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Who says Bill Belichick is a boring quote?
As the Patriots coach walked off the MetLife Stadium field, he threw his arm around his son, Stephen, and added an exclamation mark to the Patriots' 37-16 victory over the Jets.
"Thirty-seven points on the best defense in the league, s--- my d---," the Patriots coach said in celebration.


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A system and method for biomolecular sensing are disclosed. The system includes a receptor for a target, a source of p-polarized light positioned to direct light toward the receptor in a manner effective to result in a condition of near perfect interference in the absence of target binding; and a detector positioned to measure any light reflected from the front and back surfaces of the coating. The receptor includes a substrate and a translucent coating on the substrate having front and back surfaces, wherein the incident angle for one of the substrate/coating interface and the medium/coating (probe) interface is greater than its Brewster angle and the incident angle for the other interface is less than its Brewster angle.
1. A sensor system for sensing at least one target in a medium, the system comprising:
a receptor for the at least one target, the receptor comprising a silicon substrate and a translucent native oxide coating on the substrate, the coating having front and back surfaces and one or more adsorbates attached to the front surface of the coating, said one or more adsorbates being capable of recognizing the at least one target;
a source of p-polarized light positioned to direct at least a portion of the p-polarized light from the source toward the coating on the receptor in a manner effective to result in a condition of near perfect interference where reflectivity is less than 10−3 in the absence of a target bound to the one or more adsorbates on the receptor, wherein the incident angle for one of the substrate/coating interface and the medium/coating interface is greater than its Brewster angle and the incident angle for the other interface is less than its Brewster angle; and
a detector positioned to measure the light reflected from the front and back surfaces of the coating, the detector identifying presence of at least one target based on a change in the measured reflected light.
2. The system according to
3. The system according to
4. The system according to
5. The system according to
6. The system according to
7. The system according to
8. The system according to
9. The system according to
10. The system according to
11. The system according to
a non-polarized light source and
a polarizer that induces p-polarization of at least a portion of light emitted by the non-polarized light source or reflected from the receptor.
12. The system according to
13. The system according to
14. The system according to
15. The system according to
16. The system according to
17. A method for sensing at least one target, the method comprising:
providing a system according to
directing p-polarized light at the receptor in a manner effective to achieve, in the absence of at least one target, a condition of near perfect interference between light reflected from the medium/probe interface and light reflected from the substrate/coating interface; and
measuring the light reflected from the interfaces of the receptor, wherein measurement of light reflected the interfaces indicates presence of the at least one target.
18. The method according to
providing an output identifying the at least one target based on the measured reflected light.
19. The method according to
20. The method according to
repeating said measuring before and after exposure of the receptor to a sample comprising the at least one target; and
comparing the measurement of reflected light from said measurements.
21. The method according to
quantifying the amount of at least one target present on the receptor.
22. The method according to
quantifying the concentration of the at least one target present in the sample.
23. The method according to
24. The method according to
25. A method of inspecting a semiconductor wafer comprising:
providing a semiconductor wafer comprising a substrate and a coating thereon;
directing p-polarized light toward the semiconductor wafer in a manner effective to result in a condition of near perfect interference where reflectivity is less than 10−3 in the absence of any debris on the surface of the semiconductor wafer, wherein the incident angle for one of the substrate/coating interface and the medium/coating interface is greater than its Brewster angle and the incident angle for the other interface is less than its Brewster angle; and
measuring the light reflected from the interfaces of the semiconductor wafer at one or more locations over the surface of the semiconductor wafer, wherein the measuring of a change in the reflected light indicates the presence of debris on the surface of the semiconductor wafer.
26. The method according to
27. The method according to
This application claims the priority benefit of U.S. Provisional Patent Application Ser. No. 60/718,248, filed Sep. 16, 2005, which is hereby incorporated by reference in its entirety.
This invention relates to a system and method for molecular sensing or detection that utilizes Brewster angle straddle interferometry, also referred herein as p-polarized reflective interferometry ("RI").
Microarraying and biological sensing are important emerging technologies with huge potential impact on clinical and research medicine. Present methodologies for microarraying and biological sensing are based on fluorescence, radioactive, colorimetry, or Surface Plasmon Resonance ("SPR") assays of molecular recognition chemistry. To date, the former approach has garnered the most attention.
Although these methodologies work, there are problems with each of them. Fluorescence and radioactivity require a special tagging chemistry and, thus, are time-consuming and cumbersome to use. Additionally, methodologies based on radiation are hard to scale to arrays, and have associated safety and environmental problems. Colorimetry requires chemical amplification when there are large changes in the thickness of the coating and, thus, is very complicated to adapt to arraying.
Reflective interferometry ("RI") has been demonstrated to be a powerful method for detection of adsorbate layers on surfaces. When combined with probes immobilized on a surface that are capable of selectively binding target biomolecules, RI can be used for sensitive detection of important pathogens and other applications. Experimental sensitivity to 2 Angstrom layers of adsorbates has been demonstrated and theoretical comparison with SPR predicts substantial improvements over the sensitivity of SPR if optimal geometries can be implemented. This is not surprising given the exquisite sensitivity of ellipsometric methods where the state-of-the-art is resolution in the picometer range.
The present invention is directed to overcoming these and other deficiencies in the art. The novel method of molecular sensing using Brewster angle straddle interferometry according to the present invention is capable of achieving suitably reproducible sensitivity at much lower cost using simpler equipment and less complex substrate design.
A first aspect of the present invention relates to a sensor system for sensing at least one target in a medium, the system including: a receptor for the at least one target, the receptor including a substrate and a translucent coating on the substrate having front and back surfaces; a source of p-polarized light positioned to direct at least a portion of the p-polarized light from the source toward the coating on the receptor in a manner effective to result in a condition of near perfect interference in the absence of a target bound to the receptor, wherein the incident angle for one of the substrate/coating interface and the medium/coating interface is greater than its Brewster angle and the incident angle for the other interface is less than its Brewster angle; and a detector positioned to measure the light reflected from the front and back surfaces of the coating, the detector identifying presence of at least one target based on the measured reflected light.
A second aspect of the present invention relates to a method for sensing at least one target, the method including the steps of: providing a system according to the first aspect of the present invention; directing p-polarized light at the receptor in a manner effective to achieve, in the absence of at least one target, a condition of near perfect interference between light reflected from the medium/coating interface and light reflected from the substrate/coating interface; and measuring the light reflected from the interfaces of the receptor, wherein measurement of light reflected the interfaces indicates presence of the at least one target.
A third aspect of the present invention relates to a method of quantifying the amount of a target present in a sample. This method includes repeating the measuring step according to the second aspect of the present invention both before and after exposing the receptor to a sample that contains the at least one target; and comparing the measurement of reflected light from said measurements. In addition, by comparing the difference in the two measurements, it is possible to quantify the amount of target present on the substrate based upon the degree of difference between the two measurements. This difference can be used to quantify the amount present in a sample based upon the volume of sample exposed to the receptor.
A fourth aspect of the present invention relates to a method inspecting a semiconductor wafer that includes the steps of performing the method according to the second aspect of the present invention on a semiconductor wafer, wherein said measuring is performed in one or more locations over a surface of the semiconductor wafer, and wherein the measuring of reflected light indicates the presence of debris, as the target, on the surface of the semiconductor wafer.
The present invention provides a system and method for detecting molecular adsorption based on Brewster angle straddle interferometry, which utilizes the reflectivity of p-polarized light from the medium/coating interface and the substrate/coating interface. In summary, it is possible to realize reflective interferometry with a p-polarized probe when the incidence angle on one of two interfaces is greater than its Brewster angle and the incidence angle on the other of the two interfaces is less than its Brewster angle, so that a phase flip of the reflected polarization allows nearly complete destructive interference when the coating is very thin. Measurement of films under air and water using standard polished silicon wafers with a native oxide has been performed. This has a number of salutary consequences that make this invention important for imaging of very thin (nanometer and subnanometer) films of adsorbates, as appropriate for biomolecular sensing for example. Some of these advantages include:
Another advantage of this reflective technique is that it works without any special tagging chemistry as is required for fluorescence or radioactivity. Further, the present invention can be easily adapted to arraying on a large scale and can be done in situ under standard aqueous biological media. The present invention also scales favorably with the size of adsorbate so that it should be extraordinarily sensitive to targets such as proteins, antibodies, and viruses that have been selectively bound using appropriate probes or adsorbates.
A biomolecular sensing system 20 in accordance with one embodiment of the present invention is illustrated in
Referring more specifically to
According to one embodiment, the polarizer 24 is positioned in the path of the light from the light source 22 and polarizes the light in a single direction, to pass substantially only p-polarized light (i.e., s-polarized light is not passed).
As an alternative to using a polarizer in addition to a non-polarized light source, a polarized light source can be utilized. A number of lasers are known to emit polarized light, such as special argon, HeNe or dye lasers.
According to another embodiment, the light incident upon the receptor can include both s- and p-polarized light, but preferably only reflected p-polarized light is detected from the reflection from the receptor. To achieve this, a polarizer can be positioned between the receptor and the detector.
According to a still further embodiment, described in greater detail below, both s- and p-polarized light can contact the receptor in a process of phase mismatch correction, which should boost sensitivity of the Brewster straddle interferometry.
Although the incident and reflected light can contain both s- and p-polarized light, from the embodiments described above it should be appreciated that the p-polarized component can be used alone as the incident light whereas the s-polarized component is never used alone.
The receptor 26 is positioned in the path of the polarized light from the polarizer 24 and includes a surface which is receptive to adsorption of one or more targets. In this particular embodiment, the receptor 26 has a substrate 30 made of silicon with a coating 32 made of silicon dioxide on one surface as shown in
Depending on the particular selection of coating/substrate, it is always possible to find an angle of incidence where near perfect interference can be achieved for a very thin coating when the refractive indices of the medium/coating/substrate are appropriate stepped (i.e., up or down), for example, with reference to
As used herein, "near perfect interference" refers to the condition where the reflectivity of the coating/substrate is close to zero, preferably less than 10−4, more preferably less than 10−5, and most preferably less than 10−6. In accordance with the present invention, and distinctly different from the use of s-polarized light described in the hereinafter-referenced U.S. patent application Ser. No. 10/282,274 to Miller et al., the angle of incidence is tolerant of relatively significant deviation, up to about +1.0 degrees from incidence angle that correlates to the reflectivity minimum, while maintaining the condition of near perfect interference.
According to one embodiment, the angle of incidence for the substrate/coating interface is less than its Brewster angle and the angle of incidence for the coating/medium interface is greater than its Brewster angle. This is desired where the ratio of the substrate/coating refractive indices is greater than 1 (more preferably between about 1.2 to about 3), and the ratio of the coating/medium refractive indices is greater than 1 (more preferably between about 1.2 and about 2). An example of this embodiment includes a silicon substrate/silicon dioxide coating, and a medium that is either air or aqueous.
According to a second embodiment, the angle of incidence for the substrate/coating interface is greater than its Brewster angle and the angle of incidence for the coating/medium interface is less than its Brewster angle. This is desired where the ratio of the substrate/coating refractive indices is less than 1 (preferably between about 0.3 and about 0.9), and the ratio of the coating/medium refractive indices is less than 1 (preferably between about 0.3 and about 0.9).
It should be appreciated by those of ordinary skill in the art that any of a variety of substrates/coating can be employed in the present invention as long as their refractive indices are suitably matched to allow for angles of incidence where one but not both are above the Brewster angle for its interface.
As described in further detail hereinafter, the presence of any material on the surface of the coating, whether undesirable debris or adsorbing target molecules, effectively changes the coating thickness to afford a change in the destructive interference pattern of reflected light.
A number of suitable coatings can be employed on the substrate. Silicon dioxide (glass) is a convenient coating because it can be grown very transparent and the binding chemistries are already worked out in many cases. Other transparent glasses and glass ceramics can also be employed. In addition, the coating can be a polymer layer or silicon nitride or an evaporated molecular layer. Coating procedures for application of such coatings onto substrates are well known in the art. It should also be appreciated that certain materials inherently contain a transparent oxidized coating thereon and, therefore, such receptor surfaces inherently include a suitable coating. As noted above, a preferred substrate is silicon (e.g., a silicon wafer) because it inherently contains a substantially uniform silicon dioxide coating that is between about 1 to 3 nm (more specifically between about 2.2 to about 2.8 nm, or about 2.5 nm).
The coating itself may be capable of adsorbing a biomolecule under certain conditions. By altering the aqueous environment in which a target molecule resides, it is possible to precipitate target molecules onto the coating surfaces. Approaches for modifying the aqueous environment include, without limitation, altering pH, altering ionic strength of salt concentrations, or introducing modifiers such as non-surface bound antibodies capable of binding to and precipitating target molecules. Other known approaches can also be employed; however, such techniques are distinguishable from the use of blocking agents (e.g., bovine serum albumin or TWEEN-20) that inhibit nonspecific binding.
Alternatively, the coating of the receptor can be functionalized to include an adsorbate that is specific for a desired target molecule. In the embodiment illustrated in
As used herein, the term adsorbate refers to a compound that is attached to the coating on the receptor via a coating-binding group and also includes one or more target-binding groups. Suitable adsorbates include, without limitation, non-polymeric small molecules, polypeptides or proteins, and oligonucleotides, although other biological and non-biological adsorbates can be utilized. The coating-binding group is typically a hydroxyl or epoxy group, particularly where an oxidized coating surface is provided on the receptor. The one or more target-binding groups can include, without limitation, an amino group, a thiol, a hydroxyl, an alkyl chain, an ester, a carboxylic acid, an aromatic, a heterocycle, or a combination thereof.
Exemplary non-polymeric small molecules include, without limitation: avidin, peptido-mimetic compounds, and vancomycin. One class of peptido-mimetic compounds is disclosed in U.S. patent application Ser. No. 09/568,403 to Miller et al., filed May 10, 2000, which is hereby incorporated herein by reference in its entirety. A preferred peptido-mimetic compound which binds to lipopolysaccharide is a tetratryptophan ter-cyclopentane ("TWTCP") as disclosed in the above-noted application to Miller et al. Another class of peptidomimetic compounds that binds to the E. coli membrane protein Intimin is disclosed in U.S. Provisional Patent Application Ser. No. 60/408,403, filed Sep. 5, 2002, which is hereby incorporated herein by reference in its entirety.
Exemplary polypeptides include, without limitation, a receptor for cell surface molecule or fragment thereof, a lipid A receptor; an antibody or fragment thereof, peptide monobodies of the type disclosed in U.S. patent application Ser. No. 09/096,749 to Koide, filed Jun. 12, 1998, and U.S. patent application Ser. No. 10/006,760 to Koide, filed Nov. 19, 2001, each of which is hereby incorporated by reference in its entirety; a lipopolysaccharide-binding polypeptide; a peptidoglycan-binding polypeptide; a carbohydrate-binding polypeptide; a phosphate-binding polypeptide; a nucleic acid-binding polypeptide; and polypeptides which bind organic warfare agents such as tabun, sarin, soman, GF, VX, mustard agents, botulinium toxin, Staphylococcus entertoxin B, and saitotoxin.
Exemplary oligonucleotide adsorbates can be DNA, RNA, or modified (e.g., propynylated) oligonucleotides of the type disclosed in Barnes et al., J. Am. Chem. Soc. 123:4107-4118 (2001), and Barnes et al., J. Am. Chem. Soc. 123:9186-9187 (2001), each of which is hereby incorporated by reference in its entirety. The oligonucleotide adsorbates can be any length which is suitable to provide specificity for the intended target. Typically, oligonucleotide adsorbates which do not contain modified nucleotides will be at least about 12 to about 100 nucleotides in length. For oligonucleotides which contain modified bases, oligonucleotides should be at least about 7 nucleotides in length, up to about 100 nucleotides in length.
Target molecules that can be bound by the adsorbate include, without limitation: proteins (including without limitation enzymes, antibodies or fragments thereof), glycoproteins, peptidoglycans, carbohydrates, lipoproteins, a lipoteichoic acid, lipid A, phosphates, nucleic acids which are possessed or expressed by certain pathogens (e.g., bacteria, viruses, multicellular fungi, yeasts, protozoans, multicellular parasites, etc.), whole cells or particles such as viral particles, or organic compounds such as naturally occurring toxins or organic warfare agents, etc. These target molecules can be detected from any source, including food samples, water samples, homogenized tissue from organisms, air, etc.
A number of strategies are available for attaching the one or more adsorbates to the coating surface of the receptor, depending upon the type of adsorbate which is ultimately to be attached thereto.
The available strategies for attaching the one or more adsorbates include, without limitation, covalently bonding an adsorbate to the coating, ionically associating the adsorbate with the coating, adsorbing the adsorbate onto the coating, or the like. Such association can also include covalently or noncovalently attaching the adsorbate to another moiety (of a coupling agent), which in turn is covalently or non-covalently attached to the coating of the receptor.
Basically, the oxidized and hydrolyzed surface of the coating is first functionalized (i.e., primed) with a coupling agent which is attached to the surface thereof. This is achieved by providing a coupling agent precursor and then covalently or non-covalently binding the coupling agent precursor to the coating surface. The primed surface is denoted 32′ in
Suitable coupling agent precursors include, without limitation, silanes functionalized with an epoxide group, a thiol, or an alkenyl; and halide containing compounds.
Silanes include a first moiety which binds to the coating surface and a second moiety which binds to the adsorbate. Preferred silanes include, without limitation, 3-glycidoxypropyltrialkoxysilanes with C1-6 alkoxy groups, trialkoxy(oxiranylalkyl)silanes with C2-12 alkyl groups and C1-6 alkoxy groups, 2-(1,2-epoxycyclohexyl)ethyltrialkoxysilane with C1-6 alkoxy groups, 3-butenyl trialkoxysilanes with C1-6 alkoxy groups, alkenyltrialkoxysilanes with C2-12 alkenyl groups and C1-6 alkoxy groups, tris[(1-methylethenyl)oxy]3-oxiranylalkyl silanes with C2-12 alkyl groups, [5-(3,3-dimethyloxiranyl)-3-methyl-2-pentenyl]trialkoxysilane with C1-6 alkoxy groups, (2,3-oxiranediyldi-2,1-ethanediyl)bis-triethoxysilane, trialkoxy[2-(3-methyloxiranyl)alkyl]silane with C1-6 alkoxy groups and C2-12 alkyl groups, trimethoxy[2-[3-(17,17,17-trifluoroheptadecyl)oxiranyl]ethyl]silane, tributoxy[3-[3-(chloromethyl)oxiranyl]-2-methylpropyl]silane, and combinations thereof. Silanes can be coupled to the receptor coating according to a silanization reaction scheme shown in
Halides can also be coupled to the receptor coating according to the reaction scheme set in
Thereafter, the one or more adsorbates are bound to the receptor coating according to the type of functionality provided by the coupling agent. Typically, adsorbates are attached to the coupling agent or displace the coupling agent for attachment to the receptor coating in aqueous conditions or aqueous/alcohol conditions.
Epoxide functional groups can be opened to allow binding of amino groups according to the reaction scheme set forth in
Alkenyl functional groups can be reacted to allow binding of alkenyl groups according to the reaction scheme set forth in
Where a halide coupling agent is employed, the halide coupling agent is typically displaced upon exposing the primed receptor coating to one or more adsorbates which contain alcohol groups as the coating-binding groups. The displacement can be carried out according to the reaction scheme set forth in
Where the one or more adsorbates contain two or more target-binding groups, it is possible that the target-binding groups may also interact and bind to the primed surface of the receptor coating. To preclude this from occurring to any significant extent, the primed receptor coating can also be exposed to a blocking agent. The blocking agent essentially minimizes the number of sites where the one or more adsorbates can attach to the surface of the receptor coating. Exposure to the blocking agent can be carried out prior to exposing the primed receptor coating to the adsorbates or simultaneous therewith, although simultaneous exposure is generally preferred. The blocking agents can be structurally similar to the adsorbates except that they lack a target-binding group or the blocking agents can simply be simple end-capping agents. By way of example, an amino acid alkyl ester (e.g., glycine methyl ester, glycine ethyl ester, 3-alanine methyl ester, etc.) blocking agent can be introduced to an epoxide-functionalized receptor coating as shown in
Referring back to
The reflection R from the structure shown in
One solution for achieving near perfect interference is described in U.S. patent application Ser. No. 10/282,274 to Miller et al., filed Oct. 28, 2002, which is hereby incorporated by reference in its entirety. The implementation described therein achieves the condition that R≈0 by engineering 2β≈π and r12≈r23. The first criterion (2β≈π) specifies a relationship between the wavelength, angle of incidence and layer 2 (coating) thickness, d. In particular, dmin/λ=1/(4n2 cos θ2) must be satisfied. Physically, this means that light reflecting from the interface between layers 2 and 3 (coating and substrate) should travel an extra distance given by half its wavelength in medium 1. The second criterion (r12≈r23) can be met for TE (s-polarization) where the Fresnel coefficients are given by rjk=(nj cos θj−nk cos θk)/(nj cos θj+njk cos θk). Physically, the second criterion makes the magnitudes of the reflections from the two interfaces equal, so that when the first criterion is satisfied, there can be near perfect destructive interference. This specifies the angle of incidence on the structure required to be θ1 min=sin−1({(n3 2−n2 4/n1 2)/(n1 2+n3 2−2n2 2)}1/2). That angle is fairly large for the choices of materials in
The above scheme is presumed viable and has produced results. However, a number of challenges have arisen, particularly from the single color version that would be most practical for compact and inexpensive field applications. The major challenges encountered included: (1) the need for perfect, i.e., uniform and accurate, oxide thickness, (2) coherence produces fringes that confuse pictures of microarrays, and (3) an inability to obtain quantitative data without wavelength scanning. These difficulties are described in greater detail below.
Oxide films: Criterion 1 above requires very stringent control of optical probe bandwidth so that the condition can be met exactly. The narrow bandwidth typically associated with a laser source is helpful. Criterion 2 above requires precise angle of incidence and therefore excellent collimation of the optical probe as is much more easily obtained with a laser. To use a single color laser source such as HeNe (632.8 nm), criterion 1 specifies what the coating thickness must be to achieve good destructive interference. The half-wavelength criterion leads to oxide layer thicknesses of roughly 142 nm for 632.8 nm probe radiation. Thermally grown oxides cannot be grown with such tight tolerances and, moreover, are not even perfectly uniform across a given wafer. Contrast between reflection with and without target degrades very rapidly as the oxide thickness deviates from its ideal value. An additional nuisance is that oxides that are too thin can give anomalous behavior where reflectivity decreases with target binding.
Coherence: While a laser source is desirable for the reasons noted above, the spatial and temporal coherence inherent in using a laser combined with the interferometric nature of the technique inevitably leads to fringes that complicate interpretations of reflectivity patterns associated with microarrays of molecular probe spots.
Quantitative analysis: Ideally, it would be possible to say how much target has bound for a given change in reflectivity. Because the wafer thickness is not precisely known and the collimation is imperfect, this is difficult to do in single color measurements. Calibration is not a straightforward option since each substrate has a slightly different oxide thickness. Hence, calibration bumps would be needed on every sample. Wavelength scanning gets around this problem but may have practical challenges and may prove uneconomical for a point-of-care diagnostics system. Tunable lasers may be employed but can be expensive and temperamental.
There is another approximate solution to Equation (1) for TM (p-polarization), and that solution is implemented in one embodiment of the present invention. It is readily seen that zero reflection is also achieved when 2β≈0 and r12≈−r23. Physically, the reason this solution is realizable is that there is a 180� phase flip in the reflected field for TM (but not TE) polarized light when the incident angle is above the Brewster angle for an interface. It turns out that it is possible to construct a system that implements a phase flip at the air (or water)/oxide interface but no phase flip at the oxide/silicon interface. For judicious choice of angle, it is therefore possible to realize r12=−r23. Thus, nearly complete destructive interference can be obtained when the waves travel nearly the same distance (2β≈0)—in other words, for a very thin oxide layer. Implementation of this condition with the ˜2.5 nm native oxide on silicon is therefore possible and, in fact, has been successfully accomplished. Detailed solutions to the relevant equations and predicted sensitivity to target binding for this configuration are described below, but an explanation of how this variation of reflective interferometry ("RI") solves each of the problems itemized above is first presented.
First, the problem of coating thickness engineering is essentially eliminated. The thickness of the oxide is very small compared to any wavelength one can reasonably use so the condition 2β≈0 is always achievable. In fact, modeling shows that there is little wavelength dependence to the reflectivity when used in the TM configuration. This is not surprising because the accumulated phase difference between the two interfacial reflections is very small regardless of wavelength. One consequence of this is that a well-collimated lamp with a broadband filter or a bright LED is an excellent source in this implementation of RI. Because of the finite oxide thickness, slightly less perfect interference is obtained than for the ideal TE polarized geometry (10−4-10−5 for TM versus 10−5-10−9 for TE), but modeling suggests this will not turn out to be a practical limitation since suitable reflectivity is still obtainable and changes in reflectivity of factors of ˜2 for 1 nm target adsorption are expected. One very welcome consequence is that any polished silicon wafer can be utilized to implement RI so that the expense, delay and imprecision associated with growing thermal oxide films can be eliminated with the preferred embodiment. Moreover, as described below, other embodiments of the invention can overcome this reduction in interference.
Second, the problem of coherence is also reduced. While the TM implementation remains an interference effect, coherence problems appear to be diminished empirically with a laser and, moreover, the lack of narrow bandwidth requirement means that even incoherent light sources can be used.
Third, the problem of being quantitative with a single color probe is also greatly simplified. The native oxide thickness is very reproducibly 2.5 nm thick and the absolute reflectivity has a straightforward relationship to the thickness of layer 2 via solution of Equation (1). Reflectivity can never decrease with target binding so there is never any ambiguity in interpreting reflectivity maps as is possible using TE with the previously identified implementation of RI. The only unknown is the angular divergence of the incident light source and this is easily measured by comparing the experimental ratio of TM to TE reflection on the bare oxide to the theoretical value since the laser bandwidth is negligible and the oxide thickness is reproducible and is known precisely.
There is even one more benefit to the p-polarized RI, which is that it turns out to be relatively insensitive to angular divergence and almost completely insensitive to source bandwidth. As described below, angular divergences of up to about a degree or more and probe bandwidths even larger than 50 nm can be utilized with substantial sensitivity. Broader probe bandwidths do not appreciably degrade the ability to measure surface topology with a few Angstroms resolution. For example, 2 nm spots can be visualized with white light (300 nm bandwidth).
Using an approximate numerical model it is possible to numerically compute an approximate angle where r12=−r23 by plotting the Fresnel equations that define these reflection coefficients. This can be done for both the case of air above the oxide and water above the oxide.
Once the optimal angle where near cancellation can occur is determined, both the value of the reflectivity minimum from Equation (1) and how it varies when layers are adsorbed on the oxide can be estimated. This is computed in
In the case of working under water, the physics is very similar and the angle for a reflectivity minimum is approximately 71� in water (see
Using approximate analytical theory, an analytic approximation to Equation (1) can be made if it is assumed that the adsorbates have the same refractive index as the oxide. It is instructive to do so and it turns out to give results very close to the full numerical solution. Hence, it is possible to quantify the amount of adsorbate by comparison with the reflectivity of the native oxide. In other words, a nearly quantitative topological map of the substrate based on its reflectivity using the simple analytical theory can be extracted. When r12≈−r23=r0, Equation (1) can be approximated as:
The most important consequence of Equation (3) is that the value of the reflectivity minimum is expected to be parabolic with layer 2 thickness. To the extent that the refractive index of the adsorbates matches that of the oxide, one can write:
A full numerical theory to verify the above approximate computations was carried out using a transfer matrix formalism. In that theory, dispersion of the refractive index and differences in refractive index between oxide and the probe and target adsorbates can be accounted. Moreover, it is straightforward to model how the reflectivity minimum degrades with finite probe source divergence and bandwidth.
The scheme outlined according to the present invention is distinct from Brewster angle microscopy. A common approach to imaging submonolayer patterns of adsorbates at an interface is Brewster angle microscopy ("BAM"). The idea in BAM is that there is no reflection at the interface between materials 1 and 2 for p-polarized light when the incidence angle is Brewster's angle (=tan−1(n2/n1)). Adding adsorbates at the interface with n≠n1 or n2 will turn on some reflectivity and enable imaging. This method is used to look at LB monolayers on the air-water interface, for example. In principle, this method could be used for biomolecular sensing at the glass-water interface where the substrate was a glass slide but there would be problems if, for example, the adsorbate index matched that of the glass.
The p-polarized RI method according to the present invention relies on interference between reflections from two separate interfaces, each of which has substantial reflection in that the probe light is not incident at the Brewster angle for either of the interfaces involved. Unlike BAM, the method outlined here would be effective even if the probe and target adsorbates have a refractive index identical to the oxide (they could not, however, have an index identical to the water in the aqueous measurement case). Brewster angle microscopy is, in principle, precisely a null method whereas the present method is not rigorously null. According to the present method, there is reflection from the Si/SiO2 wafer even in the absence of any adsorbates. However, as shown above, that reflection can be used for quantitative calibration of the apparatus since the native oxide thickness is very uniform and reproducible.
Referring to
The aqueous embodiment is illustrated in
Working in aqueous environment has many advantages, such as being able to use bodily fluids directly, eliminating the need for a rinsing step, and being able to monitor the binding kinetics in real time (i.e., through cumulative changes in reflectivity monitored continuously over a period of time, with greater reflectivity being detected as the concentration of adsorbed target molecules increases. The ability to monitor the kinetics can be useful in differentiating perfect oligonucleotide sequence matches from analytes with single base pair mismatches. Using fluorescent detection in an aqueous measurement is problematic since the entire liquid above the functionalized substrate 30 could contain fluorescent analytes. Since the present invention is only sensitive to changes at the interface, working under liquid will not pose analogous difficulties.
Sensitivity of the measurements can be improved to achieve near perfect interference comparable to that achieved using the s-polarized approach of Miller et al., described above. In other words, reflectivity of less than 10−5 or less than 10−6 can be achieved. According to one approach, the coating thickness can be adjusted from the very thin (<<λ) coating described above. According to another approach, background subtracted p-polarized RI can be utilized. Each of these approaches is described in greater detail below.
Sensitivity can be improved by adjusting coating thickness according to the formula
Sensitivity can also be improved by using background subtracted p-polarized RI. The system illustrated in
As described above, the control and receptor substrates may or may not be identical with regard to functionalization of the coating surface. According to one embodiment, the two receptors are identical but the control receptor is not exposed to the analyte. According to another embodiment, the control receptor has a non-functionalized surface, in which case it can be exposed to the analyte without consequence. According to a further embodiment, the control receptor has a modified surface that is similar to the functionalized surface of the sample receptor. In this case, the adsorbate on the control receptor is structurally similar to the adsorbate of the sample receptor (i.e., similar thickness and refractive index), but the adsorbate of the control receptor is incapable of binding to the analyte of interest, in which case it can be exposed to the analyte without consequence. It is also worth noting that polarizations other than 45 degrees might work a little better empirically if the substrates are not identical. For example, if the control substrate were oxide only while the working substrate contained a layer for probe attachment chemistry that made it effectively thicker, subtraction would be imperfect when equal amounts of s- and p-light were used. Some of that imperfect subtraction could be improved by choosing to use slightly more s-light (i.e., incident polarizer not exactly 45 degrees) in order to approximately null the additional p-light that would be reflected from the thicker coating. An angle other than 45 degrees and, in general, also different than that for the incident polarizer would be optimal for the analyzing polarizer in this case to achieve best subtraction.
Although orthogonal polarizers are described in conjunction with the embodiment shown in
The structures in
Incorporating the modeling and the different possible arrangements discussed above, the operation of the sensing system 20 will be discussed with reference to
Next, a sample with one or more targets (of the type described above) is introduced, near the receptor 26, thereby allowing the targets to attach to and/or be the coating 32 in the receptor 26. Another measurement is taken after the sample is introduced to the receptor 26. The light source again transmits p-polarized light towards the coating 32 on the substrate 30 in the receptor 26, and is reflected off of the coating 32 absorbed targets. Adsorbing the targets at the surface of the coating 32 disturbs the interference condition and leads to increased reflectivity. The detector 28 measures the reflected light which can be used to determine the amount of adsorbed species. A variety of different processing techniques can be used on the initial and exposed measurement as required by the particular application, such as monitoring the growth of a particular target or identifying the presence of a particular target. The monitoring can also be carried out continuously to monitor reaction kinetics real time.
In another possible implementation, the mere presence of molecular debris on the surface of a silicon wafer can be detected. Basically, near perfect interference is achieved only in the absence of any material on the oxide surface, and the presence of any debris can be detected relative to a clean oxide coating. This use of the present invention is highly desirable in, e.g., quality control analysis of semiconductor wafer fabrication processes.
The simple scheme for the sensor discussed above can also be used for larger scale arraying of biological materials. The only difference is that the detector 28, such as a CCD camera, images a substantial portion of the coating 32 of the receptor 26. The advantages of arraying are numerous. One can do many simultaneous experiments, look for many different analytes, or do pattern analysis where binding is not perfectly specific. Another advantage is that untreated areas can be easily used as a reference to more accurately measure the additional thickness due to analyte binding. Often, adsorption occurs non-uniformly (perhaps due to solvent evaporation during dosing causing droplets to shrink) so that the actual deposition of binder and analyte can be quite inhomogeneous. This can be detected more easily with an imaging method and one could apply numerical procedures similar to those used for fluorescent assays to properly account for the non-uniformity.
The following examples are provided to illustrate embodiments of the present invention but are by no means intended to limit its scope.
P-polarized RI has been reduced to practice both under air and under aqueous media by imaging reflection from adsorbate layers that have been independently measured with spectroscopic ellipsometry. P-polarized RI also has potential uses for sensing. The apparatus is essentially identical to that used in standard reflective interferometry except that the incident probe light is p-polarized, the incidence angle is as computed above and the substrate under test is a silicon wafer with only a ˜2.5 nm native oxide. For the data shown below, the probe source was a spatially filtered, collimated and apertured HeNe laser beam.
The intensity data from
To determine whether the result agrees with theory, the trick of moving the substrate so that the center of the probe beam where the intensity is fairly uniform resides at the interface between the bare oxide and OTS was employed. These data are shown in
Finally, it is possible to show that p-polarized RI can also be applied under water. The angle of incidence is much less steep than for s-polarized RI which is likely to be helpful in properly implementing the method. Prism coupling to achieve that angle is, however, still necessary.
Any selective binding chemistry that can be implemented on the receptor can produce an adequate sensor. In one example, the receptor is rinsed and dried before imaging the surface topology of the coating. This is important to do to reduce any non-selective binding.
In this example, the surface is functionalized by silanization with 3-aminopropyltrimethoxysilane ("APTES") followed by glutaraldehyde ("GA") This in turn binds to streptavidin. This initial surface is relatively easy and rapid to prepare. The streptavidin surface is reasonably immune to non-specific binding and strongly binds biotinylated compounds. Since many biotinylated oligomers and antibodies are commercially available, this chemistry is easily implemented to make the receptor.
Two 2-O-methyl RNA probes were assembled for detection of a 47-mer fragment of mutant Ha-ras mRNA, an important therapeutic target for antisense oligonucleotide treatments of cancer (Lima et al., Biochemistry 31:12055-12061 (1992), which is hereby incorporated by reference in its entirety). The probes, designated M3291 (strongly binding) and M3292 (very weak binding), have solution affinities as reported previously by Lima et al. (cited above). M3291 is complementary to the hairpin loop while M3291 is complementary to the stem and a small part of the hairpin loop. The latter is found to bind 107 times more slowly in solution than the former. The chip had immobilized 2O′-methyl RNA oligos and was organized as shown in
This array was mounted in an aqueous system of the type illustrated in
These results are useful not only in detection of the presence of R47 RNA, for example, but can also be used to determine what R47 sequences are surface exposed on the three-dimension structure thereof (i.e., the probe sequences are known). Hence, knowing the probe sequence, the array data can be used infer (or confirm its predicted) three-dimensional structure. Data like those in
Having thus described the basic concept of the invention, it will be rather apparent to those skilled in the art that the foregoing detailed disclosure is intended to be presented by way of example only, and is not limiting. Various alterations, improvements, and modifications will occur and are intended to those skilled in the art, though not expressly stated herein. Additionally, the recited order of processing elements or sequences, or the use of numbers, letters, or other designations therefore, is not intended to limit the claimed processes to any order except as may be specified in the claims. These alterations, improvements, and modifications are intended to be suggested hereby, and are within the spirit and scope of the invention. Accordingly, the invention is limited only by the following claims and equivalents thereto.
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Talented design generalist from a storytelling background with a long history in content, technology, communications & media with some of the biggest brands in the world. I now specialise in human-centred experience design, consulting and project work for government.
I am a design thinking practitioner and craft product designer, with previous specialisms in TV, digital film, semantic metadata, and narrative modelling. I have a passion for quality and attention to detail, and will fight to make outcomes I am involved in greater than the sum of their parts.
March '15
Mostly leading App development, design and 'portfolio vision' at the Met Office. Also time working with the cabinet office's Policy Lab providing systems visualisation in regard to childcare provision as a service. Looking again recently at rural archive and their challenges in audience
Excited to be focusing on public services, and developing my working relationship with Government Digital Services GDS, who, I think it is widely acknowledged, are proving really effective at delivering usable digital services. GDS pro-actively steer IT provision across government, and have introduced mandatory new processes, primarily agile, lean and service design orientated approaches, to new digital product and services. This 'learn how we do it, then do it for yourselves' approach is the only sustainable approach, otherwise GDS would have to massively expand. This creates a great opportunity for external design expertise to provide their services to compliment these new ways of working. In terms of the political climate, never have ways of 'doing more with less' been quite so needed.
What cooking..
- Apps Apps Apps. In particular Weather, forecast display concepts, unique features iterated from user insight, icon animation and motion backgrounds, concepts of time and location. Products Roadmaps.
- Researching the idea that perhaps public services are too complex to reform by intervention, that instead they need to be replaced by an holistic re-interpretation
- StoryMachine. Where next for StoryMachine ? Need help to see the wood for the trees, lost sight of who the customer is I think (if you need a slightly complicated semantic co-creation tool please get in touch!)
Background Summary
I started my career in the arts before moving into page layout & graphic design, then moved into film, video and multimedia. My twenties were an exciting combination of directing pop videos and making high-end corporate productions including the launch of the Playstation, an award winning Windows 95 launch campaign, and Formula One. Pioneering a concept called Condensed TV, I began a technology startup called Frameline which looked to deliver a semantic database driven interactive content platform. Working with clients such as Paramount Pictures, Freemantle Media, Oxford Scientific Film, Harvard University & the US Libraries of Congress, I created a time-based semantic annotation structure for video logging and archive, the first commercial MPEG7 product.
Please visit LinkedIn to find out more. I look forward to hearing from you.


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Archive for Wednesday, July 18, 2001
Murder charge lodged in Jefferson County
A rural McLouth man faces a first-degree murder charge in the October 1999 shooting death of another man.
Ronald Decker, 52, rural McLouth, is charged in Jefferson County District Court in connection with the death of Lloyd Green, 45. Last week, officials dug up what they believe to be Green's body, after receiving a tip that Green's body was buried on Decker's property, which is north of McLouth.
Decker also faces an aggravated robbery charge. Officials allege he stole a wallet containing $400 from Green's body.
A preliminary hearing in the case, which had been scheduled for today, has been postponed until August. A date for that hearing has not been scheduled yet.
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The Day I Sang for Michael Jackson
David Suissa | Posted 05.25.2011 | Entertainment
Read More: Michael Jackson, 2000 Sydney Olympic Games, King of Pop, Rabbi Shmuley Boteach, Parents, Neverland, Entertainment News
There I was, completely alone with the King of Pop. I decided that I wouldn't waste this moment with mindless chatter.
Marion Jones has given up the five medals she won at the Sydney Olympics, days after admitting she used performance-enhancing drugs. It wasn't immedia...


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Over 30 Years of Performance & Quality
Some of us live to be outside. In the sun, wind rain or snow, we constantly want
to experience all Mother Nature has to offer. This drive lives deep within Glacier
Glove. We spend as much time as possible to be outdoors and enjoy it more when we
are comfortable. Since 1982 we have been striving to find new ways to protect you
without sacrificing dexterity. At Glacier Glove, we seek out the best materials,
best practices and undying passion to be outside, and that is our mission that goes
into every product design.
The Glacier Glove legacy began in 1982 when we made our first fishing gloves.
Standing on the cold shores of Pyramid Lake, Nevada, the inspiration for our
first model was born. Since that day we have continued to enhance the products
by finding better fabrics and improved designs, striving to make the outdoor
experience more enjoyable. In 1998 we launched into sun protection gloves and
hats and today we are continuing to expand our line with products that will carry
the same high level of quality and performance.
Those who have used Glacier Gloves include a wide and diverse audience.
We started by reaching out to fishermen, and then hunters. In time, we found
paddlers, ice climbers, hikers, and horseback riders. Several governmental
and military sources started using Glacier Gloves, including Navy Seals, and
the U.S. Coast Guard. Professional teams on Antarctic Expeditions, climbers on
Mt. Everest and Aconcagua have used our gloves. The U.S. Treasury Department
used our product during the 2002 Winter Olympics. We are proud to have met the
needs of all these different groups.
Glacier Glove continues to set the standards in the materials, workmanship,
and quality. We strive to offer the best value to our customers.


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Key ingredient for Lehigh Valley's Top Workplaces: Appreciation
Appreciated — that, in a word, is how people who work for the Lehigh Valley's top employers feel.
Appreciated — that, in a word, is how people who work for the Lehigh Valley's top employers feel.
Victaulic Co. gets its name from the combination of two words, "victory" and "hydraulics," offering an etymological glimpse of the company's history.
Actress Bette Davis famously said that old age isn't for sissies.
There was a time in Lehigh Carbon Community College's 48-year history when some joked that the first two letters of LCCC stood for "last chance."
Olympus was founded in Japan in 1919 by Takeshi Yamashita under the original name Takachiho Seisakusho. The name changed to Olympus in 1949. Like Mount Olympus in Greek mythology, Mount Takachiho is said to be home to gods in Japanese folklore.
Justin Ruhe had worked for the city of Allentown just shy of eight years when, in summer 2013, he was diagnosed with an aggressive form of multiple sclerosis.
Webster's defines "fellowship" as "friendly association," and the colleagues who work at the Whitehall-based Fellowship Community couldn't agree more.
For nearly 35 years, Community Services for Children has given underprivileged preschoolers a Head Start and employees a leg up.
At Presbyterian Senior Living at Kirkland Village, caring for seniors is not just a job, it's a calling.
Corporate takeovers can leave employees feeling like pawns in a colossal chess game. Yet after Buckeye Partners, an international petroleum distribution service provider, bought the family-run Farm & Home Oil Co. in 2008, the new owners kept their word and kept the workers.
The list of reasons a real estate agent or broker might want to work for Berkshire Hathaway HomeServices Fox & Roach Realtors/The Trident Group goes on and on, much like the company name.
For a while, real estate agent Chris Young thought he'd never find the right home — for his ambitions. Some agencies were too small. Some left him light on income.
You know the buildings: the outdoor concert lovers' Levitt Pavilion at SteelStacks in Bethlehem, the family-friendly Crayola Experience in Easton, the BrewWorks restaurant in Allentown.
The way the Rev. Alf Halvorson sees it, church is a noun and a verb.
Chocolate may have lured teacher Jean Calpas out of retirement to stand behind a counter at Josh Early Candies, but what is keeping her there two years later, she said, are the sweet working conditions.
The idea that a company that performs hospice services could be a great place to work sounds a bit like an oxymoron. How can a business that routinely deals with death have happy workers?


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Narrow your search
Despite a couple of small flaws, the Monster iSport Victory offers a great fit, is water-resistant, and one of the better sounding in-ear sports headphones out there.
Whether you're out listening to your MP3 player or out at home with your high-end stereo, your headphone choice is critical. Here we've picked our five favorites across every style and category, but if you already know which type of headphones you want, use the links at the left to get more options.
The Samsung Galaxy Victory 4G LTE is a good Android choice, but for the same price, the LG Viper gives you greater camera power.
John Riccitiello also criticizes Microsoft for what he called "unfocused execution" of the Xbox One's launch.
Technically Incorrect: Both the White House Facebook account and President Obama's Twitter account immediately react to the Supreme Court decision on gay marriage.
Technically Incorrect: A man is bored and invents a battle in a fictional Iraqi town called "Cheese Bladder." He tweets it. The rest isn't history.
Ford introduced the its new GT supercar at this year's Detroit auto show to great fanfare, and today Ford revealed the model would participate in next year's Le Mans GTE Pro class.
Technically Incorrect: Apple co-founder Steve Wozniak says that the FCC overseeing the Web will be a positive step in controlling illegality. He also describes it as a victory for consumers.
The original series wins Amazon its first-ever Golden Globe awards at Sunday night's ceremony, while Netflix nabs one for "House of Cards" actor Kevin Spacey.
The multiplayer online battle arena genre of games is tough to get into, but whether you choose a classic or modern version, the work you do learning them will pay off enormously.
It's a little pricey, but the $150 iSport Victory is a winner overall.


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(based on 16 reviews)
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Nice Jersey
By Icemann
from Florida
About Me Avid Cyclist
Comments about Cannondale Ride Jersey:
True size nice fit fast ship
Bottom Line Yes, I would recommend this to a friend
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(1 of 1 customers found this review helpful)
Well made
By TonyRome
from Portsmouth Va
See all my reviews
This is a good club-fit jersey. It is well made and fits a little loose as a club-fit should. I use it for commuting. For the money, this is one of my best buys ever.
Nice jersey and the size fits
By Griz
from Phonex, AZ
Fits right for us big guys, 2XL fits like a 2XL.
Nice low cost bike jersey
By Johnny909
from Little Rock, AR
About Me Casual/ Recreational
I have a bike jersey rotation, and this one is in it. Good lightweight bike jersey. I like loose fit, and this fills the bill.
Great product
By Larry
from Medford, ny
I am 5'4" 205 in weight. Over weight because of medications. Very hard to find a riding shirt that works for me. I purchased the x large and loved the shirt. Fit me perfect. I like it a little loose. Purchased another one and am waiting for them to restock in the black and blue one. I will purchase it. Stays dry extremely comfortable.Excellent price. Even better on sale with free shipping
Great Jersey Great Price
By Ken S
from clarksville
Ride 4-5 times a week and this jersey is great during summer months
By TangoTango
from Italy
Perfect fit!
Nice jersery. A bit large
By Mark
from Boston
It's a little large -- so if you're a little large around the middle, go with your normal size. I'm not a small guy by any means, but I think I would have dropped a size. But, it's a really nice jersey, especially for the short money I paid when it was offered on sale.
2 pockets, lose around midsection
By Bruce
from Los Angeles, CA
it is a good quality shirt and very stylish. It fit well accept it wasn't snug around the mid-section so when I stood up to pedal the weight of the items in the pockets (1 cliff bar and cell phone)caused the shirt to move/shift around way too much! To say the least it was very annoying. Also it only had two pockets and not the 3 I prefer. I like a tighter fitting jersey around the waist.
Bottom Line No, I would not recommend this to a friend
A great shirt for the price
By bob c
from Midwest
You can't go wrong with the Cannondale shirt. It fits according to the size and is my go-to wear for weekend cycling.
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A semiconductor device having a self test circuit including an embedded dynamic random access memory array for storing data, a self test controller for internally generating test data patterns and expected resulting data and for comparing the expected resulting data with actual resulting data, test interface circuitry for loading the test data patterns into the memory and reading back the actual resulting data from the memory, means for selectively programming a voltage level to be applied to a selected cell plate of the memory according to predetermined test requirements and means for storing an address of a defective memory cell. In addition, the semiconductor device includes means for repairing a defective memory row or column in response to a signal received from the self test controller.
1. A semiconductor device having a self test circuit comprising:
a) an embedded dynamic random access memory array for storing data;
b) a self test controller for internally generating test data patterns and expected resulting data and for comparing said expected resulting data with actual resulting data;
c) test interface circuitry for loading said test data patterns into said memory and reading back said actual resulting data from said memory during a test sequence; and
d) a voltage generator responsive to a control signal for selectively applying one of a plurality of voltages to a selected cell plate of the memory during said test sequence.
2. A semiconductor device as defined in claim 1, including a circuit for storing an address of a defective memory cell.
3. A semiconductor device as defined in claim 2, including a circuit for repairing a defective memory cell in response to a signal received from said self test controller.
4. A method for testing a semiconductor device having an embedded dynamic random access memory array for storing data therein, said method comprising the steps of:
(a) generating test data patterns and expected resulting data in a self test controller;
(b) loading said test data patterns into said memory in a test sequence;
(c) applying a bump test to said memory array cells in accordance with said test data patterns during said test sequence;
(d) reading back said actual resulting data from said memory; and
(e) comparing said expected resulting data with said actual resulting data.
5. A method as defined in claim 4, including initiating said test sequence in response to a control signal external to said device.
6. A method as defined in claim 4, including storing each memory address location in a temporary storage within said controller.
7. A method as defined in claim 4, said step of applying a bump test including:
(a) applying a first voltage to a selected memory cell;
(b) writing a test bit to said cell; and
(c) subsequently applying a second voltage to said memory cell.
8. A method as defined in claim 7, said first voltage being higher than said second voltage if said test bit is a one.
9. A method as defined in claim 7, said first voltage being lower than said second voltage if said test bit is a zero.
This invention relates generally to apparatus method for testing and repairing semiconductor memories and more specifically, to a built-in self test and repair system.
Built-in self test (BIST) systems usually operate under fixed test conditions; i.e. fixed temperature and fixed voltages. This limits the range of possible scenarios which may be tested and not all scenarios faced by a device once it is in full production usage may be tested. Specifically, data storage integrity in dynamic random access memories (DRAM) can be compromised by cell leakage caused by a variety of reasons including alpha particles, hot electrons, and substrate current. Memory cells have certain operation margins which, if exceeded, will cause the cell to lose data stored therein. As a result, it is important to test a device under the worst-case scenarios in order to determine the cell's retention capabilities.
A supply voltage fluctuation test or voltage bump test is a standard test performed on standard DRAMs which is capable of testing operating margins of these cells, using an external tester. However, embedded memories cannot use standard memory testers to perform this and other tests due to the multitude of other functions contained in the integrated circuit. As a result, BIST systems provide a practical solution to testing embedded memories. BIST systems, however, usually operate at nominal temperature and voltage levels. As a result, the extreme conditions tested by the bump test are not covered. Our production testing the operating conditions are usually extended well beyond device ratings to ensure there is adequate operating margin.
Further, in standard DRAM and SDRAM applications, external testers perform a variety of tests including the voltage bump test to verify the memory cells' data retention capabilities. Under normal operations, the DRAM cell plate is held at a DC voltage, typically VCC/2. During the cell plate voltage bump test, two different voltage values are used, for example VCC/2−ΔV and VCC/2+ΔV. During the bump test, bits are written with one value of the cell plate voltage and read back with the other value. When the value of the cell plate is higher when writing than reading, the operation margin on stored '1's is tested. When the value of the cell plate is lower when writing than reading, the operation margin on stored '0's is tested.
Referring to FIG. 1(a), the concept of the voltage bump test is illustrated. A typical DRAM memory cell, word line WL and bit line BL structure is shown. Under nominal operating conditions, the cell plate voltage VCP=VCC/2, the bit line BL is precharged to VCC/2, the word line receives a voltage VPP for reading or writing the data stored in the memory Ccell. The charge delivered to the bit line BL is given by the formula:
where Vcell=VSS ('0') or VCC ('1')
When the voltage bump test is performed, a �ΔV bump step is applied to VCP before reading. The charge delivered to the bit line is now given by:
Based on whether ΔV is a positive bump or a negative bump, the charge delivered to the bit line will benefit either a stored '0' or '1'. FIGS. 1(b), 1(c) and 1(d) illustrate the voltage versus capacitance charge distributions for the three cases: nominal, ΔV positive and ΔV negative, respectively. Q0 represents the charge for a stored '0' and Q1 represents the charge for a stored '1'. As can be seen, when ΔV is positive, a stored '1' provides more charge to the bit line and therefore has a higher margin than a stored '0' which provides less charge to the bit line. Conversely, when ΔV is negative, the stored '0' has better retention capabilities than a stored '1'. By performing these tests, the margin on each cell for storing a '0' or a '1' can be verified. A voltage bump test circuit is described in U.S. Pat. No. 5,051,995.
Secondly, embedded memories usually employ a BIST system to perform the testing of the memory. The main concept of BIST is to move most of the test functionality into the silicon of the device being tested. Embedded memories require this type of testing since they do not have any external access pads or other means to connect to the external testers for testing. As a result, test systems integrated directly into the embedded memory device. U.S. Pat. No. 5,173,906 entitled "BUILT-IN SELF TEST FOR INTEGRATED CIRCUITS" illustrates such a system for an embedded SRAM macro. This system includes an input data pattern generator for generating predetermined data to be applied to the data inputs of the memory, an address counter for applying test address signals to the address inputs of the memory, an expected data pattern generator, which may be the same as the input data pattern generator, for generating expected data, a comparison circuit for comparing the expected data and the resulting data. The system is controlled by a state machine during the test sequence. The test patterns available are unique address ripple word (UARW), unique address ripple bit (UARB), checkerboard, (CHKBD), word line strip (WLS), blanket (BL) and programmable (PG). Since this BIST is designed for embedded SRAM's however, there is no provision for a voltage bump test. This system, however, does not perform a volt bump test on embedded memories, neither does it provide a facility for repairing defective memory. Recently embedded DRAMs have become widely used. Thus, here exists a need for a system that is capable of providing a built in self test along with an automatic repair of defective memory.
This invention seeks to provide a BIST system for an embedded dynamic random access memory, integrated in a single semiconductor device, including a provision for performing a voltage bump test of the embedded memory and using the test results to repair faulty memory locations.
According to an embodiment of the present invention, a semiconductor device capable of performing self test comprises: an embedded dynamic random access memory array for storing data, a built-in self test controller for internally generating test data patterns and expected resulting data and for comparing the expected resulting data with actual resulting data, test interface circuitry for loading the test data patterns into the memory and reading back the actual resulting data from the memory, means for selectively programming a voltage level to be applied to the cell plate of the memory according to predetermined test requirements.
The memory further including redundancy circuitry for replacing faulty elements with redundant elements using the results from a test sequence.
An advantage of the present invention is that the data retention abilities of an embedded dynamic random access memory can be tested quickly and efficiently. An additional advantage of the present invention is that its additional test capabilities occupy minimal silicon area in addition to the existing BIST circuitry area. A further advantage of the present invention is the ability to detect errors and subsequently correct them without external interference in the form of standard redundancy replacement techniques.
A better understanding of the invention will be obtained by reference to detailed description below in conjunction with the following drawings in which:
FIG. 1(a) is a circuit diagram illustrating a standard dynamic random access memory cell combination;
FIG. 1(b) is a graph showing a voltage versus capacitance plot for nominal operating conditions of a memory cell;
FIG. 1(c) is a graph showing a voltage versus capacitance plot for positive voltage bump test applied to a memory cell;
FIG. 1(d) is a graph showing a voltage versus capacitance plot for negative voltage bump test applied to a memory cell;
FIG. 2 is a block diagram of a BIST system according to an embodiment of the present invention;
FIG. 3 is a flow chart illustrating a test methodology according to the present invention;
FIG. 4 shows a schematic circuit diagram of a cell plate voltage generator according to an embodiment of the present invention; and
FIG. 5 shows a redundancy programming circuit according to an embodiment of the present invention.
Referring to FIG. 2, a block diagram illustrating the main components of the built-in self test and repair system according to an embodiment of the present invention is shown generally by numeral 20. The system comprises an embedded dynamic random access memory (DRAM or SDRAM), a test interface circuit TIC22, a BIST controller 23, a normal access data bus 24, an address bus 25 and control signals 26. The BIST controller 23 includes a data-in bus 27, an address bus 28 and control signals 29. The memory 21 further comprises memory cells 38, cell plate voltage VCP generator 30 which receives a signal BVCP 31 for selectively setting the value of VCP according to the test requirements (discussed later). The memory also includes redundancy circuitry 32 which in turn receives redundant addresses signals 33 from the BIST controller 23 based on faulty address locations located during the test sequence. The TIC22 is basically a multiplexer implementation for selecting between normal or BIST operation mode. A data-out bus 36 for the memory 21 is routed to a de-multiplexer 15, which selectively routes the data-out 36 to either the BIST controller 23 along a BIST resulting data line 34 or to an external data-out bus 37.
In addition, the preferred embodiment allows for selectively setting the value of the cell plate voltage at various stages of the test sequence.
The operation of the system shown in FIG. 2 will now be discussed with reference to FIG. 3 and in which like elements are referred to by similar numerals. Thus, referencing both FIGS. 2 and 3, the BIST controller 23 initiates its test sequence in response to the external control signal 39 by indicating via the TEST/NORMAL signal line 40 that the memory is beginning self test, a typical BIST test pattern known in the art is used to test the memory. The controller 23 independently generates the test pattern and begins the shifting of test data via the data-in lines 27. The BIST address input 28 specifies the memory locations to test. The BIST control input 29 provides the test interface circuitry with the TIC 22 control signals required to control the test sequence. The test interface circuitry allows the data 27, address 28 and control signals 29 to be passed on from the BIST controller 23 to the memory 21.
Each address location is temporarily stored in address latches (not shown) within the controller 23. The controller 23 begins with a start address at step 40. For every address location; the controller 23 determines and indicates, via the BVCP signal 31, a value of VCP for writing of the test bit shown in step 42. The test bit is then written to the specific address location at step 44. Once the write operation has been successfully completed, the BIST resets VCP to the voltage required for the read portion of the test step 46. The resulting bit is then read back step 48 and routed back to the BIST controller for comparison with an expected bit generated earlier by the BIST controller step 50. If the bits match, the cell passes that margin test, and the address is incremented to the next address step 52 according to the specific test pattern. If the address is the last address in the test sequence step 54 and no faults have been detected, the device is deemed to pass the overall voltage bump test.
If, on the other hand, the bits for the address location under test do not match, the cell has failed its margin test and as a result, must be replaced. The address location of the faulty cell is loaded into a redundant register step 58 which is part of the redundancy circuitry to be described below. Since there is a finite number of possible replacements, if the current replacement exceeds the number of replacement available, the overall device will be deemed to have failed the bump test. If, on the other hand, there are more replacements possible, the test resumes by re-testing the redundant cell in the same manner as the normal cell was tested. If the redundant cell passes, the test continues on to the next address in the test sequence. If the redundant cell fails, another replacement is attempted until all replacements are exhausted.
It should be noted that the replacement portion of the algorithm is not essential to the operation of the rest of the system. In fact, the replacement of the faulty locations is a further enhancement of an embodiment of the current invention by making use of the information obtained through the bump test. The faulty locations could alternately simply be stored or output to the system for further use.
Turning now to FIG. 4, the cell-plate voltage generator 30 shown in FIG. 2 is described in greater detail. The circuit includes a controllable voltage divider string indicated by block 60 followed by a low impedance driver 62 is used to generate VCP. The transistor connected diode string acts as a voltage divider, comprises PMOS transistors 64 and 66 having their source/drain circuits connected in parallel between the power supply VCC and a node 67. The PMOS transistor 64 is preferably a long channel device whose resistance is much greater than that of PMOS 66. The well connections for both PMOS transistors 64 and 66 are connected to VCC. Further connected to node 67 is the drain and gate of NMOS transistor 68 which also acts as a diode. The substrate of NMOS transistor 68 is connected to VBB, a negative on-chip generated voltage used to prevent forward biasing of the implant-well junctions. Other NMOS transistors may be connected similarly to NMOS transistor 68 to form a string of diode-connected NMOS transistors. Similarly, a diode-connected PMOS 52 transistor is connected to the source of NMOS transistor 68. Finally, NMOS transistors 70 and 72 are connected in parallel between a node 74 and ground, where NMOS transistor 70 preferably has a much larger resistance than that of NMOS transistor 72. The gates of the long channel devices 64 and 70 are connected to ground and VCC respectively. The gates of devices 66 and 72 receive {overscore (VCPH)} and VCPL respectively the phrase "which comprise the BVCP signal".
In operation, the cell-plate voltage generator selectably sets the value of VCP based on whether a nominal VCC/2 cell plate voltage or a bump VCC/2�ΔV cell plate voltage is required. When the embedded memory is not undergoing any test, the control signals VCPL and {overscore (VCPH)} are inactive and the voltage is generated purely from the voltage divider action of transistors 64, 68, 65, and 70 (and any other transistors connected in that string if necessary). More specifically, {overscore (VCPH)} is 'high', and VCPL is 'low'. During a test sequence initiated by the BIST system, one of two possible states of the control signals the phrase "VCPL, {overscore (VCPH)}" can be selected by the BIST controller, as indicated by Table 1:
The second combination marked 'invalid' should not be used since it will provide a short circuit path between VCC and ground VSS.
By selectively enabling the above mentioned transistors according to the states described in Table 1, the VCP output can be varied and can therefore be used to perform voltage bump tests on the embedded memory. For example, if testing the data retention capabilities of a '1', VCP would begin at a value higher than VCC/2, for example, VCC/2+ΔV, subsequently, a '1' would be written into the cell. VCP would then be bumped low to a lower value VCC/2−ΔV and the bit stored in the cell would be subsequently read out. If a '1' would result, then the cell has an adequate '1' margin. If the '1' would have changed into a '0', the cell would not have passed the bump test and its address location would be loaded into the redundancy circuitry for repair as will be described below. Similarly, if a '0' margin is to be tested, VCP would be started at a value lower than VCC/2, for example VCC/2−ΔV, subsequently a '0' would be written into the cell. VCP would then be bumped high to a high value VCC/2+ΔV and the bit stored in the cell would be subsequently read out. If a '0' would result then the cell has an adequate '0' margin. If the '0' would have changed into a '1' the cell would not have passed the bump test and its address location would be loaded into the redundancy circuit for repair. This procedure can be repeated for all memory cell locations based on the specific BIST test pattern.
Referring now to FIG. 5 an embodiment of the redundant programming circuit according to the present invention is shown generally by numeral 100. In this circuit both column or row replacement can be implemented. Various decoders and drivers which are well known in the art may be used.
The circuit provides for the storage and usage of the faulty address locations resulting from the BIST test sequence to replace faulty locations identified during the BIST controller test operation. The programming circuit comprises a reset device 142 coupled between VCC and an output 146 and a half-latch 140 and 141 also coupled between VCC and the output 146. Redundant programming devices 130-135 are coupled in parallel between the output 146 and ground, and receive redundant address bits RA0, {overscore (RA0)} . . . RAn, {overscore (RA)}AN at their gate inputs. These redundant addresses are each obtained from a redundant address generator 148 consisting of a 1-bit register receiving the faulty address location loaded by the BIST controller 23 upon detection of a fault during the test sequence, and some compare and enabling logic. The registers are indicated by numerals 143, 144 and are implemented by standard D-type flip/flops which receive the faulty address bit FAi, F {overscore (Ai)} on their D-inputs and provide alternating Q, {overscore (Q)} outputs to an exclusive-OR gate, which in turn additionally receives the actual address location being tested.
An additional control signal from the BIST controller, redundant register control RRCk, is used to enable the register. The output from the exclusive-OR gate 145 is input into a NAND gate 146 which combines the result of the comparison with the precharge signal {overscore (PRE)} which is 'low' during precharge and 'high' during active read or write memory mode. This structure is repeated for each complementary address bit from 0 to (m−1) of an m-bit address, as shown by the dashed boxes 148 i, 148 i+1, . . . 148 2n.
The described redundant address generator 100 simulates the action of a fuse connected in series with one of the redundant programming devices 130-135 which would, in that case, receive the actual address location at the inputs. That implementation is common in the art, but if fuses are not available due to the device application, a register redundancy scheme, as described in the embodiment of the present invention, should be used. The BIST environment, in fact, provides an ideal setting for register redundancy implementation since the testing and detection of faulty locations can and do occur after manufacturing. Therefore, the faulty address must be internally managed to repair the damaged location.
To cover the case when no redundancy is required, a separate device 150 receives at its input the combination of the precharge signal {overscore (PRE)} and a redundancy enabled signal RE which is first stored in a register under the same BIST control as the redundant address generator registers, namely RRC. This additional register plays the role of a master redundancy fuse.
The redundancy programming circuit, generally indicated by numeral 149, represents one of p existing redundancy programming circuits. The output RAS(0:p−1) 146 is input into a redundant decoder (not shown) as is well known in the art, used to select the redundant row or column and to disable the normal row or column. The output 146 can be further used to indicate whether a redundancy programming circuit has been already used for 23 replacement; this can be accomplished by feeding back output 146 to the BIST controller. If the RAS(0:p−1) signal is 'low', the BIST controller knows that that particular programming circuit is still available for replacing faulty elements. If the RAS(0:p−1) sign is 'high' however, the BIST controller knows that that particular programming circuit has already been used. Alternately, a register counter system could be used inside the BIST controller to keep count of how many registers have been used and how many are still available for replacement.
In operation, during precharge, the redundancy precharge signal {overscore (PRE)} is brought 'low', thereby bringing RAS(0:p−1) 'high'. This state is latched by the half latch 140, 141. At the start of an active cycle, the {overscore (PRE)} signal is brought 'high'. If no redundancy is required, the RAS(0:p−1) 146 is pulled 'low' by pull-down transistor 150, in response to a low RE signal into register 151; the 'high' {overscore (PRE)} signal combined with the {overscore (Q)} output of the register in the AND gate 152 will result in a 'high' being applied to the gate of transistor 150. If on the other hand, a faulty memory location is identified during the course of the BIST test sequence, the faulty address FAi, F {overscore (Ai)} is loaded into the redundant address registers 143-145 and the registers are enabled by the BIST controller 23. Based on an address match between say the test address location A0 input into EOR gates 145, and the 'low' {overscore (Q)} output from the register 143 based on the faulty address FA0 location, a 'high' will be output from the exclusive-OR gate 145. Since the {overscore (PRE)} signal is 'high' in the active mode, the 'high' from the exclusive-OR gate 145 will produce a 'low' on the input of the redundancy programming device 130 for example, thus allowing the output 146 to remain latched 'high'. This logic comparison is repeated for all the complementary bits. The output 146 will be used to decode a particular redundant memory location in order to replace the faulty normal location (not shown) and it may also be used to indicate to the BIST controller 23 that that particular redundancy programming circuit has been utilized.
Once the redundant cell has replaced the faulty normal cell, the VCP bump test is re-run on the redundant cell. The redundancy replacement process can be continued as the test sequence continues until all the redundancy programming circuits have been used up at which time, any additional attempts to implement redundancy will result in a 'failed device' result.
While the invention has been described in connection with the specific embodiment thereof, and in a specific use, various modifications thereof will occur to those skilled in the art without departing from the spirit of the invention as set forth in the appended claims.
The terms and expressions which have been employed in this specification are used as terms of description and not of limitations, there is no intention in the use of such terms and expressions to exclude any equivalence of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the claims to the invention.
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It is now 12 years since "Ladies And Gentlemen We Are Floating In Space' made a
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Thu Feb. 26, 2015
'I Jumped Up, Reached for the Ball … and My Life Changed Forever'
I was supposed to block for Jordy Nelson on the now infamous onside kick in the NFC Championship Game. But my mind went blank and instinct just kicked in. The mishap led to death threats, my release from Green Bay and a recurring nightmare. I hope to one day be remembered for something else


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Home › Building Directory › Clermont Brooklyn
Clermont Brooklyn
Luxury Living
375 Myrtle Avenue
New York, NY 11205
Cross streets:
Clermont Avenue, Adelphi Street
Fort Greene
New York, NY 11205
Cross streets:
Clermont Avenue, Adelphi Street
Fort Greene
Urban Edge has no apartments listed for Clermont Brooklyn at this time.
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Building Features & Amenities
- Concierge
- Fitness Center
- Terrace
- Covered Parking
- Video Intercom
- Low-rise (1-6 Floors)
- Rental Property
Pet policy: Pets OK
Gorgeously apportioned and luxuriously designed, the Clermont Brooklyn is the place to be in the up-and-coming Fort Greene neighborhood. The building is situated near Fort Greene Park and a plethora of Fort Greene's popular restaurants and cafes, and residents can be at peace knowing that they are living in one of Brooklyn's most popular neighborhoods.
With an ultra-modern sleek design, the residences at the Clermont Brooklyn offer the utmost in comfort and convenience. Tenants can take advantage of the spectacularly landscaped common outdoor space and beautiful views of the City. Within each unit, tenants will find high-end stainless steel appliances and dishwashers, as well as limestone kitchen countertops and spacious walk-in closets. Spectacular bamboo floors line the floors of the apartments creating a Far East ambience. Washers and dryers come standard within each residence, while many also offer a comfortable private outdoor space. Quaint porcelain tiled bathrooms and honey colored wooden cabinetry give the rooms an ambience that is both modern and personable. Better yet, this building is a pet friendly establishment that offers indoor parking to residents for a small fee. Chic and contemporary, the Clermont Brooklyn is one Fort Greene building that cannot be missed.
Neighborhood / Parking / Transportation
- Highway Nearby
Walking Distance to:
- Laundromat
- Dry Cleaners
- Grocery Store
- Convenience Store/Bodega
- Pharmacy
- Park
- Playground
- School
- Restaurants
- Shopping
- College/University
- Bus
Owner / Manager / Leasing Information
For more information on this building, contact: