII are presented. We give the same characteristics for the scientific high performance cooled CCD camera system ALTA E47. Comparing results for tests of Canon 5D MarkIII and CCD ALTA E47 show that present-day commercial colour CMOS cameras can seriously compete with the scientific CCD cameras in deep astronomical imaging.
High-speed multicolour photometry with CMOS cameras
NASA Astrophysics Data System (ADS)
Pokhvala, S. M.; Zhilyaev, B. E.; Reshetnyk, V. M.
We present the results of testing the commercial digital camera Nikon D90 with a CMOS sensor for high-speed photometry with a small telescope Celestron 11'' at the Peak Terskol Observatory. CMOS sensor allows to perform photometry in 3 filters simultaneously that gives a great advantage compared with monochrome CCD detectors. The Bayer BGR colour system of CMOS sensors is close to the Johnson BVR system. The results of testing show that one can carry out photometric measurements with CMOS cameras for stars with the V-magnitude up to ≃14^{m} with the precision of 0.01^{m}. Stars with the V-magnitude up to ˜10 can be shot at 24 frames per second in the video mode.
Depleted CMOS pixels for LHC proton-proton experiments
NASA Astrophysics Data System (ADS)
Wermes, N.
While so far monolithic pixel detectors have remained in the realm of comparatively low rate and radiation applications outside LHC, new developments exploiting high resistivity substrates with three or four well CMOS process options allow reasonably large depletion depths and full CMOS circuitry in a monolithic structure. This opens up the possibility to target CMOS pixel detectors also for high radiation pp-experiments at the LHC upgrade, either in a hybrid-type fashion or even fully monolithic. Several pixel matrices have been prototyped with high ohmic substrates, high voltage options, and full CMOS electronics. They were characterized in the lab and in test beams. An overview of the necessary development steps and different approaches as well as prototype results are presented in this paper.
Hybridization and Selective Release of DNA Microarrays
Beer, N R; Baker, B; Piggott, T; Maberry, S; Hara, C M; DeOtte, J; Benett, W; Mukerjee, E; Dzenitis, J; Wheeler, E K
DNA microarrays contain sequence specific probes arrayed in distinct spots numbering from 10,000 to over 1,000,000, depending on the platform. This tremendous degree of multiplexing gives microarrays great potential for environmental background sampling, broad-spectrum clinical monitoring, and continuous biological threat detection. In practice, their use in these applications is not common due to limited information content, long processing times, and high cost. The work focused on characterizing the phenomena of microarray hybridization and selective release that will allow these limitations to be addressed. This will revolutionize the ways that microarrays can be used for LLNL's Global Security missions. The goals of this project were two-fold: automated faster hybridizations and selective release of hybridized features. The first study area involves hybridization kinetics and mass-transfer effects. the standard hybridization protocol uses an overnight incubation to achieve the best possible signal for any sample type, as well as for convenience in manual processing. There is potential to significantly shorten this time based on better understanding and control of the rate-limiting processes and knowledge of the progress of the hybridization. In the hybridization work, a custom microarray flow cell was used to manipulate the chemical and thermal environment of the array and autonomously image the changes over time during hybridization. The second study area is selective release. Microarrays easily generate hybridization patterns and signatures, but there is still an unmet need for methodologies enabling rapid and selective analysis of these patterns and signatures. Detailed analysis of individual spots by subsequent sequencing could potentially yield significant information for rapidly mutating and emerging (or deliberately engineered) pathogens. In the selective release work, optical energy deposition with coherent light quickly provides the thermal energy to
Analysis of High-Throughput ELISA Microarray Data
White, Amanda M.; Daly, Don S.; Zangar, Richard C.
Our research group develops analytical methods and software for the high-throughput analysis of quantitative enzyme-linked immunosorbent assay (ELISA) microarrays. ELISA microarrays differ from DNA microarrays in several fundamental aspects and most algorithms for analysis of DNA microarray data are not applicable to ELISA microarrays. In this review, we provide an overview of the steps involved in ELISA microarray data analysis and how the statistically sound algorithms we have developed provide an integrated software suite to address the needs of each data-processing step. The algorithms discussed are available in a set of open-source software tools (http://www.pnl.gov/statistics/ProMAT).
Overview of DNA microarrays: types, applications, and their future.
Bumgarner, Roger
This unit provides an overview of DNA microarrays. Microarrays are a technology in which thousands of nucleic acids are bound to a surface and are used to measure the relative concentration of nucleic acid sequences in a mixture via hybridization and subsequent detection of the hybridization events. This overview first discusses the history of microarrays and the antecedent technologies that led to their development. This is followed by discussion of the methods of manufacture of microarrays and the most common biological applications. The unit ends with a brief description of the limitations of microarrays and discusses how microarrays are being rapidly replaced by DNA sequencing technologies. PMID:23288464
Pineal function: impact of microarray analysis.
Klein, David C; Bailey, Michael J; Carter, David A; Kim, Jong-so; Shi, Qiong; Ho, Anthony K; Chik, Constance L; Gaildrat, Pascaline; Morin, Fabrice; Ganguly, Surajit; Rath, Martin F; Møller, Morten; Sugden, David; Rangel, Zoila G; Munson, Peter J; Weller, Joan L; Coon, Steven L
Microarray analysis has provided a new understanding of pineal function by identifying genes that are highly expressed in this tissue relative to other tissues and also by identifying over 600 genes that are expressed on a 24-h schedule. This effort has highlighted surprising similarity to the retina and has provided reason to explore new avenues of study including intracellular signaling, signal transduction, transcriptional cascades, thyroid/retinoic acid hormone signaling, metal biology, RNA splicing, and the role the pineal gland plays in the immune/inflammation response. The new foundation that microarray analysis has provided will broadly support future research on pineal function. PMID:19622385
MicroRNA expression profiling using microarrays.
Love, Cassandra; Dave, Sandeep
MicroRNAs are small noncoding RNAs which are able to regulate gene expression at both the transcriptional and translational levels. There is a growing recognition of the role of microRNAs in nearly every tissue type and cellular process. Thus there is an increasing need for accurate quantitation of microRNA expression in a variety of tissues. Microarrays provide a robust method for the examination of microRNA expression. In this chapter, we describe detailed methods for the use of microarrays to measure microRNA expression and discuss methods for the analysis of microRNA expression data. PMID:23666707
Protein Microarrays for the Detection of Biothreats
NASA Astrophysics Data System (ADS)
Herr, Amy E.
Although protein microarrays have proven to be an important tool in proteomics research, the technology is emerging as useful for public health and defense applications. Recent progress in the measurement and characterization of biothreat agents is reviewed in this chapter. Details concerning validation of various protein microarray formats, from contact-printed sandwich assays to supported lipid bilayers, are presented. The reviewed technologies have important implications for in vitro characterization of toxin-ligand interactions, serotyping of bacteria, screening of potential biothreat inhibitors, and as core components of biosensors, among others, research and engineering applications.
Delta Doping High Purity CCDs and CMOS for LSST
NASA Technical Reports Server (NTRS)
Blacksberg, Jordana; Nikzad, Shouleh; Hoenk, Michael; Elliott, S. Tom; Bebek, Chris; Holland, Steve; Kolbe, Bill
A viewgraph presentation describing delta doping high purity CCD's and CMOS for LSST is shown. The topics include: 1) Overview of JPL s versatile back-surface process for CCDs and CMOS; 2) Application to SNAP and ORION missions; 3) Delta doping as a back-surface electrode for fully depleted LBNL CCDs; 4) Delta doping high purity CCDs for SNAP and ORION; 5) JPL CMP thinning process development; and 6) Antireflection coating process development.
CMOS front end electronics for the ATLAS muon detector
Huth, J.; Oliver, J.; Hazen, E.; Shank, J.
An all-CMOS design for an integrated ASD (Amplifier-Shaper-Discriminator) chip for readout of the ATLAS Monitored Drift Tubes (MDTs) is presented. Eight channels of charge-sensitive preamp, two-stage pole/zero shaper, Wilkinson ADC and discriminator with programmable hysteresis are integrated on a single IC. Key elements have been prototyped in 1.2 and 0.5 micron CMOS operating at 5V and 3.3V respectively.
Design and image-quality performance of high resolution CMOS-based X-ray imaging detectors for digital mammography
NASA Astrophysics Data System (ADS)
Cha, B. K.; Kim, J. Y.; Kim, Y. J.; Yun, S.; Cho, G.; Kim, H. K.; Seo, C.-W.; Jeon, S.; Huh, Y.
In digital X-ray imaging systems, X-ray imaging detectors based on scintillating screens with electronic devices such as charge-coupled devices (CCDs), thin-film transistors (TFT), complementary metal oxide semiconductor (CMOS) flat panel imagers have been introduced for general radiography, dental, mammography and non-destructive testing (NDT) applications. Recently, a large-area CMOS active-pixel sensor (APS) in combination with scintillation films has been widely used in a variety of digital X-ray imaging applications. We employed a scintillator-based CMOS APS image sensor for high-resolution mammography. In this work, both powder-type Gd2O2S:Tb and a columnar structured CsI:Tl scintillation screens with various thicknesses were fabricated and used as materials to convert X-ray into visible light. These scintillating screens were directly coupled to a CMOS flat panel imager with a 25 × 50 mm2 active area and a 48 μm pixel pitch for high spatial resolution acquisition. We used a W/Al mammographic X-ray source with a 30 kVp energy condition. The imaging characterization of the X-ray detector was measured and analyzed in terms of linearity in incident X-ray dose, modulation transfer function (MTF), noise-power spectrum (NPS) and detective quantum efficiency (DQE).
An investigation of medical radiation detection using CMOS image sensors in smartphones
NASA Astrophysics Data System (ADS)
Kang, Han Gyu; Song, Jae-Jun; Lee, Kwonhee; Nam, Ki Chang; Hong, Seong Jong; Kim, Ho Chul
Medical radiation exposure to patients has increased with the development of diagnostic X-ray devices and multi-channel computed tomography (CT). Despite the fact that the low-dose CT technique can significantly reduce medical radiation exposure to patients, the increasing number of CT examinations has increased the total medical radiation exposure to patients. Therefore, medical radiation exposure to patients should be monitored to prevent cancers caused by diagnostic radiation. However, without using thermoluminescence or glass dosimeters, it is hardly measure doses received by patients during medical examinations accurately. Hence, it is necessary to develop radiation monitoring devices and algorithms that are reasonably priced and have superior radiation detection efficiencies. The aim of this study is to investigate the feasibility of medical dose measurement using complementary metal oxide semiconductor (CMOS) sensors in smartphone cameras with an algorithm to extract the X-ray interacted pixels. We characterized the responses of the CMOS sensors in a smartphone with respect to the X-rays generated by a general diagnostic X-ray system. The characteristics of the CMOS sensors in a smartphone camera, such as dose response linearity, dose rate dependence, energy dependence, angular dependence, and minimum detectable activity were evaluated. The high energy gamma-ray of 662 keV from Cs-137 can be detected using the smartphone camera. The smartphone cameras which employ the developed algorithm can detect medical radiations.
RF Design of a Wideband CMOS Integrated Receiver for Phased Array Applications
NASA Astrophysics Data System (ADS)
Jackson, Suzy A.
New silicon CMOS processes developed primarily for the burgeoning wireless networking market offer significant promise as a vehicle for the implementation of highly integrated receivers, especially at the lower end of the frequency range proposed for the Square Kilometre Array (SKA). An RF-CMOS 'Receiver-on-a-Chip' is being developed as part of an Australia Telescope program looking at technologies associated with the SKA. The receiver covers the frequency range 500 1700 MHz, with instantaneous IF bandwidth of 500 MHz and, on simulation, yields an input noise temperature of < 50 K at mid-band. The receiver will contain all active circuitry (LNA, bandpass filter, quadrature mixer, anti-aliasing filter, digitiser and serialiser) on one 0.18 μm RF-CMOS integrated circuit. This paper outlines receiver front-end development work undertaken to date, including design and simulation of an LNA using noise cancelling techniques to achieve a wideband input-power-match with little noise penalty.
CMOS micromachined probes by die-level fabrication for extracellular neural recording
NASA Astrophysics Data System (ADS)
Ho, Meng-Han; Chen, Hsin; Tseng, Fouriers; Yeh, Shih-Rung; S-C Lu, Michael
In this paper, we present the design, fabrication and characterization of CMOS micromachined probes for extracellular neural recording. A convenient fabrication process is proposed for making integrated recording probes at the die level, providing a low-cost solution for academic research as compared to the more expensive wafer-level approach adopted in prior work. The devices are fabricated in a standard 0.35 µm CMOS process, followed by post-CMOS micromachining steps to form the probes. The on-chip circuit, used for recording action potential signals of neural activities, provides a stable dc bias when operating in electrolyte. The subthreshold transistor at the circuit input provides a tunable resistance value between 10 MΩ up to GΩ. The circuit consumes a total power of 790 µW and has an output noise of 19.3 µV Hz-1/2 at 100 Hz. The recorded action potential from the stimulated ventral nerve cord of a crayfish is about 0.6 mV with a pulse width of about 1.2 ms.
Low-dose performance of wafer-scale CMOS-based X-ray detectors
NASA Astrophysics Data System (ADS)
Maes, Willem H.; Peters, Inge M.; Smit, Chiel; Kessener, Yves; Bosiers, Jan
Compared to published amorphous-silicon (TFT) based X-ray detectors, crystalline silicon CMOS-based active-pixel detectors exploit the benefits of low noise, high speed, on-chip integration and featuring offered by CMOS technology. This presentation focuses on the specific advantage of high image quality at very low dose levels. The measurement of very low dose performance parameters like Detective Quantum Efficiency (DQE) and Noise Equivalent Dose (NED) is a challenge by itself. Second-order effects like defect pixel behavior, temporal and quantization noise effects, dose measurement accuracy and limitation of the x-ray source settings will influence the measurements at very low dose conditions. Using an analytical model to predict the low dose behavior of a detector from parameters extracted from shot-noise limited dose levels is presented. These models can also provide input for a simulation environment for optimizing the performance of future detectors. In this paper, models for predicting NED and the DQE at very low dose are compared to measurements on different CMOS detectors. Their validity for different sensor and optical stack combinations as well as for different x-ray beam conditions was validated.
Radiation damage studies on STAR250 CMOS sensor at 300 keV for electron microscopy
NASA Astrophysics Data System (ADS)
Faruqi, A. R.; Henderson, R.; Holmes, J.
There is a pressing need for better electronic detectors to replace film for recording high-resolution images using electron cryomicroscopy. Our previous work has shown that direct electron detection in CMOS sensors is promising in terms of resolution and efficiency at 120 keV [A.R. Faruqi, R. Henderson, M. Prydderch, R. Turchetta, P. Allport, A. Evans, Nucl. Instr. and Meth. 546 (2005) 170], but in addition, the detectors must not be damaged by the electron irradiation. We now present new measurements on the radiation tolerance of a 25 μm pitch CMOS active-pixel sensor, the STAR250, which was designed by FillFactory using radiation-hard technology for space applications. Our tests on the STAR250 aimed to establish the imaging performance at 300 keV following irradiation. The residual contrast, measured on shadow images of a 300 mesh grid, was >80% after corrections for increased dark current, following irradiation with up to 5×10 7 electrons/pixel (equivalent to 80,000 electron/μm 2). A CMOS sensor with this degree of radiation tolerance would survive a year of normal usage for low-dose electron cryomicroscopy, which is a very useful advance.
Design of an ultra low power CMOS pixel sensor for a future neutron personal dosimeter
Zhang, Y.; Hu-Guo, C.; Husson, D.; Hu, Y.
Despite a continuously increasing demand, neutron electronic personal dosimeters (EPDs) are still far from being completely established because their development is a very difficult task. A low-noise, ultra low power consumption CMOS pixel sensor for a future neutron personal dosimeter has been implemented in a 0.35 {mu}m CMOS technology. The prototype is composed of a pixel array for detection of charged particles, and the readout electronics is integrated on the same substrate for signal processing. The excess electrons generated by an impinging particle are collected by the pixel array. The charge collection time and the efficiency are the crucial points of a CMOS detector. The 3-D device simulations using the commercially available Synopsys-SENTAURUS package address the detailed charge collection process. Within a time of 1.9 {mu}s, about 59% electrons created by the impact particle are collected in a cluster of 4 x 4 pixels with the pixel pitch of 80 {mu}m. A charge sensitive preamplifier (CSA) and a shaper are employed in the frond-end readout. The tests with electrical signals indicate that our prototype with a total active area of 2.56 x 2.56 mm{sup 2} performs an equivalent noise charge (ENC) of less than 400 e - and 314 {mu}W power consumption, leading to a promising prototype. (authors)
Applications of the Integrated High-Performance CMOS Image Sensor to Range Finders — from Optical Triangulation to the Automotive Field
Wu, Jih-Huah; Pen, Cheng-Chung; Jiang, Joe-Air
With their significant features, the applications of complementary metal-oxide semiconductor (CMOS) image sensors covers a very extensive range, from industrial automation to traffic applications such as aiming systems, blind guidance, active/passive range finders, etc. In this paper CMOS image sensor-based active and passive range finders are presented. The measurement scheme of the proposed active/passive range finders is based on a simple triangulation method. The designed range finders chiefly consist of a CMOS image sensor and some light sources such as lasers or LEDs. The implementation cost of our range finders is quite low. Image processing software to adjust the exposure time (ET) of the CMOS image sensor to enhance the performance of triangulation-based range finders was also developed. An extensive series of experiments were conducted to evaluate the performance of the designed range finders. From the experimental results, the distance measurement resolutions achieved by the active range finder and the passive range finder can be better than 0.6% and 0.25% within the measurement ranges of 1 to 8 m and 5 to 45 m, respectively. Feasibility tests on applications of the developed CMOS image sensor-based range finders to the automotive field were also conducted. The experimental results demonstrated that our range finders are well-suited for distance measurements in this field.
Low-noise CMOS SPAD arrays with in-pixel time-to-digital converters
NASA Astrophysics Data System (ADS)
Tosi, Alberto; Villa, Federica; Bronzi, Danilo; Zou, Yu; Lussana, Rudi; Tamborini, Davide; Tisa, Simone; Durini, Daniel; Weyers, Sascha; Pashen, Uwe; Brockherde, Werner; Zappa, Franco
We present our latest results concerning CMOS Single-Photon Avalanche Diode (SPAD) arrays for high-throughput parallel single-photon counting. We exploited a high-voltage 0.35 μm CMOS technology in order to develop low-noise CMOS SPADs. The Dark Count Rate is 30 cps at room temperature for 30 μm devices, increases to 2 kcps for 100 μm SPADs and just to 100 kcps for 500 μm ones. Afterpulsing is less than 1% for hold-off time longer than 50 ns, thus allowing to reach high count rates. Photon Detection Efficiency is > 50% at 420 nm, > 40% below 500 nm and is still 5% at 850 nm. Timing jitter is less than 100 ps (FWHM) in SPADs with active area diameter up to 50 μm. We developed CMOS SPAD imagers with 150 μm pixel pitch and 30 μm SPADs. A 64×32 SPAD array is based on pixels including three 9-bit counters for smart phase-resolved photon counting up to 100 kfps. A 32x32 SPAD array includes 1024 10-bit Time-to-Digital Converters (TDC) with 300 ps resolution and 450 ps single-shot precision, for 3D ranging and FLIM. We developed also linear arrays with up to 60 pixels (with 100 μm SPAD, 150 μm pitch and in-pixel 250 ps TDC) for time-resolved parallel spectroscopy with high fill factor.
On-chip polarizer on image sensor using advanced CMOS technology
NASA Astrophysics Data System (ADS)
Sasagawa, Kiyotaka; Wakama, Norimitsu; Noda, Toshihiko; Tokuda, Takashi; Kakiuchi, Kiyomi; Ohta, Jun
The structures in advanced complementary metal-oxide-semiconductor (CMOS) integrated circuit technology are in the range of deep-submicron. It allows designing and integrating nano-photonic structures for the visible to near infrared region on a chip. In this work, we designed and fabricated an image sensor with on-pixel metal wire grid polarizers by using a 65-nm standard CMOS technology. It is known that the extinction ratio of a metal wire grid polarizer is increased with decrease in the grid pitch. With the metal wire layers of the 65-nm technology, the grid pitch sufficiently smaller than the wavelengths of visible light can be realized. The extinction ratio of approximately 20 dB has been successfully achieved at a wavelength of 750 nm. In the CMOS technologies, it is usual to include multiple metal layers. This feature is also useful to increase the extinction ratio of polarizers. We designed dual layer polarizers. Each layer partially reflects incident light. Thus, the layers form a cavity and its transmission spectrum depends on the layer position. The extinction ratio of 19.2 dB at 780 nm was achieved with the grid pitch greater than the single layer polarizer. The high extinction ratio is obtained only red to near infrared region because the fine metal layers of deepsubmicron standard CMOS process is usually composed of Cu. Thus, it should be applied for measurement or observation where wide spectrum is not required such as optical rotation measurement of optically active materials or electro-optic imaging of RF/THz wave.
Advancement of CMOS Doping Technology in an External Development Framework
NASA Astrophysics Data System (ADS)
Jain, Amitabh; Chambers, James J.; Shaw, Judy B.
The consumer appetite for a rich multimedia experience drives technology development for mobile hand-held devices and the infrastructure to support them. Enhancements in functionality, speed, and user experience are derived from advancements in CMOS technology. The technical challenges in developing each successive CMOS technology node to support these enhancements have become increasingly difficult. These trends have motivated the CMOS business towards a collaborative approach based on strategic partnerships. This paper describes our model and experience of CMOS development, based on multi-dimensional industrial and academic partnerships. We provide to our process equipment, materials, and simulation partners, as well as to our silicon foundry partners, the detailed requirements for future integrated circuit products. This is done very early in the development cycle to ensure that these requirements can be met. In order to determine these fundamental requirements, we rely on a strategy that requires strong interaction between process and device simulation, physical and chemical analytical methods, and research at academic institutions. This learning is shared with each project partner to address integration and manufacturing issues encountered during CMOS technology development from its inception through product ramp. We utilize TI's core strengths in physical analysis, unit processes and integration, yield ramp, reliability, and product engineering to support this technological development. Finally, this paper presents examples of the advancement of CMOS doping technology for the 28 nm node and beyond through this development model.
Analysis of porcine MHC using microarrays.
Gao, Yu; Wahlberg, Per; Marthey, Sylvain; Esquerré, Diane; Jaffrézic, Florence; Lecardonnel, Jérome; Hugot, Karine; Rogel-Gaillard, Claire
The major histocompatibility complex (MHC) in Mammals is one of the most gene dense regions of the genome and contains the polymorphic histocompatibility gene families known to be involved in pathogen response and control of auto-immunity. The MHC is a complex genetic system that provides an interesting model system to study genome expression regulation and genetic diversity at the megabase scale. The pig MHC or SLA (Swine Leucocyte Antigen) complex spans 2.4 megabases and 151 loci have been annotated. We will review key results from previous RNA expression studies using microarrays containing probes specific to annotated loci within SLA and in addition present novel data obtained using high-density tiling arrays encompassing the whole SLA complex. We have focused on transcriptome modifications of porcine peripheral blood mononuclear cells stimulated with a mixture of phorbol myristate acetate and ionomycin known to activate B and T cell proliferation. Our results show that numerous loci mapping to the SLA complex are affected by the treatment. A general decreased level of expression for class I and II genes and an up-regulation of genes involved in peptide processing and transport were observed. Tiling array-based experiments contributed to refined gene annotations as presented for one SLA class I gene referred to as SLA-11. In conclusion, high-density tiling arrays can serve as an excellent tool to draw comprehensive transcription maps, and improve genome annotations for the SLA complex. We are currently studying their relevance to characterize SLA genetic diversity in combination with high throughput next generation sequencing. PMID:21561666
Novel integrated CMOS pixel structures for vertex detectors
Kleinfelder, Stuart; Bieser, Fred; Chen, Yandong; Gareus, Robin; Matis, Howard S.; Oldenburg, Markus; Retiere, Fabrice; Ritter, Hans Georg; Wieman, Howard H.; Yamamoto, Eugene
Novel CMOS active pixel structures for vertex detector applications have been designed and tested. The overriding goal of this work is to increase the signal to noise ratio of the sensors and readout circuits. A large-area native epitaxial silicon photogate was designed with the aim of increasing the charge collected per struck pixel and to reduce charge diffusion to neighboring pixels. The photogate then transfers the charge to a low capacitance readout node to maintain a high charge to voltage conversion gain. Two techniques for noise reduction are also presented. The first is a per-pixel kT/C noise reduction circuit that produces results similar to traditional correlated double sampling (CDS). It has the advantage of requiring only one read, as compared to two for CDS, and no external storage or subtraction is needed. The technique reduced input-referred temporal noise by a factor of 2.5, to 12.8 e{sup -}. Finally, a column-level active reset technique is explored that suppresses kT/C noise during pixel reset. In tests, noise was reduced by a factor of 7.6 times, to an estimated 5.1 e{sup -} input-referred noise. The technique also dramatically reduces fixed pattern (pedestal) noise, by up to a factor of 21 in our tests. The latter feature may possibly reduce pixel-by-pixel pedestal differences to levels low enough to permit sparse data scan without per-pixel offset corrections.
A new architecture of current-mode CMOS TDI Sensor
NASA Astrophysics Data System (ADS)
Ji, Cheng; Chen, Yongping
Nowadays, CMOS sensors still suffer from the problem of low SNR, especially in the stage of low illumination and high relative scanning velocity. Lots of methods have been develop to overcome this problem. Among these researches, TDI (Time Delay Integration) architecture is a more natural choice, which is natively supported by CCD sensors. In this paper a new kind of proposed current-mode sensor is used to achieve TDI operation in analog domain. The circuit is composed of three main parts. At first, a current-type pixel is proposed, in which the active MOSFET is operated in the triode region to ensure the output current is linearly dependent on the gate voltage and avoid the reduction of threshold voltage in the traditional voltage mode pixels, such as 3T, 4T which use the source followers as its active part. Then a discrete double sampling (DDS) unit, which is operated in the form of currents is used to efficiently reduce the fixed pattern noise (FPN) and make the output is independent of reset voltage of pixels. For accumulation, an improved current mirror adder under controlled of timing circuits is proposed to overcome the problem of saturation suffered in voltage domain. Some main noise sources, especially come from analog sample and holds capacitors and switches is analyzed. Finally, simulation results with CSMC 0.5um technology and Cadence IC show that the proposed method is reasonable and efficient to improve the SNR.
Measurements of Si hybrid CMOS x-ray detector characteristics
NASA Astrophysics Data System (ADS)
Bongiorno, Stephen D.; Falcone, Abraham D.; Burrows, David N.; Cook, Robert
The recent development of active pixel sensors as X-Ray focal plane arrays will place them in contention with CCDs on future satellite missions. Penn State University (PSU) is working with Teledyne Imaging Sensors (TIS) to develop X-Ray Hybrid CMOS devices (HCDs), a type of active pixel sensor with fast frame rates, adaptable readout timing and geometry, low power consumption, and inherent radiation hardness. CCDs have been used with great success on the current generation of X-Ray telescopes (e.g. Chandra, XMM, Suzaku, and Swift). However, their bucket-brigade readout architecture, which transfers charge across the chip with discrete component readout electronics, results in clockrate limited readout speeds that cause pileup (saturation) of bright sources and an inherent susceptibility to radiation induced displacement damage that limits mission lifetime. In contrast, HCDs read pixels through the detector substrate with low power, on-chip readout integrated circuits. Faster frame rates, achieved with adaptable readout timing and geometry, will allow the next generation's larger effective area telescopes to observe brighter sources free of pileup. In HCDs, radiation damaged lattice sites affect a single pixel instead of an entire row. The PSU X-ray group is currently testing 4 Teledyne HCDs, with low cross-talk CTIA devices in development. We will report laboratory measurements of HCD readnoise, interpixel-capacitance and its impact on event selection, linearity, and energy resolution as a function of energy.
Thoughtful data analysis is as important as experimental design, biological sample quality, and appropriate experimental procedures for making microarrays a useful supplement to traditional toxicology. In the present study, spotted oligonucleotide microarrays were used to profile...
Microarray Data Analysis Using Multiple Statistical Models
Wenjun Bao1, Judith E. Schmid1, Amber K. Goetz1, Ming Ouyang2, William J. Welsh2,Andrew I. Brooks3,4, ChiYi Chu3,Mitsunori Ogihara3,4, Yinhe Cheng5, David J. Dix1. 1National Health and Environmental Effects Researc...
Microarrays (DNA Chips) for the Classroom Laboratory
ERIC Educational Resources Information Center
Barnard, Betsy; Sussman, Michael; BonDurant, Sandra Splinter; Nienhuis, James; Krysan, Patrick
We have developed and optimized the necessary laboratory materials to make DNA microarray technology accessible to all high school students at a fraction of both cost and data size. The primary component is a DNA chip/array that students "print" by hand and then analyze using research tools that have been adapted for classroom use. The primary…
Microarray technology as applied to areas that include genomics, diagnostics, environmental, and drug discovery, is an interesting research topic for which different chip-based devices have been developed. As an alternative, we have explored the principle of compact disc-based...
Microarray data classified by artificial neural networks.
Linder, Roland; Richards, Tereza; Wagner, Mathias
Systems biology has enjoyed explosive growth in both the number of people participating in this area of research and the number of publications on the topic. The field of systems biology encompasses the in silico analysis of high-throughput data as provided by DNA or protein microarrays. Along with the increasing availability of microarray data, attention is focused on methods of analyzing the expression rates. One important type of analysis is the classification task, for example, distinguishing different types of cell functions or tumors. Recently, interest has been awakened toward artificial neural networks (ANN), which have many appealing characteristics such as an exceptional degree of accuracy. Nonlinear relationships or independence from certain assumptions regarding the data distribution are also considered. The current work reviews advantages as well as disadvantages of neural networks in the context of microarray analysis. Comparisons are drawn to alternative methods. Selected solutions are discussed, and finally algorithms for the effective combination of multiple ANNs are presented. The development of approaches to use ANN-processed microarray data applicable to run cell and tissue simulations may be slated for future investigation. PMID:18220242
Data Analysis Strategies for Protein Microarrays
Díez, Paula; Dasilva, Noelia; González-González, María; Matarraz, Sergio; Casado-Vela, Juan; Orfao, Alberto; Fuentes, Manuel
Microarrays constitute a new platform which allows the discovery and characterization of proteins. According to different features, such as content, surface or detection system, there are many types of protein microarrays which can be applied for the identification of disease biomarkers and the characterization of protein expression patterns. However, the analysis and interpretation of the amount of information generated by microarrays remain a challenge. Further data analysis strategies are essential to obtain representative and reproducible results. Therefore, the experimental design is key, since the number of samples and dyes, among others aspects, would define the appropriate analysis method to be used. In this sense, several algorithms have been proposed so far to overcome analytical difficulties derived from fluorescence overlapping and/or background noise. Each kind of microarray is developed to fulfill a specific purpose. Therefore, the selection of appropriate analytical and data analysis strategies is crucial to achieve successful biological conclusions. In the present review, we focus on current algorithms and main strategies for data interpretation.
Diagnostic Oligonucleotide Microarray Fingerprinting of Bacillus Isolates
Chandler, Darrell P.; Alferov, Oleg; Chernov, Boris; Daly, Don S.; Golova, Julia; Perov, Alexander N.; Protic, Miroslava; Robison, Richard; Shipma, Matthew; White, Amanda M.; Willse, Alan R.
A diagnostic, genome-independent microbial fingerprinting method using DNA oligonucleotide microarrays was used for high-resolution differentiation between closely related Bacillus strains, including two strains of Bacillus anthracis that are monomorphic (indistinguishable) via amplified fragment length polymorphism fingerprinting techniques. Replicated hybridizations on 391-probe nonamer arrays were used to construct a prototype fingerprint library for quantitative comparisons. Descriptive analysis of the fingerprints, including phylogenetic reconstruction, is consistent with previous taxonomic organization of the genus. Newly developed statistical analysis methods were used to quantitatively compare and objectively confirm apparent differences in microarray fingerprints with the statistical rigor required for microbial forensics and clinical diagnostics. These data suggest that a relatively simple fingerprinting microarray and statistical analysis method can differentiate between species in the Bacillus cereus complex, and between strains of B. anthracis. A synthetic DNA standard was used to understand underlying microarray and process-level variability, leading to specific recommendations for the development of a standard operating procedure and/or continued technology enhancements for microbial forensics and diagnostics.
Shrinkage covariance matrix approach for microarray data
NASA Astrophysics Data System (ADS)
Karjanto, Suryaefiza; Aripin, Rasimah
Microarray technology was developed for the purpose of monitoring the expression levels of thousands of genes. A microarray data set typically consists of tens of thousands of genes (variables) from just dozens of samples due to various constraints including the high cost of producing microarray chips. As a result, the widely used standard covariance estimator is not appropriate for this purpose. One such technique is the Hotelling's T2 statistic which is a multivariate test statistic for comparing means between two groups. It requires that the number of observations (n) exceeds the number of genes (p) in the set but in microarray studies it is common that n < p. This leads to a biased estimate of the covariance matrix. In this study, the Hotelling's T2 statistic with the shrinkage approach is proposed to estimate the covariance matrix for testing differential gene expression. The performance of this approach is then compared with other commonly used multivariate tests using a widely analysed diabetes data set as illustrations. The results across the methods are consistent, implying that this approach provides an alternative to existing techniques.
Raman-based microarray readout: a review.
Haisch, Christoph
For a quarter of a century, microarrays have been part of the routine analytical toolbox. Label-based fluorescence detection is still the commonest optical readout strategy. Since the 1990s, a continuously increasing number of label-based as well as label-free experiments on Raman-based microarray readout concepts have been reported. This review summarizes the possible concepts and methods and their advantages and challenges. A common label-based strategy is based on the binding of selective receptors as well as Raman reporter molecules to plasmonic nanoparticles in a sandwich immunoassay, which results in surface-enhanced Raman scattering signals of the reporter molecule. Alternatively, capture of the analytes can be performed by receptors on a microarray surface. Addition of plasmonic nanoparticles again leads to a surface-enhanced Raman scattering signal, not of a label but directly of the analyte. This approach is mostly proposed for bacteria and cell detection. However, although many promising readout strategies have been discussed in numerous publications, rarely have any of them made the step from proof of concept to a practical application, let alone routine use. Graphical Abstract Possible realization of a SERS (Surface-Enhanced Raman Scattering) system for microarray readout. PMID:26973235
Multiband CMOS sensor simplify FPA design
NASA Astrophysics Data System (ADS)
Wang, Weng Lyang B.; Ling, Jer
Push broom multi-band Focal Plane Array (FPA) design needs to consider optics, image sensor, electronic, mechanic as well as thermal. Conventional FPA use two or several CCD device as an image sensor. The CCD image sensor requires several high speed, high voltage and high current clock drivers as well as analog video processors to support their operation. Signal needs to digitize using external sample / hold and digitized circuit. These support circuits are bulky, consume a lot of power, must be shielded and placed in close to the CCD to minimize the introduction of unwanted noise. The CCD also needs to consider how to dissipate power. The end result is a very complicated FPA and hard to make due to more weighs and draws more power requiring complex heat transfer mechanisms. In this paper, we integrate microelectronic technology and multi-layer soft / hard Printed Circuit Board (PCB) technology to design electronic portion. Since its simplicity and integration, the optics, mechanic, structure and thermal design will become very simple. The whole FPA assembly and dis-assembly reduced to a few days. A multi-band CMOS Sensor (dedicated as C468) was used for this design. The CMOS Sensor, allow for the incorporation of clock drivers, timing generators, signal processing and digitization onto the same Integrated Circuit (IC) as the image sensor arrays. This keeps noise to a minimum while providing high functionality at reasonable power levels. The C468 is a first Multiple System-On-Chip (MSOC) IC. This device used our proprietary wafer butting technology and MSOC technology to combine five long sensor arrays into a size of 120 mm x 23.2 mm and 155 mm x 60 mm for chip and package, respectively. The device composed of one Panchromatic (PAN) and four different Multi- Spectral (MS) sensors. Due to its integration on the electronic design, a lot of room is clear for the thermal design. The optical and mechanical design is become very straight forward. The flight model FPA
Examining microarray slide quality for the EPA using SNL's hyperspectral microarray scanner.
Rohde, Rachel M.; Timlin, Jerilyn Ann
This report summarizes research performed at Sandia National Laboratories (SNL) in collaboration with the Environmental Protection Agency (EPA) to assess microarray quality on arrays from two platforms of interest to the EPA. Custom microarrays from two novel, commercially produced array platforms were imaged with SNL's unique hyperspectral imaging technology and multivariate data analysis was performed to investigate sources of emission on the arrays. No extraneous sources of emission were evident in any of the array areas scanned. This led to the conclusions that either of these array platforms could produce high quality, reliable microarray data for the EPA toxicology programs. Hyperspectral imaging results are presented and recommendations for microarray analyses using these platforms are detailed within the report.
Microarray analysis at single molecule resolution
Mureşan, Leila; Jacak, Jarosław; Klement, Erich Peter; Hesse, Jan; Schütz, Gerhard J.
Bioanalytical chip-based assays have been enormously improved in sensitivity in the recent years; detection of trace amounts of substances down to the level of individual fluorescent molecules has become state of the art technology. The impact of such detection methods, however, has yet not fully been exploited, mainly due to a lack in appropriate mathematical tools for robust data analysis. One particular example relates to the analysis of microarray data. While classical microarray analysis works at resolutions of two to 20 micrometers and quantifies the abundance of target molecules by determining average pixel intensities, a novel high resolution approach [1] directly visualizes individual bound molecules as diffraction limited peaks. The now possible quantification via counting is less susceptible to labeling artifacts and background noise. We have developed an approach for the analysis of high-resolution microarray images. It consists first of a single molecule detection step, based on undecimated wavelet transforms, and second, of a spot identification step via spatial statistics approach (corresponding to the segmentation step in the classical microarray analysis). The detection method was tested on simulated images with a concentration range of 0.001 to 0.5 molecules per square micron and signal-to-noise ratio (SNR) between 0.9 and 31.6. For SNR above 15 the false negatives relative error was below 15%. Separation of foreground/background proved reliable, in case foreground density exceeds background by a factor of 2. The method has also been applied to real data from high-resolution microarray measurements. PMID:20123580
Facilitating functional annotation of chicken microarray data
Background Modeling results from chicken microarray studies is challenging for researchers due to little functional annotation associated with these arrays. The Affymetrix GenChip chicken genome array, one of the biggest arrays that serve as a key research tool for the study of chicken functional genomics, is among the few arrays that link gene products to Gene Ontology (GO). However the GO annotation data presented by Affymetrix is incomplete, for example, they do not show references linked to manually annotated functions. In addition, there is no tool that facilitates microarray researchers to directly retrieve functional annotations for their datasets from the annotated arrays. This costs researchers amount of time in searching multiple GO databases for functional information. Results We have improved the breadth of functional annotations of the gene products associated with probesets on the Affymetrix chicken genome array by 45% and the quality of annotation by 14%. We have also identified the most significant diseases and disorders, different types of genes, and known drug targets represented on Affymetrix chicken genome array. To facilitate functional annotation of other arrays and microarray experimental datasets we developed an Array GO Mapper (AGOM) tool to help researchers to quickly retrieve corresponding functional information for their dataset. Conclusion Results from this study will directly facilitate annotation of other chicken arrays and microarray experimental datasets. Researchers will be able to quickly model their microarray dataset into more reliable biological functional information by using AGOM tool. The disease, disorders, gene types and drug targets revealed in the study will allow researchers to learn more about how genes function in complex biological systems and may lead to new drug discovery and development of therapies. The GO annotation data generated will be available for public use via AgBase website and will be updated on regular
Identifying Fishes through DNA Barcodes and Microarrays
Kochzius, Marc; Seidel, Christian; Antoniou, Aglaia; Botla, Sandeep Kumar; Campo, Daniel; Cariani, Alessia; Vazquez, Eva Garcia; Hauschild, Janet; Hervet, Caroline; Hjörleifsdottir, Sigridur; Hreggvidsson, Gudmundur; Kappel, Kristina; Landi, Monica; Magoulas, Antonios; Marteinsson, Viggo; Nölte, Manfred; Planes, Serge; Tinti, Fausto; Turan, Cemal; Venugopal, Moleyur N.; Weber, Hannes; Blohm, Dietmar
Background International fish trade reached an import value of 62.8 billion Euro in 2006, of which 44.6% are covered by the European Union. Species identification is a key problem throughout the life cycle of fishes: from eggs and larvae to adults in fisheries research and control, as well as processed fish products in consumer protection. Methodology/Principal Findings This study aims to evaluate the applicability of the three mitochondrial genes 16S rRNA (16S), cytochrome b (cyt b), and cytochrome oxidase subunit I (COI) for the identification of 50 European marine fish species by combining techniques of "DNA barcoding" and microarrays. In a DNA barcoding approach, neighbour Joining (NJ) phylogenetic trees of 369 16S, 212 cyt b, and 447 COI sequences indicated that cyt b and COI are suitable for unambiguous identification, whereas 16S failed to discriminate closely related flatfish and gurnard species. In course of probe design for DNA microarray development, each of the markers yielded a high number of potentially species-specific probes in silico, although many of them were rejected based on microarray hybridisation experiments. None of the markers provided probes to discriminate the sibling flatfish and gurnard species. However, since 16S-probes were less negatively influenced by the "position of label" effect and showed the lowest rejection rate and the highest mean signal intensity, 16S is more suitable for DNA microarray probe design than cty b and COI. The large portion of rejected COI-probes after hybridisation experiments (>90%) renders the DNA barcoding marker as rather unsuitable for this high-throughput technology. Conclusions/Significance Based on these data, a DNA microarray containing 64 functional oligonucleotide probes for the identification of 30 out of the 50 fish species investigated was developed. It represents the next step towards an automated and easy-to-handle method to identify fish, ichthyoplankton, and fish products. PMID
Development of a large-area CMOS-based detector for real-time x-ray imaging
NASA Astrophysics Data System (ADS)
Heo, Sung Kyn; Park, Sung Kyu; Hwang, Sung Ha; Im, Dong Ak; Kosonen, Jari; Kim, Tae Woo; Yun, Seungman; Kim, Ho Kyung
Complementary metal-oxide-semiconductor (CMOS) active pixel sensors (APSs) with high electrical and optical performances are now being attractive for digital radiography (DR) and dental cone-beam computed tomography (CBCT). In this study, we report our prototype CMOS-based detectors capable of real-time imaging. The field-of-view of the detector is 12 × 14.4 cm. The detector employs a CsI:Tl scintillator as an x-ray-to-light converter. The electrical performance of the CMOS APS, such as readout noise and full-well capacity, was evaluated. The x-ray imaging characteristics of the detector were evaluated in terms of characteristic curve, pre-sampling modulation transfer function, noise power spectrum, detective quantum efficiency, and image lag. The overall performance of the detector is demonstrated with phantom images obtained for DR and CBCT applications. The detailed development description and measurement results are addressed. With the results, we suggest that the prototype CMOS-based detector has the potential for CBCT and real-time x-ray imaging applications.
A CMOS readout circuit for microstrip detectors
NASA Astrophysics Data System (ADS)
Nasri, B.; Fiorini, C.
In this work, we present the design and the results of a CMOS analog channel for silicon microstrips detectors. The readout circuit was initially conceived for the outer layers of the SuperB silicon vertex tracker (SVT), but can serve more generally other microstrip-based detection systems. The strip detectors considered show a very high stray capacitance and high series resistance. Therefore, the noise optimization was the first priority design concern. A necessary compromise on the best peaking time to achieve an acceptable noise level together with efficiency and timing accuracy has been investigated. The ASIC is composed by a preamplifier, shaping amplifier and a Time over Threshold (T.o.T) block for the digitalization of the signals. The chosen shaping function is the third-order semi-Gaussian function implemented with complex poles. An inverter stage is employed in the analog channel in order to operate with signals delivered from both p and n strips. The circuit includes the possibility to select the peaking time of the shaper output from four values: 250 ns, 375 ns, 500 ns and 750 ns. In this way, the noise performances and the signal occupancy can be optimized according to the real background during the experiment. The ASIC prototype has been fabricated in the 130 nm IBM technology which is considered intrinsically radiation hard. The results of the experimental characterization of a produced prototype are satisfactorily matched with simulation.
NSC 800, 8-bit CMOS microprocessor
NASA Technical Reports Server (NTRS)
Suszko, S. F.
The NSC 800 is an 8-bit CMOS microprocessor manufactured by National Semiconductor Corp., Santa Clara, California. The 8-bit microprocessor chip with 40-pad pin-terminals has eight address buffers (A8-A15), eight data address -- I/O buffers (AD(sub 0)-AD(sub 7)), six interrupt controls and sixteen timing controls with a chip clock generator and an 8-bit dynamic RAM refresh circuit. The 22 internal registers have the capability of addressing 64K bytes of memory and 256 I/O devices. The chip is fabricated on N-type (100) silicon using self-aligned polysilicon gates and local oxidation process technology. The chip interconnect consists of four levels: Aluminum, Polysi 2, Polysi 1, and P(+) and N(+) diffusions. The four levels, except for contact interface, are isolated by interlevel oxide. The chip is packaged in a 40-pin dual-in-line (DIP), side brazed, hermetically sealed, ceramic package with a metal lid. The operating voltage for the device is 5 V. It is available in three operating temperature ranges: 0 to +70 C, -40 to +85 C, and -55 to +125 C. Two devices were submitted for product evaluation by F. Stott, MTS, JPL Microprocessor Specialist. The devices were pencil-marked and photographed for identification.
Simulation of SEU transients in CMOS ICs
Kaul, N.; Bhuva, B.L.; Kerns, S.E. )
This paper reports that available analytical models of the number of single-event-induced errors (SEU) in combinational logic systems are not easily applicable to real integrated circuits (ICs). An efficient computer simulation algorithm set, SITA, predicts the vulnerability of data stored in and processed by complex combinational logic circuits to SEU. SITA is described in detail to allow researchers to incorporate it into their error analysis packages. Required simulation algorithms are based on approximate closed-form equations modeling individual device behavior in CMOS logic units. Device-level simulation is used to estimate the probability that ion-device interactions produce erroneous signals capable of propagating to a latch (or n output node), and logic-level simulation to predict the spread of such erroneous, latched information through the IC. Simulation results are compared to those from SPICE for several circuit and logic configurations. SITA results are comparable to this established circuit-level code, and SITA can analyze circuits with state-of-the-art device densities (which SPICE cannot). At all IC complexity levels, SITAS offers several factors of 10 savings in simulation time over SPICE.
On noise in time-delay integration CMOS image sensors
NASA Astrophysics Data System (ADS)
Levski, Deyan; Choubey, Bhaskar
Time delay integration sensors are of increasing interest in CMOS processes owing to their low cost, power and ability to integrate with other circuit readout blocks. This paper presents an analysis of the noise contributors in current day CMOS Time-Delay-Integration image sensors with various readout architectures. An analysis of charge versus voltage domain readout modes is presented, followed by a noise classification of the existing Analog Accumulator Readout (AAR) and Digital Accumulator Readout (DAR) schemes for TDI imaging. The analysis and classification of existing readout schemes include, pipelined charge transfer, buffered direct injection, voltage as well as current-mode analog accumulators and all-digital accumulator techniques. Time-Delay-Integration imaging modes in CMOS processes typically use an N-number of readout steps, equivalent to the number of TDI pixel stages. In CMOS TDI sensors, where voltage domain readout is used, the requirements over speed and noise of the ADC readout chain are increased due to accumulation of the dominant voltage readout and ADC noise with every stage N. Until this day, the latter is the primary reason for a leap-back of CMOS TDI sensors as compared to their CCD counterparts. Moreover, most commercial CMOS TDI implementations are still based on a charge-domain readout, mimicking a CCD-like operation mode. Thus, having a good understanding of each noise contributor in the signal chain, as well as its magnitude in different readout architectures, is vital for the design of future generation low-noise CMOS TDI image sensors based on a voltage domain readout. This paper gives a quantitative classification of all major noise sources for all popular implementations in the literature.
A 16-channel CMOS preamplifier for laser ranging radar receivers
NASA Astrophysics Data System (ADS)
Liu, Ru-qing; Zhu, Jing-guo; Jiang, Yan; Li, Meng-lin; Li, Feng
A 16-channal front-end preamplifier array has been design in a 0.18um CMOS process for pulse Laser ranging radar receiver. This front-end preamplifier array incorporates transimpedance amplifiers(TIAs) and differential voltage post-amplifier(PAMP),band gap reference and other interface circuits. In the circuit design, the regulated cascade (RGC) input stage, Cherry-Hooper and active inductor peaking were employed to enhance the bandwidth. And in the layout design, by applying the layout isolation structure combined with P+ guard-ring(PGR), N+ guard-ring(NGR),and deep-n-well(DNW) for amplifier array, the crosstalk and the substrate noise coupling was reduced effectively. The simulations show that a single channel receiver front-end preamplifier achieves 95 dBΩ transimpedance gain and 600MHz bandwidth for 3 PF photodiode capacitance. The total power of 16-channel front-end amplifier array is about 800mW for 1.8V supply.
High quality epoxysilane substrate for clinical multiplex serodiagnostic proteomic microarrays
NASA Astrophysics Data System (ADS)
Ewart, Tom; Carmichael, Stuart; Lea, Peter
Polylysine and aminopropylsilane treated glass comprised the majority of substrates employed in first generation genetic microarray substrates. Second generation single stranded long oligo libraries with amino termini provided for controlled terminal specific attachment, and rationally designed unique sequence libraries with normalized melting temperatures. These libraries benefit from active covalent coupling surfaces such as Epoxysilane. The latter's oxime ring shows versatile reactivity with amino-, thiol- and hydroxyl- groups thus encompassing small molecule, oligo and proteomic microarray applications. Batch-to-batch production uniformity supports entry of the Epoxysilane process into clinical diagnostics. We carried out multiple print runs of 21 clinically relevant bacterial and viral antigens at optimized concentrations, plus human IgG and IgM standards in triplicate on multiple batches of Epoxysilane substrates. A set of 45 patient sera were assayed in a 35 minute protocol using 10 microliters per array in a capillary-fill format (15 minute serum incubation, wash, 15 minute incubation with Cy3-labeled anti-hIgG plus Dy647-labeled anti-hIgM, final wash). The LOD (3 SD above background) was better than 1 microgram/ml for IgG, and standard curves were regular and monotonically increasing over the range 0 to 1000 micrograms/ml. Ninety-five percent of the CVs for the standards were under 10%, and 90% percent of CVs for antigen responses were under 10% across all batches of Epoxysilane and print runs. In addition, where SDs are larger than expected, microarray images may be readily reviewed for quality control purposes and pin misprints quickly identified. In order to determine the influence of stirring on sensitivity and speed of the microarray assay, we printed 10 common ToRCH antigens (H. pylori, T. gondii, Rubella, Rubeola, C. trachomatis, Herpes 1 and 2, CMV, C. jejuni, and EBV) in Epoxysilane-activated slide-wells. Anti-IgG-Cy3 direct binding to printed Ig
Monitoring enzyme-catalyzed reactions in micromachined nanoliter wells using a conventional microscope-based microarray reader
NASA Astrophysics Data System (ADS)
van den Doel, L. Richard; Moerman, R.; van Dedem, G. W. K.; Young, Ian T.; van Vliet, Lucas J.
Yeast-Saccharomyces cerevisiae - it widely used as a model system for other higher eukaryotes, including man. One of the basic fermentation processes in yeast is the glycolytic pathway, which is the conversion of glucose to ethanol and carbon dioxide. This pathway consists of 12 enzyme-catalyzed reactions. With the approach of microarray technology we want to explore the metabolic regulation of this pathway in yeast. This paper will focus on the design of a conventional microscope based microarray reader, which is used to monitor these enzymatic reactions in microarrays. These microarrays are fabricated in silicon and have sizes of 300 by 300 micrometers 2. The depth varies from 20 to 50 micrometers . Enzyme activity levels can be derived by monitoring the production or consumption rate of NAD(P)H, which is excited at 360nm and emits around 450nm. This fluorophore is involved in all 12 reactions of the pathway. The microarray reader is equipped with a back-illuminated CCD camera in order to obtain a high quantum efficiency for the lower wavelengths. The dynamic range of our microarray reader varies form 5(mu) Molar to 1mMolar NAD(P)H. With this microarray reader enzyme activity levels down to 0.01 unit per milliliter can be monitored. The acquisition time per well is 0.1s. The total scan cycle time for a 5 X 5 microarray is less than half a minute. The number of cycles for a proper estimation of the enzyme activity is inversely proportional to the enzyme activity: long measurement times are needed to determine low enzyme activity levels.
Environmental microarray analyses of Antarctic soil microbial communities.
Yergeau, Etienne; Schoondermark-Stolk, Sung A; Brodie, Eoin L; Déjean, Sébastien; DeSantis, Todd Z; Gonçalves, Olivier; Piceno, Yvette M; Andersen, Gary L; Kowalchuk, George A
Antarctic ecosystems are fascinating in their limited trophic complexity, with decomposition and nutrient cycling functions being dominated by microbial activities. Not only are Antarctic habitats exposed to extreme environmental conditions, the Antarctic Peninsula is also experiencing unequalled effects of global warming. Owing to their uniqueness and the potential impact of global warming on these pristine systems, there is considerable interest in determining the structure and function of microbial communities in the Antarctic. We therefore utilized a recently designed 16S rRNA gene microarray, the PhyloChip, which targets 8741 bacterial and archaeal taxa, to interrogate microbial communities inhabiting densely vegetated and bare fell-field soils along a latitudinal gradient ranging from 51 degrees S (Falkland Islands) to 72 degrees S (Coal Nunatak). Results indicated a clear decrease in diversity with increasing latitude, with the two southernmost sites harboring the most distinct Bacterial and Archaeal communities. The microarray approach proved more sensitive in detecting the breadth of microbial diversity than polymerase chain reaction-based bacterial 16S rRNA gene libraries of modest size ( approximately 190 clones per library). Furthermore, the relative signal intensities summed for phyla and families on the PhyloChip were significantly correlated with the relative occurrence of these taxa in clone libraries. PhyloChip data were also compared with functional gene microarray data obtained earlier, highlighting numerous significant relationships and providing evidence for a strong link between community composition and functional gene distribution in Antarctic soils. Integration of these PhyloChip data with other complementary methods provides an unprecedented understanding of the microbial diversity and community structure of terrestrial Antarctic habitats. PMID:19020556
Immobilization strategies for single-chain antibody microarrays
Seurynck-Servoss, Shannon L.; Baird, Cheryl L.; Miller, Keith D.; Pefaur, Noah B.; Gonzalez, Rachel M.; Apiyo, David O.; Engelmann, Heather E.; Srinivastava, Sudhir; Kagan, Jacob; Rodland, Karin D.; Zangar, Richard C.
Sandwich enzyme-linked immunosorbent assay (ELISA) microarrays have great potential for validating biomarkers of disease. ELISA relies on robust affinity reagents that retain activity when immobilized or when labeled for detection. Single-chain antibodies (scFv) are affinity reagents that have greater potential for high-throughput production than traditional immunoglobin G (IgG). Unfortunately, scFv are typically less stabile than IgG and not always suitable for use in sandwich ELISAs. We therefore investigated different immobilization strategies and scFv structural modifications to see if we could develop a more robust scFv reagent. Two promising strategies that emerged from these studies: 1) the precapture of epitope-tagged scFv using an anti-epitope antibody and 2) the direct printing of a thioredoxin/scFv fusion protein on glass slides. The use of either strategy improved the stability of immobilized scFv and increased the sensitivity of the scFv ELISA microarray assays, although the anti-epitope precapture method had a risk of reagent transfer. Using the direct printing method, we show that anti-PSA scFv are highly specific when tested against 21 different IgG-based assays. Finally, the scFv microarray PSA assay gave comparable results (R2 = 0.95) to a commercial 96-well ELISA when tested using serum samples. Overall, these results suggest that minor modifications of the scFv protein structure are sufficiently to produce reagents that are suitable for use in multiplex assay systems.
CMOS Imaging Sensor Technology for Aerial Mapping Cameras
NASA Astrophysics Data System (ADS)
Neumann, Klaus; Welzenbach, Martin; Timm, Martin
In June 2015 Leica Geosystems launched the first large format aerial mapping camera using CMOS sensor technology, the Leica DMC III. This paper describes the motivation to change from CCD sensor technology to CMOS for the development of this new aerial mapping camera. In 2002 the DMC first generation was developed by Z/I Imaging. It was the first large format digital frame sensor designed for mapping applications. In 2009 Z/I Imaging designed the DMC II which was the first digital aerial mapping camera using a single ultra large CCD sensor to avoid stitching of smaller CCDs. The DMC III is now the third generation of large format frame sensor developed by Z/I Imaging and Leica Geosystems for the DMC camera family. It is an evolution of the DMC II using the same system design with one large monolithic PAN sensor and four multi spectral camera heads for R,G, B and NIR. For the first time a 391 Megapixel large CMOS sensor had been used as PAN chromatic sensor, which is an industry record. Along with CMOS technology goes a range of technical benefits. The dynamic range of the CMOS sensor is approx. twice the range of a comparable CCD sensor and the signal to noise ratio is significantly better than with CCDs. Finally results from the first DMC III customer installations and test flights will be presented and compared with other CCD based aerial sensors.
CMOS Cell Sensors for Point-of-Care Diagnostics
Adiguzel, Yekbun; Kulah, Haluk
The burden of health-care related services in a global era with continuously increasing population and inefficient dissipation of the resources requires effective solutions. From this perspective, point-of-care diagnostics is a demanded field in clinics. It is also necessary both for prompt diagnosis and for providing health services evenly throughout the population, including the rural districts. The requirements can only be fulfilled by technologies whose productivity has already been proven, such as complementary metal-oxide-semiconductors (CMOS). CMOS-based products can enable clinical tests in a fast, simple, safe, and reliable manner, with improved sensitivities. Portability due to diminished sensor dimensions and compactness of the test set-ups, along with low sample and power consumption, is another vital feature. CMOS-based sensors for cell studies have the potential to become essential counterparts of point-of-care diagnostics technologies. Hence, this review attempts to inform on the sensors fabricated with CMOS technology for point-of-care diagnostic studies, with a focus on CMOS image sensors and capacitance sensors for cell studies. PMID:23112587
Viral diagnosis in Indian livestock using customized microarray chips
Yadav, Brijesh S; Pokhriyal, Mayank; Ratta, Barkha; Kumar, Ajay; Saxena, Meeta; Sharma, Bhaskar
Viral diagnosis in Indian livestock using customized microarray chips is gaining momentum in recent years. Hence, it is possible to design customized microarray chip for viruses infecting livestock in India. Customized microarray chips identified Bovine herpes virus-1 (BHV-1), Canine Adeno Virus-1 (CAV-1), and Canine Parvo Virus-2 (CPV-2) in clinical samples. Microarray identified specific probes were further confirmed using RT-PCR in all clinical and known samples. Therefore, the application of microarray chips during viral disease outbreaks in Indian livestock is possible where conventional methods are unsuitable. It should be noted that customized application requires a detailed cost efficiency calculation. PMID:26912948
Advancing translational research with next-generation protein microarrays.
Yu, Xiaobo; Petritis, Brianne; LaBaer, Joshua
Protein microarrays are a high-throughput technology used increasingly in translational research, seeking to apply basic science findings to enhance human health. In addition to assessing protein levels, posttranslational modifications, and signaling pathways in patient samples, protein microarrays have aided in the identification of potential protein biomarkers of disease and infection. In this perspective, the different types of full-length protein microarrays that are used in translational research are reviewed. Specific studies employing these microarrays are presented to highlight their potential in finding solutions to real clinical problems. Finally, the criteria that should be considered when developing next-generation protein microarrays are provided. PMID:26749402
Glycan specificity of neuraminidases determined in microarray format.
McCombs, Janet E; Diaz, Jason P; Luebke, Kevin J; Kohler, Jennifer J
Neuraminidases hydrolytically remove sialic acids from glycoconjugates. Neuraminidases are produced by both humans and their pathogens, and function in normal physiology and in pathological events. Identification of neuraminidase substrates is needed to reveal their mechanism of action, but high-throughput methods to determine glycan specificity of neuraminidases are limited. Here we use two glycan labeling reactions to monitor neuraminidase activity toward glycan substrates. While both periodate oxidation and aniline-catalyzed oxime ligation (PAL) and galactose oxidase and aniline-catalyzed oxime ligation (GAL) can be used to monitor neuraminidase activity toward glycans in microtiter plates, only GAL accurately measured neuraminidase activity toward glycans displayed on a commercial glass slide microarray. Using GAL, we confirm known linkage specificities of three pneumococcal neuraminidases and obtain new information about underlying glycan specificity. PMID:27131125
A tiling microarray for global analysis of chloroplast genome expression in cucumber and other plants
Plastids are small organelles equipped with their own genomes (plastomes). Although these organelles are involved in numerous plant metabolic pathways, current knowledge about the transcriptional activity of plastomes is limited. To solve this problem, we constructed a plastid tiling microarray (PlasTi-microarray) consisting of 1629 oligonucleotide probes. The oligonucleotides were designed based on the cucumber chloroplast genomic sequence and targeted both strands of the plastome in a non-contiguous arrangement. Up to 4 specific probes were designed for each gene/exon, and the intergenic regions were covered regularly, with 70-nt intervals. We also developed a protocol for direct chemical labeling and hybridization of as little as 2 micrograms of chloroplast RNA. We used this protocol for profiling the expression of the cucumber chloroplast plastome on the PlasTi-microarray. Owing to the high sequence similarity of plant plastomes, the newly constructed microarray can be used to study plants other than cucumber. Comparative hybridization of chloroplast transcriptomes from cucumber, Arabidopsis, tomato and spinach showed that the PlasTi-microarray is highly versatile. PMID:21952044
High-quality gene assembly directly from unpurified mixtures of microarray-synthesized oligonucleotides
Borovkov, Alex Y.; Loskutov, Andrey V.; Robida, Mark D.; Day, Kristen M.; Cano, Jose A.; Le Olson, Tien; Patel, Hetal; Brown, Kevin; Hunter, Preston D.; Sykes, Kathryn F.
To meet the growing demand for synthetic genes more robust, scalable and inexpensive gene assembly technologies must be developed. Here, we present a protocol for high-quality gene assembly directly from low-cost marginal-quality microarray-synthesized oligonucleotides. Significantly, we eliminated the time- and money-consuming oligonucleotide purification steps through the use of hybridization-based selection embedded in the assembly process. The protocol was tested on mixtures of up to 2000 oligonucleotides eluted directly from microarrays obtained from three different chip manufacturers. These mixtures containing <5% perfect oligos, and were used directly for assembly of 27 test genes of different sizes. Gene quality was assessed by sequencing, and their activity was tested in coupled in vitro transcription/translation reactions. Genes assembled from the microarray-eluted material using the new protocol matched the quality of the genes assembled from >95% pure column-synthesized oligonucleotides by the standard protocol. Both averaged only 2.7 errors/kb, and genes assembled from microarray-eluted material without clonal selection produced only 30% less protein than sequence-confirmed clones. This report represents the first demonstration of cost-efficient gene assembly from microarray-synthesized oligonucleotides. The overall cost of assembly by this method approaches 5¢ per base, making gene synthesis more affordable than traditional cloning. PMID:20693531
Microarray analysis of potential genes in the pathogenesis of recurrent oral ulcer
Han, Jingying; He, Zhiwei; Li, Kun; Hou, Lu
Recurrent oral ulcer seriously threatens patients' daily life and health. This study investigated potential genes and pathways that participate in the pathogenesis of recurrent oral ulcer by high throughput bioinformatic analysis. RT-PCR and Western blot were applied to further verify screened interleukins effect. Recurrent oral ulcer related genes were collected from websites and papers, and further found out from Human Genome 280 6.0 microarray data. Each pathway of recurrent oral ulcer related genes were got through chip hybridization. RT-PCR was applied to test four recurrent oral ulcer related genes to verify the microarray data. Data transformation, scatter plot, clustering analysis, and expression pattern analysis were used to analyze recurrent oral ulcer related gene expression changes. Recurrent oral ulcer gene microarray was successfully established. Microarray showed that 551 genes involved in recurrent oral ulcer activity and 196 genes were recurrent oral ulcer related genes. Of them, 76 genes up-regulated, 62 genes down-regulated, and 58 genes up-/down-regulated. Total expression level up-regulated 752 times (60%) and down-regulated 485 times (40%). IL-2 plays an important role in the occurrence, development and recurrence of recurrent oral ulcer on the mRNA and protein levels. Gene microarray can be used to analyze potential genes and pathways in recurrent oral ulcer. IL-2 may be involved in the pathogenesis of recurrent oral ulcer. PMID:26722428
Global Analysis of Human Nonreceptor Tyrosine Kinase Specificity Using High-Density Peptide Microarrays
Protein kinases phosphorylate substrates in the context of specific phosphorylation site sequence motifs. The knowledge of the specific sequences that are recognized by kinases is useful for mapping sites of phosphorylation in protein substrates and facilitates the generation of model substrates to monitor kinase activity. Here, we have adapted a positional scanning peptide library method to a microarray format that is suitable for the rapid determination of phosphorylation site motifs for tyrosine kinases. Peptide mixtures were immobilized on glass slides through a layer of a tyrosine-free Y33F mutant avidin to facilitate the analysis of phosphorylation by radiolabel assay. A microarray analysis provided qualitatively similar results in comparison with the solution phase peptide library "macroarray" method. However, much smaller quantities of kinases were required to phosphorylate peptides on the microarrays, which thus enabled a proteome scale analysis of kinase specificity. We illustrated this capability by microarray profiling more than 80% of the human nonreceptor tyrosine kinases (NRTKs). Microarray results were used to generate a universal NRTK substrate set of 11 consensus peptides for in vitro kinase assays. Several substrates were highly specific for their cognate kinases, which should facilitate their incorporation into kinase-selective biosensors. PMID:25164267
Enhancing Interdisciplinary Mathematics and Biology Education: A Microarray Data Analysis Course Bridging These Disciplines
Evans, Irene M.
BIO2010 put forth the goal of improving the mathematical educational background of biology students. The analysis and interpretation of microarray high-dimensional data can be very challenging and is best done by a statistician and a biologist working and teaching in a collaborative manner. We set up such a collaboration and designed a course on microarray data analysis. We started using Genome Consortium for Active Teaching (GCAT) materials and Microarray Genome and Clustering Tool software and added R statistical software along with Bioconductor packages. In response to student feedback, one microarray data set was fully analyzed in class, starting from preprocessing to gene discovery to pathway analysis using the latter software. A class project was to conduct a similar analysis where students analyzed their own data or data from a published journal paper. This exercise showed the impact that filtering, preprocessing, and different normalization methods had on gene inclusion in the final data set. We conclude that this course achieved its goals to equip students with skills to analyze data from a microarray experiment. We offer our insight about collaborative teaching as well as how other faculty might design and implement a similar interdisciplinary course. PMID:20810954
PMD: A Resource for Archiving and Analyzing Protein Microarray data
Xu, Zhaowei; Huang, Likun; Zhang, Hainan; Li, Yang; Guo, Shujuan; Wang, Nan; Wang, Shi-hua; Chen, Ziqing; Wang, Jingfang; Tao, Sheng-ce
Protein microarray is a powerful technology for both basic research and clinical study. However, because there is no database specifically tailored for protein microarray, the majority of the valuable original protein microarray data is still not publically accessible. To address this issue, we constructed Protein Microarray Database (PMD), which is specifically designed for archiving and analyzing protein microarray data. In PMD, users can easily browse and search the entire database by experimental name, protein microarray type, and sample information. Additionally, PMD integrates several data analysis tools and provides an automated data analysis pipeline for users. With just one click, users can obtain a comprehensive analysis report for their protein microarray data. The report includes preliminary data analysis, such as data normalization, candidate identification, and an in-depth bioinformatics analysis of the candidates, which include functional annotation, pathway analysis, and protein-protein interaction network analysis. PMD is now freely available at www.proteinmicroarray.cn. PMID:26813635
Plasmonically amplified fluorescence bioassay with microarray format
NASA Astrophysics Data System (ADS)
Gogalic, S.; Hageneder, S.; Ctortecka, C.; Bauch, M.; Khan, I.; Preininger, Claudia; Sauer, U.; Dostalek, J.
Plasmonic amplification of fluorescence signal in bioassays with microarray detection format is reported. A crossed relief diffraction grating was designed to couple an excitation laser beam to surface plasmons at the wavelength overlapping with the absorption and emission bands of fluorophore Dy647 that was used as a label. The surface of periodically corrugated sensor chip was coated with surface plasmon-supporting gold layer and a thin SU8 polymer film carrying epoxy groups. These groups were employed for the covalent immobilization of capture antibodies at arrays of spots. The plasmonic amplification of fluorescence signal on the developed microarray chip was tested by using interleukin 8 sandwich immunoassay. The readout was performed ex situ after drying the chip by using a commercial scanner with high numerical aperture collecting lens. Obtained results reveal the enhancement of fluorescence signal by a factor of 5 when compared to a regular glass chip.
Immobilization Techniques for Microarray: Challenges and Applications
Nimse, Satish Balasaheb; Song, Keumsoo; Sonawane, Mukesh Digambar; Sayyed, Danishmalik Rafiq; Kim, Taisun
The highly programmable positioning of molecules (biomolecules, nanoparticles, nanobeads, nanocomposites materials) on surfaces has potential applications in the fields of biosensors, biomolecular electronics, and nanodevices. However, the conventional techniques including self-assembled monolayers fail to position the molecules on the nanometer scale to produce highly organized monolayers on the surface. The present article elaborates different techniques for the immobilization of the biomolecules on the surface to produce microarrays and their diagnostic applications. The advantages and the drawbacks of various methods are compared. This article also sheds light on the applications of the different technologies for the detection and discrimination of viral/bacterial genotypes and the detection of the biomarkers. A brief survey with 115 references covering the last 10 years on the biological applications of microarrays in various fields is also provided. PMID:25429408
Use of microarray technologies in toxicology research.
Vrana, Kent E; Freeman, Willard M; Aschner, Michael
Microarray technology provides a unique tool for the determination of gene expression at the level of messenger RNA (mRNA). The simultaneous measurement of the entire human genome (thousands of genes) will facilitate the uncovering of specific gene expression patterns that are associated with disease. One important application of microarray technology, within the context of neurotoxicological studies, is its use as a screening tool for the identification of molecular mechanisms of toxicity. Such approaches enable researchers to identify those genes and their products (either single or whole pathways) that are involved in conferring resistance or sensitivity to toxic substances. This review addresses: (1) the potential uses of array data; (2) the various array platforms, highlighting both their advantages and disadvantages; (3) insights into data analysis and presentation strategies; and (4) concrete examples of DNA array studies in neurotoxicological research. PMID:12782098
A Flexible Microarray Data Simulation Model
Dembélé, Doulaye
Microarray technology allows monitoring of gene expression profiling at the genome level. This is useful in order to search for genes involved in a disease. The performances of the methods used to select interesting genes are most often judged after other analyzes (qPCR validation, search in databases...), which are also subject to error. A good evaluation of gene selection methods is possible with data whose characteristics are known, that is to say, synthetic data. We propose a model to simulate microarray data with similar characteristics to the data commonly produced by current platforms. The parameters used in this model are described to allow the user to generate data with varying characteristics. In order to show the flexibility of the proposed model, a commented example is given and illustrated. An R package is available for immediate use.
Microarrays: how many do you need?
Zien, Alexander; Fluck, Juliane; Zimmer, Ralf; Lengauer, Thomas
We estimate the number of microarrays that is required in order to gain reliable results from a common type of study: the pairwise comparison of different classes of samples. We show that current knowledge allows for the construction of models that look realistic with respect to searches for individual differentially expressed genes and derive prototypical parameters from real data sets. Such models allow investigation of the dependence of the required number of samples on the relevant parameters: the biological variability of the samples within each class, the fold changes in expression that are desired to be detected, the detection sensitivity of the microarrays, and the acceptable error rates of the results. We supply experimentalists with general conclusions as well as a freely accessible Java applet at www.scai.fhg.de/special/bio/howmanyarrays/ for fine tuning simulations to their particular settings. PMID:12935350
Glycan microarrays for decoding the glycome
Rillahan, Cory D.; Paulson, James C.
In the last decade glycan microarrays have revolutionized the analysis of the specificity of glycan binding proteins, providing information that simultaneously illuminates the biology mediated by them and decodes the information content of the glycome. Numerous methods have emerged for arraying glycans in a 'chip' format, and glycan libraries have been assembled that address the diversity of the human glycome. Such arrays have been successfully used for analysis of glycan binding proteins that mediate mammalian biology, host-pathogen interactions, immune recognition of glycans relevant to vaccine production and cancer antigens. This review covers the development of glycan microarrays and applications that have provided insights into the roles of mammalian and microbial glycan binding proteins. PMID:21469953
ESD protection design for advanced CMOS
NASA Astrophysics Data System (ADS)
Huang, Jin B.; Wang, Gewen
ESD effects in integrated circuits have become a major concern as today's technologies shrink to sub-micron/deep- sub-micron dimensions. The thinner gate oxide and shallower junction depth used in the advanced technologies make them very vulnerable to ESD damages. The advanced techniques like silicidation and STI (shallow trench insulation) used for improving other device performances make ESD design even more challenging. For non-silicided technologies, a certain DCGS (drain contact to gate edge spacing) is needed to achieve ESD hardness for nMOS output drivers and nMOS protection transistors. The typical DCGS values are 4-5um and 2-3um for 0.5um and 0.25um CMOS, respectively. The silicidation reduces the ballast resistance provided by DCGS with at least a factor of 10. As a result, scaling of the ESD performance with device width is lost and even zero ESD performance is reported for standard silicided devices. The device level ESD design is focused in this paper, which includes GGNMOS (gate grounded NMOS) and GCNMOS (gate coupled NMOS). The device level ESD testing including TLP (transmission line pulse) is given. Several ESD issues caused by advanced technologies have been pointed out. The possible solutions have been developed and summarized including silicide blocking, process optimization, back-end ballasting, and new protection scheme, dummy gate/n-well resistor ballsting, etc. Some of them require process cost increase, and others provide novel, compact, and simple design but involving royalty/IP (intellectual property) issue. Circuit level ESD design and layout design considerations are covered. The top-level ESD protection strategies are also given.
Adiabatic circuits: converter for static CMOS signals
NASA Astrophysics Data System (ADS)
Fischer, J.; Amirante, E.; Bargagli-Stoffi, A.; Schmitt-Landsiedel, D.
Ultra low power applications can take great advantages from adiabatic circuitry. In this technique a multiphase system is used which consists ideally of trapezoidal voltage signals. The input signals to be processed will often come from a function block realized in static CMOS. The static rectangular signals must be converted for the oscillating multiphase system of the adiabatic circuitry. This work shows how to convert the input signals to the proposed pulse form which is synchronized to the appropriate supply voltage. By means of adder structures designed for a 0.13µm technology in a 4-phase system there will be demonstrated, which additional circuits are necessary for the conversion. It must be taken into account whether the data arrive in parallel or serial form. Parallel data are all in one phase and therefore it is advantageous to use an adder structure with a proper input stage, e.g. a Carry Lookahead Adder (CLA). With a serial input stage it is possible to read and to process four signals during one cycle due to the adiabatic 4-phase system. Therefore input signals with a frequency four times higher than the adiabatic clock frequency can be used. This reduces the disadvantage of the slow clock period typical for adiabatic circuits. By means of an 8 bit Ripple Carry Adder (8 bit RCA) the serial reading will be introduced. If the word width is larger than 4 bits the word can be divided in 4 bit words which are processed in parallel. This is the most efficient way to minimize the number of input lines and pads. At the same time a high throughput is achieved.
Radiation tolerant back biased CMOS VLSI
NASA Technical Reports Server (NTRS)
Maki, Gary K. (Inventor); Gambles, Jody W. (Inventor); Hass, Kenneth J. (Inventor)
A CMOS circuit formed in a semiconductor substrate having improved immunity to total ionizing dose radiation, improved immunity to radiation induced latch up, and improved immunity to a single event upset. The architecture of the present invention can be utilized with the n-well, p-well, or dual-well processes. For example, a preferred embodiment of the present invention is described relative to a p-well process wherein the p-well is formed in an n-type substrate. A network of NMOS transistors is formed in the p-well, and a network of PMOS transistors is formed in the n-type substrate. A contact is electrically coupled to the p-well region and is coupled to first means for independently controlling the voltage in the p-well region. Another contact is electrically coupled to the n-type substrate and is coupled to second means for independently controlling the voltage in the n-type substrate. By controlling the p-well voltage, the effective threshold voltages of the n-channel transistors both drawn and parasitic can be dynamically tuned. Likewise, by controlling the n-type substrate, the effective threshold voltages of the p-channel transistors both drawn and parasitic can also be dynamically tuned. Preferably, by optimizing the threshold voltages of the n-channel and p-channel transistors, the total ionizing dose radiation effect will be neutralized and lower supply voltages can be utilized for the circuit which would result in the circuit requiring less power.
The Potentials and Pitfalls of Microarrays in Neglected Tropical Diseases: A Focus on Human Filarial Infections.
Kwarteng, Alexander; Ahuno, Samuel Terkper
Data obtained from expression microarrays enables deeper understanding of the molecular signatures of infectious diseases. It provides rapid and accurate information on how infections affect the clustering of gene expression profiles, pathways and networks that are transcriptionally active during various infection states compared to conventional diagnostic methods, which primarily focus on single genes or proteins. Thus, microarray technologies offer advantages in understanding host-parasite interactions associated with filarial infections. More importantly, the use of these technologies can aid diagnostics and helps translate current genomic research into effective treatment and interventions for filarial infections. Studying immune responses via microarray following infection can yield insight into genetic pathways and networks that can have a profound influence on the development of anti-parasitic vaccines. PMID:27600086
Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus
Lee, Jung-Rok; Haddon, D. James; Wand, Hannah E.; Price, Jordan V.; Diep, Vivian K.; Hall, Drew A.; Petri, Michelle; Baechler, Emily C.; Balboni, Imelda M.; Utz, Paul J.; Wang, Shan X.
High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides. We used the microarrays to analyze serum samples from SLE patients and found individuals with high chemokine scores had significantly greater reactivity to 13 autoantigens than individuals with low chemokine scores. Our findings demonstrate that multiple autoantibodies, including antibodies to U1-70K and modified histone H2B tails, are associated with IFN dysregulation in SLE. Further, they show the microarrays are capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice. PMID:27279139
Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus
NASA Astrophysics Data System (ADS)
Lee, Jung-Rok; Haddon, D. James; Wand, Hannah E.; Price, Jordan V.; Diep, Vivian K.; Hall, Drew A.; Petri, Michelle; Baechler, Emily C.; Balboni, Imelda M.; Utz, Paul J.; Wang, Shan X.
High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides. We used the microarrays to analyze serum samples from SLE patients and found individuals with high chemokine scores had significantly greater reactivity to 13 autoantigens than individuals with low chemokine scores. Our findings demonstrate that multiple autoantibodies, including antibodies to U1-70K and modified histone H2B tails, are associated with IFN dysregulation in SLE. Further, they show the microarrays are capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice.
A CMOS Humidity Sensor for Passive RFID Sensing Applications
Deng, Fangming; He, Yigang; Zhang, Chaolong; Feng, Wei
This paper presents a low-cost low-power CMOS humidity sensor for passive RFID sensing applications. The humidity sensing element is implemented in standard CMOS technology without any further post-processing, which results in low fabrication costs. The interface of this humidity sensor employs a PLL-based architecture transferring sensor signal processing from the voltage domain to the frequency domain. Therefore this architecture allows the use of a fully digital circuit, which can operate on ultra-low supply voltage and thus achieves low-power consumption. The proposed humidity sensor has been fabricated in the TSMC 0.18 μm CMOS process. The measurements show this humidity sensor exhibits excellent linearity and stability within the relative humidity range. The sensor interface circuit consumes only 1.05 μW at 0.5 V supply voltage and reduces it at least by an order of magnitude compared to previous designs. PMID:24841250
A CMOS humidity sensor for passive RFID sensing applications.
Deng, Fangming; He, Yigang; Zhang, Chaolong; Feng, Wei
This paper presents a low-cost low-power CMOS humidity sensor for passive RFID sensing applications. The humidity sensing element is implemented in standard CMOS technology without any further post-processing, which results in low fabrication costs. The interface of this humidity sensor employs a PLL-based architecture transferring sensor signal processing from the voltage domain to the frequency domain. Therefore this architecture allows the use of a fully digital circuit, which can operate on ultra-low supply voltage and thus achieves low-power consumption. The proposed humidity sensor has been fabricated in the TSMC 0.18 μm CMOS process. The measurements show this humidity sensor exhibits excellent linearity and stability within the relative humidity range. The sensor interface circuit consumes only 1.05 µW at 0.5 V supply voltage and reduces it at least by an order of magnitude compared to previous designs. PMID:24841250
Design of CMOS logic gates for TID radiation
NASA Technical Reports Server (NTRS)
Attia, John Okyere; Sasabo, Maria L.
The rise time, fall time and propagation delay of the logic gates were derived. The effects of total ionizing dose (TID) radiation on the fall and rise times of CMOS logic gates were obtained using C program calculations and PSPICE simulations. The variations of mobility and threshold voltage on MOSFET transistors when subjected to TID radiation were used to determine the dependence of switching times on TID. The results of this work indicate that by increasing the size of P-channel transistor with respect to the N-channel transistors of the CMOS gates, the propagation delay of CMOS logic gate can be made to decrease with, or be independent of an increase in TID radiation.
VHF NEMS-CMOS piezoresistive resonators for advanced sensing applications
NASA Astrophysics Data System (ADS)
Arcamone, Julien; Dupré, Cécilia; Arndt, Grégory; Colinet, Eric; Hentz, Sébastien; Ollier, Eric; Duraffourg, Laurent
This work reports on top-down nanoelectromechanical resonators, which are among the smallest resonators listed in the literature. To overcome the fact that their electromechanical transduction is intrinsically very challenging due to their very high frequency (100 MHz) and ultimate size (each resonator is a 1.2 μm long, 100 nm wide, 20 nm thick silicon beam with 100 nm long and 30 nm wide piezoresistive lateral nanowire gauges), they have been monolithically integrated with an advanced fully depleted SOI CMOS technology. By advantageously combining the unique benefits of nanomechanics and nanoelectronics, this hybrid NEMS-CMOS device paves the way for novel breakthrough applications, such as NEMS-based mass spectrometry or hybrid NEMS/CMOS logic, which cannot be fully implemented without this association.
Operation and biasing for single device equivalent to CMOS
Welch, James D.
Disclosed are semiconductor devices including at least one junction which is rectifying whether the semiconductor is caused to be N or P-type, by the presence of field induced carriers. In particular, inverting and non-inverting gate voltage channel induced semiconductor single devices with operating characteristics similar to conventional multiple device CMOS systems, which can be operated as modulators, are disclosed as are a non-latching SCR and an approach to blocking parasitic currents. Operation of the gate voltage channel induced semiconductor single devices with operating characteristics similar to multiple device CMOS systems under typical bias schemes is described, and simple demonstrative five mask fabrication procedures for the inverting and non-inverting gate voltage channel induced semiconductor single devices with operating characteristics similar to multiple device CMOS systems are also presented.
Fabrication of the planar angular rotator using the CMOS process
NASA Astrophysics Data System (ADS)
Dai, Ching-Liang; Chang, Chien-Liu; Chen, Hung-Lin; Chang, Pei-Zen
In this investigation we propose a novel planar angular rotator fabricated by the conventional complementary metal-oxide semiconductor (CMOS) process. Following the 0.6 μm single poly triple metal (SPTM) CMOS process, the device is completed by a simple maskless, post-process etching step. The rotor of the planar angular rotator rotates around its geometric center with electrostatic actuation. The proposed design adopts an intelligent mechanism including the slider-crank system to permit simultaneous motion. The CMOS planar angular rotator could be driven with driving voltages of around 40 V. The design proposed here has a shorter response time and longer life, without problems of friction and wear, compared to the more common planar angular micromotor.
IGBT scaling principle toward CMOS compatible wafer processes
NASA Astrophysics Data System (ADS)
Tanaka, Masahiro; Omura, Ichiro
A scaling principle for trench gate IGBT is proposed. CMOS technology on large diameter wafer enables to produce various digital circuits with higher performance and lower cost. The transistor cell structure becomes laterally smaller and smaller and vertically shallower and shallower. In contrast, latest IGBTs have rather deeper trench structure to obtain lower on-state voltage drop and turn-off loss. In the aspect of the process uniformity and wafer warpage, manufacturing such structure in the CMOS factory is difficult. In this paper, we show the scaling principle toward shallower structure and better performance. The principle is theoretically explained by our previously proposed "Structure Oriented" analytical model. The principle represents a possibility of technology direction and roadmap for future IGBT for improving the device performance consistent with lower cost and high volume productivity with CMOS compatible large diameter wafer technologies.
Metadata Management and Semantics in Microarray Repositories
Kocabaş, F; Can, T; Baykal, N
The number of microarray and other high-throughput experiments on primary repositories keeps increasing as do the size and complexity of the results in response to biomedical investigations. Initiatives have been started on standardization of content, object model, exchange format and ontology. However, there are backlogs and inability to exchange data between microarray repositories, which indicate that there is a great need for a standard format and data management. We have introduced a metadata framework that includes a metadata card and semantic nets that make experimental results visible, understandable and usable. These are encoded in syntax encoding schemes and represented in RDF (Resource Description Frame-word), can be integrated with other metadata cards and semantic nets, and can be exchanged, shared and queried. We demonstrated the performance and potential benefits through a case study on a selected microarray repository. We concluded that the backlogs can be reduced and that exchange of information and asking of knowledge discovery questions can become possible with the use of this metadata framework. PMID:24052712
Development and Applications of the Lectin Microarray.
Hirabayashi, Jun; Kuno, Atsushi; Tateno, Hiroaki
The lectin microarray is an emerging technology for glycomics. It has already found maximum use in diverse fields of glycobiology by providing simple procedures for differential glycan profiling in a rapid and high-throughput manner. Since its first appearance in the literature in 2005, many application methods have been developed essentially on the same platform, comprising a series of glycan-binding proteins immobilized on an appropriate substrate such as a glass slide. Because the lectin microarray strategy does not require prior liberation of glycans from the core protein in glycoprotein analysis, it should encourage researchers not familiar with glycotechnology to use glycan analysis in future work. This feasibility should provide a broader range of experimental scientists with good opportunities to investigate novel aspects of glycoscience. Applications of the technology include not only basic sciences but also the growing fields of bio-industry. This chapter describes first the essence of glycan profiling and the basic fabrication of the lectin microarray for this purpose. In the latter part the focus is on diverse applications to both structural and functional glycomics, with emphasis on the wide applicability now available with this new technology. Finally, the importance of developing advanced lectin engineering is discussed. PMID:25821171
RNAi microarray analysis in cultured mammalian cells.
Mousses, Spyro; Caplen, Natasha J; Cornelison, Robert; Weaver, Don; Basik, Mark; Hautaniemi, Sampsa; Elkahloun, Abdel G; Lotufo, Roberto A; Choudary, Ashish; Dougherty, Edward R; Suh, Ed; Kallioniemi, Olli
RNA interference (RNAi) mediated by small interfering RNAs (siRNAs) is a powerful new tool for analyzing gene knockdown phenotypes in living mammalian cells. To facilitate large-scale, high-throughput functional genomics studies using RNAi, we have developed a microarray-based technology for highly parallel analysis. Specifically, siRNAs in a transfection matrix were first arrayed on glass slides, overlaid with a monolayer of adherent cells, incubated to allow reverse transfection, and assessed for the effects of gene silencing by digital image analysis at a single cell level. Validation experiments with HeLa cells stably expressing GFP showed spatially confined, sequence-specific, time- and dose-dependent inhibition of green fluorescence for those cells growing directly on microspots containing siRNA targeting the GFP sequence. Microarray-based siRNA transfections analyzed with a custom-made quantitative image analysis system produced results that were identical to those from traditional well-based transfection, quantified by flow cytometry. Finally, to integrate experimental details, image analysis, data display, and data archiving, we developed a prototype information management system for high-throughput cell-based analyses. In summary, this RNAi microarray platform, together with ongoing efforts to develop large-scale human siRNA libraries, should facilitate genomic-scale cell-based analyses of gene function. PMID:14525932
Integrating data from heterogeneous DNA microarray platforms.
Valente, Eduardo; Rocha, Miguel
DNA microarrays are one of the most used technologies for gene expression measurement. However, there are several distinct microarray platforms, from different manufacturers, each with its own measurement protocol, resulting in data that can hardly be compared or directly integrated. Data integration from multiple sources aims to improve the assertiveness of statistical tests, reducing the data dimensionality problem. The integration of heterogeneous DNA microarray platforms comprehends a set of tasks that range from the re-annotation of the features used on gene expression, to data normalization and batch effect elimination. In this work, a complete methodology for gene expression data integration and application is proposed, which comprehends a transcript-based re-annotation process and several methods for batch effect attenuation. The integrated data will be used to select the best feature set and learning algorithm for a brain tumor classification case study. The integration will consider data from heterogeneous Agilent and Affymetrix platforms, collected from public gene expression databases, such as The Cancer Genome Atlas and Gene Expression Omnibus. PMID:26673932
An imputation approach for oligonucleotide microarrays.
Li, Ming; Wen, Yalu; Lu, Qing; Fu, Wenjiang J
Oligonucleotide microarrays are commonly adopted for detecting and qualifying the abundance of molecules in biological samples. Analysis of microarray data starts with recording and interpreting hybridization signals from CEL images. However, many CEL images may be blemished by noises from various sources, observed as "bright spots", "dark clouds", and "shadowy circles", etc. It is crucial that these image defects are correctly identified and properly processed. Existing approaches mainly focus on detecting defect areas and removing affected intensities. In this article, we propose to use a mixed effect model for imputing the affected intensities. The proposed imputation procedure is a single-array-based approach which does not require any biological replicate or between-array normalization. We further examine its performance by using Affymetrix high-density SNP arrays. The results show that this imputation procedure significantly reduces genotyping error rates. We also discuss the necessary adjustments for its potential extension to other oligonucleotide microarrays, such as gene expression profiling. The R source code for the implementation of approach is freely available upon request. PMID:23505547
[Genomic medicine. Polymorphisms and microarray applications].
Spalvieri, Mónica P; Rotenberg, Rosa G
This update shows new concepts related to the significance of DNA variations among individuals, as well as to their detection by using a new technology. The sequencing of the human genome is only the beginning of what will enable us to understand genetic diversity. The unit of DNA variability is the polymorphism of a single nucleotide (SNP). At present, studies on SNPs are restricted to basic research but the large number of papers on this subject makes feasible their entrance into clinical practice. We illustrate here the use of SNPs as molecular markers in ethnical genotyping, gene expression in some diseases and as potential targets in pharmacological response, and also introduce the technology of arrays. Microarrays experiments allow the quantification and comparison of gene expression on a large scale, at the same time, by using special chips and array designs. Conventional methods provide data from up to 20 genes, while a single microarray may provide information about thousands of them simultaneously, leading to a more rapid and accurate genotyping. Biotechnology improvements will facilitate our knowledge of each gene sequence, the frequency and exact location of SNPs and their influence on cellular behavior. Although experimental efficiency and validity of results from microarrays are still controversial, the knowledge and characterization of a patient's genetic profile will lead, undoubtedly, to advances in prevention, diagnosis, prognosis and treatment of human diseases. PMID:15637833
High-Throughput Enzyme Kinetics Using Microarrays
Guoxin Lu; Edward S. Yeung
We report a microanalytical method to study enzyme kinetics. The technique involves immobilizing horseradish peroxidase on a poly-L-lysine (PLL)- coated glass slide in a microarray format, followed by applying substrate solution onto the enzyme microarray. Enzyme molecules are immobilized on the PLL-coated glass slide through electrostatic interactions, and no further modification of the enzyme or glass slide is needed. In situ detection of the products generated on the enzyme spots is made possible by monitoring the light intensity of each spot using a scientific-grade charged-coupled device (CCD). Reactions of substrate solutions of various types and concentrations can be carried out sequentially on one enzyme microarray. To account for the loss of enzyme from washing in between runs, a standard substrate solution is used for calibration. Substantially reduced amounts of substrate solution are consumed for each reaction on each enzyme spot. The Michaelis constant K{sub m} obtained by using this method is comparable to the result for homogeneous solutions. Absorbance detection allows universal monitoring, and no chemical modification of the substrate is needed. High-throughput studies of native enzyme kinetics for multiple enzymes are therefore possible in a simple, rapid, and low-cost manner.
77 FR 26787 - Certain CMOS Image Sensors and Products Containing Same; Notice of Receipt of Complaint...
Federal Register 2010, 2011, 2012, 2013, 2014
... COMMISSION Certain CMOS Image Sensors and Products Containing Same; Notice of Receipt of Complaint... complaint entitled Certain CMOS Image Sensors and Products Containing Same, DN 2895; the Commission is... importation of certain CMOS image sensors and products containing same. The complaint names as...
Spectrometer with CMOS demodulation of fiber optic Bragg grating sensors
NASA Astrophysics Data System (ADS)
Christiansen, Martin Brokner
A CMOS imager based spectrometer is developed to interrogate a network containing a large number of Bragg grating sensors. The spectrometer uses a Prism-Grating- Prism (PGP) to spectrally separate serially multiplexed Bragg reflections on a single fiber. As a result, each Bragg grating produces a discrete spot on the CMOS imager that shifts horizontally as the Bragg grating experiences changes in strain or temperature. The reflected wavelength of the spot can be determined by finding the center of the spot produced. The use of a randomly addressable CMOS imager enables a flexible sampling rate. Some fibers can be interrogated at a high sampling rate while others can be interrogated at a low sampling rate. However, the use of a CMOS imager leads to several unique problems in terms of signal processing. These include a logarithmic pixel response, a low signal-to-noise ratio, a long pixel time constant, and software issues. The expected capabilities of the CMOS imager based spectrometer are determined with a theoretical model. The theoretical model tests three algorithms for determining the center of the spot: single row centroid, single row parabolic fit, and entire spot centroid. The theoretical results are compared to laboratory test data and field test data. The CMOS based spectrometer is capable of interrogating many optical fibers, and in the configuration tested, the fiber bundle consisted of 23 fibers. Using this system, a single fiber can be interrogated from 778 nm to 852 nm at 2100 Hz or multiple fibers can be interrogated over the same wavelength so that the total number of fiber interrogations is up to 2100 per second. The reflected Bragg wavelength can be determined within +/-3pm, corresponding to a +/-3μɛ uncertainty.
Reduction of CMOS Image Sensor Read Noise to Enable Photon Counting
Guidash, Michael; Ma, Jiaju; Vogelsang, Thomas; Endsley, Jay
Recent activity in photon counting CMOS image sensors (CIS) has been directed to reduction of read noise. Many approaches and methods have been reported. This work is focused on providing sub 1 e− read noise by design and operation of the binary and small signal readout of photon counting CIS. Compensation of transfer gate feed-through was used to provide substantially reduced CDS time and source follower (SF) bandwidth. SF read noise was reduced by a factor of 3 with this method. This method can be applied broadly to CIS devices to reduce the read noise for small signals to enable use as a photon counting sensor. PMID:27070625
Reduction of CMOS Image Sensor Read Noise to Enable Photon Counting.
Guidash, Michael; Ma, Jiaju; Vogelsang, Thomas; Endsley, Jay
Recent activity in photon counting CMOS image sensors (CIS) has been directed to reduction of read noise. Many approaches and methods have been reported. This work is focused on providing sub 1 e(-) read noise by design and operation of the binary and small signal readout of photon counting CIS. Compensation of transfer gate feed-through was used to provide substantially reduced CDS time and source follower (SF) bandwidth. SF read noise was reduced by a factor of 3 with this method. This method can be applied broadly to CIS devices to reduce the read noise for small signals to enable use as a photon counting sensor. PMID:27070625
A 65 nm CMOS LNA for Bolometer Application
NASA Astrophysics Data System (ADS)
Huang, Tom Nan; Boon, Chirn Chye; Zhu, Forest Xi; Yi, Xiang; He, Xiaofeng; Feng, Guangyin; Lim, Wei Meng; Liu, Bei
Modern bolometers generally consist of large-scale arrays of detectors. Implemented in conventional technologies, such bolometer arrays suffer from integrability and productivity issues. Recently, the development of CMOS technologies has presented an opportunity for the massive production of high-performance and highly integrated bolometers. This paper presents a 65-nm CMOS LNA designed for a millimeter-wave bolometer's pre-amplification stage. By properly applying some positive feedback, the noise figure of the proposed LNA is minimized at under 6 dB and the bandwidth is extended to 30 GHz.
Impact of technology trends on SEU in CMOS SRAMs
Dodd, P.E.; Sexton, F.W.; Hash, G.L.; Shaneyfelt, M.R.; Draper, B.L.; Farino, A.J.; Flores, R.S.
The impact of technology trends on the SEU hardness of epitaxial CMOS SRAMs is investigated using three-dimensional simulation. The authors study trends in SEU susceptibility with parameter variations across and within technology generations. Upset mechanisms for various strike locations and their dependence on gate-length scaling are explored. Such studies are useful for technology development and providing input for process and design decisions. An application of SEU simulation to the development of a 0.5-{micro}m radiation-hardened CMOS SRAM is presented.
DNA Microarray for Detection of Gastrointestinal Viruses
Martínez, Miguel A.; Soto-del Río, María de los Dolores; Gutiérrez, Rosa María; Chiu, Charles Y.; Greninger, Alexander L.; Contreras, Juan Francisco; López, Susana; Arias, Carlos F.
Gastroenteritis is a clinical illness of humans and other animals that is characterized by vomiting and diarrhea and caused by a variety of pathogens, including viruses. An increasing number of viral species have been associated with gastroenteritis or have been found in stool samples as new molecular tools have been developed. In this work, a DNA microarray capable in theory of parallel detection of more than 100 viral species was developed and tested. Initial validation was done with 10 different virus species, and an additional 5 species were validated using clinical samples. Detection limits of 1 × 103 virus particles of Human adenovirus C (HAdV), Human astrovirus (HAstV), and group A Rotavirus (RV-A) were established. Furthermore, when exogenous RNA was added, the limit for RV-A detection decreased by one log. In a small group of clinical samples from children with gastroenteritis (n = 76), the microarray detected at least one viral species in 92% of the samples. Single infection was identified in 63 samples (83%), and coinfection with more than one virus was identified in 7 samples (9%). The most abundant virus species were RV-A (58%), followed by Anellovirus (15.8%), HAstV (6.6%), HAdV (5.3%), Norwalk virus (6.6%), Human enterovirus (HEV) (9.2%), Human parechovirus (1.3%), Sapporo virus (1.3%), and Human bocavirus (1.3%). To further test the specificity and sensitivity of the microarray, the results were verified by reverse transcription-PCR (RT-PCR) detection of 5 gastrointestinal viruses. The RT-PCR assay detected a virus in 59 samples (78%). The microarray showed good performance for detection of RV-A, HAstV, and calicivirus, while the sensitivity for HAdV and HEV was low. Furthermore, some discrepancies in detection of mixed infections were observed and were addressed by reverse transcription-quantitative PCR (RT-qPCR) of the viruses involved. It was observed that differences in the amount of genetic material favored the detection of the most abundant
Pattern recognition techniques in microarray data analysis: a survey.
Valafar, Faramarz
Recent development of technologies (e.g., microarray technology) that are capable of producing massive amounts of genetic data has highlighted the need for new pattern recognition techniques that can mine and discover biologically meaningful knowledge in large data sets. Many researchers have begun an endeavor in this direction to devise such data-mining techniques. As such, there is a need for survey articles that periodically review and summarize the work that has been done in the area. This article presents one such survey. The first portion of the paper is meant to provide the basic biology (mostly for non-biologists) that is required in such a project. This part is only meant to be a starting point for those experts in the technical fields who wish to embark on this new area of bioinformatics. The second portion of the paper is a survey of various data-mining techniques that have been used in mining microarray data for biological knowledge and information (such as sequence information). This survey is not meant to be treated as complete in any form, since the area is currently one of the most active, and the body of research is very large. Furthermore, the applications of the techniques mentioned here are not meant to be taken as the most significant applications of the techniques, but simply as examples among many. PMID:12594081
A microarray for assessing transcription from pelagic marine microbial taxa
Shilova, Irina N; Robidart, Julie C; James Tripp, H; Turk-Kubo, Kendra; Wawrik, Boris; Post, Anton F; Thompson, Anne W; Ward, Bess; Hollibaugh, James T; Millard, Andy; Ostrowski, Martin; J Scanlan, David; Paerl, Ryan W; Stuart, Rhona; Zehr, Jonathan P
Metagenomic approaches have revealed unprecedented genetic diversity within microbial communities across vast expanses of the world's oceans. Linking this genetic diversity with key metabolic and cellular activities of microbial assemblages is a fundamental challenge. Here we report on a collaborative effort to design MicroTOOLs (Microbiological Targets for Ocean Observing Laboratories), a high-density oligonucleotide microarray that targets functional genes of diverse taxa in pelagic and coastal marine microbial communities. MicroTOOLs integrates nucleotide sequence information from disparate data types: genomes, PCR-amplicons, metagenomes, and metatranscriptomes. It targets 19 400 unique sequences over 145 different genes that are relevant to stress responses and microbial metabolism across the three domains of life and viruses. MicroTOOLs was used in a proof-of-concept experiment that compared the functional responses of microbial communities following Fe and P enrichments of surface water samples from the North Pacific Subtropical Gyre. We detected transcription of 68% of the gene targets across major taxonomic groups, and the pattern of transcription indicated relief from Fe limitation and transition to N limitation in some taxa. Prochlorococcus (eHLI), Synechococcus (sub-cluster 5.3) and Alphaproteobacteria SAR11 clade (HIMB59) showed the strongest responses to the Fe enrichment. In addition, members of uncharacterized lineages also responded. The MicroTOOLs microarray provides a robust tool for comprehensive characterization of major functional groups of microbes in the open ocean, and the design can be easily amended for specific environments and research questions. PMID:24477198
DNA Microarray Data Analysis: A Novel Biclustering Algorithm Approach
NASA Astrophysics Data System (ADS)
Tchagang, Alain B.; Tewfik, Ahmed H.
Biclustering algorithms refer to a distinct class of clustering algorithms that perform simultaneous row-column clustering. Biclustering problems arise in DNA microarray data analysis, collaborative filtering, market research, information retrieval, text mining, electoral trends, exchange analysis, and so forth. When dealing with DNA microarray experimental data for example, the goal of biclustering algorithms is to find submatrices, that is, subgroups of genes and subgroups of conditions, where the genes exhibit highly correlated activities for every condition. In this study, we develop novel biclustering algorithms using basic linear algebra and arithmetic tools. The proposed biclustering algorithms can be used to search for all biclusters with constant values, biclusters with constant values on rows, biclusters with constant values on columns, and biclusters with coherent values from a set of data in a timely manner and without solving any optimization problem. We also show how one of the proposed biclustering algorithms can be adapted to identify biclusters with coherent evolution. The algorithms developed in this study discover all valid biclusters of each type, while almost all previous biclustering approaches will miss some.
CMOS SPADs with up to 500 μm diameter and 55% detection efficiency at 420 nm
NASA Astrophysics Data System (ADS)
Villa, Federica; Bronzi, Danilo; Zou, Yu; Scarcella, Carmelo; Boso, Gianluca; Tisa, Simone; Tosi, Alberto; Zappa, Franco; Durini, Daniel; Weyers, Sascha; Paschen, Uwe; Brockherde, Werner
Many demanding applications require single-photon detectors with very large active area, very low noise, high detection efficiency, and precise time response. Single-photon avalanche diodes (SPADs) provide all the advantages of solid-state devices, but in many applications other single-photon detectors, like photomultiplier tubes, have been preferred so far due to their larger active area. We developed silicon SPADs with active area diameters as large as 500 μm in a fully standard CMOS process. The 500 μm SPAD exhibits 55% peak photon detection efficiency at 420 nm, 8 kcps of dark counting rate at 0°C, and high uniformity of the sensitivity in the active area. These devices can be used with on-chip integrated quenching circuitry, which reduces the afterpulsing probability, or with external circuits to achieve even better photon-timing performances, as good as 92 ps FWHM for a 100 μm diameter SPAD. Owing to the state-of-the-art performance, not only compared to CMOS SPADs but also SPADs developed in custom technologies, very high uniformity and low crosstalk probability, these CMOS SPADs can be successfully employed in detector arrays and single-chip imagers for single-photon counting and timing applications.
CMOS image sensor integrated with micro-LED and multielectrode arrays for the patterned photostimulation and multichannel recording of neuronal tissue.
Nakajima, Arata; Kimura, Hiroshi; Sawadsaringkarn, Yosmongkol; Maezawa, Yasuyo; Kobayashi, Takuma; Noda, Toshihiko; Sasagawa, Kiyotaka; Tokuda, Takashi; Ishikawa, Yasuyuki; Shiosaka, Sadao; Ohta, Jun
We developed a complementary metal oxide semiconductor (CMOS) integrated device for optogenetic applications. This device can interface via neuronal tissue with three functional modalities: imaging, optical stimulation and electrical recording. The CMOS image sensor was fabricated on 0.35 μm standard CMOS process with built-in control circuits for an on-chip blue light-emitting diode (LED) array. The effective imaging area was 2.0 × 1.8 mm². The pixel array was composed of 7.5 × 7.5 μm² 3-transistor active pixel sensors (APSs). The LED array had 10 × 8 micro-LEDs measuring 192 × 225 μm². We integrated the device with a commercial multichannel recording system to make electrical recordings. PMID:22418489
Assessing Statistical Significance in Microarray Experiments Using the Distance Between Microarrays
Hayden, Douglas; Lazar, Peter; Schoenfeld, David
We propose permutation tests based on the pairwise distances between microarrays to compare location, variability, or equivalence of gene expression between two populations. For these tests the entire microarray or some pre-specified subset of genes is the unit of analysis. The pairwise distances only have to be computed once so the procedure is not computationally intensive despite the high dimensionality of the data. An R software package, permtest, implementing the method is freely available from the Comprehensive R Archive Network at http://cran.r-project.org. PMID:19529777
Identification of significant features in DNA microarray data
Bair, Eric
DNA microarrays are a relatively new technology that can simultaneously measure the expression level of thousands of genes. They have become an important tool for a wide variety of biological experiments. One of the most common goals of DNA microarray experiments is to identify genes associated with biological processes of interest. Conventional statistical tests often produce poor results when applied to microarray data owing to small sample sizes, noisy data, and correlation among the expression levels of the genes. Thus, novel statistical methods are needed to identify significant genes in DNA microarray experiments. This article discusses the challenges inherent in DNA microarray analysis and describes a series of statistical techniques that can be used to overcome these challenges. The problem of multiple hypothesis testing and its relation to microarray studies are also considered, along with several possible solutions. PMID:24244802
High-throughput allogeneic antibody detection using protein microarrays.
Paul, Jed; Sahaf, Bita; Perloff, Spenser; Schoenrock, Kelsi; Wu, Fang; Nakasone, Hideki; Coller, John; Miklos, David
Enzyme-linked immunosorbent assays (ELISAs) have traditionally been used to detect alloantibodies in patient plasma samples post hematopoietic cell transplantation (HCT); however, protein microarrays have the potential to be multiplexed, more sensitive, and higher throughput than ELISAs. Here, we describe the development of a novel and sensitive microarray method for detection of allogeneic antibodies against minor histocompatibility antigens encoded on the Y chromosome, called HY antigens. Six microarray surfaces were tested for their ability to bind recombinant protein and peptide HY antigens. Significant allogeneic immune responses were determined in male patients with female donors by considering normal male donor responses as baseline. HY microarray results were also compared with our previous ELISA results. Our overall goal was to maximize antibody detection for both recombinant protein and peptide epitopes. For detection of HY antigens, the Epoxy (Schott) protein microarray surface was both most sensitive and reliable and has become the standard surface in our microarray platform. PMID:26902899
Low light level CMOS sensor for night vision systems
NASA Astrophysics Data System (ADS)
Gross, Elad; Ginat, Ran; Nesher, Ofer
For many years image intensifier tubes were used for night vision systems. In 2014, Elbit systems developed a digital low-light level CMOS sensor, with similar sensitivity to a Gen II image-intensifiers, down to starlight conditions. In this work we describe: the basic principle behind this sensor, physical model for low-light performance estimation and results of field testing.
Mechanically Flexible and High-Performance CMOS Logic Circuits.
Honda, Wataru; Arie, Takayuki; Akita, Seiji; Takei, Kuniharu
Low-power flexible logic circuits are key components required by the next generation of flexible electronic devices. For stable device operation, such components require a high degree of mechanical flexibility and reliability. Here, the mechanical properties of low-power flexible complementary metal-oxide-semiconductor (CMOS) logic circuits including inverter, NAND, and NOR are investigated. To fabricate CMOS circuits on flexible polyimide substrates, carbon nanotube (CNT) network films are used for p-type transistors, whereas amorphous InGaZnO films are used for the n-type transistors. The power consumption and voltage gain of CMOS inverters are <500 pW/mm at Vin = 0 V (<7.5 nW/mm at Vin = 5 V) and >45, respectively. Importantly, bending of the substrate is not found to cause significant changes in the device characteristics. This is also observed to be the case for more complex flexible NAND and NOR logic circuits for bending states with a curvature radius of 2.6 mm. The mechanical stability of these CMOS logic circuits makes them ideal candidates for use in flexible integrated devices. PMID:26459882
Research-grade CMOS image sensors for remote sensing applications
NASA Astrophysics Data System (ADS)
Saint-Pe, Olivier; Tulet, Michel; Davancens, Robert; Larnaudie, Franck; Magnan, Pierre; Martin-Gonthier, Philippe; Corbiere, Franck; Belliot, Pierre; Estribeau, Magali
Imaging detectors are key elements for optical instruments and sensors on board space missions dedicated to Earth observation (high resolution imaging, atmosphere spectroscopy...), Solar System exploration (micro cameras, guidance for autonomous vehicle...) and Universe observation (space telescope focal planes, guiding sensors...). This market has been dominated by CCD technology for long. Since the mid-90s, CMOS Image Sensors (CIS) have been competing with CCDs for consumer domains (webcams, cell phones, digital cameras...). Featuring significant advantages over CCD sensors for space applications (lower power consumption, smaller system size, better radiations behaviour...), CMOS technology is also expanding in this field, justifying specific R&D and development programs funded by national and European space agencies (mainly CNES, DGA and ESA). All along the 90s and thanks to their increasingly improving performances, CIS have started to be successfully used for more and more demanding space applications, from vision and control functions requiring low-level performances to guidance applications requiring medium-level performances. Recent technology improvements have made possible the manufacturing of research-grade CIS that are able to compete with CCDs in the high-performances arena. After an introduction outlining the growing interest of optical instruments designers for CMOS image sensors, this paper will present the existing and foreseen ways to reach high-level electro-optics performances for CIS. The developments and performances of CIS prototypes built using an imaging CMOS process will be presented in the corresponding section.
Research-grade CMOS image sensors for demanding space applications
NASA Astrophysics Data System (ADS)
Saint-Pé, Olivier; Tulet, Michel; Davancens, Robert; Larnaudie, Franck; Magnan, Pierre; Corbière, Franck; Martin-Gonthier, Philippe; Belliot, Pierre
Imaging detectors are key elements for optical instruments and sensors on board space missions dedicated to Earth observation (high resolution imaging, atmosphere spectroscopy...), Solar System exploration (micro cameras, guidance for autonomous vehicle...) and Universe observation (space telescope focal planes, guiding sensors...). This market has been dominated by CCD technology for long. Since the mid-90s, CMOS Image Sensors (CIS) have been competing with CCDs for more and more consumer domains (webcams, cell phones, digital cameras...). Featuring significant advantages over CCD sensors for space applications (lower power consumption, smaller system size, better radiations behaviour...), CMOS technology is also expanding in this field, justifying specific R&D and development programs funded by national and European space agencies (mainly CNES, DGA, and ESA). All along the 90s and thanks to their increasingly improving performances, CIS have started to be successfully used for more and more demanding applications, from vision and control functions requiring low-level performances to guidance applications requiring medium-level performances. Recent technology improvements have made possible the manufacturing of research-grade CIS that are able to compete with CCDs in the high-performances arena. After an introduction outlining the growing interest of optical instruments designers for CMOS image sensors, this talk will present the existing and foreseen ways to reach high-level electro-optics performances for CIS. The developments of CIS prototypes built using an imaging CMOS process and of devices based on improved designs will be presented.
CMOS image sensors as an efficient platform for glucose monitoring.
Devadhasan, Jasmine Pramila; Kim, Sanghyo; Choi, Cheol Soo
Complementary metal oxide semiconductor (CMOS) image sensors have been used previously in the analysis of biological samples. In the present study, a CMOS image sensor was used to monitor the concentration of oxidized mouse plasma glucose (86-322 mg dL(-1)) based on photon count variation. Measurement of the concentration of oxidized glucose was dependent on changes in color intensity; color intensity increased with increasing glucose concentration. The high color density of glucose highly prevented photons from passing through the polydimethylsiloxane (PDMS) chip, which suggests that the photon count was altered by color intensity. Photons were detected by a photodiode in the CMOS image sensor and converted to digital numbers by an analog to digital converter (ADC). Additionally, UV-spectral analysis and time-dependent photon analysis proved the efficiency of the detection system. This simple, effective, and consistent method for glucose measurement shows that CMOS image sensors are efficient devices for monitoring glucose in point-of-care applications. PMID:23900281
Effects Of Dose Rates On Radiation Damage In CMOS Parts
NASA Technical Reports Server (NTRS)
Goben, Charles A.; Coss, James R.; Price, William E.
Report describes measurements of effects of ionizing-radiation dose rate on consequent damage to complementary metal oxide/semiconductor (CMOS) electronic devices. Depending on irradiation time and degree of annealing, survivability of devices in outer space, or after explosion of nuclear weapons, enhanced. Annealing involving recovery beyond pre-irradiation conditions (rebound) detrimental. Damage more severe at lower dose rates.
Fabrication and characterization of CMOS-MEMS thermoelectric micro generators.
Kao, Pin-Hsu; Shih, Po-Jen; Dai, Ching-Liang; Liu, Mao-Chen
This work presents a thermoelectric micro generator fabricated by the commercial 0.35 μm complementary metal oxide semiconductor (CMOS) process and the post-CMOS process. The micro generator is composed of 24 thermocouples in series. Each thermocouple is constructed by p-type and n-type polysilicon strips. The output power of the generator depends on the temperature difference between the hot and cold parts in the thermocouples. In order to prevent heat-receiving in the cold part in the thermocouples, the cold part is covered with a silicon dioxide layer with low thermal conductivity to insulate the heat source. The hot part of the thermocouples is suspended and connected to an aluminum plate, to increases the heat-receiving area in the hot part. The generator requires a post-CMOS process to release the suspended structures. The post-CMOS process uses an anisotropic dry etching to remove the oxide sacrificial layer and an isotropic dry etching to etch the silicon substrate. Experimental results show that the micro generator has an output voltage of 67 μV at the temperature difference of 1 K. PMID:22205869
Upper-Bound Estimates Of SEU in CMOS
NASA Technical Reports Server (NTRS)
Edmonds, Larry D.
Theory of single-event upsets (SEU) (changes in logic state caused by energetic charged subatomic particles) in complementary metal oxide/semiconductor (CMOS) logic devices extended to provide upper-bound estimates of rates of SEU when limited experimental information available and configuration and dimensions of SEU-sensitive regions of devices unknown. Based partly on chord-length-distribution method.
An SEU-hardened CMOS data latch design
Rockett, L.R. Jr.
A Single Event Upset (SEU)-hardened Complementary Metal-Oxide Semiconductor (CMOS) data latch design is described. The hardness is achieved by virtue of the latch design, thus no fabrication process or design groundrule development is required. Hardness is gained with comparatively little adverse impact on performance. Cyclotron tests provided hardness verification.
CMOS VLSI Layout and Verification of a SIMD Computer
NASA Technical Reports Server (NTRS)
Zheng, Jianqing
A CMOS VLSI layout and verification of a 3 x 3 processor parallel computer has been completed. The layout was done using the MAGIC tool and the verification using HSPICE. Suggestions for expanding the computer into a million processor network are presented. Many problems that might be encountered when implementing a massively parallel computer are discussed.
Attributes and drawbacks of submicron CMOS for IR FPA readouts
NASA Astrophysics Data System (ADS)
Kozlowski, L. J.
The availability of submicron CMOS has enabled the development of shingle-chip IR cameras having performance capabilities and on-chip functions which were previously impossible. Sensor designers are, however, encoutering and overcoming several challanges including steadily decreasing operating voltage.
Relationship between IBICC imaging and SEU in CMOS ICs
Sexton, F.W.; Horn, K.M.; Doyle, B.L.; Laird, J.S.; Cholewa, M.; Saint, A.; Legge, G.J.F.
Ion-beam-induced charge-collection (IBICC) images of the TA670 16K-bit CMOS SRAM are analyzed and compared to previous SEU images. Enhanced charge collection was observed in the n-source/drains regions consistent with bipolar amplification or shunting.
Relationship between IBICC imaging and SEU in CMOS ICs
Sexton, F.W.; Horn, K.M.; Doyle, B.L. ); Laird, J.S.; Cholewa, M.; Saint, A.; Legge, G.J.F. )
Ion-beam-induced charge-collection (IBICC) images of the TA670 16K-bit CMOS SRAM are analyzed and compared to previous SEU images. Enhanced charge collection was observed in the n-source/drains regions consistent with bipolar amplification or shunting.
Overcoming scaling concerns in a radiation-hardening CMOS technology
Maimon, J.; Haddad, N.
Scaling efforts to develop an advanced radiation-hardened CMOS process to support a 4M SRAM are described. Issues encountered during scaling of transistor, isolation, and resistor elements are discussed, as well as the solutions used to overcome these issues. Transistor data, total dose radiation results, and the performance of novel resistors for prevention of single event upsets (SEU) are presented.
Reliability design of CMOS image sensor for space applications
NASA Astrophysics Data System (ADS)
Xie, Ning; Chen, Shijun; Chen, Yongping
In space applications, sensors work in very harsh space environment. Thus the reliability design must be carefully considered. This paper addresses the techniques which effectively increase the reliability of CMOS image sensors. A radiation tolerant pixel design which is implemented in a sun tracker sensor is presented. Measurement results of total dose radiation, SEL, SEU, etc prove the radiation immunity of the sensor.
Fabrication and Characterization of CMOS-MEMS Thermoelectric Micro Generators
Kao, Pin-Hsu; Shih, Po-Jen; Dai, Ching-Liang; Liu, Mao-Chen
This work presents a thermoelectric micro generator fabricated by the commercial 0.35 μm complementary metal oxide semiconductor (CMOS) process and the post-CMOS process. The micro generator is composed of 24 thermocouples in series. Each thermocouple is constructed by p-type and n-type polysilicon strips. The output power of the generator depends on the temperature difference between the hot and cold parts in the thermocouples. In order to prevent heat-receiving in the cold part in the thermocouples, the cold part is covered with a silicon dioxide layer with low thermal conductivity to insulate the heat source. The hot part of the thermocouples is suspended and connected to an aluminum plate, to increases the heat-receiving area in the hot part. The generator requires a post-CMOS process to release the suspended structures. The post-CMOS process uses an anisotropic dry etching to remove the oxide sacrificial layer and an isotropic dry etching to etch the silicon substrate. Experimental results show that the micro generator has an output voltage of 67 μV at the temperature difference of 1 K. PMID:22205869
CMOS Ultra Low Power Radiation Tolerant (CULPRiT) Microelectronics
NASA Technical Reports Server (NTRS)
Yeh, Penshu; Maki, Gary
Space Electronics needs Radiation Tolerance or hardness to withstand the harsh space environment: high-energy particles can change the state of the electronics or puncture transistors making them disfunctional. This viewgraph document reviews the use of CMOS Ultra Low Power Radiation Tolerant circuits for NASA's electronic requirements.
Higher quantum efficiency in near-IR, narrower point spread function and higher readout speed than with conventional sensors have been receiving increased emphasis in the development of CCDs and silicon PIN-CMOS sensors for use in large optical telescopes. Some key aspects in the development of such devices are reviewed.
Mechanically Flexible and High-Performance CMOS Logic Circuits
Honda, Wataru; Arie, Takayuki; Akita, Seiji; Takei, Kuniharu
Low-power flexible logic circuits are key components required by the next generation of flexible electronic devices. For stable device operation, such components require a high degree of mechanical flexibility and reliability. Here, the mechanical properties of low-power flexible complementary metal–oxide–semiconductor (CMOS) logic circuits including inverter, NAND, and NOR are investigated. To fabricate CMOS circuits on flexible polyimide substrates, carbon nanotube (CNT) network films are used for p-type transistors, whereas amorphous InGaZnO films are used for the n-type transistors. The power consumption and voltage gain of CMOS inverters are <500 pW/mm at Vin = 0 V (<7.5 nW/mm at Vin = 5 V) and >45, respectively. Importantly, bending of the substrate is not found to cause significant changes in the device characteristics. This is also observed to be the case for more complex flexible NAND and NOR logic circuits for bending states with a curvature radius of 2.6 mm. The mechanical stability of these CMOS logic circuits makes them ideal candidates for use in flexible integrated devices. PMID:26459882
Neutron induced soft errors in CMOS memories under reduced bias
Hazucha, P.; Svensson, C.; Johansson, K.
A custom designed 16 kbit CMOS memory was irradiated by 14 MeV neutrons and 100 MeV neutrons. SEU cross sections were evaluated under different supply voltages. The cross section values are compared to those predicted by the BGR model.
Direct readout of gaseous detectors with tiled CMOS circuits
NASA Astrophysics Data System (ADS)
Visschers, J. L.; Blanco Carballo, V.; Chefdeville, M.; Colas, P.; van der Graaf, H.; Schmitz, J.; Smits, S.; Timmermans, J.
A coordinated design effort is underway, exploring the three-dimensional direct readout of gaseous detectors by an anode plate equipped with a tiled array of many CMOS pixel readout ASICs, having amplification grids integrated on their topsides and being contacted on their backside.
Hybrid CMOS SiPIN detectors as astronomical imagers
NASA Astrophysics Data System (ADS)
Simms, Lance Michael
Charge Coupled Devices (CCDs) have dominated optical and x-ray astronomy since their inception in 1969. Only recently, through improvements in design and fabrication methods, have imagers that use Complimentary Metal Oxide Semiconductor (CMOS) technology gained ground on CCDs in scientific imaging. We are now in the midst of an era where astronomers might begin to design optical telescope cameras that employ CMOS imagers. The first three chapters of this dissertation are primarily composed of introductory material. In them, we discuss the potential advantages that CMOS imagers offer over CCDs in astronomical applications. We compare the two technologies in terms of the standard metrics used to evaluate and compare scientific imagers: dark current, read noise, linearity, etc. We also discuss novel features of CMOS devices and the benefits they offer to astronomy. In particular, we focus on a specific kind of hybrid CMOS sensor that uses Silicon PIN photodiodes to detect optical light in order to overcome deficiencies of commercial CMOS sensors. The remaining four chapters focus on a specific type of hybrid CMOS Silicon PIN sensor: the Teledyne Hybrid Visible Silicon PIN Imager (HyViSI). In chapters four and five, results from testing HyViSI detectors in the laboratory and at the Kitt Peak 2.1m telescope are presented. We present our laboratory measurements of the standard detector metrics for a number of HyViSI devices, ranging from 1k×1k to 4k×4k format. We also include a description of the SIDECAR readout circuit that was used to control the detectors. We then show how they performed at the telescope in terms of photometry, astrometry, variability measurement, and telescope focusing and guiding. Lastly, in the final two chapters we present results on detector artifacts such as pixel crosstalk, electronic crosstalk, and image persistence. One form of pixel crosstalk that has not been discussed elsewhere in the literature, which we refer to as Interpixel Charge
CMOS Image Sensor and System for Imaging Hemodynamic Changes in Response to Deep Brain Stimulation.
Zhang, Xiao; Noor, Muhammad S; McCracken, Clinton B; Kiss, Zelma H T; Yadid-Pecht, Orly; Murari, Kartikeya
Deep brain stimulation (DBS) is a therapeutic intervention used for a variety of neurological and psychiatric disorders, but its mechanism of action is not well understood. It is known that DBS modulates neural activity which changes metabolic demands and thus the cerebral circulation state. However, it is unclear whether there are correlations between electrophysiological, hemodynamic and behavioral changes and whether they have any implications for clinical benefits. In order to investigate these questions, we present a miniaturized system for spectroscopic imaging of brain hemodynamics. The system consists of a 144 ×144, [Formula: see text] pixel pitch, high-sensitivity, analog-output CMOS imager fabricated in a standard 0.35 μm CMOS process, along with a miniaturized imaging system comprising illumination, focusing, analog-to-digital conversion and μSD card based data storage. This enables stand alone operation without a computer, nor electrical or fiberoptic tethers. To achieve high sensitivity, the pixel uses a capacitive transimpedance amplifier (CTIA). The nMOS transistors are in the pixel while pMOS transistors are column-parallel, resulting in a fill factor (FF) of 26%. Running at 60 fps and exposed to 470 nm light, the CMOS imager has a minimum detectable intensity of 2.3 nW/cm(2) , a maximum signal-to-noise ratio (SNR) of 49 dB at 2.45 μW/cm(2) leading to a dynamic range (DR) of 61 dB while consuming 167 μA from a 3.3 V supply. In anesthetized rats, the system was able to detect temporal, spatial and spectral hemodynamic changes in response to DBS. PMID:26357405
Prenatal chromosomal microarray for the Catholic physician
Bringman, Jay J.
Prenatal chromosomal microarray (CMA) is a test that is used to diagnose certain genetic problems in the fetus. While the test has been used in the pediatric setting for several years, it is now being introduced for use in the prenatal setting. The test offers great hope for detection of certain genetic defects in the fetus so that early intervention can be performed to improve the outcome for that individual. As with many biotechnical advances, CMA comes with certain bioethical issues that need to be addressed prior to its implementation. This paper is intended to provide guidance to all those that provide counseling regarding genetic testing options during pregnancy. PMID:24899750
Protein Microarrays--Without a Trace
Camarero, J A
Many experimental approaches in biology and biophysics, as well as applications in diagnosis and drug discovery, require proteins to be immobilized on solid supports. Protein microarrays, for example, provide a high-throughput format to study biomolecular interactions. The technique employed for protein immobilization is a key to the success of these applications. Recent biochemical developments are allowing, for the first time, the selective and traceless immobilization of proteins generated by cell-free systems without the need for purification and/or reconcentration prior to the immobilization step.
ProMAT: protein microarray analysis tool
White, Amanda M.; Daly, Don S.; Varnum, Susan M.; Anderson, Kevin K.; Bollinger, Nikki; Zangar, Richard C.
Summary: ProMAT is a software tool for statistically analyzing data from ELISA microarray experiments. The software estimates standard curves, sample protein concentrations and their uncertainties for multiple assays. ProMAT generates a set of comprehensive figures for assessing results and diagnosing process quality. The tool is available for Windows or Mac, and is distributed as open-source Java and R code. Availability: ProMAT is available at http://www.pnl.gov/statistics/ProMAT. ProMAT requires Java version 1.5.0 and R version 1.9.1 (or more recent versions) which are distributed with the tool.
A novel multi-actuation CMOS RF MEMS switch
NASA Astrophysics Data System (ADS)
Lee, Chiung-I.; Ko, Chih-Hsiang; Huang, Tsun-Che
This paper demonstrates a capacitive shunt type RF MEMS switch, which is actuated by electro-thermal actuator and electrostatic actuator at the same time, and than latching the switching status by electrostatic force only. Since thermal actuators need relative low voltage compare to electrostatic actuators, and electrostatic force needs almost no power to maintain the switching status, the benefits of the mechanism are very low actuation voltage and low power consumption. Moreover, the RF MEMS switch has considered issues for integrated circuit compatible in design phase. So the switch is fabricated by a standard 0.35um 2P4M CMOS process and uses wet etching and dry etching technologies for postprocess. This compatible ability is important because the RF characteristics are not only related to the device itself. If a packaged RF switch and a packaged IC wired together, the parasitic capacitance will cause the problem for optimization. The structure of the switch consists of a set of CPW transmission lines and a suspended membrane. The CPW lines and the membrane are in metal layers of CMOS process. Besides, the electro-thermal actuators are designed by polysilicon layer of the CMOS process. So the RF switch is only CMOS process layers needed for both electro-thermal and electrostatic actuations in switch. The thermal actuator is composed of a three-dimensional membrane and two heaters. The membrane is a stacked step structure including two metal layers in CMOS process, and heat is generated by poly silicon resistors near the anchors of membrane. Measured results show that the actuation voltage of the switch is under 7V for electro-thermal added electrostatic actuation.
Refractive index change detection based on porous silicon microarray
NASA Astrophysics Data System (ADS)
Chen, Weirong; Jia, Zhenhong; Li, Peng; Lv, Guodong; Lv, Xiaoyi
By combining photolithography with the electrochemical anodization method, a microarray device of porous silicon (PS) photonic crystal was fabricated on the crystalline silicon substrate. The optical properties of the microarray were analyzed with the transfer matrix method. The relationship between refractive index and reflectivity of each array element of the microarray at 633 nm was also studied, and the array surface reflectivity changes were observed through digital imaging. By means of the reflectivity measurement method, reflectivity changes below 10-3 can be observed based on PS microarray. The results of this study can be applied to the detection of biosensor arrays.
Gene Expression Browser: large-scale and cross-experiment microarray data integration, management, search & visualization
Background In the last decade, a large amount of microarray gene expression data has been accumulated in public repositories. Integrating and analyzing high-throughput gene expression data have become key activities for exploring gene functions, gene networks and biological pathways. Effectively utilizing these invaluable microarray data remains challenging due to a lack of powerful tools to integrate large-scale gene-expression information across diverse experiments and to search and visualize a large number of gene-expression data points. Results Gene Expression Browser is a microarray data integration, management and processing system with web-based search and visualization functions. An innovative method has been developed to define a treatment over a control for every microarray experiment to standardize and make microarray data from different experiments homogeneous. In the browser, data are pre-processed offline and the resulting data points are visualized online with a 2-layer dynamic web display. Users can view all treatments over control that affect the expression of a selected gene via Gene View, and view all genes that change in a selected treatment over control via treatment over control View. Users can also check the changes of expression profiles of a set of either the treatments over control or genes via Slide View. In addition, the relationships between genes and treatments over control are computed according to gene expression ratio and are shown as co-responsive genes and co-regulation treatments over control. Conclusion Gene Expression Browser is composed of a set of software tools, including a data extraction tool, a microarray data-management system, a data-annotation tool, a microarray data-processing pipeline, and a data search & visualization tool. The browser is deployed as a free public web service (http://www.ExpressionBrowser.com) that integrates 301 ATH1 gene microarray experiments from public data repositories (viz. the Gene
A reliable ground bounce noise reduction technique for nanoscale CMOS circuits
NASA Astrophysics Data System (ADS)
Sharma, Vijay Kumar; Pattanaik, Manisha
Power gating is the most effective method to reduce the standby leakage power by adding header/footer high-VTH sleep transistors between actual and virtual power/ground rails. When a power gating circuit transitions from sleep mode to active mode, a large instantaneous charge current flows through the sleep transistors. Ground bounce noise (GBN) is the high voltage fluctuation on real ground rail during sleep mode to active mode transitions of power gating circuits. GBN disturbs the logic states of internal nodes of circuits. A novel and reliable power gating structure is proposed in this article to reduce the problem of GBN. The proposed structure contains low-VTH transistors in place of high-VTH footer. The proposed power gating structure not only reduces the GBN but also improves other performance metrics. A large mitigation of leakage power in both modes eliminates the need of high-VTH transistors. A comprehensive and comparative evaluation of proposed technique is presented in this article for a chain of 5-CMOS inverters. The simulation results are compared to other well-known GBN reduction circuit techniques at 22 nm predictive technology model (PTM) bulk CMOS model using HSPICE tool. Robustness against process, voltage and temperature (PVT) variations is estimated through Monte-Carlo simulations.
Progress in voltage and current mode on-chip analog-to-digital converters for CMOS image sensors
NASA Astrophysics Data System (ADS)
Panicacci, Roger; Pain, Bedabrata; Zhou, Zhimin; Nakamura, Junichi; Fossum, Eric R.
Two 8 bit successive approximation analog-to-digital converter (ADC) designs and a 12 bit current mode incremental sigma delta ((Sigma) -(Delta) ) ADC have been designed, fabricated, and tested. The successive approximation test chip designs are compatible with active pixel sensor (APS) column parallel architectures with a 20.4 micrometers pitch in a 1.2 micrometers n-well CMOS process and a 40 micrometers pitch in a 2 micrometers n-well CMOS process. The successive approximation designs consume as little as 49 (mu) W at a 500 KHz conversion rate meeting the low power requirements inherent in column parallel architectures. The current mode incremental (Sigma) -(Delta) ADC test chip is designed to be multiplexed among 8 columns in a semi-column parallel current mode APS architecture. The higher accuracy ADC consumes 800 (mu) W at a 5 KHz conversion rate.
Probing small molecule microarrays with tagged proteins in cell lysates
Pop, Marius S.; Wassaf, Dina; Koehler, Angela N.
The technique of small-molecule microarray (SMM) screening is based on the ability of small molecules to bind to various soluble proteins. This type of interaction is easily detected by the presence of a fluorescence signal produced by labeled antibodies that specifically recognize a unique sequence (tag) present on the target protein. The fluorescent signal intensity values are determined based on signal-to-noise ratios (SNR). SMM screening is a high throughput, unbiased method that can rapidly identify novel direct ligands for various protein targets. This binding-based assay format is generally applicable to most proteins, but it is especially useful for protein targets that do not possess an enzymatic activity. SMMs enable screening a protein in a purified form or in the context of a cellular lysate, likely providing a more physiologically relevant screening environment. PMID:25445177
Analyzing microarray data with transitive directed acyclic graphs.
Phan, Vinhthuy; Olusegun George, E; Tran, Quynh T; Goodwin, Shirlean; Bodreddigari, Sridevi; Sutter, Thomas R
Post hoc assignment of patterns determined by all pairwise comparisons in microarray experiments with multiple treatments has been proven to be useful in assessing treatment effects. We propose the usage of transitive directed acyclic graphs (tDAG) as the representation of these patterns and show that such representation can be useful in clustering treatment effects, annotating existing clustering methods, and analyzing sample sizes. Advantages of this approach include: (1) unique and descriptive meaning of each cluster in terms of how genes respond to all pairs of treatments; (2) insensitivity of the observed patterns to the number of genes analyzed; and (3) a combinatorial perspective to address the sample size problem by observing the rate of contractible tDAG as the number of replicates increases. The advantages and overall utility of the method in elaborating drug structure activity relationships are exemplified in a controlled study with real and simulated data. PMID:19226664
Neuron-based microarray sensors for environmental sensing.
Prasad, Shalini; Zhang, Xuan; Ozkan, Cengiz S; Ozkan, Mihrimah
We present a novel sensing scheme for detecting the effects of unburned fossil fuels by integrating microarray technology and dielectrophoresis to develop single-neuron arrays. These arrays have the capability to sense and identify the two fuels, at parts per billion (ppb) concentrations, as well to determine the associated physiological changes at the single-cell level. Identification is achieved through frequency domain analysis of the measured changes to the extracellular electrical activity due to the effect of the fossil fuels. This yields unique electrical identifiers known as "signature patterns". Simultaneous optical visualization to the physiological changes is obtained by specific fluorescent staining. The correlation between the signature patterns and the cellular biological behavior establishes the veracity of this identification technique. PMID:15565684
An RF Energy Harvester System Using UHF Micropower CMOS Rectifier Based on a Diode Connected CMOS Transistor
Shokrani, Mohammad Reza; Hamidon, Mohd Nizar B.; Rokhani, Fakhrul Zaman; Shafie, Suhaidi Bin
This paper presents a new type diode connected MOS transistor to improve CMOS conventional rectifier's performance in RF energy harvester systems for wireless sensor networks in which the circuits are designed in 0.18 μm TSMC CMOS technology. The proposed diode connected MOS transistor uses a new bulk connection which leads to reduction in the threshold voltage and leakage current; therefore, it contributes to increment of the rectifier's output voltage, output current, and efficiency when it is well important in the conventional CMOS rectifiers. The design technique for the rectifiers is explained and a matching network has been proposed to increase the sensitivity of the proposed rectifier. Five-stage rectifier with a matching network is proposed based on the optimization. The simulation results shows 18.2% improvement in the efficiency of the rectifier circuit and increase in sensitivity of RF energy harvester circuit. All circuits are designed in 0.18 μm TSMC CMOS technology. PMID:24782680
An RF energy harvester system using UHF micropower CMOS rectifier based on a diode connected CMOS transistor.
Shokrani, Mohammad Reza; Khoddam, Mojtaba; Hamidon, Mohd Nizar B; Kamsani, Noor Ain; Rokhani, Fakhrul Zaman; Shafie, Suhaidi Bin
This paper presents a new type diode connected MOS transistor to improve CMOS conventional rectifier's performance in RF energy harvester systems for wireless sensor networks in which the circuits are designed in 0.18 μm TSMC CMOS technology. The proposed diode connected MOS transistor uses a new bulk connection which leads to reduction in the threshold voltage and leakage current; therefore, it contributes to increment of the rectifier's output voltage, output current, and efficiency when it is well important in the conventional CMOS rectifiers. The design technique for the rectifiers is explained and a matching network has been proposed to increase the sensitivity of the proposed rectifier. Five-stage rectifier with a matching network is proposed based on the optimization. The simulation results shows 18.2% improvement in the efficiency of the rectifier circuit and increase in sensitivity of RF energy harvester circuit. All circuits are designed in 0.18 μm TSMC CMOS technology. PMID:24782680
A low-power and small-area column-level ADC for high frame-rate CMOS pixel sensor
NASA Astrophysics Data System (ADS)
Zhang, L.; Morel, F.; Hu-Guo, C.; Hu, Y.
CMOS pixel sensors (CPS) have demonstrated performances meeting the specifications of the International Linear Collider (ILC) vertex detector (VTX). This paper presents a low-power and small-area 4-bit column-level analog-to-digital converter (ADC) for CMOS pixel sensors. The ADC employs a self-timed trigger and completes the conversion by performing a multi-bit/step approximation. As in the outer layers of the ILC vertex detector hit density is of the order of a few per thousand, in order to reduce power consumption, the ADC is designed to work in two modes: active mode and idle mode. The ADC is fabricated in a 0.35 μm CMOS process with a pixel pitch of 35 μm. It is implemented with 48 columns in a sensor prototype. Each column ADC covers an area of 35 ×545 μm2. The measured temporal noise and Fixed Pattern Noise (FPN) are 0.96 mV and 0.40 mV, respectively. The power consumption, for a 3 V supply and 6.25 MS/s sampling rate, is 486 μW during idle time, which is by far the most frequently employed one. This value rises to 714 μW in the case of the active mode. The measured differential nonlinearity (DNL) and integral nonlinearity (INL) are 0.49/-0.28 LSB and 0.29/-0.20 LSB, respectively.
Inferring genetic networks from microarray data.
May, Elebeoba Eni; Davidson, George S.; Martin, Shawn Bryan; Werner-Washburne, Margaret C.; Faulon, Jean-Loup Michel
In theory, it should be possible to infer realistic genetic networks from time series microarray data. In practice, however, network discovery has proved problematic. The three major challenges are: (1) inferring the network; (2) estimating the stability of the inferred network; and (3) making the network visually accessible to the user. Here we describe a method, tested on publicly available time series microarray data, which addresses these concerns. The inference of genetic networks from genome-wide experimental data is an important biological problem which has received much attention. Approaches to this problem have typically included application of clustering algorithms [6]; the use of Boolean networks [12, 1, 10]; the use of Bayesian networks [8, 11]; and the use of continuous models [21, 14, 19]. Overviews of the problem and general approaches to network inference can be found in [4, 3]. Our approach to network inference is similar to earlier methods in that we use both clustering and Boolean network inference. However, we have attempted to extend the process to better serve the end-user, the biologist. In particular, we have incorporated a system to assess the reliability of our network, and we have developed tools which allow interactive visualization of the proposed network.
Laser direct writing of biomolecule microarrays
NASA Astrophysics Data System (ADS)
Serra, P.; Fernández-Pradas, J. M.; Berthet, F. X.; Colina, M.; Elvira, J.; Morenza, J. L.
Protein-based biosensors are highly efficient tools for protein detection and identification. The production of these devices requires the manipulation of tiny amounts of protein solutions in conditions preserving their biological properties. In this work, laser induced forward transfer (LIFT) was used for spotting an array of a purified bacterial antigen in order to check the viability of this technique for the production of protein microarrays. A pulsed Nd:YAG laser beam (355 nm wavelength, 10 ns pulse duration) was used to transfer droplets of a solution containing the Treponema pallidum 17 kDa protein antigen on a glass slide. Optical microscopy showed that a regular array of micrometric droplets could be precisely and uniformly spotted onto a solid substrate. Subsequently, it was proved that LIFT deposition of a T. pallidum 17 kDa antigen onto nylon-coated glass slides preserves its antigenic reactivity and diagnostic properties. These results support that LIFT is suitable for the production of protein microarrays and pave the way for future diagnostics applications.
Segmentation of prostate cancer tissue microarray images
NASA Astrophysics Data System (ADS)
Cline, Harvey E.; Can, Ali; Padfield, Dirk
Prostate cancer is diagnosed by histopathology interpretation of hematoxylin and eosin (H and E)-stained tissue sections. Gland and nuclei distributions vary with the disease grade. The morphological features vary with the advance of cancer where the epithelial regions grow into the stroma. An efficient pathology slide image analysis method involved using a tissue microarray with known disease stages. Digital 24-bit RGB images were acquired for each tissue element on the slide with both 10X and 40X objectives. Initial segmentation at low magnification was accomplished using prior spectral characteristics from a training tissue set composed of four tissue clusters; namely, glands, epithelia, stroma and nuclei. The segmentation method was automated by using the training RGB values as an initial guess and iterating the averaging process 10 times to find the four cluster centers. Labels were assigned to the nearest cluster center in red-blue spectral feature space. An automatic threshold algorithm separated the glands from the tissue. A visual pseudo color representation of 60 segmented tissue microarray image was generated where white, pink, red, blue colors represent glands, epithelia, stroma and nuclei, respectively. The higher magnification images provided refined nuclei morphology. The nuclei were detected with a RGB color space principle component analysis that resulted in a grey scale image. The shape metrics such as compactness, elongation, minimum and maximum diameters were calculated based on the eigenvalues of the best-fitting ellipses to the nuclei.
Mining microarray expression data by literature profiling
Chaussabel, Damien; Sher, Alan
Background The rapidly expanding fields of genomics and proteomics have prompted the development of computational methods for managing, analyzing and visualizing expression data derived from microarray screening. Nevertheless, the lack of efficient techniques for assessing the biological implications of gene-expression data remains an important obstacle in exploiting this information. Results To address this need, we have developed a mining technique based on the analysis of literature profiles generated by extracting the frequencies of certain terms from thousands of abstracts stored in the Medline literature database. Terms are then filtered on the basis of both repetitive occurrence and co-occurrence among multiple gene entries. Finally, clustering analysis is performed on the retained frequency values, shaping a coherent picture of the functional relationship among large and heterogeneous lists of genes. Such data treatment also provides information on the nature and pertinence of the associations that were formed. Conclusions The analysis of patterns of term occurrence in abstracts constitutes a means of exploring the biological significance of large and heterogeneous lists of genes. This approach should contribute to optimizing the exploitation of microarray technologies by providing investigators with an interface between complex expression data and large literature resources. PMID:12372143
Label-free detection repeatability of protein microarrays by oblique-incidence reflectivity difference method
NASA Astrophysics Data System (ADS)
Dai, Jun; Li, Lin; Wang, JingYi; He, LiPing; Lu, HuiBin; Ruan, KangCheng; Jin, KuiJuan; Yang, GuoZhen
We examine the repeatabilities of oblique-incidence reflectivity difference (OIRD) method for label-free detecting biological molecular interaction using protein microarrays. The experimental results show that the repeatabilities are the same in a given microarray or microarray-microarray and are consistent, indicating that OIRD is a promising label-free detection technique for biological microarrays.
High-Voltage-Input Level Translator Using Standard CMOS
NASA Technical Reports Server (NTRS)
Yager, Jeremy A.; Mojarradi, Mohammad M.; Vo, Tuan A.; Blalock, Benjamin J.
proposed integrated circuit would translate (1) a pair of input signals having a low differential potential and a possibly high common-mode potential into (2) a pair of output signals having the same low differential potential and a low common-mode potential. As used here, "low" and "high" refer to potentials that are, respectively, below or above the nominal supply potential (3.3 V) at which standard complementary metal oxide/semiconductor (CMOS) integrated circuits are designed to operate. The input common-mode potential could lie between 0 and 10 V; the output common-mode potential would be 2 V. This translation would make it possible to process the pair of signals by use of standard 3.3-V CMOS analog and/or mixed-signal (analog and digital) circuitry on the same integrated-circuit chip. A schematic of the circuit is shown in the figure. Standard 3.3-V CMOS circuitry cannot withstand input potentials greater than about 4 V. However, there are many applications that involve low-differential-potential, high-common-mode-potential input signal pairs and in which standard 3.3-V CMOS circuitry, which is relatively inexpensive, would be the most appropriate circuitry for performing other functions on the integrated-circuit chip that handles the high-potential input signals. Thus, there is a need to combine high-voltage input circuitry with standard low-voltage CMOS circuitry on the same integrated-circuit chip. The proposed circuit would satisfy this need. In the proposed circuit, the input signals would be coupled into both a level-shifting pair and a common-mode-sensing pair of CMOS transistors. The output of the level-shifting pair would be fed as input to a differential pair of transistors. The resulting differential current output would pass through six standoff transistors to be mirrored into an output branch by four heterojunction bipolar transistors. The mirrored differential current would be converted back to potential by a pair of diode-connected transistors
Advances in lectin microarray technology: Optimized protocols for piezoelectric print conditions
Pilobello, Kanoelani T.; Agrawal, Praveen; Rouse, Richard; Mahal, Lara K.
Lectin microarray technology has been used to profile the glycosylation of a multitude of biological and clinical samples, leading to new clinical biomarkers and advances in glycobiology. Lectin microarrays, which include over 90 plant lectins, recombinant lectins, and selected antibodies, are used to profile N-linked, O-linked, and glycolipid glycans. The specificity and depth of glycan profiling depends upon the carbohydrate-binding proteins arrayed. Our current set targets mammalian carbohydrates including fucose, high mannose, branched and complex N-linked, α- and β- Galactose and GalNAc, α-2,3- and α-2,6- sialic acid, LacNAc and Lewis X epitopes. In previous protocols, we have described the use of a contact microarray printer for lectin microarray manufacture. Herein, we present an updated protocol using a non-contact, piezoelectric printer, which leads to increased lectin activity on the array. We describe optimization of print conditions and sample hybridization, and methods of analysis. PMID:23788322
A Bayesian Approach to Pathway Analysis by Integrating Gene–Gene Functional Directions and Microarray Data
Zhao, Yifang; Chen, Ming-Hui; Pei, Baikang; Rowe, David; Shin, Dong-Guk; Xie, Wangang; Yu, Fang; Kuo, Lynn
Many statistical methods have been developed to screen for differentially expressed genes associated with specific phenotypes in the microarray data. However, it remains a major challenge to synthesize the observed expression patterns with abundant biological knowledge for more complete understanding of the biological functions among genes. Various methods including clustering analysis on genes, neural network, Bayesian network and pathway analysis have been developed toward this goal. In most of these procedures, the activation and inhibition relationships among genes have hardly been utilized in the modeling steps. We propose two novel Bayesian models to integrate the microarray data with the putative pathway structures obtained from the KEGG database and the directional gene–gene interactions in the medical literature. We define the symmetric Kullback–Leibler divergence of a pathway, and use it to identify the pathway(s) most supported by the microarray data. Monte Carlo Markov Chain sampling algorithm is given for posterior computation in the hierarchical model. The proposed method is shown to select the most supported pathway in an illustrative example. Finally, we apply the methodology to a real microarray data set to understand the gene expression profile of osteoblast lineage at defined stages of differentiation. We observe that our method correctly identifies the pathways that are reported to play essential roles in modulating bone mass. PMID:23482678
High-Throughput Nano-Biofilm Microarray for Antifungal Drug Discovery
Srinivasan, Anand; Leung, Kai P.; Lopez-Ribot, Jose L.; Ramasubramanian, Anand K.
ABSTRACT Micro- and nanoscale technologies have radically transformed biological research from genomics to tissue engineering, with the relative exception of microbial cell culture, which is still largely performed in microtiter plates and petri dishes. Here, we present nanoscale culture of the opportunistic fungal pathogen Candida albicans on a microarray platform. The microarray consists of 1,200 individual cultures of 30 nl of C. albicans biofilms ("nano-biofilms") encapsulated in an inert alginate matrix. We demonstrate that these nano-biofilms are similar to conventional macroscopic biofilms in their morphological, architectural, growth, and phenotypic characteristics. We also demonstrate that the nano-biofilm microarray is a robust and efficient tool for accelerating the drug discovery process: (i) combinatorial screening against a collection of 28 antifungal compounds in the presence of immunosuppressant FK506 (tacrolimus) identified six drugs that showed synergistic antifungal activity, and (ii) screening against the NCI challenge set small-molecule library identified three heretofore-unknown hits. This cell-based microarray platform allows for miniaturization of microbial cell culture and is fully compatible with other high-throughput screening technologies. PMID:23800397
A high efficiency PWM CMOS class-D audio power amplifier
NASA Astrophysics Data System (ADS)
Zhangming, Zhu; Lianxi, Liu; Yintang, Yang; Han, Lei
Based on the difference close-loop feedback technique and the difference pre-amp, a high efficiency PWM CMOS class-D audio power amplifier is proposed. A rail-to-rail PWM comparator with window function has been embedded in the class-D audio power amplifier. Design results based on the CSMC 0.5 μm CMOS process show that the max efficiency is 90%, the PSRR is -75 dB, the power supply voltage range is 2.5-5.5 V, the THD+N in 1 kHz input frequency is less than 0.20%, the quiescent current in no load is 2.8 mA, and the shutdown current is 0.5 μA. The active area of the class-D audio power amplifier is about 1.47 × 1.52 mm2. With the good performance, the class-D audio power amplifier can be applied to several audio power systems.
Measuring the X-ray quantum efficiency of a hybrid CMOS detector with 55Fe
NASA Astrophysics Data System (ADS)
Bongiorno, S. D.; Falcone, A. D.; Prieskorn, Z.; Griffith, C.; Burrows, D. N.
Charge coupled devices (CCDs) are currently the workhorse focal plane arrays operating aboard many orbiting astrophysics X-ray telescopes, e.g. Chandra, XMM-Newton, Swift, and Suzaku. In order to meet the count rate, power, and mission duration requirements defined by next-generation X-ray telescopes, future detectors will need to be read out faster, consume less power, and be more resistant to radiation and micrometeoroid damage than current-generation devices. The hybrid CMOS detector (HCD), a type of active pixel sensor, is currently being developed to meet these requirements. With a design architecture that involves bump bonding two semiconductor substrates together at the pixel level, these devices exhibit both the high read speed and low power consumption of CMOS readout circuitry and the high quantum efficiency (QE) of a deeply depleted silicon absorber. These devices are expected to exhibit the same excellent, high-energy quantum efficiency (QE) as deep-depletion CCDs (QE > 0.9 at 6 keV), while at the same time exhibiting superior readout flexibility, power consumption, and radiation hardness than CCDs. In this work we present a QE model for a Teledyne Imaging Sensors HyViSI HCD, which predicts QE=96% at 55Fe source energies (5.89 and 6.49 keV). We then present a QE measurement of the modeled device at the same energies, which shows QE=97±5% and is in good agreement with the model.
(Invited) Comprehensive Assessment of Oxide Memristors As Post-CMOS Memory and Logic Devices
Gao, X.; Mamaluy, D.; Cyr, E. C.; Marinella, M. J.
As CMOS technology approaches the end of its scaling, oxide-based memristors have become one of the leading candidates for post-CMOS memory and logic devices. In orderTo facilitate the understanding of physical switching mechanisms and accelerate experimental development of memristors, we have developed a three-dimensional fully-coupled electrical and thermal transport model, which captures all the important processes that drive memristive switching and is applicable for simulating a wide range of memristors. Moreover, the model is applied to simulate the RESET and SET switching in a 3D filamentary TaOx memristor. Extensive simulations show that the switching dynamics of the bipolar device ismore » determined by thermally-activated field-dominant processes: with Joule heating, the raised temperature enables the movement of oxygen vacancies, and the field drift dominates the overall motion of vacancies. Simulated current-voltage hysteresis and device resistance profiles as a function of time and voltage during RESET and SET switching show good agreement with experimental measurement.« less
CMOS Amperometric ADC With High Sensitivity, Dynamic Range and Power Efficiency for Air Quality Monitoring.
Li, Haitao; Boling, C Sam; Mason, Andrew J
Airborne pollutants are a leading cause of illness and mortality globally. Electrochemical gas sensors show great promise for personal air quality monitoring to address this worldwide health crisis. However, implementing miniaturized arrays of such sensors demands high performance instrumentation circuits that simultaneously meet challenging power, area, sensitivity, noise and dynamic range goals. This paper presents a new multi-channel CMOS amperometric ADC featuring pixel-level architecture for gas sensor arrays. The circuit combines digital modulation of input currents and an incremental Σ∆ ADC to achieve wide dynamic range and high sensitivity with very high power efficiency and compact size. Fabricated in 0.5 [Formula: see text] CMOS, the circuit was measured to have 164 dB cross-scale dynamic range, 100 fA sensitivity while consuming only 241 [Formula: see text] and 0.157 [Formula: see text] active area per channel. Electrochemical experiments with liquid and gas targets demonstrate the circuit's real-time response to a wide range of analyte concentrations. PMID:27352395
Proton-counting radiography for proton therapy: a proof of principle using CMOS APS technology
Poludniowski, G; Allinson, N M; Anaxagoras, T; Esposito, M; Green, S; Manolopoulos, S; Nieto-Camero, J; Parker, D J; Price, T; Evans, P M
Despite the early recognition of the potential of proton imaging to assist proton therapy the modality is still removed from clinical practice, with various approaches in development. For proton-counting radiography applications such as Computed Tomography (CT), the Water-Equivalent-Path-Length (WEPL) that each proton has travelled through an imaged object must be inferred. Typically, scintillator-based technology has been used in various energy/range telescope designs. Here we propose a very different alternative of using radiation-hard CMOS Active Pixel Sensor (APS) technology. The ability of such a sensor to resolve the passage of individual protons in a therapy beam has not been previously shown. Here, such capability is demonstrated using a 36 MeV cyclotron beam (University of Birmingham Cyclotron, Birmingham, UK) and a 200 MeV clinical radiotherapy beam (iThemba LABS, Cape Town, SA). The feasibility of tracking individual protons through multiple CMOS layers is also demonstrated using a two-layer stack of sensors. The chief advantages of this solution are the spatial discrimination of events intrinsic to pixelated sensors, combined with the potential provision of information on both the range and residual energy of a proton. The challenges in developing a practical system are discussed. PMID:24785680
Characterization of Si Hybrid CMOS Detectors for use in the Soft X-ray Band
NASA Astrophysics Data System (ADS)
Prieskorn, Zachary; Griffith, C.; Bongiorno, S.; Falcone, A.; Burrows, D. N.
In a joint program between Penn State University and Teledyne Imaging Sensors a soft X-ray detector based on the HAWAII Hybrid Si CMOS detector (HCD) has been developed. HCDs could potentially be the optimum detectors for the next generation of X-ray missions, especially those with focused optics and/or large effective area. These innovative detectors are active pixel sensors (APS) which allow a pixel to be read through individual in-pixel electronics, without the need to transfer charge across many pixels, in contrast to a CCD. They are made by bonding a Si absorbing layer to a pixelated CMOS readout, allowing the two layers to be optimized independently. The advantages of this design compared to CCDs are high speed timing 100 μs in full imaging mode), a flexible windowed readout to reduce pile-up, dramatically improved radiation hardness and resistance to micrometeoroid damage, and reduced power requirements. We present recent measurements of energy resolution, read noise, inter-pixel crosstalk, quantum efficiency, and dark current for four of these devices.
The Importance of Normalization on Large and Heterogeneous Microarray Datasets
DNA microarray technology is a powerful functional genomics tool increasingly used for investigating global gene expression in environmental studies. Microarrays can also be used in identifying biological networks, as they give insight on the complex gene-to-gene interactions, ne...
Experimental Approaches to Microarray Analysis of Tumor Samples
ERIC Educational Resources Information Center
Furge, Laura Lowe; Winter, Michael B.; Meyers, Jacob I.; Furge, Kyle A.
Comprehensive measurement of gene expression using high-density nucleic acid arrays (i.e. microarrays) has become an important tool for investigating the molecular differences in clinical and research samples. Consequently, inclusion of discussion in biochemistry, molecular biology, or other appropriate courses of microarray technologies has…
Removal of hybridization and scanning noise from microarrays.
Gopalappa, Chaitra; Das, Tapas K; Enkemann, Steven; Eschrich, Steven
Microarray technology for measuring gene expression values has created significant opportunities for advances in disease diagnosis and individualized treatment planning. However, the random noise introduced by the sample preparation, hybridization, and scanning stages of microarray processing creates significant inaccuracies in the gene expression levels, and hence presents a major barrier in realizing the anticipated advances. Literature presents several methodologies for noise reduction, which can be broadly categorized as: 1) model based approaches for estimation and removal of hybridization noise; 2) approaches using commonly available image denoising tools; and 3) approaches involving the need for control sample(s). In this paper, we present a novel methodology for identifying and removing hybridization and scanning noise from microarray images, using a dual-tree-complex-wavelet-transform-based multiresolution analysis coupled with bivariate shrinkage thresholding. The key features of our methodology include consideration of inherent features and type of noise specific to microarray images, and the ability to work with a single microarray without needing a control. Our methodology is first benchmarked on a fabricated dataset that mimics a real microarray probe dataset. Thereafter, our methodology is tested on datasets obtained from a number of Affymetrix GeneChip human genome HG-U133 Plus 2.0 arrays, processed on HCT-116 cell line at the Microarray Core Facility of Moffitt Cancer Center and Research Institute. The results indicate an appreciable improvement in the quality of the microarray data. PMID:20051337
Applications of microarray technology in breast cancer research
Cooper, Colin S
Microarrays provide a versatile platform for utilizing information from the Human Genome Project to benefit human health. This article reviews the ways in which microarray technology may be used in breast cancer research. Its diverse applications include monitoring chromosome gains and losses, tumour classification, drug discovery and development, DNA resequencing, mutation detection and investigating the mechanism of tumour development. PMID:11305951