A method for treating a disease selected from diabetes mellitus and atherosclerosis, and a method for reducing triglycerides and/or increasing HDL cholesterol levels in the plasma of a subject. The method comprises administrating to a subject an effective amount of crude Dunaliella powder, optionally together with an activator of nuclear receptors.

Two strains of Dunaliella, a unicellular, biflagellate, wall-less green alga, are capable of producing very large amounts of β-carotene, Dunaliella salina Teod. and Dunaliella bardawil(1). D. bardawil is a halotolerant alga whose β-carotene content comprises about 50% all-trans-β-carotene with the remainder composed mostly of 9-cis β-carotene and a few other β-carotene isomers(2). A process has been described for cultivating D. bardawil so as to obtain algae containing up to about 5% by weight of β-carotene(3). Later developments of the process increased the percentage to more than 8%. It has been shown that the natural isomer mixture of β-carotene which is accumulated in the alga Dunaliella bardawil is accumulated in fatty tissues of rats and chicks to an extent which is about 10 fold higher than that observed by feeding the synthetic all-trans β-carotene(4).
Various carotenoid-enriched Dunaliella commercial products are available such as Betatene™ (produced by the Henkel Corp., Germany) and Nutrilite™ (Amway, Inc., U.S.A.). These products are oil extracts of carotenoids from Dunaliella.
Retinoids are essential for a living organism for vision, cellular growth, differentiation, and to maintain the general health of the organism. 9-cis-retinoic-acid and all-trans-retinoic-acid are produced in the body by the cleavage of β-carotene (BC). The retinoid nuclear receptors, also known as orphan receptors RAR and RXR, have distinct physiologic properties by activating transcriptional factors. All-trans retinoic-acid binds to RAR but not to RXR, while 9-cis retinoic-acid binds to RXR, which plays a key role in important biological processes.
The activation of nuclear receptors is essential to cell metabolism, especially with respect to lipids and glucose. Several nuclear receptors have been implicated in cholesterol homeostasis. These receptors include: the liver X receptors (LXRa/NR1H3 and LXRb/NR1H2) and farnesoid X receptor (FXR/NR1H4) that are bound and activated by oxysterols and bile acids, respectively. LXR and FXR form obligate heterodimers with RXR that is activated by 9-cis retinoic acid and synthetic agonists (termed rexinoids). It was recently found that the activation of RXR by its ligands can affect two central processes of cholesterol metabolism: I. Cholesterol absorption in the intestine (activation of RXR/FXR heterodimer repressed cholesterol 7α-hydroxylase (CYP7A1) expression, resulting in decreased bile acid synthesis and cholesterol absorption). II. Reverse cholesterol transport from peripheral tissues (activation of RXR/LXR heterodimer inhibited cholesterol absorption and induced reverse cholesterol transport in peripheral tissues).
The following nuclear receptors are known to form heterodimers with RXR and hence, can be potentially activated by 9-cis retinoic acid administration: thyroid hormone (TRa/b); vitamin D (VDR); fatty acid/eicosanoids (PPARα/βγ); oxysterols (LXRa/b); bile acids (FXR); pregnanes/bile acids/xenobiotics (PXR); androstanes/xenobiotics (CAR).
Fibrates (clofibrate, fenofibrate, bezafibrate, ciprofibrate, beclofibrate and gemfibrozil) are currently recommended for the treatment of patients with hypertriglyceridemia (high plasma TG). The treatment of hypertriglycerdemia results in decreased plasma levels of triglyceride-rich lipoproteins. HDL cholesterol levels are usually increased when the baseline levels are low. The increase in HDL cholesterol is usually concomitant with increased levels of the HDL apolipoprotein A-I and A-II. In addition, fibrates reduce the atherogenic apoC-III-containing particles, effect post-prandial lipemia and some fibrate lower plasma fibrinogen and CRP levels.
As a consequence of their effect on lipid metabolism, fibrates have been shown to affect specific lipoprotein disorders such as in combined hyperlipidemia, primary hypertriglyceredemia, type III dysbetalipoprotenemia, and non-insulin dependent diabetes mellitus (NIDDM).
Fibrates are considered to be well tolerated, with an excellent safety profile. A low toxicity has been reported in almost every organ system. Fenofibrate treatment revealed low frequency of side effects. Long-term administration revealed no effect on peroxisome proliferation in human liver and no evidence for carcinogenesis. Clinically relevant interaction of fibrates with other anti-hyperlipedemic drugs include rhabdomyolysis and decreased bioavailibility when combined with some bile acid sequestrants. Potentiation of the anticoagulant effect of coumarin may cause bleeding.
Fibrates mediate at least part of their effects by peroxisome proliferator-activated receptor α (PPAR-α). Upon activation with fibrates, PPARs heterodimerize with another nuclear receptor, the 9-cis retinoic acid receptor (RXR). The dimer binds to specific response elements, termed peroxisome proliferator response elements (PPREs) and regulates gene expression.
Low plasma levels of high-density lipoprotein (HDL) and high triglyceride (TG) plasma levels are risk factors for atherosclerosis. Low levels of plasma HDL cholesterol, apolipoprotein AI (apoA-I) and high levels of triglycerides (TG) are associated with increased risk for atherosclerosis, the major cause of morbidity and mortality in Western societies. A recent study showed that the rate of coronary events is reduced by 22 percent by raising HDL cholesterol levels and lowering the plasma TG levels in patients treated with the fibrate gemfibrozil.
Several modes of action were proposed for the fibrate beneficial effects on atherosclerosis: Induction of lipoprotein lipolysis by reducing apoC-III levels and/or by increasing lipoprotein lipase activity. Induction of hepatic fatty acid (FA) uptake by the induction of FA-transporter protein and acyl-CoA synthetase. Decrease apoB and VLDL production. Reduction of hepatic TG production by induction of peroxisome (in rodents only) or mitochondrial β-oxidation pathway and inhibition of FA synthesis. Most important, fibrates increase the production of apoA-I and apoA-II in the liver, which probably contribute to the process of reverse cholesterol transport.
Type 2 diabetes mellitus is a serious health problem. It arises when resistance to the glucose lowering effects of insulin combines with impaired insulin secretion to raise the levels of glucose in the blood beyond the normal range. Thiazolidinediones are a new class of antidiabetic agents that improve insulin sensitivity and reduce plasma glucose and blood pressure in subjects with type 2 diabetes(5). The drugs bind and activate PPARγ that binds to DNA as heterodimers with a common partner, retinoid X receptor (RXR) to regulate transcription. RXR agonists have been shown to function as insulin sensitizers, markedly decreasing serum glucose, triglycerides and insulin in obese mice(6).
WO 93/24454 describes a carotenoid composition derived from Dunaliella algae in which the β-carotene content is predominantly 9-cis β-carotene. There is no mention of any medical applications.
U.S. Pat. No. 5,219,888 (Katocs) discloses a method to increase plasma HDL levels for the treatment and prevention of coronary artery disease by administrating a therapeutic amount of the retinoids all trans-retinoic acid and 9-cis-retinoic acid.
U.S. Pat. No. 5,948,823 discloses use of a substantially crude Dunaliella algae preparation in protecting mammals against the detrimental effects of medical and nuclear irradiation.
WO 97/10819 teaches a new treatment for non-insulin dependent diabetes mellitus by administration of RXR agonists and optionally, peroxisome proliferation activated receptor gamma agonists.
WO 99/50658 identifies compounds which modulate nuclear receptor activity, used for treating e.g. cancer, cardiovascular disease, osteoporosis, diabetes, postmenopausal disorders and inflammatory conditions.
WO 2001119770 reveals new retinoid X analogs, useful as retinoid X receptor modulators for lowering blood glucose levels, for modulating lipid metabolism and in treatment of e.g. diabetes, obesity, cardiovascular diseases and breast cancer.
U.S. Pat. Nos. 5,972,881 and 6,028,052 (Heyman) disclose methods and compositions for the treatment of non-insulin dependent diabetes using an RXR agonist together with a PPARγ agonist.
WO 03/027090 provides novel retinoid compounds that have selectivity as RXR agonists, and are effective in reducing blood glucose and maintaining body weight, thus being useful for the treatment of diabetes (NIDDIM) and obesity.
Colagiuri S. and Best, J. Lipid-lowering therapy in people with type 2 diabetes. Current Opinion in Lipidology (2002) 13:617-623, teaches that lipid powering with statins and fibrates is effective in improving cardiovascular disease outcome in diabetes.
Levy, Y. et al. Dietary supplementation of a natural isomer mixture of Beta-carotene inhibits oxidation of LDL derived from patients with diabetes mellitus. Nutrition & Metabolism (2000) 44:54-60, describes experiments in which Dunaliella bardawil-derived β-carotene was supplemented to the diet of diabetic patients. The dietary supplementation normalized the enhanced LDL susceptibility to oxidation in these patients.

Tel Hashomer Medical Research Infrastructure and Services Ltd.


An electrical discharge ozone generation cell has first and second electrode base plates which are separated by a nonconductive flat spacer plate. Within a central opening in the spacer plate is fitted an electrode plate in close contact with the first electrode base plate. A dielectric plate in close contact with the second electrode base plate and with the spacer plate helps define a gas discharge chamber with the interior edges of the spacer plate and the electrode plate. Gaskets on the two sides of the spacer plate around the central opening displaced away from the interior edges of the spacer plate ensure a gas seal for the electrical discharge chamber.

This invention relates to electrical discharge cells and, more particularly, to electrical discharge cells for generation of ozone.
There are many applications for ozone, including waste and water treatment, disinfection, cleaning, odor removal, pest extermination, and sterilization. Hence many ozone generation systems are very large, such as those for municipal waste and water treatment plants, while other ozone generation systems are smaller, such as systems for small industrial and domestic applications.
In a typical ozone generation system a feed gas source supplies the feed gas to an ozone generation cell through a flow controller. Besides oxygen, the feed gas may be ambient air or oxygen-concentrated air. A power supply provides the energy for the cell to generate ozone for an application process.
The ozone generation cell may operate in many ways, including the ionization of oxygen using electrical discharge (also called corona discharge) to create ozone. The present invention uses such electrical discharge in its ozone generation cell. But there are many problems with ozone and its generation. Ozone is highly corrosive which leads to problems in the selection of materials and the costs of those materials which are resistant to ozone. The corroded elements in the generation cell are required to be replaced occasionally. Hence any ozone generation cell should be easily repairable, and/or the corroded elements easily replaceable. The generation cell should also be designed for the optimum production of ozone at relatively low cost.
The present invention relates to an electrical discharge ozone generation cell which addresses these issues. The ozone generation cell has relatively low-cost parts with easy assembly and disassembly for simple replacement of parts and repair of the cell. The electric discharge chamber of the cell is designed for a high output of ozone.

Electrical discharge cell for generating ozone


A method of manufacturing a semiconductor device, includes: preparing a semiconductor IC chip and an external electrode terminal which is positioned away from the semiconductor IC chip, wherein the semiconductor IC chip has first and second electrode pads thereon, the second electrode pad being positioned between the first electrode pad and the external electrode terminal; connecting the first electrode pad and the external electrode terminal by a loop-like wire; and pressing a portion of the loop-like wire toward the semiconductor IC chip, thereby connecting the portion of the loop-like wire with the second electrode pad.

1. Field of the Invention
The present invention relates to a semiconductor device which has a structure that a semiconductor IC chip and an external electrode terminal are connected through a loop-like wire formed by wire bonding, a method of manufacturing the semiconductor device, and a wire bonding method.
2. Description of the Related Art
Various methods have been suggested to produce an electrical connection between an electrode pad of a semiconductor IC chip and an inner lead by wire bonding, at manufacturing a semiconductor device, in Japanese Patent Kokai Publication No. 2008-117888 (Patent Document 1) and Japanese Patent Kokai Publication No. 2008-34567 (Patent Document 2), for example. FIG. 13 illustrates a typical wire bonding method which has the steps of: bonding a gold ball 5 to an electrode pad 4 of a semiconductor IC chip 3, which is fixed on a die pad 1 with an adhesive agent 2, by using a wire bonding apparatus (not illustrated in the drawing), forming a loop-like wire 6 so that a neck (a part standing straight) 6a of a predetermined length H6a is formed in a direction of right above a top 5a of the gold ball 5, and extending the wire to the inner lead 40 and bonding the extended loop-like wire 6 to an inner lead 40.
However, in the wire bonding of the conventional manufacturing method, it is necessary that the length H6a of the neck 6a of the loop-like wire 6 is considerably long in order to reduce stress occurring at the top 5a of the gold ball 5. For this reason, the conventional semiconductor device which includes the semiconductor IC chip 3 and the loop-like wire 6 has the following problem that: it is difficult to reduce a height H6 of the loop-like wire 6 sufficiently, and thus the semiconductor device cannot be sufficiently reduced in thickness.

Method of manufacturing semiconductor device


The carrying device comprises a folded material, such as cardboard, which surrounds a pair of weights in a frame. The frame comprises an upwardly extending center panel and two side panels. The side panels are disposed parallel to the center panel and are separated from the center panel by a distance which is slightly larger than the thickness of the weights. The side panels are connected to the center panel by bottom panels. A wooden rod is placed through the center holes of the athletic weights, and anchored into the side of the cardboard frame. A handle located in the frame allows the weights to be easily carried.

Athletic weights typically have the shape of a flat disc with a hole disposed in the center. They somewhat resemble a flattened doughnut in appearance. These weights are manufactured from a suitable material such as steel or concrete filled plastic. Because of their very nature, these athletic weights may be heavy, weighing in the range of one (1) pound to over fifty (50) pounds. Depending on the amount of weight which is desired, athletic weights come in a range of diameters and thicknesses.
Because of the weights' unusual shape, it has been difficult for a user, in the past, to easily transport the weights from location to location. Also, when the weights are sold, such as in a sporting goods store, there has not been an effective way to display the athletic weights in an attractive or safe manner. Previously, the weights were simply stacked in large piles or packaged within boxes. When the weights were stacked up, it was difficult for the user to transport them home after making a purchase. Conversely, when the weights were placed within boxes, the prospective purchaser would be unable to view the actual product which he would be buying.


Apparatuses and methods for adjusting wireless-derived positions of a mobile station using a motion sensor are presented. One method includes estimating a position of a mobile station based upon wireless signal measurements and measuring a movement of the mobile station using a relative motion sensor. The method further includes detecting a displacement of the mobile station based upon the measured movement, determining that the displacement is below a threshold and then adjusting the estimated position of the mobile station using information from the relative motion sensor. An apparatus includes a wireless transceiver, a relative motion sensor, a processor coupled to the wireless transceiver and the relative motion sensor, and a memory coupled to the processor. The memory stores executable instructions and data for causing the processor to execute methods for adjusting wireless-derived positions using a motion sensor.

Mobile communications networks are in the process of offering increasingly sophisticated capabilities associated with the motion and/or position location sensing of a mobile device. New software applications, such as, for example, those related to personal productivity, collaborative communications, social networking, and/or data acquisition, may utilize motion and/or position sensors to provide new features and services to consumers. Moreover, some regulatory requirements of various jurisdictions may require a network operator to report the location of a mobile device when the mobile device places a call to an emergency service, such as a 911 call in the United States.
Such motion and/or position determination capability has conventionally been provided using both digital cellular positioning techniques and/or Satellite Positioning Systems (SPS). Additionally, with the increasing proliferation of miniaturized motion sensors (e.g., simple switches, accelerometers, angle sensors, etc), such on-board devices may be used to provide relative position, velocity, acceleration and/or orientation information.
In conventional digital cellular networks, position location capability can be provided by various time and/or phase measurement techniques. For example, in CDMA networks, one position determination approach used is Advanced Forward Link Trilateration (AFLT). Using AFLT, a mobile device may compute its position from phase measurements of pilot signals transmitted from a plurality of base stations.
Improvements to AFLT have been realized by utilizing hybrid position location techniques, where the mobile station may employ a Satellite Positioning System (SPS) receiver. The SPS receiver may provides position information independent of the information derived from the signals transmitted by the base stations. Moreover, position accuracy can be improved by combining measurements derived from both SPS and AFLT systems using conventional techniques.
However, conventional position location techniques based upon signals provided by SPS and/or cellular base stations may encounter difficulties when the mobile device is operating within a building and/or within urban environments. In such situations, signal reflection and refraction, multipath, and/or signal attenuation can significantly reduce position accuracy, and can slow the "time-to-fix" to unacceptably long time periods. These shortcomings may be overcome by having the mobile device exploit signals from other existing wireless networks, such as, for example, Wi-Fi (e.g., 801.11x standards), to derive position information. Conventional position determination techniques used in other existing wireless networks may utilize round trip time (RTT) measurements derived from signals utilized within these networks.
Utilizing RTT measurement techniques to accurately determine position typically involves knowledge of time delays incurred by the wireless signals as they propagate through various devices comprising the network. Such delays may be spatially variant due to, for example, multipath and/or signal interference. Moreover, such processing delays may change over time based upon the type of network device and/or the network device's current networking load. In practice, when employing conventional RTT positioning techniques, estimating processing delay times may involve hardware changes in the wireless access points, and/or time-consuming pre-deployment fingerprinting and/or calibration of the operational environment.
Accordingly, when using RTT techniques for position determination, it may be desirable to exploit on-board relative motion sensors to assist in the estimation of processing delays. Such techniques may improve the position location accuracy and performance a mobile device in a cost-efficient manner.

Wireless-based positioning adjustments using a motion sensor


A piezo valve is actuated by way of at least one actuator which is formed by a piezoelectric bender transducer (12) having two piezo actuators (14, 16). An actuating method has the steps of generating an actuator control signal (out), which can be output at either one of the two piezo actuators (14, 16), depending on at least one actuating control signal (in), of detecting an electric measurement quantity at one of the piezo actuators (14, 16) which is currently not controlled (16), and of generating a vibration damping signal (fb) on the basis of the detected measurement quantity and use thereof for active vibration damping for the currently controlled piezo actuator (14).

Such a circuit arrangement and such a method are known e.g. from DE 103 46 693 A1. The known circuit arrangements serves for actuating a piezo valve used for controlling a closed-off volume of air. The valve can provide e.g. the three states "filling", "maintaining pressure" and "venting".
In the case of the piezo valve actuated by the known circuit arrangement, the two piezo actuators form a piezo stack composed of two piezoelectrically active components acting in opposite senses, in order to enable a deflection in both directions (transversely with respect to the longitudinal direction) with respect to an undeflected rest position.
Such piezo valves very generally have diverse fields of application. Such valves can be used very advantageously for example as controllable air valves in systems for changing the contour of motor vehicles seats.
One fundamental problem on using a piezoelectric bending transducer ("piezo bender") as actuator in a piezo valve is that the bending transducer constitutes a system having more or less pronounced mechanical resonances and can thus perform undesirable vibrations.
Such vibrations of the bending transducer can constitute an impediment of the quantitative valve function (setting of a precise degree of opening of the valve). Further disadvantageous effects are e.g. development of noise that is undesirable in many fields of application and/or an inherently unnecessary additional mechanical loading of the bending transducer.
Undesirable vibrations of the bending transducer can be brought about e.g. on account of relatively abrupt valve actuation processes. Moreover, even in the case of slow or unchanged degree of opening of the valve, such vibrations can also be brought about by the (turbulent) mass flow flowing through the valve.
The flow of the relevant medium (e.g. air, hydraulic oil, etc.) through the valve produces an excitation that is broadband in terms of frequency, whereby primarily the mechanical resonant frequencies of the bending transducer can be excited (mouth organ effect). This effect occurs to different degrees depending on the instantaneous operating conditions (inlet pressure, back pressure, effective valve cross section, viscosity of the medium, mechanical bending travel limitation, etc.).

Circuit arrangement and method for actuating a piezo valve


A method for processing a substrate includes performing a cyclic plasma etch process including a plurality of cycles, where each cycle of the plurality of cycles includes: causing chemical reactions with the surface of the substrate by exposing a surface of the substrate to fluorine radicals extracted from a first gas discharge plasma formed using a first gaseous mixture including a non-polymerizing fluorine compound; cooling the substrate and concurrently removing residual gaseous byproducts by flowing a second gaseous mixture over the substrate, and at the same time, suppressing the chemical reactions with the surface of the substrate; and performing a plasma surface modification process by exposing the surface of the substrate to hydrogen radicals extracted from a second gas discharge plasma formed using a third gaseous mixture including gases including nitrogen and hydrogen.

Generally, a semiconductor device, such as an integrated circuit (IC) is fabricated by sequentially depositing and patterning layers of dielectric, conductive, and semiconductor materials over a substrate to form a network of electronic components and interconnect elements (e.g., transistors, resistors, capacitors, metal lines, contacts, and vias) integrated in a monolithic structure. Many of the processing steps used to form the constituent structures of semiconductor devices are performed using plasma processes. Plasma processing techniques include chemical dry etching (CDE) (e.g., plasma ashing), physical or sputter etching, reactive ion etching (RIE), plasma-enhanced chemical vapor deposition (PECVD), plasma-enhanced atomic layer etch (PEALE), and atomic layer deposition (PEALD).
Driven by an insatiable demand for low cost electronics with high functionality, the minimum feature sizes have been shrunk to reduce cost by roughly doubling the component packing density at each successive technology node. Innovations in patterning such as immersion photolithography, multiple patterning, and 13.5 nm wavelength extreme ultraviolet (EUV) optical systems have brought critical feature sizes down close to ten nanometers. Concurrently, unconventional materials such as organics, ferroelectrics, and chalcogenides are being increasingly used in products. This scenario poses a challenge for plasma technology to provide processes for patterning features with accuracy, precision, and profile control, often at atomic scale dimensions. Meeting this challenge along with the uniformity and repeatability needed for high volume IC manufacturing requires further innovations.


An arrangement for reproducing a digital signal from a track on a magnetic record carrier (20) includes a magnetic read head (21) having a magneto resistive element ( 107), and an equalizer filter circuit (23) for equalizing the output signal of the read head. The equalizer filter circuit (23) includes an IIR filter (29) and FIR (30). The IIR filter (29) equalizes magnitude and group delay of the signal applied to its input in a low frequency region of the signal frequency range. The FIR filter equalizes at least the magnitude of the signal applied to its input in a higher frequency region of the signal frequency range. Viewed in the direction of transport of the record carrier, the MR head has a front side and a back side. One of the sides (41) has a magnetic shielding for the MR element (107) which is larger than the magnetic shielding of the other side (40). The MR head (21) is positioned relative to the track so that the front side (40) has the lesser magnetic shielding.

1. Field of the Invention
The invention relates to an arrangement for reproducing a digital signal from a track on a magnetic record carder, the arrangement including
a magnetic read head having a magneto resistive (MR) element, and wherein, viewed in the direction of transport of the track relative to the head, the magnetic head has a first side (front) and a second side (back), one of the sides having a magnetic shielding for the MR element which is larger than the magnetic shielding on the other side, PA1 an equalizer filter means, having an input coupled to an output of the magnetic read head, and an output, the equalizer filter means being adapted to supply an output signal at its output which has been substantially equalized as regards magnitude and group delay as a function of frequency, the equalizer filter means including finite impulse response (FIR) filter means, and PA1 transport means for moving the track in a certain direction past the magnetic read head.
2. Description of the Related Art
Thin film heads of the MRH type as described in the foregoing have been disclosed in the Journal `Electrotechnology`, April 1988, pages 61 to 64. When used in an arrangement for reproducing a digital signal from a track on a magnetic record carrier, an equalizer filter means is needed so as to compensate for the non-flat frequency characteristic of the reproducing system. The frequency characteristic of a system is expressed as a magnitude response and a phase response of the system as a function of frequency. The group delay of the system has a relation to the phase response of the system in that the group delay is proportional to the first derivative with respect to frequency of the phase response, or D(f).div..delta..PHI.(f)/.delta.f, where D is the group delay of the system as a function of frequency and .PHI. is the phase response of the system as a function of frequency.
It is known to use a FIR filter in the equalizer filter means. FIR filters are also called transversal filters, and are well known in the art of digital filter technology.
Prior art reproducing arrangements have the disadvantage that the equalizer filter means becomes very complex in that a large number of coefficients are needed in the FIR filter means in order to sufficiently equalize the signal read from the track. Such filter means realized in the form of an integrated circuit results in a large surface area of the substrate of the IC being occupied. Attempts to decrease the complexity of the equalizer filter means have led to a deterioration after equalization of the signal read from the tape.

Arrangement for reproducing a digital signal from a track on a magnetic record carrier using a read head with magneto-resistive element and an equalizer filter


A wireless electromagnetic telemetry system for broadcasting signals across a bottomhole assembly disposed in a borehole drilled through a subterranean formation includes an insulated gap at a first point in the bottomhole assembly, at least one magnetic field sensor at a second point in the bottomhole assembly which measures a magnetic field, and a circuitry which modulates a voltage across the insulated gap, wherein the voltage creates an axial current along the bottomhole assembly that results in the magnetic field.

The invention relates generally to methods and systems for passing signals between a surface unit and downhole tools disposed in a borehole penetrating a subterranean formation.
The lower portion of a drill string for drilling a borehole in a subterranean formation is typically referred to as a bottomhole assembly. In general, the bottomhole assembly includes downhole tools that perform various downhole operations in the borehole. It is often necessary to send commands to one or more of these downhole tools in order to control operation of the downhole tool. For example, the bottomhole assembly may include a rotary steerable system that allows a borehole to be drilled in a formation directionally. To set the direction and inclination of the borehole segment being drilled, a command is sent from a surface location to the rotary steerable system.
In another example, the bottomhole assembly may include various formation evaluation tools, such as a logging-while-drilling (LWD) tool or measurement while drilling (MWD) tool designed to measure formation parameters. Certain formation evaluation tools, such as a formation pressure while drilling tool as described in US Patent Application No. 20050109538, may also be used to measure pressure using a probe that extends to contact the formation. For this operation, the pressure in the probe is momentarily brought below the formation pressure to draw formation fluid into the probe. Once the probe stabilizes at the formation pressure, the probe is retracted. These formation evaluation tools typically require commands to be sent from a surface location to the downhole tool. Typically, commands are sent to downhole tools using a telemetry system, such as a mud pulse system that manipulates flow of drilling mud through the drill string to create pressure pulses. This generally requires that the rate of surface mud pumps is adjusted manually, a process that can take several minutes and interferes with the drilling process.
MWD tools are typically provided with a telemetry component adapted to communicate with a surface unit. The telemetry component may be a mud pulse, electromagnetic (EMAG), acoustic or other telemetry device. In cases involving MWD tools having EMAG telemetry, the MWD-EMAG telemetry tools use relatively low frequency EMAG waves to communicate from a downhole location to a surface location. A typical MWD-EMAG telemetry tool includes a drill collar having an insulated gap and circuitry that creates a modulated voltage across the insulated gap. See, for example, U.S. Pat. No. 4,348,672. If the MWD-EMAG telemetry tool is included in a bottomhole assembly, the voltage across the insulated gap typically results in a large electric current flow along the drill string near the MWD-EMAG telemetry tool. Some current typically also flows through the earth and produces a weak electric field that is detected at the surface with two or more electrodes driven into the ground.
MWD-EMAG telemetry tools can be configured to receive signals from the surface via electric currents generated at the surface. These received signals may be communicated to other downhole tools in the bottomhole assembly if the MWD-EMAG telemetry tools can communicate with these downhole tools. One possibility is for internal or external wire links to be formed between an MWD-EMAG telemetry tool and other downhole tools to enable transmission of signals. However, it is sometimes impossible or impractical to run wires between downhole tools in a bottomhole assembly. For example, in a bottomhole assembly including a rotary steerable system, a mud motor may be positioned between the MWD-EMAG telemetry tool and the rotary steerable system. Passing a wire through the mud motor and connecting the wire to tools below the mud motor would be very difficult since the mud motor shaft rotates at a high speed and is attached to collars and/or the drill bit. A rotating connector would be required to make the wire connection, but such a rotating connector is unlikely to be reliable. Other methods of communicating through a mud motor can be complex (see, for example, U.S. Pat. No. 5,160,925) and may be unavailable on standard commercially available motors.
There are other examples where it may be cumbersome or impossible to form internal or external wire links between the MWD-EMAG telemetry tool and other downhole tools in a bottomhole assembly. For example, a typical power-drive rotary steerable system has a control unit that is held geostationary while the drill collar containing the control unit rotates about the control unit. In this case, running an electrical connection from the MWD-EMAG telemetry tool to the drill collar and control unit would be very difficult. The connection between the rotating drill collar and the geostationary control unit would require a rotating connection, which is unlikely to be reliable in a borehole environment. In cases where purely mechanical hardware, such as under-reamers and jars, are placed between the MWD-EMAG telemetry tool and a downhole tool, these mechanical hardware would likely have to be wired as well.
In another example, the bottomhole assembly may include a LWD seismic tool having an array of geophones or hydrophones for detecting seismic waves. These seismic sensors (geophones or hydrophones) are typically required to be placed 60 to 70 feet apart along the drill string and can acquire data only when the drill string is stationary and when the mud pumps are off, as described in, for example, U.S. Pat. No. 6,308,137. An MWD-EMAG telemetry tool could be useful in this case if it can communicate with the LWD tool. For example, the MWD-EMAG telemetry tool could detect the desirable conditions for LWD seismic measurement, i.e., stationary drill string and no mud circulation, and could communicate this to the seismic sensors in the LWD tool so that the seismic sensors can make the measurement. However, it would be impractical to run the long wires needed to make the signal transmission links between the MWD-EMAG telemetry tool and each of the seismic sensors in the LWD tool.
From the foregoing, it would be desirable in many situations to have a wireless telemetry system to transmit signals between an MWD-EMAG telemetry tool and other downhole tools in a bottomhole assembly or as a backup for other communications systems, such as wired systems. Wireless telemetry systems have been used in a bottomhole assembly. In one example, electromagnetic induction is generated using coils wrapped around drill collars, as described in U.S. Pat. No. 6,057,784. In another example, transformer coupling are formed using toroids mounted externally on drill collars, as described in U.S. Pat. Nos. 5,359,324 and 5,467,832. These wireless telemetry systems work well, but adding either type to an MWD-EMAG telemetry tool and other downhole tools, such as a rotary steerable system, in a bottomhole assembly would significantly increase the cost of the bottomhole assembly, increase the length of the bottomhole assembly, and add components to the bottomhole assembly that can easily fail. A wireless telemetry system that enables communication between the EMAG telemetry tool and downhole tools without these drawbacks may be beneficial.

Wireless electromagnetic telemetry system and method for bottomhole assembly


The present invention is directed to a method for forming porous oxide dispersion strengthened molten carbonate fuel cell anodes having improved anode creep resistance. The method comprises the steps of forming an alloy powder comprised of a base metal and an alloy metal, forming the alloy into a porous anode structure by sintering, and then placing the porous anode structure under conditions in which the base metal is reduced and the alloy metal is oxidized, thereby internally oxidizing the alloy metal to form oxide particles therein. Alternatively, the method of the present invention can comprise the steps of forming an alloy powder comprised of a base metal and an alloy metal, placing the alloy powder under conditions wherein the powder is oxidized only on its surface, thereby forming oxides of both the base metal and the alloy metal, and forming the oxidized alloy powder into a porous anode structure by simultaneous sintering and internally oxidizing the remaining unoxidized alloy metal by an oxygen exchange reaction between the base metal oxide the internal alloy metal.

Molten carbonate fuel cells generally comprise two electrodes with their current collectors, a cathode and an anode, an electrolyte tile making contact with both the electrodes, and a cell housing to physically retain the cell components and to provide contacts between the electrodes and the reactant gases. Under fuel cell operating conditions, in the range of about 500.degree. C. to about 700.degree. C., the entire electrolyte tile consisting of the carbonate, and the inert support material, form a paste and thus, the electrolyte diaphragms of this type are known as paste electrolytes. The electrolyte is in direct contact with the electrodes where the three phase reactions (gas-electrolyte-electrode) take place. Hydrogen is consumed in the anode area producing water, carbon dioxide and electrons. The electrons flow to the cathode through an external circuit producing the desired current flow. At the anode, there must be ready entry for the reactant gas, ready exit for the chemical reaction products and ready exit for the product electrons. To maintain a high level of stable performance, both electrolyte and electrode design and properties must be optimize and stabilized at the gas-electrolyte-electrode interface.
Porous anodes of cobalt, copper, or nickel have been previously used in molten carbonate fuel cells. These anodes typically require stabilizing agents to maintain porosity and surface area during fuel cell operation. The stabilizing agents are usually added in about 1-10 weight percent, based upon the metal. The stabilizing particles are dispersed on the base metal surface, prohibiting the structure from sintering at molten carbonate fuel cell temperatures of 500.degree. C. to 700.degree. C.
The molten carbonate fuel cells have typically used nickel, cobalt, and copper-based anode structures. These anodes tend to be dimensionally unstable, losing thickness by creep deformation within the fuel cell stack.
The porous anodes described have problems in that they are prone to creep deformation which occurs as a result of a holding force applied to keep the components in good contact. Creep of electrodes occurs by a combination of at least three different creep mechanisms: particle rearrangement, sintering, and dislocation movement. The surface dispersion of stabilizing particles used in prior art methods does not inhibit creep by dislocation movement. The creep of these anodes under the loaded conditions of a fuel cell stack is not acceptable.
Various methods have been used to attempt to inhibit creep deformation in the anode structures. One method has been to internally oxidize the alloying metal used in the base metal-alloying metal composition typically used to form the porous anode structures.
For example, U.S. Pat. No. 4,315,777 to Nadkarni discloses the internal oxidation of a powder that is precompacted. The powder is a blend of an alloy powder and an oxidant base metal. Upon heat treatment, the alloying metal becomes internally oxidized by oxygen supplied by the metal oxide contained in the oxide powder. Thus, the structure of Nadkarni contains oxidant particles which are, in effect, additives and which provide oxygen for internal oxidation of the alloying metal. This method of dispersion strengthening utilizing an oxidant additive is disadvantageous since the properties of the alloy are compromised by side reactions with the additive which detracts from the performance of the dispersion strengthened alloy. Moreover, the method disclosed in Nadkarni produces a solid, highly dense end product which is not suitable for use as an electrode, which requires high porosity.
U.S. Pat. No. 4,594,217 to Samal discloses a process of forming highly dense bodies from oxide dispersion strengthened powders by cold rolling to a sheet having a density of at least 90% of the theoretical value prior to subsequent heat treatments. Samal uses a metal alloy as a starting material which is already dispersion strengthened and, thus, is not directed to a novel method of dispersion strengthening. Samal utilizes high pressure to bond the particles of the alloy composition together, creating highly dense bodies that are unsuitable for use as electrodes, which require high porosity.
U.S. Pat. No. 4,714,586 to Swarr discloses a method for forming dimensionally stable nickel-chromium anodes by internally oxidizing the alloying metal at high water vapor pressures. The oxygen used to internally oxidize the alloying metal is obtained externally from a gas atmosphere. Swarr is limited to the formation of nickel-chromium anodes.
U.S. Pat. No. 3,525,609 to Roberts discloses a dispersion strengthened copper alloy, which is alloyed with silver, cadmium, or zinc and strengthened by internally oxidized aluminum. The dispersion strengthened alloy is formed by internally oxidizing the alloy. The alloy is surface oxidized at 300.degree. C. and the internal alloying metal is then oxidized by heat treatment in a subsequent step. The alloy of Roberts forms highly dense bodies by the use of high pressure compaction techniques. These bodies are not suitable for use as porous anode structures as they are too dense.
U.S. Pat. No. 3,578,443 to Grant et al. discloses a method for producing an oxide dispersion strengthened alloy by surface oxidizing copper aluminum powder by intensive communition of the powder with an alcohol suspension. The surface oxidized powder is then heat treated in an air tight tube at 750.degree. C. to internally oxidize the entire powder. The communition can deform the powder particles to undesirable shapes, since they are unsuitable for anode microstructure design. The alloy is sintered in a later step. This process produces a highly dense body, unsuitable for use as a porous anode structure.
Thus, it is an object of the present invention to provide a method of preparing a porous anode structure which is dimensionally stable for molten carbonate fuel cell use.
It is a further object of the present invention to provide a method of preparing an anode of nickel and titanium that remains structurally stable with a minimum of creep deformation when in extended use under fuel cell stack conditions.
It is another object of the present invention to provide a method of preparing an anode of nickel and aluminum that remains structurally stable with a minimum of creep deformation when in extended use under fuel cell stack conditions.
It is still another object of the present invention to provide a method of preparing a porous anode structure that has improved creep resistance by internally oxidizing the alloying metal of the base metal-alloying metal composition which forms the alloying powder of the present invention by controlling the oxidation potential of the atmosphere and without using oxidant additives to the alloying powder.
It is a further object of the present invention to provide a method of preparing an oxide dispersion strengthened porous anode by surface oxidizing the alloying metal and base metal of the alloy powder, and subsequently simultaneously internally oxidizing the alloying metal and sintering, in one step, to form the anode structure.

Method for forming porous oxide dispersion strengthened carbonate fuel cell anodes with improved anode creep resistance


Metadata is replicated. For instance, in response to receiving a request for replicating metadata to a target node, information of an index structure associated with the metadata is obtained. The index structure may include terminal nodes for storing the metadata and index nodes for storing index information of the terminal nodes. Next, the metadata from the terminal nodes is extracted based on the information of the index structure. Further, a sequence is generated to be replicated of the metadata. The sequence to be replicated includes items of the metadata, and locations of the items in the sequence to be replicated are determined based on key information corresponding to the items. In addition, the items of the metadata, in the sequence to be replicated, are replicated to the target node. In this way, only the metadata in the index structure is replicated, thereby reducing the data amount of replication.

Remote backup systems, such as Elastic Cloud Storage (ECS), enhance the protection for a storage device against failures/interruption at the geographic level by having a plurality of data copies. In a remote backup system, all types of data (including data and metadata) are stored in chunks. Currently, the metadata are typically stored in copy-on-write (COW)-based index structure (for example, B+ Tree) for fast indexing the locations of data. In the current remote backup system, the whole chunk including data or metadata is typically transmitted from a source node to a target node, such as a newly added remote node, thereby implementing backup of the data or metadata. For example, when backing up the metadata, the whole index structure is replicated to the target node. However, in the data chunks related to the metadata replicated from the source node to the target node, the percentage of the index structure is rather low. This may lead to unnecessary resource (bandwidth, memory, IO, or the like) overhead, or even make the service unavailable for a certain period of time.

Methods, electronic devices and computer program product for replicating metadata


A current clamp meter includes a current meter body and a jaw assembly. The jaw assembly is configured so that the current clamp meter may be used to reach and readily single-out a desired wire from amongst adjacent wires.

Electrical current can be measured by connecting a current meter in series with the wire. In many cases, however, disconnecting the wire to connect the current meter can be inconvenient. For example, the wire can be tightly grouped in a bundle with several other wires making it difficult to individually disconnect the wire of interest. Another example of the inconvenience is where a terminal to which the wire is connected is not conveniently located or is inaccessible, requiring the wire to be cut for the current meter to be connected in series. It is time consuming to reconnect the two ends of the cut wire after a measurement is taken, and can be dangerous in situations where relatively high current is carried by the wire. Additionally, the integrity of the wire is compromised by cutting and reconnecting, thus, potentially raising reliability problems.
A clamp probe connected to a conventional multimeter can be used to measure electrical current without the need for disconnecting a wire. The clamp probe is opened, the wire is inserted into the clamp, and the clamp is closed to take a current measurement. The closed clamp includes a core of ferromagnetic material, which when closed, represents the core of a transformer. The wire passing through the clamp represents the primary winding. As known, a current flowing in the wire induces a magnetic flux in the core of the transformer, which in turn, induces a current in a secondary winding of the transformer. Using these physical phenomena, the magnitude and polarity of the current in the clamped wire can be determined based on the current induced in the secondary winding and the characteristics of the transformer formed by the clamped wire.
A known clamp meter is designed with the clamp integrated into the body of the meter, which can provide the convenience of taking a measurement using one hand. That is, only one hand is used to open and close the clamp for clamping a wire and to take a current reading. "One-handed" clamp meters are generally acceptable for applications where the display can be easily viewed by the technician with the meter clamped to the wire for measurement. However, problems with reading the measurement can arise where the wire is difficult to reach or cannot be readily singled-out from amongst adjacent wires.
FIG. 6 illustrates an exploded view of a known jaw assembly. The known jaw assembly includes housings that are split in two approximately equal pieces. In particular, neither housing piece of the known jaw assembly has a volume approximately sufficient to individually contain a current sensing core. Additionally, the known jaw assembly includes separate end caps that are not integrally formed with either piece of the housing. It is therefore more difficult to use the known jaw assembly to select an individual wire from a group of wires because the cross-section of the known jaw assembly is enlarged due to the location of the joints between the housing pieces and the separate end caps.

Simplified jaw assembly for a clamp meter


A container refrigeration unit mounted on a container body (1a) includes a casing body (11) partitioning the container into the internal side and the external side thereof. A protruding portion (12) protruding toward the internal side is formed in a lower portion of the casing body (11), and the side stays (50) each extending vertically are mounted on both sides of the rear surface of the protruding portion (12). On the contrary, evaporator frames (40) each located above the protruding portion (12) and extending from the casing body (11) to a top end of the side stay (50) are mounted on both sides of an upper portion of a rear surface in the casing body (11). The bottom tip of the side frame (40) and the top end of the side stay (50) are fixed by a bolt.

Conventionally, there have been container refrigeration units for cooling an interior of a container used in marine transport or other transports.
Patent Document 1 discloses a container refrigeration unit of this type. The container refrigeration unit is provided in an opening of a container body one end of which is opened. In a lower part of a casing of the container, an external storage space communicating with an exterior of a container body is formed. The external storage space contains a compressor, a condenser, and an external fan, for example.
On the contrary, in an upper part of the casing, an internal storage space communicating with an interior of the container body is formed. At a rear surface of the casing, a partition plate is placed upright to partition the interior of the container body and the internal storage space. The partition plate is coupled to and supported by side stays (pillar members) respectively provided at both ends of the casing. In the casing, an air passageway is formed between a casing body partitioning the container into the internal side and the external side thereof, and a partition plate. The internal storage space is provided with an internal fan and an evaporator.
When the container refrigeration unit is operated, internal air is suctioned into the internal storage space by the internal fan. The air is cooled in passing through the evaporator. The cooled air passes through the air passageway, and is sent to the interior of the container again. As described above, the container refrigeration unit is configured to circulate the internal air while cooling the internal air in the air passageway, thereby freezing and refrigerating stored goods in the interior of the container.


Embodiments of the present invention pertain to maintaining an acceptable level of relative humidity inside of a disk drive. According to one embodiment, clean dry air is blow over a cover of the disk drive. The cover includes an unsealed servo write slot. The amount of clean dry air blown over the cover is regulated while a servo write process is performed so that a portion of the clean dry air is introduced into the disk drive.

Disk drives are manufactured in clean rooms in order to prevent damage to the disk drives from particles getting inside of the disk drives. Disk drives are also subject to being damaged from electrostatic discharge (ESD), which is the discharge of electrostatic charge between components that have different potentials, during the manufacturing process. In order to minimize the possibility of ESD, the relative humidity inside of a clean room is typically maintained at approximately 55 percent.
However, it is desirable that the relative humidity inside of a disk drive after it has been manufactured is approximately 25 percent to 30 percent in order to avoid the failure of disk drive components, such as the magnetic read write heads, due to corrosion of the components. Desiccants are typically placed inside of disk drives in order to maintain a relative humidity of approximately 25 percent to 30 percent inside of the disk drive. However, since the clean room typically has a relative humidity of approximately 55 percent much of the life span of the desiccant is used up while the disk drive is being manufactured. Thus, the life of the disk drive is shortened.
FIG. 1 depicts a plan view of a prior art disk drive in order to facilitate the discussion of using desiccants inside of disk drives. The disk drive 110 includes a base casting 113, a motor hub assembly 130, a disk 112, actuator shaft 132, actuator arm 134, suspension assembly 137, a hub 140, voice coil motor 150, a magnetic read write head 156, a slider 155, and desiccant 160.
The components are assembled into a base casting 113, which provides attachment and registration points for components and sub assemblies. A plurality of suspension assemblies 137 (one shown) can be attached to the actuator arms 134 (one shown) in the form of a comb. A plurality of transducer heads or sliders 155 (one shown) can be attached respectively to the suspension assemblies 137. Sliders 155 are located proximate to the disk 112's surface 135 for reading and writing data with magnetic heads 156 (one shown). The rotary voice coil motor 150 rotates actuator arms 135 about the actuator shaft 132 in order to move the suspension assemblies 150 to the desired radial position on a disk 112. The desiccant 160 is typically placed near the voice coil motor 150. The actuator shaft 132, hub 140, actuator arms 134, and voice coil motor 150 may be referred to collectively as a rotary actuator assembly.
Data is recorded onto disk surfaces 135 in a pattern of concentric rings known as data tracks 136. Disk surface 135 is spun at high speed by means of a motor-hub assembly 130. Data tracks 136 are recorded onto spinning disk surfaces 135 by means of magnetic heads 156, which typically reside at the end of sliders 155.
FIG. 1 being a plan view shows only one head, slider and disk surface combination. One skilled in the art understands that what is described for one head-disk combination applies to multiple head-disk combinations, such as disk stacks (not shown). However, for purposes of brevity and clarity, FIG. 1 only shows on head and one disk surface.

Method and a system for maintaining an acceptable level of relative humidity inside of a disk drive

Hitachi Global Storage Technologies Netherlands, B.V.


A ceramic and metal bonded composite comprising an intermediate metal plate interposed between a ceramic member and a metal member and brazed thereto, the intermediate metal plates carries on its juncture surface a central square projection having substantial area, pins arranged near the four corners and fins between the corners, the central square projection mechanically and thermally couples the ceramic member and the metal member together with the brazing layer and the pins and fins also mechanically and thermally couple the both members together with the brazing layer, while permitting relative displacement between the both members through their plastic deformation, thereby preventing crack generation in the ceramic member.

Since the thermal expansion coefficients of ceramics are smaller than those of metals, the ceramic and metal bonded composite has to include some measures to reduce, buffer or relax a strain caused in the ceramic member of the composite due to a thermal expansion difference between the ceramic member and the metal member.
U.S. Pat. No. 4,690,793 issued Sept. 1, 1987 discloses a ceramic and metal bonded composite first wall for a nuclear fusion reactor, wherein a copper clad carbon (Cu-C) fiber layer having an intermediate thermal expansion coefficient between those of ceramic and metal is interposed in the juncture surface of a ceramic tile and a metal substrate in order to buffer the strain caused in the ceramic tile due to their thermal expansion difference. However the heat resistance of the Cu-C fiber is as low as 350.degree. C., an application of the disclosed composite wall under a high heat flux condition was impossible.
Japanese patent application Laid-Open No. 59-137378 (1984) discloses a ceramic and metal bonded composite, wherein the juncture surface of the metal plate is provided with plurality of two kinds of slits or grooves crossing each other so as to allow the slitted metal portion at the juncture a plastic deformation and to reduce the strain caused in the ceramic plate due to their thermal expansion difference. However the soldered contacting area of the metal plate to the ceramic plate of the disclosed composite is relatively small, the thermal conductivity of the composite as a whole as well as the bonding strength thereof are considered low.
Japanese patent application Laid-Open No. 61-117170 (1986) also discloses a ceramic and metal bonded composite, wherein five identical disc shaped metal plates are interposed between a ceramic plate and a metal plate, and one disc plate is disposed in the center of the juncture and the remaining four disc plates are disposed in the four corners of the juncture so as to reduce the strain caused in the ceramic plate due to their thermal expansion difference and to avoid generation of crack in the ceramic plate. However the displacement due to their thermal expansion difference is large at the corners, cracks may generate in the ceramic plate of the disclosed composite at its corners, because the strain thereat may exceed a withstandable level of the ceramic plate.


Systems and methods are disclosed method for rendering reality for an object by performing motion tracking and area learning of an environment; selecting a pattern or color from a plurality of product variations; blending the pattern or color of the object and the environment; and displaying the color on the object as an augmented reality view.

In fields such as surgery, clothing, footwear, and 3D printing, among others, needs exists for a method to capture the anatomy in the world and either reproduce them with a 3D printer, share, or virtually operate on the anatomical 3D model. Existing system to scan the user in three dimensions require specialized hardware. For example, some systems can create an estimate of the depth of a body by simultaneously acquiring images with multiple image capture devices, by using a known and structured light source, by using a laser solution, or some combination thereof. This creates additional expenses and software requirements for the user.


A device and method for accurately performing quantitative diffuse optical spectroscopy on a sample includes a light source and a source optical fiber that is optically coupled to the light source. A diffuser material is interposed between the source optical fiber and the sample, the diffuser material comprising a high scattering, low absorption material. The diffuser material effectively increases the photon path length from the light source to the sample, which limits the depth of interrogation to superficial volumes despite the penetrating nature of the radiation typically used. A detector optical fiber is provided adjacent to or laterally disposed from the source optical fiber. The detector optical fiber is coupled to a detector which detects photons collected in the detector optical fiber. The detector optical fiber and the source optical fiber may be separated by a distance of less than 5 mm while still permitting the diffusion approximation to remain valid.

Diffuse optical spectroscopy (DOS) using frequency modulated light has been employed to quantify in-vivo tissue constituents as well as the optical properties of in-vivo tissue. Diffuse optical spectroscopy may also be used to quantify chromophore concentration in biological material. Diffusion approximation to the equation of radiative transport provides a useful modeling framework for diffuse optical spectroscopy methods, and generally gives an accurate description of light propagation in thick tissues provided detected photons have undergone at least 10 scattering events before they reach the detector. For example, U.S. Pat. No. 5,424,843 and U.S. patent application Publication No. 20030023172, both of which are incorporated by reference as if set forth fully herein, describe frequency domain spectroscopy methods and devices used in analyzing light scattered from a sample. While the '843 patent and the '172 published application provide a general framework for recovering chromophore concentration and optical properties, neither describes a means for accurately recovering these quantities for superficial tissues or under conditions when the source-detector separation becomes smaller than that allowed by diffusion approximation.
Consequently, current diffuse optical spectroscopy methods are limited to situations in which the reduced scattering coefficient, μs′ is greater (by an order of magnitude) than the absorption coefficient, μa. In practical terms, this limits the DOS technique to source-detector separations of about 5 mm in most tissues (with interrogation depths of about 2.5 mm), wavelengths between 650-1000 nm, and modulation frequencies between 50 and 600 MHz.
As source-detector separation is reduced to distances smaller than 5 mm, the validity of diffusion approximation is reduced along with ability to accurately recover optical properties and chromophore concentrations in existing diffuse optical spectroscopy methods and devices. As the distance between the source and detector becomes smaller, the average number of scattering events that photons experience before detection is also reduced. Similarly as one moves to more highly absorbing spectral domains (e.g., wavelengths shorter than 650 nm and wavelengths longer than 1000 nm), a reduction in source-detector separation is necessary in order to collect light with a reasonable signal to noise (SNR) ratio. In each of these scenarios, however, a simple application of diffusion approximation-based modeling will yield inaccurate tissue optical properties and chromophore concentrations.
U.S. Pat. No. 6,678,541, which is incorporated by reference as if set forth fully herein, discloses an optical fiber probe and methods for measuring optical properties. This approach, however, requires a multi-fiber probe geometry in order to recover tissue optical properties under continuous illumination. The disadvantage of a multi-fiber probe geometry is that each fiber samples a slightly different volume of tissue so there is inherent inaccuracy in the method.
With respect to the problem of quantifying superficial chromophores and their optical properties, prior methods have solved this by primarily using multivariate calibration techniques such as the method of Partial Least Squares (PLS). In this method, signals are acquired from a set of samples that are representative of the sample of interest. The concentration of the analyte of interest must be known for each sample included in the calibration. By sampling many "reference" samples, an empirical model relating spectral shapes to analyte concentration can be developed. The problem with this approach is that the calibration samples have to be very similar to the target (unknown) sample set of interest. In addition, there has to be a way of recovering the true concentration of the analyte of interest in each of those samples, using a separate method, so that a correlative model can be developed.
There thus is a need for device and method which can perform reliable diffuse optical spectroscopy measurements where the source-detector distance is reduced (for example, less than 5 mm). Reducing the distance between the source and detector while still allowing for accurate quantification using diffusion approximation would advantageously allow smaller probe-type devices to be manufactured. In addition, smaller source-detector distances would permit diffuse optical spectroscopy analysis of superficial volumes in biological tissue. The analysis of superficial volumes using diffuse optical spectroscopy has applications for the quantitative characterization of epithelial malignant transformation in tissues which generally occurs at depths of a few tens of microns to a few hundred microns. The method and device would also be able to determine the optical properties and even quantify chromophore (e.g., glucose) concentrations of tissue components in-vivo at superficial depths (tissue depths for determining interstitial tissue glucose concentration/distribution range from a few tens of microns to a few hundreds of microns depending on body site probed). The method and device would have potential intravascular applications to characterize vulnerable plaques, sub-surface pools of lipids, and inflammatory changes occurring in vascular tissue. The method and device would have potential applications in the assessment of effectiveness of pharmaceutical and/or cosmetic formulations that may be used to alter the appearance or "quality" of skin. For example, the device is particularly amenable to measuring changes in superficial tissue hydration. The method and device would have potential applications in the in-situ characterization of skin surface preparations such as sunscreens. Finally, the method may be used in connection with non-biological samples such as, for example, quantifying chemical species in tablet formulations.

Method and apparatus for quantification of optical properties of superficial volumes

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