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Sample records for active cmos microarray

  1. Time-resolved Förster-resonance-energy-transfer DNA assay on an active CMOS microarray

    PubMed Central

    Schwartz, David Eric; Gong, Ping; Shepard, Kenneth L.

    2008-01-01

    We present an active oligonucleotide microarray platform for time-resolved Förster resonance energy transfer (TR-FRET) assays. In these assays, immobilized probe is labeled with a donor fluorophore and analyte target is labeled with a fluorescence quencher. Changes in the fluorescence decay lifetime of the donor are measured to determine the extent of hybridization. In this work, we demonstrate that TR-FRET assays have reduced sensitivity to variances in probe surface density compared with standard fluorescence-based microarray assays. Use of an active array substrate, fabricated in a standard complementary metal-oxide-semiconductor (CMOS) process, provides the additional benefits of reduced system complexity and cost. The array consists of 4096 independent single-photon avalanche diode (SPAD) pixel sites and features on-chip time-to-digital conversion. We demonstrate the functionality of our system by measuring a DNA target concentration series using TR-FRET with semiconductor quantum dot donors. PMID:18515059

  2. CMOS Imaging of Temperature Effects on Pin-Printed Xerogel Sensor Microarrays.

    PubMed

    Lei Yao; Ka Yi Yung; Chodavarapu, Vamsy P; Bright, Frank V

    2011-04-01

    In this paper, we study the effect of temperature on the operation and performance of a xerogel-based sensor microarrays coupled to a complementary metal-oxide semiconductor (CMOS) imager integrated circuit (IC) that images the photoluminescence response from the sensor microarray. The CMOS imager uses a 32 × 32 (1024 elements) array of active pixel sensors and each pixel includes a high-gain phototransistor to convert the detected optical signals into electrical currents. A correlated double sampling circuit and pixel address/digital control/signal integration circuit are also implemented on-chip. The CMOS imager data are read out as a serial coded signal. The sensor system uses a light-emitting diode to excite target analyte responsive organometallic luminophores doped within discrete xerogel-based sensor elements. As a proto type, we developed a 3 × 3 (9 elements) array of oxygen (O2) sensors. Each group of three sensor elements in the array (arranged in a column) is designed to provide a different and specific sensitivity to the target gaseous O2 concentration. This property of multiple sensitivities is achieved by using a mix of two O2 sensitive luminophores in each pin-printed xerogel sensor element. The CMOS imager is designed to be low noise and consumes a static power of 320.4 μW and an average dynamic power of 624.6 μW when operating at 100-Hz sampling frequency and 1.8-V dc power supply.

  3. A 256 pixel magnetoresistive biosensor microarray in 0.18μm CMOS

    PubMed Central

    Hall, Drew A.; Gaster, Richard S.; Makinwa, Kofi; Wang, Shan X.; Murmann, Boris

    2014-01-01

    Magnetic nanotechnologies have shown significant potential in several areas of nanomedicine such as imaging, therapeutics, and early disease detection. Giant magnetoresistive spin-valve (GMR SV) sensors coupled with magnetic nanotags (MNTs) possess great promise as ultra-sensitive biosensors for diagnostics. We report an integrated sensor interface for an array of 256 GMR SV biosensors designed in 0.18 μm CMOS. Arranged like an imager, each of the 16 column level readout channels contains an analog front- end and a compact ΣΔ modulator (0.054 mm2) with 84 dB of dynamic range and an input referred noise of 49 nT/√Hz. Performance is demonstrated through detection of an ovarian cancer biomarker, secretory leukocyte peptidase inhibitor (SLPI), spiked at concentrations as low as 10 fM. This system is designed as a replacement for optical protein microarrays while also providing real-time kinetics monitoring. PMID:24761029

  4. Fluorescence lifetime biosensing with DNA microarrays and a CMOS-SPAD imager

    PubMed Central

    Giraud, Gerard; Schulze, Holger; Li, Day-Uei; Bachmann, Till T.; Crain, Jason; Tyndall, David; Richardson, Justin; Walker, Richard; Stoppa, David; Charbon, Edoardo; Henderson, Robert; Arlt, Jochen

    2010-01-01

    Fluorescence lifetime of dye molecules is a sensitive reporter on local microenvironment which is generally independent of fluorophores concentration and can be used as a means of discrimination between molecules with spectrally overlapping emission. It is therefore a potentially powerful multiplexed detection modality in biosensing but requires extremely low light level operation typical of biological analyte concentrations, long data acquisition periods and on-chip processing capability to realize these advantages. We report here fluorescence lifetime data obtained using a CMOS-SPAD imager in conjunction with DNA microarrays and TIRF excitation geometry. This enables acquisition of single photon arrival time histograms for a 320 pixel FLIM map within less than 26 seconds exposure time. From this, we resolve distinct lifetime signatures corresponding to dye-labelled HCV and quantum-dot-labelled HCMV nucleic acid targets at concentrations as low as 10 nM. PMID:21258550

  5. A 256 pixel magnetoresistive biosensor microarray in 0.18μm CMOS.

    PubMed

    Hall, Drew A; Gaster, Richard S; Makinwa, Kofi; Wang, Shan X; Murmann, Boris

    2013-05-01

    Magnetic nanotechnologies have shown significant potential in several areas of nanomedicine such as imaging, therapeutics, and early disease detection. Giant magnetoresistive spin-valve (GMR SV) sensors coupled with magnetic nanotags (MNTs) possess great promise as ultra-sensitive biosensors for diagnostics. We report an integrated sensor interface for an array of 256 GMR SV biosensors designed in 0.18 μm CMOS. Arranged like an imager, each of the 16 column level readout channels contains an analog front- end and a compact ΣΔ modulator (0.054 mm(2)) with 84 dB of dynamic range and an input referred noise of 49 nT/√Hz. Performance is demonstrated through detection of an ovarian cancer biomarker, secretory leukocyte peptidase inhibitor (SLPI), spiked at concentrations as low as 10 fM. This system is designed as a replacement for optical protein microarrays while also providing real-time kinetics monitoring.

  6. Microarrays Made Simple: "DNA Chips" Paper Activity

    ERIC Educational Resources Information Center

    Barnard, Betsy

    2006-01-01

    DNA microarray technology is revolutionizing biological science. DNA microarrays (also called DNA chips) allow simultaneous screening of many genes for changes in expression between different cells. Now researchers can obtain information about genes in days or weeks that used to take months or years. The paper activity described in this article…

  7. Targeted Deposition of Antibodies on a Multiplex CMOS Microarray and Optimization of a Sensitive Immunoassay Using Electrochemical Detection

    DTIC Science & Technology

    2010-03-19

    sandwich immunoassay used a capture Ab adsorbed to the Ppy and a reporter Ab labeled for fluorescence detection or ECD, and results from these methods of...Targeted Deposition of Antibodies on a Multiplex CMOS Microarray and Optimization of a Sensitive Immunoassay Using Electrochemical Detection John...Sensitive Immunoassay Using Electrochemical Detection 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT

  8. CMOS Imaging of Pin-Printed Xerogel-Based Luminescent Sensor Microarrays.

    PubMed

    Yao, Lei; Yung, Ka Yi; Khan, Rifat; Chodavarapu, Vamsy P; Bright, Frank V

    2010-12-01

    We present the design and implementation of a luminescence-based miniaturized multisensor system using pin-printed xerogel materials which act as host media for chemical recognition elements. We developed a CMOS imager integrated circuit (IC) to image the luminescence response of the xerogel-based sensor array. The imager IC uses a 26 × 20 (520 elements) array of active pixel sensors and each active pixel includes a high-gain phototransistor to convert the detected optical signals into electrical currents. The imager includes a correlated double sampling circuit and pixel address/digital control circuit; the image data is read-out as coded serial signal. The sensor system uses a light-emitting diode (LED) to excite the target analyte responsive luminophores doped within discrete xerogel-based sensor elements. As a prototype, we developed a 4 × 4 (16 elements) array of oxygen (O2) sensors. Each group of 4 sensor elements in the array (arranged in a row) is designed to provide a different and specific sensitivity to the target gaseous O2 concentration. This property of multiple sensitivities is achieved by using a strategic mix of two oxygen sensitive luminophores ([Ru(dpp)3](2+) and ([Ru(bpy)3](2+)) in each pin-printed xerogel sensor element. The CMOS imager consumes an average power of 8 mW operating at 1 kHz sampling frequency driven at 5 V. The developed prototype system demonstrates a low cost and miniaturized luminescence multisensor system.

  9. CMOS Imaging of Pin-Printed Xerogel-Based Luminescent Sensor Microarrays

    PubMed Central

    Yao, Lei; Yung, Ka Yi; Khan, Rifat; Chodavarapu, Vamsy P.; Bright, Frank V.

    2014-01-01

    We present the design and implementation of a luminescence-based miniaturized multisensor system using pin-printed xerogel materials which act as host media for chemical recognition elements. We developed a CMOS imager integrated circuit (IC) to image the luminescence response of the xerogel-based sensor array. The imager IC uses a 26 × 20 (520 elements) array of active pixel sensors and each active pixel includes a high-gain phototransistor to convert the detected optical signals into electrical currents. The imager includes a correlated double sampling circuit and pixel address/digital control circuit; the image data is read-out as coded serial signal. The sensor system uses a light-emitting diode (LED) to excite the target analyte responsive luminophores doped within discrete xerogel-based sensor elements. As a prototype, we developed a 4 × 4 (16 elements) array of oxygen (O2) sensors. Each group of 4 sensor elements in the array (arranged in a row) is designed to provide a different and specific sensitivity to the target gaseous O2 concentration. This property of multiple sensitivities is achieved by using a strategic mix of two oxygen sensitive luminophores ([Ru(dpp)3]2+ and ([Ru(bpy)3]2+) in each pin-printed xerogel sensor element. The CMOS imager consumes an average power of 8 mW operating at 1 kHz sampling frequency driven at 5 V. The developed prototype system demonstrates a low cost and miniaturized luminescence multisensor system. PMID:24489484

  10. CMOS Active Pixel Sensor Technology and Reliability Characterization Methodology

    NASA Technical Reports Server (NTRS)

    Chen, Yuan; Guertin, Steven M.; Pain, Bedabrata; Kayaii, Sammy

    2006-01-01

    This paper describes the technology, design features and reliability characterization methodology of a CMOS Active Pixel Sensor. Both overall chip reliability and pixel reliability are projected for the imagers.

  11. Microarrays

    ERIC Educational Resources Information Center

    Plomin, Robert; Schalkwyk, Leonard C.

    2007-01-01

    Microarrays are revolutionizing genetics by making it possible to genotype hundreds of thousands of DNA markers and to assess the expression (RNA transcripts) of all of the genes in the genome. Microarrays are slides the size of a postage stamp that contain millions of DNA sequences to which single-stranded DNA or RNA can hybridize. This…

  12. CMOS Active-Pixel Image Sensor With Simple Floating Gates

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R.; Nakamura, Junichi; Kemeny, Sabrina E.

    1996-01-01

    Experimental complementary metal-oxide/semiconductor (CMOS) active-pixel image sensor integrated circuit features simple floating-gate structure, with metal-oxide/semiconductor field-effect transistor (MOSFET) as active circuit element in each pixel. Provides flexibility of readout modes, no kTC noise, and relatively simple structure suitable for high-density arrays. Features desirable for "smart sensor" applications.

  13. CMOS VLSI Active-Pixel Sensor for Tracking

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata; Sun, Chao; Yang, Guang; Heynssens, Julie

    2004-01-01

    An architecture for a proposed active-pixel sensor (APS) and a design to implement the architecture in a complementary metal oxide semiconductor (CMOS) very-large-scale integrated (VLSI) circuit provide for some advanced features that are expected to be especially desirable for tracking pointlike features of stars. The architecture would also make this APS suitable for robotic- vision and general pointing and tracking applications. CMOS imagers in general are well suited for pointing and tracking because they can be configured for random access to selected pixels and to provide readout from windows of interest within their fields of view. However, until now, the architectures of CMOS imagers have not supported multiwindow operation or low-noise data collection. Moreover, smearing and motion artifacts in collected images have made prior CMOS imagers unsuitable for tracking applications. The proposed CMOS imager (see figure) would include an array of 1,024 by 1,024 pixels containing high-performance photodiode-based APS circuitry. The pixel pitch would be 9 m. The operations of the pixel circuits would be sequenced and otherwise controlled by an on-chip timing and control block, which would enable the collection of image data, during a single frame period, from either the full frame (that is, all 1,024 1,024 pixels) or from within as many as 8 different arbitrarily placed windows as large as 8 by 8 pixels each. A typical prior CMOS APS operates in a row-at-a-time ( grolling-shutter h) readout mode, which gives rise to exposure skew. In contrast, the proposed APS would operate in a sample-first/readlater mode, suppressing rolling-shutter effects. In this mode, the analog readout signals from the pixels corresponding to the windows of the interest (which windows, in the star-tracking application, would presumably contain guide stars) would be sampled rapidly by routing them through a programmable diagonal switch array to an on-chip parallel analog memory array. The

  14. Profiling glycosyltransferase activities by tritium imaging of glycan microarrays.

    PubMed

    Serna, Sonia; Hokke, Cornelis H; Weissenborn, Martin; Flitsch, Sabine; Martin-Lomas, Manuel; Reichardt, Niels-Christian

    2013-05-10

    High-throughput microarray technology has been combined with ultrasensitive and high-resolution tritium autoradiography to create a new platform for the quantitative detection of glycosyltransferase activity on glycan arrays. In addition, we show full compatibility with the use of fluorescently labeled lectins to help with the stereochemical assignment of newly formed glycoside linkages.

  15. Proof of principle study of the use of a CMOS active pixel sensor for proton radiography

    SciTech Connect

    Seco, Joao; Depauw, Nicolas

    2011-02-15

    Purpose: Proof of principle study of the use of a CMOS active pixel sensor (APS) in producing proton radiographic images using the proton beam at the Massachusetts General Hospital (MGH). Methods: A CMOS APS, previously tested for use in s-ray radiation therapy applications, was used for proton beam radiographic imaging at the MGH. Two different setups were used as a proof of principle that CMOS can be used as proton imaging device: (i) a pen with two metal screws to assess spatial resolution of the CMOS and (ii) a phantom with lung tissue, bone tissue, and water to assess tissue contrast of the CMOS. The sensor was then traversed by a double scattered monoenergetic proton beam at 117 MeV, and the energy deposition inside the detector was recorded to assess its energy response. Conventional x-ray images with similar setup at voltages of 70 kVp and proton images using commercial Gafchromic EBT 2 and Kodak X-Omat V films were also taken for comparison purposes. Results: Images were successfully acquired and compared to x-ray kVp and proton EBT2/X-Omat film images. The spatial resolution of the CMOS detector image is subjectively comparable to the EBT2 and Kodak X-Omat V film images obtained at the same object-detector distance. X-rays have apparent higher spatial resolution than the CMOS. However, further studies with different commercial films using proton beam irradiation demonstrate that the distance of the detector to the object is important to the amount of proton scatter contributing to the proton image. Proton images obtained with films at different distances from the source indicate that proton scatter significantly affects the CMOS image quality. Conclusion: Proton radiographic images were successfully acquired at MGH using a CMOS active pixel sensor detector. The CMOS demonstrated spatial resolution subjectively comparable to films at the same object-detector distance. Further work will be done in order to establish the spatial and energy resolution of the

  16. Integrated imaging sensor systems with CMOS active pixel sensor technology

    NASA Technical Reports Server (NTRS)

    Yang, G.; Cunningham, T.; Ortiz, M.; Heynssens, J.; Sun, C.; Hancock, B.; Seshadri, S.; Wrigley, C.; McCarty, K.; Pain, B.

    2002-01-01

    This paper discusses common approaches to CMOS APS technology, as well as specific results on the five-wire programmable digital camera-on-a-chip developed at JPL. The paper also reports recent research in the design, operation, and performance of APS imagers for several imager applications.

  17. Radiation tolerance of CMOS monolithic active pixel sensors with self-biased pixels

    NASA Astrophysics Data System (ADS)

    Deveaux, M.; Amar-Youcef, S.; Besson, A.; Claus, G.; Colledani, C.; Dorokhov, M.; Dritsa, C.; Dulinski, W.; Fröhlich, I.; Goffe, M.; Grandjean, D.; Heini, S.; Himmi, A.; Hu, C.; Jaaskelainen, K.; Müntz, C.; Shabetai, A.; Stroth, J.; Szelezniak, M.; Valin, I.; Winter, M.

    2010-12-01

    CMOS monolithic active pixel sensors (MAPS) are proposed as a technology for various vertex detectors in nuclear and particle physics. We discuss the mechanisms of ionizing radiation damage on MAPS hosting the dead time free, so-called self bias pixel. Moreover, we introduce radiation hardened sensor designs which allow operating detectors after exposing them to irradiation doses above 1 Mrad.

  18. Passive radiation detection using optically active CMOS sensors

    NASA Astrophysics Data System (ADS)

    Dosiek, Luke; Schalk, Patrick D.

    2013-05-01

    Recently, there have been a number of small-scale and hobbyist successes in employing commodity CMOS-based camera sensors for radiation detection. For example, several smartphone applications initially developed for use in areas near the Fukushima nuclear disaster are capable of detecting radiation using a cell phone camera, provided opaque tape is placed over the lens. In all current useful implementations, it is required that the sensor not be exposed to visible light. We seek to build a system that does not have this restriction. While building such a system would require sophisticated signal processing, it would nevertheless provide great benefits. In addition to fulfilling their primary function of image capture, cameras would also be able to detect unknown radiation sources even when the danger is considered to be low or non-existent. By experimentally profiling the image artifacts generated by gamma ray and β particle impacts, algorithms are developed to identify the unique features of radiation exposure, while discarding optical interaction and thermal noise effects. Preliminary results focus on achieving this goal in a laboratory setting, without regard to integration time or computational complexity. However, future work will seek to address these additional issues.

  19. Which Members of the Microbial Communities Are Active? Microarrays

    NASA Astrophysics Data System (ADS)

    Morris, Brandon E. L.

    only at the early stages of understanding the microbial processes that occur in petroliferous formations and the surrounding subterranean environment. Important first steps in characterising the microbiology of oilfield systems involve identifying the microbial community structure and determining how population diversity changes are affected by the overall geochemical and biological parameters of the system. This is relatively easy to do today by using general 16S rRNA primers for PCR and building clone libraries. For example, previous studies using molecular methods characterised many dominant prokaryotes in petroleum reservoirs (Orphan et al., 2000) and in two Alaskan North Slope oil facilities (Duncan et al., 2009; Pham et al., 2009). However, the problem is that more traditional molecular biology approaches, such as 16S clone libraries, fail to detect large portions of the community perhaps missing up to half of the biodiversity (see Hong et al., 2009) and require significant laboratory time to construct large libraries necessary to increase the probability of detecting the majority of even bacterial biodiversity. In the energy sector, the overarching desire would be to quickly assess the extent of in situ hydrocarbon biodegradation or to disrupt detrimental processes such as biofouling, and in these cases it may not be necessary to identify specific microbial species. Rather, it would be more critical to evaluate metabolic processes or monitor gene products that are implicated in the specific activity of interest. Research goals such as these are well suited for a tailored application of microarray technology.

  20. A Highly Linear and Wide Input Range Four-Quadrant CMOS Analog Multiplier Using Active Feedback

    NASA Astrophysics Data System (ADS)

    Huang, Zhangcai; Jiang, Minglu; Inoue, Yasuaki

    Analog multipliers are one of the most important building blocks in analog signal processing circuits. The performance with high linearity and wide input range is usually required for analog four-quadrant multipliers in most applications. Therefore, a highly linear and wide input range four-quadrant CMOS analog multiplier using active feedback is proposed in this paper. Firstly, a novel configuration of four-quadrant multiplier cell is presented. Its input dynamic range and linearity are improved significantly by adding two resistors compared with the conventional structure. Then based on the proposed multiplier cell configuration, a four-quadrant CMOS analog multiplier with active feedback technique is implemented by two operational amplifiers. Because of both the proposed multiplier cell and active feedback technique, the proposed multiplier achieves a much wider input range with higher linearity than conventional structures. The proposed multiplier was fabricated by a 0.6µm CMOS process. Experimental results show that the input range of the proposed multiplier can be up to 5.6Vpp with 0.159% linearity error on VX and 4.8Vpp with 0.51% linearity error on VY for ±2.5V power supply voltages, respectively.

  1. Performance of a novel wafer scale CMOS active pixel sensor for bio-medical imaging

    NASA Astrophysics Data System (ADS)

    Esposito, M.; Anaxagoras, T.; Konstantinidis, A. C.; Zheng, Y.; Speller, R. D.; Evans, P. M.; Allinson, N. M.; Wells, K.

    2014-07-01

    Recently CMOS active pixels sensors (APSs) have become a valuable alternative to amorphous silicon and selenium flat panel imagers (FPIs) in bio-medical imaging applications. CMOS APSs can now be scaled up to the standard 20 cm diameter wafer size by means of a reticle stitching block process. However, despite wafer scale CMOS APS being monolithic, sources of non-uniformity of response and regional variations can persist representing a significant challenge for wafer scale sensor response. Non-uniformity of stitched sensors can arise from a number of factors related to the manufacturing process, including variation of amplification, variation between readout components, wafer defects and process variations across the wafer due to manufacturing processes. This paper reports on an investigation into the spatial non-uniformity and regional variations of a wafer scale stitched CMOS APS. For the first time a per-pixel analysis of the electro-optical performance of a wafer CMOS APS is presented, to address inhomogeneity issues arising from the stitching techniques used to manufacture wafer scale sensors. A complete model of the signal generation in the pixel array has been provided and proved capable of accounting for noise and gain variations across the pixel array. This novel analysis leads to readout noise and conversion gain being evaluated at pixel level, stitching block level and in regions of interest, resulting in a coefficient of variation ⩽1.9%. The uniformity of the image quality performance has been further investigated in a typical x-ray application, i.e. mammography, showing a uniformity in terms of CNR among the highest when compared with mammography detectors commonly used in clinical practice. Finally, in order to compare the detection capability of this novel APS with the technology currently used (i.e. FPIs), theoretical evaluation of the detection quantum efficiency (DQE) at zero-frequency has been performed, resulting in a higher DQE for this

  2. Performance of a novel wafer scale CMOS active pixel sensor for bio-medical imaging.

    PubMed

    Esposito, M; Anaxagoras, T; Konstantinidis, A C; Zheng, Y; Speller, R D; Evans, P M; Allinson, N M; Wells, K

    2014-07-07

    Recently CMOS active pixels sensors (APSs) have become a valuable alternative to amorphous silicon and selenium flat panel imagers (FPIs) in bio-medical imaging applications. CMOS APSs can now be scaled up to the standard 20 cm diameter wafer size by means of a reticle stitching block process. However, despite wafer scale CMOS APS being monolithic, sources of non-uniformity of response and regional variations can persist representing a significant challenge for wafer scale sensor response. Non-uniformity of stitched sensors can arise from a number of factors related to the manufacturing process, including variation of amplification, variation between readout components, wafer defects and process variations across the wafer due to manufacturing processes. This paper reports on an investigation into the spatial non-uniformity and regional variations of a wafer scale stitched CMOS APS. For the first time a per-pixel analysis of the electro-optical performance of a wafer CMOS APS is presented, to address inhomogeneity issues arising from the stitching techniques used to manufacture wafer scale sensors. A complete model of the signal generation in the pixel array has been provided and proved capable of accounting for noise and gain variations across the pixel array. This novel analysis leads to readout noise and conversion gain being evaluated at pixel level, stitching block level and in regions of interest, resulting in a coefficient of variation ⩽1.9%. The uniformity of the image quality performance has been further investigated in a typical x-ray application, i.e. mammography, showing a uniformity in terms of CNR among the highest when compared with mammography detectors commonly used in clinical practice. Finally, in order to compare the detection capability of this novel APS with the technology currently used (i.e. FPIs), theoretical evaluation of the detection quantum efficiency (DQE) at zero-frequency has been performed, resulting in a higher DQE for this

  3. Assessing Design Activity in Complex CMOS Circuit Design.

    ERIC Educational Resources Information Center

    Biswas, Gautam; And Others

    This report characterizes human problem solving in digital circuit design. Protocols of 11 different designers with varying degrees of training were analyzed by identifying the designers' problem solving strategies and discussing activity patterns that differentiate the designers. These methods are proposed as a tentative basis for assessing…

  4. Peptide microarrays for the profiling of cytotoxic T-lymphocyte activity using minimum numbers of cells.

    PubMed

    Hoff, Antje; Bagû, Ana-Cristina; André, Thomas; Roth, Günter; Wiesmüller, Karl-Heinz; Gückel, Brigitte; Brock, Roland

    2010-09-01

    The identification of epitopes that elicit cytotoxic T-lymphocyte activity is a prerequisite for the development of cancer-specific immunotherapies. However, especially the parallel characterization of several epitopes is limited by the availability of T cells. Microarrays have enabled an unprecedented miniaturization and parallelization in biological assays. Here, we developed peptide microarrays for the detection of CTL activity. MHC class I-binding peptide epitopes were pipetted onto polymer-coated glass slides. Target cells, loaded with the cell-impermeant dye calcein, were incubated on these arrays, followed by incubation with antigen-expanded CTLs. Cytotoxic activity was detected by release of calcein and detachment of target cells. With only 200,000 cells per microarray, CTLs could be detected at a frequency of 0.5% corresponding to 1,000 antigen-specific T cells. Target cells and CTLs only settled on peptide spots enabling a clear separation of individual epitopes. Even though no physical boundaries were present between the individual spots, peptide loading only occurred locally and cytolytic activity was confined to the spots carrying the specific epitope. The peptide microarrays provide a robust platform that implements the whole process from antigen presentation to the detection of CTL activity in a miniaturized format. The method surpasses all established methods in the minimum numbers of cells required. With antigen uptake occurring on the microarray, further applications are foreseen in the testing of antigen precursors that require uptake and processing prior to presentation.

  5. A CMOS Active Pixel Sensor for Charged Particle Detection

    SciTech Connect

    Matis, Howard S.; Bieser, Fred; Kleinfelder, Stuart; Rai, Gulshan; Retiere, Fabrice; Ritter, Hans George; Singh, Kunal; Wurzel, Samuel E.; Wieman, Howard; Yamamoto, Eugene

    2002-12-02

    Active Pixel Sensor (APS) technology has shown promise for next-generation vertex detectors. This paper discusses the design and testing of two generations of APS chips. Both are arrays of 128 by 128 pixels, each 20 by 20 {micro}m. Each array is divided into sub-arrays in which different sensor structures (4 in the first version and 16 in the second) and/or readout circuits are employed. Measurements of several of these structures under Fe{sup 55} exposure are reported. The sensors have also been irradiated by 55 MeV protons to test for radiation damage. The radiation increased the noise and reduced the signal. The noise can be explained by shot noise from the increased leakage current and the reduction in signal is due to charge being trapped in the epi layer. Nevertheless, the radiation effect is small for the expected exposures at RHIC and RHIC II. Finally, we describe our concept for mechanically supporting a thin silicon wafer in an actual detector.

  6. Development of a new electronic personal neutron dosemeter using a CMOS active pixel sensor.

    PubMed

    Trocmé, M; Higueret, S; Husson, D; Nourreddine, A; Lê, T D

    2007-01-01

    A CMOS active pixel sensor, originally designed for the tracking of minimum ionising charged particles in high-energy physics, has been recently used for the detection of fast neutrons. Data were taken at the IRSN Cadarache facility with a (241)Am-Be ISO source and a polyethylene radiator. A high-intrinsic efficiency (1.2 x 10(-3)) has been obtained. It is in good agreement with both calculations and a MCNPX Monte Carlo simulation. This experiment paves the way for a fully electronic personal neutron dosemeter.

  7. Development of CMOS Active Pixel Image Sensors for Low Cost Commercial Applications

    NASA Technical Reports Server (NTRS)

    Fossum, E.; Gee, R.; Kemeny, S.; Kim, Q.; Mendis, S.; Nakamura, J.; Nixon, R.; Ortiz, M.; Pain, B.; Zhou, Z.; Ackland, B.; Dickinson, A.; Eid, E.; Inglis, D.

    1994-01-01

    This paper describes ongoing research and development of CMOS active pixel image sensors for low cost commercial applications. A number of sensor designs have been fabricated and tested in both p-well and n-well technologies. Major elements in the development of the sensor include on-chip analog signal processing circuits for the reduction of fixed pattern noise, on-chip timing and control circuits and on-chip analog-to-digital conversion (ADC). Recent results and continuing efforts in these areas will be presented.

  8. Use of a multiplexed CMOS microarray to optimize and compare oligonucleotide binding to DNA probes synthesized or immobilized on individual electrodes.

    PubMed

    Maurer, Karl; Yazvenko, Nina; Wilmoth, Jodi; Cooper, John; Lyon, Wanda; Danley, David

    2010-01-01

    The CombiMatrix microarray with 12,544 electrodes supports in situ electrochemical synthesis of user-defined DNA probes. As an alternative, we immobilized commercially synthesized DNA probes on individual electrodes coated with electropolymerized polypyrrole (Ppy). Hybridization was measured using a biotinylated target oligonucleotide and either Cy5-streptavidin and fluorescence detection or horseradish peroxidase-streptavidin and enzyme-enhanced electrochemical detection. Detection efficiencies were optimized by varying the deposition of the Ppy, the terminal groups on the DNA probes, and other factors that impacted fluorescence quenching and electrical conductivity. Optimized results were compared against those obtained using a microarray with the same DNA sequences synthesized in situ. Immobilized probes produced higher fluorescence signals, possibly by providing a greater stand off between the Cy5 on the target oligonucleotide and the quenching effects of the Ppy and the platinum electrode.

  9. A CMOS Energy Harvesting and Imaging (EHI) Active Pixel Sensor (APS) Imager for Retinal Prosthesis.

    PubMed

    Ay, S U

    2011-12-01

    A CMOS image sensor capable of imaging and energy harvesting on same focal plane is presented for retinal prosthesis. The energy harvesting and imaging (EHI) active pixel sensor (APS) imager was designed, fabricated, and tested in a standard 0.5 μm CMOS process. It has 54 × 50 array of 21 × 21 μm(2) EHI pixels, 10-bit supply boosted (SB) SAR ADC, and charge pump circuits consuming only 14.25 μW from 1.2 V and running at 7.4 frames per second. The supply boosting technique (SBT) is used in an analog signal chain of the EHI imager. Harvested solar energy on focal plane is stored on an off-chip capacitor with the help of a charge pump circuit with better than 70% efficiency. Energy harvesting efficiency of the EHI pixel was measured at different light levels. It was 9.4% while producing 0.41 V open circuit voltage. The EHI imager delivers 3.35 μW of power was delivered to a resistive load at maximum power point operation. The measured pixel array figure of merit (FoM) was 1.32 pW/frame/pixel while imager figure of merit (iFoM) including whole chip power consumption was 696 fJ/pixel/code for the EHI imager.

  10. Evaluation of Quantum dot immunofluorescence and a digital CMOS imaging system as an alternative to conventional organic fluorescence dyes and laser scanning for quantifying protein microarrays

    PubMed Central

    Jain, Aarti; Taghavian, Omid; Vallejo, Derek; Dotsey, Emmanuel; Schwartz, Dan; Bell, Florian G.; Greef, Chad; Davies, D. Huw; Grudzien, Jennipher; Lee, Abraham P.; Felgner, Philip; Liang, Li

    2016-01-01

    Organic fluorescent dyes are widely used for the visualization of bound antibody in a variety of immunofluorescence assays. However, the detection equipment is often expensive, fragile and hard to deploy widely. Quantum dots (Qdot®) are nanocrystals made of semiconductor materials that emit light at different wavelengths according to the size of the crystal, with increased brightness and stability. Here we have evaluated a small benchtop ‘personal’ optical imager (ArrayCAM™) developed for quantification of protein arrays probed by Qdot -based indirect immunofluorescence. The aim was to determine if the Qdot imager system provides equivalent data to the conventional organic dye-labelled antibody/laser scanner system. To do this, duplicate proteome microarrays of Vaccinia virus, Brucella melitensis and Plasmodium falciparum were probed with identical samples of immune sera, and IgG, IgA and IgM profiles visualized using biotinylated secondary antibodies followed by a tertiary reagent of streptavidin coupled to either P3 (an organic cyanine dye typically used for microarrays) or Q800 (Qdot). The data show excellent correlation for all samples tested (R>0.8) with no significant change of antibody reactivity profiles. We conclude that Qdot detection provides data equivalent to that obtained using conventional organic dye detection. The portable imager offers an economical, more robust and deployable alternative to conventional laser array scanners. PMID:26842269

  11. CMOS common-mode rejection filter with floating active transformer operation

    NASA Astrophysics Data System (ADS)

    Uchida, Daisuke; Ikebe, Masayuki; Motohisa, Junichi; Sano, Eiichi; Kondou, Akira

    2014-01-01

    We propose an inductorless common-mode rejection filter with a gyrator-C network for common-mode-noise reduction. By adopting a gyrator-C network and ladder structure, high-order and small filter circuits with active transformer operation were fabricated. The filter was designed and fabricated in a Taiwan Semiconductor Manufacturing Company (TSMC) 0.18 µm CMOS process. This filter exhibited a CMRR of 80 dB, output noise voltage of 103 nV/Hz1/2, third-order input intercept point of 8.8 dBm at 1 MHz operation, and cutoff frequency of under 6 MHz. The total power consumption was 14.8 mW with a 2.5 V supply, and the chip area was 0.7 × 0.4 mm2.

  12. Improved Design of Active Pixel CMOS Sensors for Charged Particle Detection

    SciTech Connect

    Deptuch, Grzegorz

    2007-11-12

    The Department of Energy (DOE) nuclear physics program requires developments in detector instrumentation electronics with improved energy, position and timing resolution, sensitivity, rate capability, stability, dynamic range, and background suppression. The current Phase-I project was focused on analysis of standard-CMOS photogate Active Pixel Sensors (APS) as an efficient solution to this challenge. The advantages of the CMOS APS over traditional hybrid approaches (i.e., separate detection regions bump-bonded to readout circuits) include greatly reduced cost, low power and the potential for vastly larger pixel counts and densities. However, challenges remain in terms of the signal-to-noise ratio (SNR) and readout speed (currently on the order of milliseconds), which is the major problem for this technology. Recent work has shown that the long readout time for photogate APS is due to the presence of (interface) traps at the semiconductor-oxide interface. This Phase-I work yielded useful results in two areas: (a) Advanced three-dimensional (3D) physics-based simulation models and simulation-based analysis of the impact of interface trap density on the transient charge collection characteristics of existing APS structures; and (b) Preliminary analysis of the feasibility of an improved photogate pixel structure (i.e., new APS design) with an induced electric field under the charge collecting electrode to enhance charge collection. Significant effort was dedicated in Phase-I to the critical task of implementing accurate interface trap models in CFDRC's NanoTCAD 3D semiconductor device-physics simulator. This resulted in validation of the new NanoTCAD models and simulation results against experimental (published) data, within the margin of uncertainty associated with obtaining device geometry, material properties, and experimentation details. Analyses of the new, proposed photogate APS design demonstrated several promising trends.

  13. Screening for novel human genes associated with CRE pathway activation with cell microarray.

    PubMed

    Tian, Linjie; Wang, Pingzhang; Guo, Jinhai; Wang, Xinyu; Deng, Weiwei; Zhang, Chenying; Fu, Dongxu; Gao, Xia; Shi, Taiping; Ma, Dalong

    2007-07-01

    In this study, cell microarray technology is used to identify novel human genes associated with CRE pathway activation. By reverse transfection, expression plasmids containing full-length cDNAs were cotransfected with the reporter plasmid pCRE-d2EGFP to monitor the activation of the CRE pathway via enhanced green fluorescence protein (EGFP) expression. Of the 575 predominantly novel genes screened, 22 exhibited relatively higher EGFP fluorescence compared with a negative control. After a functional validation with a dual luciferase reporter system that included both cis- and trans-luciferase assays, 4 of the 22 genes (RNF41, C8orf32, C6orf208, and MEIS3P1) were confirmed as CRE-pathway activators. Western blot analysis revealed that RNF41 can promote CREB phosphorylation. These results demonstrate the successful combination of cell microarray technology with this reporting system and the potential of this tool to characterize functions of novel genes in a highly parallel format.

  14. A perforated CMOS microchip for immobilization and activity monitoring of electrogenic cells

    NASA Astrophysics Data System (ADS)

    Greve, F.; Lichtenberg, J.; Kirstein, K.-U.; Frey, U.; Perriard, J.-C.; Hierlemann, A.

    2007-03-01

    CMOS-based microelectrode systems offer decisive advantages over conventional micro-electrode arrays, which include the possibility to perform on-chip signal conditioning or to efficiently use larger numbers of electrodes to obtain statistically relevant data, e.g., in pharmacological drug screening. A larger number of electrodes can only be realized with the help of on-chip multiplexing and readout schemes, which require integrated electronics. Another fundamental issue in performing high-fidelity recordings from electrogenic cells is a good electrical coupling between the cells and the microelectrodes, in particular, since the recorded extracellular signals are in the range of only 10-1000 µV. In this paper we present the first CMOS microelectrode system with integrated micromechanical cell-placement features fabricated in a commercial CMOS process with subsequent post-CMOS bulk micromachining. This new microdevice aims at enabling the precise placement of single cells in the center of the electrodes to ensure an efficient use of the available electrodes, even for low-density cell cultures. Small through-chip holes have been generated at the metal-electrode sites by using a combination of bulk micromachining and reactive-ion etching. These holes act as orifices so that cell immobilization can be achieved by means of pneumatic anchoring. The chip additionally hosts integrated circuitry, i.e., multiplexers to select the respective readout electrodes, an amplifier with selectable gain (2×, 10×, 100×), and a high-pass filter (100 Hz cut-off). In this paper we show that electrical signals from most of the electrodes can be recorded, even in low-density cultures of neonatal rat cardiomyocytes, by using perforated metal electrodes and by applying a small underpressure from the backside of the chip. The measurements evidenced that, in most cases, about 90% of the electrodes were covered with single cells, approximately 4% were covered with more than one cell due to

  15. Active pixel sensors in AMS H18/H35 HV-CMOS technology for the ATLAS HL-LHC upgrade

    NASA Astrophysics Data System (ADS)

    Ristic, Branislav

    2016-09-01

    Deep sub micron HV-CMOS processes offer the opportunity for sensors built by industry standard techniques while being HV tolerant, making them good candidates for drift-based, fast collecting, thus radiation-hard pixel detectors. For the upgrade of the ATLAS Pixel Detector towards the HL-LHC requirements, active pixel sensors in HV-CMOS technology were investigated. These implement signal processing electronics in deep n-wells, which also act as collecting electrodes. The deep n-wells allow for bias voltages up to 150 V leading to a depletion depth of several 10 μm. Prototype sensors in the AMS H18 180 nm and H35 350 nm HV-CMOS processes were thoroughly tested in lab measurements as well as in testbeam experiments. Irradiations with X-rays and protons revealed a tolerance to ionizing doses of 1 Grad while Edge-TCT studies assessed the effects of radiation on the charge collection. The sensors showed high detection efficiencies after neutron irradiation to 1015neq cm-2 in testbeam experiments. A full reticle size demonstrator chip, implemented in the H35 process is being submitted to prove the large scale feasibility of the HV-CMOS concept.

  16. The Dexela 2923 CMOS X-ray detector: A flat panel detector based on CMOS active pixel sensors for medical imaging applications

    NASA Astrophysics Data System (ADS)

    Konstantinidis, Anastasios C.; Szafraniec, Magdalena B.; Speller, Robert D.; Olivo, Alessandro

    2012-10-01

    Complementary metal-oxide-semiconductors (CMOS) active pixel sensors (APS) have been introduced recently in many scientific applications. This work reports on the performance (in terms of signal and noise transfer) of an X-ray detector that uses a novel CMOS APS which was developed for medical X-ray imaging applications. For a full evaluation of the detector's performance, electro-optical and X-ray characterizations were carried out. The former included measuring read noise, full well capacity and dynamic range. The latter, which included measuring X-ray sensitivity, presampling modulation transfer function (pMTF), noise power spectrum (NPS) and the resulting detective quantum efficiency (DQE), was assessed under three beam qualities (28 kV, 50 kV (RQA3) and 70 kV (RQA5) using W/Al) all in accordance with the IEC standard. The detector features an in-pixel option for switching the full well capacity between two distinct modes, high full well (HFW) and low full well (LFW). Two structured CsI:Tl scintillators of different thickness (a “thin” one for high resolution and a thicker one for high light efficiency) were optically coupled to the sensor array to optimize the performance of the system for different medical applications. The electro-optical performance evaluation of the sensor results in relatively high read noise (∼360 e-), high full well capacity (∼1.5×106 e-) and wide dynamic range (∼73 dB) under HFW mode operation. When the LFW mode is used, the read noise is lower (∼165) at the expense of a reduced full well capacity (∼0.5×106 e-) and dynamic range (∼69 dB). The maximum DQE values at low frequencies (i.e. 0.5 lp/mm) are high for both HFW (0.69 for 28 kV, 0.71 for 50 kV and 0.75 for 70 kV) and LFW (0.69 for 28 kV and 0.7 for 50 kV) modes. The X-ray performance of the studied detector compares well to that of other mammography and general radiography systems, obtained under similar experimental conditions. This demonstrates the suitability

  17. Wavelet-based detection of transcriptional activity on a novel Staphylococcus aureus tiling microarray

    PubMed Central

    2012-01-01

    Background High-density oligonucleotide microarray is an appropriate technology for genomic analysis, and is particulary useful in the generation of transcriptional maps, ChIP-on-chip studies and re-sequencing of the genome.Transcriptome analysis of tiling microarray data facilitates the discovery of novel transcripts and the assessment of differential expression in diverse experimental conditions. Although new technologies such as next-generation sequencing have appeared, microarrays might still be useful for the study of small genomes or for the analysis of genomic regions with custom microarrays due to their lower price and good accuracy in expression quantification. Results Here, we propose a novel wavelet-based method, named ZCL (zero-crossing lines), for the combined denoising and segmentation of tiling signals. The denoising is performed with the classical SUREshrink method and the detection of transcriptionally active regions is based on the computation of the Continuous Wavelet Transform (CWT). In particular, the detection of the transitions is implemented as the thresholding of the zero-crossing lines. The algorithm described has been applied to the public Saccharomyces cerevisiae dataset and it has been compared with two well-known algorithms: pseudo-median sliding window (PMSW) and the structural change model (SCM). As a proof-of-principle, we applied the ZCL algorithm to the analysis of the custom tiling microarray hybridization results of a S. aureus mutant deficient in the sigma B transcription factor. The challenge was to identify those transcripts whose expression decreases in the absence of sigma B. Conclusions The proposed method archives the best performance in terms of positive predictive value (PPV) while its sensitivity is similar to the other algorithms used for the comparison. The computation time needed to process the transcriptional signals is low as compared with model-based methods and in the same range to those based on the use of

  18. Linear analysis of signal and noise characteristics of a nonlinear CMOS active-pixel detector for mammography

    NASA Astrophysics Data System (ADS)

    Yun, Seungman; Kim, Ho Kyung; Han, Jong Chul; Kam, Soohwa; Youn, Hanbean; Cunningham, Ian A.

    2017-03-01

    The imaging properties of a complementary metal-oxide-semiconductor (CMOS) active-pixel photodiode array coupled to a thin gadolinium-based granular phosphor screen with a fiber-optic faceplate are investigated. It is shown that this system has a nonlinear response at low detector exposure levels (<10 mR), resulting in an over-estimation of the detective quantum efficiency (DQE) by a factor of two in some cases. Errors in performance metrics on this scale make it difficult to compare new technologies with established systems and predict performance benchmarks that can be achieved in practice and help understand performance bottlenecks. It is shown the CMOS response is described by a power-law model that can be used to linearize image data. Linearization removed an unexpected dependence of the DQE on detector exposure level.

  19. Characterization of CMOS Active Pixel Sensors for particle detection: Beam test of the four-sensors RAPS03 stacked system

    NASA Astrophysics Data System (ADS)

    Passeri, Daniele; Servoli, Leonello; Biagetti, Daniele; Meroli, Stefano

    2010-05-01

    In this work, in order to check the suitability of CMOS Active Pixel Sensors (APS) detectors for vertexing/tracking applications, four stacked CMOS APS sensors featuring 256×256 pixels with 10×10 μm 2 size have been tested at the INFN Beam Test Facility (BFT), Frascati (Rome). For this purpose, a dedicated mechanical and electrical set-up has been devised and implemented, allowing for the simultaneous read-out of four sensors arranged in a stacked structure. A compact and fast system (up to 64 MHz read-out clock) based on external ADCs and FPGA allows for the PC communication through USB2.0. Preliminary results in terms of track reconstructions of electrons of different energies (up to 496 MeV) are presented. This work has been carried out within the framework of the SHARPS project, supported by INFN.

  20. Quantification of the activity of biomolecules in microarrays obtained by direct laser transfer.

    PubMed

    Dinca, V; Ranella, A; Farsari, M; Kafetzopoulos, D; Dinescu, M; Popescu, A; Fotakis, C

    2008-10-01

    The direct-writing technique laser-induced forward transfer has been employed for the micro-array printing of liquid solutions of the enzyme horseradish peroxidase and the protein Titin on nitrocellulose solid surfaces. The effect of two UV laser pulse lengths, femtosecond and nanosecond has been studied in relation with maintaining the activity of the transferred biomolecules. The quantification of the active biomolecules after transfer has been carried out using Bradford assay, quantitative colorimetric enzymatic assay and fluorescence techniques. Spectrophotometric measurements of the HRP and the Titin activity as well as chromatogenic and fluorescence assay studies have revealed a connection between the properties of the deposited, biologically active biomolecules, the experimental conditions and the target composition. The bioassays have shown that up to 78% of the biomolecules remained active after femtosecond laser transfer, while this value reduced to 54% after nanosecond laser transfer. The addition of glycerol in a percentage up to 70% in the solution to be transferred has contributed to the stabilization of the micro-array patterns and the increase of their resolution.

  1. High-End CMOS Active Pixel Sensors For Space-Borne Imaging Instruments

    DTIC Science & Technology

    2005-07-13

    sur la technologie CCD, alors que les capteurs CMOS à pixel actifs (APS) ont des nombreux avantages pour des applications embarquées. Cette...Les capteurs optiques intégrés sont utilisés dans le domaine spatial dans un large éventail d’applications. Beaucoup d’entres elles reposent toujours...publication présente des capteurs CMOS hautes performances d’aujourd’hui et met en lumière leurs avantages par rapport à leur équivalent CCD. Ces capteurs

  2. Large area CMOS active pixel sensor x-ray imager for digital breast tomosynthesis: Analysis, modeling, and characterization

    SciTech Connect

    Zhao, Chumin; Kanicki, Jerzy; Konstantinidis, Anastasios C.; Patel, Tushita

    2015-11-15

    Purpose: Large area x-ray imagers based on complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology have been proposed for various medical imaging applications including digital breast tomosynthesis (DBT). The low electronic noise (50–300 e{sup −}) of CMOS APS x-ray imagers provides a possible route to shrink the pixel pitch to smaller than 75 μm for microcalcification detection and possible reduction of the DBT mean glandular dose (MGD). Methods: In this study, imaging performance of a large area (29 × 23 cm{sup 2}) CMOS APS x-ray imager [Dexela 2923 MAM (PerkinElmer, London)] with a pixel pitch of 75 μm was characterized and modeled. The authors developed a cascaded system model for CMOS APS x-ray imagers using both a broadband x-ray radiation and monochromatic synchrotron radiation. The experimental data including modulation transfer function, noise power spectrum, and detective quantum efficiency (DQE) were theoretically described using the proposed cascaded system model with satisfactory consistency to experimental results. Both high full well and low full well (LFW) modes of the Dexela 2923 MAM CMOS APS x-ray imager were characterized and modeled. The cascaded system analysis results were further used to extract the contrast-to-noise ratio (CNR) for microcalcifications with sizes of 165–400 μm at various MGDs. The impact of electronic noise on CNR was also evaluated. Results: The LFW mode shows better DQE at low air kerma (K{sub a} < 10 μGy) and should be used for DBT. At current DBT applications, air kerma (K{sub a} ∼ 10 μGy, broadband radiation of 28 kVp), DQE of more than 0.7 and ∼0.3 was achieved using the LFW mode at spatial frequency of 0.5 line pairs per millimeter (lp/mm) and Nyquist frequency ∼6.7 lp/mm, respectively. It is shown that microcalcifications of 165–400 μm in size can be resolved using a MGD range of 0.3–1 mGy, respectively. In comparison to a General Electric GEN2 prototype DBT system (at

  3. Mechanism of activation of the mouse c-mos oncogene by the LTR of an intracisternal A-particle gene.

    PubMed Central

    Horowitz, M; Luria, S; Rechavi, G; Givol, D

    1984-01-01

    In the mouse myeloma XRPC-24 the DNA of an intracisternal A-particle (IAP) is inserted within the coding region of c-mos. This insertion splits the c-mos into a 3' rc-mos and a 5' rc-mos separated by approximately 4.7 kb of IAP DNA. The insertion is in a head-to-head orientation and brings the 5' LTR of the IAP in juxtaposition to the 3' rc-mos such that the IAP and the 3' rc-mos are transcribed in opposite directions. The intact c-mos gene is usually dormant, whereas the 3' rc-mos is actively transcribed and is capable of transforming NIH3T3 cells. In an effort to understand the nature of this activation we mapped the 5' ends of the 3' rc-mos mRNA present in XPRC-24. We found two main mRNA start sites, one mapping to the junction of the 3' rc-mos and the 5' LTR, and the other located 10 nucleotides upstream to this junction, within the 5' LTR. This result indicates that the 3' rc-mos in XRPC-24 was activated by insertion of a promoter provided by the LTR of an IAP genome. Furthermore, the 5' LTR appears to possess promoter activities in two directions. This conclusion was confirmed by the fact that this 5' LTR, in both orientations, was able to activate the bacterial gene coding for chloramphenicol acetyltransferase (CAT) in the modular vector pSVOCAT. Images Fig. 2. Fig. 5. PMID:6098457

  4. A high frequency active voltage doubler in standard CMOS using offset-controlled comparators for inductive power transmission.

    PubMed

    Lee, Hyung-Min; Ghovanloo, Maysam

    2013-06-01

    In this paper, we present a fully integrated active voltage doubler in CMOS technology using offset-controlled high speed comparators for extending the range of inductive power transmission to implantable microelectronic devices (IMD) and radio-frequency identification (RFID) tags. This active voltage doubler provides considerably higher power conversion efficiency (PCE) and lower dropout voltage compared to its passive counterpart and requires lower input voltage than active rectifiers, leading to reliable and efficient operation with weakly coupled inductive links. The offset-controlled functions in the comparators compensate for turn-on and turn-off delays to not only maximize the forward charging current to the load but also minimize the back current, optimizing PCE in the high frequency (HF) band. We fabricated the active voltage doubler in a 0.5-μm 3M2P std . CMOS process, occupying 0.144 mm(2) of chip area. With 1.46 V peak AC input at 13.56 MHz, the active voltage doubler provides 2.4 V DC output across a 1 kΩ load, achieving the highest PCE = 79% ever reported at this frequency. In addition, the built-in start-up circuit ensures a reliable operation at lower voltages.

  5. A High Frequency Active Voltage Doubler in Standard CMOS Using Offset-Controlled Comparators for Inductive Power Transmission

    PubMed Central

    Lee, Hyung-Min; Ghovanloo, Maysam

    2014-01-01

    In this paper, we present a fully integrated active voltage doubler in CMOS technology using offset-controlled high speed comparators for extending the range of inductive power transmission to implantable microelectronic devices (IMD) and radio-frequency identification (RFID) tags. This active voltage doubler provides considerably higher power conversion efficiency (PCE) and lower dropout voltage compared to its passive counterpart and requires lower input voltage than active rectifiers, leading to reliable and efficient operation with weakly coupled inductive links. The offset-controlled functions in the comparators compensate for turn-on and turn-off delays to not only maximize the forward charging current to the load but also minimize the back current, optimizing PCE in the high frequency (HF) band. We fabricated the active voltage doubler in a 0.5-μm 3M2P std. CMOS process, occupying 0.144 mm2 of chip area. With 1.46 V peak AC input at 13.56 MHz, the active voltage doubler provides 2.4 V DC output across a 1 kΩ load, achieving the highest PCE = 79% ever reported at this frequency. In addition, the built-in start-up circuit ensures a reliable operation at lower voltages. PMID:23853321

  6. Accelerated life testing effects on CMOS microcircuit characteristics

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Accelerated life tests were performed on CMOS microcircuits to predict their long term reliability. The consistency of the CMOS microcircuit activation energy between the range of 125 C to 200 C and the range 200 C to 250 C was determined. Results indicate CMOS complexity and the amount of moisture detected inside the devices after testing influences time to failure of tested CMOS devices.

  7. Development and Validation of a Method for Profiling Post-Translational Modification Activities Using Protein Microarrays

    PubMed Central

    Widschwendter, Martin; Sun, Dahui; Sieburg, Hans B.; Spruck, Charles

    2010-01-01

    Background Post-translational modifications (PTMs) impact on the stability, cellular location, and function of a protein thereby achieving a greater functional diversity of the proteome. To fully appreciate how PTMs modulate signaling networks, proteome-wide studies are necessary. However, the evaluation of PTMs on a proteome-wide scale has proven to be technically difficult. To facilitate these analyses we have developed a protein microarray-based assay that is capable of profiling PTM activities in complex biological mixtures such as whole-cell extracts and pathological specimens. Methodology/Principal Findings In our assay, protein microarrays serve as a substrate platform for in vitro enzymatic reactions in which a recombinant ligase, or extracts prepared from whole cells or a pathological specimen is overlaid. The reactions include labeled modifiers (e.g., ubiquitin, SUMO1, or NEDD8), ATP regenerating system, and other required components (depending on the assay) that support the conjugation of the modifier. In this report, we apply this methodology to profile three molecularly complex PTMs (ubiquitylation, SUMOylation, and NEDDylation) using purified ligase enzymes and extracts prepared from cultured cell lines and pathological specimens. We further validate this approach by confirming the in vivo modification of several novel PTM substrates identified by our assay. Conclusions/Significance This methodology offers several advantages over currently used PTM detection methods including ease of use, rapidity, scale, and sample source diversity. Furthermore, by allowing for the intrinsic enzymatic activities of cell populations or pathological states to be directly compared, this methodology could have widespread applications for the study of PTMs in human diseases and has the potential to be directly applied to most, if not all, basic PTM research. PMID:20596523

  8. A new versatile microarray-based method for high throughput screening of carbohydrate-active enzymes.

    PubMed

    Vidal-Melgosa, Silvia; Pedersen, Henriette L; Schückel, Julia; Arnal, Grégory; Dumon, Claire; Amby, Daniel B; Monrad, Rune Nygaard; Westereng, Bjørge; Willats, William G T

    2015-04-03

    Carbohydrate-active enzymes have multiple biological roles and industrial applications. Advances in genome and transcriptome sequencing together with associated bioinformatics tools have identified vast numbers of putative carbohydrate-degrading and -modifying enzymes including glycoside hydrolases and lytic polysaccharide monooxygenases. However, there is a paucity of methods for rapidly screening the activities of these enzymes. By combining the multiplexing capacity of carbohydrate microarrays with the specificity of molecular probes, we have developed a sensitive, high throughput, and versatile semiquantitative enzyme screening technique that requires low amounts of enzyme and substrate. The method can be used to assess the activities of single enzymes, enzyme mixtures, and crude culture broths against single substrates, substrate mixtures, and biomass samples. Moreover, we show that the technique can be used to analyze both endo-acting and exo-acting glycoside hydrolases, polysaccharide lyases, carbohydrate esterases, and lytic polysaccharide monooxygenases. We demonstrate the potential of the technique by identifying the substrate specificities of purified uncharacterized enzymes and by screening enzyme activities from fungal culture broths.

  9. A New Versatile Microarray-based Method for High Throughput Screening of Carbohydrate-active Enzymes*

    PubMed Central

    Vidal-Melgosa, Silvia; Pedersen, Henriette L.; Schückel, Julia; Arnal, Grégory; Dumon, Claire; Amby, Daniel B.; Monrad, Rune Nygaard; Westereng, Bjørge; Willats, William G. T.

    2015-01-01

    Carbohydrate-active enzymes have multiple biological roles and industrial applications. Advances in genome and transcriptome sequencing together with associated bioinformatics tools have identified vast numbers of putative carbohydrate-degrading and -modifying enzymes including glycoside hydrolases and lytic polysaccharide monooxygenases. However, there is a paucity of methods for rapidly screening the activities of these enzymes. By combining the multiplexing capacity of carbohydrate microarrays with the specificity of molecular probes, we have developed a sensitive, high throughput, and versatile semiquantitative enzyme screening technique that requires low amounts of enzyme and substrate. The method can be used to assess the activities of single enzymes, enzyme mixtures, and crude culture broths against single substrates, substrate mixtures, and biomass samples. Moreover, we show that the technique can be used to analyze both endo-acting and exo-acting glycoside hydrolases, polysaccharide lyases, carbohydrate esterases, and lytic polysaccharide monooxygenases. We demonstrate the potential of the technique by identifying the substrate specificities of purified uncharacterized enzymes and by screening enzyme activities from fungal culture broths. PMID:25657012

  10. Integrated X-ray and charged particle active pixel CMOS sensor arrays using an epitaxial silicon sensitive region

    SciTech Connect

    Kleinfelder, Stuart; Bichsel, Hans; Bieser, Fred; Matis, Howard S.; Rai, Gulshan; Retiere, Fabrice; Weiman, Howard; Yamamoto, Eugene

    2002-07-01

    Integrated CMOS Active Pixel Sensor (APS) arrays have been fabricated and tested using X-ray and electron sources. The 128 by 128 pixel arrays, designed in a standard 0.25 micron process, use a {approx}10 micron epitaxial silicon layer as a deep detection region. The epitaxial layer has a much greater thickness than the surface features used by standard CMOS APS, leading to stronger signals and potentially better signal-to-noise ratio (SNR). On the other hand, minority carriers confined within the epitaxial region may diffuse to neighboring pixels, blur images and reduce peak signal intensity. But for low-rate, sparse-event images, centroid analysis of this diffusion may be used to increase position resolution. Careful trade-offs involving pixel size and sense-node area verses capacitance must be made to optimize overall performance. The prototype sensor arrays, therefore, include a range of different pixel designs, including different APS circuits and a range of different epitaxial layer contact structures. The fabricated arrays were tested with 1.5 GeV electrons and Fe-55 X-ray sources, yielding a measured noise of 13 electrons RMS and an SNR for single Fe-55 X-rays of greater than 38.

  11. Microarray and network-based identification of functional modules and pathways of active tuberculosis.

    PubMed

    Bian, Zhong-Rui; Yin, Juan; Sun, Wen; Lin, Dian-Jie

    2017-02-08

    Diagnose of active tuberculosis (TB) is challenging and treatment response is also difficult to efficiently monitor. The aim of this study was to use an integrated analysis of microarray and network-based method to the samples from publically available datasets to obtain a diagnostic module set and pathways in active TB. Towards this goal, background protein-protein interactions (PPI) network was generated based on global PPI information and gene expression data, following by identification of differential expression network (DEN) from the background PPI network. Then, ego genes were extracted according to the degree features in DEN. Next, module collection was conducted by ego gene expansion based on EgoNet algorithm. After that, differential expression of modules between active TB and controls was evaluated using random permutation test. Finally, biological significance of differential modules was detected by pathways enrichment analysis based on Reactome database, and Fisher's exact test was implemented to extract differential pathways for active TB. Totally, 47 ego genes and 47 candidate modules were identified from the DEN. By setting the cutoff-criteria of gene size >5 and classification accuracy ≥0.9, 7 ego modules (Module 4, Module 7, Module 9, Module 19, Module 25, Module 38 and Module 43) were extracted, and all of them had the statistical significance between active TB and controls. Then, Fisher's exact test was conducted to capture differential pathways for active TB. Interestingly, genes in Module 4, Module 25, Module 38, and Module 43 were enriched in the same pathway, formation of a pool of free 40S subunits. Significant pathway for Module 7 and Module 9 was eukaryotic translation termination, and for Module 19 was nonsense mediated decay enhanced by the exon junction complex (EJC). Accordingly, differential modules and pathways might be potential biomarkers for treating active TB, and provide valuable clues for better understanding of molecular

  12. Signal and noise transfer properties of CMOS based active pixel flat panel imager coupled to structured CsI:Tl.

    PubMed

    Arvanitis, C D; Bohndiek, S E; Blakesley, J; Olivo, A; Speller, R D

    2009-01-01

    Complementary metal-oxide-semiconductors (CMOS) active pixel sensors can be optically coupled to CsI:Tl phosphors forming a indirect active pixel flat panel imager (APFPI) for high performance medical imaging. The aim of this work is to determine the x-ray imaging capabilities of CMOS-based APFPI and study the signal and noise transfer properties of CsI:Tl phosphors. Three different CsI:Tl phosphors from two different vendors have been used to produce three system configurations. The performance of each system configuration has been studied in terms of the modulation transfer function (MTF), noise power spectra, and detective quantum efficiency (DQE) in the mammographic energy range. A simple method to determine quantum limited systems in this energy range is also presented. In addition, with aid of monochromatic synchrotron radiation, the effect of iodine characteristic x-rays of the CsI:Tl on the MTF has been determined. A Monte Carlo simulation of the signal transfer properties of the imager is also presented in order to study the stages that degrade the spatial resolution of our current system. The effect of using substrate patterning during the growth of CsI:Tl columnar structure was also studied, along with the effect of CsI:Tl fixed pattern noise due to local variations in the scintillation light. CsI:Tl fixed pattern noise appears to limit the performance of our current system configurations. All the system configurations are quantum limited at 0.23 microC/kg with two of them having DQE (0) equal to 0.57. Active pixel flat panel imagers are shown to be digital x-ray imagers with almost constant DQE throughout a significant part of their dynamic range and in particular at very low exposures.

  13. Resistance exercise training influences skeletal muscle immune activation: a microarray analysis

    PubMed Central

    Liu, Dongmei; Sartor, Maureen A.; IglayReger, Heidi B.; Pistilli, Emidio E.; Gutmann, Laurie; Nader, Gustavo A.; Hoffman, Eric P.

    2012-01-01

    The primary aim of this investigation was to evaluate the effect of training on the immune activation in skeletal muscle in response to an acute bout of resistance exercise (RE). Seven young healthy men and women underwent a 12-wk supervised progressive unilateral arm RE training program. One week after the last training session, subjects performed an acute bout of bilateral RE in which the trained and the untrained arm exercised at the same relative intensity. Muscle biopsies were obtained 4 h postexercise from the biceps brachii of both arms and assessed for global transcriptom using Affymetrix U133 plus 2.0 microarrays. Significantly regulated biological processes and gene groups were analyzed using a logistic regression-based method following differential (trained vs. untrained) gene expression testing via an intensity-based Bayesian moderated t-test. The results from the present study suggest that training blunts the transcriptional upregulation of immune activation by minimizing expression of genes involved in monocyte recruitment and enhancing gene expression involved in macrophage anti-inflammatory polarization. Additionally, our data suggest that training blunts the transcriptional upregulation of the stress response and the downregulation of glucose metabolism, mitochondrial structure, and oxidative phosphorylation, and it enhances the transcriptional upregulation of the extracellular matrix and cytoskeleton development and organization and the downregulation of gene transcription and muscle contraction. This study provides novel insight into the molecular processes involved in the adaptive response of skeletal muscle following RE training and the cellular and molecular events implicating the protective role of training on muscle stress and damage inflicted by acute mechanical loading. PMID:22052873

  14. Characterization of high resolution CMOS monolithic active pixel detector in SOI technology

    NASA Astrophysics Data System (ADS)

    Ahmed, M. I.; Arai, Y.; Glab, S.; Idzik, M.; Kapusta, P.; Miyoshi, T.; Takeda, A.; Turala, M.

    2015-05-01

    Novel CMOS monolithic pixel detectors designed at KEK and fabricated at Lapis Semiconductor in 0.2 μm Silicon-on-Insulator (SOI) technology are presented. A thin layer of silicon oxide separates high and low resistivity silicon layers, allowing for optimization of design of detector and readout parts. Shallow wells buried under the oxide in the detector part screen the entire pixel electronics from electrical field applied to the detector. Several integration type SOI pixel detectors have been developed with pixel sizes 8-20 μm. The general features of 14 × 14 μm2 detectors designed on different wafers (CZ-n, FZ-n and FZ-p) were measured and compared. The detector performance was studied under irradiation with visible and infra-red laser, and also X-ray ionizing source. Using X-rays from an Am-241 source the noise of readout electronics was measured at different working conditions, showing the ENC in the range of 88-120 e-. The pixel current was calculated from average DC pedestal shift while varying the pixel integration time. The operation of the detector was studied under partial and full depletion conditions. The effects of temperature and detector bias voltage on noise and leakage current were studied. Characteristics of an ADC integrated in the front-end chip are also presented.

  15. A 0.18-µm CMOS Array Sensor for Integrated Time-Resolved Fluorescence Detection

    PubMed Central

    Huang, Ta-chien D.; Sorgenfrei, Sebastian; Gong, Ping; Levicky, Rastislav; Shepard, Kenneth L.

    2010-01-01

    This paper describes the design of an active, integrated CMOS sensor array for fluorescence applications which enables time-gated, time-resolved fluorescence spectroscopy. The 64-by-64 array is sensitive to photon densities as low as 8.8 × 106 photons/cm2 with 64-point averaging and, through a differential pixel design, has a measured impulse response of better than 800 ps. Applications include both active microarrays and high-frame-rate imagers for fluorescence lifetime imaging microscopy. PMID:20436922

  16. Three-dimensional cascaded system analysis of a 50 µm pixel pitch wafer-scale CMOS active pixel sensor x-ray detector for digital breast tomosynthesis

    NASA Astrophysics Data System (ADS)

    Zhao, C.; Vassiljev, N.; Konstantinidis, A. C.; Speller, R. D.; Kanicki, J.

    2017-03-01

    High-resolution, low-noise x-ray detectors based on the complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology have been developed and proposed for digital breast tomosynthesis (DBT). In this study, we evaluated the three-dimensional (3D) imaging performance of a 50 µm pixel pitch CMOS APS x-ray detector named DynAMITe (Dynamic Range Adjustable for Medical Imaging Technology). The two-dimensional (2D) angle-dependent modulation transfer function (MTF), normalized noise power spectrum (NNPS), and detective quantum efficiency (DQE) were experimentally characterized and modeled using the cascaded system analysis at oblique incident angles up to 30°. The cascaded system model was extended to the 3D spatial frequency space in combination with the filtered back-projection (FBP) reconstruction method to calculate the 3D and in-plane MTF, NNPS and DQE parameters. The results demonstrate that the beam obliquity blurs the 2D MTF and DQE in the high spatial frequency range. However, this effect can be eliminated after FBP image reconstruction. In addition, impacts of the image acquisition geometry and detector parameters were evaluated using the 3D cascaded system analysis for DBT. The result shows that a wider projection angle range (e.g.  ±30°) improves the low spatial frequency (below 5 mm‑1) performance of the CMOS APS detector. In addition, to maintain a high spatial resolution for DBT, a focal spot size of smaller than 0.3 mm should be used. Theoretical analysis suggests that a pixelated scintillator in combination with the 50 µm pixel pitch CMOS APS detector could further improve the 3D image resolution. Finally, the 3D imaging performance of the CMOS APS and an indirect amorphous silicon (a-Si:H) thin-film transistor (TFT) passive pixel sensor (PPS) detector was simulated and compared.

  17. Three-dimensional cascaded system analysis of a 50 µm pixel pitch wafer-scale CMOS active pixel sensor x-ray detector for digital breast tomosynthesis.

    PubMed

    Zhao, C; Vassiljev, N; Konstantinidis, A C; Speller, R D; Kanicki, J

    2017-03-07

    High-resolution, low-noise x-ray detectors based on the complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology have been developed and proposed for digital breast tomosynthesis (DBT). In this study, we evaluated the three-dimensional (3D) imaging performance of a 50 µm pixel pitch CMOS APS x-ray detector named DynAMITe (Dynamic Range Adjustable for Medical Imaging Technology). The two-dimensional (2D) angle-dependent modulation transfer function (MTF), normalized noise power spectrum (NNPS), and detective quantum efficiency (DQE) were experimentally characterized and modeled using the cascaded system analysis at oblique incident angles up to 30°. The cascaded system model was extended to the 3D spatial frequency space in combination with the filtered back-projection (FBP) reconstruction method to calculate the 3D and in-plane MTF, NNPS and DQE parameters. The results demonstrate that the beam obliquity blurs the 2D MTF and DQE in the high spatial frequency range. However, this effect can be eliminated after FBP image reconstruction. In addition, impacts of the image acquisition geometry and detector parameters were evaluated using the 3D cascaded system analysis for DBT. The result shows that a wider projection angle range (e.g.  ±30°) improves the low spatial frequency (below 5 mm(-1)) performance of the CMOS APS detector. In addition, to maintain a high spatial resolution for DBT, a focal spot size of smaller than 0.3 mm should be used. Theoretical analysis suggests that a pixelated scintillator in combination with the 50 µm pixel pitch CMOS APS detector could further improve the 3D image resolution. Finally, the 3D imaging performance of the CMOS APS and an indirect amorphous silicon (a-Si:H) thin-film transistor (TFT) passive pixel sensor (PPS) detector was simulated and compared.

  18. CMOS Image Sensors for High Speed Applications

    PubMed Central

    El-Desouki, Munir; Deen, M. Jamal; Fang, Qiyin; Liu, Louis; Tse, Frances; Armstrong, David

    2009-01-01

    Recent advances in deep submicron CMOS technologies and improved pixel designs have enabled CMOS-based imagers to surpass charge-coupled devices (CCD) imaging technology for mainstream applications. The parallel outputs that CMOS imagers can offer, in addition to complete camera-on-a-chip solutions due to being fabricated in standard CMOS technologies, result in compelling advantages in speed and system throughput. Since there is a practical limit on the minimum pixel size (4∼5 μm) due to limitations in the optics, CMOS technology scaling can allow for an increased number of transistors to be integrated into the pixel to improve both detection and signal processing. Such smart pixels truly show the potential of CMOS technology for imaging applications allowing CMOS imagers to achieve the image quality and global shuttering performance necessary to meet the demands of ultrahigh-speed applications. In this paper, a review of CMOS-based high-speed imager design is presented and the various implementations that target ultrahigh-speed imaging are described. This work also discusses the design, layout and simulation results of an ultrahigh acquisition rate CMOS active-pixel sensor imager that can take 8 frames at a rate of more than a billion frames per second (fps). PMID:22389609

  19. CMOS Image Sensors for High Speed Applications.

    PubMed

    El-Desouki, Munir; Deen, M Jamal; Fang, Qiyin; Liu, Louis; Tse, Frances; Armstrong, David

    2009-01-01

    Recent advances in deep submicron CMOS technologies and improved pixel designs have enabled CMOS-based imagers to surpass charge-coupled devices (CCD) imaging technology for mainstream applications. The parallel outputs that CMOS imagers can offer, in addition to complete camera-on-a-chip solutions due to being fabricated in standard CMOS technologies, result in compelling advantages in speed and system throughput. Since there is a practical limit on the minimum pixel size (4∼5 μm) due to limitations in the optics, CMOS technology scaling can allow for an increased number of transistors to be integrated into the pixel to improve both detection and signal processing. Such smart pixels truly show the potential of CMOS technology for imaging applications allowing CMOS imagers to achieve the image quality and global shuttering performance necessary to meet the demands of ultrahigh-speed applications. In this paper, a review of CMOS-based high-speed imager design is presented and the various implementations that target ultrahigh-speed imaging are described. This work also discusses the design, layout and simulation results of an ultrahigh acquisition rate CMOS active-pixel sensor imager that can take 8 frames at a rate of more than a billion frames per second (fps).

  20. Synchrotron based planar imaging and digital tomosynthesis of breast and biopsy phantoms using a CMOS active pixel sensor.

    PubMed

    Szafraniec, Magdalena B; Konstantinidis, Anastasios C; Tromba, Giuliana; Dreossi, Diego; Vecchio, Sara; Rigon, Luigi; Sodini, Nicola; Naday, Steve; Gunn, Spencer; McArthur, Alan; Olivo, Alessandro

    2015-03-01

    The SYRMEP (SYnchrotron Radiation for MEdical Physics) beamline at Elettra is performing the first mammography study on human patients using free-space propagation phase contrast imaging. The stricter spatial resolution requirements of this method currently force the use of conventional films or specialized computed radiography (CR) systems. This also prevents the implementation of three-dimensional (3D) approaches. This paper explores the use of an X-ray detector based on complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology as a possible alternative, for acquisitions both in planar and tomosynthesis geometry. Results indicate higher quality of the images acquired with the synchrotron set-up in both geometries. This improvement can be partly ascribed to the use of parallel, collimated and monochromatic synchrotron radiation (resulting in scatter rejection, no penumbra-induced blurring and optimized X-ray energy), and partly to phase contrast effects. Even though the pixel size of the used detector is still too large - and thus suboptimal - for free-space propagation phase contrast imaging, a degree of phase-induced edge enhancement can clearly be observed in the images.

  1. 50 μm pixel pitch wafer-scale CMOS active pixel sensor x-ray detector for digital breast tomosynthesis.

    PubMed

    Zhao, C; Konstantinidis, A C; Zheng, Y; Anaxagoras, T; Speller, R D; Kanicki, J

    2015-12-07

    Wafer-scale CMOS active pixel sensors (APSs) have been developed recently for x-ray imaging applications. The small pixel pitch and low noise are very promising properties for medical imaging applications such as digital breast tomosynthesis (DBT). In this work, we evaluated experimentally and through modeling the imaging properties of a 50 μm pixel pitch CMOS APS x-ray detector named DynAMITe (Dynamic Range Adjustable for Medical Imaging Technology). A modified cascaded system model was developed for CMOS APS x-ray detectors by taking into account the device nonlinear signal and noise properties. The imaging properties such as modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) were extracted from both measurements and the nonlinear cascaded system analysis. The results show that the DynAMITe x-ray detector achieves a high spatial resolution of 10 mm(-1) and a DQE of around 0.5 at spatial frequencies  <1 mm(-1). In addition, the modeling results were used to calculate the image signal-to-noise ratio (SNRi) of microcalcifications at various mean glandular dose (MGD). For an average breast (5 cm thickness, 50% glandular fraction), 165 μm microcalcifications can be distinguished at a MGD of 27% lower than the clinical value (~1.3 mGy). To detect 100 μm microcalcifications, further optimizations of the CMOS APS x-ray detector, image aquisition geometry and image reconstruction techniques should be considered.

  2. CMOS analog switches for adaptive filters

    NASA Technical Reports Server (NTRS)

    Dixon, C. E.

    1980-01-01

    Adaptive active low-pass filters incorporate CMOS (Complimentary Metal-Oxide Semiconductor) analog switches (such as 4066 switch) that reduce variation in switch resistance when filter is switched to any selected transfer function.

  3. Chromosome Microarray.

    PubMed

    Anderson, Sharon

    2016-01-01

    Over the last half century, knowledge about genetics, genetic testing, and its complexity has flourished. Completion of the Human Genome Project provided a foundation upon which the accuracy of genetics, genomics, and integration of bioinformatics knowledge and testing has grown exponentially. What is lagging, however, are efforts to reach and engage nurses about this rapidly changing field. The purpose of this article is to familiarize nurses with several frequently ordered genetic tests including chromosomes and fluorescence in situ hybridization followed by a comprehensive review of chromosome microarray. It shares the complexity of microarray including how testing is performed and results analyzed. A case report demonstrates how this technology is applied in clinical practice and reveals benefits and limitations of this scientific and bioinformatics genetic technology. Clinical implications for maternal-child nurses across practice levels are discussed.

  4. Effect of Lactobacillus brevis KB290 on the cell-mediated cytotoxic activity of mouse splenocytes: a DNA microarray analysis.

    PubMed

    Fukui, Yuichiro; Sasaki, Erika; Fuke, Nobuo; Nakai, Yuji; Ishijima, Tomoko; Abe, Keiko; Yajima, Nobuhiro

    2013-11-14

    Lactic acid bacteria confer a variety of health benefits. Here, we investigate the mechanisms by which Lactobacillus brevis KB290 (KB290) enhances cell-mediated cytotoxic activity. Female BALB/c mice aged 9 weeks were fed a diet containing KB290 (3 × 10(9) colony-forming units/g) or starch for 1 d. The resulting cytotoxic activity of splenocytes against YAC-1 cells was measured using flow cytometry and analysed for gene expression using DNA microarray technology. KB290 enhanced the cell-mediated cytotoxic activity of splenocytes. DNA microarray analysis identified 327 up-regulated and 347 down-regulated genes that characterised the KB290 diet group. The up-regulated genes were significantly enriched in Gene Ontology terms related to immunity, and, especially, a positive regulation of T-cell-mediated cytotoxicity existed among these terms. Almost all the genes included in the term encoded major histocompatibility complex (MHC) class I molecules involved in the presentation of antigen to CD8(+) cytotoxic T cells. Marco and Signr1 specific to marginal zone macrophages (MZM), antigen-presenting cells, were also up-regulated. Flow cytometric analysis confirmed that the proportion of MZM was significantly increased by KB290 ingestion. Additionally, the over-represented Kyoto Encyclopedia of Genes and Genomes pathways among the up-regulated genes were those for natural killer (NK) cell-mediated cytotoxicity and antigen processing and presentation. The results for the selected genes associated with NK cells and CD8(+) cytotoxic T cells were confirmed by quantitative RT-PCR. These results suggest that enhanced cytotoxic activity could be caused by the activation of NK cells and/or of CD8(+) cytotoxic T cells stimulated via MHC class I presentation.

  5. Fluorescent activated cell sorting (FACS) combined with gene expression microarrays for transcription enrichment profiling of zebrafish lateral line cells.

    PubMed

    Gallardo, Viviana E; Behra, Martine

    2013-08-15

    Transgenic lines carrying fluorescent reporter genes like GFP have been of great value in the elucidation of developmental features and physiological processes in various animal models, including zebrafish. The lateral line (LL), which is a fish specific superficial sensory organ, is an emerging organ model for studying complex cellular processes in the context of the whole living animal. Cell migration, mechanosensory cell development/differentiation and regeneration are some examples. This sensory system is made of superficial and sparse small sensory patches called neuromasts, with less than 50 cells in any given patch. The paucity of cells is a real problem in any effort to characterize those cells at the transcriptional level. We describe here a method which we applied to efficiently separate subpopulation of cells of the LL, using two distinct stable transgenic zebrafish lines, Tg(cldnb:gfp) and Tg(tnks1bp1:EGFP). In both cases, the GFP positive (GFP+) cells were separated from the remainder of the animal by using a Fluorescent Activated Cell Sorter (FACS). The transcripts of the GFP+ cells were subsequently analyzed on gene expression microarrays. The combination of FACS and microarrays is an efficient method to establish a transcriptional signature for discrete cell populations which would otherwise be masked in whole animal preparation.

  6. Development of CMOS Active Pixel Image Sensors for Low Cost Commercial Applications

    NASA Technical Reports Server (NTRS)

    Gee, R.; Kemeny, S.; Kim, Q.; Mendis, S.; Nakamura, J.; Nixon, R.; Ortiz, M.; Pain, B.; Staller, C.; Zhou, Z; Fossum, E.

    1994-01-01

    JPL, under sponsorship from the NASA Office of Advanced Concepts and Technology, has been developing a second-generation solid-state image sensor technology. Charge-coupled devices (CCD) are a well-established first generation image sensor technology. For both commercial and NASA applications, CCDs have numerous shortcomings. In response, the active pixel sensor (APS) technology has been under research. The major advantages of APS technology are the ability to integrate on-chip timing, control, signal-processing and analog-to-digital converter functions, reduced sensitivity to radiation effects, low power operation, and random access readout.

  7. Turn-on circuits based on standard CMOS technology for active RFID labels

    NASA Astrophysics Data System (ADS)

    Hall, David; Ranasinghe, Damith C.; Jamali, Behnam; Cole, Peter H.

    2005-06-01

    The evolution of RFID Systems has lead to the development of a class hierarchy in which the battery powered labels are a set of higher class labels referred to as active labels. The battery powering active transponders must last for an acceptable time, so the electronics of the label must have very low current consumption in order to prolong the life of the battery. However due to circuit complexity or the desired operating range the electronics may drain the battery more rapidly than desired but use of a turn-on circuit allows the battery to be connected only when communication is needed, thus lengthening the life of the battery. Two solutions available for the development of a turn on circuit use resonance in a label rectification circuit to provide a high sensitivity result. This paper presents the results of experiments conducted to evaluate resonance in a label rectification circuit and the designs of fully integrable turn-on circuits. We have also presented test results showing a successful practical implementation of one of the turn on circuit designs.

  8. High-density tiling microarray analysis of the full transcriptional activity of yeast.

    PubMed

    David, Lior; Clauder-Münster, Sandra; Steinmetz, Lars M

    2014-01-01

    Understanding the relationship between DNA sequence variation and phenotypic variation in complex or quantitative traits is one of the major challenges in modern biology. We are witnessing a deluge of DNA sequence information and association studies of genetic polymorphisms with phenotypes of interest in families and populations. In addition, it has become clear that large portions of eukaryotic genomes beyond protein-coding genes are transcribed, generating numerous noncoding RNA (ncRNA) molecules whose functions remain mostly unknown.DNA oligonucleotide microarrays constitute a powerful technology for studying the expression of genes in different organisms. The Saccharomyces cerevisiae tiling array presents a significant advance over previous array-based platforms. It has a high density of overlapping probes that start on average every 8 bp along each strand of the genome, enabling precise definition of transcript structure. Furthermore, the array includes probes specific for the polymorphic positions of another, distantly related yeast strain, allowing accurate measurement of allele-specific expression in a hybrid of the two strains. This technology thus allows high-resolution, quantitative, strand- and allele-specific measurements of transcription from a full eukaryotic genome. In this chapter, we describe the methods for extracting RNA, synthesizing first-strand cDNA, fragmenting, and labeling of samples for hybridization to the tiling array. Combining genome-wide information on variation in DNA sequence with variation in transcript structure and levels promises to increase our understanding of the genotype-to-phenotype relationship.

  9. Pathway modeling of microarray data: A case study of pathway activity changes in the testis following in utero exposure to dibutyl phthalate (DBP)

    SciTech Connect

    Ovacik, Meric A.; Sen, Banalata; Euling, Susan Y.; Gaido, Kevin W.; Ierapetritou, Marianthi G.; Androulakis, Ioannis P.

    2013-09-15

    Pathway activity level analysis, the approach pursued in this study, focuses on all genes that are known to be members of metabolic and signaling pathways as defined by the KEGG database. The pathway activity level analysis entails singular value decomposition (SVD) of the expression data of the genes constituting a given pathway. We explore an extension of the pathway activity methodology for application to time-course microarray data. We show that pathway analysis enhances our ability to detect biologically relevant changes in pathway activity using synthetic data. As a case study, we apply the pathway activity level formulation coupled with significance analysis to microarray data from two different rat testes exposed in utero to Dibutyl Phthalate (DBP). In utero DBP exposure in the rat results in developmental toxicity of a number of male reproductive organs, including the testes. One well-characterized mode of action for DBP and the male reproductive developmental effects is the repression of expression of genes involved in cholesterol transport, steroid biosynthesis and testosterone synthesis that lead to a decreased fetal testicular testosterone. Previous analyses of DBP testes microarray data focused on either individual gene expression changes or changes in the expression of specific genes that are hypothesized, or known, to be important in testicular development and testosterone synthesis. However, a pathway analysis may inform whether there are additional affected pathways that could inform additional modes of action linked to DBP developmental toxicity. We show that Pathway activity analysis may be considered for a more comprehensive analysis of microarray data.

  10. CAOS-CMOS camera.

    PubMed

    Riza, Nabeel A; La Torre, Juan Pablo; Amin, M Junaid

    2016-06-13

    Proposed and experimentally demonstrated is the CAOS-CMOS camera design that combines the coded access optical sensor (CAOS) imager platform with the CMOS multi-pixel optical sensor. The unique CAOS-CMOS camera engages the classic CMOS sensor light staring mode with the time-frequency-space agile pixel CAOS imager mode within one programmable optical unit to realize a high dynamic range imager for extreme light contrast conditions. The experimentally demonstrated CAOS-CMOS camera is built using a digital micromirror device, a silicon point-photo-detector with a variable gain amplifier, and a silicon CMOS sensor with a maximum rated 51.3 dB dynamic range. White light imaging of three different brightness simultaneously viewed targets, that is not possible by the CMOS sensor, is achieved by the CAOS-CMOS camera demonstrating an 82.06 dB dynamic range. Applications for the camera include industrial machine vision, welding, laser analysis, automotive, night vision, surveillance and multispectral military systems.

  11. Microarray analysis of active cardiac remodeling genes in a familial hypertrophic cardiomyopathy mouse model rescued by a phospholamban knockout

    PubMed Central

    Rajan, Sudarsan; Pena, James R.; Jegga, Anil G.; Aronow, Bruce J.; Wolska, Beata M.

    2013-01-01

    Familial hypertrophic cardiomyopathy (FHC) is a disease characterized by ventricular hypertrophy, fibrosis, and aberrant systolic and/or diastolic function. Our laboratories have previously developed two mouse models that affect cardiac performance. One mouse model encodes an FHC-associated mutation in α-tropomyosin: Glu → Gly at amino acid 180, designated as Tm180. These mice display a phenotype that is characteristic of FHC, including severe cardiac hypertrophy with fibrosis and impaired physiological performance. The other model was a gene knockout of phospholamban (PLN KO), a regulator of calcium uptake in the sarcoplasmic reticulum of cardiomyocytes; these hearts exhibit hypercontractility with no pathological abnormalities. Previous work in our laboratories shows that when mice were genetically crossed between the PLN KO and Tm180, the progeny (PLN KO/Tm180) display a rescued hypertrophic phenotype with improved morphology and cardiac function. To understand the changes in gene expression that occur in these models undergoing cardiac remodeling (Tm180, PLN KO, PLN KO/Tm180, and nontransgenic control mice), we conducted microarray analyses of left ventricular tissue at 4 and 12 mo of age. Expression profiling reveals that 1,187 genes changed expression in direct response to the three genetic models. With these 1,187 genes, 11 clusters emerged showing normalization of transcript expression in the PLN KO/Tm180 hearts. In addition, 62 transcripts are highly involved in suppression of the hypertrophic phenotype. Confirmation of the microarray analysis was conducted by quantitative RT-PCR. These results provide insight into genes that alter expression during cardiac remodeling and are active during modulation of the cardiomyopathic phenotype. PMID:23800848

  12. Decreased Expression of Inhibitor of Caspase-Activated DNase (ICAD) in Renal Cell Carcinoma – Tissue Microarray of Human Samples

    PubMed Central

    Rajandram, Retnagowri; Razack, Azad H. A.; Ng, Keng Lim

    2016-01-01

    Although primary localised tumours of renal cell carcinoma (RCC) can be treated relatively successfully with surgery, metastatic RCC has poor prognosis because of late diagnosis and resistance to therapies. In the present study, we were interested in profiling the protein expression of “inhibitor of caspase-activated DNase” (ICAD), an apoptosis inhibitor, in kidney cancer and its paired normal kidney. Immunohistochemistry with automated batch staining and morphometry using digital pathology were used to compare ICAD in 121 RCC specimens with their paired normal kidney tissue. Tissue microarray of formalin-fixed, paraffin-embedded archival tissue was used. Intensity and localisation of ICAD were compared between normal and cancer samples, and against grading within the cancers. The results demonstrated that, in this cohort, ICAD was highly expressed in the proximal tubular epithelium of normal kidney, and significantly decreased in clear cell RCC tissue (p < 0.05) as well as other subtypes of RCC (p < 0.01) compared with normal kidney. There was a tendency towards nuclear localisation of ICAD in clear cell RCC, but not in other subtypes of RCC. No significant association was found between ICAD intensity and grade of RCC. In summary, down-regulation of ICAD occurs in RCC. ICAD normally inhibits DNA fragmentation and apoptosis; thus, its down-regulation was unexpected in a cancer known for its resistance to apoptosis. However, these RCC samples were from primary, not metastatic, RCC sites, and down-regulated ICAD may be part of a progressive pathway that promotes RCC metastasis.

  13. Activity Based High-Throughput Screening for Novel O-GlcNAc Transferase Substrates Using a Dynamic Peptide Microarray

    PubMed Central

    Shi, Jie; Sharif, Suhela; Ruijtenbeek, Rob; Pieters, Roland J.

    2016-01-01

    O-GlcNAcylation is a reversible and dynamic protein post-translational modification in mammalian cells. The O-GlcNAc cycle is catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). O-GlcNAcylation plays important role in many vital cellular events including transcription, cell cycle regulation, stress response and protein degradation, and altered O-GlcNAcylation has long been implicated in cancer, diabetes and neurodegenerative diseases. Recently, numerous approaches have been developed to identify OGT substrates and study their function, but there is still a strong demand for highly efficient techniques. Here we demonstrated the utility of the peptide microarray approach to discover novel OGT substrates and study its specificity. Interestingly, the protein RBL-2, which is a key regulator of entry into cell division and may function as a tumor suppressor, was identified as a substrate for three isoforms of OGT. Using peptide Ala scanning, we found Ser 420 is one possible O-GlcNAc site in RBL-2. Moreover, substitution of Ser 420, on its own, inhibited OGT activity, raising the possibility of mechanism-based development for selective OGT inhibitors. This approach will prove useful for both discovery of novel OGT substrates and studying OGT specificity. PMID:26960196

  14. Angiogenesis Interactome and Time Course Microarray Data Reveal the Distinct Activation Patterns in Endothelial Cells

    PubMed Central

    Chu, Liang-Hui; Lee, Esak; Bader, Joel S.; Popel, Aleksander S.

    2014-01-01

    Angiogenesis involves stimulation of endothelial cells (EC) by various cytokines and growth factors, but the signaling mechanisms are not completely understood. Combining dynamic gene expression time-course data for stimulated EC with protein-protein interactions associated with angiogenesis (the “angiome”) could reveal how different stimuli result in different patterns of network activation and could implicate signaling intermediates as points for control or intervention. We constructed the protein-protein interaction networks of positive and negative regulation of angiogenesis comprising 367 and 245 proteins, respectively. We used five published gene expression datasets derived from in vitro assays using different types of blood endothelial cells stimulated by VEGFA (vascular endothelial growth factor A). We used the Short Time-series Expression Miner (STEM) to identify significant temporal gene expression profiles. The statistically significant patterns between 2D fibronectin and 3D type I collagen substrates for telomerase-immortalized EC (TIME) show that different substrates could influence the temporal gene activation patterns in the same cell line. We investigated the different activation patterns among 18 transmembrane tyrosine kinase receptors, and experimentally measured the protein level of the tyrosine-kinase receptors VEGFR1, VEGFR2 and VEGFR3 in human umbilical vein EC (HUVEC) and human microvascular EC (MEC). The results show that VEGFR1–VEGFR2 levels are more closely coupled than VEGFR1–VEGFR3 or VEGFR2–VEGFR3 in HUVEC and MEC. This computational methodology can be extended to investigate other molecules or biological processes such as cell cycle. PMID:25329517

  15. Active Fail-Safe Micro-Array Flow Control for Advanced Embedded Propulsion Systems

    NASA Technical Reports Server (NTRS)

    Anderson, Bernhard H.; Mace, James L.; Mani, Mori

    2009-01-01

    The primary objective of this research effort was to develop and analytically demonstrate enhanced first generation active "fail-safe" hybrid flow-control techniques to simultaneously manage the boundary layer on the vehicle fore-body and to control the secondary flow generated within modern serpentine or embedded inlet S-duct configurations. The enhanced first-generation technique focused on both micro-vanes and micro-ramps highly-integrated with micro -jets to provide nonlinear augmentation for the "strength' or effectiveness of highly-integrated flow control systems. The study focused on the micro -jet mass flow ratio (Wjet/Waip) range from 0.10 to 0.30 percent and jet total pressure ratios (Pjet/Po) from 1.0 to 3.0. The engine bleed airflow range under study represents about a 10 fold decrease in micro -jet airflow than previously required. Therefore, by pre-conditioning, or injecting a very small amount of high-pressure jet flow into the vortex generated by the micro-vane and/or micro-ramp, active flow control is achieved and substantial augmentation of the controlling flow is realized.

  16. High responsivity CMOS imager pixel implemented in SOI technology

    NASA Technical Reports Server (NTRS)

    Zheng, X.; Wrigley, C.; Yang, G.; Pain, B.

    2000-01-01

    Availability of mature sub-micron CMOS technology and the advent of the new low noise active pixel sensor (APS) concept have enabled the development of low power, miniature, single-chip, CMOS digital imagers in the decade of the 1990's.

  17. Bacillus subtilis RNase Y Activity In Vivo Analysed by Tiling Microarrays

    PubMed Central

    Rocca, Anna; Zig, Léna; Nicolas, Pierre; Putzer, Harald

    2013-01-01

    RNase Y is a key endoribonuclease affecting global mRNA stability in Bacillus subtilis. Its characterization provided the first evidence that endonucleolytic cleavage plays a major role in the mRNA metabolism of this organism. RNase Y shares important functional features with the RNA decay initiating RNase E from Escherichia coli, notably a similar cleavage specificity and a preference for 5′ monophosphorylated substrates. We used high-resolution tiling arrays to analyze the effect of RNase Y depletion on RNA abundance covering the entire genome. The data confirm that this endoribonuclease plays a key role in initiating the decay of a large number of mRNAs as well as non coding RNAs. The downstream cleavage products are likely to be degraded by the 5′ exonucleolytic activity of RNases J1/J2 as we show for a specific case. Comparison of the data with that of two other recent studies revealed very significant differences. About two thirds of the mRNAs upregulated following RNase Y depletion were different when compared to either one of these studies and only about 10% were in common in all three studies. This highlights that experimental conditions and data analysis play an important role in identifying RNase Y substrates by global transcriptional profiling. Our data confirmed already known RNase Y substrates and due to the precision and reproducibility of the profiles allow an exceptionally detailed view of the turnover of hundreds of new RNA substrates. PMID:23326572

  18. CMOS detectors at Rome "Tor Vergata" University

    NASA Astrophysics Data System (ADS)

    Berrilli, F.; Cantarano, S.; Egidi, A.; Giordano, S.

    The new class of CMOS panoramic detectors represents an innovative tool for the experimental astronomy of the forthcoming years. While current charge-coupled device (CCD) technology can produce nearly ideal detectors for astronomical use, the scientific quality CMOS detectors made today have characteristics similar to those of CCD devices but a simpler electronics and a reduced cost. Moreover, the high frame rate capability and the amplification of each pixel - active pixel - in a CMOS detector, allows the implementation of a specific data management. So, it is possible to design cameras with very high dynamic range suitable for the imaging of solar active regions. In fact, in such regions, the onset of a flare can produce problems of saturation in a CCD-based camera. In this work we present the preliminary result obtained with the Tor Vergata C-Cam APS camera used at the University Solar Station.

  19. Josephson-CMOS Hybrid Memories

    DTIC Science & Technology

    2007-04-25

    Liu, X . Meng, S. R. Whiteley, and T. Van Duzer, “Characterization of 4 K CMOS devices and circuits for hybrid Josephson- CMOS systems,” IEEE Trans. on...Josephson- CMOS hybrid memories Qingguo Liu Electrical Engineering and Computer Sciences University of California at Berkeley Technical Report No. UCB...to 00-00-2007 4. TITLE AND SUBTITLE Josephson- CMOS hybrid memories 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

  20. CMOS foveal image sensor chip

    NASA Technical Reports Server (NTRS)

    Bandera, Cesar (Inventor); Scott, Peter (Inventor); Sridhar, Ramalingam (Inventor); Xia, Shu (Inventor)

    2002-01-01

    A foveal image sensor integrated circuit comprising a plurality of CMOS active pixel sensors arranged both within and about a central fovea region of the chip. The pixels in the central fovea region have a smaller size than the pixels arranged in peripheral rings about the central region. A new photocharge normalization scheme and associated circuitry normalizes the output signals from the different size pixels in the array. The pixels are assembled into a multi-resolution rectilinear foveal image sensor chip using a novel access scheme to reduce the number of analog RAM cells needed. Localized spatial resolution declines monotonically with offset from the imager's optical axis, analogous to biological foveal vision.

  1. Ion traps fabricated in a CMOS foundry

    SciTech Connect

    Mehta, K. K.; Ram, R. J.; Eltony, A. M.; Chuang, I. L.; Bruzewicz, C. D.; Sage, J. M. Chiaverini, J.

    2014-07-28

    We demonstrate trapping in a surface-electrode ion trap fabricated in a 90-nm CMOS (complementary metal-oxide-semiconductor) foundry process utilizing the top metal layer of the process for the trap electrodes. The process includes doped active regions and metal interconnect layers, allowing for co-fabrication of standard CMOS circuitry as well as devices for optical control and measurement. With one of the interconnect layers defining a ground plane between the trap electrode layer and the p-type doped silicon substrate, ion loading is robust and trapping is stable. We measure a motional heating rate comparable to those seen in surface-electrode traps of similar size. This demonstration of scalable quantum computing hardware utilizing a commercial CMOS process opens the door to integration and co-fabrication of electronics and photonics for large-scale quantum processing in trapped-ion arrays.

  2. CMOS sensor for face tracking and recognition

    NASA Astrophysics Data System (ADS)

    Ginhac, Dominique; Prasetyo, Eri; Paindavoine, Michel

    2005-03-01

    This paper describes the main principles of a vision sensor dedicated to the detecting and tracking faces in video sequences. For this purpose, a current mode CMOS active sensor has been designed using an array of pixels that are amplified by using current mirrors of column amplifier. This circuit is simulated using Mentor Graphics software with parameters of a 0.6 μm CMOS process. The circuit design is added with a sequential control unit which purpose is to realise capture of subwindows at any location and any size in the whole image.

  3. Implantable CMOS Biomedical Devices

    PubMed Central

    Ohta, Jun; Tokuda, Takashi; Sasagawa, Kiyotaka; Noda, Toshihiko

    2009-01-01

    The results of recent research on our implantable CMOS biomedical devices are reviewed. Topics include retinal prosthesis devices and deep-brain implantation devices for small animals. Fundamental device structures and characteristics as well as in vivo experiments are presented. PMID:22291554

  4. Analysis and Enhancement of Low-Light-Level Performance of Photodiode-Type CMOS Active Pixel Images Operated with Sub-Threshold Reset

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata; Yang, Guang; Ortiz, Monico; Wrigley, Christopher; Hancock, Bruce; Cunningham, Thomas

    2000-01-01

    Noise in photodiode-type CMOS active pixel sensors (APS) is primarily due to the reset (kTC) noise at the sense node, since it is difficult to implement in-pixel correlated double sampling for a 2-D array. Signal integrated on the photodiode sense node (SENSE) is calculated by measuring difference between the voltage on the column bus (COL) - before and after the reset (RST) is pulsed. Lower than kTC noise can be achieved with photodiode-type pixels by employing "softreset" technique. Soft-reset refers to resetting with both drain and gate of the n-channel reset transistor kept at the same potential, causing the sense node to be reset using sub-threshold MOSFET current. However, lowering of noise is achieved only at the expense higher image lag and low-light-level non-linearity. In this paper, we present an analysis to explain the noise behavior, show evidence of degraded performance under low-light levels, and describe new pixels that eliminate non-linearity and lag without compromising noise.

  5. All-CMOS night vision viewer with integrated microdisplay

    NASA Astrophysics Data System (ADS)

    Goosen, Marius E.; Venter, Petrus J.; du Plessis, Monuko; Faure, Nicolaas M.; Janse van Rensburg, Christo; Rademeyer, Pieter

    2014-02-01

    The unrivalled integration potential of CMOS has made it the dominant technology for digital integrated circuits. With the advent of visible light emission from silicon through hot carrier electroluminescence, several applications arose, all of which rely upon the advantages of mature CMOS technologies for a competitive edge in a very active and attractive market. In this paper we present a low-cost night vision viewer which employs only standard CMOS technologies. A commercial CMOS imager is utilized for near infrared image capturing with a 128x96 pixel all-CMOS microdisplay implemented to convey the image to the user. The display is implemented in a standard 0.35 μm CMOS process, with no process alterations or post processing. The display features a 25 μm pixel pitch and a 3.2 mm x 2.4 mm active area, which through magnification presents the virtual image to the user equivalent of a 19-inch display viewed from a distance of 3 meters. This work represents the first application of a CMOS microdisplay in a low-cost consumer product.

  6. Building strong partnerships with CMOs.

    PubMed

    Dye, Carson F

    2014-07-01

    CFOs and chief medical officers (CMOs) can build on common traits to form productive partnerships in guiding healthcare organizations through the changes affecting the industry. CFOs can strengthen bonds with CMOs by taking steps to engage physicians on their own turf--by visiting clinical locations and attending medical-executive committee meetings, for example. Steps CFOs can take to help CMOs become more acquainted with the financial operations of health systems include demonstrating the impact of clinical decisions on costs and inviting CMOs to attend finance-related meetings.

  7. The c-mos proto-oncogene protein kinase turns on and maintains the activity of MAP kinase, but not MPF, in cell-free extracts of Xenopus oocytes and eggs.

    PubMed Central

    Nebreda, A R; Hunt, T

    1993-01-01

    During studies of the activation and inactivation of the cyclin B-p34cdc2 protein kinase (MPF) in cell-free extracts of Xenopus oocytes and eggs, we found that a bacterially expressed fusion protein between the Escherichia coli maltose-binding protein and the Xenopus c-mos protein kinase (malE-mos) activated a 42 kDa MAP kinase. The activation of MAP kinase on addition of malE-mos was consistent, whereas the activation of MPF was variable and failed to occur in some oocyte extracts in which cyclin A or okadaic acid activated both MPF and MAP kinase. In cases when MPF activation was transient, MAP kinase activity declined after MPF activity was lost, and MAP kinase, but not MPF, could be maintained at a high level by the presence of malE-mos. When intact oocytes were treated with progesterone, however, the activation of MPF and MAP kinase occurred simultaneously, in contrast to the behaviour of extracts. These observations suggest that one role of c-mos may be to maintain high MAP kinase activity in meiosis. They also imply that the activation of MPF and MAP kinase in vivo are synchronous events that normally rely on an agent that has still to be identified. Images PMID:8387916

  8. Overview of Protein Microarrays

    PubMed Central

    Reymond Sutandy, FX; Qian, Jiang; Chen, Chien-Sheng; Zhu, Heng

    2013-01-01

    Protein microarray is an emerging technology that provides a versatile platform for characterization of hundreds of thousands of proteins in a highly parallel and high-throughput way. Two major classes of protein microarrays are defined to describe their applications: analytical and functional protein microarrays. In addition, tissue or cell lysates can also be fractionated and spotted on a slide to form a reverse-phase protein microarray. While the fabrication technology is maturing, applications of protein microarrays, especially functional protein microarrays, have flourished during the past decade. Here, we will first review recent advances in the protein microarray technologies, and then present a series of examples to illustrate the applications of analytical and functional protein microarrays in both basic and clinical research. The research areas will include detection of various binding properties of proteins, study of protein posttranslational modifications, analysis of host-microbe interactions, profiling antibody specificity, and identification of biomarkers in autoimmune diseases. As a powerful technology platform, it would not be surprising if protein microarrays will become one of the leading technologies in proteomic and diagnostic fields in the next decade. PMID:23546620

  9. Microarray Applications in Microbial Ecology Research.

    SciTech Connect

    Gentry, T.; Schadt, C.; Zhou, J.

    2006-04-06

    Microarray technology has the unparalleled potential tosimultaneously determine the dynamics and/or activities of most, if notall, of the microbial populations in complex environments such as soilsand sediments. Researchers have developed several types of arrays thatcharacterize the microbial populations in these samples based on theirphylogenetic relatedness or functional genomic content. Several recentstudies have used these microarrays to investigate ecological issues;however, most have only analyzed a limited number of samples withrelatively few experiments utilizing the full high-throughput potentialof microarray analysis. This is due in part to the unique analyticalchallenges that these samples present with regard to sensitivity,specificity, quantitation, and data analysis. This review discussesspecific applications of microarrays to microbial ecology research alongwith some of the latest studies addressing the difficulties encounteredduring analysis of complex microbial communities within environmentalsamples. With continued development, microarray technology may ultimatelyachieve its potential for comprehensive, high-throughput characterizationof microbial populations in near real-time.

  10. CMOS monolithic pixel sensors research and development at LBNL

    NASA Astrophysics Data System (ADS)

    Contarato, D.; Bussat, J.-M.; Denes, P.; Greiner, L.; Kim, T.; Stezelberger, T.; Wieman, H.; Battaglia, M.; Hooberman, B.; Tompkins, L.

    2007-12-01

    This paper summarizes the recent progress in the design and characterization of CMOS pixel sensors at LBNL. Results of lab tests, beam tests and radiation hardness tests carried out at LBNL on a test structure with pixels of various sizes are reported. The first results of the characterization of back-thinned CMOS pixel sensors are also reported, and future plans and activities are discussed.

  11. Regenerative switching CMOS system

    DOEpatents

    Welch, James D.

    1998-01-01

    Complementary Metal Oxide Semiconductor (CMOS) Schottky barrier Field Effect Transistor systems, which are a seriesed combination of N and P-Channel MOSFETS, in which Source Schottky barrier junctions of the N and P-Channel Schottky barrier MOSFETS are electically interconnected, (rather than the Drains as in conventional diffused junction CMOS), which Schottky barrier MOSFET system demonstrates Regenerative Inverting Switching Characteristics in use are disclosed. Both the N and P-Channel Schottky barrier MOSFET devices are unique in that they provide operational Drain Current vs. Drain to Source voltage as a function of Gate voltage only where the polarities of the Drain voltage and Gate voltage are opposite, referenced to the Source as a common terminal, and where the polarity of the voltage applied to the Gate is appropriate to cause Channel inversion. Experimentally derived results which demonstrate and verify the operation of N and P-Channel Schottky barrier MOSFETS actually fabricated on P and N-type Silicon respectively, by a common procedure using vacuum deposited Chromium as a Schottky barrier forming metal, are also provided.

  12. Regenerative switching CMOS system

    DOEpatents

    Welch, J.D.

    1998-06-02

    Complementary Metal Oxide Semiconductor (CMOS) Schottky barrier Field Effect Transistor systems, which are a series combination of N and P-Channel MOSFETS, in which Source Schottky barrier junctions of the N and P-Channel Schottky barrier MOSFETS are electrically interconnected, (rather than the Drains as in conventional diffused junction CMOS), which Schottky barrier MOSFET system demonstrates Regenerative Inverting Switching Characteristics in use are disclosed. Both the N and P-Channel Schottky barrier MOSFET devices are unique in that they provide operational Drain Current vs. Drain to Source voltage as a function of Gate voltage only where the polarities of the Drain voltage and Gate voltage are opposite, referenced to the Source as a common terminal, and where the polarity of the voltage applied to the Gate is appropriate to cause Channel inversion. Experimentally derived results which demonstrate and verify the operation of N and P-Channel Schottky barrier MOSFETS actually fabricated on P and N-type Silicon respectively, by a common procedure using vacuum deposited Chromium as a Schottky barrier forming metal, are also provided. 14 figs.

  13. Microarray in parasitic infections

    PubMed Central

    Sehgal, Rakesh; Misra, Shubham; Anand, Namrata; Sharma, Monika

    2012-01-01

    Modern biology and genomic sciences are rooted in parasitic disease research. Genome sequencing efforts have provided a wealth of new biological information that promises to have a major impact on our understanding of parasites. Microarrays provide one of the major high-throughput platforms by which this information can be exploited in the laboratory. Many excellent reviews and technique articles have recently been published on applying microarrays to organisms for which fully annotated genomes are at hand. However, many parasitologists work on organisms whose genomes have been only partially sequenced. This review is mainly focused on how to use microarray in these situations. PMID:23508469

  14. Microarray-integrated optoelectrofluidic immunoassay system.

    PubMed

    Han, Dongsik; Park, Je-Kyun

    2016-05-01

    A microarray-based analytical platform has been utilized as a powerful tool in biological assay fields. However, an analyte depletion problem due to the slow mass transport based on molecular diffusion causes low reaction efficiency, resulting in a limitation for practical applications. This paper presents a novel method to improve the efficiency of microarray-based immunoassay via an optically induced electrokinetic phenomenon by integrating an optoelectrofluidic device with a conventional glass slide-based microarray format. A sample droplet was loaded between the microarray slide and the optoelectrofluidic device on which a photoconductive layer was deposited. Under the application of an AC voltage, optically induced AC electroosmotic flows caused by a microarray-patterned light actively enhanced the mass transport of target molecules at the multiple assay spots of the microarray simultaneously, which reduced tedious reaction time from more than 30 min to 10 min. Based on this enhancing effect, a heterogeneous immunoassay with a tiny volume of sample (5 μl) was successfully performed in the microarray-integrated optoelectrofluidic system using immunoglobulin G (IgG) and anti-IgG, resulting in improved efficiency compared to the static environment. Furthermore, the application of multiplex assays was also demonstrated by multiple protein detection.

  15. Protein Microarrays: Novel Developments and Applications

    PubMed Central

    Berrade, Luis; Garcia, Angie E.

    2011-01-01

    Protein microarray technology possesses some of the greatest potential for providing direct information on protein function and potential drug targets. For example, functional protein microarrays are ideal tools suited for the mapping of biological pathways. They can be used to study most major types of interactions and enzymatic activities that take place in biochemical pathways and have been used for the analysis of simultaneous multiple biomolecular interactions involving protein-protein, protein-lipid, protein-DNA and protein-small molecule interactions. Because of this unique ability to analyze many kinds of molecular interactions en masse, the requirement of very small sample amount and the potential to be miniaturized and automated, protein microarrays are extremely well suited for protein profiling, drug discovery, drug target identification and clinical prognosis and diagnosis. The aim of this review is to summarize the most recent developments in the production, applications and analysis of protein microarrays. PMID:21116694

  16. 2-amino-nonyl-6-methoxyl-tetralin muriate activity against Candida albicans augments endogenous reactive oxygen species production --a microarray analysis study.

    PubMed

    Liang, Rong Mei; Yong, Xiao Lan; Jiang, Yun Ping; Tan, Yong Hong; Dai, Bao Di; Wang, Shi Hua; Hu, Ting Ting; Chen, Xi; Li, Nan; Dong, Zhao Hui; Huang, Xiao Chun; Chen, Jun; Cao, Yong Bing; Jiang, Yuan Ying

    2011-04-01

    Candida infections have become an increasingly significant problem, mainly because of the widespread nature of Candida and drug resistance. There is an urgent need to develop new classes of drugs for the treatment of opportunistic Candida infections, especially in medically complex patients. Previous studies have confirmed that 2-amino-nonyl-6-methoxyl-tetralin muriate (10b) possesses powerful antifungal activity in vitro against Candia albicans. To clarify the underlying action mechanism, an oligonucleotide microarray study was performed in C. albicans SC5314 without and with 10b treatment. The analytical results showed that energy metabolism-related genes, including glycolysis-related genes (PFK1, CDC19 and HXK2), fermentation-related genes (PDC11, ALD5 and ADH1) and respiratory electron transport chain-related genes (CBP3, COR1 and QCR8), were downregulated significantly. Functional analysis revealed that 10b treatment increased the generation of endogenous reactive oxygen species, and decreased mitochondrial membrane potential, ubiquinone-cytochrome c reductase (complex III) activity and intracellular ATP levels in C. albicans SC5314. Also, addition of the antioxidant ascorbic acid reduced the antifungal activity of 10b significantly. These results suggest that mitochondrial aerobic respiration shift and endogenous reactive oxygen species augmentation might contribute to the antifungal activity of 10b against C. albicans. This information may prove to be useful for the development of new strategies to treat Candida infections.

  17. Dynamic of active microorganisms inhabiting a bioleaching industrial heap of low‐grade copper sulfide ore monitored by real‐time PCR and oligonucleotide prokaryotic acidophile microarray

    PubMed Central

    Remonsellez, Francisco; Galleguillos, Felipe; Moreno‐Paz, Mercedes; Parro, Víctor; Acosta, Mauricio; Demergasso, Cecilia

    2009-01-01

    Summary The bioleaching of metal sulfide has developed into a very important industrial process and understanding the microbial dynamic is key to advancing commercial bioleaching operations. Here we report the first quantitative description of the dynamic of active communities in an industrial bioleaching heap. Acidithiobacillus ferrooxidans was the most abundant during the first part of the leaching cycle, while the abundance of Leptospirillum ferriphilum and Ferroplasma acidiphilum increased with age of the heap. Acidithiobacillus thiooxidans kept constant throughout the leaching cycle, and Firmicutes group showed a low and a patchy distribution in the heap. The Acidiphilium‐like bacteria reached their highest abundance corresponding to the amount of autotrophs. The active microorganisms in the leaching system were determined using two RNA‐based sensitive techniques. In most cases, the 16S rRNA copy numbers of At. ferrooxidans, L. ferriphilum, At. thiooxidans and F. acidiphilum, was concomitant with the DNA copy numbers, whereas Acidiphilium‐like bacteria and some Firmicutes members did not show a clear correlation between 16S rRNA accumulation and DNA copy numbers. However, the prokaryotic acidophile microarray (PAM) analysis showed active members of Alphaproteobacteria in all samples and of Sulfobacillus genus in older ones. Also, new active groups such as Actinobacteria and Acidobacterium genus were detected by PAM. The results suggest that changes during the leaching cycle in chemical and physical conditions, such as pH and Fe3+/Fe2+ ion rate, are primary factors shaping the microbial dynamic in the heap. PMID:21255296

  18. CMOS array design automation techniques

    NASA Technical Reports Server (NTRS)

    Lombardi, T.; Feller, A.

    1976-01-01

    The design considerations and the circuit development for a 4096-bit CMOS SOS ROM chip, the ATL078 are described. Organization of the ATL078 is 512 words by 8 bits. The ROM was designed to be programmable either at the metal mask level or by a directed laser beam after processing. The development of a 4K CMOS SOS ROM fills a void left by available ROM chip types, and makes the design of a totally major high speed system more realizable.

  19. Microarray data and pathway analyses for primary human activated hepatic stellate cells compared to HepG2 human hepatoma cells.

    PubMed

    Hetherington, Alexandra M; Sawyez, Cynthia G; Borradaile, Nica M

    2017-02-01

    As nonalcoholic fatty liver disease progresses to end-stage diseases, including fibrosis, cirrhosis and hepatocellular carcinoma, fibrotic activated hepatic stellate cells and cancerous epithelial cells can become abundant, changing the cellular composition of this organ. Despite potentially residing within the same diseased tissue, direct comparisons of global gene expression between activated hepatic stellate cells and hepatocellular carcinoma cells are lacking. Here we provide data collected using Affymetrix GeneChip microarrays to identify differential gene expression in cultured primary human activated hepatic stellate cells compared to HepG2 human hepatoma cells. The dataset includes many genes involved in intermediary metabolism which were investigated in greater depth in our associated article (A.M. Hetherington, C.G. Sawyez, E. Zilberman, A.M. Stoianov, D.L. Robson, J.M. Hughes-Large, et al., 2016) [1]. Pathway analyses of known protein coding genes down-regulated or up-regulated by greater than 2.0-fold are also provided.

  20. Multievidence microarray mining.

    PubMed

    Seifert, Martin; Scherf, Matthias; Epple, Anton; Werner, Thomas

    2005-10-01

    Microarray mining is a challenging task because of the superposition of several processes in the data. We believe that the combination of microarray data-based analyses (statistical significance analysis of gene expression) with array-independent analyses (literature-mining and promoter analysis) enables some of the problems of traditional array analysis to be overcome. As a proof-of-principle, we revisited publicly available microarray data derived from an experiment with platelet-derived growth factor (PDGF)-stimulated fibroblasts. Our strategy revealed results beyond the detection of the major metabolic pathway known to be linked to the PDGF response: we were able to identify the crosstalking regulatory networks underlying the metabolic pathway without using a priori knowledge about the experiment.

  1. Design and Fabrication of Vertically-Integrated CMOS Image Sensors

    PubMed Central

    Skorka, Orit; Joseph, Dileepan

    2011-01-01

    Technologies to fabricate integrated circuits (IC) with 3D structures are an emerging trend in IC design. They are based on vertical stacking of active components to form heterogeneous microsystems. Electronic image sensors will benefit from these technologies because they allow increased pixel-level data processing and device optimization. This paper covers general principles in the design of vertically-integrated (VI) CMOS image sensors that are fabricated by flip-chip bonding. These sensors are composed of a CMOS die and a photodetector die. As a specific example, the paper presents a VI-CMOS image sensor that was designed at the University of Alberta, and fabricated with the help of CMC Microsystems and Micralyne Inc. To realize prototypes, CMOS dies with logarithmic active pixels were prepared in a commercial process, and photodetector dies with metal-semiconductor-metal devices were prepared in a custom process using hydrogenated amorphous silicon. The paper also describes a digital camera that was developed to test the prototype. In this camera, scenes captured by the image sensor are read using an FPGA board, and sent in real time to a PC over USB for data processing and display. Experimental results show that the VI-CMOS prototype has a higher dynamic range and a lower dark limit than conventional electronic image sensors. PMID:22163860

  2. Design and fabrication of vertically-integrated CMOS image sensors.

    PubMed

    Skorka, Orit; Joseph, Dileepan

    2011-01-01

    Technologies to fabricate integrated circuits (IC) with 3D structures are an emerging trend in IC design. They are based on vertical stacking of active components to form heterogeneous microsystems. Electronic image sensors will benefit from these technologies because they allow increased pixel-level data processing and device optimization. This paper covers general principles in the design of vertically-integrated (VI) CMOS image sensors that are fabricated by flip-chip bonding. These sensors are composed of a CMOS die and a photodetector die. As a specific example, the paper presents a VI-CMOS image sensor that was designed at the University of Alberta, and fabricated with the help of CMC Microsystems and Micralyne Inc. To realize prototypes, CMOS dies with logarithmic active pixels were prepared in a commercial process, and photodetector dies with metal-semiconductor-metal devices were prepared in a custom process using hydrogenated amorphous silicon. The paper also describes a digital camera that was developed to test the prototype. In this camera, scenes captured by the image sensor are read using an FPGA board, and sent in real time to a PC over USB for data processing and display. Experimental results show that the VI-CMOS prototype has a higher dynamic range and a lower dark limit than conventional electronic image sensors.

  3. DNA microarray technology. Introduction.

    PubMed

    Pollack, Jonathan R

    2009-01-01

    DNA microarray technology has revolutionized biological research by enabling genome-scale explorations. This chapter provides an overview of DNA microarray technology and its application to characterizing the physical genome, with a focus on cancer genomes. Specific areas discussed include investigations of DNA copy number alteration (and loss of heterozygosity), DNA methylation, DNA-protein (i.e., chromatin and transcription factor) interactions, DNA replication, and the integration of diverse genome-scale data types. Also provided is a perspective on recent advances and future directions in characterizing the physical genome.

  4. Study of antimutagenic and antioxidant activities of gallic acid and 1,2,3,4,6-pentagalloylglucose from Pistacia lentiscus. Confirmation by microarray expression profiling.

    PubMed

    Abdelwahed, Afef; Bouhlel, Ines; Skandrani, Ines; Valenti, Kita; Kadri, Malika; Guiraud, Pascal; Steiman, Régine; Mariotte, Anne-Marie; Ghedira, Kamel; Laporte, François; Dijoux-Franca, Marie-Geneviève; Chekir-Ghedira, Leila

    2007-01-05

    In vitro antioxidant and antimutagenic activities of two polyphenols isolated from the fruits of Pistacia lentiscus was assessed. Antioxidant activity was determined by the ability of each compound to scavenge the free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH*), to inhibit xanthine oxidase and to inhibit the lipid peroxidation induced by H(2)O(2) in K562 cell line. Antimutagenic activity was assayed with SOS chromotest using Escherichia coli PQ37 as tester strain and Comet assay using K562 cell line. 1,2,3,4,6-Pentagalloylglucose was found to be more effective to scavenge DPPH* radical and protect against lipid peroxidation. Moreover, these two compounds induced an inhibitory activity against nifuroxazide and aflatoxin B1 mutagenicity. The protective effect exhibited by these molecules was also determined by analysis of gene expression as response to an oxidative stress. For this purpose, we used a cDNA-microarray containing 82 genes related to cell defense, essentially represented by antioxidant and DNA repair proteins. We found that 1,2,3,4,6-pentagalloylglucose induced a decrease in the expression of 11 transcripts related to antioxidant enzymes family (GPX1, TXN, AOE372, SHC1 and SEPW1) and DNA repair (POLD1, APEX, POLD2, MPG, PARP and XRCC5). The use of Gallic acid, induced expression of TXN, TXNRD1, AOE372, GSS (antioxidant enzymes) and LIG4, POLD2, MPG, GADD45A, PCNA, RPA2, DDIT3, HMOX2, XPA, TDG, ERCC1 and GTF2H1 (DNA repair) as well as the repression of GPX1, SEPW1, POLD1 and SHC1 gene expression.

  5. Protein Microarray Technology

    PubMed Central

    Hall, David A.; Ptacek, Jason

    2007-01-01

    Protein chips have emerged as a promising approach for a wide variety of applications including the identification of protein-protein interactions, protein-phospholipid interactions, small molecule targets, and substrates of proteins kinases. They can also be used for clinical diagnostics and monitoring disease states. This article reviews current methods in the generation and applications of protein microarrays. PMID:17126887

  6. Microarrays for Undergraduate Classes

    ERIC Educational Resources Information Center

    Hancock, Dale; Nguyen, Lisa L.; Denyer, Gareth S.; Johnston, Jill M.

    2006-01-01

    A microarray experiment is presented that, in six laboratory sessions, takes undergraduate students from the tissue sample right through to data analysis. The model chosen, the murine erythroleukemia cell line, can be easily cultured in sufficient quantities for class use. Large changes in gene expression can be induced in these cells by…

  7. Direct immobilization of DNA oligomers onto the amine-functionalized glass surface for DNA microarray fabrication through the activation-free reaction of oxanine

    PubMed Central

    Pack, Seung Pil; Kamisetty, Nagendra Kumar; Nonogawa, Mitsuru; Devarayapalli, Kamakshaiah Charyulu; Ohtani, Kairi; Yamada, Kazunari; Yoshida, Yasuko; Kodaki, Tsutomu; Makino, Keisuke

    2007-01-01

    Oxanine having an O-acylisourea structure was explored to see if its reactivity with amino group is useful in DNA microarray fabrication. By the chemical synthesis, a nucleotide unit of oxanine (Oxa-N) was incorporated into the 5′-end of probe DNA with or without the -(CH2)n- spacers (n = 3 and 12) and found to immobilize the probe DNA covalently onto the NH2-functionalized glass slide by one-pot reaction, producing the high efficiency of the target hybridization. The methylene spacer, particularly the longer one, generated higher efficiency of the target recognition although there was little effect on the amount of the immobilized DNA oligomers. The post-spotting treatment was also carried out under the mild conditions (at 25 or 42°C) and the efficiencies of the immobilization and the target recognition were evaluated similarly, and analogous trends were obtained. It has also been determined under the mild conditions that the humidity and time of the post-spotting treatment, pH of the spotting solution and the synergistic effects with UV-irradiation largely contribute to the desired immobilization and resulting target recognition. Immobilization of DNA oligomer by use of Oxa-N on the NH2-functionalized surface without any activation step would be employed as one of the advanced methods for generating DNA-conjugated solid surface. PMID:17715142

  8. A CMOS floating point multiplier

    NASA Astrophysics Data System (ADS)

    Uya, M.; Kaneko, K.; Yasui, J.

    1984-10-01

    This paper describes a 32-bit CMOS floating point multiplier. The chip can perform 32-bit floating point multiplication (based on the proposed IEEE Standard format) and 24-bit fixed point multiplication (two's complement format) in less than 78.7 and 71.1 ns, respectively, and the typical power dissipation is 195 mW at 10 million operations per second. High-speed multiplication techniques - a modified Booth's allgorithm, a carry save adder scheme, a high-speed CMOS full adder, and a modified carry select adder - are used to achieve the above high performance. The chip is designed for compatibility with 16-bit microcomputer systems, and is fabricated in 2 micron n-well CMOS technology; it contains about 23000 transistors of 5.75 x 5.67 sq mm in size.

  9. MonoColor CMOS sensor

    NASA Astrophysics Data System (ADS)

    Wang, Ynjiun P.

    2009-02-01

    A new breed of CMOS color sensor called MonoColor sensor is developed for a barcode reading application in AIDC industry. The RGBW color filter array (CFA) in a MonoColor sensor is arranged in a 8 x 8 pixels CFA with only 4 pixels of them are color (RGB) pixels and the rest of 60 pixels are transparent or monochrome. Since the majority of pixels are monochrome, MonoColor sensor maintains 98% barcode decode performance compared with a pure monochrome CMOS sensor. With the help of monochrome and color pixel fusion technique, the resulting color pictures have similar color quality in terms of Color Semantic Error (CSE) compared with a Bayer pattern (RGB) CMOS color camera. Since monochrome pixels are more sensitive than color pixels, a MonoColor sensor produces in general about 2X brighter color picture and higher luminance pixel resolution.

  10. Improved Space Object Observation Techniques Using CMOS Detectors

    NASA Astrophysics Data System (ADS)

    Schildknecht, T.; Hinze, A.; Schlatter, P.; Silha, J.; Peltonen, J.; Santti, T.; Flohrer, T.

    2013-08-01

    CMOS-sensors, or in general Active Pixel Sensors (APS), are rapidly replacing CCDs in the consumer camera market. Due to significant technological advances during the past years these devices start to compete with CCDs also for demanding scientific imaging applications, in particular in the astronomy community. CMOS detectors offer a series of inherent advantages compared to CCDs, due to the structure of their basic pixel cells, which each contain their own amplifier and readout electronics. The most prominent advantages for space object observations are the extremely fast and flexible readout capabilities, feasibility for electronic shuttering and precise epoch registration, and the potential to perform image processing operations on-chip and in real-time. Presently applied and proposed optical observation strategies for space debris surveys and space surveillance applications had to be analyzed. The major design drivers were identified and potential benefits from using available and future CMOS sensors were assessed. The major challenges and design drivers for ground-based and space-based optical observation strategies have been analyzed. CMOS detector characteristics were critically evaluated and compared with the established CCD technology, especially with respect to the above mentioned observations. Similarly, the desirable on-chip processing functionalities which would further enhance the object detection and image segmentation were identified. Finally, the characteristics of a particular CMOS sensor available at the Zimmerwald observatory were analyzed by performing laboratory test measurements.

  11. Application of DNA microarray technology to gerontological studies.

    PubMed

    Masuda, Kiyoshi; Kuwano, Yuki; Nishida, Kensei; Rokutan, Kazuhito

    2013-01-01

    Gene expression patterns change dramatically in aging and age-related events. The DNA microarray is now recognized as a useful device in molecular biology and widely used to identify the molecular mechanisms of aging and the biological effects of drugs for therapeutic purpose in age-related diseases. Recently, numerous technological advantages have led to the evolution of DNA microarrays and microarray-based techniques, revealing the genomic modification and all transcriptional activity. Here, we show the step-by-step methods currently used in our lab to handling the oligonucleotide microarray and miRNA microarray. Moreover, we introduce the protocols of ribonucleoprotein [RNP] immunoprecipitation followed by microarray analysis (RIP-chip) which reveal the target mRNA of age-related RNA-binding proteins.

  12. Studying cellular processes and detecting disease with protein microarrays

    SciTech Connect

    Zangar, Richard C.; Varnum, Susan M.; Bollinger, Nikki

    2005-10-31

    Protein microarrays are a rapidly developing analytic tool with diverse applications in biomedical research. These applications include profiling of disease markers or autoimmune responses, understanding molecular pathways, protein modifications and protein activities. One factor that is driving this expanding usage is the wide variety of experimental formats that protein microarrays can take. In this review, we provide a short, conceptual overview of the different approaches for protein microarray. We then examine some of the most significant applications of these microarrays to date, with an emphasis on how global protein analyses can be used to facilitate biomedical research.

  13. CMOS Integrated Carbon Nanotube Sensor

    SciTech Connect

    Perez, M. S.; Lerner, B.; Boselli, A.; Lamagna, A.; Obregon, P. D. Pareja; Julian, P. M.; Mandolesi, P. S.; Buffa, F. A.

    2009-05-23

    Recently carbon nanotubes (CNTs) have been gaining their importance as sensors for gases, temperature and chemicals. Advances in fabrication processes simplify the formation of CNT sensor on silicon substrate. We have integrated single wall carbon nanotubes (SWCNTs) with complementary metal oxide semiconductor process (CMOS) to produce a chip sensor system. The sensor prototype was designed and fabricated using a 0.30 um CMOS process. The main advantage is that the device has a voltage amplifier so the electrical measure can be taken and amplified inside the sensor. When the conductance of the SWCNTs varies in response to media changes, this is observed as a variation in the output tension accordingly.

  14. Microarray Analysis of Genes Involved with Shell Strength in Layer Shell Gland at the Early Stage of Active Calcification

    PubMed Central

    Liu, Zhangguo; Zheng, Qi; Zhang, Xueyu; Lu, Lizhi

    2013-01-01

    The objective of this study was to get a comprehensive understanding of how genes in chicken shell gland modulate eggshell strength at the early stage of active calcification. Four 32-week old of purebred Xianju hens with consistent high or low shell breakage strength were grouped into two pairs. Using Affymetrix Chicken Array, a whole-transcriptome analysis was performed on hen’s shell gland at 9 h post oviposition. Gene ontology enrichment analysis for differentially expressed (DE) transcripts was performed using the web-based GOEAST, and the validation of DE-transcripts was tested by qRT-PCR. 1,195 DE-transcripts, corresponding to 941 unique genes were identified in hens with strong eggshell compared to weak shell hens. According to gene ontology annotations, there are 77 DE-transcripts encoding ion transporters and secreted extracellular matrix proteins, and at least 26 DE-transcripts related to carbohydrate metabolism or post-translation glycosylation modification; furthermore, there are 88 signaling DE-transcripts. GO term enrichment analysis suggests that some DE-transcripts mediate reproductive hormones or neurotransmitters to affect eggshell quality through a complex suite of biophysical processes. These results reveal some candidate genes involved with eggshell strength at the early stage of active calcification which may facilitate our understanding of regulating mechanisms of eggshell quality. PMID:25049830

  15. Reliability in CMOS IC processing

    NASA Technical Reports Server (NTRS)

    Shreeve, R.; Ferrier, S.; Hall, D.; Wang, J.

    1990-01-01

    Critical CMOS IC processing reliability monitors are defined in this paper. These monitors are divided into three categories: process qualifications, ongoing production workcell monitors, and ongoing reliability monitors. The key measures in each of these categories are identified and prioritized based on their importance.

  16. Development of CMOS integrated circuits

    NASA Technical Reports Server (NTRS)

    Bertino, F.; Feller, A.; Greenhouse, J.; Lombardi, T.; Merriam, A.; Noto, R.; Ozga, S.; Pryor, R.; Ramondetta, P.; Smith, A.

    1979-01-01

    Report documents life cycles of two custom CMOS integrated circuits: (1) 4-bit multiplexed register with shift left and shift right capabilities, and (2) dual 4-bit registers. Cycles described include conception as logic diagrams through design, fabrication, testing, and delivery.

  17. Microarray and Pathway Analysis Reveal Distinct Mechanisms Underlying Cannabinoid-Mediated Modulation of LPS-Induced Activation of BV-2 Microglial Cells

    PubMed Central

    Juknat, Ana; Kozela, Ewa; Rimmerman, Neta; Levy, Rivka; Gao, Fuying; Coppola, Giovanni; Geschwind, Daniel; Vogel, Zvi

    2013-01-01

    Cannabinoids are known to exert immunosuppressive activities. However, the mechanisms which contribute to these effects are unknown. Using lipopolysaccharide (LPS) to activate BV-2 microglial cells, we examined how Δ9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, and cannabidiol (CBD) the non-psychoactive component, modulate the inflammatory response. Microarray analysis of genome-wide mRNA levels was performed using Illumina platform and the resulting expression patterns analyzed using the Ingenuity Pathway Analysis to identify functional subsets of genes, and the Ingenuity System Database to denote the gene networks regulated by CBD and THC. From the 5338 transcripts that were differentially expressed across treatments, 400 transcripts were found to be upregulated by LPS, 502 by CBD+LPS and 424 by THC+LPS, while 145 were downregulated by LPS, 297 by CBD+LPS and 149 by THC+LPS, by 2-fold or more (p≤0.005). Results clearly link the effects of CBD and THC to inflammatory signaling pathways and identify new cannabinoid targets in the MAPK pathway (Dusp1, Dusp8, Dusp2), cell cycle related (Cdkn2b, Gadd45a) as well as JAK/STAT regulatory molecules (Socs3, Cish, Stat1). The impact of CBD on LPS-stimulated gene expression was greater than that of THC. We attribute this difference to the fact that CBD highly upregulated several genes encoding negative regulators of both NFκB and AP-1 transcriptional activities, such as Trib3 and Dusp1 known to be modulated through Nrf2 activation. The CBD-specific expression profile reflected changes associated with oxidative stress and glutathione depletion via Trib3 and expression of ATF4 target genes. Furthermore, the CBD affected genes were shown to be controlled by nuclear factors usually involved in regulation of stress response and inflammation, mainly via Nrf2/Hmox1 axis and the Nrf2/ATF4-Trib3 pathway. These observations indicate that CBD, and less so THC, induce a cellular stress response and

  18. Analyzing Microarray Data.

    PubMed

    Hung, Jui-Hung; Weng, Zhiping

    2017-03-01

    Because there is no widely used software for analyzing RNA-seq data that has a graphical user interface, this protocol provides an example of analyzing microarray data using Babelomics. This analysis entails performing quantile normalization and then detecting differentially expressed genes associated with the transgenesis of a human oncogene c-Myc in mice. Finally, hierarchical clustering is performed on the differentially expressed genes using the Cluster program, and the results are visualized using TreeView.

  19. Membrane-based microarrays

    NASA Astrophysics Data System (ADS)

    Dawson, Elliott P.; Hudson, James; Steward, John; Donnell, Philip A.; Chan, Wing W.; Taylor, Richard F.

    1999-11-01

    Microarrays represent a new approach to the rapid detection and identification of analytes. Studies to date have shown that the immobilization of receptor molecules (such as DNA, oligonucleotides, antibodies, enzymes and binding proteins) onto silicon and polymeric substrates can result in arrays able to detect hundreds of analytes in a single step. The formation of the receptor/analyte complex can, itself, lead to detection, or the complex can be interrogated through the use of fluorescent, chemiluminescent or radioactive probes and ligands.

  20. Planar CMOS analog SiPMs: design, modeling, and characterization

    NASA Astrophysics Data System (ADS)

    Zou, Yu; Villa, Federica; Bronzi, Danilo; Tisa, Simone; Tosi, Alberto; Zappa, Franco

    2015-11-01

    Silicon photomultipliers (SiPMs) are large area detectors consisting of an array of single-photon-sensitive microcells, which make SiPMs extremely attractive to substitute the photomultiplier tubes in many applications. We present the design, fabrication, and characterization of analog SiPMs in standard planar 0.35 μm CMOS technology, with about 1 mm × 1 mm total area and different kinds of microcells, based on single-photon avalanche diodes with 30 μm diameter reaching 21.0% fill-factor (FF), 50 μm diameter (FF = 58.3%) or 50 μm square active area with rounded corner of 5 μm radius (FF = 73.7%). We also developed the electrical SPICE model for CMOS SiPMs. Our CMOS SiPMs have 25 V breakdown voltage, in line with most commercial SiPMs and higher gain (8.8 × 106, 13.2 × 106, and 15.0 × 106, respectively). Although dark count rate density is slightly higher than state-of-the-art analog SiPMs, the proposed standard CMOS processing opens the feasibility of integration with active electronics, for switching hot pixels off, drastically reducing the overall dark count rate, or for further on-chip processing.

  1. Surface chemistries for antibody microarrays

    SciTech Connect

    Seurynck-Servoss, Shannon L.; Baird, Cheryl L.; Rodland, Karin D.; Zangar, Richard C.

    2007-05-01

    Enzyme-linked immunosorbent assay (ELISA) microarrays promise to be a powerful tool for the detection of disease biomarkers. The original technology for printing ELISA microarray chips and capturing antibodies on slides was derived from the DNA microarray field. However, due to the need to maintain antibody structure and function when immobilized, surface chemistries used for DNA microarrays are not always appropriate for ELISA microarrays. In order to identify better surface chemistries for antibody capture, a number of commercial companies and academic research groups have developed new slide types that could improve antibody function in microarray applications. In this review we compare and contrast the commercially available slide chemistries, as well as highlight some promising recent advances in the field.

  2. Digital-Centric RF CMOS Technologies

    NASA Astrophysics Data System (ADS)

    Matsuzawa, Akira

    Analog-centric RFCMOS technology has played an important role in motivating the change of technology from conventional discrete device technology or bipolar IC technology to CMOS technology. However it introduces many problems such as poor performance, susceptibility to PVT fluctuation, and cost increase with technology scaling. The most important advantage of CMOS technology compared with legacy RF technology is that CMOS can use more high performance digital circuits for very low cost. In fact, analog-centric RF-CMOS technology has failed the FM/AM tuner business and the digital-centric CMOS technology is becoming attractive for many users. It has many advantages; such as high performance, no external calibration points, high yield, and low cost. From the above facts, digital-centric CMOS technology which utilizes the advantages of digital technology must be the right path for future RF technology. Further investment in this technology is necessary for the advancement of RF technology.

  3. Research on evaluation method of CMOS camera

    NASA Astrophysics Data System (ADS)

    Zhang, Shaoqiang; Han, Weiqiang; Cui, Lanfang

    2014-09-01

    In some professional image application fields, we need to test some key parameters of the CMOS camera and evaluate the performance of the device. Aiming at this requirement, this paper proposes a perfect test method to evaluate the CMOS camera. Considering that the CMOS camera has a big fixed pattern noise, the method proposes the `photon transfer curve method' based on pixels to measure the gain and the read noise of the camera. The advantage of this method is that it can effectively wipe out the error brought by the response nonlinearity. Then the reason of photoelectric response nonlinearity of CMOS camera is theoretically analyzed, and the calculation formula of CMOS camera response nonlinearity is deduced. Finally, we use the proposed test method to test the CMOS camera of 2560*2048 pixels. In addition, we analyze the validity and the feasibility of this method.

  4. CMOS output buffer wave shaper

    NASA Technical Reports Server (NTRS)

    Albertson, L.; Whitaker, S.; Merrell, R.

    1990-01-01

    As the switching speeds and densities of Digital CMOS integrated circuits continue to increase, output switching noise becomes more of a problem. A design technique which aids in the reduction of switching noise is reported. The output driver stage is analyzed through the use of an equivalent RLC circuit. The results of the analysis are used in the design of an output driver stage. A test circuit based on these techniques is being submitted to MOSIS for fabrication.

  5. The use of microarrays in microbial ecology

    SciTech Connect

    Andersen, G.L.; He, Z.; DeSantis, T.Z.; Brodie, E.L.; Zhou, J.

    2009-09-15

    Microarrays have proven to be a useful and high-throughput method to provide targeted DNA sequence information for up to many thousands of specific genetic regions in a single test. A microarray consists of multiple DNA oligonucleotide probes that, under high stringency conditions, hybridize only to specific complementary nucleic acid sequences (targets). A fluorescent signal indicates the presence and, in many cases, the abundance of genetic regions of interest. In this chapter we will look at how microarrays are used in microbial ecology, especially with the recent increase in microbial community DNA sequence data. Of particular interest to microbial ecologists, phylogenetic microarrays are used for the analysis of phylotypes in a community and functional gene arrays are used for the analysis of functional genes, and, by inference, phylotypes in environmental samples. A phylogenetic microarray that has been developed by the Andersen laboratory, the PhyloChip, will be discussed as an example of a microarray that targets the known diversity within the 16S rRNA gene to determine microbial community composition. Using multiple, confirmatory probes to increase the confidence of detection and a mismatch probe for every perfect match probe to minimize the effect of cross-hybridization by non-target regions, the PhyloChip is able to simultaneously identify any of thousands of taxa present in an environmental sample. The PhyloChip is shown to reveal greater diversity within a community than rRNA gene sequencing due to the placement of the entire gene product on the microarray compared with the analysis of up to thousands of individual molecules by traditional sequencing methods. A functional gene array that has been developed by the Zhou laboratory, the GeoChip, will be discussed as an example of a microarray that dynamically identifies functional activities of multiple members within a community. The recent version of GeoChip contains more than 24,000 50mer

  6. CMOS imager for pointing and tracking applications

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata (Inventor); Sun, Chao (Inventor); Yang, Guang (Inventor); Heynssens, Julie B. (Inventor)

    2006-01-01

    Systems and techniques to realize pointing and tracking applications with CMOS imaging devices. In general, in one implementation, the technique includes: sampling multiple rows and multiple columns of an active pixel sensor array into a memory array (e.g., an on-chip memory array), and reading out the multiple rows and multiple columns sampled in the memory array to provide image data with reduced motion artifact. Various operation modes may be provided, including TDS, CDS, CQS, a tracking mode to read out multiple windows, and/or a mode employing a sample-first-read-later readout scheme. The tracking mode can take advantage of a diagonal switch array. The diagonal switch array, the active pixel sensor array and the memory array can be integrated onto a single imager chip with a controller. This imager device can be part of a larger imaging system for both space-based applications and terrestrial applications.

  7. Analysis of pixel circuits in CMOS image sensors

    NASA Astrophysics Data System (ADS)

    Mei, Zou; Chen, Nan; Yao, Li-bin

    2015-04-01

    CMOS image sensors (CIS) have lower power consumption, lower cost and smaller size than CCD image sensors. However, generally CCDs have higher performance than CIS mainly due to lower noise. The pixel circuit used in CIS is the first part of the signal processing circuit and connected to photodiode directly, so its performance will greatly affect the CIS or even the whole imaging system. To achieve high performance, CMOS image sensors need advanced pixel circuits. There are many pixel circuits used in CIS, such as passive pixel sensor (PPS), 3T and 4T active pixel sensor (APS), capacitive transimpedance amplifier (CTIA), and passive pixel sensor (PPS). At first, the main performance parameters of each pixel structure including the noise, injection efficiency, sensitivity, power consumption, and stability of bias voltage are analyzed. Through the theoretical analysis of those pixel circuits, it is concluded that CTIA pixel circuit has good noise performance, high injection efficiency, stable photodiode bias, and high sensitivity with small integrator capacitor. Furthermore, the APS and CTIA pixel circuits are simulated in a standard 0.18-μm CMOS process and using a n-well/p-sub photodiode by SPICE and the simulation result confirms the theoretical analysis result. It shows the possibility that CMOS image sensors can be extended to a wide range of applications requiring high performance.

  8. High-content analysis of single cells directly assembled on CMOS sensor based on color imaging.

    PubMed

    Tanaka, Tsuyoshi; Saeki, Tatsuya; Sunaga, Yoshihiko; Matsunaga, Tadashi

    2010-12-15

    A complementary metal oxide semiconductor (CMOS) image sensor was applied to high-content analysis of single cells which were assembled closely or directly onto the CMOS sensor surface. The direct assembling of cell groups on CMOS sensor surface allows large-field (6.66 mm×5.32 mm in entire active area of CMOS sensor) imaging within a second. Trypan blue-stained and non-stained cells in the same field area on the CMOS sensor were successfully distinguished as white- and blue-colored images under white LED light irradiation. Furthermore, the chemiluminescent signals of each cell were successfully visualized as blue-colored images on CMOS sensor only when HeLa cells were placed directly on the micro-lens array of the CMOS sensor. Our proposed approach will be a promising technique for real-time and high-content analysis of single cells in a large-field area based on color imaging.

  9. Microarrays in cancer research.

    PubMed

    Grant, Geraldine M; Fortney, Amanda; Gorreta, Francesco; Estep, Michael; Del Giacco, Luca; Van Meter, Amy; Christensen, Alan; Appalla, Lakshmi; Naouar, Chahla; Jamison, Curtis; Al-Timimi, Ali; Donovan, Jean; Cooper, James; Garrett, Carleton; Chandhoke, Vikas

    2004-01-01

    Microarray technology has presented the scientific community with a compelling approach that allows for simultaneous evaluation of all cellular processes at once. Cancer, being one of the most challenging diseases due to its polygenic nature, presents itself as a perfect candidate for evaluation by this approach. Several recent articles have provided significant insight into the strengths and limitations of microarrays. Nevertheless, there are strong indications that this approach will provide new molecular markers that could be used in diagnosis and prognosis of cancers. To achieve these goals it is essential that there is a seamless integration of clinical and molecular biological data that allows us to elucidate genes and pathways involved in various cancers. To this effect we are currently evaluating gene expression profiles in human brain, ovarian, breast and hematopoetic, lung, colorectal, head and neck and biliary tract cancers. To address the issues we have a joint team of scientists, doctors and computer scientists from two Virginia Universities and a major healthcare provider. The study has been divided into several focus groups that include; Tissue Bank Clinical & Pathology Laboratory Data, Chip Fabrication, QA/QC, Tissue Devitalization, Database Design and Data Analysis, using multiple microarray platforms. Currently over 300 consenting patients have been enrolled in the study with the largest number being that of breast cancer patients. Clinical data on each patient is being compiled into a secure and interactive relational database and integration of these data elements will be accomplished by a common programming interface. This clinical database contains several key parameters on each patient including demographic (risk factors, nutrition, co-morbidity, familial history), histopathology (non genetic predictors), tumor, treatment and follow-up information. Gene expression data derived from the tissue samples will be linked to this database, which

  10. The Genopolis Microarray Database

    PubMed Central

    Splendiani, Andrea; Brandizi, Marco; Even, Gael; Beretta, Ottavio; Pavelka, Norman; Pelizzola, Mattia; Mayhaus, Manuel; Foti, Maria; Mauri, Giancarlo; Ricciardi-Castagnoli, Paola

    2007-01-01

    Background Gene expression databases are key resources for microarray data management and analysis and the importance of a proper annotation of their content is well understood. Public repositories as well as microarray database systems that can be implemented by single laboratories exist. However, there is not yet a tool that can easily support a collaborative environment where different users with different rights of access to data can interact to define a common highly coherent content. The scope of the Genopolis database is to provide a resource that allows different groups performing microarray experiments related to a common subject to create a common coherent knowledge base and to analyse it. The Genopolis database has been implemented as a dedicated system for the scientific community studying dendritic and macrophage cells functions and host-parasite interactions. Results The Genopolis Database system allows the community to build an object based MIAME compliant annotation of their experiments and to store images, raw and processed data from the Affymetrix GeneChip® platform. It supports dynamical definition of controlled vocabularies and provides automated and supervised steps to control the coherence of data and annotations. It allows a precise control of the visibility of the database content to different sub groups in the community and facilitates exports of its content to public repositories. It provides an interactive users interface for data analysis: this allows users to visualize data matrices based on functional lists and sample characterization, and to navigate to other data matrices defined by similarity of expression values as well as functional characterizations of genes involved. A collaborative environment is also provided for the definition and sharing of functional annotation by users. Conclusion The Genopolis Database supports a community in building a common coherent knowledge base and analyse it. This fills a gap between a local

  11. DNA Microarray-Based Diagnostics.

    PubMed

    Marzancola, Mahsa Gharibi; Sedighi, Abootaleb; Li, Paul C H

    2016-01-01

    The DNA microarray technology is currently a useful biomedical tool which has been developed for a variety of diagnostic applications. However, the development pathway has not been smooth and the technology has faced some challenges. The reliability of the microarray data and also the clinical utility of the results in the early days were criticized. These criticisms added to the severe competition from other techniques, such as next-generation sequencing (NGS), impacting the growth of microarray-based tests in the molecular diagnostic market.Thanks to the advances in the underlying technologies as well as the tremendous effort offered by the research community and commercial vendors, these challenges have mostly been addressed. Nowadays, the microarray platform has achieved sufficient standardization and method validation as well as efficient probe printing, liquid handling and signal visualization. Integration of various steps of the microarray assay into a harmonized and miniaturized handheld lab-on-a-chip (LOC) device has been a goal for the microarray community. In this respect, notable progress has been achieved in coupling the DNA microarray with the liquid manipulation microsystem as well as the supporting subsystem that will generate the stand-alone LOC device.In this chapter, we discuss the major challenges that microarray technology has faced in its almost two decades of development and also describe the solutions to overcome the challenges. In addition, we review the advancements of the technology, especially the progress toward developing the LOC devices for DNA diagnostic applications.

  12. An integrating CMOS APS for X-ray imaging with an in-pixel preamplifier

    NASA Astrophysics Data System (ADS)

    Abdalla, M. A.; Fröjdh, C.; Petersson, C. S.

    2001-06-01

    We present in this paper an integrating CMOS Active Pixel Sensor (APS) circuit coated with scintillator type sensors for intra-oral dental X-ray imaging systems. The photosensing element in the pixel is formed by the p-diffusion on the n-well diode. The advantage of this photosensor is its very low direct absorption of X-rays compared to the other available photosensing elements in the CMOS pixel. The pixel features an integrating capacitor in the feedback loop of a preamplifier of a finite gain in order to increase the optical sensitivity. To verify the effectiveness of this in-pixel preamplification, a prototype 32×80 element CMOS active pixel array was implemented in a 0.8 μm CMOS double poly, n-well process with a pixel pitch of 50 μm. Measured results confirmed the improved optical sensitivity performance of the APS. Various measurements on device performance are presented.

  13. Molecular diagnosis and prognosis with DNA microarrays.

    PubMed

    Wiltgen, Marco; Tilz, Gernot P

    2011-05-01

    Microarray analysis makes it possible to determine thousands of gene expression values simultaneously. Changes in gene expression, as a response to diseases, can be detected allowing a better understanding and differentiation of diseases at a molecular level. By comparing different kinds of tissue, for example healthy tissue and cancer tissue, the microarray analysis indicates induced gene activity, repressed gene activity or when there is no change in the gene activity level. Fundamental patterns in gene expression are extracted by several clustering and machine learning algorithms. Certain kinds of cancer can be divided into subtypes, with different clinical outcomes, by their specific gene expression patterns. This enables a better diagnosis and tailoring of individual patient treatments.

  14. Living-cell microarrays.

    PubMed

    Yarmush, Martin L; King, Kevin R

    2009-01-01

    Living cells are remarkably complex. To unravel this complexity, living-cell assays have been developed that allow delivery of experimental stimuli and measurement of the resulting cellular responses. High-throughput adaptations of these assays, known as living-cell microarrays, which are based on microtiter plates, high-density spotting, microfabrication, and microfluidics technologies, are being developed for two general applications: (a) to screen large-scale chemical and genomic libraries and (b) to systematically investigate the local cellular microenvironment. These emerging experimental platforms offer exciting opportunities to rapidly identify genetic determinants of disease, to discover modulators of cellular function, and to probe the complex and dynamic relationships between cells and their local environment.

  15. CMOS digital pixel sensors: technology and applications

    NASA Astrophysics Data System (ADS)

    Skorka, Orit; Joseph, Dileepan

    2014-04-01

    CMOS active pixel sensor technology, which is widely used these days for digital imaging, is based on analog pixels. Transition to digital pixel sensors can boost signal-to-noise ratios and enhance image quality, but can increase pixel area to dimensions that are impractical for the high-volume market of consumer electronic devices. There are two main approaches to digital pixel design. The first uses digitization methods that largely rely on photodetector properties and so are unique to imaging. The second is based on adaptation of a classical analog-to-digital converter (ADC) for in-pixel data conversion. Imaging systems for medical, industrial, and security applications are emerging lower-volume markets that can benefit from these in-pixel ADCs. With these applications, larger pixels are typically acceptable, and imaging may be done in invisible spectral bands.

  16. Contact CMOS imaging of gaseous oxygen sensor array

    PubMed Central

    Daivasagaya, Daisy S.; Yao, Lei; Yi Yung, Ka; Hajj-Hassan, Mohamad; Cheung, Maurice C.; Chodavarapu, Vamsy P.; Bright, Frank V.

    2014-01-01

    We describe a compact luminescent gaseous oxygen (O2) sensor microsystem based on the direct integration of sensor elements with a polymeric optical filter and placed on a low power complementary metal-oxide semiconductor (CMOS) imager integrated circuit (IC). The sensor operates on the measurement of excited-state emission intensity of O2-sensitive luminophore molecules tris(4,7-diphenyl-1,10-phenanthroline) ruthenium(II) ([Ru(dpp)3]2+) encapsulated within sol–gel derived xerogel thin films. The polymeric optical filter is made with polydimethylsiloxane (PDMS) that is mixed with a dye (Sudan-II). The PDMS membrane surface is molded to incorporate arrays of trapezoidal microstructures that serve to focus the optical sensor signals on to the imager pixels. The molded PDMS membrane is then attached with the PDMS color filter. The xerogel sensor arrays are contact printed on top of the PDMS trapezoidal lens-like microstructures. The CMOS imager uses a 32 × 32 (1024 elements) array of active pixel sensors and each pixel includes a high-gain phototransistor to convert the detected optical signals into electrical currents. Correlated double sampling circuit, pixel address, digital control and signal integration circuits are also implemented on-chip. The CMOS imager data is read out as a serial coded signal. The CMOS imager consumes a static power of 320 µW and an average dynamic power of 625 µW when operating at 100 Hz sampling frequency and 1.8 V DC. This CMOS sensor system provides a useful platform for the development of miniaturized optical chemical gas sensors. PMID:24493909

  17. Contact CMOS imaging of gaseous oxygen sensor array.

    PubMed

    Daivasagaya, Daisy S; Yao, Lei; Yi Yung, Ka; Hajj-Hassan, Mohamad; Cheung, Maurice C; Chodavarapu, Vamsy P; Bright, Frank V

    2011-10-01

    We describe a compact luminescent gaseous oxygen (O2) sensor microsystem based on the direct integration of sensor elements with a polymeric optical filter and placed on a low power complementary metal-oxide semiconductor (CMOS) imager integrated circuit (IC). The sensor operates on the measurement of excited-state emission intensity of O2-sensitive luminophore molecules tris(4,7-diphenyl-1,10-phenanthroline) ruthenium(II) ([Ru(dpp)3](2+)) encapsulated within sol-gel derived xerogel thin films. The polymeric optical filter is made with polydimethylsiloxane (PDMS) that is mixed with a dye (Sudan-II). The PDMS membrane surface is molded to incorporate arrays of trapezoidal microstructures that serve to focus the optical sensor signals on to the imager pixels. The molded PDMS membrane is then attached with the PDMS color filter. The xerogel sensor arrays are contact printed on top of the PDMS trapezoidal lens-like microstructures. The CMOS imager uses a 32 × 32 (1024 elements) array of active pixel sensors and each pixel includes a high-gain phototransistor to convert the detected optical signals into electrical currents. Correlated double sampling circuit, pixel address, digital control and signal integration circuits are also implemented on-chip. The CMOS imager data is read out as a serial coded signal. The CMOS imager consumes a static power of 320 µW and an average dynamic power of 625 µW when operating at 100 Hz sampling frequency and 1.8 V DC. This CMOS sensor system provides a useful platform for the development of miniaturized optical chemical gas sensors.

  18. Design of a covalently bonded glycosphingolipid microarray.

    PubMed

    Arigi, Emma; Blixt, Ola; Buschard, Karsten; Clausen, Henrik; Levery, Steven B

    2012-01-01

    Glycosphingolipids (GSLs) are well known ubiquitous constituents of all eukaryotic cell membranes, yet their normal biological functions are not fully understood. As with other glycoconjugates and saccharides, solid phase display on microarrays potentially provides an effective platform for in vitro study of their functional interactions. However, with few exceptions, the most widely used microarray platforms display only the glycan moiety of GSLs, which not only ignores potential modulating effects of the lipid aglycone, but inherently limits the scope of application, excluding, for example, the major classes of plant and fungal GSLs. In this work, a prototype "universal" GSL-based covalent microarray has been designed, and preliminary evaluation of its potential utility in assaying protein-GSL binding interactions investigated. An essential step in development involved the enzymatic release of the fatty acyl moiety of the ceramide aglycone of selected mammalian GSLs with sphingolipid N-deacylase (SCDase). Derivatization of the free amino group of a typical lyso-GSL, lyso-G(M1), with a prototype linker assembled from succinimidyl-[(N-maleimidopropionamido)-diethyleneglycol] ester and 2-mercaptoethylamine, was also tested. Underivatized or linker-derivatized lyso-GSL were then immobilized on N-hydroxysuccinimide- or epoxide-activated glass microarray slides and probed with carbohydrate binding proteins of known or partially known specificities (i.e., cholera toxin B-chain; peanut agglutinin, a monoclonal antibody to sulfatide, Sulph 1; and a polyclonal antiserum reactive to asialo-G(M2)). Preliminary evaluation of the method indicated successful immobilization of the GSLs, and selective binding of test probes. The potential utility of this methodology for designing covalent microarrays that incorporate GSLs for serodiagnosis is discussed.

  19. Nanosecond monolithic CMOS readout cell

    DOEpatents

    Souchkov, Vitali V.

    2004-08-24

    A pulse shaper is implemented in monolithic CMOS with a delay unit formed of a unity gain buffer. The shaper is formed of a difference amplifier having one input connected directly to an input signal and a second input connected to a delayed input signal through the buffer. An elementary cell is based on the pulse shaper and a timing circuit which gates the output of an integrator connected to the pulse shaper output. A detector readout system is formed of a plurality of elementary cells, each connected to a pixel of a pixel array, or to a microstrip of a plurality of microstrips, or to a detector segment.

  20. Deciphering the glycosaminoglycan code with the help of microarrays.

    PubMed

    de Paz, Jose L; Seeberger, Peter H

    2008-07-01

    Carbohydrate microarrays have become a powerful tool to elucidate the biological role of complex sugars. Microarrays are particularly useful for the study of glycosaminoglycans (GAGs), a key class of carbohydrates. The high-throughput chip format enables rapid screening of large numbers of potential GAG sequences produced via a complex biosynthesis while consuming very little sample. Here, we briefly highlight the most recent advances involving GAG microarrays built with synthetic or naturally derived oligosaccharides. These chips are powerful tools for characterizing GAG-protein interactions and determining structure-activity relationships for specific sequences. Thereby, they contribute to decoding the information contained in specific GAG sequences.

  1. Microarray simulator as educational tool.

    PubMed

    Ruusuvuori, Pekka; Nykter, Matti; Mäkiraatikka, Eeva; Lehmussola, Antti; Korpelainen, Tomi; Erkkilä, Timo; Yli-Harja, Olli

    2007-01-01

    As many real-world applications, microarray measurements are inapplicable for large-scale teaching purposes due to their laborious preparation process and expense. Fortunately, many phases of the array preparation process can be efficiently demonstrated by using a software simulator tool. Here we propose the use of microarray simulator as an aiding tool in teaching of computational biology. Three case studies on educational use of the simulator are presented, which demonstrate the effect of gene knock-out, synthetic time series, and effect of noise sources. We conclude that the simulator, used for teaching the principles of microarray measurement technology, proved to be a useful tool in education.

  2. A CMOS silicon spin qubit

    NASA Astrophysics Data System (ADS)

    Maurand, R.; Jehl, X.; Kotekar-Patil, D.; Corna, A.; Bohuslavskyi, H.; Laviéville, R.; Hutin, L.; Barraud, S.; Vinet, M.; Sanquer, M.; de Franceschi, S.

    2016-11-01

    Silicon, the main constituent of microprocessor chips, is emerging as a promising material for the realization of future quantum processors. Leveraging its well-established complementary metal-oxide-semiconductor (CMOS) technology would be a clear asset to the development of scalable quantum computing architectures and to their co-integration with classical control hardware. Here we report a silicon quantum bit (qubit) device made with an industry-standard fabrication process. The device consists of a two-gate, p-type transistor with an undoped channel. At low temperature, the first gate defines a quantum dot encoding a hole spin qubit, the second one a quantum dot used for the qubit read-out. All electrical, two-axis control of the spin qubit is achieved by applying a phase-tunable microwave modulation to the first gate. The demonstrated qubit functionality in a basic transistor-like device constitutes a promising step towards the elaboration of scalable spin qubit geometries in a readily exploitable CMOS platform.

  3. A CMOS silicon spin qubit

    PubMed Central

    Maurand, R.; Jehl, X.; Kotekar-Patil, D.; Corna, A.; Bohuslavskyi, H.; Laviéville, R.; Hutin, L.; Barraud, S.; Vinet, M.; Sanquer, M.; De Franceschi, S.

    2016-01-01

    Silicon, the main constituent of microprocessor chips, is emerging as a promising material for the realization of future quantum processors. Leveraging its well-established complementary metal–oxide–semiconductor (CMOS) technology would be a clear asset to the development of scalable quantum computing architectures and to their co-integration with classical control hardware. Here we report a silicon quantum bit (qubit) device made with an industry-standard fabrication process. The device consists of a two-gate, p-type transistor with an undoped channel. At low temperature, the first gate defines a quantum dot encoding a hole spin qubit, the second one a quantum dot used for the qubit read-out. All electrical, two-axis control of the spin qubit is achieved by applying a phase-tunable microwave modulation to the first gate. The demonstrated qubit functionality in a basic transistor-like device constitutes a promising step towards the elaboration of scalable spin qubit geometries in a readily exploitable CMOS platform. PMID:27882926

  4. A CMOS silicon spin qubit.

    PubMed

    Maurand, R; Jehl, X; Kotekar-Patil, D; Corna, A; Bohuslavskyi, H; Laviéville, R; Hutin, L; Barraud, S; Vinet, M; Sanquer, M; De Franceschi, S

    2016-11-24

    Silicon, the main constituent of microprocessor chips, is emerging as a promising material for the realization of future quantum processors. Leveraging its well-established complementary metal-oxide-semiconductor (CMOS) technology would be a clear asset to the development of scalable quantum computing architectures and to their co-integration with classical control hardware. Here we report a silicon quantum bit (qubit) device made with an industry-standard fabrication process. The device consists of a two-gate, p-type transistor with an undoped channel. At low temperature, the first gate defines a quantum dot encoding a hole spin qubit, the second one a quantum dot used for the qubit read-out. All electrical, two-axis control of the spin qubit is achieved by applying a phase-tunable microwave modulation to the first gate. The demonstrated qubit functionality in a basic transistor-like device constitutes a promising step towards the elaboration of scalable spin qubit geometries in a readily exploitable CMOS platform.

  5. Accelerated life testing effects on CMOS microcircuit characteristics, phase 1

    NASA Technical Reports Server (NTRS)

    Maximow, B.

    1976-01-01

    An accelerated life test of sufficient duration to generate a minimum of 50% cumulative failures in lots of CMOS devices was conducted to provide a basis for determining the consistency of activation energy at 250 C. An investigation was made to determine whether any thresholds were exceeded during the high temperature testing, which could trigger failure mechanisms unique to that temperature. The usefulness of the 250 C temperature test as a predictor of long term reliability was evaluated.

  6. Chemistry of Natural Glycan Microarray

    PubMed Central

    Song, Xuezheng; Heimburg-Molinaro, Jamie; Cummings, Richard D.; Smith, David F.

    2014-01-01

    Glycan microarrays have become indispensable tools for studying protein-glycan interactions. Along with chemo-enzymatic synthesis, glycans isolated from natural sources have played important roles in array development and will continue to be a major source of glycans. N- and O-glycans from glycoproteins, and glycans from glycosphingolipids can be released from corresponding glycoconjugates with relatively mature methods, although isolation of large numbers and quantities of glycans are still very challenging. Glycosylphosphatidylinositol (GPI)-anchors and glycosaminoglycans (GAGs) are less represented on current glycan microarrays. Glycan microarray development has been greatly facilitated by bifunctional fluorescent linkers, which can be applied in a “Shotgun Glycomics” approach to incorporate isolated natural glycans. Glycan presentation on microarrays may affect glycan binding by GBPs, often through multivalent recognition by the GBP. PMID:24487062

  7. An OTA-based CMOS bandpass filter for NMR applications

    NASA Astrophysics Data System (ADS)

    Shesharaman, K. N.; Kittur, Harish M.

    2012-12-01

    One of the very popular medical imaging techniques used in present-day radiology is the magnetic resonance imaging (MRI) which is based on the phenomenon of nuclear magnetic resonance (NMR) in the hydrogen atoms present in the body. There is ever-increasing research in electronic circuit design for biomedical applications using NMR. Earlier magnetic resonance imagers operated at a magnetic field strength of 0.3 T. The present imagers operate at a magnetic field of 1.5 T, the resonance frequency of the nuclei being 64 MHz. This article presents a CMOS bandpass filter (BPF) design for NMR applications. The overall BPF design is realised in 180 nm CMOS technology which occupies an active area of 24.23 × 33.125 µm2 and consumes 0.165 mW of power from a 1.5 V supply.

  8. Micromachined high-performance RF passives in CMOS substrate

    NASA Astrophysics Data System (ADS)

    Li, Xinxin; Ni, Zao; Gu, Lei; Wu, Zhengzheng; Yang, Chen

    2016-11-01

    This review systematically addresses the micromachining technologies used for the fabrication of high-performance radio-frequency (RF) passives that can be integrated into low-cost complementary metal-oxide semiconductor (CMOS)-grade (i.e. low-resistivity) silicon wafers. With the development of various kinds of post-CMOS-compatible microelectromechanical systems (MEMS) processes, 3D structural inductors/transformers, variable capacitors, tunable resonators and band-pass/low-pass filters can be compatibly integrated into active integrated circuits to form monolithic RF system-on-chips. By using MEMS processes, including substrate modifying/suspending and LIGA-like metal electroplating, both the highly lossy substrate effect and the resistive loss can be largely eliminated and depressed, thereby meeting the high-performance requirements of telecommunication applications.

  9. Development of CMOS-compatible membrane projection lithography

    NASA Astrophysics Data System (ADS)

    Burckel, D. Bruce; Samora, Sally; Wiwi, Mike; Wendt, Joel R.

    2013-09-01

    Recently we have demonstrated membrane projection lithography (MPL) as a fabrication approach capable of creating 3D structures with sub-micron metallic inclusions for use in metamaterial and plasmonic applications using polymer material systems. While polymers provide several advantages in processing, they are soft and subject to stress-induced buckling. Furthermore, in next generation active photonic structures, integration of photonic components with CMOS electronics is desirable. While the MPL process flow is conceptually simple, it requires matrix, membrane and backfill materials with orthogonal processing deposition/removal chemistries. By transitioning the MPL process flow into an entirely inorganic material set based around silicon and standard CMOS-compatible materials, several elements of silicon microelectronics can be integrated into photonic devices at the unit-cell scale. This paper will present detailed fabrication and characterization data of these materials, emphasizing the processing trade space as well as optical characterization of the resulting structures.

  10. Monolithic CMOS-MEMS integration for high-g accelerometers

    NASA Astrophysics Data System (ADS)

    Narasimhan, Vinayak; Li, Holden; Tan, Chuan Seng

    2014-10-01

    This paper highlights work-in-progress towards the conceptualization, simulation, fabrication and initial testing of a silicon-germanium (SiGe) integrated CMOS-MEMS high-g accelerometer for military, munition, fuze and shock measurement applications. Developed on IMEC's SiGe MEMS platform, the MEMS offers a dynamic range of 5,000 g and a bandwidth of 12 kHz. The low noise readout circuit adopts a chopper-stabilization technique implementing the CMOS through the TSMC 0.18 µm process. The device structure employs a fully differential split comb-drive set up with two sets of stators and a rotor all driven separately. Dummy structures acting as protective over-range stops were designed to protect the active components when under impacts well above the designed dynamic range.

  11. Spectrometry with consumer-quality CMOS cameras.

    PubMed

    Scheeline, Alexander

    2015-01-01

    Many modern spectrometric instruments use diode arrays, charge-coupled arrays, or CMOS cameras for detection and measurement. As portable or point-of-use instruments are desirable, one would expect that instruments using the cameras in cellular telephones and tablet computers would be the basis of numerous instruments. However, no mass market for such devices has yet developed. The difficulties in using megapixel CMOS cameras for scientific measurements are discussed, and promising avenues for instrument development reviewed. Inexpensive alternatives to use of the built-in camera are also mentioned, as the long-term question is whether it is better to overcome the constraints of CMOS cameras or to bypass them.

  12. Carbon nanotube integration with a CMOS process.

    PubMed

    Perez, Maximiliano S; Lerner, Betiana; Resasco, Daniel E; Pareja Obregon, Pablo D; Julian, Pedro M; Mandolesi, Pablo S; Buffa, Fabian A; Boselli, Alfredo; Lamagna, Alberto

    2010-01-01

    This work shows the integration of a sensor based on carbon nanotubes using CMOS technology. A chip sensor (CS) was designed and manufactured using a 0.30 μm CMOS process, leaving a free window on the passivation layer that allowed the deposition of SWCNTs over the electrodes. We successfully investigated with the CS the effect of humidity and temperature on the electrical transport properties of SWCNTs. The possibility of a large scale integration of SWCNTs with CMOS process opens a new route in the design of more efficient, low cost sensors with high reproducibility in their manufacture.

  13. Carbon Nanotube Integration with a CMOS Process

    PubMed Central

    Perez, Maximiliano S.; Lerner, Betiana; Resasco, Daniel E.; Pareja Obregon, Pablo D.; Julian, Pedro M.; Mandolesi, Pablo S.; Buffa, Fabian A.; Boselli, Alfredo; Lamagna, Alberto

    2010-01-01

    This work shows the integration of a sensor based on carbon nanotubes using CMOS technology. A chip sensor (CS) was designed and manufactured using a 0.30 μm CMOS process, leaving a free window on the passivation layer that allowed the deposition of SWCNTs over the electrodes. We successfully investigated with the CS the effect of humidity and temperature on the electrical transport properties of SWCNTs. The possibility of a large scale integration of SWCNTs with CMOS process opens a new route in the design of more efficient, low cost sensors with high reproducibility in their manufacture. PMID:22319330

  14. Nanopore-CMOS Interfaces for DNA Sequencing.

    PubMed

    Magierowski, Sebastian; Huang, Yiyun; Wang, Chengjie; Ghafar-Zadeh, Ebrahim

    2016-08-06

    DNA sequencers based on nanopore sensors present an opportunity for a significant break from the template-based incumbents of the last forty years. Key advantages ushered by nanopore technology include a simplified chemistry and the ability to interface to CMOS technology. The latter opportunity offers substantial promise for improvement in sequencing speed, size and cost. This paper reviews existing and emerging means of interfacing nanopores to CMOS technology with an emphasis on massively-arrayed structures. It presents this in the context of incumbent DNA sequencing techniques, reviews and quantifies nanopore characteristics and models and presents CMOS circuit methods for the amplification of low-current nanopore signals in such interfaces.

  15. Improved Space Object Orbit Determination Using CMOS Detectors

    NASA Astrophysics Data System (ADS)

    Schildknecht, T.; Peltonen, J.; Sännti, T.; Silha, J.; Flohrer, T.

    2014-09-01

    CMOS-sensors, or in general Active Pixel Sensors (APS), are rapidly replacing CCDs in the consumer camera market. Due to significant technological advances during the past years these devices start to compete with CCDs also for demanding scientific imaging applications, in particular in the astronomy community. CMOS detectors offer a series of inherent advantages compared to CCDs, due to the structure of their basic pixel cells, which each contains their own amplifier and readout electronics. The most prominent advantages for space object observations are the extremely fast and flexible readout capabilities, feasibility for electronic shuttering and precise epoch registration, and the potential to perform image processing operations on-chip and in real-time. The major challenges and design drivers for ground-based and space-based optical observation strategies have been analyzed. CMOS detector characteristics were critically evaluated and compared with the established CCD technology, especially with respect to the above mentioned observations. Similarly, the desirable on-chip processing functionalities which would further enhance the object detection and image segmentation were identified. Finally, we simulated several observation scenarios for ground- and space-based sensor by assuming different observation and sensor properties. We will introduce the analyzed end-to-end simulations of the ground- and space-based strategies in order to investigate the orbit determination accuracy and its sensitivity which may result from different values for the frame-rate, pixel scale, astrometric and epoch registration accuracies. Two cases were simulated, a survey using a ground-based sensor to observe objects in LEO for surveillance applications, and a statistical survey with a space-based sensor orbiting in LEO observing small-size debris in LEO. The ground-based LEO survey uses a dynamical fence close to the Earth shadow a few hours after sunset. For the space-based scenario

  16. System-on-Chip Considerations for Heterogeneous Integration of CMOS and Fluidic Bio-Interfaces.

    PubMed

    Datta-Chaudhuri, Timir; Smela, Elisabeth; Abshire, Pamela A

    2016-04-21

    CMOS chips are increasingly used for direct sensing and interfacing with fluidic and biological systems. While many biosensing systems have successfully combined CMOS chips for readout and signal processing with passive sensing arrays, systems that co-locate sensing with active circuits on a single chip offer significant advantages in size and performance but increase the complexity of multi-domain design and heterogeneous integration. This emerging class of lab-on-CMOS systems also poses distinct and vexing technical challenges that arise from the disparate requirements of biosensors and integrated circuits (ICs). Modeling these systems must address not only circuit design, but also the behavior of biological components on the surface of the IC and any physical structures. Existing tools do not support the cross-domain simulation of heterogeneous lab-on-CMOS systems, so we recommend a two-step modeling approach: using circuit simulation to inform physics-based simulation, and vice versa. We review the primary lab-on-CMOS implementation challenges and discuss practical approaches to overcome them. Issues include new versions of classical challenges in system-on-chip integration, such as thermal effects, floor-planning, and signal coupling, as well as new challenges that are specifically attributable to biological and fluidic domains, such as electrochemical effects, non-standard packaging, surface treatments, sterilization, microfabrication of surface structures, and microfluidic integration. We describe these concerns as they arise in lab-on-CMOS systems and discuss solutions that have been experimentally demonstrated.

  17. System-on-Chip Considerations for Heterogeneous Integration of CMOS and Fluidic Bio-Interfaces.

    PubMed

    Datta-Chaudhuri, Timir; Smela, Elisabeth; Abshire, Pamela A

    2016-12-01

    CMOS chips are increasingly used for direct sensing and interfacing with fluidic and biological systems. While many biosensing systems have successfully combined CMOS chips for readout and signal processing with passive sensing arrays, systems that co-locate sensing with active circuits on a single chip offer significant advantages in size and performance but increase the complexity of multi-domain design and heterogeneous integration. This emerging class of lab-on-CMOS systems also poses distinct and vexing technical challenges that arise from the disparate requirements of biosensors and integrated circuits (ICs). Modeling these systems must address not only circuit design, but also the behavior of biological components on the surface of the IC and any physical structures. Existing tools do not support the cross-domain simulation of heterogeneous lab-on-CMOS systems, so we recommend a two-step modeling approach: using circuit simulation to inform physics-based simulation, and vice versa. We review the primary lab-on-CMOS implementation challenges and discuss practical approaches to overcome them. Issues include new versions of classical challenges in system-on-chip integration, such as thermal effects, floor-planning, and signal coupling, as well as new challenges that are specifically attributable to biological and fluidic domains, such as electrochemical effects, non-standard packaging, surface treatments, sterilization, microfabrication of surface structures, and microfluidic integration. We describe these concerns as they arise in lab-on-CMOS systems and discuss solutions that have been experimentally demonstrated.

  18. Fully depleted and backside biased monolithic CMOS image sensor

    NASA Astrophysics Data System (ADS)

    Stefanov, Konstantin D.; Clarke, Andrew S.; Holland, Andrew D.

    2016-07-01

    We are presenting a novel concept for a fully depleted, monolithic, pinned photodiode CMOS image sensor using reverse substrate bias. The principle of operation allows the manufacture of backside illuminated CMOS sensors with active thickness in excess of 100 μm. This helps increase the QE at near-IR and soft X-ray wavelengths, while preserving the excellent characteristics associated with the pinned photodiode sensitive elements. Such sensors are relevant to a wide range of applications, including scientific imaging, astronomy, Earth observation and surveillance. A prototype device with 10 μm and 5.4 μm pixels using this concept has been designed and is being manufactured on a 0.18 μm CMOS image sensor process. Only one additional implantation step has been introduced to the normal manufacturing flow to make this device. The paper discusses the design of the sensor and the challenges that had to be overcome to realise it in practice, and in particular the method of achieving full depletion without parasitic substrate currents. It is expected that this new technology can be competitive with modern backside illuminated thick CCDs for use at visible to near-IR telescopes and synchrotron light sources.

  19. Microarray Technologies in Fungal Diagnostics.

    PubMed

    Rupp, Steffen

    2017-01-01

    Microarray technologies have been a major research tool in the last decades. In addition they have been introduced into several fields of diagnostics including diagnostics of infectious diseases. Microarrays are highly parallelized assay systems that initially were developed for multiparametric nucleic acid detection. From there on they rapidly developed towards a tool for the detection of all kind of biological compounds (DNA, RNA, proteins, cells, nucleic acids, carbohydrates, etc.) or their modifications (methylation, phosphorylation, etc.). The combination of closed-tube systems and lab on chip devices with microarrays further enabled a higher automation degree with a reduced contamination risk. Microarray-based diagnostic applications currently complement and may in the future replace classical methods in clinical microbiology like blood cultures, resistance determination, microscopic and metabolic analyses as well as biochemical or immunohistochemical assays. In addition, novel diagnostic markers appear, like noncoding RNAs and miRNAs providing additional room for novel nucleic acid based biomarkers. Here I focus an microarray technologies in diagnostics and as research tools, based on nucleic acid-based arrays.

  20. Comparing Bacterial DNA Microarray Fingerprints

    SciTech Connect

    Willse, Alan R.; Chandler, Darrell P.; White, Amanda M.; Protic, Miroslava; Daly, Don S.; Wunschel, Sharon C.

    2005-08-15

    Detecting subtle genetic differences between microorganisms is an important problem in molecular epidemiology and microbial forensics. In a typical investigation, gel electrophoresis is used to compare randomly amplified DNA fragments between microbial strains, where the patterns of DNA fragment sizes are proxies for a microbe's genotype. The limited genomic sample captured on a gel is often insufficient to discriminate nearly identical strains. This paper examines the application of microarray technology to DNA fingerprinting as a high-resolution alternative to gel-based methods. The so-called universal microarray, which uses short oligonucleotide probes that do not target specific genes or species, is intended to be applicable to all microorganisms because it does not require prior knowledge of genomic sequence. In principle, closely related strains can be distinguished if the number of probes on the microarray is sufficiently large, i.e., if the genome is sufficiently sampled. In practice, we confront noisy data, imperfectly matched hybridizations, and a high-dimensional inference problem. We describe the statistical problems of microarray fingerprinting, outline similarities with and differences from more conventional microarray applications, and illustrate the statistical fingerprinting problem for 10 closely related strains from three Bacillus species, and 3 strains from non-Bacillus species.

  1. Fundamental study on identification of CMOS cameras

    NASA Astrophysics Data System (ADS)

    Kurosawa, Kenji; Saitoh, Naoki

    2003-08-01

    In this study, we discussed individual camera identification of CMOS cameras, because CMOS (complementary-metal-oxide-semiconductor) imaging detectors have begun to make their move into the CCD (charge-coupled-device) fields for recent years. It can be identified whether or not the given images have been taken with the given CMOS camera by detecting the imager's intrinsic unique fixed pattern noise (FPN) just like the individual CCD camera identification method proposed by the authors. Both dark and bright pictures taken with the CMOS cameras can be identified by the method, because not only dark current in the photo detectors but also MOS-FET amplifiers incorporated in each pixel may produce pixel-to-pixel nonuniformity in sensitivity. Each pixel in CMOS detectors has the amplifier, which degrades image quality of bright images due to the nonuniformity of the amplifier gain. Two CMOS cameras were evaluated in our experiments. They were WebCamGoPlus (Creative), and EOS D30 (Canon). WebCamGoPlus is a low-priced web camera, whereas EOS D30 is for professional use. Image of a white plate were recorded with the cameras under the plate's luminance condition of 0cd/m2 and 150cd/m2. The recorded images were multiply integrated to reduce the random noise component. From the images of both cameras, characteristic dots patterns were observed. Some bright dots were observed in the dark images, whereas some dark dots were in the bright images. The results show that the camera identification method is also effective for CMOS cameras.

  2. Microarray Analysis Reveals Increased Transcriptional Repression and Reduced Metabolic Activity but Not Major Changes in the Core Apoptotic Machinery during Maturation of Sympathetic Neurons

    PubMed Central

    Raba, Mikk; Palgi, Jaan; Lehtivaara, Maria; Arumäe, Urmas

    2016-01-01

    Postnatal maturation of the neurons whose main phenotype and basic synaptic contacts are already established includes neuronal growth, refinement of synaptic contacts, final steps of differentiation, programmed cell death period (PCD) etc. In the sympathetic neurons, postnatal maturation includes permanent end of the PCD that occurs with the same time schedule in vivo and in vitro suggesting that the process could be genetically determined. Also many other changes in the neuronal maturation could be permanent and thus based on stable changes in the genome expression. However, postnatal maturation of the neurons is poorly studied. Here we compared the gene expression profiles of immature and mature sympathetic neurons using Affymetrix microarray assay. We found 1310 significantly up-regulated and 1151 significantly down-regulated genes in the mature neurons. Gene ontology analysis reveals up-regulation of genes related to neuronal differentiation, chromatin and epigenetic changes, extracellular factors and their receptors, and cell adhesion, whereas many down-regulated genes were related to metabolic and biosynthetic processes. We show that termination of PCD is not related to major changes in the expression of classical genes for apoptosis or cell survival. Our dataset is deposited to the ArrayExpress database and is a valuable source to select candidate genes in the studies of neuronal maturation. As an example, we studied the changes in the expression of selected genes Igf2bp3, Coro1A, Zfp57, Dcx, and Apaf1 in the young and mature sympathetic ganglia by quantitative PCR and show that these were strongly downregulated in the mature ganglia. PMID:27013977

  3. CG methylated microarrays identify a novel methylated sequence bound by the CEBPB|ATF4 heterodimer that is active in vivo.

    PubMed

    Mann, Ishminder K; Chatterjee, Raghunath; Zhao, Jianfei; He, Ximiao; Weirauch, Matthew T; Hughes, Timothy R; Vinson, Charles

    2013-06-01

    To evaluate the effect of CG methylation on DNA binding of sequence-specific B-ZIP transcription factors (TFs) in a high-throughput manner, we enzymatically methylated the cytosine in the CG dinucleotide on protein binding microarrays. Two Agilent DNA array designs were used. One contained 40,000 features using de Bruijn sequences where each 8-mer occurs 32 times in various positions in the DNA sequence. The second contained 180,000 features with each CG containing 8-mer occurring three times. The first design was better for identification of binding motifs, while the second was better for quantification. Using this novel technology, we show that CG methylation enhanced binding for CEBPA and CEBPB and inhibited binding for CREB, ATF4, JUN, JUND, CEBPD, and CEBPG. The CEBPB|ATF4 heterodimer bound a novel motif CGAT|GCAA 10-fold better when methylated. The electrophoretic mobility shift assay (EMSA) confirmed these results. CEBPB ChIP-seq data using primary female mouse dermal fibroblasts with 50× methylome coverage for each strand indicate that the methylated sequences well-bound on the arrays are also bound in vivo. CEBPB bound 39% of the methylated canonical 10-mers ATTGC|GCAAT in the mouse genome. After ATF4 protein induction by thapsigargin which results in ER stress, CEBPB binds methylated CGAT|GCAA in vivo, recapitulating what was observed on the arrays. This methodology can be used to identify new methylated DNA sequences preferentially bound by TFs, which may be functional in vivo.

  4. Photonic circuits integrated with CMOS compatible photodetectors

    NASA Astrophysics Data System (ADS)

    Cristea, Dana; Craciunoiu, F.; Modreanu, M.; Caldararu, M.; Cernica, I.

    2001-06-01

    This paper presents the integration of photodetectors and photonic circuits (waveguides and interferometers, coupling elements and chemo-optical transducing layer) on one silicon chip. Different materials: silicon, doped or undoped silica, SiO xN y, polymers, and different technologies: LPCVD, APCVD, sol-gel, spinning, micromachining have been used to realize the photonic and micromechanical components and the transducers. Also, MOS compatible processes have been used for optoelectronic circuits. The attention was focused on the matching of all the involved technologies, to allow the monolithic integration of all components, and also on the design and fabrication of special structures of photodetectors. Two types of high responsivity photodetectors, a photo-FET and a bipolar NPN phototransistor, with modified structures that allow the optical coupling to the waveguides have been designed and experimented. An original 3-D model was developed for the system: opto-FET-coupler-waveguide. A test circuit for sensor applications was experimented. All the components of the test circuits, photodetectors, waveguides, couplers, were obtained using CMOS-compatible processes. The aim of our research activity was to obtain microsensors with optical read-out.

  5. Microfluidic microarray systems and methods thereof

    SciTech Connect

    West, Jay A. A.; Hukari, Kyle W.; Hux, Gary A.

    2009-04-28

    Disclosed are systems that include a manifold in fluid communication with a microfluidic chip having a microarray, an illuminator, and a detector in optical communication with the microarray. Methods for using these systems for biological detection are also disclosed.

  6. Optical waveguide taps on silicon CMOS circuits

    NASA Astrophysics Data System (ADS)

    Stenger, Vincent E.; Beyette, Fred R., Jr.

    2000-11-01

    As silicon CMOS circuit technology is scaled beyond the GHz range, both chipmakers and board makers face increasingly difficult challenges in implementing high speed metal interconnects. Metal traces are limited in density-speed performance due to the skin effect, electrical conductivity, and cross talk. Optical based interconnects have higher available bandwidth by virtue of the extremely high carrier frequencies of optical signals (> 100 THz). For this work, an effort has been made to determine an optimal optical tap receiver design for integration with commercial CMOS processes. Candidate waveguide tap technologies were considered in terms of optical loss, bandwidth, economy, and CMOS process compatibility. A new device, which is based on a variation of the multimode interference effect, has been found to be especially promising. BeamProp simulation results show nearly zero excess optical loss for the design, and up to 70% coupling into a 25 micrometer traveling wave CMOS photodetector device. Single-mode waveguides make the design readily compatible with wavelength multiplexing/demultiplexing elements. Polymer waveguide materials are targeted for fabrication due to planarization properties, low cost, broad index control, and poling abilities for modulation/tuning functions. Low cost, silicon CMOS based processing makes the new tap technology especially suitable for computer chip and board level interconnects, as well as metro fiber-to-the- home/desk telecommunications applications.

  7. The Microarray Revolution: Perspectives from Educators

    ERIC Educational Resources Information Center

    Brewster, Jay L.; Beason, K. Beth; Eckdahl, Todd T.; Evans, Irene M.

    2004-01-01

    In recent years, microarray analysis has become a key experimental tool, enabling the analysis of genome-wide patterns of gene expression. This review approaches the microarray revolution with a focus upon four topics: 1) the early development of this technology and its application to cancer diagnostics; 2) a primer of microarray research,…

  8. Nanopore-CMOS Interfaces for DNA Sequencing

    PubMed Central

    Magierowski, Sebastian; Huang, Yiyun; Wang, Chengjie; Ghafar-Zadeh, Ebrahim

    2016-01-01

    DNA sequencers based on nanopore sensors present an opportunity for a significant break from the template-based incumbents of the last forty years. Key advantages ushered by nanopore technology include a simplified chemistry and the ability to interface to CMOS technology. The latter opportunity offers substantial promise for improvement in sequencing speed, size and cost. This paper reviews existing and emerging means of interfacing nanopores to CMOS technology with an emphasis on massively-arrayed structures. It presents this in the context of incumbent DNA sequencing techniques, reviews and quantifies nanopore characteristics and models and presents CMOS circuit methods for the amplification of low-current nanopore signals in such interfaces. PMID:27509529

  9. Experiments with synchronized sCMOS cameras

    NASA Astrophysics Data System (ADS)

    Steele, Iain A.; Jermak, Helen; Copperwheat, Chris M.; Smith, Robert J.; Poshyachinda, Saran; Soonthorntham, Boonrucksar

    2016-07-01

    Scientific-CMOS (sCMOS) cameras can combine low noise with high readout speeds and do not suffer the charge multiplication noise that effectively reduces the quantum efficiency of electron multiplying CCDs by a factor 2. As such they have strong potential in fast photometry and polarimetry instrumentation. In this paper we describe the results of laboratory experiments using a pair of commercial off the shelf sCMOS cameras based around a 4 transistor per pixel architecture. In particular using a both stable and a pulsed light sources we evaluate the timing precision that may be obtained when the cameras readouts are synchronized either in software or electronically. We find that software synchronization can introduce an error of 200-msec. With electronic synchronization any error is below the limit ( 50-msec) of our simple measurement technique.

  10. Deposition of titanium dioxide nanoparticles on the membrane of a CMOS-MEMS resonator

    NASA Astrophysics Data System (ADS)

    Ahmed, A. Y.; Dennis, J. O.; Khir, M. H. Md; Saad, M. N. Mohamad

    2014-10-01

    A CMOS-MEMS resonator is optimized as a highly sensitive gas sensor. The principle of detection is based on change in resonant frequency of the resonator due to adsorption/absorption of trace gases onto the active material on the resonator membrane. The resonator was successfully fabricated using 0.35 μm CMOS technology and post-CMOS micromachining process. The post-CMOS process is used to etch the silicon substrate and silicon oxide to release the suspended structures of the devices. Preliminary trials of nanocrystalline Titania paste (TiO2) was screen-printed on three aluminum plates of sizes 2mm × 2 mm. One of the samples was analysed as prepared while the other two samples were sintered at 300°C and 550°C, respectively. Physical observation indicated a change of the color for heated samples as compared to the unheated one. EDX results indicates a carbon (C) peak with average weight % of 18.816 in the as prepared sample and absence of the peaks for the samples sintered at 300°C and 550°C. EDX results also show that the TiO2 used consists of a uniform distribution of spherical shaped nanoparticles with a diameter of about 13.49 to 48.42 nm. Finally, the Titania paste was successfully deposit on the membrane of the CMOS-MEMS resonator for use as the gas sensitive membrane of the sensor.

  11. High-sensitivity chemiluminescence detection of cytokines using an antibody-immobilized CMOS image sensor

    NASA Astrophysics Data System (ADS)

    Hong, Dong-Gu; Joung, Hyou-Arm; Kim, Sang-Hyo; Kim, Min-Gon

    2013-05-01

    In this study, we used a Complementary Metal Oxide Semiconductor (CMOS) image sensor with immobilizing antibodies on its surface to detect human cytokines, which are activators that mediate intercellular communication including expression and control of immune responses. The CMOS image sensor has many advantages over the Charge Couple Device, including lower power consumption, operation voltage, and cost. The photodiode, a unit pixel component in the CMOS image sensor, receives light from the detection area and generates digital image data. About a million pixels are embedded, and size of each pixel is 3 x 3 μm. The chemiluminescence reaction produces light from the chemical reaction of luminol and hydrogen peroxide. To detect cytokines, antibodies were immobilized on the surface of the CMOS image sensor, and a sandwich immunoassay using an HRP-labeled antibody was performed. An HRP-catalyzed chemiluminescence reaction was measured by each pixel of the CMOS image sensor. Pixels with stronger signals indicated higher cytokine concentrations; thus, we were able to measure human interleukin-5 (IL-5) at femtomolar concentrations.

  12. Resistor Extends Life Of Battery In Clocked CMOS Circuit

    NASA Technical Reports Server (NTRS)

    Wells, George H., Jr.

    1991-01-01

    Addition of fixed resistor between battery and clocked complementary metal oxide/semiconductor (CMOS) circuit reduces current drawn from battery. Basic idea to minimize current drawn from battery by operating CMOS circuit at lowest possible current consistent with use of simple, fixed off-the-shelf components. Prolongs lives of batteries in such low-power CMOS circuits as watches and calculators.

  13. High-temperature Complementary Metal Oxide Semiconductors (CMOS)

    NASA Technical Reports Server (NTRS)

    Mcbrayer, J. D.

    1981-01-01

    The results of an investigation into the possibility of using complementary metal oxide semiconductor (CMOS) technology for high temperature electronics are presented. A CMOS test chip was specifically developed as the test bed. This test chip incorporates CMOS transistors that have no gate protection diodes; these diodes are the major cause of leakage in commercial devices.

  14. Low power, CMOS digital autocorrelator spectrometer for spaceborne applications

    NASA Technical Reports Server (NTRS)

    Chandra, Kumar; Wilson, William J.

    1992-01-01

    A 128-channel digital autocorrelator spectrometer using four 32 channel low power CMOS correlator chips was built and tested. The CMOS correlator chip uses a 2-bit multiplication algorithm and a full-custom CMOS VLSI design to achieve low DC power consumption. The digital autocorrelator spectrometer has a 20 MHz band width, and the total DC power requirement is 6 Watts.

  15. Solution processed organic microarray with inverted structure

    NASA Astrophysics Data System (ADS)

    Toglia, Patrick; Lewis, Jason; Lafalce, Evan; Jiang, Xiaomei

    2011-03-01

    We have fabricated inverted organic microarray using a novel solution-based technique. The array consists of 60 small (1 square mm) solar cells on a one inch by one inch glass substrate. The device utilizes photoactive materials such as a blend of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C61-butyric acid methyl ester (PCBM). Manipulation of active layer nanomorphology has been done by choice of solvents and annealing conditions. Detailed analysis of device physics including current voltage characteristics, external quantum efficiency and carrier recombinations will be presented and complimented by AFM images and glazing angle XRD of the active layer under different processing conditions. The procedure described here has the full potential for use in future fabrication of microarrays with single cell as small as 0.01 square mm for application in DC power supplies for electrostatic Microelectromechanical systems (MEMS) devices. This work was supported by New Energy Technology Inc. and Florida High Tech Corridor Matching Fund (FHT 09-18).

  16. Microarray Technology Applied to Human Allergic Disease

    PubMed Central

    Hamilton, Robert G.

    2017-01-01

    IgE antibodies serve as the gatekeeper for the release of mediators from sensitized (IgE positive) mast cells and basophils following a relevant allergen exposure which can lead to an immediate-type hypersensitivity (allergic) reaction. Purified recombinant and native allergens were combined in the 1990s with state of the art chip technology to establish the first microarray-based IgE antibody assay. Triplicate spots to over 100 allergenic molecules are immobilized on an amine-activated glass slide to form a single panel multi-allergosorbent assay. Human antibodies, typically of the IgE and IgG isotypes, specific for one or many allergens bind to their respective allergen(s) on the chip. Following removal of unbound serum proteins, bound IgE antibody is detected with a fluorophore-labeled anti-human IgE reagent. The fluorescent profile from the completed slide provides a sensitization profile of an allergic patient which can identify IgE antibodies that bind to structurally similar (cross-reactive) allergen families versus molecules that are unique to a single allergen specificity. Despite its ability to rapidly analyze many IgE antibody specificities in a single simple assay format, the chip-based microarray remains less analytically sensitive and quantitative than its singleplex assay counterpart (ImmunoCAP, Immulite). Microgram per mL quantities of allergen-specific IgG antibody can also complete with nanogram per mL quantities of specific IgE for limited allergen binding sites on the chip. Microarray assays, while not used in clinical immunology laboratories for routine patient IgE antibody testing, will remain an excellent research tool for defining sensitization profiles of populations in epidemiological studies. PMID:28134842

  17. Optical addressing technique for a CMOS RAM

    NASA Technical Reports Server (NTRS)

    Wu, W. H.; Bergman, L. A.; Allen, R. A.; Johnston, A. R.

    1988-01-01

    Progress on optically addressing a CMOS RAM for a feasibility demonstration of free space optical interconnection is reported in this paper. The optical RAM chip has been fabricated and functional testing is in progress. Initial results seem promising. New design and SPICE simulation of optical gate cell (OGC) circuits have been carried out to correct the slow fall time of the 'weak pull down' OGC, which has been characterized experimentally. Methods of reducing the response times of the photodiodes and the associated circuits are discussed. Even with the current photodiode, it appears that an OGC can be designed with a performance that is compatible with a CMOS circuit such as the RAM.

  18. End-of-fabrication CMOS process monitor

    NASA Technical Reports Server (NTRS)

    Buehler, M. G.; Allen, R. A.; Blaes, B. R.; Hannaman, D. J.; Lieneweg, U.; Lin, Y.-S.; Sayah, H. R.

    1990-01-01

    A set of test 'modules' for verifying the quality of a complementary metal oxide semiconductor (CMOS) process at the end of the wafer fabrication is documented. By electrical testing of specific structures, over thirty parameters are collected characterizing interconnects, dielectrics, contacts, transistors, and inverters. Each test module contains a specification of its purpose, the layout of the test structure, the test procedures, the data reduction algorithms, and exemplary results obtained from 3-, 2-, or 1.6-micrometer CMOS/bulk processes. The document is intended to establish standard process qualification procedures for Application Specific Integrated Circuits (ASIC's).

  19. The application of phenotypic microarray analysis to anti-fungal drug development.

    PubMed

    Greetham, Darren; Lappin, David F; Rajendran, Ranjith; O'Donnell, Lindsay; Sherry, Leighann; Ramage, Gordon; Nile, Christopher

    2017-03-01

    Candida albicans metabolic activity in the presence and absence of acetylcholine was measured using phenotypic microarray analysis. Acetylcholine inhibited C. albicans biofilm formation by slowing metabolism independent of biofilm forming capabilities. Phenotypic microarray analysis can therefore be used for screening compound libraries for novel anti-fungal drugs and measuring antifungal resistance.

  20. Transcriptional analysis of the innate immune response using the avian innate immunity microarray

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The avian innate immunity microarray (AIIM) is a genomics tool designed to study the transcriptional activity of the avian immune response (Cytogenet. Genome Res. 117:139-145, 2007). It is an avian cDNA microarray representing 4,959 avian genes spotted in triplicate. The AIIM contains 25 avian int...

  1. A 512-channels, whole array readout, CMOS implantable probe for acute recordings from the brain.

    PubMed

    Angotzi, G N; Malerba, M; Zucca, S; Berdondini, L

    2015-08-01

    The integration of implantable CMOS neural probes with thousands of simultaneously recording microelectrodes is a promising approach for neuroscience and might allow to literally image electrophysiological neuronal activity in multiple brain circuits as we have previously shown in vitro. Here, we present a complete system based on a fully multiplexed CMOS neural probe that was designed for in-vivo acute recordings with a scalable circuit architecture. In particular, a first prototype of a single-shaft probe with 512 electrodes was realized in a standard CMOS 0.18μm technology and post-processed to structure the shaft with a wedge-like geometry of 30μm in thickness at the tip and 80μm at the base. The design of the system and of the probe as well as the post-processing techniques are discussed. Finally, preliminary results on electrical, mechanical and implantation tests are presented to demonstrate the feasibility of our approach.

  2. The Current Status of DNA Microarrays

    NASA Astrophysics Data System (ADS)

    Shi, Leming; Perkins, Roger G.; Tong, Weida

    DNA microarray technology that allows simultaneous assay of thousands of genes in a single experiment has steadily advanced to become a mainstream method used in research, and has reached a stage that envisions its use in medical applications and personalized medicine. Many different strategies have been developed for manufacturing DNA microarrays. In this chapter, we discuss the manufacturing characteristics of seven microarray platforms that were used in a recently completed large study by the MicroArray Quality Control (MAQC) consortium, which evaluated the concordance of results across these platforms. The platforms can be grouped into three categories: (1) in situ synthesis of oligonucleotide probes on microarrays (Affymetrix GeneChip® arrays based on photolithography synthesis and Agilent's arrays based on inkjet synthesis); (2) spotting of presynthesized oligonucleotide probes on microarrays (GE Healthcare's CodeLink system, Applied Biosystems' Genome Survey Microarrays, and the custom microarrays printed with Operon's oligonucleotide set); and (3) deposition of presynthesized oligonucleotide probes on bead-based microarrays (Illumina's BeadChip microarrays). We conclude this chapter with our views on the challenges and opportunities toward acceptance of DNA microarray data in clinical and regulatory settings.

  3. The Current Status of DNA Microarrays

    NASA Astrophysics Data System (ADS)

    Shi, Leming; Perkins, Roger G.; Tong, Weida

    DNA microarray technology that allows simultaneous assay of thousands of genes in a single experiment has steadily advanced to become a mainstream method used in research, and has reached a stage that envisions its use in medical applications and personalized medicine. Many different strategies have been developed for manufacturing DNA microarrays. In this chapter, we discuss the manu facturing characteristics of seven microarray platforms that were used in a recently completed large study by the MicroArray Quality Control (MAQC) consortium, which evaluated the concordance of results across these platforms. The platforms can be grouped into three categories: (1) in situ synthesis of oligonucleotide probes on microarrays (Affymetrix GeneChip® arrays based on photolithography synthesis and Agilent's arrays based on inkjet synthesis); (2) spotting of presynthe-sized oligonucleotide probes on microarrays (GE Healthcare's CodeLink system, Applied Biosystems' Genome Survey Microarrays, and the custom microarrays printed with Operon's oligonucleotide set); and (3) deposition of presynthesized oligonucleotide probes on bead-based microarrays (Illumina's BeadChip microar-rays). We conclude this chapter with our views on the challenges and opportunities toward acceptance of DNA microarray data in clinical and regulatory settings.

  4. Microarray analysis in pulmonary hypertension

    PubMed Central

    Hoffmann, Julia; Wilhelm, Jochen; Olschewski, Andrea

    2016-01-01

    Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions. They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles. Combined, they provide important information on development, progression and the end-stage disease. In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance. PMID:27076594

  5. DNA microarray technology in dermatology.

    PubMed

    Kunz, Manfred

    2008-03-01

    In recent years, DNA microarray technology has been used for the analysis of gene expression patterns in a variety of skin diseases, including malignant melanoma, psoriasis, lupus erythematosus, and systemic sclerosis. Many of the studies described herein confirmed earlier results on individual genes or functional groups of genes. However, a plethora of new candidate genes, gene patterns, and regulatory pathways have been identified. Major progresses were reached by the identification of a prognostic gene pattern in malignant melanoma, an immune signaling cluster in psoriasis, and a so-called interferon signature in systemic lupus erythematosus. In future, interference with genes or regulatory pathways with the use of different RNA interference technologies or targeted therapy may not only underscore the functional significance of microarray data but also may open interesting therapeutic perspectives. Large-scale gene expression analyses may also help to design more individualized treatment approaches of cutaneous diseases.

  6. Microarray analysis in pulmonary hypertension.

    PubMed

    Hoffmann, Julia; Wilhelm, Jochen; Olschewski, Andrea; Kwapiszewska, Grazyna

    2016-07-01

    Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions. They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles. Combined, they provide important information on development, progression and the end-stage disease. In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance.

  7. Do DNA Microarrays Tell the Story of Gene Expression?

    PubMed Central

    Rosenfeld, Simon

    2010-01-01

    Poor reproducibility of microarray measurements is a major obstacle to their application as an instrument for clinical diagnostics. In this paper, several aspects of poor reproducibility are analyzed. All of them belong to the category of interpretive weaknesses of DNA microarray technology. First, the attention is drawn to the fact that absence of the information regarding post-transcriptional mRNA stability makes it impossible to evaluate the level of gene activity from the relative mRNA abundances, the quantities available from microarray measurements. Second, irreducible intracellular variability with persistent patterns of stochasticity and burstiness put natural limits to reproducibility. Third, strong interactions within intracellular biomolecular networks make it highly problematic to build a bridge between transcription rates of individual genes and structural fidelity of their genetic codes. For these reasons, the microarray measurements of relative mRNA abundances are more appropriate in laboratory settings as a tool for scientific research, hypotheses generating and producing the leads for subsequent validation through more sophisticated technologies. As to clinical settings, where firm conclusive diagnoses, not the leads for further experimentation, are required, microarrays still have a long way to go until they become a reliable instrument in patient-related decision making. PMID:20628535

  8. A novel CMOS sensor with in-pixel auto-zeroed discrimination for charged particle tracking

    NASA Astrophysics Data System (ADS)

    Degerli, Y.; Guilloux, F.; Orsini, F.

    2014-05-01

    With the aim of developing fast and granular Monolithic Active Pixels Sensors (MAPS) as new charged particle tracking detectors for high energy physics experiments, a new rolling shutter binary pixel architecture concept (RSBPix) with in-pixel correlated double sampling, amplification and discrimination is presented. The discriminator features auto-zeroing in order to compensate process-related transistor mismatches. In order to validate the pixel, a first monolithic CMOS sensor prototype, including a pixel array of 96 × 64 pixels, has been designed and fabricated in the Tower-Jazz 0.18 μm CMOS Image Sensor (CIS) process. Results of laboratory tests are presented.

  9. Results of the 2015 testbeam of a 180 nm AMS High-Voltage CMOS sensor prototype

    SciTech Connect

    Benoit, M.; de Mendizabal, J. Bilbao; Casse, G.; Chen, H.; Chen, K.; Bello, F. A. Di; Ferrere, D.; Golling, T.; Gonzalez-Sevilla, S.; Iacobucci, G.; Lanni, F.; Liu, H.; Meloni, F.; Meng, L.; Miucci, A.; Muenstermann, D.; Nessi, M.; Perić, I.; Rimoldi, M.; Ristic, B.; Pinto, M. Vicente Barrero; Vossebeld, J.; Weber, M.; Wu, W.; Xu, L.

    2016-07-21

    We investigated the active pixel sensors based on the High-Voltage CMOS technology as a viable option for the future pixel tracker of the ATLAS experiment at the High-Luminosity LHC. Our paper reports on the testbeam measurements performed at the H8 beamline of the CERN Super Proton Synchrotron on a High-Voltage CMOS sensor prototype produced in 180 nm AMS technology. These results in terms of tracking efficiency and timing performance, for different threshold and bias conditions, are shown.

  10. Microarrays, antiobesity and the liver

    PubMed Central

    Castro-Chávez, Fernando

    2013-01-01

    In this review, the microarray technology and especially oligonucleotide arrays are exemplified with a practical example taken from the perilipin−/− mice and using the dChip software, available for non-lucrative purposes. It was found that the liver of perilipin−/− mice was healthy and normal, even under high-fat diet when compared with the results published for the scd1−/− mice, which under high-fat diets had a darker liver, suggestive of hepatic steatosis. Scd1 is required for the biosynthesis of monounsaturated fatty acids and plays a key role in the hepatic synthesis of triglycerides and of very-low-density lipoproteins. Both models of obesity resistance share many similar phenotypic antiobesity features, however, the perilipin−/− mice had a significant downregulation of stearoyl CoA desaturases scd1 and scd2 in its white adipose tissue, but a normal level of both genes inside the liver, even under high-fat diet. Here, different microarray methodologies are discussed, and also some of the most recent discoveries and perspectives regarding the use of microarrays, with an emphasis on obesity gene expression, and a personal remark on my findings of increased expression for hemoglobin transcripts and other hemo related genes (hemo-like), and for leukocyte like (leuko-like) genes inside the white adipose tissue of the perilipin−/− mice. In conclusion, microarrays have much to offer in comparative studies such as those in antiobesity, and also they are methodologies adequate for new astounding molecular discoveries [free full text of this article PMID:15657555

  11. Improving CMOS-compatible Germanium photodetectors.

    PubMed

    Li, Guoliang; Luo, Ying; Zheng, Xuezhe; Masini, Gianlorenzo; Mekis, Attila; Sahni, Subal; Thacker, Hiren; Yao, Jin; Shubin, Ivan; Raj, Kannan; Cunningham, John E; Krishnamoorthy, Ashok V

    2012-11-19

    We report design improvements for evanescently coupled Germanium photodetectors grown at low temperature. The resulting photodetectors with 10 μm Ge length manufactured in a commercial CMOS process achieve >0.8 A/W responsivity over the entire C-band, with a device capacitance of <7 fF based on measured data.

  12. Design and realization of CMOS image sensor

    NASA Astrophysics Data System (ADS)

    Xu, Jian; Xiao, Zexin

    2008-02-01

    A project was presented that instrumental design of an economical CMOS microscope image sensor. A high performance, low price, black-white camera chip OV5116P was used as the core of the sensor circuit; Designing and realizing peripheral control circuit of sensor; Through the control on dial switch to realize different functions of the sensor chip in the system. For example: auto brightness level descending function on or off; gamma correction function on or off; auto and manual backlight compensation mode conversion and so on. The optical interface of sensor is designed for commercialization and standardization. The images of sample were respectively gathered with CCD and CMOS. Result of the experiment indicates that both performances were identical in several aspects as follows: image definition, contrast control, heating degree and the function can be adjusted according to the demand of user etc. The imperfection was that the CMOS with smaller field and higher noise than CCD; nevertheless, the maximal advantage of choosing the CMOS chip is its low cost. And its imaging quality conformed to requirement of the economical microscope image sensor.

  13. SEU hardening of CMOS memory circuit

    NASA Technical Reports Server (NTRS)

    Whitaker, S.; Canaris, J.; Liu, K.

    1990-01-01

    This paper reports a design technique to harden CMOS memory circuits against Single Event Upset (SEU) in the space environment. A RAM cell and Flip Flop design are presented to demonstrate the method. The Flip Flop was used in the control circuitry for a Reed Solomon encoder designed for the Space Station.

  14. Fully CMOS-compatible titanium nitride nanoantennas

    SciTech Connect

    Briggs, Justin A.; Naik, Gururaj V.; Baum, Brian K.; Dionne, Jennifer A.; Petach, Trevor A.; Goldhaber-Gordon, David

    2016-02-01

    CMOS-compatible fabrication of plasmonic materials and devices will accelerate the development of integrated nanophotonics for information processing applications. Using low-temperature plasma-enhanced atomic layer deposition (PEALD), we develop a recipe for fully CMOS-compatible titanium nitride (TiN) that is plasmonic in the visible and near infrared. Films are grown on silicon, silicon dioxide, and epitaxially on magnesium oxide substrates. By optimizing the plasma exposure per growth cycle during PEALD, carbon and oxygen contamination are reduced, lowering undesirable loss. We use electron beam lithography to pattern TiN nanopillars with varying diameters on silicon in large-area arrays. In the first reported single-particle measurements on plasmonic TiN, we demonstrate size-tunable darkfield scattering spectroscopy in the visible and near infrared regimes. The optical properties of this CMOS-compatible material, combined with its high melting temperature and mechanical durability, comprise a step towards fully CMOS-integrated nanophotonic information processing.

  15. Low energy CMOS for space applications

    NASA Technical Reports Server (NTRS)

    Panwar, Ramesh; Alkalaj, Leon

    1992-01-01

    The current focus of NASA's space flight programs reflects a new thrust towards smaller, less costly, and more frequent space missions, when compared to missions such as Galileo, Magellan, or Cassini. Recently, the concept of a microspacecraft was proposed. In this concept, a small, compact spacecraft that weighs tens of kilograms performs focused scientific objectives such as imaging. Similarly, a Mars Lander micro-rover project is under study that will allow miniature robots weighing less than seven kilograms to explore the Martian surface. To bring the microspacecraft and microrover ideas to fruition, one will have to leverage compact 3D multi-chip module-based multiprocessors (MCM) technologies. Low energy CMOS will become increasingly important because of the thermodynamic considerations in cooling compact 3D MCM implementations and also from considerations of the power budget for space applications. In this paper, we show how the operating voltage is related to the threshold voltage of the CMOS transistors for accomplishing a task in VLSI with minimal energy. We also derive expressions for the noise margins at the optimal operating point. We then look at a low voltage CMOS (LVCMOS) technology developed at Stanford University which improves the power consumption over conventional CMOS by a couple of orders of magnitude and consider the suitability of the technology for space applications by characterizing its SEU immunity.

  16. A Hybrid CMOS-Memristor Neuromorphic Synapse.

    PubMed

    Azghadi, Mostafa Rahimi; Linares-Barranco, Bernabe; Abbott, Derek; Leong, Philip H W

    2017-04-01

    Although data processing technology continues to advance at an astonishing rate, computers with brain-like processing capabilities still elude us. It is envisioned that such computers may be achieved by the fusion of neuroscience and nano-electronics to realize a brain-inspired platform. This paper proposes a high-performance nano-scale Complementary Metal Oxide Semiconductor (CMOS)-memristive circuit, which mimics a number of essential learning properties of biological synapses. The proposed synaptic circuit that is composed of memristors and CMOS transistors, alters its memristance in response to timing differences among its pre- and post-synaptic action potentials, giving rise to a family of Spike Timing Dependent Plasticity (STDP). The presented design advances preceding memristive synapse designs with regards to the ability to replicate essential behaviours characterised in a number of electrophysiological experiments performed in the animal brain, which involve higher order spike interactions. Furthermore, the proposed hybrid device CMOS area is estimated as [Formula: see text] in a [Formula: see text] process-this represents a factor of ten reduction in area with respect to prior CMOS art. The new design is integrated with silicon neurons in a crossbar array structure amenable to large-scale neuromorphic architectures and may pave the way for future neuromorphic systems with spike timing-dependent learning features. These systems are emerging for deployment in various applications ranging from basic neuroscience research, to pattern recognition, to Brain-Machine-Interfaces.

  17. CMOS preamplifiers for detectors large and small

    SciTech Connect

    O`Connor, P.

    1997-12-31

    We describe four CMOS preamplifiers developed for multiwire proportional chambers (MWPC) and silicon drift detectors (SDD) covering a capacitance range from 150 pF to 0.15 pF. Circuit techniques to optimize noise performance, particularly in the low-capacitance regime, are discussed.

  18. Radiation Tolerance of 65nm CMOS Transistors

    DOE PAGES

    Krohn, M.; Bentele, B.; Christian, D. C.; ...

    2015-12-11

    We report on the effects of ionizing radiation on 65 nm CMOS transistors held at approximately -20°C during irradiation. The pattern of damage observed after a total dose of 1 Grad is similar to damage reported in room temperature exposures, but we observe less damage than was observed at room temperature.

  19. SOI CMOS Imager with Suppression of Cross-Talk

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata; Zheng, Xingyu; Cunningham, Thomas J.; Seshadri, Suresh; Sun, Chao

    2009-01-01

    A monolithic silicon-on-insulator (SOI) complementary metal oxide/semiconductor (CMOS) image-detecting integrated circuit of the active-pixel-sensor type, now undergoing development, is designed to operate at visible and near-infrared wavelengths and to offer a combination of high quantum efficiency and low diffusion and capacitive cross-talk among pixels. The imager is designed to be especially suitable for astronomical and astrophysical applications. The imager design could also readily be adapted to general scientific, biological, medical, and spectroscopic applications. One of the conditions needed to ensure both high quantum efficiency and low diffusion cross-talk is a relatively high reverse bias potential (between about 20 and about 50 V) on the photodiode in each pixel. Heretofore, a major obstacle to realization of this condition in a monolithic integrated circuit has been posed by the fact that the required high reverse bias on the photodiode is incompatible with metal oxide/semiconductor field-effect transistors (MOSFETs) in the CMOS pixel readout circuitry. In the imager now being developed, the SOI structure is utilized to overcome this obstacle: The handle wafer is retained and the photodiode is formed in the handle wafer. The MOSFETs are formed on the SOI layer, which is separated from the handle wafer by a buried oxide layer. The electrical isolation provided by the buried oxide layer makes it possible to bias the MOSFETs at CMOS-compatible potentials (between 0 and 3 V), while biasing the photodiode at the required higher potential, and enables independent optimization of the sensory and readout portions of the imager.

  20. Low-Power SOI CMOS Transceiver

    NASA Technical Reports Server (NTRS)

    Fujikawa, Gene (Technical Monitor); Cheruiyot, K.; Cothern, J.; Huang, D.; Singh, S.; Zencir, E.; Dogan, N.

    2003-01-01

    The work aims at developing a low-power Silicon on Insulator Complementary Metal Oxide Semiconductor (SOI CMOS) Transceiver for deep-space communications. RF Receiver must accomplish the following tasks: (a) Select the desired radio channel and reject other radio signals, (b) Amplify the desired radio signal and translate them back to baseband, and (c) Detect and decode the information with Low BER. In order to minimize cost and achieve high level of integration, receiver architecture should use least number of external filters and passive components. It should also consume least amount of power to minimize battery cost, size, and weight. One of the most stringent requirements for deep-space communication is the low-power operation. Our study identified that two candidate architectures listed in the following meet these requirements: (1) Low-IF receiver, (2) Sub-sampling receiver. The low-IF receiver uses minimum number of external components. Compared to Zero-IF (Direct conversion) architecture, it has less severe offset and flicker noise problems. The Sub-sampling receiver amplifies the RF signal and samples it using track-and-hold Subsampling mixer. These architectures provide low-power solution for the short- range communications missions on Mars. Accomplishments to date include: (1) System-level design and simulation of a Double-Differential PSK receiver, (2) Implementation of Honeywell SOI CMOS process design kit (PDK) in Cadence design tools, (3) Design of test circuits to investigate relationships between layout techniques, geometry, and low-frequency noise in SOI CMOS, (4) Model development and verification of on-chip spiral inductors in SOI CMOS process, (5) Design/implementation of low-power low-noise amplifier (LNA) and mixer for low-IF receiver, and (6) Design/implementation of high-gain LNA for sub-sampling receiver. Our initial results show that substantial improvement in power consumption is achieved using SOI CMOS as compared to standard CMOS

  1. CMOS-compatible spintronic devices: a review

    NASA Astrophysics Data System (ADS)

    Makarov, Alexander; Windbacher, Thomas; Sverdlov, Viktor; Selberherr, Siegfried

    2016-11-01

    For many decades CMOS devices have been successfully scaled down to achieve higher speed and increased performance of integrated circuits at lower cost. Today’s charge-based CMOS electronics encounters two major challenges: power dissipation and variability. Spintronics is a rapidly evolving research and development field, which offers a potential solution to these issues by introducing novel ‘more than Moore’ devices. Spin-based magnetoresistive random-access memory (MRAM) is already recognized as one of the most promising candidates for future universal memory. Magnetic tunnel junctions, the main elements of MRAM cells, can also be used to build logic-in-memory circuits with non-volatile storage elements on top of CMOS logic circuits, as well as versatile compact on-chip oscillators with low power consumption. We give an overview of CMOS-compatible spintronics applications. First, we present a brief introduction to the physical background considering such effects as magnetoresistance, spin-transfer torque (STT), spin Hall effect, and magnetoelectric effects. We continue with a comprehensive review of the state-of-the-art spintronic devices for memory applications (STT-MRAM, domain wall-motion MRAM, and spin-orbit torque MRAM), oscillators (spin torque oscillators and spin Hall nano-oscillators), logic (logic-in-memory, all-spin logic, and buffered magnetic logic gate grid), sensors, and random number generators. Devices with different types of resistivity switching are analyzed and compared, with their advantages highlighted and challenges revealed. CMOS-compatible spintronic devices are demonstrated beginning with predictive simulations, proceeding to their experimental confirmation and realization, and finalized by the current status of application in modern integrated systems and circuits. We conclude the review with an outlook, where we share our vision on the future applications of the prospective devices in the area.

  2. Changes in hepatic gene expression related to innate immunity, growth and iron metabolism in GH-transgenic amago salmon (Oncorhynchus masou) by cDNA subtraction and microarray analysis, and serum lysozyme activity.

    PubMed

    Mori, Tsukasa; Hiraka, Ikuei; Kurata, Youichi; Kawachi, Hiroko; Mano, Nobuhiro; Devlin, Robert H; Nagoya, Hiroyuki; Araki, Kazuo

    2007-03-01

    Growth hormone (GH) transgenic amago salmon (Oncorhynchus masou) were generated with a construct containing the sockeye salmon GH1 gene fused to the metallothionein-B (MT-B) promoter from the same species. This transgene directed significant growth enhancement with transgenic fish reaching approximately four to five times greater weight than control salmon in F(2) and F(3) generations. This drastic growth enhancement by GH transgene is well known in fish species compared with mammals, however, such fish can show morphological abnormalities and physiological disorders like other GH transgenic animals. GH is known to have many acute effects, but currently there are no data describing the chronic effects of over-expression of GH on various hepatic genes in GH transgenic fish. Hepatic gene expression is anticipated to play very important roles in many physiological functions and growth performance of transgenic and control salmon. To examine these effects, we performed subtractive hybridization (using cDNA generated from liver RNA) in both directions to identify genes both increased and decreased in transgenic salmon relative to controls (576 clones were isolated and sequenced in total). Heme oxygenase, vitelline envelope protein, Acyl-coA binding protein, NADH dehydrogenase, mannose binding lectin-associated serine protease, hemopexin-like protein, leucyte-derived chemotaxin2 (LECT2), and many other genes were obtained in higher clone frequencies suggesting enhanced expression. In contrast, complement C3-1, lectin, rabin, alcohol dehydrogenase, Tc1-like transposase, Delta6-desaturase, and pentraxin genes were obtained in lower frequencies. Microarray analysis was also performed to obtain quantitative expression data for these subtracted cDNA clones. Analysis of fish across seasons was also conducted using both F(2) and F(3) salmon. Results of the microarray data essentially corresponded with those of the subtraction data when both F(2) and F(3) fish were completely

  3. Fabrication and Characterization of a CMOS-MEMS Humidity Sensor

    PubMed Central

    Dennis, John-Ojur; Ahmed, Abdelaziz-Yousif; Khir, Mohd-Haris

    2015-01-01

    This paper reports on the fabrication and characterization of a Complementary Metal Oxide Semiconductor-Microelectromechanical System (CMOS-MEMS) device with embedded microheater operated at relatively elevated temperatures (40 °C to 80 °C) for the purpose of relative humidity measurement. The sensing principle is based on the change in amplitude of the device due to adsorption or desorption of humidity on the active material layer of titanium dioxide (TiO2) nanoparticles deposited on the moving plate, which results in changes in the mass of the device. The sensor has been designed and fabricated through a standard 0.35 µm CMOS process technology and post-CMOS micromachining technique has been successfully implemented to release the MEMS structures. The sensor is operated in the dynamic mode using electrothermal actuation and the output signal measured using a piezoresistive (PZR) sensor connected in a Wheatstone bridge circuit. The output voltage of the humidity sensor increases from 0.585 mV to 30.580 mV as the humidity increases from 35% RH to 95% RH. The output voltage is found to be linear from 0.585 mV to 3.250 mV as the humidity increased from 35% RH to 60% RH, with sensitivity of 0.107 mV/% RH; and again linear from 3.250 mV to 30.580 mV as the humidity level increases from 60% RH to 95% RH, with higher sensitivity of 0.781 mV/% RH. On the other hand, the sensitivity of the humidity sensor increases linearly from 0.102 mV/% RH to 0.501 mV/% RH with increase in the temperature from 40 °C to 80 °C and a maximum hysteresis of 0.87% RH is found at a relative humidity of 80%. The sensitivity is also frequency dependent, increasing from 0.500 mV/% RH at 2 Hz to reach a maximum value of 1.634 mV/% RH at a frequency of 12 Hz, then decreasing to 1.110 mV/% RH at a frequency of 20 Hz. Finally, the CMOS-MEMS humidity sensor showed comparable response, recovery, and repeatability of measurements in three cycles as compared to a standard sensor that directly

  4. Fabrication and Characterization of a CMOS-MEMS Humidity Sensor.

    PubMed

    Dennis, John-Ojur; Ahmed, Abdelaziz-Yousif; Khir, Mohd-Haris

    2015-07-10

    This paper reports on the fabrication and characterization of a Complementary Metal Oxide Semiconductor-Microelectromechanical System (CMOS-MEMS) device with embedded microheater operated at relatively elevated temperatures (40 °C to 80 °C) for the purpose of relative humidity measurement. The sensing principle is based on the change in amplitude of the device due to adsorption or desorption of humidity on the active material layer of titanium dioxide (TiO2) nanoparticles deposited on the moving plate, which results in changes in the mass of the device. The sensor has been designed and fabricated through a standard 0.35 µm CMOS process technology and post-CMOS micromachining technique has been successfully implemented to release the MEMS structures. The sensor is operated in the dynamic mode using electrothermal actuation and the output signal measured using a piezoresistive (PZR) sensor connected in a Wheatstone bridge circuit. The output voltage of the humidity sensor increases from 0.585 mV to 30.580 mV as the humidity increases from 35% RH to 95% RH. The output voltage is found to be linear from 0.585 mV to 3.250 mV as the humidity increased from 35% RH to 60% RH, with sensitivity of 0.107 mV/% RH; and again linear from 3.250 mV to 30.580 mV as the humidity level increases from 60% RH to 95% RH, with higher sensitivity of 0.781 mV/% RH. On the other hand, the sensitivity of the humidity sensor increases linearly from 0.102 mV/% RH to 0.501 mV/% RH with increase in the temperature from 40 °C to 80 °C and a maximum hysteresis of 0.87% RH is found at a relative humidity of 80%. The sensitivity is also frequency dependent, increasing from 0.500 mV/% RH at 2 Hz to reach a maximum value of 1.634 mV/% RH at a frequency of 12 Hz, then decreasing to 1.110 mV/% RH at a frequency of 20 Hz. Finally, the CMOS-MEMS humidity sensor showed comparable response, recovery, and repeatability of measurements in three cycles as compared to a standard sensor that directly

  5. Surface characterization of carbohydrate microarrays.

    PubMed

    Scurr, David J; Horlacher, Tim; Oberli, Matthias A; Werz, Daniel B; Kroeck, Lenz; Bufali, Simone; Seeberger, Peter H; Shard, Alexander G; Alexander, Morgan R

    2010-11-16

    Carbohydrate microarrays are essential tools to determine the biological function of glycans. Here, we analyze a glycan array by time-of-flight secondary ion mass spectrometry (ToF-SIMS) to gain a better understanding of the physicochemical properties of the individual spots and to improve carbohydrate microarray quality. The carbohydrate microarray is prepared by piezo printing of thiol-terminated sugars onto a maleimide functionalized glass slide. The hyperspectral ToF-SIMS imaging data are analyzed by multivariate curve resolution (MCR) to discern secondary ions from regions of the array containing saccharide, linker, salts from the printing buffer, and the background linker chemistry. Analysis of secondary ions from the linker common to all of the sugar molecules employed reveals a relatively uniform distribution of the sugars within the spots formed from solutions with saccharide concentration of 0.4 mM and less, whereas a doughnut shape is often formed at higher-concentration solutions. A detailed analysis of individual spots reveals that in the larger spots the phosphate buffered saline (PBS) salts are heterogeneously distributed, apparently resulting in saccharide concentrated at the rim of the spots. A model of spot formation from the evaporating sessile drop is proposed to explain these observations. Saccharide spot diameters increase with saccharide concentration due to a reduction in surface tension of the saccharide solution compared to PBS. The multivariate analytical partial least squares (PLS) technique identifies ions from the sugars that in the complex ToF-SIMS spectra correlate with the binding of galectin proteins.

  6. Spoked-ring microcavities: enabling seamless integration of nanophotonics in unmodified advanced CMOS microelectronics chips

    NASA Astrophysics Data System (ADS)

    Wade, Mark T.; Shainline, Jeffrey M.; Orcutt, Jason S.; Ram, Rajeev J.; Stojanovic, Vladimir; Popovic, Milos A.

    2014-03-01

    We present the spoked-ring microcavity, a nanophotonic building block enabling energy-efficient, active photonics in unmodified, advanced CMOS microelectronics processes. The cavity is realized in the IBM 45nm SOI CMOS process - the same process used to make many commercially available microprocessors including the IBM Power7 and Sony Playstation 3 processors. In advanced SOI CMOS processes, no partial etch steps and no vertical junctions are available, which limits the types of optical cavities that can be used for active nanophotonics. To enable efficient active devices with no process modifications, we designed a novel spoked-ring microcavity which is fully compatible with the constraints of the process. As a modulator, the device leverages the sub-100nm lithography resolution of the process to create radially extending p-n junctions, providing high optical fill factor depletion-mode modulation and thereby eliminating the need for a vertical junction. The device is made entirely in the transistor active layer, low-loss crystalline silicon, which eliminates the need for a partial etch commonly used to create ridge cavities. In this work, we present the full optical and electrical design of the cavity including rigorous mode solver and FDTD simulations to design the Qlimiting electrical contacts and the coupling/excitation. We address the layout of active photonics within the mask set of a standard advanced CMOS process and show that high-performance photonic devices can be seamlessly monolithically integrated alongside electronics on the same chip. The present designs enable monolithically integrated optoelectronic transceivers on a single advanced CMOS chip, without requiring any process changes, enabling the penetration of photonics into the microprocessor.

  7. Diagnostic challenges for multiplexed protein microarrays.

    PubMed

    Master, Stephen R; Bierl, Charlene; Kricka, Larry J

    2006-11-01

    Multiplexed protein analysis using planar microarrays or microbeads is growing in popularity for simultaneous assays of antibodies, cytokines, allergens, drugs and hormones. However, this new assay format presents several new operational issues for the clinical laboratory, such as the quality control of protein-microarray-based assays, the release of unrequested test data and the use of diagnostic algorithms to transform microarray data into diagnostic results.

  8. Automated Microarray Image Analysis Toolbox for MATLAB

    SciTech Connect

    White, Amanda M.; Daly, Don S.; Willse, Alan R.; Protic, Miroslava; Chandler, Darrell P.

    2005-09-01

    The Automated Microarray Image Analysis (AMIA) Toolbox for MATLAB is a flexible, open-source microarray image analysis tool that allows the user to customize analysis of sets of microarray images. This tool provides several methods of identifying and quantify spot statistics, as well as extensive diagnostic statistics and images to identify poor data quality or processing. The open nature of this software allows researchers to understand the algorithms used to provide intensity estimates and to modify them easily if desired.

  9. Graphene/Si CMOS Hybrid Hall Integrated Circuits

    NASA Astrophysics Data System (ADS)

    Huang, Le; Xu, Huilong; Zhang, Zhiyong; Chen, Chengying; Jiang, Jianhua; Ma, Xiaomeng; Chen, Bingyan; Li, Zishen; Zhong, Hua; Peng, Lian-Mao

    2014-07-01

    Graphene/silicon CMOS hybrid integrated circuits (ICs) should provide powerful functions which combines the ultra-high carrier mobility of graphene and the sophisticated functions of silicon CMOS ICs. But it is difficult to integrate these two kinds of heterogeneous devices on a single chip. In this work a low temperature process is developed for integrating graphene devices onto silicon CMOS ICs for the first time, and a high performance graphene/CMOS hybrid Hall IC is demonstrated. Signal amplifying/process ICs are manufactured via commercial 0.18 um silicon CMOS technology, and graphene Hall elements (GHEs) are fabricated on top of the passivation layer of the CMOS chip via a low-temperature micro-fabrication process. The sensitivity of the GHE on CMOS chip is further improved by integrating the GHE with the CMOS amplifier on the Si chip. This work not only paves the way to fabricate graphene/Si CMOS Hall ICs with much higher performance than that of conventional Hall ICs, but also provides a general method for scalable integration of graphene devices with silicon CMOS ICs via a low-temperature process.

  10. Graphene/Si CMOS hybrid hall integrated circuits.

    PubMed

    Huang, Le; Xu, Huilong; Zhang, Zhiyong; Chen, Chengying; Jiang, Jianhua; Ma, Xiaomeng; Chen, Bingyan; Li, Zishen; Zhong, Hua; Peng, Lian-Mao

    2014-07-07

    Graphene/silicon CMOS hybrid integrated circuits (ICs) should provide powerful functions which combines the ultra-high carrier mobility of graphene and the sophisticated functions of silicon CMOS ICs. But it is difficult to integrate these two kinds of heterogeneous devices on a single chip. In this work a low temperature process is developed for integrating graphene devices onto silicon CMOS ICs for the first time, and a high performance graphene/CMOS hybrid Hall IC is demonstrated. Signal amplifying/process ICs are manufactured via commercial 0.18 um silicon CMOS technology, and graphene Hall elements (GHEs) are fabricated on top of the passivation layer of the CMOS chip via a low-temperature micro-fabrication process. The sensitivity of the GHE on CMOS chip is further improved by integrating the GHE with the CMOS amplifier on the Si chip. This work not only paves the way to fabricate graphene/Si CMOS Hall ICs with much higher performance than that of conventional Hall ICs, but also provides a general method for scalable integration of graphene devices with silicon CMOS ICs via a low-temperature process.

  11. THE ABRF MARG MICROARRAY SURVEY 2005: TAKING THE PULSE ON THE MICROARRAY FIELD

    EPA Science Inventory

    Over the past several years microarray technology has evolved into a critical component of any discovery based program. Since 1999, the Association of Biomolecular Resource Facilities (ABRF) Microarray Research Group (MARG) has conducted biennial surveys designed to generate a pr...

  12. Living Cell Microarrays: An Overview of Concepts

    PubMed Central

    Jonczyk, Rebecca; Kurth, Tracy; Lavrentieva, Antonina; Walter, Johanna-Gabriela; Scheper, Thomas; Stahl, Frank

    2016-01-01

    Living cell microarrays are a highly efficient cellular screening system. Due to the low number of cells required per spot, cell microarrays enable the use of primary and stem cells and provide resolution close to the single-cell level. Apart from a variety of conventional static designs, microfluidic microarray systems have also been established. An alternative format is a microarray consisting of three-dimensional cell constructs ranging from cell spheroids to cells encapsulated in hydrogel. These systems provide an in vivo-like microenvironment and are preferably used for the investigation of cellular physiology, cytotoxicity, and drug screening. Thus, many different high-tech microarray platforms are currently available. Disadvantages of many systems include their high cost, the requirement of specialized equipment for their manufacture, and the poor comparability of results between different platforms. In this article, we provide an overview of static, microfluidic, and 3D cell microarrays. In addition, we describe a simple method for the printing of living cell microarrays on modified microscope glass slides using standard DNA microarray equipment available in most laboratories. Applications in research and diagnostics are discussed, e.g., the selective and sensitive detection of biomarkers. Finally, we highlight current limitations and the future prospects of living cell microarrays. PMID:27600077

  13. Clustering Short Time-Series Microarray

    NASA Astrophysics Data System (ADS)

    Ping, Loh Wei; Hasan, Yahya Abu

    2008-01-01

    Most microarray analyses are carried out on static gene expressions. However, the dynamical study of microarrays has lately gained more attention. Most researches on time-series microarray emphasize on the bioscience and medical aspects but few from the numerical aspect. This study attempts to analyze short time-series microarray mathematically using STEM clustering tool which formally preprocess data followed by clustering. We next introduce the Circular Mould Distance (CMD) algorithm with combinations of both preprocessing and clustering analysis. Both methods are subsequently compared in terms of efficiencies.

  14. SOI-CMOS-MEMS electrothermal micromirror arrays

    NASA Astrophysics Data System (ADS)

    Gilgunn, Peter J.

    A fabrication technology called SOI-CMOS-MEMS is developed to realize arrays of electrothermally actuated micromirror arrays with fill factors up to 90% and mechanical scan ranges up to +/-45°. SOI-CMOS-MEMS features bonding of a CMOS-MEMS folded electrothermal actuator chip with a SOI mirror chip. Actuators and micromirrors are separately released using Bosch-type and isotropic Si etch processes. A 1-D, 3 x 3 SOI-CMOS-MEMS mirror array is characterized at a 1 mm scale that meets fill factor and scan range targets with a power sensitivity of 1.9 deg·m W-1 and -0.9 deg·m W-1 on inner and outer actuator legs, respectively. Issues preventing fabrication of SOI-CMOS-MEMS micromirror arrays designed for 1-D and 3-D motion at scales from 500 microm to 50 microm are discussed. Electrothermomechanical analytic models of power response of a generic folded actuator topology are developed that provide insight into the trends in actuator behavior for actuator design elements such as beam geometry and heater type, among others. Adverse power and scan range scaling and favorable speed scaling are demonstrated. Mechanical constraints on device geometry are derived. Detailed material, process, test structure and device characterization is presented that demonstrates the consistency of measured device behavior with analytic models. A unified model for aspect ratio dependent etch modulation is developed that achieves depth prediction accuracy of better than 10% up to 160 microm depth over a range of feature shapes and dimensions. The technique is applied extensively in the SOI-CMOS-MEMS process to produce deep multi-level structures in Si with a single etch mask and to control uniformity and feature profiles. TiW attack during release etch is shown to be the driving factor in mirror coplanarity loss. The effect is due to thermally accelerated etching caused by heating of released structures by the exothermic reaction of Si and F. The effect is quantified using in situ infrared

  15. Solution Processable Organic Solar Cell Microarrays for Use in MEMS

    NASA Astrophysics Data System (ADS)

    Trinh, Jennifer; Lewis, Jason; Toglia, Patrick; Jiang, Xiaomei

    2011-03-01

    We have developed an innovative way to fabricate organic solar arrays for application as DC power supplies in electrostatic MEMS devices. The generation 1 microarray consists of 20 small (1 mm2) solar cells connected in series (total device area of 2.2 cm2). The device uses an active layer of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C61-butyric acid methyl ester (PC61 BM), which are mixed together (1:1 mass ratio) in appropriate solvent. We manipulated active layer nanomorphology by choice of solvents and annealing conditions. The optimized generation 1 device has an open-circuit voltage of 11.5V, short-circuit current density of 1 mA/cm2 , and a power conversion efficiency of 2% under simulated solar AM1.5 illumination. The generation 2 microarray has a new design with reduced series resistance and improved cell occupancy. The generation 2 arrays have demonstrated improved device efficiency and power output density. Detailed analysis of device physics in both generation microarrays will be presented. The procedure described has potential for producing microarrays as small as 0.01 mm2 . This work was supported by the NSF REU program (award No DMR-1004873). Authors at USF would like to thank New Energy Technology Inc. and Florida High Tech Corridor Matching Fund (FHT 09-18).

  16. Review of radiation damage studies on DNW CMOS MAPS

    NASA Astrophysics Data System (ADS)

    Traversi, G.; Gaioni, L.; Manazza, A.; Manghisoni, M.; Ratti, L.; Re, V.; Zucca, S.; Bettarini, S.; Rizzo, G.; Morsani, F.; Bosisio, L.; Rashevskaya, I.; Cindro, V.

    2013-12-01

    Monolithic active pixel sensors fabricated in a bulk CMOS technology with no epitaxial layer and standard resistivity (10 Ω cm) substrate, featuring a deep N-well as the collecting electrode (DNW MAPS), have been exposed to γ-rays, up to a final dose of 10 Mrad (SiO2), and to neutrons from a nuclear reactor, up to a total 1 MeV neutron equivalent fluence of about 3.7 ·1013cm-2. The irradiation campaign was aimed at studying the effects of radiation on the most significant parameters of the front-end electronics and on the charge collection properties of the sensors. Device characterization has been carried out before and after irradiations. The DNW MAPS irradiated with 60Co γ-rays were also subjected to high temperature annealing (100 °C for 168 h). Measurements have been performed through a number of different techniques, including electrical characterization of the front-end electronics and of DNW diodes, laser stimulation of the sensors and tests with 55Fe and 90Sr radioactive sources. This paper reviews the measurement results, their relation with the damage mechanisms underlying performance degradation and provides a new comparison between DNW devices and MAPS fabricated in a CMOS process with high resistivity (1 kΩ cm) epitaxial layer.

  17. Applications of the Integrated High-Performance CMOS Image Sensor to Range Finders - from Optical Triangulation to the Automotive Field.

    PubMed

    Wu, Jih-Huah; Pen, Cheng-Chung; Jiang, Joe-Air

    2008-03-13

    With their significant features, the applications of complementary metal-oxidesemiconductor (CMOS) image sensors covers a very extensive range, from industrialautomation to traffic applications such as aiming systems, blind guidance, active/passiverange finders, etc. In this paper CMOS image sensor-based active and passive rangefinders are presented. The measurement scheme of the proposed active/passive rangefinders is based on a simple triangulation method. The designed range finders chieflyconsist of a CMOS image sensor and some light sources such as lasers or LEDs. Theimplementation cost of our range finders is quite low. Image processing software to adjustthe exposure time (ET) of the CMOS image sensor to enhance the performance oftriangulation-based range finders was also developed. An extensive series of experimentswere conducted to evaluate the performance of the designed range finders. From theexperimental results, the distance measurement resolutions achieved by the active rangefinder and the passive range finder can be better than 0.6% and 0.25% within themeasurement ranges of 1 to 8 m and 5 to 45 m, respectively. Feasibility tests onapplications of the developed CMOS image sensor-based range finders to the automotivefield were also conducted. The experimental results demonstrated that our range finders arewell-suited for distance measurements in this field.

  18. Versatile High Resolution Oligosaccharide Microarrays for Plant Glycobiology and Cell Wall Research*

    PubMed Central

    Pedersen, Henriette L.; Fangel, Jonatan U.; McCleary, Barry; Ruzanski, Christian; Rydahl, Maja G.; Ralet, Marie-Christine; Farkas, Vladimir; von Schantz, Laura; Marcus, Susan E.; Andersen, Mathias C. F.; Field, Rob; Ohlin, Mats; Knox, J. Paul; Clausen, Mads H.; Willats, William G. T.

    2012-01-01

    Microarrays are powerful tools for high throughput analysis, and hundreds or thousands of molecular interactions can be assessed simultaneously using very small amounts of analytes. Nucleotide microarrays are well established in plant research, but carbohydrate microarrays are much less established, and one reason for this is a lack of suitable glycans with which to populate arrays. Polysaccharide microarrays are relatively easy to produce because of the ease of immobilizing large polymers noncovalently onto a variety of microarray surfaces, but they lack analytical resolution because polysaccharides often contain multiple distinct carbohydrate substructures. Microarrays of defined oligosaccharides potentially overcome this problem but are harder to produce because oligosaccharides usually require coupling prior to immobilization. We have assembled a library of well characterized plant oligosaccharides produced either by partial hydrolysis from polysaccharides or by de novo chemical synthesis. Once coupled to protein, these neoglycoconjugates are versatile reagents that can be printed as microarrays onto a variety of slide types and membranes. We show that these microarrays are suitable for the high throughput characterization of the recognition capabilities of monoclonal antibodies, carbohydrate-binding modules, and other oligosaccharide-binding proteins of biological significance and also that they have potential for the characterization of carbohydrate-active enzymes. PMID:22988248

  19. One-chip electronic detection of DNA hybridization using precision impedance-based CMOS array sensor.

    PubMed

    Lee, Kang-Ho; Lee, Jeong-Oen; Sohn, Mi-Jin; Lee, Byunghun; Choi, Suk-Hwan; Kim, Sang Kyu; Yoon, Jun-Bo; Cho, Gyu-Hyeong

    2010-12-15

    This paper describes a label-free and fully electronic detection method of DNA hybridization, which is achieved through the use of a 16×8 microarray sensor in conjunction with a new type of impedance spectroscopy constructed with standard complementary metal-oxide-semiconductor (CMOS) technology. The impedance-based method is based on changes in the reactive capacitance and the charge-transfer resistance after hybridization with complementary DNA targets. In previously published label-free techniques, the measured capacitance presented unstable capacitive properties due to the parallel resistance that is not infinite and can cause a leakage by discharging the charge on the capacitor. This paper presents an impedance extraction method that uses excitation by triangular wave voltage, which enables a reliable measurement of both C and R producing a highly sensitive sensor with a stable operation independent of external variables. The system was fabricated in an industrial 0.35-μm 4-metal 2-poly CMOS process, integrating working electrodes and readout electronics into one chip. The integrated readout, which uses a parasitic insensitive integrator, achieves an enlarged detection range and improved noise performance. The maximum average relative variations of C and R are 31.5% and 68.6%, respectively, after hybridization with a 1 μM target DNA. The proposed sensor allows quantitative evaluation of the molecule densities on the chip with distinguishable variation in the impedance. This fully electronic microsystem has great potential for use with bioanalytical tools and point-of-care diagnosis.

  20. THE ABRF-MARG MICROARRAY SURVEY 2004: TAKING THE PULSE OF THE MICROARRAY FIELD

    EPA Science Inventory

    Over the past several years, the field of microarrays has grown and evolved drastically. In its continued efforts to track this evolution, the ABRF-MARG has once again conducted a survey of international microarray facilities and individual microarray users. The goal of the surve...

  1. 2008 Microarray Research Group (MARG Survey): Sensing the State of Microarray Technology

    EPA Science Inventory

    Over the past several years, the field of microarrays has grown and evolved drastically. In its continued efforts to track this evolution and transformation, the ABRF-MARG has once again conducted a survey of international microarray facilities and individual microarray users. Th...

  2. A portable optical waveguide resonance light-scattering scanner for microarray detection.

    PubMed

    Xing, Xuefeng; Liu, Wanyao; Li, Tao; Xing, Shu; Fu, Xueqi; Wu, Dongyang; Liu, Dianjun; Wang, Zhenxin

    2016-01-07

    In the present work, a portable and low-cost planar waveguide based resonance light scattering (RLS) scanner (termed as: PW-RLS scanner) has been developed for microarray detection. The PW-RLS scanner employs a 2 × 4 white light emitting diode array (WLEDA) as the excitation light source, a folded optical path with a complementary metal oxide semiconductor (CMOS) as the signal/image acquisition device and stepper motors with gear drives as the mechanical drive system. The biological binding/recognizing events on the microarray can be detected with an evanescent waveguide-directed illumination and light-scattering label (e.g., nanoparticles) while the microarray slide acts as an evanescent waveguide substrate. The performance of the as-developed PW-RLS scanner has been evaluated by analyzing type 2 diabetes mellitus (T2DM) risk genes. Highly selective and sensitive (less than 1% allele frequency at the attomole-level) T2DM risk gene detection is achieved using single-stranded DNA functionalized gold nanoparticles (ssDNA-GNPs) as detection probes. Additionally, the successful simultaneous analysis of 15 T2DM patient genotypes suggests that the device has great potential for the realization of a personalized diagnostic test for a given disease or patient follow-up.

  3. Ultralow-Loss CMOS Copper Plasmonic Waveguides.

    PubMed

    Fedyanin, Dmitry Yu; Yakubovsky, Dmitry I; Kirtaev, Roman V; Volkov, Valentyn S

    2016-01-13

    Surface plasmon polaritons can give a unique opportunity to manipulate light at a scale well below the diffraction limit reducing the size of optical components down to that of nanoelectronic circuits. At the same time, plasmonics is mostly based on noble metals, which are not compatible with microelectronics manufacturing technologies. This prevents plasmonic components from integration with both silicon photonics and silicon microelectronics. Here, we demonstrate ultralow-loss copper plasmonic waveguides fabricated in a simple complementary metal-oxide semiconductor (CMOS) compatible process, which can outperform gold plasmonic waveguides simultaneously providing long (>40 μm) propagation length and deep subwavelength (∼λ(2)/50, where λ is the free-space wavelength) mode confinement in the telecommunication spectral range. These results create the backbone for the development of a CMOS plasmonic platform and its integration in future electronic chips.

  4. Gene-set activity toolbox (GAT): A platform for microarray-based cancer diagnosis using an integrative gene-set analysis approach.

    PubMed

    Engchuan, Worrawat; Meechai, Asawin; Tongsima, Sissades; Doungpan, Narumol; Chan, Jonathan H

    2016-08-01

    Cancer is a complex disease that cannot be diagnosed reliably using only single gene expression analysis. Using gene-set analysis on high throughput gene expression profiling controlled by various environmental factors is a commonly adopted technique used by the cancer research community. This work develops a comprehensive gene expression analysis tool (gene-set activity toolbox: (GAT)) that is implemented with data retriever, traditional data pre-processing, several gene-set analysis methods, network visualization and data mining tools. The gene-set analysis methods are used to identify subsets of phenotype-relevant genes that will be used to build a classification model. To evaluate GAT performance, we performed a cross-dataset validation study on three common cancers namely colorectal, breast and lung cancers. The results show that GAT can be used to build a reasonable disease diagnostic model and the predicted markers have biological relevance. GAT can be accessed from http://gat.sit.kmutt.ac.th where GAT's java library for gene-set analysis, simple classification and a database with three cancer benchmark datasets can be downloaded.

  5. Radiation effects on scientific CMOS image sensor

    NASA Astrophysics Data System (ADS)

    Yuanfu, Zhao; Liyan, Liu; Xiaohui, Liu; Xiaofeng, Jin; Xiang, Li

    2015-11-01

    A systemic solution for radiation hardened design is presented. Besides, a series of experiments have been carried out on the samples, and then the photoelectric response characteristic and spectral characteristic before and after the experiments have been comprehensively analyzed. The performance of the CMOS image sensor with the radiation hardened design technique realized total-dose resilience up to 300 krad(Si) and resilience to single-event latch up for LET up to 110 MeV·cm2/mg.

  6. CMOS-array design-automation techniques

    NASA Technical Reports Server (NTRS)

    Feller, A.; Lombardt, T.

    1979-01-01

    Thirty four page report discusses design of 4,096-bit complementary metal oxide semiconductor (CMOS) read-only memory (ROM). CMOSROM is either mask or laser programable. Report is divided into six sections; section one describes background of ROM chips; section two presents design goals for chip; section three discusses chip implementation and chip statistics; conclusions and recommendations are given in sections four thru six.

  7. Advanced CMOS Radiation Effects Testing and Analysis

    NASA Technical Reports Server (NTRS)

    Pellish, J. A.; Marshall, P. W.; Rodbell, K. P.; Gordon, M. S.; LaBel, K. A.; Schwank, J. R.; Dodds, N. A.; Castaneda, C. M.; Berg, M. D.; Kim, H. S.; Phan, A. M.; Seidleck, C. M.

    2014-01-01

    Presentation at the annual NASA Electronic Parts and Packaging (NEPP) Program Electronic Technology Workshop (ETW). The material includes an update of progress in this NEPP task area over the past year, which includes testing, evaluation, and analysis of radiation effects data on the IBM 32 nm silicon-on-insulator (SOI) complementary metal oxide semiconductor (CMOS) process. The testing was conducted using test vehicles supplied by directly by IBM.

  8. CMOS Camera Array With Onboard Memory

    NASA Technical Reports Server (NTRS)

    Gat, Nahum

    2009-01-01

    A compact CMOS (complementary metal oxide semiconductor) camera system has been developed with high resolution (1.3 Megapixels), a USB (universal serial bus) 2.0 interface, and an onboard memory. Exposure times, and other operating parameters, are sent from a control PC via the USB port. Data from the camera can be received via the USB port and the interface allows for simple control and data capture through a laptop computer.

  9. CMOS-controlled rapidly tunable photodetectors

    NASA Astrophysics Data System (ADS)

    Chen, Ray

    With rapidly increasing data bandwidth demands, wavelength-division-multiplexing (WDM) optical access networks seem unavoidable in the near future. To operate WDM optical networks in an efficient scheme, wavelength reconfigurability and scalability of the network are crucial. Unfortunately, most of the existing wavelength tunable technologies are neither rapidly tunable nor spectrally programmable. This dissertation presents a tunable photodetector that is designed for dynamic-wavelength allocation WDM network environments. The wavelength tuning mechanism is completely different from existing technologies. The spectrum of this detector is programmable through low-voltage digital patterns. Since the wavelength selection is achieved by electronic means, the device wavelength reconfiguration time is as fast as the electronic switching time. In this dissertation work, we have demonstrated a tunable detector that is hybridly integrated with its customized CMOS driver and receiver with nanosecond wavelength reconfiguration time. In addition to its nanosecond wavelength reconfiguration time, the spectrum of this detector is digitally programmable, which means that it can adapt to system changes without re-fabrication. We have theoretically developed and experimentally demonstrated two device operating algorithms based on the same orthogonal device-optics basis. Both the rapid wavelength tuning time and the scalability make this novel device very viable for new reconfigurable WDM networks. By taking advantage of CMOS circuit design, this detector concept can be further extended for simultaneous multiple wavelength detection. We have developed one possible chip architecture and have designed a CMOS tunable optical demux for simultaneous controllable two-wavelength detection.

  10. A CMOS compatible, ferroelectric tunnel junction.

    PubMed

    Ambriz Vargas, Fabian; Kolhatkar, Gitanjali; Broyer, Maxime; Hadj Youssef, Azza; Nouar, Rafik; Sarkissian, Andranik; Thomas, Reji; Gomez-Yanez, Carlos; Gauthier, Marc A; Ruediger, Andreas

    2017-04-03

    In recent years, the experimental demonstration of Ferroelectric Tunnel Junctions (FTJ) based on perovskite tunnel barriers has been reported. However, integrating these perovskite materials into conventional silicon memory technology remains challenging due to their lack of compatibility with the complementary metal oxide semiconductor process (CMOS). The present communication reports the fabrication of an FTJ based on a CMOS compatible tunnel barrier Hf0.5Zr0.5O2 (6 unit cells thick) on an equally CMOS compatible TiN electrode. Analysis of the FTJ by grazing angle incidence X-ray diffraction confirmed the formation of the non-centrosymmetric orthorhombic phase (Pbc2_1, ferroelectric phase). The FTJ characterization is followed by the reconstruction of the electrostatic potential profile in the as-grown TiN/Hf0.5Zr0.5O2/Pt heterostructure. A direct tunneling current model across a trapezoidal barrier was used to correlate the electronic and electrical properties of our FTJ devices. The good agreement between the experimental and the theoretical model attests to the tunneling electroresistance effect (TER) in our FTJ device. A TER ratio of ~15 was calculated for the present FTJ device at low read voltage (+0.2 V). This study makes Hf0.5Zr0.5O2 a promising candidate for integration into conventional Si memory technology.

  11. Correct CMOS IC defect models for quality testing

    NASA Technical Reports Server (NTRS)

    Soden, Jerry M.; Hawkins, Charles F.

    1993-01-01

    Leading edge, high reliability, and low escape CMOS IC test practices have now virtually removed the stuck-at fault model and replaced it with more defect-orientated models. Quiescent power supply current testing (I(sub DDQ)) combined with strategic use of high speed test patterns is the recommended approach to zero defect and high reliability testing goals. This paper reviews the reasons for the change in CMOS IC test practices and outlines an improved CMOS IC test methodology.

  12. Behavior of faulty double BJT BiCMOS logic gates

    NASA Technical Reports Server (NTRS)

    Menon, Sankaran M.; Malaiya, Yashwant K.; Jayasumana, Anura P.

    1992-01-01

    Logic Behavior of a Double BJT BiCMOS device under transistor level shorts and opens is examined. In addition to delay faults, faults that cause the gate to exhibit sequential behavior were observed. Several faults can be detected only by monitoring the current. The faulty behavior of Bipolar (TTL) and CMOS logic families is compared with BiCMOS, to bring out the testability differences.

  13. Accelerated life testing effects on CMOS microcircuit characteristics

    NASA Technical Reports Server (NTRS)

    1980-01-01

    The 250 C, 200C and 125C accelerated tests are described. The wear-out distributions from the 250 and 200 C tests were used to estimate the activation energy between the two test temperatures. The duration of the 125 C test was not sufficient to bring the test devices into the wear-out region. It was estimated that, for the most complex of the three devices types, the activation energy between 200 C and 125 C should be at least as high as that between 250 C and 200 C. The practicality of the use of high temperature for the accelerated life tests from the point of view of durability of equipment is assessed. Guidlines for the development of accelerated life-test conditions are proposed. The use of the silicon nitride overcoat to improve the high temperature accelerated life-test characteristics of CMOS microcircuits is described.

  14. Small-area and compact CMOS emulator circuit for CMOS/nanoscale memristor co-design.

    PubMed

    Shin, Sanghak; Choi, Jun-Myung; Cho, Seongik; Min, Kyeong-Sik

    2013-11-01

    In this paper, a CMOS emulator circuit that can reproduce nanoscale memristive behavior is proposed. The proposed emulator circuit can mimic the pinched hysteresis loops of nanoscale memristor memory's current-voltage relationship without using any resistor array, complicated circuit blocks, etc. that may occupy very large layout area. Instead of using a resistor array, other complicated circuit blocks, etc., the proposed emulator circuit can describe the nanoscale memristor's current-voltage relationship using a simple voltage-controlled resistor, where its resistance can be programmed by the stored voltage at the state variable capacitor. Comparing the layout area between the previous emulator circuit and the proposed one, the layout area of the proposed emulator circuit is estimated to be 32 times smaller than the previous emulator circuit. The proposed CMOS emulator circuit of nanoscale memristor memory will be very useful in developing hybrid circuits of CMOS/nanoscale memristor memory.

  15. Disc-based microarrays: principles and analytical applications.

    PubMed

    Morais, Sergi; Puchades, Rosa; Maquieira, Ángel

    2016-07-01

    The idea of using disk drives to monitor molecular biorecognition events on regular optical discs has received considerable attention during the last decade. CDs, DVDs, Blu-ray discs and other new optical discs are universal and versatile supports with the potential for development of protein and DNA microarrays. Besides, standard disk drives incorporated in personal computers can be used as compact and affordable optical reading devices. Consequently, a CD technology, resulting from the audio-video industry, has been used to develop analytical applications in health care, environmental monitoring, food safety and quality assurance. The review presents and critically evaluates the current state of the art of disc-based microarrays with illustrative examples, including past, current and future developments. Special mention is made of the analytical developments that use either chemically activated or raw standard CDs where proteins, oligonucleotides, peptides, haptens or other biological probes are immobilized. The discs are also used to perform the assays and must maintain their readability with standard optical drives. The concept and principle of evolving disc-based microarrays and the evolution of disk drives as optical detectors are also described. The review concludes with the most relevant uses ordered chronologically to provide an overview of the progress of CD technology applications in the life sciences. Also, it provides a selection of important references to the current literature. Graphical Abstract High density disc-based microarrays.

  16. Interferometric comparison of the performance of a CMOS and sCMOS detector

    NASA Astrophysics Data System (ADS)

    Flores-Moreno, J. M.; De la Torre I., Manuel H.; Hernández-Montes, M. S.; Pérez-López, Carlos; Mendoza S., Fernando

    2015-08-01

    We present an analysis of the imaging performance of two state-of-the-art sensors widely used in the nondestructive- testing area (NDT). The analysis is based on the quantification of the signal-to-noise (SNR) ratio from an optical phase image. The calculation of the SNR is based on the relation of the median (average) and standard deviation measurements over specific areas of interest in the phase images of both sensors. This retrieved phase is coming from the vibrational behavior of a large object by means of an out-of-plane holographic interferometer. The SNR is used as a figure-of-merit to evaluate and compare the performance of the CMOS and scientific CMOS (sCMOS) camera as part of the experimental set-up. One of the cameras has a high speed CMOS sensor while the other has a high resolution sCMOS sensor. The object under study is a metallically framed table with a Formica cover with an observable area of 1.1 m2. The vibration induced to the sample is performed by a linear step motor with an attached tip in the motion stage. Each camera is used once at the time to record the deformation keeping the same experimental conditions for each case. These measurements may complement the conventional procedures or technical information commonly used to evaluate a camerás performance such as: quantum efficiency, spatial resolution and others. Results present post processed images from both cameras, but showing a smoother and easy to unwrap optical phase coming from those recorded with the sCMOS camera.

  17. Fundamental performance differences of CMOS and CCD imagers: part V

    NASA Astrophysics Data System (ADS)

    Janesick, James R.; Elliott, Tom; Andrews, James; Tower, John; Pinter, Jeff

    2013-02-01

    Previous papers delivered over the last decade have documented developmental progress made on large pixel scientific CMOS imagers that match or surpass CCD performance. New data and discussions presented in this paper include: 1) a new buried channel CCD fabricated on a CMOS process line, 2) new data products generated by high performance custom scientific CMOS 4T/5T/6T PPD pixel imagers, 3) ultimate CTE and speed limits for large pixel CMOS imagers, 4) fabrication and test results of a flight 4k x 4k CMOS imager for NRL's SoloHi Solar Orbiter Mission, 5) a progress report on ultra large stitched Mk x Nk CMOS imager, 6) data generated by on-chip sub-electron CDS signal chain circuitry used in our imagers, 7) CMOS and CMOSCCD proton and electron radiation damage data for dose levels up to 10 Mrd, 8) discussions and data for a new class of PMOS pixel CMOS imagers and 9) future CMOS development work planned.

  18. Development of a Depleted Monolithic CMOS Sensor in a 150 nm CMOS Technology for the ATLAS Inner Tracker Upgrade

    NASA Astrophysics Data System (ADS)

    Wang, T.; Rymaszewski, P.; Barbero, M.; Degerli, Y.; Godiot, S.; Guilloux, F.; Hemperek, T.; Hirono, T.; Krüger, H.; Liu, J.; Orsini, F.; Pangaud, P.; Rozanov, A.; Wermes, N.

    2017-01-01

    The recent R&D focus on CMOS sensors with charge collection in a depleted zone has opened new perspectives for CMOS sensors as fast and radiation hard pixel devices. These sensors, labelled as depleted CMOS sensors (DMAPS), have already shown promising performance as feasible candidates for the ATLAS Inner Tracker (ITk) upgrade, possibly replacing the current passive sensors. A further step to exploit the potential of DMAPS is to investigate the suitability of equipping the outer layers of the ATLAS ITk upgrade with fully monolithic CMOS sensors. This paper presents the development of a depleted monolithic CMOS pixel sensor designed in the LFoundry 150 nm CMOS technology, with the focus on design details and simulation results.

  19. High-speed binary CMOS image sensor using a high-responsivity MOSFET-type photodetector

    NASA Astrophysics Data System (ADS)

    Choi, Byoung-Soo; Jo, Sung-Hyun; Bae, Myunghan; Choi, Pyung; Shin, Jang-Kyoo

    2015-03-01

    In this paper, a complementary metal oxide semiconductor (CMOS) binary image sensor based on a gate/body-tied (GBT) MOSFET-type photodetector is proposed. The proposed CMOS binary image sensor was simulated and measured using a standard CMOS 0.18-μm process. The GBT MOSFET-type photodetector is composed of a floating gate (n+- polysilicon) tied to the body (n-well) of the p-type MOSFET. The size of the active pixel sensor (APS) using GBT photodetector is smaller than that of APS using the photodiode. This means that the resolution of the image can be increased. The high-gain GBT photodetector has a higher photosensitivity compared to the p-n junction photodiode that is used in a conventional APS. Because GBT has a high sensitivity, fast operation of the binary processing is possible. A CMOS image sensor with the binary processing can be designed with simple circuits composed of a comparator and a Dflip- flop while a complex analog to digital converter (ADC) is not required. In addition, the binary image sensor has low power consumption and high speed operation with the ability to switch back and forth between a binary mode and an analog mode.

  20. Tissue Microarrays in Clinical Oncology

    PubMed Central

    Voduc, David; Kenney, Challayne; Nielsen, Torsten O.

    2008-01-01

    The tissue microarray is a recently-implemented, high-throughput technology for the analysis of molecular markers in oncology. This research tool permits the rapid assessment of a biomarker in thousands of tumor samples, using commonly available laboratory assays such as immunohistochemistry and in-situ hybridization. Although introduced less than a decade ago, the TMA has proven to be invaluable in the study of tumor biology, the development of diagnostic tests, and the investigation of oncological biomarkers. This review describes the impact of TMA-based research in clinical oncology and its potential future applications. Technical aspects of TMA construction, and the advantages and disadvantages inherent to this technology are also discussed. PMID:18314063

  1. Analysis of DNA microarray expression data.

    PubMed

    Simon, Richard

    2009-06-01

    DNA microarrays are powerful tools for studying biological mechanisms and for developing prognostic and predictive classifiers for identifying the patients who require treatment and are best candidates for specific treatments. Because microarrays produce so much data from each specimen, they offer great opportunities for discovery and great dangers or producing misleading claims. Microarray based studies require clear objectives for selecting cases and appropriate analysis methods. Effective analysis of microarray data, where the number of measured variables is orders of magnitude greater than the number of cases, requires specialized statistical methods which have recently been developed. Recent literature reviews indicate that serious problems of analysis exist a substantial proportion of publications. This manuscript attempts to provide a non-technical summary of the key principles of statistical design and analysis for studies that utilize microarray expression profiling.

  2. In control: systematic assessment of microarray performance.

    PubMed

    van Bakel, Harm; Holstege, Frank C P

    2004-10-01

    Expression profiling using DNA microarrays is a powerful technique that is widely used in the life sciences. How reliable are microarray-derived measurements? The assessment of performance is challenging because of the complicated nature of microarray experiments and the many different technology platforms. There is a mounting call for standards to be introduced, and this review addresses some of the issues that are involved. Two important characteristics of performance are accuracy and precision. The assessment of these factors can be either for the purpose of technology optimization or for the evaluation of individual microarray hybridizations. Microarray performance has been evaluated by at least four approaches in the past. Here, we argue that external RNA controls offer the most versatile system for determining performance and describe how such standards could be implemented. Other uses of external controls are discussed, along with the importance of probe sequence availability and the quantification of labelled material.

  3. Chaotic mixer improves microarray hybridization.

    PubMed

    McQuain, Mark K; Seale, Kevin; Peek, Joel; Fisher, Timothy S; Levy, Shawn; Stremler, Mark A; Haselton, Frederick R

    2004-02-15

    Hybridization is an important aspect of microarray experimental design which influences array signal levels and the repeatability of data within an array and across different arrays. Current methods typically require 24h and use target inefficiently. In these studies, we compare hybridization signals obtained in conventional static hybridization, which depends on diffusional target delivery, with signals obtained in a dynamic hybridization chamber, which employs a fluid mixer based on chaotic advection theory to deliver targets across a conventional glass slide array. Microarrays were printed with a pattern of 102 identical probe spots containing a 65-mer oligonucleotide capture probe. Hybridization of a 725-bp fluorescently labeled target was used to measure average target hybridization levels, local signal-to-noise ratios, and array hybridization uniformity. Dynamic hybridization for 1h with 1 or 10ng of target DNA increased hybridization signal intensities approximately threefold over a 24-h static hybridization. Similarly, a 10- or 60-min dynamic hybridization of 10ng of target DNA increased hybridization signal intensities fourfold over a 24h static hybridization. In time course studies, static hybridization reached a maximum within 8 to 12h using either 1 or 10ng of target. In time course studies using the dynamic hybridization chamber, hybridization using 1ng of target increased to a maximum at 4h and that using 10ng of target did not vary over the time points tested. In comparison to static hybridization, dynamic hybridization reduced the signal-to-noise ratios threefold and reduced spot-to-spot variation twofold. Therefore, we conclude that dynamic hybridization based on a chaotic mixer design improves both the speed of hybridization and the maximum level of hybridization while increasing signal-to-noise ratios and reducing spot-to-spot variation.

  4. A Guided Materials Screening Approach for Developing Quantitative Sol-gel Derived Protein Microarrays

    PubMed Central

    Helka, Blake-Joseph; Brennan, John D.

    2013-01-01

    Microarrays have found use in the development of high-throughput assays for new materials and discovery of small-molecule drug leads. Herein we describe a guided material screening approach to identify sol-gel based materials that are suitable for producing three-dimensional protein microarrays. The approach first identifies materials that can be printed as microarrays, narrows down the number of materials by identifying those that are compatible with a given enzyme assay, and then hones in on optimal materials based on retention of maximum enzyme activity. This approach is applied to develop microarrays suitable for two different enzyme assays, one using acetylcholinesterase and the other using a set of four key kinases involved in cancer. In each case, it was possible to produce microarrays that could be used for quantitative small-molecule screening assays and production of dose-dependent inhibitor response curves. Importantly, the ability to screen many materials produced information on the types of materials that best suited both microarray production and retention of enzyme activity. The materials data provide insight into basic material requirements necessary for tailoring optimal, high-density sol-gel derived microarrays. PMID:24022739

  5. Independent component analysis of Alzheimer's DNA microarray gene expression data

    PubMed Central

    Kong, Wei; Mou, Xiaoyang; Liu, Qingzhong; Chen, Zhongxue; Vanderburg, Charles R; Rogers, Jack T; Huang, Xudong

    2009-01-01

    Background Gene microarray technology is an effective tool to investigate the simultaneous activity of multiple cellular pathways from hundreds to thousands of genes. However, because data in the colossal amounts generated by DNA microarray technology are usually complex, noisy, high-dimensional, and often hindered by low statistical power, their exploitation is difficult. To overcome these problems, two kinds of unsupervised analysis methods for microarray data: principal component analysis (PCA) and independent component analysis (ICA) have been developed to accomplish the task. PCA projects the data into a new space spanned by the principal components that are mutually orthonormal to each other. The constraint of mutual orthogonality and second-order statistics technique within PCA algorithms, however, may not be applied to the biological systems studied. Extracting and characterizing the most informative features of the biological signals, however, require higher-order statistics. Results ICA is one of the unsupervised algorithms that can extract higher-order statistical structures from data and has been applied to DNA microarray gene expression data analysis. We performed FastICA method on DNA microarray gene expression data from Alzheimer's disease (AD) hippocampal tissue samples and consequential gene clustering. Experimental results showed that the ICA method can improve the clustering results of AD samples and identify significant genes. More than 50 significant genes with high expression levels in severe AD were extracted, representing immunity-related protein, metal-related protein, membrane protein, lipoprotein, neuropeptide, cytoskeleton protein, cellular binding protein, and ribosomal protein. Within the aforementioned categories, our method also found 37 significant genes with low expression levels. Moreover, it is worth noting that some oncogenes and phosphorylation-related proteins are expressed in low levels. In comparison to the PCA and support

  6. Chemical microarray: a new tool for drug screening and discovery.

    PubMed

    Ma, Haiching; Horiuchi, Kurumi Y

    2006-07-01

    HTS with microtiter plates has been the major tool used in the pharmaceutical industry to explore chemical diversity space and to identify active compounds and pharmacophores for specific biological targets. However, HTS faces a daunting challenge regarding the fast-growing numbers of drug targets arising from genomic and proteomic research, and large chemical libraries generated from high-throughput synthesis. There is an urgent need to find new ways to profile the activity of large numbers of chemicals against hundreds of biological targets in a fast, low-cost fashion. Chemical microarray can rise to this challenge because it has the capability of identifying and evaluating small molecules as potential therapeutic reagents. During the past few years, chemical microarray technology, with different surface chemistries and activation strategies, has generated many successes in the evaluation of chemical-protein interactions, enzyme activity inhibition, target identification, signal pathway elucidation and cell-based functional analysis. The success of chemical microarray technology will provide unprecedented possibilities and capabilities for parallel functional analysis of tremendous amounts of chemical compounds.

  7. Faint-meteor survey with a large-format CMOS sensor

    NASA Astrophysics Data System (ADS)

    Watanabe, J.; Enomoto, T.; Terai, T.; Kasuga, T.; Miyazaki, S.; Oota, K.; Muraoka, F.; Onishi, T.; Yamasaki, T.; Mito, H.; Aoki, T.; Soyano, T.; Tarusawa, K.; Matsunaga, N.; Sako, S.; Kobayashi, N.; Doi, M.

    2014-07-01

    performed during the active period of the Geminid meteor shower. We could take valuable data on December 12 and 13. The result will be given in this presentation, together with the future potential of the large format CMOS sensor.

  8. Intrinsic signal imaging of brain function using a small implantable CMOS imaging device

    NASA Astrophysics Data System (ADS)

    Haruta, Makito; Sunaga, Yoshinori; Yamaguchi, Takahiro; Takehara, Hironari; Noda, Toshihiko; Sasagawa, Kiyotaka; Tokuda, Takashi; Ohta, Jun

    2015-04-01

    A brain functional imaging technique over a long period is important to understand brain functions related to animal behavior. We have developed a small implantable CMOS imaging device for measuring brain activity in freely moving animals. This device is composed of a CMOS image sensor chip and LEDs for illumination. In this study, we demonstrated intrinsic signal imaging of blood flow using the device with a green LED light source at a peak wavelength of 535 nm, which corresponds to one of the absorption spectral peaks of blood cells. Brain activity increases regional blood flow. The device light weight of about 0.02 g makes it possible to stably measure brain activity through blood flow over a long period. The device has successfully measured the intrinsic signal related to sensory stimulation on the primary somatosensory cortex.

  9. Transcriptome Analysis of Zebrafish Embryogenesis Using Microarrays

    PubMed Central

    Mathavan, Sinnakaruppan; Lee, Serene G. P; Mak, Alicia; Miller, Lance D; Murthy, Karuturi Radha Krishna; Govindarajan, Kunde R; Tong, Yan; Wu, Yi Lian; Lam, Siew Hong; Yang, Henry; Ruan, Yijun; Korzh, Vladimir; Gong, Zhiyuan; Liu, Edison T; Lufkin, Thomas

    2005-01-01

    Zebrafish (Danio rerio) is a well-recognized model for the study of vertebrate developmental genetics, yet at the same time little is known about the transcriptional events that underlie zebrafish embryogenesis. Here we have employed microarray analysis to study the temporal activity of developmentally regulated genes during zebrafish embryogenesis. Transcriptome analysis at 12 different embryonic time points covering five different developmental stages (maternal, blastula, gastrula, segmentation, and pharyngula) revealed a highly dynamic transcriptional profile. Hierarchical clustering, stage-specific clustering, and algorithms to detect onset and peak of gene expression revealed clearly demarcated transcript clusters with maximum gene activity at distinct developmental stages as well as co-regulated expression of gene groups involved in dedicated functions such as organogenesis. Our study also revealed a previously unidentified cohort of genes that are transcribed prior to the mid-blastula transition, a time point earlier than when the zygotic genome was traditionally thought to become active. Here we provide, for the first time to our knowledge, a comprehensive list of developmentally regulated zebrafish genes and their expression profiles during embryogenesis, including novel information on the temporal expression of several thousand previously uncharacterized genes. The expression data generated from this study are accessible to all interested scientists from our institute resource database (http://giscompute.gis.a-star.edu.sg/~govind/zebrafish/data_download.html). PMID:16132083

  10. Characterisation of diode-connected SiGe BiCMOS HBTs for space applications

    NASA Astrophysics Data System (ADS)

    Venter, Johan; Sinha, Saurabh; Lambrechts, Wynand

    2016-02-01

    Silicon-germanium (SiGe) bipolar complementary metal-oxide semiconductor (BiCMOS) transistors have vertical doping profiles reaching deeper into the substrate when compared to lateral CMOS transistors. Apart from benefiting from high-speed, high current gain and low-output resistance due to its vertical profile, BiCMOS technology is increasingly becoming a preferred technology for researchers to realise next-generation space-based optoelectronic applications. BiCMOS transistors have inherent radiation hardening, to an extent predictable cryogenic performance and monolithic integration potential. SiGe BiCMOS transistors and p-n junction diodes have been researched and used as a primary active component for over the last two decades. However, further research can be conducted with diode-connected heterojunction bipolar transistors (HBTs) operating at cryogenic temperatures. This work investigates these characteristics and models devices by adapting standard fabrication technology components. This work focuses on measurements of the current-voltage relationship (I-V curves) and capacitance-voltage relationships (C-V curves) of diode-connected HBTs. One configuration is proposed and measured, which is emitterbase shorted. The I-V curves are measured for various temperature points ranging from room temperature (300 K) to the temperature of liquid nitrogen (77 K). The measured datasets are used to extract a model of the formed diode operating at cryogenic temperatures and used as a standard library component in computer aided software designs. The advantage of having broad-range temperature models of SiGe transistors becomes apparent when considering implementation of application-specific integrated circuits and silicon-based infrared radiation photodetectors on a single wafer, thus shortening interconnects and lowering parasitic interference, decreasing the overall die size and improving on overall cost-effectiveness. Primary applications include space-based geothermal

  11. MARS: Microarray analysis, retrieval, and storage system

    PubMed Central

    Maurer, Michael; Molidor, Robert; Sturn, Alexander; Hartler, Juergen; Hackl, Hubert; Stocker, Gernot; Prokesch, Andreas; Scheideler, Marcel; Trajanoski, Zlatko

    2005-01-01

    Background Microarray analysis has become a widely used technique for the study of gene-expression patterns on a genomic scale. As more and more laboratories are adopting microarray technology, there is a need for powerful and easy to use microarray databases facilitating array fabrication, labeling, hybridization, and data analysis. The wealth of data generated by this high throughput approach renders adequate database and analysis tools crucial for the pursuit of insights into the transcriptomic behavior of cells. Results MARS (Microarray Analysis and Retrieval System) provides a comprehensive MIAME supportive suite for storing, retrieving, and analyzing multi color microarray data. The system comprises a laboratory information management system (LIMS), a quality control management, as well as a sophisticated user management system. MARS is fully integrated into an analytical pipeline of microarray image analysis, normalization, gene expression clustering, and mapping of gene expression data onto biological pathways. The incorporation of ontologies and the use of MAGE-ML enables an export of studies stored in MARS to public repositories and other databases accepting these documents. Conclusion We have developed an integrated system tailored to serve the specific needs of microarray based research projects using a unique fusion of Web based and standalone applications connected to the latest J2EE application server technology. The presented system is freely available for academic and non-profit institutions. More information can be found at . PMID:15836795

  12. Microarray analysis of gene expression profiles in ripening pineapple fruits

    PubMed Central

    2012-01-01

    Background Pineapple (Ananas comosus) is a tropical fruit crop of significant commercial importance. Although the physiological changes that occur during pineapple fruit development have been well characterized, little is known about the molecular events that occur during the fruit ripening process. Understanding the molecular basis of pineapple fruit ripening will aid the development of new varieties via molecular breeding or genetic modification. In this study we developed a 9277 element pineapple microarray and used it to profile gene expression changes that occur during pineapple fruit ripening. Results Microarray analyses identified 271 unique cDNAs differentially expressed at least 1.5-fold between the mature green and mature yellow stages of pineapple fruit ripening. Among these 271 sequences, 184 share significant homology with genes encoding proteins of known function, 53 share homology with genes encoding proteins of unknown function and 34 share no significant homology with any database accession. Of the 237 pineapple sequences with homologs, 160 were up-regulated and 77 were down-regulated during pineapple fruit ripening. DAVID Functional Annotation Cluster (FAC) analysis of all 237 sequences with homologs revealed confident enrichment scores for redox activity, organic acid metabolism, metalloenzyme activity, glycolysis, vitamin C biosynthesis, antioxidant activity and cysteine peptidase activity, indicating the functional significance and importance of these processes and pathways during pineapple fruit development. Quantitative real-time PCR analysis validated the microarray expression results for nine out of ten genes tested. Conclusions This is the first report of a microarray based gene expression study undertaken in pineapple. Our bioinformatic analyses of the transcript profiles have identified a number of genes, processes and pathways with putative involvement in the pineapple fruit ripening process. This study extends our knowledge of the

  13. DNA Microarrays in Herbal Drug Research

    PubMed Central

    Chavan, Preeti; Joshi, Kalpana; Patwardhan, Bhushan

    2006-01-01

    Natural products are gaining increased applications in drug discovery and development. Being chemically diverse they are able to modulate several targets simultaneously in a complex system. Analysis of gene expression becomes necessary for better understanding of molecular mechanisms. Conventional strategies for expression profiling are optimized for single gene analysis. DNA microarrays serve as suitable high throughput tool for simultaneous analysis of multiple genes. Major practical applicability of DNA microarrays remains in DNA mutation and polymorphism analysis. This review highlights applications of DNA microarrays in pharmacodynamics, pharmacogenomics, toxicogenomics and quality control of herbal drugs and extracts. PMID:17173108

  14. Progress in the application of DNA microarrays.

    PubMed Central

    Lobenhofer, E K; Bushel, P R; Afshari, C A; Hamadeh, H K

    2001-01-01

    Microarray technology has been applied to a variety of different fields to address fundamental research questions. The use of microarrays, or DNA chips, to study the gene expression profiles of biologic samples began in 1995. Since that time, the fundamental concepts behind the chip, the technology required for making and using these chips, and the multitude of statistical tools for analyzing the data have been extensively reviewed. For this reason, the focus of this review will be not on the technology itself but on the application of microarrays as a research tool and the future challenges of the field. PMID:11673116

  15. Lab-on-CMOS integration of microfluidics and electrochemical sensors.

    PubMed

    Huang, Yue; Mason, Andrew J

    2013-10-07

    This paper introduces a CMOS-microfluidics integration scheme for electrochemical microsystems. A CMOS chip was embedded into a micro-machined silicon carrier. By leveling the CMOS chip and carrier surface to within 100 nm, an expanded obstacle-free surface suitable for photolithography was achieved. Thin film metal planar interconnects were microfabricated to bridge CMOS pads to the perimeter of the carrier, leaving a flat and smooth surface for integrating microfluidic structures. A model device containing SU-8 microfluidic mixers and detection channels crossing over microelectrodes on a CMOS integrated circuit was constructed using the chip-carrier assembly scheme. Functional integrity of microfluidic structures and on-CMOS electrodes was verified by a simultaneous sample dilution and electrochemical detection experiment within multi-channel microfluidics. This lab-on-CMOS integration process is capable of high packing density, is suitable for wafer-level batch production, and opens new opportunities to combine the performance benefits of on-CMOS sensors with lab-on-chip platforms.

  16. High-performance VGA-resolution digital color CMOS imager

    NASA Astrophysics Data System (ADS)

    Agwani, Suhail; Domer, Steve; Rubacha, Ray; Stanley, Scott

    1999-04-01

    This paper discusses the performance of a new VGA resolution color CMOS imager developed by Motorola on a 0.5micrometers /3.3V CMOS process. This fully integrated, high performance imager has on chip timing, control, and analog signal processing chain for digital imaging applications. The picture elements are based on 7.8micrometers active CMOS pixels that use pinned photodiodes for higher quantum efficiency and low noise performance. The image processing engine includes a bank of programmable gain amplifiers, line rate clamping for dark offset removal, real time auto white balancing, per column gain and offset calibration, and a 10 bit pipelined RSD analog to digital converter with a programmable input range. Post ADC signal processing includes features such as bad pixel replacement based on user defined thresholds levels, 10 to 8 bit companding and 5 tap FIR filtering. The sensor can be programmed via a standard I2C interface that runs on 3.3V clocks. Programmable features include variable frame rates using a constant frequency master clock, electronic exposure control, continuous or single frame capture, progressive or interlace scanning modes. Each pixel is individually addressable allowing region of interest imaging and image subsampling. The sensor operates with master clock frequencies of up to 13.5MHz resulting in 30FPS. A total programmable gain of 27dB is available. The sensor power dissipation is 400mW at full speed of operation. The low noise design yields a measured 'system on a chip' dynamic range of 50dB thus giving over 8 true bits of resolution. Extremely high conversion gain result in an excellent peak sensitivity of 22V/(mu) J/cm2 or 3.3V/lux-sec. This monolithic image capture and processing engine represent a compete imaging solution making it a true 'camera on a chip'. Yet in its operation it remains extremely easy to use requiring only one clock and a 3.3V power supply. Given the available features and performance levels, this sensor will be

  17. CMOS-integrated geometrically tunable optical filters.

    PubMed

    Lerose, Damiana; Hei, Evie Kho Siaw; Ching, Bong Ching; Sterger, Martin; Yaw, Liau Chu; Schulze, Frank Michael; Schmidt, Frank; Schmidt, Andrei; Bach, Konrad

    2013-03-10

    We present a method for producing monolithically integrated complementary metal-oxide-semiconductor (CMOS) optical filters with different and customer-specific responses. The filters are constituted by a Fabry-Perot resonator formed by two Bragg mirrors separated by a patterned cavity. The filter response can be tuned by changing the geometric parameters of the patterning, and consequently the cavity effective refractive index. In this way, many different filters can be produced at once on a single chip, allowing multichanneling. The filter has been designed, produced, and characterized. The results for a chip with 24 filters are presented.

  18. Monolithic CMOS imaging x-ray spectrometers

    NASA Astrophysics Data System (ADS)

    Kenter, Almus; Kraft, Ralph; Gauron, Thomas; Murray, Stephen S.

    2014-07-01

    The Smithsonian Astrophysical Observatory (SAO) in collaboration with SRI/Sarnoff is developing monolithic CMOS detectors optimized for x-ray astronomy. The goal of this multi-year program is to produce CMOS x-ray imaging spectrometers that are Fano noise limited over the 0.1-10keV energy band while incorporating the many benefits of CMOS technology. These benefits include: low power consumption, radiation "hardness", high levels of integration, and very high read rates. Small format test devices from a previous wafer fabrication run (2011-2012) have recently been back-thinned and tested for response below 1keV. These devices perform as expected in regards to dark current, read noise, spectral response and Quantum Efficiency (QE). We demonstrate that running these devices at rates ~> 1Mpix/second eliminates the need for cooling as shot noise from any dark current is greatly mitigated. The test devices were fabricated on 15μm, high resistivity custom (~30kΩ-cm) epitaxial silicon and have a 16 by 192 pixel format. They incorporate 16μm pitch, 6 Transistor Pinned Photo Diode (6TPPD) pixels which have ~40μV/electron sensitivity and a highly parallel analog CDS signal chain. Newer, improved, lower noise detectors have just been fabricated (October 2013). These new detectors are fabricated on 9μm epitaxial silicon and have a 1k by 1k format. They incorporate similar 16μm pitch, 6TPPD pixels but have ~ 50% higher sensitivity and much (3×) lower read noise. These new detectors have undergone preliminary testing for functionality in Front Illuminated (FI) form and are presently being prepared for back thinning and packaging. Monolithic CMOS devices such as these, would be ideal candidate detectors for the focal planes of Solar, planetary and other space-borne x-ray astronomy missions. The high through-put, low noise and excellent low energy response, provide high dynamic range and good time resolution; bright, time varying x-ray features could be temporally and

  19. Vertical Isolation for Photodiodes in CMOS Imagers

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata

    2008-01-01

    In a proposed improvement in complementary metal oxide/semi conduct - or (CMOS) image detectors, two additional implants in each pixel would effect vertical isolation between the metal oxide/semiconductor field-effect transistors (MOSFETs) and the photodiode of the pixel. This improvement is expected to enable separate optimization of the designs of the photodiode and the MOSFETs so as to optimize their performances independently of each other. The purpose to be served by enabling this separate optimization is to eliminate or vastly reduce diffusion cross-talk, thereby increasing sensitivity, effective spatial resolution, and color fidelity while reducing noise.

  20. Diurnal measurements with prototype CMOS Omega receivers

    NASA Technical Reports Server (NTRS)

    Burhans, R. W.

    1976-01-01

    Diurnal signals from eight omega channels have been monitored at 10.2 KHz for selected station pairs. All eight Omega stations have been received at least 50 percent of the time over a 24 hour period during the month of October 1976. The data presented confirm the expected performance of the CMOS omega sensor processor in being able to digsignals out of a noisy environment. Of particular interest are possibilities for use of antipodal reception phenomena and a need for some ways of correcting for multi-modal propagation effects.

  1. Design of high speed camera based on CMOS technology

    NASA Astrophysics Data System (ADS)

    Park, Sei-Hun; An, Jun-Sick; Oh, Tae-Seok; Kim, Il-Hwan

    2007-12-01

    The capacity of a high speed camera in taking high speed images has been evaluated using CMOS image sensors. There are 2 types of image sensors, namely, CCD and CMOS sensors. CMOS sensor consumes less power than CCD sensor and can take images more rapidly. High speed camera with built-in CMOS sensor is widely used in vehicle crash tests and airbag controls, golf training aids, and in bullet direction measurement in the military. The High Speed Camera System made in this study has the following components: CMOS image sensor that can take about 500 frames per second at a resolution of 1280*1024; FPGA and DDR2 memory that control the image sensor and save images; Camera Link Module that transmits saved data to PC; and RS-422 communication function that enables control of the camera from a PC.

  2. Mutational analysis using oligonucleotide microarrays

    PubMed Central

    Hacia, J.; Collins, F.

    1999-01-01

    The development of inexpensive high throughput methods to identify individual DNA sequence differences is important to the future growth of medical genetics. This has become increasingly apparent as epidemiologists, pathologists, and clinical geneticists focus more attention on the molecular basis of complex multifactorial diseases. Such undertakings will rely upon genetic maps based upon newly discovered, common, single nucleotide polymorphisms. Furthermore, candidate gene approaches used in identifying disease associated genes necessitate screening large sequence blocks for changes tracking with the disease state. Even after such genes are isolated, large scale mutational analyses will often be needed for risk assessment studies to define the likely medical consequences of carrying a mutated gene.
This review concentrates on the use of oligonucleotide arrays for hybridisation based comparative sequence analysis. Technological advances within the past decade have made it possible to apply this technology to many different aspects of medical genetics. These applications range from the detection and scoring of single nucleotide polymorphisms to mutational analysis of large genes. Although we discuss published scientific reports, unpublished work from the private sector12 could also significantly affect the future of this technology.


Keywords: mutational analysis; oligonucleotide microarrays; DNA chips PMID:10528850

  3. Integrating Microarray Data and GRNs.

    PubMed

    Koumakis, L; Potamias, G; Tsiknakis, M; Zervakis, M; Moustakis, V

    2016-01-01

    With the completion of the Human Genome Project and the emergence of high-throughput technologies, a vast amount of molecular and biological data are being produced. Two of the most important and significant data sources come from microarray gene-expression experiments and respective databanks (e,g., Gene Expression Omnibus-GEO (http://www.ncbi.nlm.nih.gov/geo)), and from molecular pathways and Gene Regulatory Networks (GRNs) stored and curated in public (e.g., Kyoto Encyclopedia of Genes and Genomes-KEGG (http://www.genome.jp/kegg/pathway.html), Reactome (http://www.reactome.org/ReactomeGWT/entrypoint.html)) as well as in commercial repositories (e.g., Ingenuity IPA (http://www.ingenuity.com/products/ipa)). The association of these two sources aims to give new insight in disease understanding and reveal new molecular targets in the treatment of specific phenotypes.Three major research lines and respective efforts that try to utilize and combine data from both of these sources could be identified, namely: (1) de novo reconstruction of GRNs, (2) identification of Gene-signatures, and (3) identification of differentially expressed GRN functional paths (i.e., sub-GRN paths that distinguish between different phenotypes). In this chapter, we give an overview of the existing methods that support the different types of gene-expression and GRN integration with a focus on methodologies that aim to identify phenotype-discriminant GRNs or subnetworks, and we also present our methodology.

  4. A CMOS high speed imaging system design based on FPGA

    NASA Astrophysics Data System (ADS)

    Tang, Hong; Wang, Huawei; Cao, Jianzhong; Qiao, Mingrui

    2015-10-01

    CMOS sensors have more advantages than traditional CCD sensors. The imaging system based on CMOS has become a hot spot in research and development. In order to achieve the real-time data acquisition and high-speed transmission, we design a high-speed CMOS imaging system on account of FPGA. The core control chip of this system is XC6SL75T and we take advantages of CameraLink interface and AM41V4 CMOS image sensors to transmit and acquire image data. AM41V4 is a 4 Megapixel High speed 500 frames per second CMOS image sensor with global shutter and 4/3" optical format. The sensor uses column parallel A/D converters to digitize the images. The CameraLink interface adopts DS90CR287 and it can convert 28 bits of LVCMOS/LVTTL data into four LVDS data stream. The reflected light of objects is photographed by the CMOS detectors. CMOS sensors convert the light to electronic signals and then send them to FPGA. FPGA processes data it received and transmits them to upper computer which has acquisition cards through CameraLink interface configured as full models. Then PC will store, visualize and process images later. The structure and principle of the system are both explained in this paper and this paper introduces the hardware and software design of the system. FPGA introduces the driven clock of CMOS. The data in CMOS is converted to LVDS signals and then transmitted to the data acquisition cards. After simulation, the paper presents a row transfer timing sequence of CMOS. The system realized real-time image acquisition and external controls.

  5. Theoretical performance analysis for CMOS based high resolution detectors.

    PubMed

    Jain, Amit; Bednarek, Daniel R; Rudin, Stephen

    2013-03-06

    High resolution imaging capabilities are essential for accurately guiding successful endovascular interventional procedures. Present x-ray imaging detectors are not always adequate due to their inherent limitations. The newly-developed high-resolution micro-angiographic fluoroscope (MAF-CCD) detector has demonstrated excellent clinical image quality; however, further improvement in performance and physical design may be possible using CMOS sensors. We have thus calculated the theoretical performance of two proposed CMOS detectors which may be used as a successor to the MAF. The proposed detectors have a 300 μm thick HL-type CsI phosphor, a 50 μm-pixel CMOS sensor with and without a variable gain light image intensifier (LII), and are designated MAF-CMOS-LII and MAF-CMOS, respectively. For the performance evaluation, linear cascade modeling was used. The detector imaging chains were divided into individual stages characterized by one of the basic processes (quantum gain, binomial selection, stochastic and deterministic blurring, additive noise). Ranges of readout noise and exposure were used to calculate the detectors' MTF and DQE. The MAF-CMOS showed slightly better MTF than the MAF-CMOS-LII, but the MAF-CMOS-LII showed far better DQE, especially for lower exposures. The proposed detectors can have improved MTF and DQE compared with the present high resolution MAF detector. The performance of the MAF-CMOS is excellent for the angiography exposure range; however it is limited at fluoroscopic levels due to additive instrumentation noise. The MAF-CMOS-LII, having the advantage of the variable LII gain, can overcome the noise limitation and hence may perform exceptionally for the full range of required exposures; however, it is more complex and hence more expensive.

  6. Real-time, multiplexed electrochemical DNA detection using an active complementary metal-oxide-semiconductor biosensor array with integrated sensor electronics.

    PubMed

    Levine, Peter M; Gong, Ping; Levicky, Rastislav; Shepard, Kenneth L

    2009-03-15

    Optical biosensing based on fluorescence detection has arguably become the standard technique for quantifying extents of hybridization between surface-immobilized probes and fluorophore-labeled analyte targets in DNA microarrays. However, electrochemical detection techniques are emerging which could eliminate the need for physically bulky optical instrumentation, enabling the design of portable devices for point-of-care applications. Unlike fluorescence detection, which can function well using a passive substrate (one without integrated electronics), multiplexed electrochemical detection requires an electronically active substrate to analyze each array site and benefits from the addition of integrated electronic instrumentation to further reduce platform size and eliminate the electromagnetic interference that can result from bringing non-amplified signals off chip. We report on an active electrochemical biosensor array, constructed with a standard complementary metal-oxide-semiconductor (CMOS) technology, to perform quantitative DNA hybridization detection on chip using targets conjugated with ferrocene redox labels. A 4 x 4 array of gold working electrodes and integrated potentiostat electronics, consisting of control amplifiers and current-input analog-to-digital converters, on a custom-designed 5 mm x 3 mm CMOS chip drive redox reactions using cyclic voltammetry, sense DNA binding, and transmit digital data off chip for analysis. We demonstrate multiplexed and specific detection of DNA targets as well as real-time monitoring of hybridization, a task that is difficult, if not impossible, with traditional fluorescence-based microarrays.

  7. Real-time, multiplexed electrochemical DNA detection using an active complementary metal-oxide-semiconductor biosensor array with integrated sensor electronics

    PubMed Central

    Levine, Peter M.; Gong, Ping; Levicky, Rastislav; Shepard, Kenneth L.

    2009-01-01

    Optical biosensing based on fluorescence detection has arguably become the standard technique for quantifying extents of hybridization between surface-immobilized probes and fluorophore-labeled analyte targets in DNA microarrays. However, electrochemical detection techniques are emerging which could eliminate the need for physically bulky optical instrumentation, enabling the design of portable devices for point-of-care applications. Unlike fluorescence detection, which can function well using a passive substrate (one without integrated electronics), multiplexed electrochemical detection requires an electronically-active substrate to analyze each array site and benefits from the addition of integrated electronic instrumentation to further reduce platform size and eliminate the electromagnetic interference that can result from bringing non-amplified signals off chip. We report on an active electrochemical biosensor array, constructed with a standard complementary metal-oxide-semiconductor (CMOS) technology, to perform quantitative DNA hybridization detection on chip using targets conjugated with ferrocene redox labels. A 4×4 array of gold working electrodes and integrated potentiostat electronics, consisting of control amplifiers and current-input analog-to-digital converters, on a custom-designed 5×3 mm2 CMOS chip drive redox reactions using cyclic voltammetry, sense DNA binding, and transmit digital data off chip for analysis. We demonstrate multiplexed and specific detection of DNA targets as well as real-time monitoring of hybridization, a task that is difficult, if not impossible, with traditional fluorescence-based microarrays. PMID:19054661

  8. Radiation hardness studies of AMS HV-CMOS 350 nm prototype chip HVStripV1

    NASA Astrophysics Data System (ADS)

    Kanisauskas, K.; Affolder, A.; Arndt, K.; Bates, R.; Benoit, M.; Di Bello, F.; Blue, A.; Bortoletto, D.; Buckland, M.; Buttar, C.; Caragiulo, P.; Das, D.; Dopke, J.; Dragone, A.; Ehrler, F.; Fadeyev, V.; Galloway, Z.; Grabas, H.; Gregor, I. M.; Grenier, P.; Grillo, A.; Hiti, B.; Hoeferkamp, M.; Hommels, L. B. A.; Huffman, B. T.; John, J.; Kenney, C.; Kramberger, J.; Liang, Z.; Mandic, I.; Maneuski, D.; Martinez-Mckinney, F.; MacMahon, S.; Meng, L.; Mikuž, M.; Muenstermann, D.; Nickerson, R.; Peric, I.; Phillips, P.; Plackett, R.; Rubbo, F.; Segal, J.; Seidel, S.; Seiden, A.; Shipsey, I.; Song, W.; Staniztki, M.; Su, D.; Tamma, C.; Turchetta, R.; Vigani, L.; Volk, J.; Wang, R.; Warren, M.; Wilson, F.; Worm, S.; Xiu, Q.; Zhang, J.; Zhu, H.

    2017-02-01

    CMOS active pixel sensors are being investigated for their potential use in the ATLAS inner tracker upgrade at the HL-LHC. The new inner tracker will have to handle a significant increase in luminosity while maintaining a sufficient signal-to-noise ratio and pulse shaping times. This paper focuses on the prototype chip "HVStripV1" (manufactured in the AMS HV-CMOS 350nm process) characterization before and after irradiation up to fluence levels expected for the strip region in the HL-LHC environment. The results indicate an increase of depletion region after irradiation for the same bias voltage by a factor of ≈2.4 and ≈2.8 for two active pixels on the test chip. There was also a notable increase in noise levels from 85 e‑ to 386 e‑ and from 75 e‑ to 277 e‑ for the corresponding pixels.

  9. Packaging commercial CMOS chips for lab on a chip integration.

    PubMed

    Datta-Chaudhuri, Timir; Abshire, Pamela; Smela, Elisabeth

    2014-05-21

    Combining integrated circuitry with microfluidics enables lab-on-a-chip (LOC) devices to perform sensing, freeing them from benchtop equipment. However, this integration is challenging with small chips, as is briefly reviewed with reference to key metrics for package comparison. In this paper we present a simple packaging method for including mm-sized, foundry-fabricated dies containing complementary metal oxide semiconductor (CMOS) circuits within LOCs. The chip is embedded in an epoxy handle wafer to yield a level, large-area surface, allowing subsequent photolithographic post-processing and microfluidic integration. Electrical connection off-chip is provided by thin film metal traces passivated with parylene-C. The parylene is patterned to selectively expose the active sensing area of the chip, allowing direct interaction with a fluidic environment. The method accommodates any die size and automatically levels the die and handle wafer surfaces. Functionality was demonstrated by packaging two different types of CMOS sensor ICs, a bioamplifier chip with an array of surface electrodes connected to internal amplifiers for recording extracellular electrical signals and a capacitance sensor chip for monitoring cell adhesion and viability. Cells were cultured on the surface of both types of chips, and data were acquired using a PC. Long term culture (weeks) showed the packaging materials to be biocompatible. Package lifetime was demonstrated by exposure to fluids over a longer duration (months), and the package was robust enough to allow repeated sterilization and re-use. The ease of fabrication and good performance of this packaging method should allow wide adoption, thereby spurring advances in miniaturized sensing systems.

  10. A CMOS Neural Interface for a Multichannel Vestibular Prosthesis

    PubMed Central

    Hageman, Kristin N.; Kalayjian, Zaven K.; Tejada, Francisco; Chiang, Bryce; Rahman, Mehdi A.; Fridman, Gene Y.; Dai, Chenkai; Pouliquen, Philippe O.; Georgiou, Julio; Della Santina, Charles C.; Andreou, Andreas G.

    2015-01-01

    We present a high-voltage CMOS neural-interface chip for a multichannel vestibular prosthesis (MVP) that measures head motion and modulates vestibular nerve activity to restore vision- and posture-stabilizing reflexes. This application specific integrated circuit neural interface (ASIC-NI) chip was designed to work with a commercially available microcontroller, which controls the ASIC-NI via a fast parallel interface to deliver biphasic stimulation pulses with 9-bit programmable current amplitude via 16 stimulation channels. The chip was fabricated in the ONSemi C5 0.5 micron, high-voltage CMOS process and can accommodate compliance voltages up to 12 V, stimulating vestibular nerve branches using biphasic current pulses up to 1.45 ± 0.06 mA with durations as short as 10 µs/phase. The ASIC-NI includes a dedicated digital-to-analog converter for each channel, enabling it to perform complex multipolar stimulation. The ASIC-NI replaces discrete components that cover nearly half of the 2nd generation MVP (MVP2) printed circuit board, reducing the MVP system size by 48% and power consumption by 17%. Physiological tests of the ASIC-based MVP system (MVP2A) in a rhesus monkey produced reflexive eye movement responses to prosthetic stimulation similar to those observed when using the MVP2. Sinusoidal modulation of stimulus pulse rate from 68–130 pulses per second at frequencies from 0.1 to 5 Hz elicited appropriately-directed slow phase eye velocities ranging in amplitude from 1.9–16.7°/s for the MVP2 and 2.0–14.2°/s for the MVP2A. The eye velocities evoked by MVP2 and MVP2A showed no significant difference (t-test, p = 0.034), suggesting that the MVP2A achieves performance at least as good as the larger MVP2. PMID:25974945

  11. Bulk CMOS VLSI Technology Studies. Part 1. Scalable CMOS Design Rules. Part 2. CMOS Approaches to PLA (Programmable Logic Array) Design.

    DTIC Science & Technology

    2014-09-26

    microns %H*SIC dimensions. Part 2: Various Programmable Logic Array (PLA) implementations with clocked CMOS technology are explored inthis project...Previous research at MSU has dealt with clocked CMOS circuit styles with some application to gate array and microprocessor applications. Work under this...in this report deals with structured logic schemes based on Programmable Logic Arrays (PLAs). Three different PLA design methods are reported with a

  12. Novel Fluorescent Glycan Microarray Strategy Reveals Ligands for Galectins

    PubMed Central

    Song, Xuezheng; Xia, Baoyun; Stowell, Sean R.; Lasanajak, Yi; Smith, David F.; Cummings, Richard D.

    2009-01-01

    Summary Galectin-1 (Gal-1) and galectin-3 (Gal-3) are widely expressed galectins with immunoregulatory functions in animals. To explore their glycan specificity, we developed microarrays of naturally occurring glycans using a novel bifunctional fluorescent linker, 2-amino-N-(2-aminoethyl)-benzamide (AEAB), directly conjugated through its arylamine group by reductive amination to free glycans to form glycan-AEABs (GAEABs). Glycans from natural sources were used to prepare over 200 GAEABs, which were purified by multidimensional HPLC and covalently immobilized onto NHS-activated glass slides via their free alkylamine. Fluorescence-based screening demonstrated that Gal-1 recognizes a wide variety of complex N-glycans, whereas Gal-3 primarily recognizes poly-N-acetyllactosamine-containing glycans independent of N-glycan presentation. GAEABs provide a general solution to glycan microarray preparation from natural sources for defining the specificity of glycan-binding proteins. PMID:19171304

  13. Modulated CMOS camera for fluorescence lifetime microscopy.

    PubMed

    Chen, Hongtao; Holst, Gerhard; Gratton, Enrico

    2015-12-01

    Widefield frequency-domain fluorescence lifetime imaging microscopy (FD-FLIM) is a fast and accurate method to measure the fluorescence lifetime of entire images. However, the complexity and high costs involved in construction of such a system limit the extensive use of this technique. PCO AG recently released the first luminescence lifetime imaging camera based on a high frequency modulated CMOS image sensor, QMFLIM2. Here we tested and provide operational procedures to calibrate the camera and to improve the accuracy using corrections necessary for image analysis. With its flexible input/output options, we are able to use a modulated laser diode or a 20 MHz pulsed white supercontinuum laser as the light source. The output of the camera consists of a stack of modulated images that can be analyzed by the SimFCS software using the phasor approach. The nonuniform system response across the image sensor must be calibrated at the pixel level. This pixel calibration is crucial and needed for every camera settings, e.g. modulation frequency and exposure time. A significant dependency of the modulation signal on the intensity was also observed and hence an additional calibration is needed for each pixel depending on the pixel intensity level. These corrections are important not only for the fundamental frequency, but also for the higher harmonics when using the pulsed supercontinuum laser. With these post data acquisition corrections, the PCO CMOS-FLIM camera can be used for various biomedical applications requiring a large frame and high speed acquisition.

  14. The 1.2 micron CMOS technology

    NASA Technical Reports Server (NTRS)

    Pina, C. A.

    1985-01-01

    A set of test structures was designed using the Jet Propulsion Laboratory (JPL) test chip assembler and was used to evaluate the first CMOS-bulk foundry runs with feature sizes of 1.2 microns. In addition to the problems associated with the physical scaling of the structures, this geometry provided an additional set of problems, since the design files had to be generated in such a way as to be capable of being processed through p-well, n-well, and twin-well processing lines. This requirement meant that the files containing the geometric design rules as well as the structure design files had to produce process-insensitive designs, a requirement that does not apply to the more mature 3.0-micron CMOS feature size technology. Because of the photolithographic steps required with this feature size, the maximum allowable chip size was 10 x 10 mm, and this chip was divided into 24 project areas, with each area being 1.6 x 1.6 mm in size. The JPL-designed structures occupied 13 out of the 21 allowable project sizes and provided the only test information obtained from these three preliminary runs. The structures were used to successfully evaluate three different manufacturing runs through two separate foundries.

  15. Fault detection in CMOS manufacturing using MBPCA

    NASA Astrophysics Data System (ADS)

    Lachman-Shalem, Sivan; Haimovitch, Nir; Shauly, Eitan N.; Lewin, Daniel R.

    2000-08-01

    This paper describes the application of model-based principal component analysis (MBPCA) to the identification and isolation of faults in CMOS manufacture. Some of the CMOS fabrication processing steps are well understood, with first principles mathematical models available which can describe the physical and chemical phenomena that takes place. The fabrication of the device using a known industrial process is therefore first modeled 'ideally', using ATHENA and MATLAB. Detailed furnace models are used to investigate the effect of errors in furnace control on the device fabrication and the subsequent effect on the device electrical properties. This models the distribution of device properties resulting from processing a stack of wafers in a furnace, and allows faults and production errors to be simulated for analysis. The analysis is performed using MBPCA. which has been shown to improve fault-detection resolution for batch processes. The diagnosis method is demonstrated on an industrial NMOS transistor fabrication process with faults introduced in places where they might realistically occur.

  16. Challenges of nickel silicidation in CMOS technologies

    SciTech Connect

    Breil, Nicolas; Lavoie, Christian; Ozcan, Ahmet; Baumann, Frieder; Klymko, Nancy; Nummy, Karen; Sun, Bing; Jordan-Sweet, Jean; Yu, Jian; Zhu, Frank; Narasimha, Shreesh; Chudzik, Michael

    2015-04-01

    In our paper, we review some of the key challenges associated with the Ni silicidation process in the most recent CMOS technologies. The introduction of new materials (e.g.SiGe), and of non-planar architectures bring some important changes that require fundamental investigation from a material engineering perspective. Following a discussion of the device architecture and silicide evolution through the last CMOS generations, we focus our study on a very peculiar defect, termed NiSi-Fangs. We describe a mechanism for the defect formation, and present a detailed material analysis that supports this mechanism. We highlight some of the possible metal enrichment processes of the nickel monosilicide such as oxidation or various RIE (Reactive Ion Etching) plasma process, leading to a metal source available for defect formation. Furthermore, we investigate the NiSi formation and re-formation silicidation differences between Si and SiGe materials, and between (1 0 0) and (1 1 1) orientations. Finally, we show that the thermal budgets post silicidation can lead to the formation of NiSi-Fangs if the structure and the processes are not optimized. Beyond the understanding of the defect and the discussion on the engineering solutions used to prevent its formation, the interest of this investigation also lies in the fundamental learning within the Ni–Pt–Si–Ge system and some additional perspective on Ni-based contacts to advanced microelectronic devices.

  17. Contributions to Statistical Problems Related to Microarray Data

    ERIC Educational Resources Information Center

    Hong, Feng

    2009-01-01

    Microarray is a high throughput technology to measure the gene expression. Analysis of microarray data brings many interesting and challenging problems. This thesis consists three studies related to microarray data. First, we propose a Bayesian model for microarray data and use Bayes Factors to identify differentially expressed genes. Second, we…

  18. PATMA: parser of archival tissue microarray.

    PubMed

    Roszkowiak, Lukasz; Lopez, Carlos

    2016-01-01

    Tissue microarrays are commonly used in modern pathology for cancer tissue evaluation, as it is a very potent technique. Tissue microarray slides are often scanned to perform computer-aided histopathological analysis of the tissue cores. For processing the image, splitting the whole virtual slide into images of individual cores is required. The only way to distinguish cores corresponding to specimens in the tissue microarray is through their arrangement. Unfortunately, distinguishing the correct order of cores is not a trivial task as they are not labelled directly on the slide. The main aim of this study was to create a procedure capable of automatically finding and extracting cores from archival images of the tissue microarrays. This software supports the work of scientists who want to perform further image processing on single cores. The proposed method is an efficient and fast procedure, working in fully automatic or semi-automatic mode. A total of 89% of punches were correctly extracted with automatic selection. With an addition of manual correction, it is possible to fully prepare the whole slide image for extraction in 2 min per tissue microarray. The proposed technique requires minimum skill and time to parse big array of cores from tissue microarray whole slide image into individual core images.

  19. PATMA: parser of archival tissue microarray

    PubMed Central

    2016-01-01

    Tissue microarrays are commonly used in modern pathology for cancer tissue evaluation, as it is a very potent technique. Tissue microarray slides are often scanned to perform computer-aided histopathological analysis of the tissue cores. For processing the image, splitting the whole virtual slide into images of individual cores is required. The only way to distinguish cores corresponding to specimens in the tissue microarray is through their arrangement. Unfortunately, distinguishing the correct order of cores is not a trivial task as they are not labelled directly on the slide. The main aim of this study was to create a procedure capable of automatically finding and extracting cores from archival images of the tissue microarrays. This software supports the work of scientists who want to perform further image processing on single cores. The proposed method is an efficient and fast procedure, working in fully automatic or semi-automatic mode. A total of 89% of punches were correctly extracted with automatic selection. With an addition of manual correction, it is possible to fully prepare the whole slide image for extraction in 2 min per tissue microarray. The proposed technique requires minimum skill and time to parse big array of cores from tissue microarray whole slide image into individual core images. PMID:27920955

  20. The Impact of Photobleaching on Microarray Analysis

    PubMed Central

    von der Haar, Marcel; Preuß, John-Alexander; von der Haar, Kathrin; Lindner, Patrick; Scheper, Thomas; Stahl, Frank

    2015-01-01

    DNA-Microarrays have become a potent technology for high-throughput analysis of genetic regulation. However, the wide dynamic range of signal intensities of fluorophore-based microarrays exceeds the dynamic range of a single array scan by far, thus limiting the key benefit of microarray technology: parallelization. The implementation of multi-scan techniques represents a promising approach to overcome these limitations. These techniques are, in turn, limited by the fluorophores’ susceptibility to photobleaching when exposed to the scanner’s laser light. In this paper the photobleaching characteristics of cyanine-3 and cyanine-5 as part of solid state DNA microarrays are studied. The effects of initial fluorophore intensity as well as laser scanner dependent variables such as the photomultiplier tube’s voltage on bleaching and imaging are investigated. The resulting data is used to develop a model capable of simulating the expected degree of signal intensity reduction caused by photobleaching for each fluorophore individually, allowing for the removal of photobleaching-induced, systematic bias in multi-scan procedures. Single-scan applications also benefit as they rely on pre-scans to determine the optimal scanner settings. These findings constitute a step towards standardization of microarray experiments and analysis and may help to increase the lab-to-lab comparability of microarray experiment results. PMID:26378589

  1. Imaging combined autoimmune and infectious disease microarrays

    NASA Astrophysics Data System (ADS)

    Ewart, Tom; Raha, Sandeep; Kus, Dorothy; Tarnopolsky, Mark

    2006-09-01

    Bacterial and viral pathogens are implicated in many severe autoimmune diseases, acting through such mechanisms as molecular mimicry, and superantigen activation of T-cells. For example, Helicobacter pylori, well known cause of stomach ulcers and cancers, is also identified in ischaemic heart disease (mimicry of heat shock protein 65), autoimmune pancreatitis, systemic sclerosis, autoimmune thyroiditis (HLA DRB1*0301 allele susceptibility), and Crohn's disease. Successful antibiotic eradication of H.pylori often accompanies their remission. Yet current diagnostic devices, and test-limiting cost containment, impede recognition of the linkage, delaying both diagnosis and therapeutic intervention until the chronic debilitating stage. We designed a 15 minute low cost 39 antigen microarray assay, combining autoimmune, viral and bacterial antigens1. This enables point-of-care serodiagnosis and cost-effective narrowly targeted concurrent antibiotic and monoclonal anti-T-cell and anti-cytokine immunotherapy. Arrays of 26 pathogen and 13 autoimmune antigens with IgG and IgM dilution series were printed in triplicate on epoxysilane covalent binding slides with Teflon well masks. Sera diluted 1:20 were incubated 10 minutes, washed off, anti-IgG-Cy3 (green) and anti-IgM-Dy647 (red) were incubated for 5 minutes, washed off and the slide was read in an ArrayWoRx(e) scanning CCD imager (Applied Precision, Issaquah, WA). As a preliminary model for the combined infectious disease-autoimmune diagnostic microarray we surveyed 98 unidentified, outdated sera that were discarded after Hepatitis B antibody testing. In these, significant IgG or IgM autoantibody levels were found: dsDNA 5, ssDNA 11, Ro 2, RNP 7, SSB 4, gliadin 2, thyroglobulin 13 cases. Since control sera showed no autoantibodies, the high frequency of anti-DNA and anti-thyroglobulin antibodies found in infected sera lend increased support for linkage of infection to subsequent autoimmune disease. Expansion of the antigen

  2. Monolithic CMUT on CMOS Integration for Intravascular Ultrasound Applications

    PubMed Central

    Zahorian, Jaime; Hochman, Michael; Xu, Toby; Satir, Sarp; Gurun, Gokce; Karaman, Mustafa; Degertekin, F. Levent

    2012-01-01

    One of the most important promises of capacitive micromachined ultrasonic transducer (CMUT) technology is integration with electronics. This approach is required to minimize the parasitic capacitances in the receive mode, especially in catheter based volumetric imaging arrays where the elements need to be small. Furthermore, optimization of the available silicon area and minimized number of connections occurs when the CMUTs are fabricated directly above the associated electronics. Here, we describe successful fabrication and performance evaluation of CMUT arrays for intravascular imaging on custom designed CMOS receiver electronics from a commercial IC foundry. The CMUT on CMOS process starts with surface isolation and mechanical planarization of the CMOS electronics to reduce topography. The rest of the CMUT fabrication is achieved by modifying a low temperature micromachining process through the addition of a single mask and developing a dry etching step to produce sloped sidewalls for simple and reliable CMUT to CMOS interconnection. This CMUT to CMOS interconnect method reduced the parasitic capacitance by a factor of 200 when compared with a standard wire bonding method. Characterization experiments indicate that the CMUT on CMOS elements are uniform in frequency response and are similar to CMUTs simultaneously fabricated on standard silicon wafers without electronics integration. Experiments on a 1.6 mm diameter dual-ring CMUT array with a 15 MHz center frequency show that both the CMUTs and the integrated CMOS electronics are fully functional. The SNR measurements indicate that the performance is adequate for imaging CTOs located 1 cm away from the CMUT array. PMID:23443701

  3. Chromosomal Microarray versus Karyotyping for Prenatal Diagnosis

    PubMed Central

    Wapner, Ronald J.; Martin, Christa Lese; Levy, Brynn; Ballif, Blake C.; Eng, Christine M.; Zachary, Julia M.; Savage, Melissa; Platt, Lawrence D.; Saltzman, Daniel; Grobman, William A.; Klugman, Susan; Scholl, Thomas; Simpson, Joe Leigh; McCall, Kimberly; Aggarwal, Vimla S.; Bunke, Brian; Nahum, Odelia; Patel, Ankita; Lamb, Allen N.; Thom, Elizabeth A.; Beaudet, Arthur L.; Ledbetter, David H.; Shaffer, Lisa G.; Jackson, Laird

    2013-01-01

    Background Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis. Methods Samples from women undergoing prenatal diagnosis at 29 centers were sent to a central karyotyping laboratory. Each sample was split in two; standard karyotyping was performed on one portion and the other was sent to one of four laboratories for chromosomal microarray. Results We enrolled a total of 4406 women. Indications for prenatal diagnosis were advanced maternal age (46.6%), abnormal result on Down’s syndrome screening (18.8%), structural anomalies on ultrasonography (25.2%), and other indications (9.4%). In 4340 (98.8%) of the fetal samples, microarray analysis was successful; 87.9% of samples could be used without tissue culture. Microarray analysis of the 4282 nonmosaic samples identified all the aneuploidies and unbalanced rearrangements identified on karyotyping but did not identify balanced translocations and fetal triploidy. In samples with a normal karyotype, microarray analysis revealed clinically relevant deletions or duplications in 6.0% with a structural anomaly and in 1.7% of those whose indications were advanced maternal age or positive screening results. Conclusions In the context of prenatal diagnostic testing, chromosomal microarray analysis identified additional, clinically significant cytogenetic information as compared with karyotyping and was equally efficacious in identifying aneuploidies and unbalanced rearrangements but did not identify balanced translocations and triploidies. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01279733.) PMID:23215555

  4. MNOS stack for reliable, low optical loss, Cu based CMOS plasmonic devices.

    PubMed

    Emboras, Alexandros; Najar, Adel; Nambiar, Siddharth; Grosse, Philippe; Augendre, Emmanuel; Leroux, Charles; de Salvo, Barbara; de Lamaestre, Roch Espiau

    2012-06-18

    We study the electro optical properties of a Metal-Nitride-Oxide-Silicon (MNOS) stack for a use in CMOS compatible plasmonic active devices. We show that the insertion of an ultrathin stoichiometric Si(3)N(4) layer in a MOS stack lead to an increase in the electrical reliability of a copper gate MNOS capacitance from 50 to 95% thanks to a diffusion barrier effect, while preserving the low optical losses brought by the use of copper as the plasmon supporting metal. An experimental investigation is undertaken at a wafer scale using some CMOS standard processes of the LETI foundry. Optical transmission measurments conducted in a MNOS channel waveguide configuration coupled to standard silicon photonics circuitry confirms the very low optical losses (0.39 dB.μm(-1)), in good agreement with predictions using ellipsometric optical constants of Cu.

  5. Ink-Jet Printed CMOS Electronics from Oxide Semiconductors.

    PubMed

    Garlapati, Suresh Kumar; Baby, Tessy Theres; Dehm, Simone; Hammad, Mohammed; Chakravadhanula, Venkata Sai Kiran; Kruk, Robert; Hahn, Horst; Dasgupta, Subho

    2015-08-05

    Complementary metal oxide semiconductor (CMOS) technology with high transconductance and signal gain is mandatory for practicable digital/analog logic electronics. However, high performance all-oxide CMOS logics are scarcely reported in the literature; specifically, not at all for solution-processed/printed transistors. As a major step toward solution-processed all-oxide electronics, here it is shown that using a highly efficient electrolyte-gating approach one can obtain printed and low-voltage operated oxide CMOS logics with high signal gain (≈21 at a supply voltage of only 1.5 V) and low static power dissipation.

  6. Lower-Dark-Current, Higher-Blue-Response CMOS Imagers

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata; Cunningham, Thomas; Hancock, Bruce

    2008-01-01

    Several improved designs for complementary metal oxide/semiconductor (CMOS) integrated-circuit image detectors have been developed, primarily to reduce dark currents (leakage currents) and secondarily to increase responses to blue light and increase signal-handling capacities, relative to those of prior CMOS imagers. The main conclusion that can be drawn from a study of the causes of dark currents in prior CMOS imagers is that dark currents could be reduced by relocating p/n junctions away from Si/SiO2 interfaces. In addition to reflecting this conclusion, the improved designs include several other features to counteract dark-current mechanisms and enhance performance.

  7. A monolithically integrated torsional CMOS-MEMS relay

    NASA Astrophysics Data System (ADS)

    Riverola, M.; Sobreviela, G.; Torres, F.; Uranga, A.; Barniol, N.

    2016-11-01

    We report experimental demonstrations of a torsional microelectromechanical (MEM) relay fabricated using the CMOS-MEMS approach (or intra-CMOS) which exploits the full foundry inherent characteristics enabling drastic reduction of the fabrication costs and batch production. In particular, the relay is monolithically integrated in the back end of line of a commercial standard CMOS technology (AMS 0.35 μm) and released by means of a simple one-step mask-less wet etching. The fabricated torsional relay exhibits an extremely steep switching behaviour symmetrical about both contact sides with an on-state contact resistance in the k Ω -range throughout the on-off cycling test.

  8. Fecal source tracking in water using a mitochondrial DNA microarray.

    PubMed

    Vuong, Nguyet-Minh; Villemur, Richard; Payment, Pierre; Brousseau, Roland; Topp, Edward; Masson, Luke

    2013-01-01

    A mitochondrial-based microarray (mitoArray) was developed for rapid identification of the presence of 28 animals and one family (cervidae) potentially implicated in fecal pollution in mixed activity watersheds. Oligonucleotide probes for genus or subfamily-level identification were targeted within the 12S rRNA - Val tRNA - 16S rRNA region in the mitochondrial genome. This region, called MI-50, was selected based on three criteria: 1) the ability to be amplified by universal primers 2) these universal primer sequences are present in most commercial and domestic animals of interest in source tracking, and 3) that sufficient sequence variation exists within this region to meet the minimal requirements for microarray probe discrimination. To quantify the overall level of mitochondrial DNA (mtDNA) in samples, a quantitative-PCR (Q-PCR) universal primer pair was also developed. Probe validation was performed using DNA extracted from animal tissues and, for many cases, animal-specific fecal samples. To reduce the amplification of potentially interfering fish mtDNA sequences during the MI-50 enrichment step, a clamping PCR method was designed using a fish-specific peptide nucleic acid. DNA extracted from 19 water samples were subjected to both array and independent PCR analyses. Our results confirm that the mitochondrial microarray approach method could accurately detect the dominant animals present in water samples emphasizing the potential for this methodology in the parallel scanning of a large variety of animals normally monitored in fecal source tracking.

  9. Glycan profiling of endometrial cancers using lectin microarray.

    PubMed

    Nishijima, Yoshihiro; Toyoda, Masashi; Yamazaki-Inoue, Mayu; Sugiyama, Taro; Miyazawa, Masaki; Muramatsu, Toshinari; Nakamura, Kyoko; Narimatsu, Hisashi; Umezawa, Akihiro; Mikami, Mikio

    2012-10-01

    Cell surface glycans change during the process of malignant transformation. To characterize and distinguish endometrial cancer and endometrium, we performed glycan profiling using an emerging modern technology, lectin microarray analysis. The three cell lines, two from endometrial cancers [well-differentiated type (G1) and poorly differentiated type (G3)] and one from normal endometrium, were successfully categorized into three independent groups by 45 lectins. Furthermore, in cancer cells, a clear difference between G1 and G3 type was observed for the glycans recognized with six lectins, Ulex europaeus agglutinin I (UEA-I), Sambucus sieboldiana agglutinin (SSA), Sambucus nigra agglutinin (SNA), Trichosanthes japonica agglutinin I (TJA-I), Amaranthus caudatus agglutinin (ACA), and Bauhinia purpurea lectin (BPL). The lectin microarray analysis using G3 type tissues demonstrated that stage I and stage III or IV were distinguished depending on signal pattern of three lectins, Dolichos biflorus agglutinin (DBA), BPL, and ACA. In addition, the analysis of the glycans on the ovarian cancer cells showed that only anticancer drug-sensitive cell lines had almost no activities to specific three lectins. Glycan profiling by the lectin microarray may be used to assess the characteristics of tumors and potentially to predict the success of chemotherapy treatment.

  10. Alternative post-processing on a CMOS chip to fabricate a planar microelectrode array.

    PubMed

    López-Huerta, Francisco; Herrera-May, Agustín L; Estrada-López, Johan J; Zuñiga-Islas, Carlos; Cervantes-Sanchez, Blanca; Soto, Enrique; Soto-Cruz, Blanca S

    2011-01-01

    We present an alternative post-processing on a CMOS chip to release a planar microelectrode array (pMEA) integrated with its signal readout circuit, which can be used for monitoring the neuronal activity of vestibular ganglion neurons in newborn Wistar strain rats. This chip is fabricated through a 0.6 μm CMOS standard process and it has 12 pMEA through a 4 × 3 electrodes matrix. The alternative CMOS post-process includes the development of masks to protect the readout circuit and the power supply pads. A wet etching process eliminates the aluminum located on the surface of the p+ -type silicon. This silicon is used as transducer for recording the neuronal activity and as interface between the readout circuit and neurons. The readout circuit is composed of an amplifier and tunable bandpass filter, which is placed on a 0.015 mm2 silicon area. The tunable bandpass filter has a bandwidth of 98 kHz and a common mode rejection ratio (CMRR) of 87 dB. These characteristics of the readout circuit are appropriate for neuronal recording applications.

  11. Alternative Post-Processing on a CMOS Chip to Fabricate a Planar Microelectrode Array

    PubMed Central

    López-Huerta, Francisco; Herrera-May, Agustín L.; Estrada-López, Johan J.; Zuñiga-Islas, Carlos; Cervantes-Sanchez, Blanca; Soto, Enrique; Soto-Cruz, Blanca S.

    2011-01-01

    We present an alternative post-processing on a CMOS chip to release a planar microelectrode array (pMEA) integrated with its signal readout circuit, which can be used for monitoring the neuronal activity of vestibular ganglion neurons in newborn Wistar strain rats. This chip is fabricated through a 0.6 μm CMOS standard process and it has 12 pMEA through a 4 × 3 electrodes matrix. The alternative CMOS post-process includes the development of masks to protect the readout circuit and the power supply pads. A wet etching process eliminates the aluminum located on the surface of the p+-type silicon. This silicon is used as transducer for recording the neuronal activity and as interface between the readout circuit and neurons. The readout circuit is composed of an amplifier and tunable bandpass filter, which is placed on a 0.015 mm2 silicon area. The tunable bandpass filter has a bandwidth of 98 kHz and a common mode rejection ratio (CMRR) of 87 dB. These characteristics of the readout circuit are appropriate for neuronal recording applications. PMID:22346681

  12. Radiation tolerant 1 micron CMOS technology

    NASA Astrophysics Data System (ADS)

    Crevel, P.; Rodde, K.

    1991-03-01

    Starting from a standard one micron Complementary Metal Oxide Semiconductor (CMOS) for high density, low power memory applications, the degree of radiation tolerance of the baseline process is evaluated. Implemented process modifications to improve latchup sensitivity under heavy ion irradiation as well as total dose effects without changing layout rules are described. By changing doping profiles in Metal Nitride Oxide Semiconductors (MNOS) and P-channel MOS (PMOS) device regions, it is possible to guarantee data sheet specification of a 64 K low power static RAM for total gamma dose up to 35 krad (Si) (and even higher values for the gate array family) without latch up for Linear Energy Transfer LET up to 115 MeV/(mg/cm squared).

  13. Latchup in CMOS devices from heavy ions

    NASA Technical Reports Server (NTRS)

    Soliman, K.; Nichols, D. K.

    1983-01-01

    It is noted that complementary metal oxide semiconductor (CMOS) microcircuits are inherently latchup prone. The four-layer n-p-n-p structures formed from the parasitic pnp and npn transistors make up a silicon controlled rectifier. If properly biased, this rectifier may be triggered 'ON' by electrical transients, ionizing radiation, or a single heavy ion. This latchup phenomenon might lead to a loss of functionality or device burnout. Results are presented from tests on 19 different device types from six manufacturers which investigate their latchup sensitivity with argon and krypton beams. The parasitic npnp paths are identified in general, and a qualitative rationale is given for latchup susceptibility, along with a latchup cross section for each type of device. Also presented is the correlation between bit-flip sensitivity and latchup susceptibility.

  14. Validation of affinity reagents using antigen microarrays.

    PubMed

    Sjöberg, Ronald; Sundberg, Mårten; Gundberg, Anna; Sivertsson, Asa; Schwenk, Jochen M; Uhlén, Mathias; Nilsson, Peter

    2012-06-15

    There is a need for standardised validation of affinity reagents to determine their binding selectivity and specificity. This is of particular importance for systematic efforts that aim to cover the human proteome with different types of binding reagents. One such international program is the SH2-consortium, which was formed to generate a complete set of renewable affinity reagents to the SH2-domain containing human proteins. Here, we describe a microarray strategy to validate various affinity reagents, such as recombinant single-chain antibodies, mouse monoclonal antibodies and antigen-purified polyclonal antibodies using a highly multiplexed approach. An SH2-specific antigen microarray was designed and generated, containing more than 6000 spots displayed by 14 identical subarrays each with 406 antigens, where 105 of them represented SH2-domain containing proteins. Approximately 400 different affinity reagents of various types were analysed on these antigen microarrays carrying antigens of different types. The microarrays revealed not only very detailed specificity profiles for all the binders, but also showed that overlapping target sequences of spotted antigens were detected by off-target interactions. The presented study illustrates the feasibility of using antigen microarrays for integrative, high-throughput validation of various types of binders and antigens.

  15. A Multipurpose CMOS Platform for Nanosensing

    PubMed Central

    Bonanno, Alberto; Sanginario, Alessandro; Marasso, Simone L.; Miccoli, Beatrice; Bejtka, Katarzyna; Benetto, Simone; Demarchi, Danilo

    2016-01-01

    This paper presents a customizable sensing system based on functionalized nanowires (NWs) assembled onto complementary metal oxide semiconductor (CMOS) technology. The Micro-for-Nano (M4N) chip integrates on top of the electronics an array of aluminum microelectrodes covered with gold by means of a customized electroless plating process. The NW assembly process is driven by an array of on-chip dielectrophoresis (DEP) generators, enabling a custom layout of different nanosensors on the same microelectrode array. The electrical properties of each assembled NW are singularly sensed through an in situ CMOS read-out circuit (ROC) that guarantees a low noise and reliable measurement. The M4N chip is directly connected to an external microcontroller for configuration and data processing. The processed data are then redirected to a workstation for real-time data visualization and storage during sensing experiments. As proof of concept, ZnO nanowires have been integrated onto the M4N chip to validate the approach that enables different kind of sensing experiments. The device has been then irradiated by an external UV source with adjustable power to measure the ZnO sensitivity to UV-light exposure. A maximum variation of about 80% of the ZnO-NW resistance has been detected by the M4N system when the assembled 5 μm × 500 nm single ZnO-NW is exposed to an estimated incident radiant UV-light flux in the range of 1 nW–229 nW. The performed experiments prove the efficiency of the platform conceived for exploiting any kind of material that can change its capacitance and/or resistance due to an external stimulus. PMID:27916911

  16. A Multipurpose CMOS Platform for Nanosensing.

    PubMed

    Bonanno, Alberto; Sanginario, Alessandro; Marasso, Simone L; Miccoli, Beatrice; Bejtka, Katarzyna; Benetto, Simone; Demarchi, Danilo

    2016-11-30

    This paper presents a customizable sensing system based on functionalized nanowires (NWs) assembled onto complementary metal oxide semiconductor (CMOS) technology. The Micro-for-Nano (M4N) chip integrates on top of the electronics an array of aluminum microelectrodes covered with gold by means of a customized electroless plating process. The NW assembly process is driven by an array of on-chip dielectrophoresis (DEP) generators, enabling a custom layout of different nanosensors on the same microelectrode array. The electrical properties of each assembled NW are singularly sensed through an in situ CMOS read-out circuit (ROC) that guarantees a low noise and reliable measurement. The M4N chip is directly connected to an external microcontroller for configuration and data processing. The processed data are then redirected to a workstation for real-time data visualization and storage during sensing experiments. As proof of concept, ZnO nanowires have been integrated onto the M4N chip to validate the approach that enables different kind of sensing experiments. The device has been then irradiated by an external UV source with adjustable power to measure the ZnO sensitivity to UV-light exposure. A maximum variation of about 80% of the ZnO-NW resistance has been detected by the M4N system when the assembled 5 μ m × 500 nm single ZnO-NW is exposed to an estimated incident radiant UV-light flux in the range of 1 nW-229 nW. The performed experiments prove the efficiency of the platform conceived for exploiting any kind of material that can change its capacitance and/or resistance due to an external stimulus.

  17. Accelerated life testing effects on CMOS microcircuit characteristics

    NASA Technical Reports Server (NTRS)

    1980-01-01

    This report covers the time period from May 1976 to December 1979 and encompasses the three phases of accelerated testing: Phase 1, the 250 C testing; Phase 2, the 200 C testing; and Phase 3, the 125 C testing. The duration of the test in Phase 1 and Phase 2 was sufficient to take the devices into the wear out region. The wear out distributions were used to estimate the activation energy between the 250 C and the 200 C test temperatures. The duration of the 125 C test, 20,000 hours, was not sufficient to bring the test devices into the wear out region; consequently the third data point at 125 C for determining the consistency of activation energy could not be obtained. It was estimated that, for the most complex of the three device types, the activation energy between 200 C and 125 C should be at least as high as that between 250 C and 200 C. The practicality of the use of high temperature for the accelerated life tests from the point of view of durability of equipment was assessed. Guidelines for the development of accelerated life test conditions were proposed. The use of the silicon nitride overcoat to improve the high temperature accelerated life test characteristics of CMOS microcircuits was explored in Phase 4 of this study and is attached as an appendix to this report.

  18. X-ray tomography using a CMOS area detector

    NASA Astrophysics Data System (ADS)

    Brunetti, A.; Cesareo, R.

    2007-05-01

    A flat panel based on CMOS technology represents a valid alternative to other kinds of flat panels and to ccd detectors for X-ray imaging. Although the spatial resolution of the ccd sensors is better than that of a CMOS sensor, the last has a larger sensitive-area and it can work at room temperature reaching a dynamic performance comparable to that of a cooled ccd sensor. Other kinds of flat panels, such as TFT screen are much more expensive and they have lower spatial resolution and higher noise than the CMOS detector. In this paper, an application of the CMOS sensor to X-ray tomography is described. Preliminary results are reported and discussed.

  19. Tests of commercial colour CMOS cameras for astronomical applications

    NASA Astrophysics Data System (ADS)

    Pokhvala, S. M.; Reshetnyk, V. M.; Zhilyaev, B. E.

    2013-12-01

    We present some results of testing commercial colour CMOS cameras for astronomical applications. Colour CMOS sensors allow to perform photometry in three filters simultaneously that gives a great advantage compared with monochrome CCD detectors. The Bayer BGR colour system realized in colour CMOS sensors is close to the astronomical Johnson BVR system. The basic camera characteristics: read noise (e^{-}/pix), thermal noise (e^{-}/pix/sec) and electronic gain (e^{-}/ADU) for the commercial digital camera Canon 5D MarkIII are presented. We give the same characteristics for the scientific high performance cooled CCD camera system ALTA E47. Comparing results for tests of Canon 5D MarkIII and CCD ALTA E47 show that present-day commercial colour CMOS cameras can seriously compete with the scientific CCD cameras in deep astronomical imaging.

  20. CMOS Electrochemical Instrumentation for Biosensor Microsystems: A Review.

    PubMed

    Li, Haitao; Liu, Xiaowen; Li, Lin; Mu, Xiaoyi; Genov, Roman; Mason, Andrew J

    2016-12-31

    Modern biosensors play a critical role in healthcare and have a quickly growing commercial market. Compared to traditional optical-based sensing, electrochemical biosensors are attractive due to superior performance in response time, cost, complexity and potential for miniaturization. To address the shortcomings of traditional benchtop electrochemical instruments, in recent years, many complementary metal oxide semiconductor (CMOS) instrumentation circuits have been reported for electrochemical biosensors. This paper provides a review and analysis of CMOS electrochemical instrumentation circuits. First, important concepts in electrochemical sensing are presented from an instrumentation point of view. Then, electrochemical instrumentation circuits are organized into functional classes, and reported CMOS circuits are reviewed and analyzed to illuminate design options and performance tradeoffs. Finally, recent trends and challenges toward on-CMOS sensor integration that could enable highly miniaturized electrochemical biosensor microsystems are discussed. The information in the paper can guide next generation electrochemical sensor design.

  1. CMOS Electrochemical Instrumentation for Biosensor Microsystems: A Review

    PubMed Central

    Li, Haitao; Liu, Xiaowen; Li, Lin; Mu, Xiaoyi; Genov, Roman; Mason, Andrew J.

    2016-01-01

    Modern biosensors play a critical role in healthcare and have a quickly growing commercial market. Compared to traditional optical-based sensing, electrochemical biosensors are attractive due to superior performance in response time, cost, complexity and potential for miniaturization. To address the shortcomings of traditional benchtop electrochemical instruments, in recent years, many complementary metal oxide semiconductor (CMOS) instrumentation circuits have been reported for electrochemical biosensors. This paper provides a review and analysis of CMOS electrochemical instrumentation circuits. First, important concepts in electrochemical sensing are presented from an instrumentation point of view. Then, electrochemical instrumentation circuits are organized into functional classes, and reported CMOS circuits are reviewed and analyzed to illuminate design options and performance tradeoffs. Finally, recent trends and challenges toward on-CMOS sensor integration that could enable highly miniaturized electrochemical biosensor microsystems are discussed. The information in the paper can guide next generation electrochemical sensor design. PMID:28042860

  2. CMOS serial link for fully duplexed data communication

    NASA Astrophysics Data System (ADS)

    Lee, Kyeongho; Kim, Sungjoon; Ahn, Gijung; Jeong, Deog-Kyoon

    1995-04-01

    This paper describes a CMOS serial link allowing fully duplexed 500 Mbaud serial data communication. The CMOS serial link is a robust and low-cost solution to high data rate requirements. A central charge pump PLL for generating multiphase clocks for oversampling is shared by several serial link channels. Fully duplexed serial data communication is realized in the bidirectional bridge by separating incoming data from the mixed signal on the cable end. The digital PLL accomplishes process-independent data recovery by using a low-ratio oversampling, a majority voting, and a parallel data recovery scheme. Mostly, digital approach could extend its bandwidth further with scaled CMOS technology. A single channel serial link and a charge pump PLL are integrated in a test chip using 1.2 micron CMOS process technology. The test chip confirms upto 500 Mbaud unidirectional mode operation and 320 Mbaud fully duplexed mode operation with pseudo random data patterns.

  3. Posttranslational Modification Assays on Functional Protein Microarrays.

    PubMed

    Neiswinger, Johnathan; Uzoma, Ijeoma; Cox, Eric; Rho, HeeSool; Jeong, Jun Seop; Zhu, Heng

    2016-10-03

    Protein microarray technology provides a straightforward yet powerful strategy for identifying substrates of posttranslational modifications (PTMs) and studying the specificity of the enzymes that catalyze these reactions. Protein microarray assays can be designed for individual enzymes or a mixture to establish connections between enzymes and substrates. Assays for four well-known PTMs-phosphorylation, acetylation, ubiquitylation, and SUMOylation-have been developed and are described here for use on functional protein microarrays. Phosphorylation and acetylation require a single enzyme and are easily adapted for use on an array. The ubiquitylation and SUMOylation cascades are very similar, and the combination of the E1, E2, and E3 enzymes plus ubiquitin or SUMO protein and ATP is sufficient for in vitro modification of many substrates.

  4. CMOS-Memristor Hybrid Nanoelectronics for AES Encryption

    DTIC Science & Technology

    2013-03-01

    URL: https://www.cvimellesgriot.com/ Products /Ultraviolet-325-nm-Medium-Frame-Unpolarized-Heli um- Cadmium -Laser-Systems.aspx 2. URL: http...the existing industry -standard CMOS integrated circuit manufacturing base. Our in-house facility development focused on establishing a very high...leveraging the well-proven vast functionality of the existing industry -standard CMOS integrated circuit manufacturing base. Maintaining compatibility

  5. CMOS front end electronics for the ATLAS muon detector

    SciTech Connect

    Huth, J.; Oliver, J.; Hazen, E.; Shank, J.

    1997-12-31

    An all-CMOS design for an integrated ASD (Amplifier-Shaper-Discriminator) chip for readout of the ATLAS Monitored Drift Tubes (MDTs) is presented. Eight channels of charge-sensitive preamp, two-stage pole/zero shaper, Wilkinson ADC and discriminator with programmable hysteresis are integrated on a single IC. Key elements have been prototyped in 1.2 and 0.5 micron CMOS operating at 5V and 3.3V respectively.

  6. Delta Doping High Purity CCDs and CMOS for LSST

    NASA Technical Reports Server (NTRS)

    Blacksberg, Jordana; Nikzad, Shouleh; Hoenk, Michael; Elliott, S. Tom; Bebek, Chris; Holland, Steve; Kolbe, Bill

    2006-01-01

    A viewgraph presentation describing delta doping high purity CCD's and CMOS for LSST is shown. The topics include: 1) Overview of JPL s versatile back-surface process for CCDs and CMOS; 2) Application to SNAP and ORION missions; 3) Delta doping as a back-surface electrode for fully depleted LBNL CCDs; 4) Delta doping high purity CCDs for SNAP and ORION; 5) JPL CMP thinning process development; and 6) Antireflection coating process development.

  7. Hybridization and Selective Release of DNA Microarrays

    SciTech Connect

    Beer, N R; Baker, B; Piggott, T; Maberry, S; Hara, C M; DeOtte, J; Benett, W; Mukerjee, E; Dzenitis, J; Wheeler, E K

    2011-11-29

    DNA microarrays contain sequence specific probes arrayed in distinct spots numbering from 10,000 to over 1,000,000, depending on the platform. This tremendous degree of multiplexing gives microarrays great potential for environmental background sampling, broad-spectrum clinical monitoring, and continuous biological threat detection. In practice, their use in these applications is not common due to limited information content, long processing times, and high cost. The work focused on characterizing the phenomena of microarray hybridization and selective release that will allow these limitations to be addressed. This will revolutionize the ways that microarrays can be used for LLNL's Global Security missions. The goals of this project were two-fold: automated faster hybridizations and selective release of hybridized features. The first study area involves hybridization kinetics and mass-transfer effects. the standard hybridization protocol uses an overnight incubation to achieve the best possible signal for any sample type, as well as for convenience in manual processing. There is potential to significantly shorten this time based on better understanding and control of the rate-limiting processes and knowledge of the progress of the hybridization. In the hybridization work, a custom microarray flow cell was used to manipulate the chemical and thermal environment of the array and autonomously image the changes over time during hybridization. The second study area is selective release. Microarrays easily generate hybridization patterns and signatures, but there is still an unmet need for methodologies enabling rapid and selective analysis of these patterns and signatures. Detailed analysis of individual spots by subsequent sequencing could potentially yield significant information for rapidly mutating and emerging (or deliberately engineered) pathogens. In the selective release work, optical energy deposition with coherent light quickly provides the thermal energy to

  8. Design and image-quality performance of high resolution CMOS-based X-ray imaging detectors for digital mammography

    NASA Astrophysics Data System (ADS)

    Cha, B. K.; Kim, J. Y.; Kim, Y. J.; Yun, S.; Cho, G.; Kim, H. K.; Seo, C.-W.; Jeon, S.; Huh, Y.

    2012-04-01

    In digital X-ray imaging systems, X-ray imaging detectors based on scintillating screens with electronic devices such as charge-coupled devices (CCDs), thin-film transistors (TFT), complementary metal oxide semiconductor (CMOS) flat panel imagers have been introduced for general radiography, dental, mammography and non-destructive testing (NDT) applications. Recently, a large-area CMOS active-pixel sensor (APS) in combination with scintillation films has been widely used in a variety of digital X-ray imaging applications. We employed a scintillator-based CMOS APS image sensor for high-resolution mammography. In this work, both powder-type Gd2O2S:Tb and a columnar structured CsI:Tl scintillation screens with various thicknesses were fabricated and used as materials to convert X-ray into visible light. These scintillating screens were directly coupled to a CMOS flat panel imager with a 25 × 50 mm2 active area and a 48 μm pixel pitch for high spatial resolution acquisition. We used a W/Al mammographic X-ray source with a 30 kVp energy condition. The imaging characterization of the X-ray detector was measured and analyzed in terms of linearity in incident X-ray dose, modulation transfer function (MTF), noise-power spectrum (NPS) and detective quantum efficiency (DQE).

  9. Applications of the Integrated High-Performance CMOS Image Sensor to Range Finders — from Optical Triangulation to the Automotive Field

    PubMed Central

    Wu, Jih-Huah; Pen, Cheng-Chung; Jiang, Joe-Air

    2008-01-01

    With their significant features, the applications of complementary metal-oxide semiconductor (CMOS) image sensors covers a very extensive range, from industrial automation to traffic applications such as aiming systems, blind guidance, active/passive range finders, etc. In this paper CMOS image sensor-based active and passive range finders are presented. The measurement scheme of the proposed active/passive range finders is based on a simple triangulation method. The designed range finders chiefly consist of a CMOS image sensor and some light sources such as lasers or LEDs. The implementation cost of our range finders is quite low. Image processing software to adjust the exposure time (ET) of the CMOS image sensor to enhance the performance of triangulation-based range finders was also developed. An extensive series of experiments were conducted to evaluate the performance of the designed range finders. From the experimental results, the distance measurement resolutions achieved by the active range finder and the passive range finder can be better than 0.6% and 0.25% within the measurement ranges of 1 to 8 m and 5 to 45 m, respectively. Feasibility tests on applications of the developed CMOS image sensor-based range finders to the automotive field were also conducted. The experimental results demonstrated that our range finders are well-suited for distance measurements in this field. PMID:27879789

  10. Overview of DNA microarrays: types, applications, and their future.

    PubMed

    Bumgarner, Roger

    2013-01-01

    This unit provides an overview of DNA microarrays. Microarrays are a technology in which thousands of nucleic acids are bound to a surface and are used to measure the relative concentration of nucleic acid sequences in a mixture via hybridization and subsequent detection of the hybridization events. This overview first discusses the history of microarrays and the antecedent technologies that led to their development. This is followed by discussion of the methods of manufacture of microarrays and the most common biological applications. The unit ends with a brief description of the limitations of microarrays and discusses how microarrays are being rapidly replaced by DNA sequencing technologies.

  11. Analysis of High-Throughput ELISA Microarray Data

    SciTech Connect

    White, Amanda M.; Daly, Don S.; Zangar, Richard C.

    2011-02-23

    Our research group develops analytical methods and software for the high-throughput analysis of quantitative enzyme-linked immunosorbent assay (ELISA) microarrays. ELISA microarrays differ from DNA microarrays in several fundamental aspects and most algorithms for analysis of DNA microarray data are not applicable to ELISA microarrays. In this review, we provide an overview of the steps involved in ELISA microarray data analysis and how the statistically sound algorithms we have developed provide an integrated software suite to address the needs of each data-processing step. The algorithms discussed are available in a set of open-source software tools (http://www.pnl.gov/statistics/ProMAT).

  12. Design of an ultra low power CMOS pixel sensor for a future neutron personal dosimeter

    SciTech Connect

    Zhang, Y.; Hu-Guo, C.; Husson, D.; Hu, Y.

    2011-07-01

    Despite a continuously increasing demand, neutron electronic personal dosimeters (EPDs) are still far from being completely established because their development is a very difficult task. A low-noise, ultra low power consumption CMOS pixel sensor for a future neutron personal dosimeter has been implemented in a 0.35 {mu}m CMOS technology. The prototype is composed of a pixel array for detection of charged particles, and the readout electronics is integrated on the same substrate for signal processing. The excess electrons generated by an impinging particle are collected by the pixel array. The charge collection time and the efficiency are the crucial points of a CMOS detector. The 3-D device simulations using the commercially available Synopsys-SENTAURUS package address the detailed charge collection process. Within a time of 1.9 {mu}s, about 59% electrons created by the impact particle are collected in a cluster of 4 x 4 pixels with the pixel pitch of 80 {mu}m. A charge sensitive preamplifier (CSA) and a shaper are employed in the frond-end readout. The tests with electrical signals indicate that our prototype with a total active area of 2.56 x 2.56 mm{sup 2} performs an equivalent noise charge (ENC) of less than 400 e - and 314 {mu}W power consumption, leading to a promising prototype. (authors)

  13. An investigation of medical radiation detection using CMOS image sensors in smartphones

    NASA Astrophysics Data System (ADS)

    Kang, Han Gyu; Song, Jae-Jun; Lee, Kwonhee; Nam, Ki Chang; Hong, Seong Jong; Kim, Ho Chul

    2016-07-01

    Medical radiation exposure to patients has increased with the development of diagnostic X-ray devices and multi-channel computed tomography (CT). Despite the fact that the low-dose CT technique can significantly reduce medical radiation exposure to patients, the increasing number of CT examinations has increased the total medical radiation exposure to patients. Therefore, medical radiation exposure to patients should be monitored to prevent cancers caused by diagnostic radiation. However, without using thermoluminescence or glass dosimeters, it is hardly measure doses received by patients during medical examinations accurately. Hence, it is necessary to develop radiation monitoring devices and algorithms that are reasonably priced and have superior radiation detection efficiencies. The aim of this study is to investigate the feasibility of medical dose measurement using complementary metal oxide semiconductor (CMOS) sensors in smartphone cameras with an algorithm to extract the X-ray interacted pixels. We characterized the responses of the CMOS sensors in a smartphone with respect to the X-rays generated by a general diagnostic X-ray system. The characteristics of the CMOS sensors in a smartphone camera, such as dose response linearity, dose rate dependence, energy dependence, angular dependence, and minimum detectable activity were evaluated. The high energy gamma-ray of 662 keV from Cs-137 can be detected using the smartphone camera. The smartphone cameras which employ the developed algorithm can detect medical radiations.

  14. Source/drain technologies for the scaling of nanoscale CMOS device

    NASA Astrophysics Data System (ADS)

    Song, Yi; Zhou, Huajie; Xu, Qiuxia

    2011-02-01

    Continuous shrinking CMOS device into 21 nm technology node is facing fundamental challenges. The International Technology Roadmap for Semiconductors (ITRS) forecasts specific requirements to realize acceptable CMOS performance for the semiconductor industry. The innovations of various source/drain technologies are considered to be indispensable for the continuous scaling of CMOS device due to the requirements of high-performance and effective suppression of short channel effects. One of the key points is to realize ultra-shallow junction with steep concentration profile and low resistivity. There are many innovative solutions including advanced doping technologies and annealing technologies for ultra-shallow junction formation. Additionally, new source/drain structures such as raised source/drain and Schottky barrier metal source/drain, and advanced silicidation technologies also serve as the important options. The state-of-the-arts of these new technologies are extensively discussed from the view point of technical innovation and performance gain. Source/drain technologies are promising and active areas of device research down to 21 nm technology node and even beyond.

  15. RF Design of a Wideband CMOS Integrated Receiver for Phased Array Applications

    NASA Astrophysics Data System (ADS)

    Jackson, Suzy A.

    2004-06-01

    New silicon CMOS processes developed primarily for the burgeoning wireless networking market offer significant promise as a vehicle for the implementation of highly integrated receivers, especially at the lower end of the frequency range proposed for the Square Kilometre Array (SKA). An RF-CMOS ‘Receiver-on-a-Chip’ is being developed as part of an Australia Telescope program looking at technologies associated with the SKA. The receiver covers the frequency range 500 1700 MHz, with instantaneous IF bandwidth of 500 MHz and, on simulation, yields an input noise temperature of < 50 K at mid-band. The receiver will contain all active circuitry (LNA, bandpass filter, quadrature mixer, anti-aliasing filter, digitiser and serialiser) on one 0.18 μm RF-CMOS integrated circuit. This paper outlines receiver front-end development work undertaken to date, including design and simulation of an LNA using noise cancelling techniques to achieve a wideband input-power-match with little noise penalty.

  16. CMOS micromachined probes by die-level fabrication for extracellular neural recording

    NASA Astrophysics Data System (ADS)

    Ho, Meng-Han; Chen, Hsin; Tseng, Fouriers; Yeh, Shih-Rung; S-C Lu, Michael

    2007-02-01

    In this paper, we present the design, fabrication and characterization of CMOS micromachined probes for extracellular neural recording. A convenient fabrication process is proposed for making integrated recording probes at the die level, providing a low-cost solution for academic research as compared to the more expensive wafer-level approach adopted in prior work. The devices are fabricated in a standard 0.35 µm CMOS process, followed by post-CMOS micromachining steps to form the probes. The on-chip circuit, used for recording action potential signals of neural activities, provides a stable dc bias when operating in electrolyte. The subthreshold transistor at the circuit input provides a tunable resistance value between 10 MΩ up to GΩ. The circuit consumes a total power of 790 µW and has an output noise of 19.3 µV Hz-1/2 at 100 Hz. The recorded action potential from the stimulated ventral nerve cord of a crayfish is about 0.6 mV with a pulse width of about 1.2 ms.

  17. On-chip polarizer on image sensor using advanced CMOS technology

    NASA Astrophysics Data System (ADS)

    Sasagawa, Kiyotaka; Wakama, Norimitsu; Noda, Toshihiko; Tokuda, Takashi; Kakiuchi, Kiyomi; Ohta, Jun

    2014-03-01

    The structures in advanced complementary metal-oxide-semiconductor (CMOS) integrated circuit technology are in the range of deep-submicron. It allows designing and integrating nano-photonic structures for the visible to near infrared region on a chip. In this work, we designed and fabricated an image sensor with on-pixel metal wire grid polarizers by using a 65-nm standard CMOS technology. It is known that the extinction ratio of a metal wire grid polarizer is increased with decrease in the grid pitch. With the metal wire layers of the 65-nm technology, the grid pitch sufficiently smaller than the wavelengths of visible light can be realized. The extinction ratio of approximately 20 dB has been successfully achieved at a wavelength of 750 nm. In the CMOS technologies, it is usual to include multiple metal layers. This feature is also useful to increase the extinction ratio of polarizers. We designed dual layer polarizers. Each layer partially reflects incident light. Thus, the layers form a cavity and its transmission spectrum depends on the layer position. The extinction ratio of 19.2 dB at 780 nm was achieved with the grid pitch greater than the single layer polarizer. The high extinction ratio is obtained only red to near infrared region because the fine metal layers of deepsubmicron standard CMOS process is usually composed of Cu. Thus, it should be applied for measurement or observation where wide spectrum is not required such as optical rotation measurement of optically active materials or electro-optic imaging of RF/THz wave.

  18. Advancement of CMOS Doping Technology in an External Development Framework

    NASA Astrophysics Data System (ADS)

    Jain, Amitabh; Chambers, James J.; Shaw, Judy B.

    2011-01-01

    The consumer appetite for a rich multimedia experience drives technology development for mobile hand-held devices and the infrastructure to support them. Enhancements in functionality, speed, and user experience are derived from advancements in CMOS technology. The technical challenges in developing each successive CMOS technology node to support these enhancements have become increasingly difficult. These trends have motivated the CMOS business towards a collaborative approach based on strategic partnerships. This paper describes our model and experience of CMOS development, based on multi-dimensional industrial and academic partnerships. We provide to our process equipment, materials, and simulation partners, as well as to our silicon foundry partners, the detailed requirements for future integrated circuit products. This is done very early in the development cycle to ensure that these requirements can be met. In order to determine these fundamental requirements, we rely on a strategy that requires strong interaction between process and device simulation, physical and chemical analytical methods, and research at academic institutions. This learning is shared with each project partner to address integration and manufacturing issues encountered during CMOS technology development from its inception through product ramp. We utilize TI's core strengths in physical analysis, unit processes and integration, yield ramp, reliability, and product engineering to support this technological development. Finally, this paper presents examples of the advancement of CMOS doping technology for the 28 nm node and beyond through this development model.

  19. Surface enhanced biodetection on a CMOS biosensor chip

    NASA Astrophysics Data System (ADS)

    Belloni, Federico; Sandeau, Laure; Contié, Sylvain; Vicaire, Florence; Owens, Roisin; Rigneault, Hervé

    2012-03-01

    We present a rigorous electromagnetic theory of the electromagnetic power emitted by a dipole located in the vicinity of a multilayer stack. We applied this formalism to a luminescent molecule attached to a CMOS photodiode surface and report light collection efficiency larger than 80% toward the CMOS silicon substrate. We applied this result to the development of a low-cost, simple, portable device based on CMOS photodiodes technology for the detection and quantification of biological targets through light detection, presenting high sensitivity, multiplex ability, and fast data processing. The key feature of our approach is to perform the analytical test directly on the CMOS sensor surface, improving dramatically the optical detection of the molecule emitted light into the high refractive index semiconductor CMOS material. Based on adequate surface chemistry modifications, probe spotting and micro-fluidics, we performed proof-of-concept bio-assays directed against typical immuno-markers (TNF-α and IFN-γ). We compared the developed CMOS chip with a commercial micro-plate reader and found similar intrinsic sensitivities in the pg/ml range.

  20. A low-cost CMOS neurological sensor array

    NASA Astrophysics Data System (ADS)

    Newman, Paul J.; Lisner, Peter; Yeow, Y.; Choy, Peng; Lavidis, Nick A.

    2005-02-01

    Current methods used to study neural communication have not been able to achieve both good spatial and temporal resolution of recordings. There are two ways to record synaptic potentials from nerve endings: recordings using single or dual intracellular or extra cellular metal electrodes give good temporal resolution but poor spatial resolution, and recording activity with fluorescent dyes gives good spatial resolution but poor temporal resolution. Such medical research activity in the area of neurological signal detection has thus identified a requirement for the design of a CMOS circuit that contains an array of independent sensors. As both spatial and temporal distribution of acquired data is required in this application, the circuit must be capable of continuous measurement of synaptic potentials from an array of points on a tissue sample, with a 10 μm separation between sensor points. The major requirement for the circuit is that it is capable of sensing synaptic potentials of the order of several mV, with a resolution of 0.05 mV. For data recording purposes, the circuit must amplify these synaptic potentials and digitise them together with their locations in the sensor array. Finally, the circuit must be biologically inert, to avoid specimen deterioration. This paper presents the design of a prototype single-chip circuit, which provides a 6 x 3 array of independent synaptic potential sensors. The signal from each of the sensors is amplified and time-multiplexed into an on-chip A/D converter. The circuit provides an 8-bit synaptic potential value, together with an 8-bit field containing array location and trigger signals suitable for external data acquisition instrumentation. Our test circuit is implemented in a low-cost 0.5 um, 5 V CMOS process. The fabricated die is mounted in a standard 40 pin DIP ceramic package, with no lid to allow direct contact of the die surface with the tissue sample. The only post-processing step required for these packages is to

  1. An RF energy harvester system using UHF micropower CMOS rectifier based on a diode connected CMOS transistor.

    PubMed

    Shokrani, Mohammad Reza; Khoddam, Mojtaba; Hamidon, Mohd Nizar B; Kamsani, Noor Ain; Rokhani, Fakhrul Zaman; Shafie, Suhaidi Bin

    2014-01-01

    This paper presents a new type diode connected MOS transistor to improve CMOS conventional rectifier's performance in RF energy harvester systems for wireless sensor networks in which the circuits are designed in 0.18  μm TSMC CMOS technology. The proposed diode connected MOS transistor uses a new bulk connection which leads to reduction in the threshold voltage and leakage current; therefore, it contributes to increment of the rectifier's output voltage, output current, and efficiency when it is well important in the conventional CMOS rectifiers. The design technique for the rectifiers is explained and a matching network has been proposed to increase the sensitivity of the proposed rectifier. Five-stage rectifier with a matching network is proposed based on the optimization. The simulation results shows 18.2% improvement in the efficiency of the rectifier circuit and increase in sensitivity of RF energy harvester circuit. All circuits are designed in 0.18 μm TSMC CMOS technology.

  2. Identification of candidate genes in osteoporosis by integrated microarray analysis

    PubMed Central

    Li, J. J.; Wang, B. Q.; Yang, Y.; Li, D.

    2016-01-01

    Objectives In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis. Methods We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs. Results A total of three microarray studies were selected for integrated analysis. In all, 1125 genes were found to be significantly differentially expressed between osteoporosis patients and normal controls, with 373 upregulated and 752 downregulated genes. Positive regulation of the cellular amino metabolic process (gene ontology (GO): 0033240, false discovery rate (FDR) = 1.00E + 00) was significantly enriched under the GO category for biological processes, while for molecular functions, flavin adenine dinucleotide binding (GO: 0050660, FDR = 3.66E-01) and androgen receptor binding (GO: 0050681, FDR = 6.35E-01) were significantly enriched. DEGs were enriched in many osteoporosis-related signalling pathways, including those of mitogen-activated protein kinase (MAPK) and calcium. Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57). Conclusion Analysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. Moreover, significantly enriched pathways, such as MAPK and calcium, may involve in osteoporosis through osteoblastic differentiation and

  3. Novel integrated CMOS pixel structures for vertex detectors

    SciTech Connect

    Kleinfelder, Stuart; Bieser, Fred; Chen, Yandong; Gareus, Robin; Matis, Howard S.; Oldenburg, Markus; Retiere, Fabrice; Ritter, Hans Georg; Wieman, Howard H.; Yamamoto, Eugene

    2003-10-29

    Novel CMOS active pixel structures for vertex detector applications have been designed and tested. The overriding goal of this work is to increase the signal to noise ratio of the sensors and readout circuits. A large-area native epitaxial silicon photogate was designed with the aim of increasing the charge collected per struck pixel and to reduce charge diffusion to neighboring pixels. The photogate then transfers the charge to a low capacitance readout node to maintain a high charge to voltage conversion gain. Two techniques for noise reduction are also presented. The first is a per-pixel kT/C noise reduction circuit that produces results similar to traditional correlated double sampling (CDS). It has the advantage of requiring only one read, as compared to two for CDS, and no external storage or subtraction is needed. The technique reduced input-referred temporal noise by a factor of 2.5, to 12.8 e{sup -}. Finally, a column-level active reset technique is explored that suppresses kT/C noise during pixel reset. In tests, noise was reduced by a factor of 7.6 times, to an estimated 5.1 e{sup -} input-referred noise. The technique also dramatically reduces fixed pattern (pedestal) noise, by up to a factor of 21 in our tests. The latter feature may possibly reduce pixel-by-pixel pedestal differences to levels low enough to permit sparse data scan without per-pixel offset corrections.

  4. Integration of III-V materials and Si-CMOS through double layer transfer process

    NASA Astrophysics Data System (ADS)

    Lee, Kwang Hong; Bao, Shuyu; Fitzgerald, Eugene; Tan, Chuan Seng

    2015-03-01

    A method to integrate III-V compound semiconductor and SOI-CMOS on a common Si substrate is demonstrated. The SOI-CMOS layer is temporarily bonded on a Si handle wafer. Another III-V/Si substrate is then bonded to the SOI-CMOS containing handle wafer. Finally, the handle wafer is released to realize the SOI-CMOS on III-V/Si hybrid structure on a common substrate. Through this method, high temperature III-V materials growth can be completed without the presence of the temperature sensitive CMOS layer, hence damage to the CMOS layer is avoided.

  5. DISC-BASED IMMUNOASSAY MICROARRAYS. (R825433)

    EPA Science Inventory

    Microarray technology as applied to areas that include genomics, diagnostics, environmental, and drug discovery, is an interesting research topic for which different chip-based devices have been developed. As an alternative, we have explored the principle of compact disc-based...

  6. Raman-based microarray readout: a review.

    PubMed

    Haisch, Christoph

    2016-07-01

    For a quarter of a century, microarrays have been part of the routine analytical toolbox. Label-based fluorescence detection is still the commonest optical readout strategy. Since the 1990s, a continuously increasing number of label-based as well as label-free experiments on Raman-based microarray readout concepts have been reported. This review summarizes the possible concepts and methods and their advantages and challenges. A common label-based strategy is based on the binding of selective receptors as well as Raman reporter molecules to plasmonic nanoparticles in a sandwich immunoassay, which results in surface-enhanced Raman scattering signals of the reporter molecule. Alternatively, capture of the analytes can be performed by receptors on a microarray surface. Addition of plasmonic nanoparticles again leads to a surface-enhanced Raman scattering signal, not of a label but directly of the analyte. This approach is mostly proposed for bacteria and cell detection. However, although many promising readout strategies have been discussed in numerous publications, rarely have any of them made the step from proof of concept to a practical application, let alone routine use. Graphical Abstract Possible realization of a SERS (Surface-Enhanced Raman Scattering) system for microarray readout.

  7. Annotating nonspecific SAGE tags with microarray data.

    PubMed

    Ge, Xijin; Jung, Yong-Chul; Wu, Qingfa; Kibbe, Warren A; Wang, San Ming

    2006-01-01

    SAGE (serial analysis of gene expression) detects transcripts by extracting short tags from the transcripts. Because of the limited length, many SAGE tags are shared by transcripts from different genes. Relying on sequence information in the general gene expression database has limited power to solve this problem due to the highly heterogeneous nature of the deposited sequences. Considering that the complexity of gene expression at a single tissue level should be much simpler than that in the general expression database, we reasoned that by restricting gene expression to tissue level, the accuracy of gene annotation for the nonspecific SAGE tags should be significantly improved. To test the idea, we developed a tissue-specific SAGE annotation database based on microarray data (). This database contains microarray expression information represented as UniGene clusters for 73 normal human tissues and 18 cancer tissues and cell lines. The nonspecific SAGE tag is first matched to the database by the same tissue type used by both SAGE and microarray analysis; then the multiple UniGene clusters assigned to the nonspecific SAGE tag are searched in the database under the matched tissue type. The UniGene cluster presented solely or at higher expression levels in the database is annotated to represent the specific gene for the nonspecific SAGE tags. The accuracy of gene annotation by this database was largely confirmed by experimental data. Our study shows that microarray data provide a useful source for annotating the nonspecific SAGE tags.

  8. Analytical Protein Microarrays: Advancements Towards Clinical Applications

    PubMed Central

    Sauer, Ursula

    2017-01-01

    Protein microarrays represent a powerful technology with the potential to serve as tools for the detection of a broad range of analytes in numerous applications such as diagnostics, drug development, food safety, and environmental monitoring. Key features of analytical protein microarrays include high throughput and relatively low costs due to minimal reagent consumption, multiplexing, fast kinetics and hence measurements, and the possibility of functional integration. So far, especially fundamental studies in molecular and cell biology have been conducted using protein microarrays, while the potential for clinical, notably point-of-care applications is not yet fully utilized. The question arises what features have to be implemented and what improvements have to be made in order to fully exploit the technology. In the past we have identified various obstacles that have to be overcome in order to promote protein microarray technology in the diagnostic field. Issues that need significant improvement to make the technology more attractive for the diagnostic market are for instance: too low sensitivity and deficiency in reproducibility, inadequate analysis time, lack of high-quality antibodies and validated reagents, lack of automation and portable instruments, and cost of instruments necessary for chip production and read-out. The scope of the paper at hand is to review approaches to solve these problems. PMID:28146048

  9. Analytical Protein Microarrays: Advancements Towards Clinical Applications.

    PubMed

    Sauer, Ursula

    2017-01-29

    Protein microarrays represent a powerful technology with the potential to serve as tools for the detection of a broad range of analytes in numerous applications such as diagnostics, drug development, food safety, and environmental monitoring. Key features of analytical protein microarrays include high throughput and relatively low costs due to minimal reagent consumption, multiplexing, fast kinetics and hence measurements, and the possibility of functional integration. So far, especially fundamental studies in molecular and cell biology have been conducted using protein microarrays, while the potential for clinical, notably point-of-care applications is not yet fully utilized. The question arises what features have to be implemented and what improvements have to be made in order to fully exploit the technology. In the past we have identified various obstacles that have to be overcome in order to promote protein microarray technology in the diagnostic field. Issues that need significant improvement to make the technology more attractive for the diagnostic market are for instance: too low sensitivity and deficiency in reproducibility, inadequate analysis time, lack of high-quality antibodies and validated reagents, lack of automation and portable instruments, and cost of instruments necessary for chip production and read-out. The scope of the paper at hand is to review approaches to solve these problems.

  10. Microarrays (DNA Chips) for the Classroom Laboratory

    ERIC Educational Resources Information Center

    Barnard, Betsy; Sussman, Michael; BonDurant, Sandra Splinter; Nienhuis, James; Krysan, Patrick

    2006-01-01

    We have developed and optimized the necessary laboratory materials to make DNA microarray technology accessible to all high school students at a fraction of both cost and data size. The primary component is a DNA chip/array that students "print" by hand and then analyze using research tools that have been adapted for classroom use. The…

  11. Diagnostic Oligonucleotide Microarray Fingerprinting of Bacillus Isolates

    SciTech Connect

    Chandler, Darrell P.; Alferov, Oleg; Chernov, Boris; Daly, Don S.; Golova, Julia; Perov, Alexander N.; Protic, Miroslava; Robison, Richard; Shipma, Matthew; White, Amanda M.; Willse, Alan R.

    2006-01-01

    A diagnostic, genome-independent microbial fingerprinting method using DNA oligonucleotide microarrays was used for high-resolution differentiation between closely related Bacillus strains, including two strains of Bacillus anthracis that are monomorphic (indistinguishable) via amplified fragment length polymorphism fingerprinting techniques. Replicated hybridizations on 391-probe nonamer arrays were used to construct a prototype fingerprint library for quantitative comparisons. Descriptive analysis of the fingerprints, including phylogenetic reconstruction, is consistent with previous taxonomic organization of the genus. Newly developed statistical analysis methods were used to quantitatively compare and objectively confirm apparent differences in microarray fingerprints with the statistical rigor required for microbial forensics and clinical diagnostics. These data suggest that a relatively simple fingerprinting microarray and statistical analysis method can differentiate between species in the Bacillus cereus complex, and between strains of B. anthracis. A synthetic DNA standard was used to understand underlying microarray and process-level variability, leading to specific recommendations for the development of a standard operating procedure and/or continued technology enhancements for microbial forensics and diagnostics.

  12. MICROARRAY DATA ANALYSIS USING MULTIPLE STATISTICAL MODELS

    EPA Science Inventory

    Microarray Data Analysis Using Multiple Statistical Models

    Wenjun Bao1, Judith E. Schmid1, Amber K. Goetz1, Ming Ouyang2, William J. Welsh2,Andrew I. Brooks3,4, ChiYi Chu3,Mitsunori Ogihara3,4, Yinhe Cheng5, David J. Dix1. 1National Health and Environmental Effects Researc...

  13. Shrinkage covariance matrix approach for microarray data

    NASA Astrophysics Data System (ADS)

    Karjanto, Suryaefiza; Aripin, Rasimah

    2013-04-01

    Microarray technology was developed for the purpose of monitoring the expression levels of thousands of genes. A microarray data set typically consists of tens of thousands of genes (variables) from just dozens of samples due to various constraints including the high cost of producing microarray chips. As a result, the widely used standard covariance estimator is not appropriate for this purpose. One such technique is the Hotelling's T2 statistic which is a multivariate test statistic for comparing means between two groups. It requires that the number of observations (n) exceeds the number of genes (p) in the set but in microarray studies it is common that n < p. This leads to a biased estimate of the covariance matrix. In this study, the Hotelling's T2 statistic with the shrinkage approach is proposed to estimate the covariance matrix for testing differential gene expression. The performance of this approach is then compared with other commonly used multivariate tests using a widely analysed diabetes data set as illustrations. The results across the methods are consistent, implying that this approach provides an alternative to existing techniques.

  14. A Method of Microarray Data Storage Using Array Data Type

    PubMed Central

    Tsoi, Lam C.; Zheng, W. Jim

    2009-01-01

    A well-designed microarray database can provide valuable information on gene expression levels. However, designing an efficient microarray database with minimum space usage is not an easy task since designers need to integrate the microarray data with the information of genes, probe annotation, and the descriptions of each microarray experiment. Developing better methods to store microarray data can greatly improve the efficiency and usefulness of such data. A new schema is proposed to store microarray data by using array data type in an object-relational database management system – PostgreSQL. The implemented database can store all the microarray data from the same chip in an array data structure. The variable length array data type in PostgreSQL can store microarray data from same chip. The implementation of our schema can help to increase the data retrieval and space efficiency. PMID:17392028

  15. PRACTICAL STRATEGIES FOR PROCESSING AND ANALYZING SPOTTED OLIGONUCLEOTIDE MICROARRAY DATA

    EPA Science Inventory

    Thoughtful data analysis is as important as experimental design, biological sample quality, and appropriate experimental procedures for making microarrays a useful supplement to traditional toxicology. In the present study, spotted oligonucleotide microarrays were used to profile...

  16. Development of a large-area CMOS-based detector for real-time x-ray imaging

    NASA Astrophysics Data System (ADS)

    Heo, Sung Kyn; Park, Sung Kyu; Hwang, Sung Ha; Im, Dong Ak; Kosonen, Jari; Kim, Tae Woo; Yun, Seungman; Kim, Ho Kyung

    2010-04-01

    Complementary metal-oxide-semiconductor (CMOS) active pixel sensors (APSs) with high electrical and optical performances are now being attractive for digital radiography (DR) and dental cone-beam computed tomography (CBCT). In this study, we report our prototype CMOS-based detectors capable of real-time imaging. The field-of-view of the detector is 12 × 14.4 cm. The detector employs a CsI:Tl scintillator as an x-ray-to-light converter. The electrical performance of the CMOS APS, such as readout noise and full-well capacity, was evaluated. The x-ray imaging characteristics of the detector were evaluated in terms of characteristic curve, pre-sampling modulation transfer function, noise power spectrum, detective quantum efficiency, and image lag. The overall performance of the detector is demonstrated with phantom images obtained for DR and CBCT applications. The detailed development description and measurement results are addressed. With the results, we suggest that the prototype CMOS-based detector has the potential for CBCT and real-time x-ray imaging applications.

  17. Examining microarray slide quality for the EPA using SNL's hyperspectral microarray scanner.

    SciTech Connect

    Rohde, Rachel M.; Timlin, Jerilyn Ann

    2005-11-01

    This report summarizes research performed at Sandia National Laboratories (SNL) in collaboration with the Environmental Protection Agency (EPA) to assess microarray quality on arrays from two platforms of interest to the EPA. Custom microarrays from two novel, commercially produced array platforms were imaged with SNL's unique hyperspectral imaging technology and multivariate data analysis was performed to investigate sources of emission on the arrays. No extraneous sources of emission were evident in any of the array areas scanned. This led to the conclusions that either of these array platforms could produce high quality, reliable microarray data for the EPA toxicology programs. Hyperspectral imaging results are presented and recommendations for microarray analyses using these platforms are detailed within the report.

  18. Identifying Fishes through DNA Barcodes and Microarrays

    PubMed Central

    Kochzius, Marc; Seidel, Christian; Antoniou, Aglaia; Botla, Sandeep Kumar; Campo, Daniel; Cariani, Alessia; Vazquez, Eva Garcia; Hauschild, Janet; Hervet, Caroline; Hjörleifsdottir, Sigridur; Hreggvidsson, Gudmundur; Kappel, Kristina; Landi, Monica; Magoulas, Antonios; Marteinsson, Viggo; Nölte, Manfred; Planes, Serge; Tinti, Fausto; Turan, Cemal; Venugopal, Moleyur N.; Weber, Hannes; Blohm, Dietmar

    2010-01-01

    Background International fish trade reached an import value of 62.8 billion Euro in 2006, of which 44.6% are covered by the European Union. Species identification is a key problem throughout the life cycle of fishes: from eggs and larvae to adults in fisheries research and control, as well as processed fish products in consumer protection. Methodology/Principal Findings This study aims to evaluate the applicability of the three mitochondrial genes 16S rRNA (16S), cytochrome b (cyt b), and cytochrome oxidase subunit I (COI) for the identification of 50 European marine fish species by combining techniques of “DNA barcoding” and microarrays. In a DNA barcoding approach, neighbour Joining (NJ) phylogenetic trees of 369 16S, 212 cyt b, and 447 COI sequences indicated that cyt b and COI are suitable for unambiguous identification, whereas 16S failed to discriminate closely related flatfish and gurnard species. In course of probe design for DNA microarray development, each of the markers yielded a high number of potentially species-specific probes in silico, although many of them were rejected based on microarray hybridisation experiments. None of the markers provided probes to discriminate the sibling flatfish and gurnard species. However, since 16S-probes were less negatively influenced by the “position of label” effect and showed the lowest rejection rate and the highest mean signal intensity, 16S is more suitable for DNA microarray probe design than cty b and COI. The large portion of rejected COI-probes after hybridisation experiments (>90%) renders the DNA barcoding marker as rather unsuitable for this high-throughput technology. Conclusions/Significance Based on these data, a DNA microarray containing 64 functional oligonucleotide probes for the identification of 30 out of the 50 fish species investigated was developed. It represents the next step towards an automated and easy-to-handle method to identify fish, ichthyoplankton, and fish products. PMID

  19. Network theory to understand microarray studies of complex diseases.

    PubMed

    Benson, Mikael; Breitling, Rainer

    2006-09-01

    Complex diseases, such as allergy, diabetes and obesity depend on altered interactions between multiple genes, rather than changes in a single causal gene. DNA microarray studies of a complex disease often implicate hundreds of genes in the pathogenesis. This indicates that many different mechanisms and pathways are involved. How can we understand such complexity? How can hypotheses be formulated and tested? One approach is to organize the data in network models and to analyze these in a top-down manner. Globally, networks in nature are often characterized by a small number of highly connected nodes, while the majority of nodes have few connections. The highly connected nodes serve as hubs that affect many other nodes. Such hubs have key roles in the network. In yeast cells, for example, deletion of highly connected proteins is associated with increased lethality, compared to deletion of less connected proteins. This suggests the biological relevance of networks. Moving down in the network structure, there may be sub-networks or modules with specific functions. These modules may be further dissected to analyze individual nodes. In the context of DNA microarray studies of complex diseases, gene-interaction networks may contain modules of co-regulated or interacting genes that have distinct biological functions. Such modules may be linked to specific gene polymorphisms, transcription factors, cellular functions and disease mechanisms. Genes that are reliably active only in the context of their modules can be considered markers for the activity of the modules and may thus be promising candidates for biomarkers or therapeutic targets. This review aims to give an introduction to network theory and how it can be applied to microarray studies of complex diseases.

  20. On noise in time-delay integration CMOS image sensors

    NASA Astrophysics Data System (ADS)

    Levski, Deyan; Choubey, Bhaskar

    2016-05-01

    Time delay integration sensors are of increasing interest in CMOS processes owing to their low cost, power and ability to integrate with other circuit readout blocks. This paper presents an analysis of the noise contributors in current day CMOS Time-Delay-Integration image sensors with various readout architectures. An analysis of charge versus voltage domain readout modes is presented, followed by a noise classification of the existing Analog Accumulator Readout (AAR) and Digital Accumulator Readout (DAR) schemes for TDI imaging. The analysis and classification of existing readout schemes include, pipelined charge transfer, buffered direct injection, voltage as well as current-mode analog accumulators and all-digital accumulator techniques. Time-Delay-Integration imaging modes in CMOS processes typically use an N-number of readout steps, equivalent to the number of TDI pixel stages. In CMOS TDI sensors, where voltage domain readout is used, the requirements over speed and noise of the ADC readout chain are increased due to accumulation of the dominant voltage readout and ADC noise with every stage N. Until this day, the latter is the primary reason for a leap-back of CMOS TDI sensors as compared to their CCD counterparts. Moreover, most commercial CMOS TDI implementations are still based on a charge-domain readout, mimicking a CCD-like operation mode. Thus, having a good understanding of each noise contributor in the signal chain, as well as its magnitude in different readout architectures, is vital for the design of future generation low-noise CMOS TDI image sensors based on a voltage domain readout. This paper gives a quantitative classification of all major noise sources for all popular implementations in the literature.

  1. Monolithic CMUT-on-CMOS integration for intravascular ultrasound applications.

    PubMed

    Zahorian, Jaime; Hochman, Michael; Xu, Toby; Satir, Sarp; Gurun, Gokce; Karaman, Mustafa; Degertekin, F Levent

    2011-12-01

    One of the most important promises of capacitive micromachined ultrasonic transducer (CMUT) technology is integration with electronics. This approach is required to minimize the parasitic capacitances in the receive mode, especially in catheter-based volumetric imaging arrays, for which the elements must be small. Furthermore, optimization of the available silicon area and minimized number of connections occurs when the CMUTs are fabricated directly above the associated electronics. Here, we describe successful fabrication and performance evaluation of CMUT arrays for intravascular imaging on custom-designed CMOS receiver electronics from a commercial IC foundry. The CMUT-on-CMOS process starts with surface isolation and mechanical planarization of the CMOS electronics to reduce topography. The rest of the CMUT fabrication is achieved by modifying a low-temperature micromachining process through the addition of a single mask and developing a dry etching step to produce sloped sidewalls for simple and reliable CMUT-to-CMOS interconnection. This CMUT-to-CMOS interconnect method reduced the parasitic capacitance by a factor of 200 when compared with a standard wire-bonding method. Characterization experiments indicate that the CMUT-on-CMOS elements are uniform in frequency response and are similar to CMUTs simultaneously fabricated on standard silicon wafers without electronics integration. Ex- periments on a 1.6-mm-diameter dual-ring CMUT array with a center frequency of 15 MHz show that both the CMUTs and the integrated CMOS electronics are fully functional. The SNR measurements indicate that the performance is adequate for imaging chronic total occlusions located 1 cm from the CMUT array.

  2. NSC 800, 8-bit CMOS microprocessor

    NASA Technical Reports Server (NTRS)

    Suszko, S. F.

    1984-01-01

    The NSC 800 is an 8-bit CMOS microprocessor manufactured by National Semiconductor Corp., Santa Clara, California. The 8-bit microprocessor chip with 40-pad pin-terminals has eight address buffers (A8-A15), eight data address -- I/O buffers (AD(sub 0)-AD(sub 7)), six interrupt controls and sixteen timing controls with a chip clock generator and an 8-bit dynamic RAM refresh circuit. The 22 internal registers have the capability of addressing 64K bytes of memory and 256 I/O devices. The chip is fabricated on N-type (100) silicon using self-aligned polysilicon gates and local oxidation process technology. The chip interconnect consists of four levels: Aluminum, Polysi 2, Polysi 1, and P(+) and N(+) diffusions. The four levels, except for contact interface, are isolated by interlevel oxide. The chip is packaged in a 40-pin dual-in-line (DIP), side brazed, hermetically sealed, ceramic package with a metal lid. The operating voltage for the device is 5 V. It is available in three operating temperature ranges: 0 to +70 C, -40 to +85 C, and -55 to +125 C. Two devices were submitted for product evaluation by F. Stott, MTS, JPL Microprocessor Specialist. The devices were pencil-marked and photographed for identification.

  3. Simulation of SEU transients in CMOS ICs

    SciTech Connect

    Kaul, N.; Bhuva, B.L.; Kerns, S.E. )

    1991-12-01

    This paper reports that available analytical models of the number of single-event-induced errors (SEU) in combinational logic systems are not easily applicable to real integrated circuits (ICs). An efficient computer simulation algorithm set, SITA, predicts the vulnerability of data stored in and processed by complex combinational logic circuits to SEU. SITA is described in detail to allow researchers to incorporate it into their error analysis packages. Required simulation algorithms are based on approximate closed-form equations modeling individual device behavior in CMOS logic units. Device-level simulation is used to estimate the probability that ion-device interactions produce erroneous signals capable of propagating to a latch (or n output node), and logic-level simulation to predict the spread of such erroneous, latched information through the IC. Simulation results are compared to those from SPICE for several circuit and logic configurations. SITA results are comparable to this established circuit-level code, and SITA can analyze circuits with state-of-the-art device densities (which SPICE cannot). At all IC complexity levels, SITAS offers several factors of 10 savings in simulation time over SPICE.

  4. A 16-channel CMOS preamplifier for laser ranging radar receivers

    NASA Astrophysics Data System (ADS)

    Liu, Ru-qing; Zhu, Jing-guo; Jiang, Yan; Li, Meng-lin; Li, Feng

    2015-10-01

    A 16-channal front-end preamplifier array has been design in a 0.18um CMOS process for pulse Laser ranging radar receiver. This front-end preamplifier array incorporates transimpedance amplifiers(TIAs) and differential voltage post-amplifier(PAMP),band gap reference and other interface circuits. In the circuit design, the regulated cascade (RGC) input stage, Cherry-Hooper and active inductor peaking were employed to enhance the bandwidth. And in the layout design, by applying the layout isolation structure combined with P+ guard-ring(PGR), N+ guard-ring(NGR),and deep-n-well(DNW) for amplifier array, the crosstalk and the substrate noise coupling was reduced effectively. The simulations show that a single channel receiver front-end preamplifier achieves 95 dBΩ transimpedance gain and 600MHz bandwidth for 3 PF photodiode capacitance. The total power of 16-channel front-end amplifier array is about 800mW for 1.8V supply.

  5. Toward 'smart' DNA microarrays: algorithms for improving data quality and statistical inference

    NASA Astrophysics Data System (ADS)

    Bakewell, David J. G.; Wit, Ernst

    2007-12-01

    DNA microarrays are a laboratory tool for understanding biological processes at the molecular scale and future applications of this technology include healthcare, agriculture, and environment. Despite their usefulness, however, the information microarrays make available to the end-user is not used optimally, and the data is often noisy and of variable quality. This paper describes the use of hierarchical Maximum Likelihood Estimation (MLE) for generating algorithms that improve the quality of microarray data and enhance statistical inference about gene behavior. The paper describes examples of recent work that improves microarray performance, demonstrated using data from both Monte Carlo simulations and published experiments. One example looks at the variable quality of cDNA spots on a typical microarray surface. It is shown how algorithms, derived using MLE, are used to "weight" these spots according to their morphological quality, and subsequently lead to improved detection of gene activity. Another example, briefly discussed, addresses the "noisy data about too many genes" issue confronting many analysts who are also interested in the collective action of a group of genes, often organized as a pathway or complex. Preliminary work is described where MLE is used to "share" variance information across a pre-assigned group of genes of interest, leading to improved detection of gene activity.

  6. High quality epoxysilane substrate for clinical multiplex serodiagnostic proteomic microarrays

    NASA Astrophysics Data System (ADS)

    Ewart, Tom; Carmichael, Stuart; Lea, Peter

    2005-09-01

    Polylysine and aminopropylsilane treated glass comprised the majority of substrates employed in first generation genetic microarray substrates. Second generation single stranded long oligo libraries with amino termini provided for controlled terminal specific attachment, and rationally designed unique sequence libraries with normalized melting temperatures. These libraries benefit from active covalent coupling surfaces such as Epoxysilane. The latter's oxime ring shows versatile reactivity with amino-, thiol- and hydroxyl- groups thus encompassing small molecule, oligo and proteomic microarray applications. Batch-to-batch production uniformity supports entry of the Epoxysilane process into clinical diagnostics. We carried out multiple print runs of 21 clinically relevant bacterial and viral antigens at optimized concentrations, plus human IgG and IgM standards in triplicate on multiple batches of Epoxysilane substrates. A set of 45 patient sera were assayed in a 35 minute protocol using 10 microliters per array in a capillary-fill format (15 minute serum incubation, wash, 15 minute incubation with Cy3-labeled anti-hIgG plus Dy647-labeled anti-hIgM, final wash). The LOD (3 SD above background) was better than 1 microgram/ml for IgG, and standard curves were regular and monotonically increasing over the range 0 to 1000 micrograms/ml. Ninety-five percent of the CVs for the standards were under 10%, and 90% percent of CVs for antigen responses were under 10% across all batches of Epoxysilane and print runs. In addition, where SDs are larger than expected, microarray images may be readily reviewed for quality control purposes and pin misprints quickly identified. In order to determine the influence of stirring on sensitivity and speed of the microarray assay, we printed 10 common ToRCH antigens (H. pylori, T. gondii, Rubella, Rubeola, C. trachomatis, Herpes 1 and 2, CMV, C. jejuni, and EBV) in Epoxysilane-activated slide-wells. Anti-IgG-Cy3 direct binding to printed Ig

  7. CMOS Imaging Sensor Technology for Aerial Mapping Cameras

    NASA Astrophysics Data System (ADS)

    Neumann, Klaus; Welzenbach, Martin; Timm, Martin

    2016-06-01

    In June 2015 Leica Geosystems launched the first large format aerial mapping camera using CMOS sensor technology, the Leica DMC III. This paper describes the motivation to change from CCD sensor technology to CMOS for the development of this new aerial mapping camera. In 2002 the DMC first generation was developed by Z/I Imaging. It was the first large format digital frame sensor designed for mapping applications. In 2009 Z/I Imaging designed the DMC II which was the first digital aerial mapping camera using a single ultra large CCD sensor to avoid stitching of smaller CCDs. The DMC III is now the third generation of large format frame sensor developed by Z/I Imaging and Leica Geosystems for the DMC camera family. It is an evolution of the DMC II using the same system design with one large monolithic PAN sensor and four multi spectral camera heads for R,G, B and NIR. For the first time a 391 Megapixel large CMOS sensor had been used as PAN chromatic sensor, which is an industry record. Along with CMOS technology goes a range of technical benefits. The dynamic range of the CMOS sensor is approx. twice the range of a comparable CCD sensor and the signal to noise ratio is significantly better than with CCDs. Finally results from the first DMC III customer installations and test flights will be presented and compared with other CCD based aerial sensors.

  8. Figures of merit for CMOS SPADs and arrays

    NASA Astrophysics Data System (ADS)

    Bronzi, D.; Villa, F.; Bellisai, S.; Tisa, S.; Ripamonti, G.; Tosi, A.

    2013-05-01

    SPADs (Single Photon Avalanche Diodes) are emerging as most suitable photodetectors for both single-photon counting (Fluorescence Correlation Spectroscopy, Lock-in 3D Ranging) and single-photon timing (Lidar, Fluorescence Lifetime Imaging, Diffuse Optical Imaging) applications. Different complementary metal-oxide semiconductor (CMOS) implementations have been reported in literature. We present some figure of merit able to summarize the typical SPAD performances (i.e. Dark Counting Rate, Photo Detection Efficiency, afterpulsing probability, hold-off time, timing jitter) and to identify a proper metric for SPAD comparison, both as single detectors and also as imaging arrays. The goal is to define a practical framework within which it is possible to rank detectors based on their performances in specific experimental conditions, for either photon-counting or photon-timing applications. Furthermore we review the performances of some CMOS and custom-made SPADs. Results show that CMOS SPADs performances improve as the technology scales down; moreover, miniaturization of SPADs and new solutions adopted to counteract issues related with the SPAD design (electric field uniformity, premature edge breakdown, tunneling effects, defect-rich STI interface) along with advances in standard CMOS processes led to a general improvement in all fabricated photodetectors; therefore, CMOS SPADs can be suitable for very dense and cost-effective many-pixels imagers with high performances.

  9. CMOS Cell Sensors for Point-of-Care Diagnostics

    PubMed Central

    Adiguzel, Yekbun; Kulah, Haluk

    2012-01-01

    The burden of health-care related services in a global era with continuously increasing population and inefficient dissipation of the resources requires effective solutions. From this perspective, point-of-care diagnostics is a demanded field in clinics. It is also necessary both for prompt diagnosis and for providing health services evenly throughout the population, including the rural districts. The requirements can only be fulfilled by technologies whose productivity has already been proven, such as complementary metal-oxide-semiconductors (CMOS). CMOS-based products can enable clinical tests in a fast, simple, safe, and reliable manner, with improved sensitivities. Portability due to diminished sensor dimensions and compactness of the test set-ups, along with low sample and power consumption, is another vital feature. CMOS-based sensors for cell studies have the potential to become essential counterparts of point-of-care diagnostics technologies. Hence, this review attempts to inform on the sensors fabricated with CMOS technology for point-of-care diagnostic studies, with a focus on CMOS image sensors and capacitance sensors for cell studies. PMID:23112587

  10. Silicon CMOS-based vertical multimode interference optical taps

    NASA Astrophysics Data System (ADS)

    Stenger, Vincent E.; Beyette, Fred R., Jr.

    2001-12-01

    A compact, low loss, optical tap technology is critical for the incorporation of optical interconnects into mainstream CMOS processes. A recently introduced multimode interference effect based device has the potential for very high speed performance in a compact geometry and in a CMOS compatible process. For this work, 2-D and 3-D device simulations confirm a low excess optical loss on order of 0.1 dB, and a nominal 40% (2.2 dB) optical coupling into the CMOS circuitry over a wide range of guide to substrate distances. Simulated devices are on the order of 25micrometers in length and as narrow as 1 um. High temperature, hybrid polymer materials used for commercial CMOS inter-metal dielectric layers are targeted for tap fabrication and are incorporated into the models. Low cost, silicon CMOS based processing makes the new tap technology especially suitable for computer multi-chip module and board level interconnects, as well as for metro fiber to the home and desk telecommunications applications.

  11. CMOS cell sensors for point-of-care diagnostics.

    PubMed

    Adiguzel, Yekbun; Kulah, Haluk

    2012-01-01

    The burden of health-care related services in a global era with continuously increasing population and inefficient dissipation of the resources requires effective solutions. From this perspective, point-of-care diagnostics is a demanded field in clinics. It is also necessary both for prompt diagnosis and for providing health services evenly throughout the population, including the rural districts. The requirements can only be fulfilled by technologies whose productivity has already been proven, such as complementary metal-oxide-semiconductors (CMOS). CMOS-based products can enable clinical tests in a fast, simple, safe, and reliable manner, with improved sensitivities. Portability due to diminished sensor dimensions and compactness of the test set-ups, along with low sample and power consumption, is another vital feature. CMOS-based sensors for cell studies have the potential to become essential counterparts of point-of-care diagnostics technologies. Hence, this review attempts to inform on the sensors fabricated with CMOS technology for point-of-care diagnostic studies, with a focus on CMOS image sensors and capacitance sensors for cell studies.

  12. CMOS Conductometric System for Growth Monitoring and Sensing of Bacteria.

    PubMed

    Lei Yao; Lamarche, P; Tawil, N; Khan, R; Aliakbar, A M; Hassan, M H; Chodavarapu, V P; Mandeville, R

    2011-06-01

    We present the design and implementation of a prototype complementary metal-oxide semiconductor (CMOS) conductometric integrated circuit (IC) for colony growth monitoring and specific sensing of Escherichia coli (E. coli) bacteria. The detection of E. coli is done by employing T4 bacteriophages as receptor organisms. The conductometric system operates by measuring the resistance of the test sample between the electrodes of a two-electrode electrochemical system (reference electrode and working electrode). The CMOS IC is fabricated in a TSMC 0.35-μm process and uses a current-to-frequency (I to F) conversion circuit to convert the test sample resistance into a digital output modulated in frequency. Pulsewidth control (one-shot circuit) is implemented on-chip to control the pulsewidth of the output digital signal. The novelty in the current work lies in the ability of the CMOS sensor system to monitor very low initial concentrations of bacteria (4×10(2) to 4×10(4) colony forming unit (CFU)/mL). The CMOS system is also used to record the interaction between E. coli and its specific receptor T4 bacteriophage. The prototype CMOS IC consumes an average power of 1.85 mW with a 3.3-V dc power supply.

  13. Monitoring enzyme-catalyzed reactions in micromachined nanoliter wells using a conventional microscope-based microarray reader

    NASA Astrophysics Data System (ADS)

    van den Doel, L. Richard; Moerman, R.; van Dedem, G. W. K.; Young, Ian T.; van Vliet, Lucas J.

    2002-06-01

    Yeast-Saccharomyces cerevisiae - it widely used as a model system for other higher eukaryotes, including man. One of the basic fermentation processes in yeast is the glycolytic pathway, which is the conversion of glucose to ethanol and carbon dioxide. This pathway consists of 12 enzyme-catalyzed reactions. With the approach of microarray technology we want to explore the metabolic regulation of this pathway in yeast. This paper will focus on the design of a conventional microscope based microarray reader, which is used to monitor these enzymatic reactions in microarrays. These microarrays are fabricated in silicon and have sizes of 300 by 300 micrometers 2. The depth varies from 20 to 50 micrometers . Enzyme activity levels can be derived by monitoring the production or consumption rate of NAD(P)H, which is excited at 360nm and emits around 450nm. This fluorophore is involved in all 12 reactions of the pathway. The microarray reader is equipped with a back-illuminated CCD camera in order to obtain a high quantum efficiency for the lower wavelengths. The dynamic range of our microarray reader varies form 5(mu) Molar to 1mMolar NAD(P)H. With this microarray reader enzyme activity levels down to 0.01 unit per milliliter can be monitored. The acquisition time per well is 0.1s. The total scan cycle time for a 5 X 5 microarray is less than half a minute. The number of cycles for a proper estimation of the enzyme activity is inversely proportional to the enzyme activity: long measurement times are needed to determine low enzyme activity levels.

  14. Environmental microarray analyses of Antarctic soil microbial communities.

    PubMed

    Yergeau, Etienne; Schoondermark-Stolk, Sung A; Brodie, Eoin L; Déjean, Sébastien; DeSantis, Todd Z; Gonçalves, Olivier; Piceno, Yvette M; Andersen, Gary L; Kowalchuk, George A

    2009-03-01

    Antarctic ecosystems are fascinating in their limited trophic complexity, with decomposition and nutrient cycling functions being dominated by microbial activities. Not only are Antarctic habitats exposed to extreme environmental conditions, the Antarctic Peninsula is also experiencing unequalled effects of global warming. Owing to their uniqueness and the potential impact of global warming on these pristine systems, there is considerable interest in determining the structure and function of microbial communities in the Antarctic. We therefore utilized a recently designed 16S rRNA gene microarray, the PhyloChip, which targets 8741 bacterial and archaeal taxa, to interrogate microbial communities inhabiting densely vegetated and bare fell-field soils along a latitudinal gradient ranging from 51 degrees S (Falkland Islands) to 72 degrees S (Coal Nunatak). Results indicated a clear decrease in diversity with increasing latitude, with the two southernmost sites harboring the most distinct Bacterial and Archaeal communities. The microarray approach proved more sensitive in detecting the breadth of microbial diversity than polymerase chain reaction-based bacterial 16S rRNA gene libraries of modest size ( approximately 190 clones per library). Furthermore, the relative signal intensities summed for phyla and families on the PhyloChip were significantly correlated with the relative occurrence of these taxa in clone libraries. PhyloChip data were also compared with functional gene microarray data obtained earlier, highlighting numerous significant relationships and providing evidence for a strong link between community composition and functional gene distribution in Antarctic soils. Integration of these PhyloChip data with other complementary methods provides an unprecedented understanding of the microbial diversity and community structure of terrestrial Antarctic habitats.

  15. Integrated analysis of microarray data and gene function information.

    PubMed

    Cui, Yan; Zhou, Mi; Wong, Wing Hung

    2004-01-01

    Microarray data should be interpreted in the context of existing biological knowledge. Here we present integrated analysis of microarray data and gene function classification data using homogeneity analysis. Homogeneity analysis is a graphical multivariate statistical method for analyzing categorical data. It converts categorical data into graphical display. By simultaneously quantifying the microarray-derived gene groups and gene function categories, it captures the complex relations between biological information derived from microarray data and the existing knowledge about the gene function. Thus, homogeneity analysis provides a mathematical framework for integrating the analysis of microarray data and the existing biological knowledge.

  16. Viral diagnosis in Indian livestock using customized microarray chips

    PubMed Central

    Yadav, Brijesh S; Pokhriyal, Mayank; Ratta, Barkha; Kumar, Ajay; Saxena, Meeta; Sharma, Bhaskar

    2015-01-01

    Viral diagnosis in Indian livestock using customized microarray chips is gaining momentum in recent years. Hence, it is possible to design customized microarray chip for viruses infecting livestock in India. Customized microarray chips identified Bovine herpes virus-1 (BHV-1), Canine Adeno Virus-1 (CAV-1), and Canine Parvo Virus-2 (CPV-2) in clinical samples. Microarray identified specific probes were further confirmed using RT-PCR in all clinical and known samples. Therefore, the application of microarray chips during viral disease outbreaks in Indian livestock is possible where conventional methods are unsuitable. It should be noted that customized application requires a detailed cost efficiency calculation. PMID:26912948

  17. Viral diagnosis in Indian livestock using customized microarray chips.

    PubMed

    Yadav, Brijesh S; Pokhriyal, Mayank; Ratta, Barkha; Kumar, Ajay; Saxena, Meeta; Sharma, Bhaskar

    2015-01-01

    Viral diagnosis in Indian livestock using customized microarray chips is gaining momentum in recent years. Hence, it is possible to design customized microarray chip for viruses infecting livestock in India. Customized microarray chips identified Bovine herpes virus-1 (BHV-1), Canine Adeno Virus-1 (CAV-1), and Canine Parvo Virus-2 (CPV-2) in clinical samples. Microarray identified specific probes were further confirmed using RT-PCR in all clinical and known samples. Therefore, the application of microarray chips during viral disease outbreaks in Indian livestock is possible where conventional methods are unsuitable. It should be noted that customized application requires a detailed cost efficiency calculation.

  18. ESD protection design for advanced CMOS

    NASA Astrophysics Data System (ADS)

    Huang, Jin B.; Wang, Gewen

    2001-10-01

    ESD effects in integrated circuits have become a major concern as today's technologies shrink to sub-micron/deep- sub-micron dimensions. The thinner gate oxide and shallower junction depth used in the advanced technologies make them very vulnerable to ESD damages. The advanced techniques like silicidation and STI (shallow trench insulation) used for improving other device performances make ESD design even more challenging. For non-silicided technologies, a certain DCGS (drain contact to gate edge spacing) is needed to achieve ESD hardness for nMOS output drivers and nMOS protection transistors. The typical DCGS values are 4-5um and 2-3um for 0.5um and 0.25um CMOS, respectively. The silicidation reduces the ballast resistance provided by DCGS with at least a factor of 10. As a result, scaling of the ESD performance with device width is lost and even zero ESD performance is reported for standard silicided devices. The device level ESD design is focused in this paper, which includes GGNMOS (gate grounded NMOS) and GCNMOS (gate coupled NMOS). The device level ESD testing including TLP (transmission line pulse) is given. Several ESD issues caused by advanced technologies have been pointed out. The possible solutions have been developed and summarized including silicide blocking, process optimization, back-end ballasting, and new protection scheme, dummy gate/n-well resistor ballsting, etc. Some of them require process cost increase, and others provide novel, compact, and simple design but involving royalty/IP (intellectual property) issue. Circuit level ESD design and layout design considerations are covered. The top-level ESD protection strategies are also given.

  19. Adiabatic circuits: converter for static CMOS signals

    NASA Astrophysics Data System (ADS)

    Fischer, J.; Amirante, E.; Bargagli-Stoffi, A.; Schmitt-Landsiedel, D.

    2003-05-01

    Ultra low power applications can take great advantages from adiabatic circuitry. In this technique a multiphase system is used which consists ideally of trapezoidal voltage signals. The input signals to be processed will often come from a function block realized in static CMOS. The static rectangular signals must be converted for the oscillating multiphase system of the adiabatic circuitry. This work shows how to convert the input signals to the proposed pulse form which is synchronized to the appropriate supply voltage. By means of adder structures designed for a 0.13µm technology in a 4-phase system there will be demonstrated, which additional circuits are necessary for the conversion. It must be taken into account whether the data arrive in parallel or serial form. Parallel data are all in one phase and therefore it is advantageous to use an adder structure with a proper input stage, e.g. a Carry Lookahead Adder (CLA). With a serial input stage it is possible to read and to process four signals during one cycle due to the adiabatic 4-phase system. Therefore input signals with a frequency four times higher than the adiabatic clock frequency can be used. This reduces the disadvantage of the slow clock period typical for adiabatic circuits. By means of an 8 bit Ripple Carry Adder (8 bit RCA) the serial reading will be introduced. If the word width is larger than 4 bits the word can be divided in 4 bit words which are processed in parallel. This is the most efficient way to minimize the number of input lines and pads. At the same time a high throughput is achieved.

  20. Radiation tolerant back biased CMOS VLSI

    NASA Technical Reports Server (NTRS)

    Maki, Gary K. (Inventor); Gambles, Jody W. (Inventor); Hass, Kenneth J. (Inventor)

    2003-01-01

    A CMOS circuit formed in a semiconductor substrate having improved immunity to total ionizing dose radiation, improved immunity to radiation induced latch up, and improved immunity to a single event upset. The architecture of the present invention can be utilized with the n-well, p-well, or dual-well processes. For example, a preferred embodiment of the present invention is described relative to a p-well process wherein the p-well is formed in an n-type substrate. A network of NMOS transistors is formed in the p-well, and a network of PMOS transistors is formed in the n-type substrate. A contact is electrically coupled to the p-well region and is coupled to first means for independently controlling the voltage in the p-well region. Another contact is electrically coupled to the n-type substrate and is coupled to second means for independently controlling the voltage in the n-type substrate. By controlling the p-well voltage, the effective threshold voltages of the n-channel transistors both drawn and parasitic can be dynamically tuned. Likewise, by controlling the n-type substrate, the effective threshold voltages of the p-channel transistors both drawn and parasitic can also be dynamically tuned. Preferably, by optimizing the threshold voltages of the n-channel and p-channel transistors, the total ionizing dose radiation effect will be neutralized and lower supply voltages can be utilized for the circuit which would result in the circuit requiring less power.

  1. Respiratory Tularemia: Francisella Tularensis and Microarray Probe Designing

    PubMed Central

    Ranjbar, Reza; Behzadi, Payam; Mammina, Caterina

    2016-01-01

    Background: Francisella tularensis (F. tularensis) is the etiological microorganism for tularemia. There are different forms of tularemia such as respiratory tularemia. Respiratory tularemia is the most severe form of tularemia with a high rate of mortality; if not treated. Therefore, traditional microbiological tools and Polymerase Chain Reaction (PCR) are not useful for a rapid, reliable, accurate, sensitive and specific diagnosis. But, DNA microarray technology does. DNA microarray technology needs to appropriate microarray probe designing. Objective: The main goal of this original article was to design suitable long oligo microarray probes for detection and identification of F. tularensis. Method: For performing this research, the complete genomes of F. tularensis subsp. tularensis FSC198, F. tularensis subsp. holarctica LVS, F. tularensis subsp. mediasiatica, F. tularensis subsp. novicida (F. novicida U112), and F. philomiragia subsp. philomiragia ATCC 25017 were studied via NCBI BLAST tool, GView and PanSeq Servers and finally the microarray probes were produced and processed via AlleleID 7.7 software and Oligoanalyzer tool, respectively. Results: In this in silico investigation, a number of long oligo microarray probes were designed for detecting and identifying F. tularensis. Among these probes, 15 probes were recognized as the best candidates for microarray chip designing. Conclusion: Calibrated microarray probes reduce the biasis of DNA microarray technology as an advanced, rapid, accurate and cost-effective molecular diagnostic tool with high specificity and sensitivity. Professional microarray probe designing provides us with much more facility and flexibility regarding preparation of a microarray diagnostic chip. PMID:28077973

  2. Detecting outlier samples in microarray data.

    PubMed

    Shieh, Albert D; Hung, Yeung Sam

    2009-01-01

    In this paper, we address the problem of detecting outlier samples with highly different expression patterns in microarray data. Although outliers are not common, they appear even in widely used benchmark data sets and can negatively affect microarray data analysis. It is important to identify outliers in order to explore underlying experimental or biological problems and remove erroneous data. We propose an outlier detection method based on principal component analysis (PCA) and robust estimation of Mahalanobis distances that is fully automatic. We demonstrate that our outlier detection method identifies biologically significant outliers with high accuracy and that outlier removal improves the prediction accuracy of classifiers. Our outlier detection method is closely related to existing robust PCA methods, so we compare our outlier detection method to a prominent robust PCA method.

  3. Plasmonically amplified fluorescence bioassay with microarray format

    NASA Astrophysics Data System (ADS)

    Gogalic, S.; Hageneder, S.; Ctortecka, C.; Bauch, M.; Khan, I.; Preininger, Claudia; Sauer, U.; Dostalek, J.

    2015-05-01

    Plasmonic amplification of fluorescence signal in bioassays with microarray detection format is reported. A crossed relief diffraction grating was designed to couple an excitation laser beam to surface plasmons at the wavelength overlapping with the absorption and emission bands of fluorophore Dy647 that was used as a label. The surface of periodically corrugated sensor chip was coated with surface plasmon-supporting gold layer and a thin SU8 polymer film carrying epoxy groups. These groups were employed for the covalent immobilization of capture antibodies at arrays of spots. The plasmonic amplification of fluorescence signal on the developed microarray chip was tested by using interleukin 8 sandwich immunoassay. The readout was performed ex situ after drying the chip by using a commercial scanner with high numerical aperture collecting lens. Obtained results reveal the enhancement of fluorescence signal by a factor of 5 when compared to a regular glass chip.

  4. PMD: A Resource for Archiving and Analyzing Protein Microarray data

    PubMed Central

    Xu, Zhaowei; Huang, Likun; Zhang, Hainan; Li, Yang; Guo, Shujuan; Wang, Nan; Wang, Shi-hua; Chen, Ziqing; Wang, Jingfang; Tao, Sheng-ce

    2016-01-01

    Protein microarray is a powerful technology for both basic research and clinical study. However, because there is no database specifically tailored for protein microarray, the majority of the valuable original protein microarray data is still not publically accessible. To address this issue, we constructed Protein Microarray Database (PMD), which is specifically designed for archiving and analyzing protein microarray data. In PMD, users can easily browse and search the entire database by experimental name, protein microarray type, and sample information. Additionally, PMD integrates several data analysis tools and provides an automated data analysis pipeline for users. With just one click, users can obtain a comprehensive analysis report for their protein microarray data. The report includes preliminary data analysis, such as data normalization, candidate identification, and an in-depth bioinformatics analysis of the candidates, which include functional annotation, pathway analysis, and protein-protein interaction network analysis. PMD is now freely available at www.proteinmicroarray.cn. PMID:26813635

  5. PMD: A Resource for Archiving and Analyzing Protein Microarray data.

    PubMed

    Xu, Zhaowei; Huang, Likun; Zhang, Hainan; Li, Yang; Guo, Shujuan; Wang, Nan; Wang, Shi-Hua; Chen, Ziqing; Wang, Jingfang; Tao, Sheng-Ce

    2016-01-27

    Protein microarray is a powerful technology for both basic research and clinical study. However, because there is no database specifically tailored for protein microarray, the majority of the valuable original protein microarray data is still not publically accessible. To address this issue, we constructed Protein Microarray Database (PMD), which is specifically designed for archiving and analyzing protein microarray data. In PMD, users can easily browse and search the entire database by experimental name, protein microarray type, and sample information. Additionally, PMD integrates several data analysis tools and provides an automated data analysis pipeline for users. With just one click, users can obtain a comprehensive analysis report for their protein microarray data. The report includes preliminary data analysis, such as data normalization, candidate identification, and an in-depth bioinformatics analysis of the candidates, which include functional annotation, pathway analysis, and protein-protein interaction network analysis. PMD is now freely available at www.proteinmicroarray.cn.

  6. Enhancing interdisciplinary mathematics and biology education: a microarray data analysis course bridging these disciplines.

    PubMed

    Tra, Yolande V; Evans, Irene M

    2010-01-01

    BIO2010 put forth the goal of improving the mathematical educational background of biology students. The analysis and interpretation of microarray high-dimensional data can be very challenging and is best done by a statistician and a biologist working and teaching in a collaborative manner. We set up such a collaboration and designed a course on microarray data analysis. We started using Genome Consortium for Active Teaching (GCAT) materials and Microarray Genome and Clustering Tool software and added R statistical software along with Bioconductor packages. In response to student feedback, one microarray data set was fully analyzed in class, starting from preprocessing to gene discovery to pathway analysis using the latter software. A class project was to conduct a similar analysis where students analyzed their own data or data from a published journal paper. This exercise showed the impact that filtering, preprocessing, and different normalization methods had on gene inclusion in the final data set. We conclude that this course achieved its goals to equip students with skills to analyze data from a microarray experiment. We offer our insight about collaborative teaching as well as how other faculty might design and implement a similar interdisciplinary course.

  7. Microarray analysis of potential genes in the pathogenesis of recurrent oral ulcer.

    PubMed

    Han, Jingying; He, Zhiwei; Li, Kun; Hou, Lu

    2015-01-01

    Recurrent oral ulcer seriously threatens patients' daily life and health. This study investigated potential genes and pathways that participate in the pathogenesis of recurrent oral ulcer by high throughput bioinformatic analysis. RT-PCR and Western blot were applied to further verify screened interleukins effect. Recurrent oral ulcer related genes were collected from websites and papers, and further found out from Human Genome 280 6.0 microarray data. Each pathway of recurrent oral ulcer related genes were got through chip hybridization. RT-PCR was applied to test four recurrent oral ulcer related genes to verify the microarray data. Data transformation, scatter plot, clustering analysis, and expression pattern analysis were used to analyze recurrent oral ulcer related gene expression changes. Recurrent oral ulcer gene microarray was successfully established. Microarray showed that 551 genes involved in recurrent oral ulcer activity and 196 genes were recurrent oral ulcer related genes. Of them, 76 genes up-regulated, 62 genes down-regulated, and 58 genes up-/down-regulated. Total expression level up-regulated 752 times (60%) and down-regulated 485 times (40%). IL-2 plays an important role in the occurrence, development and recurrence of recurrent oral ulcer on the mRNA and protein levels. Gene microarray can be used to analyze potential genes and pathways in recurrent oral ulcer. IL-2 may be involved in the pathogenesis of recurrent oral ulcer.

  8. Enhancing Interdisciplinary Mathematics and Biology Education: A Microarray Data Analysis Course Bridging These Disciplines

    PubMed Central

    Evans, Irene M.

    2010-01-01

    BIO2010 put forth the goal of improving the mathematical educational background of biology students. The analysis and interpretation of microarray high-dimensional data can be very challenging and is best done by a statistician and a biologist working and teaching in a collaborative manner. We set up such a collaboration and designed a course on microarray data analysis. We started using Genome Consortium for Active Teaching (GCAT) materials and Microarray Genome and Clustering Tool software and added R statistical software along with Bioconductor packages. In response to student feedback, one microarray data set was fully analyzed in class, starting from preprocessing to gene discovery to pathway analysis using the latter software. A class project was to conduct a similar analysis where students analyzed their own data or data from a published journal paper. This exercise showed the impact that filtering, preprocessing, and different normalization methods had on gene inclusion in the final data set. We conclude that this course achieved its goals to equip students with skills to analyze data from a microarray experiment. We offer our insight about collaborative teaching as well as how other faculty might design and implement a similar interdisciplinary course. PMID:20810954

  9. Improved microarray-based decision support with graph encoded interactome data.

    PubMed

    Daemen, Anneleen; Signoretto, Marco; Gevaert, Olivier; Suykens, Johan A K; De Moor, Bart

    2010-04-19

    In the past, microarray studies have been criticized due to noise and the limited overlap between gene signatures. Prior biological knowledge should therefore be incorporated as side information in models based on gene expression data to improve the accuracy of diagnosis and prognosis in cancer. As prior knowledge, we investigated interaction and pathway information from the human interactome on different aspects of biological systems. By exploiting the properties of kernel methods, relations between genes with similar functions but active in alternative pathways could be incorporated in a support vector machine classifier based on spectral graph theory. Using 10 microarray data sets, we first reduced the number of data sources relevant for multiple cancer types and outcomes. Three sources on metabolic pathway information (KEGG), protein-protein interactions (OPHID) and miRNA-gene targeting (microRNA.org) outperformed the other sources with regard to the considered class of models. Both fixed and adaptive approaches were subsequently considered to combine the three corresponding classifiers. Averaging the predictions of these classifiers performed best and was significantly better than the model based on microarray data only. These results were confirmed on 6 validation microarray sets, with a significantly improved performance in 4 of them. Integrating interactome data thus improves classification of cancer outcome for the investigated microarray technologies and cancer types. Moreover, this strategy can be incorporated in any kernel method or non-linear version of a non-kernel method.

  10. CMOS reliability issues for emerging cryogenic Lunar electronics applications

    NASA Astrophysics Data System (ADS)

    Chen, Tianbing; Zhu, Chendong; Najafizadeh, Laleh; Jun, Bongim; Ahmed, Adnan; Diestelhorst, Ryan; Espinel, Gustavo; Cressler, John D.

    2006-06-01

    We investigate the reliability issues associated with the application of CMOS devices contained within an advanced SiGe HBT BiCMOS technology to emerging cryogenic space electronics (e.g., down to 43 K, for Lunar missions). Reduced temperature operation improves CMOS device performance (e.g., transconductance, carrier mobility, subthreshold swing, and output current drive), as expected. However, operation at cryogenic temperatures also causes serious device reliability concerns, since it aggravates hot-carrier effects, effectively decreasing the inferred device lifetime significantly, especially at short gate lengths. In the paper, hot-carrier effects are demonstrated to be a stronger function of the device gate length than the temperature, suggesting that significant trade-offs between the gate length and the operational temperature must be made in order to ensure safe and reliable operation over typical projected mission lifetimes in these hostile environments.

  11. A CMOS humidity sensor for passive RFID sensing applications.

    PubMed

    Deng, Fangming; He, Yigang; Zhang, Chaolong; Feng, Wei

    2014-05-16

    This paper presents a low-cost low-power CMOS humidity sensor for passive RFID sensing applications. The humidity sensing element is implemented in standard CMOS technology without any further post-processing, which results in low fabrication costs. The interface of this humidity sensor employs a PLL-based architecture transferring sensor signal processing from the voltage domain to the frequency domain. Therefore this architecture allows the use of a fully digital circuit, which can operate on ultra-low supply voltage and thus achieves low-power consumption. The proposed humidity sensor has been fabricated in the TSMC 0.18 μm CMOS process. The measurements show this humidity sensor exhibits excellent linearity and stability within the relative humidity range. The sensor interface circuit consumes only 1.05 µW at 0.5 V supply voltage and reduces it at least by an order of magnitude compared to previous designs.

  12. A CMOS Humidity Sensor for Passive RFID Sensing Applications

    PubMed Central

    Deng, Fangming; He, Yigang; Zhang, Chaolong; Feng, Wei

    2014-01-01

    This paper presents a low-cost low-power CMOS humidity sensor for passive RFID sensing applications. The humidity sensing element is implemented in standard CMOS technology without any further post-processing, which results in low fabrication costs. The interface of this humidity sensor employs a PLL-based architecture transferring sensor signal processing from the voltage domain to the frequency domain. Therefore this architecture allows the use of a fully digital circuit, which can operate on ultra-low supply voltage and thus achieves low-power consumption. The proposed humidity sensor has been fabricated in the TSMC 0.18 μm CMOS process. The measurements show this humidity sensor exhibits excellent linearity and stability within the relative humidity range. The sensor interface circuit consumes only 1.05 μW at 0.5 V supply voltage and reduces it at least by an order of magnitude compared to previous designs. PMID:24841250

  13. IGBT scaling principle toward CMOS compatible wafer processes

    NASA Astrophysics Data System (ADS)

    Tanaka, Masahiro; Omura, Ichiro

    2013-02-01

    A scaling principle for trench gate IGBT is proposed. CMOS technology on large diameter wafer enables to produce various digital circuits with higher performance and lower cost. The transistor cell structure becomes laterally smaller and smaller and vertically shallower and shallower. In contrast, latest IGBTs have rather deeper trench structure to obtain lower on-state voltage drop and turn-off loss. In the aspect of the process uniformity and wafer warpage, manufacturing such structure in the CMOS factory is difficult. In this paper, we show the scaling principle toward shallower structure and better performance. The principle is theoretically explained by our previously proposed "Structure Oriented" analytical model. The principle represents a possibility of technology direction and roadmap for future IGBT for improving the device performance consistent with lower cost and high volume productivity with CMOS compatible large diameter wafer technologies.

  14. Silicon pixel detector prototyping in SOI CMOS technology

    NASA Astrophysics Data System (ADS)

    Dasgupta, Roma; Bugiel, Szymon; Idzik, Marek; Kapusta, Piotr; Kucewicz, Wojciech; Turala, Michal

    2016-12-01

    The Silicon-On-Insulator (SOI) CMOS is one of the most advanced and promising technology for monolithic pixel detectors design. The insulator layer that is implemented inside the silicon crystal allows to integrate sensors matrix and readout electronic on a single wafer. Moreover, the separation of electronic and substrate increases also the SOI circuits performance. The parasitic capacitances to substrate are significantly reduced, so the electronic systems are faster and consume much less power. The authors of this presentation are the members of international SOIPIX collaboration, that is developing SOI pixel detectors in 200 nm Lapis Fully-Depleted, Low-Leakage SOI CMOS. This work shows a set of advantages of SOI technology and presents possibilities for pixel detector design SOI CMOS. In particular, the preliminary results of a Cracow chip are presented.

  15. Operation and biasing for single device equivalent to CMOS

    DOEpatents

    Welch, James D.

    2001-01-01

    Disclosed are semiconductor devices including at least one junction which is rectifying whether the semiconductor is caused to be N or P-type, by the presence of field induced carriers. In particular, inverting and non-inverting gate voltage channel induced semiconductor single devices with operating characteristics similar to conventional multiple device CMOS systems, which can be operated as modulators, are disclosed as are a non-latching SCR and an approach to blocking parasitic currents. Operation of the gate voltage channel induced semiconductor single devices with operating characteristics similar to multiple device CMOS systems under typical bias schemes is described, and simple demonstrative five mask fabrication procedures for the inverting and non-inverting gate voltage channel induced semiconductor single devices with operating characteristics similar to multiple device CMOS systems are also presented.

  16. CMOS biosensors for in vitro diagnosis - transducing mechanisms and applications.

    PubMed

    Lei, Ka-Meng; Mak, Pui-In; Law, Man-Kay; Martins, Rui P

    2016-09-21

    Complementary metal oxide semiconductor (CMOS) technology enables low-cost and large-scale integration of transistors and physical sensing materials on tiny chips (e.g., <1 cm(2)), seamlessly combining the two key functions of biosensors: transducing and signal processing. Recent CMOS biosensors unified different transducing mechanisms (impedance, fluorescence, and nuclear spin) and readout electronics have demonstrated competitive sensitivity for in vitro diagnosis, such as detection of DNA (down to 10 aM), protein (down to 10 fM), or bacteria/cells (single cell). Herein, we detail the recent advances in CMOS biosensors, centering on their key principles, requisites, and applications. Together, these may contribute to the advancement of our healthcare system, which should be decentralized by broadly utilizing point-of-care diagnostic tools.

  17. Ultrahigh density microarrays of solid samples.

    PubMed

    LeBaron, Matthew J; Crismon, Heidi R; Utama, Fransiscus E; Neilson, Lynn M; Sultan, Ahmed S; Johnson, Kevin J; Andersson, Eva C; Rui, Hallgeir

    2005-07-01

    We present a sectioning and bonding technology to make ultrahigh density microarrays of solid samples, cutting edge matrix assembly (CEMA). Maximized array density is achieved by a scaffold-free, self-supporting construction with rectangular array features that are incrementally scalable. This platform technology facilitates arrays of >10,000 tissue features on a standard glass slide, inclusion of unique sample identifiers for improved manual or automated tracking, and oriented arraying of stratified or polarized samples.

  18. Complementary Metal-Oxide-Silicon (CMOS)-Memristor Hybrid Nanoelectronics for Advanced Encryption Standard (AES) Encryption

    DTIC Science & Technology

    2016-04-01

    reliability were developed and integrated with CMOS circuitry to establish an efficient hybrid nanoelectronic computing module for Advanced...node integrated with the memristors without leaving the CMOS foundry setting. 15. SUBJECT TERMS nanoelectronics, CMOS, memristor, crossbar 16...Table of Contents 1. SUMMARY ..................................................................................................................... 1 2

  19. Metadata management and semantics in microarray repositories.

    PubMed

    Kocabaş, F; Can, T; Baykal, N

    2011-12-01

    The number of microarray and other high-throughput experiments on primary repositories keeps increasing as do the size and complexity of the results in response to biomedical investigations. Initiatives have been started on standardization of content, object model, exchange format and ontology. However, there are backlogs and inability to exchange data between microarray repositories, which indicate that there is a great need for a standard format and data management. We have introduced a metadata framework that includes a metadata card and semantic nets that make experimental results visible, understandable and usable. These are encoded in syntax encoding schemes and represented in RDF (Resource Description Frame-word), can be integrated with other metadata cards and semantic nets, and can be exchanged, shared and queried. We demonstrated the performance and potential benefits through a case study on a selected microarray repository. We concluded that the backlogs can be reduced and that exchange of information and asking of knowledge discovery questions can become possible with the use of this metadata framework.

  20. Methods for fabricating microarrays of motile bacteria.

    PubMed

    Rozhok, Sergey; Shen, Clifton K-F; Littler, Pey-Lih H; Fan, Zhifang; Liu, Chang; Mirkin, Chad A; Holz, Richard C

    2005-04-01

    Motile bacterial cell microarrays were fabricated by attaching Escherichia coli K-12 cells onto predesigned 16-mercaptohexadecanoic acid patterned microarrays, which were covalently functionalized with E. coli antibodies or poly-L-lysine. By utilizing 11-mercaptoundecyl-penta(ethylene glycol) or 11-mercapto-1-undecanol as passivating molecules, nonspecific binding of E. coli was significantly reduced. Microcontact printing and dip-pen nanolithography were used to prepare microarrays for bacterial adhesion, which was studied by optical fluorescence and atomic force microscopy. These data indicate that single motile E. coli can be attached to predesigned line or dot features and binding can occur via the cell body or the flagella of bacteria. Adherent bacteria are viable (remain alive and motile after adhesion to patterned surface features) for more than four hours. Individual motile bacterial cells can be placed onto predesigned surface features that are at least 1.3 microm in diameter or larger. The importance of controlling the adhesion of single bacterial cell to a surface is discussed with regard to biomotor design.

  1. A New Distribution Family for Microarray Data.

    PubMed

    Kelmansky, Diana Mabel; Ricci, Lila

    2017-02-10

    The traditional approach with microarray data has been to apply transformations that approximately normalize them, with the drawback of losing the original scale. The alternative stand point taken here is to search for models that fit the data, characterized by the presence of negative values, preserving their scale; one advantage of this strategy is that it facilitates a direct interpretation of the results. A new family of distributions named gpower-normal indexed by p∈R is introduced and it is proven that these variables become normal or truncated normal when a suitable gpower transformation is applied. Expressions are given for moments and quantiles, in terms of the truncated normal density. This new family can be used to model asymmetric data that include non-positive values, as required for microarray analysis. Moreover, it has been proven that the gpower-normal family is a special case of pseudo-dispersion models, inheriting all the good properties of these models, such as asymptotic normality for small variances. A combined maximum likelihood method is proposed to estimate the model parameters, and it is applied to microarray and contamination data. Rcodes are available from the authors upon request.

  2. High-Throughput Enzyme Kinetics Using Microarrays

    SciTech Connect

    Guoxin Lu; Edward S. Yeung

    2007-11-01

    We report a microanalytical method to study enzyme kinetics. The technique involves immobilizing horseradish peroxidase on a poly-L-lysine (PLL)- coated glass slide in a microarray format, followed by applying substrate solution onto the enzyme microarray. Enzyme molecules are immobilized on the PLL-coated glass slide through electrostatic interactions, and no further modification of the enzyme or glass slide is needed. In situ detection of the products generated on the enzyme spots is made possible by monitoring the light intensity of each spot using a scientific-grade charged-coupled device (CCD). Reactions of substrate solutions of various types and concentrations can be carried out sequentially on one enzyme microarray. To account for the loss of enzyme from washing in between runs, a standard substrate solution is used for calibration. Substantially reduced amounts of substrate solution are consumed for each reaction on each enzyme spot. The Michaelis constant K{sub m} obtained by using this method is comparable to the result for homogeneous solutions. Absorbance detection allows universal monitoring, and no chemical modification of the substrate is needed. High-throughput studies of native enzyme kinetics for multiple enzymes are therefore possible in a simple, rapid, and low-cost manner.

  3. Reduction of CMOS Image Sensor Read Noise to Enable Photon Counting

    PubMed Central

    Guidash, Michael; Ma, Jiaju; Vogelsang, Thomas; Endsley, Jay

    2016-01-01

    Recent activity in photon counting CMOS image sensors (CIS) has been directed to reduction of read noise. Many approaches and methods have been reported. This work is focused on providing sub 1 e− read noise by design and operation of the binary and small signal readout of photon counting CIS. Compensation of transfer gate feed-through was used to provide substantially reduced CDS time and source follower (SF) bandwidth. SF read noise was reduced by a factor of 3 with this method. This method can be applied broadly to CIS devices to reduce the read noise for small signals to enable use as a photon counting sensor. PMID:27070625

  4. Reduction of CMOS Image Sensor Read Noise to Enable Photon Counting.

    PubMed

    Guidash, Michael; Ma, Jiaju; Vogelsang, Thomas; Endsley, Jay

    2016-04-09

    Recent activity in photon counting CMOS image sensors (CIS) has been directed to reduction of read noise. Many approaches and methods have been reported. This work is focused on providing sub 1 e(-) read noise by design and operation of the binary and small signal readout of photon counting CIS. Compensation of transfer gate feed-through was used to provide substantially reduced CDS time and source follower (SF) bandwidth. SF read noise was reduced by a factor of 3 with this method. This method can be applied broadly to CIS devices to reduce the read noise for small signals to enable use as a photon counting sensor.

  5. Spectrometer with CMOS demodulation of fiber optic Bragg grating sensors

    NASA Astrophysics Data System (ADS)

    Christiansen, Martin Brokner

    A CMOS imager based spectrometer is developed to interrogate a network containing a large number of Bragg grating sensors. The spectrometer uses a Prism-Grating- Prism (PGP) to spectrally separate serially multiplexed Bragg reflections on a single fiber. As a result, each Bragg grating produces a discrete spot on the CMOS imager that shifts horizontally as the Bragg grating experiences changes in strain or temperature. The reflected wavelength of the spot can be determined by finding the center of the spot produced. The use of a randomly addressable CMOS imager enables a flexible sampling rate. Some fibers can be interrogated at a high sampling rate while others can be interrogated at a low sampling rate. However, the use of a CMOS imager leads to several unique problems in terms of signal processing. These include a logarithmic pixel response, a low signal-to-noise ratio, a long pixel time constant, and software issues. The expected capabilities of the CMOS imager based spectrometer are determined with a theoretical model. The theoretical model tests three algorithms for determining the center of the spot: single row centroid, single row parabolic fit, and entire spot centroid. The theoretical results are compared to laboratory test data and field test data. The CMOS based spectrometer is capable of interrogating many optical fibers, and in the configuration tested, the fiber bundle consisted of 23 fibers. Using this system, a single fiber can be interrogated from 778 nm to 852 nm at 2100 Hz or multiple fibers can be interrogated over the same wavelength so that the total number of fiber interrogations is up to 2100 per second. The reflected Bragg wavelength can be determined within +/-3pm, corresponding to a +/-3μɛ uncertainty.

  6. Fluorescent glycosylamides produced by microscale derivatization of free glycans for natural glycan microarrays.

    PubMed

    Song, Xuezheng; Lasanajak, Yi; Xia, Baoyun; Smith, David F; Cummings, Richard D

    2009-09-18

    A novel strategy for creating naturally derived glycan microarrays has been developed. Glycosylamines are prepared from free reducing glycans and stabilized by reaction with acryloyl chloride to generate a glycosylamide in which the reducing monosaccharide has a closed-ring structure. Ozonolysis of the protected glycan yields an active aldehyde, to which a bifunctional fluorescent linker is coupled by reductive amination. The fluorescent derivatives are easily coupled through a residual primary alkylamine to generate glycan microarrays. This strategy preserves structural features of glycans required for antibody recognition and allows development of natural arrays of fluorescent glycans in which the cyclic pyranose structure of the reducing-end sugar residue is retained.

  7. Fluorescent Glycosylamides Produced by Microscale Derivatization of Free Glycans for Natural Glycan Microarrays

    PubMed Central

    Song, Xuezheng; Lasanajak, Yi; Xia, Baoyun; Smith, David F.; Cummings, Richard D.

    2009-01-01

    A novel strategy for creating naturally-derived glycan microarrays has been developed. Glycosylamines are prepared from free reducing glycans and stabilized by reaction with acryloyl chloride to generate a glycosylamide in which the reducing monosaccharide has a closed ring structure. Ozonolysis of the protected glycan yields an active aldehyde, to which a bifunctional fluorescent linker is coupled by reductive amination. The fluorescent derivatives are easily coupled through a residual primary alkylamine to generate glycan microarrays. This strategy preserves structural features of glycans required for antibody recognition, and allows development of natural arrays of fluorescent glycans in which the cyclic pyranose structure of the reducing-end sugar residue is retained. PMID:19618966

  8. Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus

    NASA Astrophysics Data System (ADS)

    Lee, Jung-Rok; Haddon, D. James; Wand, Hannah E.; Price, Jordan V.; Diep, Vivian K.; Hall, Drew A.; Petri, Michelle; Baechler, Emily C.; Balboni, Imelda M.; Utz, Paul J.; Wang, Shan X.

    2016-06-01

    High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides. We used the microarrays to analyze serum samples from SLE patients and found individuals with high chemokine scores had significantly greater reactivity to 13 autoantigens than individuals with low chemokine scores. Our findings demonstrate that multiple autoantibodies, including antibodies to U1-70K and modified histone H2B tails, are associated with IFN dysregulation in SLE. Further, they show the microarrays are capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice.

  9. Protein-Protein Interaction Inhibitors of BRCA1 Discovered Using Small Molecule Microarrays.

    PubMed

    Na, Zhenkun; Pan, Sijun; Uttamchandani, Mahesh; Yao, Shao Q

    2017-01-01

    Microarray screening technology has transformed the life sciences arena over the last decade. The platform is widely used in the area of mapping interaction networks, to molecular fingerprinting and small molecular inhibitor discovery. The technique has significantly impacted both basic and applied research. The microarray platform can likewise enable high-throughput screening and discovery of protein-protein interaction (PPI) inhibitors. Herein we demonstrate the application of microarray-guided PPI inhibitor discovery, using human BRCA1 as an example. Mutations in BRCA1 have been implicated in ~50 % of hereditary breast cancers. By targeting the (BRCT)2 domain, we showed compound 15a and its prodrug 15b inhibited BRCA1 activities in tumor cells. Unlike previously reported peptide-based PPI inhibitors of BRCA1, the compounds identified could be directly administered to tumor cells, thus making them useful in targeting BRCA1/PARP-related pathways involved in DNA damage and repair response, for cancer therapy.

  10. ADIBO-based "click" chemistry for diagnostic peptide micro-array fabrication: physicochemical and assay characteristics.

    PubMed

    Prim, Denis; Rebeaud, Fabien; Cosandey, Vincent; Marti, Roger; Passeraub, Philippe; Pfeifer, Marc E

    2013-08-16

    Several azide-derivatized and fluorescently-labeled peptides were immobilized on azadibenzocyclooctyne (ADIBO)-activated slide surfaces via a strain-promoted alkyne-azide cycloaddition (SPAAC) reaction revealing excellent immobilization kinetics, good spot homogeneities and reproducible fluorescence signal intensities. A myc-peptide micro-array immunoassay showed an antibody limit-of-detection (LOD) superior to a microtiter plate-based ELISA. Bovine serum albumin (BSA) and dextran covalently attached via "click" chemistry more efficiently reduced non-specific binding (NSB) of fluorescently-labeled IgG to the microarray surface in comparison to immobilized hexanoic acid and various types of polyethylene glycol (PEG) derivatives. Confirmation of these findings via further studies with other proteins and serum components could open up new possibilities for human sample and microarray platform-based molecular diagnostic tests.

  11. Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus

    PubMed Central

    Lee, Jung-Rok; Haddon, D. James; Wand, Hannah E.; Price, Jordan V.; Diep, Vivian K.; Hall, Drew A.; Petri, Michelle; Baechler, Emily C.; Balboni, Imelda M.; Utz, Paul J.; Wang, Shan X.

    2016-01-01

    High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides. We used the microarrays to analyze serum samples from SLE patients and found individuals with high chemokine scores had significantly greater reactivity to 13 autoantigens than individuals with low chemokine scores. Our findings demonstrate that multiple autoantibodies, including antibodies to U1-70K and modified histone H2B tails, are associated with IFN dysregulation in SLE. Further, they show the microarrays are capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice. PMID:27279139

  12. The Potentials and Pitfalls of Microarrays in Neglected Tropical Diseases: A Focus on Human Filarial Infections

    PubMed Central

    Kwarteng, Alexander; Ahuno, Samuel Terkper

    2016-01-01

    Data obtained from expression microarrays enables deeper understanding of the molecular signatures of infectious diseases. It provides rapid and accurate information on how infections affect the clustering of gene expression profiles, pathways and networks that are transcriptionally active during various infection states compared to conventional diagnostic methods, which primarily focus on single genes or proteins. Thus, microarray technologies offer advantages in understanding host-parasite interactions associated with filarial infections. More importantly, the use of these technologies can aid diagnostics and helps translate current genomic research into effective treatment and interventions for filarial infections. Studying immune responses via microarray following infection can yield insight into genetic pathways and networks that can have a profound influence on the development of anti-parasitic vaccines. PMID:27600086

  13. CMOS-compatible photonic devices for single-photon generation

    NASA Astrophysics Data System (ADS)

    Xiong, Chunle; Bell, Bryn; Eggleton, Benjamin J.

    2016-09-01

    Sources of single photons are one of the key building blocks for quantum photonic technologies such as quantum secure communication and powerful quantum computing. To bring the proof-of-principle demonstration of these technologies from the laboratory to the real world, complementary metal-oxide-semiconductor (CMOS)-compatible photonic chips are highly desirable for photon generation, manipulation, processing and even detection because of their compactness, scalability, robustness, and the potential for integration with electronics. In this paper, we review the development of photonic devices made from materials (e.g., silicon) and processes that are compatible with CMOS fabrication facilities for the generation of single photons.

  14. Statistical circuit design for yield improvement in CMOS circuits

    NASA Technical Reports Server (NTRS)

    Kamath, H. J.; Purviance, J. E.; Whitaker, S. R.

    1990-01-01

    This paper addresses the statistical design of CMOS integrated circuits for improved parametric yield. The work uses the Monte Carlo technique of circuit simulation to obtain an unbiased estimation of the yield. A simple graphical analysis tool, the yield factor histogram, is presented. The yield factor histograms are generated by a new computer program called SPICENTER. Using the yield factor histograms, the most sensitive circuit parameters are noted, and their nominal values are changed to improve the yield. Two basic CMOS example circuits, one analog and one digital, are chosen and their designs are 'centered' to illustrate the use of the yield factor histograms for statistical circuit design.

  15. Black silicon enhanced photodetectors: a path to IR CMOS

    NASA Astrophysics Data System (ADS)

    Pralle, M. U.; Carey, J. E.; Homayoon, H.; Alie, S.; Sickler, J.; Li, X.; Jiang, J.; Miller, D.; Palsule, C.; McKee, J.

    2010-04-01

    SiOnyx has developed a novel silicon processing technology for CMOS sensors that will extend spectral sensitivity into the near/shortwave infrared (NIR/SWIR) and enable a full performance digital night vision capability comparable to that of current image-intensifier based night vision goggles. The process is compatible with established CMOS manufacturing infrastructure and has the promise of much lower cost than competing approaches. The measured thin layer quantum efficiency is as much as 10x that of incumbent imaging sensors with spectral sensitivity from 400 to 1200 nm.

  16. IR CMOS: ultrafast laser-enhanced silicon detection

    NASA Astrophysics Data System (ADS)

    Pralle, M. U.; Carey, J. E.; Homayoon, H.; Sickler, J.; Li, X.; Jiang, J.; Miller, D.; Palsule, C.; McKee, J.

    2011-06-01

    SiOnyx has developed a novel silicon processing technology for CMOS sensors that will extend spectral sensitivity into the near/shortwave infrared (NIR/SWIR) and enable a full performance digital night vision capability comparable to that of current image-intensifier based night vision goggles. The process is compatible with established CMOS manufacturing infrastructure and has the promise of much lower cost than competing approaches. The measured thin layer quantum efficiency is as much as 10x that of incumbent imaging sensors with spectral sensitivity from 400 to 1200 nm.

  17. A Force-Detection NMR Sensor in CMOS-MEMS

    DTIC Science & Technology

    2003-01-01

    Lauterbur. “Design and Analysis of Microcoils for NMR Microscopy.” Journal of Magnetic Resonance B, Vol. 108, pp. 114-124. 1995. 59 [29] Protasis...A Force-Detection NMR Sensor in CMOS-MEMS by Kevin M. Frederick Bachelor of Science, 2001 Carnegie Mellon University, Pittsburgh...REPORT TYPE 3. DATES COVERED 00-00-2003 to 00-00-2003 4. TITLE AND SUBTITLE A Force-Detection NMR Sensor in CMOS-MEMS 5a. CONTRACT NUMBER 5b

  18. DNA Microarray for Detection of Gastrointestinal Viruses

    PubMed Central

    Martínez, Miguel A.; Soto-del Río, María de los Dolores; Gutiérrez, Rosa María; Chiu, Charles Y.; Greninger, Alexander L.; Contreras, Juan Francisco; López, Susana; Arias, Carlos F.

    2014-01-01

    Gastroenteritis is a clinical illness of humans and other animals that is characterized by vomiting and diarrhea and caused by a variety of pathogens, including viruses. An increasing number of viral species have been associated with gastroenteritis or have been found in stool samples as new molecular tools have been developed. In this work, a DNA microarray capable in theory of parallel detection of more than 100 viral species was developed and tested. Initial validation was done with 10 different virus species, and an additional 5 species were validated using clinical samples. Detection limits of 1 × 103 virus particles of Human adenovirus C (HAdV), Human astrovirus (HAstV), and group A Rotavirus (RV-A) were established. Furthermore, when exogenous RNA was added, the limit for RV-A detection decreased by one log. In a small group of clinical samples from children with gastroenteritis (n = 76), the microarray detected at least one viral species in 92% of the samples. Single infection was identified in 63 samples (83%), and coinfection with more than one virus was identified in 7 samples (9%). The most abundant virus species were RV-A (58%), followed by Anellovirus (15.8%), HAstV (6.6%), HAdV (5.3%), Norwalk virus (6.6%), Human enterovirus (HEV) (9.2%), Human parechovirus (1.3%), Sapporo virus (1.3%), and Human bocavirus (1.3%). To further test the specificity and sensitivity of the microarray, the results were verified by reverse transcription-PCR (RT-PCR) detection of 5 gastrointestinal viruses. The RT-PCR assay detected a virus in 59 samples (78%). The microarray showed good performance for detection of RV-A, HAstV, and calicivirus, while the sensitivity for HAdV and HEV was low. Furthermore, some discrepancies in detection of mixed infections were observed and were addressed by reverse transcription-quantitative PCR (RT-qPCR) of the viruses involved. It was observed that differences in the amount of genetic material favored the detection of the most abundant

  19. DNA microarray for detection of gastrointestinal viruses.

    PubMed

    Martínez, Miguel A; Soto-Del Río, María de Los Dolores; Gutiérrez, Rosa María; Chiu, Charles Y; Greninger, Alexander L; Contreras, Juan Francisco; López, Susana; Arias, Carlos F; Isa, Pavel

    2015-01-01

    Gastroenteritis is a clinical illness of humans and other animals that is characterized by vomiting and diarrhea and caused by a variety of pathogens, including viruses. An increasing number of viral species have been associated with gastroenteritis or have been found in stool samples as new molecular tools have been developed. In this work, a DNA microarray capable in theory of parallel detection of more than 100 viral species was developed and tested. Initial validation was done with 10 different virus species, and an additional 5 species were validated using clinical samples. Detection limits of 1 × 10(3) virus particles of Human adenovirus C (HAdV), Human astrovirus (HAstV), and group A Rotavirus (RV-A) were established. Furthermore, when exogenous RNA was added, the limit for RV-A detection decreased by one log. In a small group of clinical samples from children with gastroenteritis (n = 76), the microarray detected at least one viral species in 92% of the samples. Single infection was identified in 63 samples (83%), and coinfection with more than one virus was identified in 7 samples (9%). The most abundant virus species were RV-A (58%), followed by Anellovirus (15.8%), HAstV (6.6%), HAdV (5.3%), Norwalk virus (6.6%), Human enterovirus (HEV) (9.2%), Human parechovirus (1.3%), Sapporo virus (1.3%), and Human bocavirus (1.3%). To further test the specificity and sensitivity of the microarray, the results were verified by reverse transcription-PCR (RT-PCR) detection of 5 gastrointestinal viruses. The RT-PCR assay detected a virus in 59 samples (78%). The microarray showed good performance for detection of RV-A, HAstV, and calicivirus, while the sensitivity for HAdV and HEV was low. Furthermore, some discrepancies in detection of mixed infections were observed and were addressed by reverse transcription-quantitative PCR (RT-qPCR) of the viruses involved. It was observed that differences in the amount of genetic material favored the detection of the most abundant

  20. DNA Microarray Data Analysis: A Novel Biclustering Algorithm Approach

    NASA Astrophysics Data System (ADS)

    Tchagang, Alain B.; Tewfik, Ahmed H.

    2006-12-01

    Biclustering algorithms refer to a distinct class of clustering algorithms that perform simultaneous row-column clustering. Biclustering problems arise in DNA microarray data analysis, collaborative filtering, market research, information retrieval, text mining, electoral trends, exchange analysis, and so forth. When dealing with DNA microarray experimental data for example, the goal of biclustering algorithms is to find submatrices, that is, subgroups of genes and subgroups of conditions, where the genes exhibit highly correlated activities for every condition. In this study, we develop novel biclustering algorithms using basic linear algebra and arithmetic tools. The proposed biclustering algorithms can be used to search for all biclusters with constant values, biclusters with constant values on rows, biclusters with constant values on columns, and biclusters with coherent values from a set of data in a timely manner and without solving any optimization problem. We also show how one of the proposed biclustering algorithms can be adapted to identify biclusters with coherent evolution. The algorithms developed in this study discover all valid biclusters of each type, while almost all previous biclustering approaches will miss some.

  1. A microarray for assessing transcription from pelagic marine microbial taxa

    PubMed Central

    Shilova, Irina N; Robidart, Julie C; James Tripp, H; Turk-Kubo, Kendra; Wawrik, Boris; Post, Anton F; Thompson, Anne W; Ward, Bess; Hollibaugh, James T; Millard, Andy; Ostrowski, Martin; J Scanlan, David; Paerl, Ryan W; Stuart, Rhona; Zehr, Jonathan P

    2014-01-01

    Metagenomic approaches have revealed unprecedented genetic diversity within microbial communities across vast expanses of the world's oceans. Linking this genetic diversity with key metabolic and cellular activities of microbial assemblages is a fundamental challenge. Here we report on a collaborative effort to design MicroTOOLs (Microbiological Targets for Ocean Observing Laboratories), a high-density oligonucleotide microarray that targets functional genes of diverse taxa in pelagic and coastal marine microbial communities. MicroTOOLs integrates nucleotide sequence information from disparate data types: genomes, PCR-amplicons, metagenomes, and metatranscriptomes. It targets 19 400 unique sequences over 145 different genes that are relevant to stress responses and microbial metabolism across the three domains of life and viruses. MicroTOOLs was used in a proof-of-concept experiment that compared the functional responses of microbial communities following Fe and P enrichments of surface water samples from the North Pacific Subtropical Gyre. We detected transcription of 68% of the gene targets across major taxonomic groups, and the pattern of transcription indicated relief from Fe limitation and transition to N limitation in some taxa. Prochlorococcus (eHLI), Synechococcus (sub-cluster 5.3) and Alphaproteobacteria SAR11 clade (HIMB59) showed the strongest responses to the Fe enrichment. In addition, members of uncharacterized lineages also responded. The MicroTOOLs microarray provides a robust tool for comprehensive characterization of major functional groups of microbes in the open ocean, and the design can be easily amended for specific environments and research questions. PMID:24477198

  2. Developments and Applications of High-Performance CCD and CMOS Imaging Arrays

    NASA Astrophysics Data System (ADS)

    Janesick, James; Putnam, Gloria

    2003-12-01

    For over 20 years, charge-coupled devices (CCDs) have dominated most digital imaging applications and markets. Today, complementary metal oxide semiconductor (CMOS) arrays are displacing CCDs in some applications, and this trend is expected to continue. Low cost, low power, on-chip system integration, and high-speed operation are unique features that have generated interest in CMOS arrays. This paper reviews current CCD and CMOS sensor developments and related applications. We compare fundamental performance parameters common to these technologies and describe why the CCD is considered a mature technology, whereas CMOS arrays have significant room for growth. The paper presents custom CMOS pixel designs and related fabrication processes that address performance deficiencies of the CCD in high-performance applications. We discuss areas of development for future CCD and CMOS imagers. The paper also briefly reviews hybrid imaging arrays that combine the advantages of CCD and CMOS, producing better sensors than either technology alone can provide.

  3. Fabrication and characterization of CMOS-MEMS thermoelectric micro generators.

    PubMed

    Kao, Pin-Hsu; Shih, Po-Jen; Dai, Ching-Liang; Liu, Mao-Chen

    2010-01-01

    This work presents a thermoelectric micro generator fabricated by the commercial 0.35 μm complementary metal oxide semiconductor (CMOS) process and the post-CMOS process. The micro generator is composed of 24 thermocouples in series. Each thermocouple is constructed by p-type and n-type polysilicon strips. The output power of the generator depends on the temperature difference between the hot and cold parts in the thermocouples. In order to prevent heat-receiving in the cold part in the thermocouples, the cold part is covered with a silicon dioxide layer with low thermal conductivity to insulate the heat source. The hot part of the thermocouples is suspended and connected to an aluminum plate, to increases the heat-receiving area in the hot part. The generator requires a post-CMOS process to release the suspended structures. The post-CMOS process uses an anisotropic dry etching to remove the oxide sacrificial layer and an isotropic dry etching to etch the silicon substrate. Experimental results show that the micro generator has an output voltage of 67 μV at the temperature difference of 1 K.

  4. Single Event Upset Behavior of CMOS Static RAM Cells

    NASA Technical Reports Server (NTRS)

    Lieneweg, Udo; Jeppson, Kjell O.; Buehler, Martin G.

    1993-01-01

    An improved state-space analysis of the CMOS static RAM cell is presented. Introducing theconcept of the dividing line, the critical charge for heavy-ion-induced upset of memory cells can becalculated considering symmetrical as well as asymmetrical capacitive loads. From the criticalcharge, the upset-rate per bit-day for static RAMs can be estimated.

  5. Mechanically Flexible and High-Performance CMOS Logic Circuits

    PubMed Central

    Honda, Wataru; Arie, Takayuki; Akita, Seiji; Takei, Kuniharu

    2015-01-01

    Low-power flexible logic circuits are key components required by the next generation of flexible electronic devices. For stable device operation, such components require a high degree of mechanical flexibility and reliability. Here, the mechanical properties of low-power flexible complementary metal–oxide–semiconductor (CMOS) logic circuits including inverter, NAND, and NOR are investigated. To fabricate CMOS circuits on flexible polyimide substrates, carbon nanotube (CNT) network films are used for p-type transistors, whereas amorphous InGaZnO films are used for the n-type transistors. The power consumption and voltage gain of CMOS inverters are <500 pW/mm at Vin = 0 V (<7.5 nW/mm at Vin = 5 V) and >45, respectively. Importantly, bending of the substrate is not found to cause significant changes in the device characteristics. This is also observed to be the case for more complex flexible NAND and NOR logic circuits for bending states with a curvature radius of 2.6 mm. The mechanical stability of these CMOS logic circuits makes them ideal candidates for use in flexible integrated devices. PMID:26459882

  6. High speed CMOS/SOS standard cell notebook

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The NASA/MSFC high speed CMOS/SOS standard cell family, designed to be compatible with the PR2D (Place, Route in 2-Dimensions) automatic layout program, is described. Standard cell data sheets show the logic diagram, the schematic, the truth table, and propagation delays for each logic cell.

  7. Fundamental Problems of Hybrid CMOS/Nanodevice Circuits

    DTIC Science & Technology

    2010-12-14

    allowing individual access to each via from the peripheral contact pads . Such layout is sufficient for a broad range of experiments with CMOS...mechanical polishing ( CMP ). For that, we have modified a commercial, 2- inch CMP tool for individual chip processing. Inspection and testing of the polished

  8. Novel Ferroelectric CMOS Circuits as a Nonvolatile Logic

    NASA Astrophysics Data System (ADS)

    Takahashi, M.; Horiuchi, T.; Li, Q.-H.; Wang, S.; Yun, K. Y.; Sakai, S.

    2008-03-01

    We propose a novel and promising nonvolatile-logic circuit constructed by p channel type (Pch) and n channel type (Nch) ferroelectric gate field effect transistors (FeFETs), which we named a ferroelectric CMOS (FeCMOS) circuit. The circuit works as both logic and memory. We fabricated a NOT logic FeCMOS device which have Pt metal gates and gate oxides of ferroelectric SrBi2Ta2O9 (SBT) and high-k HfAlO on Si. Key technology was adjusting threshold voltages of the FeFETs as well as preparing those of high quality. We demonstrate basic operations of the NOT-logic response, memory writing, holding and non-destructive reading. The memory writing is done by amplifying the input node voltage to a higher level when the node was logically high and to a lower one when it was logically low just before the writing operation. The data retention was also measured. The retained high and low voltages were almost unchanged for 1.2 days. The idea of this FeCMOS will enhance flexibility of circuit designing by merging logic and memory functions. This work was partially supported by NEDO.

  9. Holographic voltage profiling on 75 nm gate architecture CMOS devices.

    PubMed

    Thesen, Alexander E; Frost, Bernhard G; Joy, David C

    2003-04-01

    Voltage profiles of the source-drain region of a CMOS transistor with 75nm gate architecture taken from an off-the-shelf Intel PIII processor are presented. The sample preparation using a dual beam system is discussed as well as details of the electron optical setup of the microscope. Special attention is given to the analysis of the reconstructed holograms.

  10. Effects Of Dose Rates On Radiation Damage In CMOS Parts

    NASA Technical Reports Server (NTRS)

    Goben, Charles A.; Coss, James R.; Price, William E.

    1990-01-01

    Report describes measurements of effects of ionizing-radiation dose rate on consequent damage to complementary metal oxide/semiconductor (CMOS) electronic devices. Depending on irradiation time and degree of annealing, survivability of devices in outer space, or after explosion of nuclear weapons, enhanced. Annealing involving recovery beyond pre-irradiation conditions (rebound) detrimental. Damage more severe at lower dose rates.

  11. Simulation toolkit with CMOS detector in the framework of hadrontherapy

    NASA Astrophysics Data System (ADS)

    Rescigno, R.; Finck, Ch.; Juliani, D.; Baudot, J.; Dauvergne, D.; Dedes, G.; Krimmer, J.; Ray, C.; Reithinger, V.; Rousseau, M.; Testa, E.; Winter, M.

    2014-03-01

    Proton imaging can be seen as a powerful technique for on-line monitoring of ion range during carbon ion therapy irradiation. The protons detection technique uses, as three-dimensional tracking system, a set of CMOS sensor planes. A simulation toolkit based on GEANT4 and ROOT is presented including detector response and reconstruction algorithm.

  12. CMOS VLSI Layout and Verification of a SIMD Computer

    NASA Technical Reports Server (NTRS)

    Zheng, Jianqing

    1996-01-01

    A CMOS VLSI layout and verification of a 3 x 3 processor parallel computer has been completed. The layout was done using the MAGIC tool and the verification using HSPICE. Suggestions for expanding the computer into a million processor network are presented. Many problems that might be encountered when implementing a massively parallel computer are discussed.

  13. Detection and compensation of bad pixel for CMOS image sensor

    NASA Astrophysics Data System (ADS)

    Xu, Youqing; Yu, Shengsheng; Zhou, Jingli; Fang, Zuyuan

    2000-05-01

    This paper presents a detailed analysis of the occurring reason and features of bad pixels in CMOS image sensor. Detect and compensate algorithms have also bee introduced. Experimental result show that the algorithms are efficiently when they are applied on CH5001 produced by Chrontel Inc.

  14. Research-grade CMOS image sensors for remote sensing applications

    NASA Astrophysics Data System (ADS)

    Saint-Pe, Olivier; Tulet, Michel; Davancens, Robert; Larnaudie, Franck; Magnan, Pierre; Martin-Gonthier, Philippe; Corbiere, Franck; Belliot, Pierre; Estribeau, Magali

    2004-11-01

    Imaging detectors are key elements for optical instruments and sensors on board space missions dedicated to Earth observation (high resolution imaging, atmosphere spectroscopy...), Solar System exploration (micro cameras, guidance for autonomous vehicle...) and Universe observation (space telescope focal planes, guiding sensors...). This market has been dominated by CCD technology for long. Since the mid-90s, CMOS Image Sensors (CIS) have been competing with CCDs for consumer domains (webcams, cell phones, digital cameras...). Featuring significant advantages over CCD sensors for space applications (lower power consumption, smaller system size, better radiations behaviour...), CMOS technology is also expanding in this field, justifying specific R&D and development programs funded by national and European space agencies (mainly CNES, DGA and ESA). All along the 90s and thanks to their increasingly improving performances, CIS have started to be successfully used for more and more demanding space applications, from vision and control functions requiring low-level performances to guidance applications requiring medium-level performances. Recent technology improvements have made possible the manufacturing of research-grade CIS that are able to compete with CCDs in the high-performances arena. After an introduction outlining the growing interest of optical instruments designers for CMOS image sensors, this paper will present the existing and foreseen ways to reach high-level electro-optics performances for CIS. The developments and performances of CIS prototypes built using an imaging CMOS process will be presented in the corresponding section.

  15. Research-grade CMOS image sensors for demanding space applications

    NASA Astrophysics Data System (ADS)

    Saint-Pé, Olivier; Tulet, Michel; Davancens, Robert; Larnaudie, Franck; Magnan, Pierre; Corbière, Franck; Martin-Gonthier, Philippe; Belliot, Pierre

    2004-06-01

    Imaging detectors are key elements for optical instruments and sensors on board space missions dedicated to Earth observation (high resolution imaging, atmosphere spectroscopy...), Solar System exploration (micro cameras, guidance for autonomous vehicle...) and Universe observation (space telescope focal planes, guiding sensors...). This market has been dominated by CCD technology for long. Since the mid-90s, CMOS Image Sensors (CIS) have been competing with CCDs for more and more consumer domains (webcams, cell phones, digital cameras...). Featuring significant advantages over CCD sensors for space applications (lower power consumption, smaller system size, better radiations behaviour...), CMOS technology is also expanding in this field, justifying specific R&D and development programs funded by national and European space agencies (mainly CNES, DGA, and ESA). All along the 90s and thanks to their increasingly improving performances, CIS have started to be successfully used for more and more demanding applications, from vision and control functions requiring low-level performances to guidance applications requiring medium-level performances. Recent technology improvements have made possible the manufacturing of research-grade CIS that are able to compete with CCDs in the high-performances arena. After an introduction outlining the growing interest of optical instruments designers for CMOS image sensors, this talk will present the existing and foreseen ways to reach high-level electro-optics performances for CIS. The developments of CIS prototypes built using an imaging CMOS process and of devices based on improved designs will be presented.

  16. CMOS Ultra Low Power Radiation Tolerant (CULPRiT) Microelectronics

    NASA Technical Reports Server (NTRS)

    Yeh, Penshu; Maki, Gary

    2007-01-01

    Space Electronics needs Radiation Tolerance or hardness to withstand the harsh space environment: high-energy particles can change the state of the electronics or puncture transistors making them disfunctional. This viewgraph document reviews the use of CMOS Ultra Low Power Radiation Tolerant circuits for NASA's electronic requirements.

  17. Mechanically Flexible and High-Performance CMOS Logic Circuits.

    PubMed

    Honda, Wataru; Arie, Takayuki; Akita, Seiji; Takei, Kuniharu

    2015-10-13

    Low-power flexible logic circuits are key components required by the next generation of flexible electronic devices. For stable device operation, such components require a high degree of mechanical flexibility and reliability. Here, the mechanical properties of low-power flexible complementary metal-oxide-semiconductor (CMOS) logic circuits including inverter, NAND, and NOR are investigated. To fabricate CMOS circuits on flexible polyimide substrates, carbon nanotube (CNT) network films are used for p-type transistors, whereas amorphous InGaZnO films are used for the n-type transistors. The power consumption and voltage gain of CMOS inverters are <500 pW/mm at Vin = 0 V (<7.5 nW/mm at Vin = 5 V) and >45, respectively. Importantly, bending of the substrate is not found to cause significant changes in the device characteristics. This is also observed to be the case for more complex flexible NAND and NOR logic circuits for bending states with a curvature radius of 2.6 mm. The mechanical stability of these CMOS logic circuits makes them ideal candidates for use in flexible integrated devices.

  18. CMOS image sensors as an efficient platform for glucose monitoring.

    PubMed

    Devadhasan, Jasmine Pramila; Kim, Sanghyo; Choi, Cheol Soo

    2013-10-07

    Complementary metal oxide semiconductor (CMOS) image sensors have been used previously in the analysis of biological samples. In the present study, a CMOS image sensor was used to monitor the concentration of oxidized mouse plasma glucose (86-322 mg dL(-1)) based on photon count variation. Measurement of the concentration of oxidized glucose was dependent on changes in color intensity; color intensity increased with increasing glucose concentration. The high color density of glucose highly prevented photons from passing through the polydimethylsiloxane (PDMS) chip, which suggests that the photon count was altered by color intensity. Photons were detected by a photodiode in the CMOS image sensor and converted to digital numbers by an analog to digital converter (ADC). Additionally, UV-spectral analysis and time-dependent photon analysis proved the efficiency of the detection system. This simple, effective, and consistent method for glucose measurement shows that CMOS image sensors are efficient devices for monitoring glucose in point-of-care applications.

  19. CMOS Image Sensor and System for Imaging Hemodynamic Changes in Response to Deep Brain Stimulation.

    PubMed

    Zhang, Xiao; Noor, Muhammad S; McCracken, Clinton B; Kiss, Zelma H T; Yadid-Pecht, Orly; Murari, Kartikeya

    2016-06-01

    Deep brain stimulation (DBS) is a therapeutic intervention used for a variety of neurological and psychiatric disorders, but its mechanism of action is not well understood. It is known that DBS modulates neural activity which changes metabolic demands and thus the cerebral circulation state. However, it is unclear whether there are correlations between electrophysiological, hemodynamic and behavioral changes and whether they have any implications for clinical benefits. In order to investigate these questions, we present a miniaturized system for spectroscopic imaging of brain hemodynamics. The system consists of a 144 ×144, [Formula: see text] pixel pitch, high-sensitivity, analog-output CMOS imager fabricated in a standard 0.35 μm CMOS process, along with a miniaturized imaging system comprising illumination, focusing, analog-to-digital conversion and μSD card based data storage. This enables stand alone operation without a computer, nor electrical or fiberoptic tethers. To achieve high sensitivity, the pixel uses a capacitive transimpedance amplifier (CTIA). The nMOS transistors are in the pixel while pMOS transistors are column-parallel, resulting in a fill factor (FF) of 26%. Running at 60 fps and exposed to 470 nm light, the CMOS imager has a minimum detectable intensity of 2.3 nW/cm(2) , a maximum signal-to-noise ratio (SNR) of 49 dB at 2.45 μW/cm(2) leading to a dynamic range (DR) of 61 dB while consuming 167 μA from a 3.3 V supply. In anesthetized rats, the system was able to detect temporal, spatial and spectral hemodynamic changes in response to DBS.

  20. Characterizations of and Radiation Effects in Several Emerging CMOS Technologies

    NASA Astrophysics Data System (ADS)

    Shufeng Ren

    As the conventional scaling of Si based CMOS is approaching its limit at 7 nm technology node, many perceive that the adoption of novel materials and/or device structures are inevitable to keep Moore's law going. High mobility channel materials such as III-V compound semiconductors or Ge are considered promising to replace Si in order to achieve high performance as well as low power consumption. However, interface and oxide traps have become a major obstacle for high-mobility semiconductors (such as Ge, GaAs, InGaAs, GaSb, etc) to replace Si CMOS technology. Therefore novel high-k dielectrics, such as epitaxially grown crystalline oxides, have been explored to be incorporated onto the high mobility channel materials. Moreover, to enable continued scaling, extremely scaled devices structures such as nanowire gate-all-around structure are needed in the near future. Moreover, as the CMOS industry moves into the 7 nm node and beyond, novel lithography techniques such as EUV are believed to be adopted soon, which can bring radiation damage to CMOS devices and circuit during the fabrication process. Therefore radiation hardening technology in future generations of CMOS devices has again become an interesting research topic to deal with the possible process-induced damage as well as damage caused by operating in radiation harsh environment such as outer space, nuclear plant, etc. In this thesis, the electrical properties of a few selected emerging novel CMOS devices are investigated, which include InGaAs based extremely scaled ultra-thin body nanowire gate-all-around MOSFETs, GOI (Ge On Insulator) CMOS with recessed channel and source/drain, GaAs MOSFETs with crystalline La based gate stack, and crystalline SrTiO3, are investigated to extend our understanding of their electrical characteristics, underlying physical mechanisms, and material properties. Furthermore, the radiation responses of these aforementioned novel devices are thoroughly investigated, with a focus on

  1. Hybrid CMOS SiPIN detectors as astronomical imagers

    NASA Astrophysics Data System (ADS)

    Simms, Lance Michael

    Charge Coupled Devices (CCDs) have dominated optical and x-ray astronomy since their inception in 1969. Only recently, through improvements in design and fabrication methods, have imagers that use Complimentary Metal Oxide Semiconductor (CMOS) technology gained ground on CCDs in scientific imaging. We are now in the midst of an era where astronomers might begin to design optical telescope cameras that employ CMOS imagers. The first three chapters of this dissertation are primarily composed of introductory material. In them, we discuss the potential advantages that CMOS imagers offer over CCDs in astronomical applications. We compare the two technologies in terms of the standard metrics used to evaluate and compare scientific imagers: dark current, read noise, linearity, etc. We also discuss novel features of CMOS devices and the benefits they offer to astronomy. In particular, we focus on a specific kind of hybrid CMOS sensor that uses Silicon PIN photodiodes to detect optical light in order to overcome deficiencies of commercial CMOS sensors. The remaining four chapters focus on a specific type of hybrid CMOS Silicon PIN sensor: the Teledyne Hybrid Visible Silicon PIN Imager (HyViSI). In chapters four and five, results from testing HyViSI detectors in the laboratory and at the Kitt Peak 2.1m telescope are presented. We present our laboratory measurements of the standard detector metrics for a number of HyViSI devices, ranging from 1k×1k to 4k×4k format. We also include a description of the SIDECAR readout circuit that was used to control the detectors. We then show how they performed at the telescope in terms of photometry, astrometry, variability measurement, and telescope focusing and guiding. Lastly, in the final two chapters we present results on detector artifacts such as pixel crosstalk, electronic crosstalk, and image persistence. One form of pixel crosstalk that has not been discussed elsewhere in the literature, which we refer to as Interpixel Charge

  2. Development of a microarray for identification of pathogenic Clostridium species

    PubMed Central

    Janvilisri, Tavan; Scaria, Joy; Gleed, Robin; Fubini, Susan; Bonkosky, Michelle M.; Gröhn, Yrjö T.; Chang, Yung-Fu

    2009-01-01

    In recent years, Clostridium species have rapidly reemerged as human and animal pathogens. The detection and identification of pathogenic Clostridium species is therefore critical for clinical diagnosis and antimicrobial therapy. Traditional diagnostic techniques for clostridia are laborious, time-consuming and may adversely affect the therapeutic outcome. In this study, we developed an oligonucleotide diagnostic microarray for pathogenic Clostridium species. The microarray specificity was tested against 65 Clostridium isolates. The applicability of this microarray in a clinical setting was assessed with the use of mock stool samples. The microarray was successful in discriminating at least four species with the limit of detection as low as 104 CFU/ml. In addition, the pattern of virulence and antibiotic resistance genes of tested strains were determined through the microarrays. This approach demonstrates the high-throughput detection and identification of Clostridium species and provides advantages over traditional methods. Microarray-based techniques are promising applications for clinical diagnosis and epidemiological investigations. PMID:19879710

  3. The fecal bifidobacterial transcriptome of adults: a microarray approach.

    PubMed

    Klaassens, Eline S; Ben-Amor, Kaouther; Vriesema, Aldwin; Vaughan, Elaine E; de Vos, Willem

    2011-01-01

    Bifidobacteria are a predominant group present among adult human intestinal microbiota and are considered to be beneficial to host health. Both the dynamics and functional activity of bifidobacteria from the intestinal tract of four adults, following ingestion of a mix consisting of short chain galactooligosaccharides, long chain fructooligosaccharides and acidic oligosaccharides from pectin hydrolysate (GFP), was investigated. The percentage of total bifidobacteria, monitored by quantitative real time PCR, was not significantly altered but marked species-specific changes occurred in all individuals over time, indicating a dynamic bifidobacterial community. Insight into the functional activity of the bifidobacteria was acquired using a clone library-based microarray comprising the genomes of various bifidobacteria to reveal the bifidobacterial transcriptome within the fecal community. Total RNA from the fecal microbial community was hybridized to the microarray and 310 clones were selected for sequencing which revealed genes belonging to a wide range of functional groups demonstrating substantial metabolic activity. While the intake of GFP did not have a significant effect on the overall change in gene expression, 82 genes showed a significant change. Most of the predicted genes were involved in metabolism of carbohydrates of plant origin, house keeping functions such as DNA replication and transcription, followed by membrane transport of a wide variety of substrates including sugars and metals and amino acid metabolism. Other genes were involved in transport, nucleotide metabolism, amino acid metabolism, environmental information processing and cellular processes and signalling. A smaller number of genes were involved in general metabolism, glycan metabolism, energy metabolism, lipid metabolism and cell surface. These results support the notion that bifidobacteria utilize mainly indigestible polysaccharides as their main source of energy and biosynthesis of

  4. Tissue microarrays for early target evaluation.

    PubMed

    Simon, Ronald; Mirlacher, Martina; Sauter, Guido

    2004-09-01

    Early assessment of the probable biological importance of drug targets, the potential market size of a successful new drug, and possible treatment side effects are critical for risk management in drug development. A comprehensive molecular epidemiology analysis involving thousands of well-characterized human tissues will thus provide vital information for strategic decision-making. Tissue microarray (TMA) technology is ideally suited for such projects. The simultaneous analysis of thousands of tissues enables highly standardized, fast and affordable translational research studies of unprecedented scale.:

  5. Protein Microarrays--Without a Trace

    SciTech Connect

    Camarero, J A

    2007-04-05

    Many experimental approaches in biology and biophysics, as well as applications in diagnosis and drug discovery, require proteins to be immobilized on solid supports. Protein microarrays, for example, provide a high-throughput format to study biomolecular interactions. The technique employed for protein immobilization is a key to the success of these applications. Recent biochemical developments are allowing, for the first time, the selective and traceless immobilization of proteins generated by cell-free systems without the need for purification and/or reconcentration prior to the immobilization step.

  6. ProMAT: protein microarray analysis tool

    SciTech Connect

    White, Amanda M.; Daly, Don S.; Varnum, Susan M.; Anderson, Kevin K.; Bollinger, Nikki; Zangar, Richard C.

    2006-04-04

    Summary: ProMAT is a software tool for statistically analyzing data from ELISA microarray experiments. The software estimates standard curves, sample protein concentrations and their uncertainties for multiple assays. ProMAT generates a set of comprehensive figures for assessing results and diagnosing process quality. The tool is available for Windows or Mac, and is distributed as open-source Java and R code. Availability: ProMAT is available at http://www.pnl.gov/statistics/ProMAT. ProMAT requires Java version 1.5.0 and R version 1.9.1 (or more recent versions) which are distributed with the tool.

  7. CMOS in-pixel optical pulse frequency modulator

    NASA Astrophysics Data System (ADS)

    Nel, Nicolaas E.; du Plessis, M.; Joubert, T.-H.

    2016-02-01

    This paper covers the design of a complementary metal oxide semiconductor (CMOS) pixel readout circuit with a built-in frequency conversion feature. The pixel contains a CMOS photo sensor along with all signal-to-frequency conversion circuitry. An 8×8 array of these pixels is also designed. Current imaging arrays often use analog-to-digital conversion (ADC) and digital signal processing (DSP) techniques that are off-chip1. The frequency modulation technique investigated in this paper is preferred over other ADC techniques due to its smaller size, and the possibility of a higher dynamic range. Careful considerations are made regarding the size of the components of the pixel, as various characteristics of CMOS devices are limited by decreasing the scale of the components2. The methodology used was the CMOS design cycle for integrated circuit design. All components of the pixel were designed from first principles to meet necessary requirements of a small pixel size (30×30 μm2) and an output resolution greater than that of an 8-bit ADC. For the photodetector, an n+-p+/p-substrate diode was designed with a parasitic capacitance of 3 fF. The analog front-end stage was designed around a Schmitt trigger circuit. The photo current is integrated on an integration capacitor of 200 fF, which is reset when the Schmitt trigger output voltage exceeds a preset threshold. The circuit schematic and layout were designed using Cadence Virtuoso and the process used was the AMS CMOS 350 nm process using a power supply of 5V. The simulation results were confirmed to comply with specifications, and the layout passed all verification checks. The dynamic range achieved is 58.828 dB per pixel, with the output frequencies ranging from 12.341kHz to 10.783 MHz. It is also confirmed that the output frequency has a linear relationship to the photocurrent generated by the photodiode.

  8. A reliable ground bounce noise reduction technique for nanoscale CMOS circuits

    NASA Astrophysics Data System (ADS)

    Sharma, Vijay Kumar; Pattanaik, Manisha

    2015-11-01

    Power gating is the most effective method to reduce the standby leakage power by adding header/footer high-VTH sleep transistors between actual and virtual power/ground rails. When a power gating circuit transitions from sleep mode to active mode, a large instantaneous charge current flows through the sleep transistors. Ground bounce noise (GBN) is the high voltage fluctuation on real ground rail during sleep mode to active mode transitions of power gating circuits. GBN disturbs the logic states of internal nodes of circuits. A novel and reliable power gating structure is proposed in this article to reduce the problem of GBN. The proposed structure contains low-VTH transistors in place of high-VTH footer. The proposed power gating structure not only reduces the GBN but also improves other performance metrics. A large mitigation of leakage power in both modes eliminates the need of high-VTH transistors. A comprehensive and comparative evaluation of proposed technique is presented in this article for a chain of 5-CMOS inverters. The simulation results are compared to other well-known GBN reduction circuit techniques at 22 nm predictive technology model (PTM) bulk CMOS model using HSPICE tool. Robustness against process, voltage and temperature (PVT) variations is estimated through Monte-Carlo simulations.

  9. Characterization of a fast CMOS imaging sensor for high-speed laser detection

    NASA Astrophysics Data System (ADS)

    Casadei, Bruno; Le Normand, J. P.; Hu, Y.; Cunin, Bernard

    2003-07-01

    CMOS active pixel sensors (APS) have performances competitive with charge-coupled device (CCD) technology, and offer advantages in on-chip functionality, system power reduction, cost and miniaturization. In this paper, we present characterization of a fast CMOS APS used in an imager for high-speed laser detections, which can replace the streak cameras. It produces the intensity information in function of one spatial dimension and time [I = f(x,t)] from one frame in two spatial dimensions. The time information is obtained for the first prototype camera to delay successively the integration phase in each pixel of the same row. The different noise sources of the APS sensors such as shot noise due to the photo sensor, the thermal noise and flicker noise due to the readout transistors and the photon shot noise are presented to determine the fundamental limits on image sensor. The first prototype FAMOSI (FAst MOS Imager) is composed of 64 x 64 active pixels. The simulation and experimental results show that a conversion gain of 6.73 +/- 0.25 μV/e- has been obtained with a noise level of 87 +/- 3e- rms. The power consumption of the chip is 25 mW at 50 images/sec.

  10. Design and characterization of high precision in-pixel discriminators for rolling shutter CMOS pixel sensors with full CMOS capability

    NASA Astrophysics Data System (ADS)

    Fu, Y.; Hu-Guo, C.; Dorokhov, A.; Pham, H.; Hu, Y.

    2013-07-01

    In order to exploit the ability to integrate a charge collecting electrode with analog and digital processing circuitry down to the pixel level, a new type of CMOS pixel sensors with full CMOS capability is presented in this paper. The pixel array is read out based on a column-parallel read-out architecture, where each pixel incorporates a diode, a preamplifier with a double sampling circuitry and a discriminator to completely eliminate analog read-out bottlenecks. The sensor featuring a pixel array of 8 rows and 32 columns with a pixel pitch of 80 μm×16 μm was fabricated in a 0.18 μm CMOS process. The behavior of each pixel-level discriminator isolated from the diode and the preamplifier was studied. The experimental results indicate that all in-pixel discriminators which are fully operational can provide significant improvements in the read-out speed and the power consumption of CMOS pixel sensors.

  11. Refractive index change detection based on porous silicon microarray

    NASA Astrophysics Data System (ADS)

    Chen, Weirong; Jia, Zhenhong; Li, Peng; Lv, Guodong; Lv, Xiaoyi

    2016-05-01

    By combining photolithography with the electrochemical anodization method, a microarray device of porous silicon (PS) photonic crystal was fabricated on the crystalline silicon substrate. The optical properties of the microarray were analyzed with the transfer matrix method. The relationship between refractive index and reflectivity of each array element of the microarray at 633 nm was also studied, and the array surface reflectivity changes were observed through digital imaging. By means of the reflectivity measurement method, reflectivity changes below 10-3 can be observed based on PS microarray. The results of this study can be applied to the detection of biosensor arrays.

  12. Chemiluminescence microarrays in analytical chemistry: a critical review.

    PubMed

    Seidel, Michael; Niessner, Reinhard

    2014-09-01

    Multi-analyte immunoassays on microarrays and on multiplex DNA microarrays have been described for quantitative analysis of small organic molecules (e.g., antibiotics, drugs of abuse, small molecule toxins), proteins (e.g., antibodies or protein toxins), and microorganisms, viruses, and eukaryotic cells. In analytical chemistry, multi-analyte detection by use of analytical microarrays has become an innovative research topic because of the possibility of generating several sets of quantitative data for different analyte classes in a short time. Chemiluminescence (CL) microarrays are powerful tools for rapid multiplex analysis of complex matrices. A wide range of applications for CL microarrays is described in the literature dealing with analytical microarrays. The motivation for this review is to summarize the current state of CL-based analytical microarrays. Combining analysis of different compound classes on CL microarrays reduces analysis time, cost of reagents, and use of laboratory space. Applications are discussed, with examples from food safety, water safety, environmental monitoring, diagnostics, forensics, toxicology, and biosecurity. The potential and limitations of research on multiplex analysis by use of CL microarrays are discussed in this review.

  13. Re-Annotator: Annotation Pipeline for Microarray Probe Sequences.

    PubMed

    Arloth, Janine; Bader, Daniel M; Röh, Simone; Altmann, Andre

    2015-01-01

    Microarray technologies are established approaches for high throughput gene expression, methylation and genotyping analysis. An accurate mapping of the array probes is essential to generate reliable biological findings. However, manufacturers of the microarray platforms typically provide incomplete and outdated annotation tables, which often rely on older genome and transcriptome versions that differ substantially from up-to-date sequence databases. Here, we present the Re-Annotator, a re-annotation pipeline for microarray probe sequences. It is primarily designed for gene expression microarrays but can also be adapted to other types of microarrays. The Re-Annotator uses a custom-built mRNA reference database to identify the positions of gene expression array probe sequences. We applied Re-Annotator to the Illumina Human-HT12 v4 microarray platform and found that about one quarter (25%) of the probes differed from the manufacturer's annotation. In further computational experiments on experimental gene expression data, we compared Re-Annotator to another probe re-annotation tool, ReMOAT, and found that Re-Annotator provided an improved re-annotation of microarray probes. A thorough re-annotation of probe information is crucial to any microarray analysis. The Re-Annotator pipeline is freely available at http://sourceforge.net/projects/reannotator along with re-annotated files for Illumina microarrays HumanHT-12 v3/v4 and MouseRef-8 v2.

  14. Application of DNA microarrays in occupational health research.

    PubMed

    Koizumi, Shinji

    2004-01-01

    The profiling of gene expression patterns with DNA microarrays is recently being widely used not only in basic molecular biological studies but also in the practical fields. In clinical application, for example, this technique is expected to be quite useful in making a correct diagnosis. In the pharmacological area, the microarray analysis can be applied to drug discovery and individualized drug treatment. Although not so popular as these examples, DNA microarrays could also be a powerful tool in studies relevant to occupational health. This review will describe the outline of gene expression profiling with DNA microarrays and prospects in occupational health research.

  15. Gene Expression Browser: large-scale and cross-experiment microarray data integration, management, search & visualization

    PubMed Central

    2010-01-01

    Background In the last decade, a large amount of microarray gene expression data has been accumulated in public repositories. Integrating and analyzing high-throughput gene expression data have become key activities for exploring gene functions, gene networks and biological pathways. Effectively utilizing these invaluable microarray data remains challenging due to a lack of powerful tools to integrate large-scale gene-expression information across diverse experiments and to search and visualize a large number of gene-expression data points. Results Gene Expression Browser is a microarray data integration, management and processing system with web-based search and visualization functions. An innovative method has been developed to define a treatment over a control for every microarray experiment to standardize and make microarray data from different experiments homogeneous. In the browser, data are pre-processed offline and the resulting data points are visualized online with a 2-layer dynamic web display. Users can view all treatments over control that affect the expression of a selected gene via Gene View, and view all genes that change in a selected treatment over control via treatment over control View. Users can also check the changes of expression profiles of a set of either the treatments over control or genes via Slide View. In addition, the relationships between genes and treatments over control are computed according to gene expression ratio and are shown as co-responsive genes and co-regulation treatments over control. Conclusion Gene Expression Browser is composed of a set of software tools, including a data extraction tool, a microarray data-management system, a data-annotation tool, a microarray data-processing pipeline, and a data search & visualization tool. The browser is deployed as a free public web service (http://www.ExpressionBrowser.com) that integrates 301 ATH1 gene microarray experiments from public data repositories (viz. the Gene

  16. Reverse transfected cell microarrays in infectious disease research.

    PubMed

    Konrad, Andreas; Jochmann, Ramona; Kuhn, Elisabeth; Naschberger, Elisabeth; Chudasama, Priya; Stürzl, Michael

    2011-01-01

    Several human pathogenic viruses encode large genomes with often more than 100 genes. Viral pathogenicity is determined by carefully orchestrated co-operative activities of several different viral genes which trigger the phenotypic functions of the infected cells. Systematic analyses of these complex interactions require high-throughput transfection technology. Here we have provided a laboratory manual for the reverse transfected cell microarray (RTCM; alternative name: cell chip) as a high-throughput transfection procedure, which has been successfully applied for the systematic analyses of single and combination effects of genes encoded by the human herpesvirus-8 on the NF-kappaB signal transduction pathway. In order to quantitatively determine the effects of viral genes in transfected cells, protocols for the use of GFP as an indicator gene and for indirect immunofluorescence staining of cellular target proteins have been included. RTCM provides a useful methodological approach to investigate systematically combination effects of viral genes on cellular functions.

  17. Genome-wide transcription analyses in rice using tiling microarrays.

    PubMed

    Li, Lei; Wang, Xiangfeng; Stolc, Viktor; Li, Xueyong; Zhang, Dongfen; Su, Ning; Tongprasit, Waraporn; Li, Songgang; Cheng, Zhukuan; Wang, Jun; Deng, Xing Wang

    2006-01-01

    Sequencing and computational annotation revealed several features, including high gene numbers, unusual composition of the predicted genes and a large number of genes lacking homology to known genes, that distinguish the rice (Oryza sativa) genome from that of other fully sequenced model species. We report here a full-genome transcription analysis of the indica rice subspecies using high-density oligonucleotide tiling microarrays. Our results provided expression data support for the existence of 35,970 (81.9%) annotated gene models and identified 5,464 unique transcribed intergenic regions that share similar compositional properties with the annotated exons and have significant homology to other plant proteins. Elucidating and mapping of all transcribed regions revealed an association between global transcription and cytological chromosome features, and an overall similarity of transcriptional activity between duplicated segments of the genome. Collectively, our results provide the first whole-genome transcription map useful for further understanding the rice genome.

  18. Zeptosens' protein microarrays: a novel high performance microarray platform for low abundance protein analysis.

    PubMed

    Pawlak, Michael; Schick, Eginhard; Bopp, Martin A; Schneider, Michael J; Oroszlan, Peter; Ehrat, Markus

    2002-04-01

    Protein microarrays are considered an enabling technology, which will significantly expand the scope of current protein expression and protein interaction analysis. Current technologies, such as two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry, allowing the identification of biologically relevant proteins, have a high resolving power, but also considerable limitations. As was demonstrated by Gygi et al. (Proc. Nat. Acad. Sci. USA 2000,97, 9390-9395), most spots in 2-DE, observed from whole cell extracts, are from high abundance proteins, whereas low abundance proteins, such as signaling molecules or kinases, are only poorly represented. Protein microarrays are expected to significantly expedite the discovery of new markers and targets of pharmaceutical interest, and to have the potential for high-throughput applications. Key factors to reach this goal are: high read-out sensitivity for quantification also of low abundance proteins, functional analysis of proteins, short assay analysis times, ease of handling and the ability to integrate a variety of different targets and new assays. Zeptosens has developed a revolutionary new bioanalytical system based on the proprietary planar waveguide technology which allows us to perform multiplexed, quantitative biomolecular interaction analysis with highest sensitivity in a microarray format upon utilizing the specific advantages of the evanescent field fluorescence detection. The analytical system, comprising an ultrasensitive fluorescence reader and microarray chips with integrated microfluidics, enables the user to generate a multitude of high fidelity data in applications such as protein expression profiling or investigating protein-protein interactions. In this paper, the important factors for developing high performance protein microarray systems, especially for targeting low abundant messengers of relevant biological information, will be discussed and the performance of the system will

  19. Manufacturing DNA microarrays from unpurified PCR products

    PubMed Central

    Diehl, Frank; Beckmann, Boris; Kellner, Nadine; Hauser, Nicole C.; Diehl, Susanne; Hoheisel, Jörg D.

    2002-01-01

    For the production of DNA microarrays from PCR products, purification of the the DNA fragments prior to spotting is a major expense in cost and time. Also, a considerable amount of material is lost during this process and contamination might occur. Here, a protocol is presented that permits the manufacture of microarrays from unpurified PCR products on aminated surfaces such as glass slides coated with the widely used poly(l-lysine) or aminosilane. The presence of primer molecules in the PCR sample does not increase the non-specific signal upon hybridisation. Overall, signal intensity on arrays made of unpurified PCR products is 94% of the intensity obtained with the respective purified molecules. This slight loss in signal, however, is offset by a reduced variation in the amount of DNA present at the individual spot positions across an array, apart from the considerable savings in time and cost. In addition, a larger number of arrays can be made from one batch of amplification products. PMID:12177307

  20. Inferring genetic networks from microarray data.

    SciTech Connect

    May, Elebeoba Eni; Davidson, George S.; Martin, Shawn Bryan; Werner-Washburne, Margaret C.; Faulon, Jean-Loup Michel

    2004-06-01

    In theory, it should be possible to infer realistic genetic networks from time series microarray data. In practice, however, network discovery has proved problematic. The three major challenges are: (1) inferring the network; (2) estimating the stability of the inferred network; and (3) making the network visually accessible to the user. Here we describe a method, tested on publicly available time series microarray data, which addresses these concerns. The inference of genetic networks from genome-wide experimental data is an important biological problem which has received much attention. Approaches to this problem have typically included application of clustering algorithms [6]; the use of Boolean networks [12, 1, 10]; the use of Bayesian networks [8, 11]; and the use of continuous models [21, 14, 19]. Overviews of the problem and general approaches to network inference can be found in [4, 3]. Our approach to network inference is similar to earlier methods in that we use both clustering and Boolean network inference. However, we have attempted to extend the process to better serve the end-user, the biologist. In particular, we have incorporated a system to assess the reliability of our network, and we have developed tools which allow interactive visualization of the proposed network.

  1. Clickable Polymeric Coating for Glycan Microarrays.

    PubMed

    Zilio, Caterina; Sola, Laura; Cretich, Marina; Bernardi, Anna; Chiari, Marcella

    2017-01-01

    The interaction of carbohydrates with a variety of biological targets, including antibodies, proteins, viruses, and cells are of utmost importance in many aspects of biology. Glycan microarrays are increasingly used to determine the binding specificity of glycan-binding proteins. In this study, a novel microarray support is reported for the fabrication of glycan arrays that combines the higher sensitivity of a layered Si-SiO2 surface with a novel polymeric coating easily modifiable by subsequent click reaction. The alkyne-containing copolymer, adsorbed from an aqueous solution, produces a coating by a single step procedure and serves as a soft, tridimensional support for the oriented immobilization of carbohydrates via azide/alkyne Cu (I) catalyzed "click" reaction. The advantages of a functional 3D polymer coating making use of a click chemistry immobilization are combined with the high fluorescence sensitivity and superior signal-to-noise ratio of a Si-SiO2 substrate. The proposed approach enables the attachment of complex sugars on a silicon oxide surface by a method that does not require skilled personnel and chemistry laboratories.

  2. High-Voltage-Input Level Translator Using Standard CMOS

    NASA Technical Reports Server (NTRS)

    Yager, Jeremy A.; Mojarradi, Mohammad M.; Vo, Tuan A.; Blalock, Benjamin J.

    2011-01-01

    proposed integrated circuit would translate (1) a pair of input signals having a low differential potential and a possibly high common-mode potential into (2) a pair of output signals having the same low differential potential and a low common-mode potential. As used here, "low" and "high" refer to potentials that are, respectively, below or above the nominal supply potential (3.3 V) at which standard complementary metal oxide/semiconductor (CMOS) integrated circuits are designed to operate. The input common-mode potential could lie between 0 and 10 V; the output common-mode potential would be 2 V. This translation would make it possible to process the pair of signals by use of standard 3.3-V CMOS analog and/or mixed-signal (analog and digital) circuitry on the same integrated-circuit chip. A schematic of the circuit is shown in the figure. Standard 3.3-V CMOS circuitry cannot withstand input potentials greater than about 4 V. However, there are many applications that involve low-differential-potential, high-common-mode-potential input signal pairs and in which standard 3.3-V CMOS circuitry, which is relatively inexpensive, would be the most appropriate circuitry for performing other functions on the integrated-circuit chip that handles the high-potential input signals. Thus, there is a need to combine high-voltage input circuitry with standard low-voltage CMOS circuitry on the same integrated-circuit chip. The proposed circuit would satisfy this need. In the proposed circuit, the input signals would be coupled into both a level-shifting pair and a common-mode-sensing pair of CMOS transistors. The output of the level-shifting pair would be fed as input to a differential pair of transistors. The resulting differential current output would pass through six standoff transistors to be mirrored into an output branch by four heterojunction bipolar transistors. The mirrored differential current would be converted back to potential by a pair of diode-connected transistors

  3. CMOS Amperometric ADC With High Sensitivity, Dynamic Range and Power Efficiency for Air Quality Monitoring.

    PubMed

    Li, Haitao; Boling, C Sam; Mason, Andrew J

    2016-08-01

    Airborne pollutants are a leading cause of illness and mortality globally. Electrochemical gas sensors show great promise for personal air quality monitoring to address this worldwide health crisis. However, implementing miniaturized arrays of such sensors demands high performance instrumentation circuits that simultaneously meet challenging power, area, sensitivity, noise and dynamic range goals. This paper presents a new multi-channel CMOS amperometric ADC featuring pixel-level architecture for gas sensor arrays. The circuit combines digital modulation of input currents and an incremental Σ∆ ADC to achieve wide dynamic range and high sensitivity with very high power efficiency and compact size. Fabricated in 0.5 [Formula: see text] CMOS, the circuit was measured to have 164 dB cross-scale dynamic range, 100 fA sensitivity while consuming only 241 [Formula: see text] and 0.157 [Formula: see text] active area per channel. Electrochemical experiments with liquid and gas targets demonstrate the circuit's real-time response to a wide range of analyte concentrations.

  4. Using a large area CMOS APS for direct chemiluminescence detection in Western blotting electrophoresis

    NASA Astrophysics Data System (ADS)

    Esposito, Michela; Newcombe, Jane; Anaxagoras, Thalis; Allinson, Nigel M.; Wells, Kevin

    2012-03-01

    Western blotting electrophoretic sequencing is an analytical technique widely used in Functional Proteomics to detect, recognize and quantify specific labelled proteins in biological samples. A commonly used label for western blotting is Enhanced ChemiLuminescence (ECL) reagents based on fluorescent light emission of Luminol at 425nm. Film emulsion is the conventional detection medium, but is characterized by non-linear response and limited dynamic range. Several western blotting digital imaging systems have being developed, mainly based on the use of cooled Charge Coupled Devices (CCDs) and single avalanche diodes that address these issues. Even so these systems present key drawbacks, such as a low frame rate and require operation at low temperature. Direct optical detection using Complementary Metal Oxide Semiconductor (CMOS) Active Pixel Sensors (APS)could represent a suitable digital alternative for this application. In this paper the authors demonstrate the viability of direct chemiluminescent light detection in western blotting electrophoresis using a CMOS APS at room temperature. Furthermore, in recent years, improvements in fabrication techniques have made available reliable processes for very large imagers, which can be now scaled up to wafer size, allowing direct contact imaging of full size western blotting samples. We propose using a novel wafer scale APS (12.8 cm×13.2 cm), with an array architecture using two different pixel geometries that can deliver an inherently low noise and high dynamic range image at the same time representing a dramatic improvement with respect to the current western blotting imaging systems.

  5. Proton-counting radiography for proton therapy: a proof of principle using CMOS APS technology.

    PubMed

    Poludniowski, G; Allinson, N M; Anaxagoras, T; Esposito, M; Green, S; Manolopoulos, S; Nieto-Camero, J; Parker, D J; Price, T; Evans, P M

    2014-06-07

    Despite the early recognition of the potential of proton imaging to assist proton therapy (Cormack 1963 J. Appl. Phys. 34 2722), the modality is still removed from clinical practice, with various approaches in development. For proton-counting radiography applications such as computed tomography (CT), the water-equivalent-path-length that each proton has travelled through an imaged object must be inferred. Typically, scintillator-based technology has been used in various energy/range telescope designs. Here we propose a very different alternative of using radiation-hard CMOS active pixel sensor technology. The ability of such a sensor to resolve the passage of individual protons in a therapy beam has not been previously shown. Here, such capability is demonstrated using a 36 MeV cyclotron beam (University of Birmingham Cyclotron, Birmingham, UK) and a 200 MeV clinical radiotherapy beam (iThemba LABS, Cape Town, SA). The feasibility of tracking individual protons through multiple CMOS layers is also demonstrated using a two-layer stack of sensors. The chief advantages of this solution are the spatial discrimination of events intrinsic to pixelated sensors, combined with the potential provision of information on both the range and residual energy of a proton. The challenges in developing a practical system are discussed.

  6. Proton-counting radiography for proton therapy: a proof of principle using CMOS APS technology

    PubMed Central

    Poludniowski, G; Allinson, N M; Anaxagoras, T; Esposito, M; Green, S; Manolopoulos, S; Nieto-Camero, J; Parker, D J; Price, T; Evans, P M

    2014-01-01

    Despite the early recognition of the potential of proton imaging to assist proton therapy the modality is still removed from clinical practice, with various approaches in development. For proton-counting radiography applications such as Computed Tomography (CT), the Water-Equivalent-Path-Length (WEPL) that each proton has travelled through an imaged object must be inferred. Typically, scintillator-based technology has been used in various energy/range telescope designs. Here we propose a very different alternative of using radiation-hard CMOS Active Pixel Sensor (APS) technology. The ability of such a sensor to resolve the passage of individual protons in a therapy beam has not been previously shown. Here, such capability is demonstrated using a 36 MeV cyclotron beam (University of Birmingham Cyclotron, Birmingham, UK) and a 200 MeV clinical radiotherapy beam (iThemba LABS, Cape Town, SA). The feasibility of tracking individual protons through multiple CMOS layers is also demonstrated using a two-layer stack of sensors. The chief advantages of this solution are the spatial discrimination of events intrinsic to pixelated sensors, combined with the potential provision of information on both the range and residual energy of a proton. The challenges in developing a practical system are discussed. PMID:24785680

  7. (Invited) Comprehensive Assessment of Oxide Memristors As Post-CMOS Memory and Logic Devices

    DOE PAGES

    Gao, X.; Mamaluy, D.; Cyr, E. C.; ...

    2016-05-10

    As CMOS technology approaches the end of its scaling, oxide-based memristors have become one of the leading candidates for post-CMOS memory and logic devices. In orderTo facilitate the understanding of physical switching mechanisms and accelerate experimental development of memristors, we have developed a three-dimensional fully-coupled electrical and thermal transport model, which captures all the important processes that drive memristive switching and is applicable for simulating a wide range of memristors. Moreover, the model is applied to simulate the RESET and SET switching in a 3D filamentary TaOx memristor. Extensive simulations show that the switching dynamics of the bipolar device ismore » determined by thermally-activated field-dominant processes: with Joule heating, the raised temperature enables the movement of oxygen vacancies, and the field drift dominates the overall motion of vacancies. Simulated current-voltage hysteresis and device resistance profiles as a function of time and voltage during RESET and SET switching show good agreement with experimental measurement.« less

  8. (Invited) Comprehensive Assessment of Oxide Memristors As Post-CMOS Memory and Logic Devices

    SciTech Connect

    Gao, X.; Mamaluy, D.; Cyr, E. C.; Marinella, M. J.

    2016-05-10

    As CMOS technology approaches the end of its scaling, oxide-based memristors have become one of the leading candidates for post-CMOS memory and logic devices. In orderTo facilitate the understanding of physical switching mechanisms and accelerate experimental development of memristors, we have developed a three-dimensional fully-coupled electrical and thermal transport model, which captures all the important processes that drive memristive switching and is applicable for simulating a wide range of memristors. Moreover, the model is applied to simulate the RESET and SET switching in a 3D filamentary TaOx memristor. Extensive simulations show that the switching dynamics of the bipolar device is determined by thermally-activated field-dominant processes: with Joule heating, the raised temperature enables the movement of oxygen vacancies, and the field drift dominates the overall motion of vacancies. Simulated current-voltage hysteresis and device resistance profiles as a function of time and voltage during RESET and SET switching show good agreement with experimental measurement.

  9. New CMOS digital pixel sensor architecture dedicated to a visual cortical implant

    NASA Astrophysics Data System (ADS)

    Trépanier, Annie; Trépanier, Jean-Luc; Sawan, Mohamad; Audet, Yves

    2004-10-01

    A CMOS image sensor with pixel level analog to digital conversion is presented. Each 16μm x 16μm pixel area contains a photodiode, with a fill factor of 22%, a comparator and an 8-bit DRAM, resulting in a total of 44 transistors per pixel. A digital to analog converter is used to deliver a voltage reference to compare with the pixel voltage for the analog to digital conversion. This sensor is required by a visual cortical stimulator, primarily to capture the image which is dedicated to stimulate the visual cortex of a blind patient. An active range finder system will be added to the implant, requiring the difference information between two images, in order to obtain the 3D information useful to the patient. For this purpose, three selectable operation modes are combined in the same pixel circuit. The linear integration, resulting from image capture at multiple exposure times, allows a high intrascene dynamic range. Random accessibility, in space and time, of the array of sensors is possible with the logarithmic mode. And the new differential mode makes the difference between two consecutive images. The circuit of a pixel has been fabricated in CMOS 0.18μm technology and it is under test to validate the full operation of the 3 modes. Also, a matrix of 45 x 90 pixels is currently being implemented for fabrication.

  10. Combined reactor neutron beam and {sup 60}Co γ-ray radiation effects on CMOS APS image sensors

    SciTech Connect

    Wang, Zujun Chen, Wei; Sheng, Jiangkun; Liu, Yan; Xiao, Zhigang; Huang, Shaoyan; Liu, Minbo

    2015-02-15

    The combined reactor neutron beam and {sup 60}Co γ-ray radiation effects on complementary metal-oxide semiconductor (CMOS) active pixel sensors (APS) have been discussed and some new experimental phenomena are presented. The samples are manufactured in the standard 0.35-μm CMOS technology. Two samples were first exposed to {sup 60}Co γ-rays up to the total ionizing dose (TID) level of 200 krad(Si) at the dose rates of 50.0 and 0.2 rad(Si)/s, and then exposed to neutron fluence up to 1 × 10{sup 11} n/cm{sup 2} (1-MeV equivalent neutron fluence). One sample was first exposed to neutron fluence up to 1 × 10{sup 11} n/cm{sup 2} (1-MeV equivalent neutron fluence), and then exposed to {sup 60}Co γ-rays up to the TID level of 200 krad(Si) at the dose rate of 0.2 rad(Si)/s. The mean dark signal (K{sub D}), the dark signal non-uniformity (DSNU), and the noise (V{sub N}) versus the total dose and neutron fluence has been investigated. The degradation mechanisms of CMOS APS image sensors have been analyzed, especially for the interaction induced by neutron displacement damage and TID damage.

  11. Ultra-thin silicon (UTSi) on insulator CMOS transceiver and time-division multiplexed switch chips for smart pixel integration

    NASA Astrophysics Data System (ADS)

    Zhang, Liping; Sawchuk, Alexander A.

    2001-12-01

    We describe the design, fabrication and functionality of two different 0.5 micron CMOS optoelectronic integrated circuit (OEIC) chips based on the Peregrine Semiconductor Ultra-Thin Silicon on insulator technology. The Peregrine UTSi silicon- on-sapphire (SOS) technology is a member of the silicon-on- insulator (SOI) family. The low-loss synthetic sapphire substrate is optically transparent and has good thermal conductivity and coefficient of thermal expansion properties, which meet the requirements for flip-chip bonding of VCSELs and other optoelectronic input-output components. One chip contains transceiver and network components, including four channel high-speed CMOS transceiver modules, pseudo-random bit stream (PRBS) generators, a voltage controlled oscillator (VCO) and other test circuits. The transceiver chips can operate in both self-testing mode and networking mode. An on- chip clock and true-single-phase-clock (TSPC) D-flip-flop have been designed to generate a PRBS at over 2.5 Gb/s for the high-speed transceiver arrays to operate in self-testing mode. In the networking mode, an even number of transceiver chips forms a ring network through free-space or fiber ribbon interconnections. The second chip contains four channel optical time-division multiplex (TDM) switches, optical transceiver arrays, an active pixel detector and additional test devices. The eventual applications of these chips will require monolithic OEICs with integrated optical input and output. After fabrication and testing, the CMOS transceiver array dies will be packaged with 850 nm vertical cavity surface emitting lasers (VCSELs), and metal-semiconductor- metal (MSM) or GaAs p-i-n detector die arrays to achieve high- speed optical interconnections. The hybrid technique could be either wire bonding or flip-chip bonding of the CMOS SOS smart-pixel arrays with arrays of VCSELs and photodetectors onto an optoelectronic chip carrier as a multi-chip module (MCM).

  12. Recognition of multiple imbalanced cancer types based on DNA microarray data using ensemble classifiers.

    PubMed

    Yu, Hualong; Hong, Shufang; Yang, Xibei; Ni, Jun; Dan, Yuanyuan; Qin, Bin

    2013-01-01

    DNA microarray technology can measure the activities of tens of thousands of genes simultaneously, which provides an efficient way to diagnose cancer at the molecular level. Although this strategy has attracted significant research attention, most studies neglect an important problem, namely, that most DNA microarray datasets are skewed, which causes traditional learning algorithms to produce inaccurate results. Some studies have considered this problem, yet they merely focus on binary-class problem. In this paper, we dealt with multiclass imbalanced classification problem, as encountered in cancer DNA microarray, by using ensemble learning. We utilized one-against-all coding strategy to transform multiclass to multiple binary classes, each of them carrying out feature subspace, which is an evolving version of random subspace that generates multiple diverse training subsets. Next, we introduced one of two different correction technologies, namely, decision threshold adjustment or random undersampling, into each training subset to alleviate the damage of class imbalance. Specifically, support vector machine was used as base classifier, and a novel voting rule called counter voting was presented for making a final decision. Experimental results on eight skewed multiclass cancer microarray datasets indicate that unlike many traditional classification approaches, our methods are insensitive to class imbalance.

  13. Development of Cell-Defined Lentivirus-Based Microarray for Mammalian Cells.

    PubMed

    Kim, Hi Chul; Shum, David; Seol, Hyang Sook; Jang, Se Jin; Cho, Ssang-Goo; Kwon, Yong-Jun

    2016-10-04

    Although reverse transfection cell microarray (RTCM) is a powerful tool for mammalian cell studies, the technique is not appropriate for cells that are difficult to transfect. The lentivirus-infected cell microarray (LICM) technique was designed to improve overall efficiency. However, LICM presents new challenges because individual lentiviral particles can spread through the cell population, leading to cross-contamination. Therefore, we designed a cell-defined lentivirus microarray (CDLM) technique using cell-friendly biomaterials that are controlled by cell attachment timing. We selected poly-l-lysine (PLL) with Matrigel as the best combination of biomaterials for cell-defined culture. We used 2 µL PLL to determine by titration the optimum concentration required (0.04% stock, 0.005% final concentration). We also determined the optimum concentration of 10 µL of lentivirus particles for maximum reverse infection efficiency (1 × 10(8) infectious units [IFU]/mL stock, 62.5% final concentration) and established the best combination of components for the lentivirus mixture (10 µL of lentivirus particles and 2 µL each of siGLO Red dye, Matrigel, and 0.04% PLL). Finally, we validated both the effect of reverse infection in various cell lines and lentivirus spot activity in CDLM by storage period. This method provides an effective lentivirus-infected cell microarray for large-scale gene function studies.

  14. Advances in lectin microarray technology: Optimized protocols for piezoelectric print conditions

    PubMed Central

    Pilobello, Kanoelani T.; Agrawal, Praveen; Rouse, Richard; Mahal, Lara K.

    2015-01-01

    Lectin microarray technology has been used to profile the glycosylation of a multitude of biological and clinical samples, leading to new clinical biomarkers and advances in glycobiology. Lectin microarrays, which include over 90 plant lectins, recombinant lectins, and selected antibodies, are used to profile N-linked, O-linked, and glycolipid glycans. The specificity and depth of glycan profiling depends upon the carbohydrate-binding proteins arrayed. Our current set targets mammalian carbohydrates including fucose, high mannose, branched and complex N-linked, α- and β- Galactose and GalNAc, α-2,3- and α-2,6- sialic acid, LacNAc and Lewis X epitopes. In previous protocols, we have described the use of a contact microarray printer for lectin microarray manufacture. Herein, we present an updated protocol using a non-contact, piezoelectric printer, which leads to increased lectin activity on the array. We describe optimization of print conditions and sample hybridization, and methods of analysis. PMID:23788322

  15. Experimental Approaches to Microarray Analysis of Tumor Samples

    ERIC Educational Resources Information Center

    Furge, Laura Lowe; Winter, Michael B.; Meyers, Jacob I.; Furge, Kyle A.

    2008-01-01

    Comprehensive measurement of gene expression using high-density nucleic acid arrays (i.e. microarrays) has become an important tool for investigating the molecular differences in clinical and research samples. Consequently, inclusion of discussion in biochemistry, molecular biology, or other appropriate courses of microarray technologies has…

  16. Demonstrating a Multi-drug Resistant Mycobacterium tuberculosis Amplification Microarray

    PubMed Central

    Linger, Yvonne; Kukhtin, Alexander; Golova, Julia; Perov, Alexander; Qu, Peter; Knickerbocker, Christopher; Cooney, Christopher G.; Chandler, Darrell P.

    2014-01-01

    Simplifying microarray workflow is a necessary first step for creating MDR-TB microarray-based diagnostics that can be routinely used in lower-resource environments. An amplification microarray combines asymmetric PCR amplification, target size selection, target labeling, and microarray hybridization within a single solution and into a single microfluidic chamber. A batch processing method is demonstrated with a 9-plex asymmetric master mix and low-density gel element microarray for genotyping multi-drug resistant Mycobacterium tuberculosis (MDR-TB). The protocol described here can be completed in 6 hr and provide correct genotyping with at least 1,000 cell equivalents of genomic DNA. Incorporating on-chip wash steps is feasible, which will result in an entirely closed amplicon method and system. The extent of multiplexing with an amplification microarray is ultimately constrained by the number of primer pairs that can be combined into a single master mix and still achieve desired sensitivity and specificity performance metrics, rather than the number of probes that are immobilized on the array. Likewise, the total analysis time can be shortened or lengthened depending on the specific intended use, research question, and desired limits of detection. Nevertheless, the general approach significantly streamlines microarray workflow for the end user by reducing the number of manually intensive and time-consuming processing steps, and provides a simplified biochemical and microfluidic path for translating microarray-based diagnostics into routine clinical practice. PMID:24796567

  17. Demonstrating a multi-drug resistant Mycobacterium tuberculosis amplification microarray.

    PubMed

    Linger, Yvonne; Kukhtin, Alexander; Golova, Julia; Perov, Alexander; Qu, Peter; Knickerbocker, Christopher; Cooney, Christopher G; Chandler, Darrell P

    2014-04-25

    Simplifying microarray workflow is a necessary first step for creating MDR-TB microarray-based diagnostics that can be routinely used in lower-resource environments. An amplification microarray combines asymmetric PCR amplification, target size selection, target labeling, and microarray hybridization within a single solution and into a single microfluidic chamber. A batch processing method is demonstrated with a 9-plex asymmetric master mix and low-density gel element microarray for genotyping multi-drug resistant Mycobacterium tuberculosis (MDR-TB). The protocol described here can be completed in 6 hr and provide correct genotyping with at least 1,000 cell equivalents of genomic DNA. Incorporating on-chip wash steps is feasible, which will result in an entirely closed amplicon method and system. The extent of multiplexing with an amplification microarray is ultimately constrained by the number of primer pairs that can be combined into a single master mix and still achieve desired sensitivity and specificity performance metrics, rather than the number of probes that are immobilized on the array. Likewise, the total analysis time can be shortened or lengthened depending on the specific intended use, research question, and desired limits of detection. Nevertheless, the general approach significantly streamlines microarray workflow for the end user by reducing the number of manually intensive and time-consuming processing steps, and provides a simplified biochemical and microfluidic path for translating microarray-based diagnostics into routine clinical practice.

  18. The Importance of Normalization on Large and Heterogeneous Microarray Datasets

    EPA Science Inventory

    DNA microarray technology is a powerful functional genomics tool increasingly used for investigating global gene expression in environmental studies. Microarrays can also be used in identifying biological networks, as they give insight on the complex gene-to-gene interactions, ne...

  19. CMOS active pixel sensor type imaging system on a chip

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R. (Inventor); Nixon, Robert (Inventor)

    2011-01-01

    A single chip camera which includes an .[.intergrated.]. .Iadd.integrated .Iaddend.image acquisition portion and control portion and which has double sampling/noise reduction capabilities thereon. Part of the .[.intergrated.]. .Iadd.integrated .Iaddend.structure reduces the noise that is picked up during imaging.

  20. Transcription factor regulation can be accurately predicted from the presence of target gene signatures in microarray gene expression data

    PubMed Central

    Essaghir, Ahmed; Toffalini, Federica; Knoops, Laurent; Kallin, Anders; van Helden, Jacques; Demoulin, Jean-Baptiste

    2010-01-01

    Deciphering transcription factor networks from microarray data remains difficult. This study presents a simple method to infer the regulation of transcription factors from microarray data based on well-characterized target genes. We generated a catalog containing transcription factors associated with 2720 target genes and 6401 experimentally validated regulations. When it was available, a distinction between transcriptional activation and inhibition was included for each regulation. Next, we built a tool (www.tfacts.org) that compares submitted gene lists with target genes in the catalog to detect regulated transcription factors. TFactS was validated with published lists of regulated genes in various models and compared to tools based on in silico promoter analysis. We next analyzed the NCI60 cancer microarray data set and showed the regulation of SOX10, MITF and JUN in melanomas. We then performed microarray experiments comparing gene expression response of human fibroblasts stimulated by different growth factors. TFactS predicted the specific activation of Signal transducer and activator of transcription factors by PDGF-BB, which was confirmed experimentally. Our results show that the expression levels of transcription factor target genes constitute a robust signature for transcription factor regulation, and can be efficiently used for microarray data mining. PMID:20215436

  1. Large-area low-temperature ultrananocrystaline diamond (UNCD) films and integration with CMOS devices for monolithically integrated diamond MEMD/NEMS-CMOS systems.

    SciTech Connect

    Sumant, A.V.; Auciello, O.; Yuan, H.-C; Ma, Z.; Carpick, R. W.; Mancini, D. C.; Univ. of Wisconsin; Univ. of Pennsylvania

    2009-05-01

    Because of exceptional mechanical, chemical, and tribological properties, diamond has a great potential to be used as a material for the development of high-performance MEMS and NEMS such as resonators and switches compatible with harsh environments, which involve mechanical motion and intermittent contact. Integration of such MEMS/NEMS devices with complementary metal oxide semiconductor (CMOS) microelectronics will provide a unique platform for CMOS-driven commercial MEMS/NEMS. The main hurdle to achieve diamond-CMOS integration is the relatively high substrate temperatures (600-800 C) required for depositing conventional diamond thin films, which are well above the CMOS operating thermal budget (400 C). Additionally, a materials integration strategy has to be developed to enable diamond-CMOS integration. Ultrananocrystalline diamond (UNCD), a novel material developed in thin film form at Argonne, is currently the only microwave plasma chemical vapor deposition (MPCVD) grown diamond film that can be grown at 400 C, and still retain exceptional mechanical, chemical, and tribological properties comparable to that of single crystal diamond. We have developed a process based on MPCVD to synthesize UNCD films on up to 200 mm in diameter CMOS wafers, which will open new avenues for the fabrication of monolithically integrated CMOS-driven MEMS/NEMS based on UNCD. UNCD films were grown successfully on individual Si-based CMOS chips and on 200 mm CMOS wafers at 400 C in a MPCVD system, using Ar-rich/CH4 gas mixture. The CMOS devices on the wafers were characterized before and after UNCD deposition. All devices were performing to specifications with very small degradation after UNCD deposition and processing. A threshold voltage degradation in the range of 0.08-0.44V and transconductance degradation in the range of 1.5-9% were observed.

  2. Electrosonic ejector microarray for drug and gene delivery.

    PubMed

    Zarnitsyn, Vladimir G; Meacham, J Mark; Varady, Mark J; Hao, Chunhai; Degertekin, F Levent; Fedorov, Andrei G

    2008-04-01

    We report on development and experimental characterization of a novel cell manipulation device-the electrosonic ejector microarray-which establishes a pathway for drug and/or gene delivery with control of biophysical action on the length scale of an individual cell. The device comprises a piezoelectric transducer for ultrasound wave generation, a reservoir for storing the sample mixture and a set of acoustic horn structures that form a nozzle array for focused application of mechanical energy. The nozzles are micromachined in silicon or plastic using simple and economical batch fabrication processes. When the device is driven at a particular resonant frequency of the acoustic horn structures, the sample mixture of cells and desired transfection agents/molecules suspended in culture medium is ejected from orifices located at the nozzle tips. During sample ejection, focused mechanical forces (pressure and shear) are generated on a microsecond time scale (dictated by nozzle size/geometry and ejection velocity) resulting in identical "active" microenvironments for each ejected cell. This process enables a number of cellular bioeffects, from uptake of small molecules and gene delivery/transfection to cell lysis. Specifically, we demonstrate successful calcein uptake and transfection of DNA plasmid encoding green fluorescent protein (GFP) into human malignant glioma cells (cell line LN443) using electrosonic microarrays with 36, 45 and 50 mum diameter nozzle orifices and operating at ultrasound frequencies between 0.91 and 0.98 MHz. Our results suggest that efficacy and the extent of bioeffects are mainly controlled by nozzle orifice size and the localized intensity of the applied acoustic field.

  3. Smart CMOS image sensor for lightning detection and imaging.

    PubMed

    Rolando, Sébastien; Goiffon, Vincent; Magnan, Pierre; Corbière, Franck; Molina, Romain; Tulet, Michel; Bréart-de-Boisanger, Michel; Saint-Pé, Olivier; Guiry, Saïprasad; Larnaudie, Franck; Leone, Bruno; Perez-Cuevas, Leticia; Zayer, Igor

    2013-03-01

    We present a CMOS image sensor dedicated to lightning detection and imaging. The detector has been designed to evaluate the potentiality of an on-chip lightning detection solution based on a smart sensor. This evaluation is performed in the frame of the predevelopment phase of the lightning detector that will be implemented in the Meteosat Third Generation Imager satellite for the European Space Agency. The lightning detection process is performed by a smart detector combining an in-pixel frame-to-frame difference comparison with an adjustable threshold and on-chip digital processing allowing an efficient localization of a faint lightning pulse on the entire large format array at a frequency of 1 kHz. A CMOS prototype sensor with a 256×256 pixel array and a 60 μm pixel pitch has been fabricated using a 0.35 μm 2P 5M technology and tested to validate the selected detection approach.

  4. A Brief Discussion of Radiation Hardening of CMOS Microelectronics

    SciTech Connect

    Myers, D.R.

    1998-12-18

    Commercial microchips work well in their intended environments. However, generic microchips will not fimction correctly if exposed to sufficient amounts of ionizing radiation, the kind that satellites encounter in outer space. Modern CMOS circuits must overcome three specific concerns from ionizing radiation: total-dose, single-event, and dose-rate effects. Minority-carrier devices such as bipolar transistors, optical receivers, and solar cells must also deal with recombination-generation centers caused by displacement damage, which are not major concerns for majority-carrier CMOS devices. There are ways to make the chips themselves more resistant to radiation. This extra protection, called radiation hardening, has been called both a science and an art. Radiation hardening requires both changing the designs of the chips and altering the ways that the chips are manufactured.

  5. Diffuse reflectance measurements using lensless CMOS imaging chip

    NASA Astrophysics Data System (ADS)

    Schelkanova, I.; Pandya, A.; Shah, D.; Lilge, L.; Douplik, A.

    2014-10-01

    To assess superficial epithelial microcirculation, a diagnostic tool should be able to detect the heterogeneity of microvasculature, and to monitor qualitative derangement of perfusion in a diseased condition. Employing a lensless CMOS imaging chip with an RGB Bayer filter, experiments were conducted with a microfluidic platform to obtain diffuse reflectance maps. Haemoglobin (Hb) solution (160 g/l) was injected in the periodic channels (grooves) of the microfluidic phantom which were covered with ~250 μm thick layer of intralipid to obtain a diffusive environment. Image processing was performed on data acquired on the surface of the phantom to evaluate the diffuse reflectance from the subsurface periodic pattern. Thickness of the microfluidic grooves, the wavelength dependent contrast between Hb and the background, and effective periodicity of the grooves were evaluated. Results demonstrate that a lens-less CMOS camera is capable of capturing images of subsurface structures with large field of view.

  6. Wide modulation bandwidth terahertz detection in 130 nm CMOS technology

    NASA Astrophysics Data System (ADS)

    Nahar, Shamsun; Shafee, Marwah; Blin, Stéphane; Pénarier, Annick; Nouvel, Philippe; Coquillat, Dominique; Safwa, Amr M. E.; Knap, Wojciech; Hella, Mona M.

    2016-11-01

    Design, manufacturing and measurements results for silicon plasma wave transistors based wireless communication wideband receivers operating at 300 GHz carrier frequency are presented. We show the possibility of Si-CMOS based integrated circuits, in which by: (i) specific physics based plasma wave transistor design allowing impedance matching to the antenna and the amplifier, (ii) engineering the shape of the patch antenna through a stacked resonator approach and (iii) applying bandwidth enhancement strategies to the design of integrated broadband amplifier, we achieve an integrated circuit of the 300 GHz carrier frequency receiver for wireless wideband operation up to/over 10 GHz. This is, to the best of our knowledge, the first demonstration of low cost 130 nm Si-CMOS technology, plasma wave transistors based fast/wideband integrated receiver operating at 300 GHz atmospheric window. These results pave the way towards future large scale (cost effective) silicon technology based terahertz wireless communication receivers.

  7. Radiation Hard 0.13 Micron CMOS Library at IHP

    NASA Astrophysics Data System (ADS)

    Jagdhold, U.

    2013-08-01

    To support space applications we have developed an 0.13 micron CMOS library which should be radiation hard up to 200 krad. The article describes the concept to come to a radiation hard digital circuit and was introduces in 2010 [1]. By introducing new radiation hard design rules we will minimize IC-level leakage and single event latch-up (SEL). To reduce single event upset (SEU) we add two p-MOS transistors to all flip flops. For reliability reasons we use double contacts in all library elements. The additional rules and the library elements are integrated in our Cadence mixed signal design kit, “Virtuoso” IC6.1 [2]. A test chip is produced with our in house 0.13 micron BiCMOS technology, see Ref. [3]. As next step we will doing radiation tests according the european space agency (ESA) specifications, see Ref. [4], [5].

  8. TID Simulation of Advanced CMOS Devices for Space Applications

    NASA Astrophysics Data System (ADS)

    Sajid, Muhammad

    2016-07-01

    This paper focuses on Total Ionizing Dose (TID) effects caused by accumulation of charges at silicon dioxide, substrate/silicon dioxide interface, Shallow Trench Isolation (STI) for scaled CMOS bulk devices as well as at Buried Oxide (BOX) layer in devices based on Silicon-On-Insulator (SOI) technology to be operated in space radiation environment. The radiation induced leakage current and corresponding density/concentration electrons in leakage current path was presented/depicted for 180nm, 130nm and 65nm NMOS, PMOS transistors based on CMOS bulk as well as SOI process technologies on-board LEO and GEO satellites. On the basis of simulation results, the TID robustness analysis for advanced deep sub-micron technologies was accomplished up to 500 Krad. The correlation between the impact of technology scaling and magnitude of leakage current with corresponding total dose was established utilizing Visual TCAD Genius program.

  9. A back-illuminated megapixel CMOS image sensor

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata; Cunningham, Thomas; Nikzad, Shouleh; Hoenk, Michael; Jones, Todd; Wrigley, Chris; Hancock, Bruce

    2005-01-01

    In this paper, we present the test and characterization results for a back-illuminated megapixel CMOS imager. The imager pixel consists of a standard junction photodiode coupled to a three transistor-per-pixel switched source-follower readout [1]. The imager also consists of integrated timing and control and bias generation circuits, and provides analog output. The analog column-scan circuits were implemented in such a way that the imager could be configured to run in off-chip correlated double-sampling (CDS) mode. The imager was originally designed for normal front-illuminated operation, and was fabricated in a commercially available 0.5 pn triple-metal CMOS-imager compatible process. For backside illumination, the imager was thinned by etching away the substrate was etched away in a post-fabrication processing step.

  10. A novel noise optimization technique for inductively degenerated CMOS LNA

    NASA Astrophysics Data System (ADS)

    Zhiqing, Geng; Haiyong, Wang; Nanjian, Wu

    2009-10-01

    This paper proposes a novel noise optimization technique. The technique gives analytical formulae for the noise performance of inductively degenerated CMOS low noise amplifier (LNA) circuits with an ideal gate inductor for a fixed bias voltage and nonideal gate inductor for a fixed power dissipation, respectively, by mathematical analysis and reasonable approximation methods. LNA circuits with required noise figure can be designed effectively and rapidly just by using hand calculations of the proposed formulae. We design a 1.8 GHz LNA in a TSMC 0.25 μm CMOS process. The measured results show a noise figure of 1.6 dB with a forward gain of 14.4 dB at a power consumption of 5 mW, demonstrating that the designed LNA circuits can achieve low noise figure levels at low power dissipation.

  11. On testing stuck-open faults in CMOS combinational circuits

    NASA Technical Reports Server (NTRS)

    Chandramouli, R.

    1982-01-01

    Recently it has been found that a class of failure related to a particular technology (CMOS) cannot be modelled as the conventional stuck-at fault model. These failures change the combinational behavior of CMOS logic gates into a sequential one. Such a failure is modelled as a fault, called the Stuck-Open fault (SOP). The object of this paper is to develop a procedure to detect single SOPs in combinational circuits. It is shown, that in general, tests generated for stuck-at faults when applied in a particular sequence will detect all single SOP faults. In case of single redundancy in the network, the SOP fault on the redundant line cannot be detected. When there is reconvergent fan-out in the network, there is a one-one correspondence between the conditions for stuck-at fault and stuck-open fault detectability.

  12. Dark current study for CMOS fully integrated-PIN-photodiodes

    NASA Astrophysics Data System (ADS)

    Teva, Jordi; Jessenig, Stefan; Jonak-Auer, Ingrid; Schrank, Franz; Wachmann, Ewald

    2011-05-01

    PIN photodiodes are semiconductor devices widely used in a huge range of applications, such as photoconductors, charge-coupled devices and pulse oximeters for medical applications. The possibility to combine and to integrate the fabrication of the sensor with its signal conditioning circuitry in a CMOS process allows device miniaturization in addition to enhance its properties lowering the production and assembly costs. This paper presents the design and characterization of silicon based PIN photodiodes integrated in a CMOS commercial process. A high-resistivity, low impurity substrate is chosen as the start material for the PIN photodiode array fabrication in order to fabricate devices with a minimum dark current. The dark current is studied, analyzed and measured for two different starting materials and for different geometries. A model previously proposed is reviewed and compared with experimental data.

  13. 324GHz CMOS VCO Using Linear Superimposition Technique

    NASA Technical Reports Server (NTRS)

    Daquan, Huang; LaRocca, Tim R.; Samoska, Lorene A; Fung, Andy; Chang, Frank

    2007-01-01

    Terahertz (frequencies ranged from 300GHz to 3THz) imaging and spectroscopic systems have drawn increasing attention recently due to their unique capabilities in detecting and possibly analyzing concealed objects. The generation of terahertz signals is nonetheless nontrivial and traditionally accomplished by using either free-electron radiation, optical lasers, Gunn diodes or fundamental oscillation by using III-V based HBT/HEMT technology[1-3]... We have substantially extended the operation range of deep-scaled CMOS by using a linear superimposition method, in which we have realized a 324GHz VCO in 90nm digital CMOS with 4GHz tuning range under 1V supply voltage. This may also pave the way for ultra-high data rate wireless communications beyond that of IEEE 802.15.3c and reach data rates comparable to that of fiber optical communications, such as OC768 (40Gbps) and beyond.

  14. Digital microarray analysis for digital artifact genomics

    NASA Astrophysics Data System (ADS)

    Jaenisch, Holger; Handley, James; Williams, Deborah

    2013-06-01

    We implement a Spatial Voting (SV) based analogy of microarray analysis for digital gene marker identification in malware code sections. We examine a famous set of malware formally analyzed by Mandiant and code named Advanced Persistent Threat (APT1). APT1 is a Chinese organization formed with specific intent to infiltrate and exploit US resources. Manidant provided a detailed behavior and sting analysis report for the 288 malware samples available. We performed an independent analysis using a new alternative to the traditional dynamic analysis and static analysis we call Spatial Analysis (SA). We perform unsupervised SA on the APT1 originating malware code sections and report our findings. We also show the results of SA performed on some members of the families associated by Manidant. We conclude that SV based SA is a practical fast alternative to dynamics analysis and static analysis.

  15. Giant Magnetoresistive Sensors for DNA Microarray

    PubMed Central

    Xu, Liang; Yu, Heng; Han, Shu-Jen; Osterfeld, Sebastian; White, Robert L.; Pourmand, Nader; Wang, Shan X.

    2009-01-01

    Giant magnetoresistive (GMR) sensors are developed for a DNA microarray. Compared with the conventional fluorescent sensors, GMR sensors are cheaper, more sensitive, can generate fully electronic signals, and can be easily integrated with electronics and microfluidics. The GMR sensor used in this work has a bottom spin valve structure with an MR ratio of 12%. The single-strand target DNA detected has a length of 20 bases. Assays with DNA concentrations down to 10 pM were performed, with a dynamic range of 3 logs. A double modulation technique was used in signal detection to reduce the 1/f noise in the sensor while circumventing electromagnetic interference. The logarithmic relationship between the magnetic signal and the target DNA concentration can be described by the Temkin isotherm. Furthermore, GMR sensors integrated with microfluidics has great potential of improving the sensitivity to 1 pM or below, and the total assay time can be reduced to less than 1 hour. PMID:20824116

  16. Uses of Dendrimers for DNA Microarrays

    PubMed Central

    Caminade, Anne-Marie; Padié, Clément; Laurent, Régis; Maraval, Alexandrine; Majoral, Jean-Pierre

    2006-01-01

    Biosensors such as DNA microarrays and microchips are gaining an increasing importance in medicinal, forensic, and environmental analyses. Such devices are based on the detection of supramolecular interactions called hybridizations that occur between complementary oligonucleotides, one linked to a solid surface (the probe), and the other one to be analyzed (the target). This paper focuses on the improvements that hyperbranched and perfectly defined nanomolecules called dendrimers can provide to this methodology. Two main uses of dendrimers for such purpose have been described up to now; either the dendrimer is used as linker between the solid surface and the probe oligonucleotide, or the dendrimer is used as a multilabeled entity linked to the target oligonucleotide. In the first case the dendrimer generally induces a higher loading of probes and an easier hybridization, due to moving away the solid phase. In the second case the high number of localized labels (generally fluorescent) induces an increased sensitivity, allowing the detection of small quantities of biological entities.

  17. Meta-analysis of incomplete microarray studies.

    PubMed

    Zollinger, Alix; Davison, Anthony C; Goldstein, Darlene R

    2015-10-01

    Meta-analysis of microarray studies to produce an overall gene list is relatively straightforward when complete data are available. When some studies lack information-providing only a ranked list of genes, for example-it is common to reduce all studies to ranked lists prior to combining them. Since this entails a loss of information, we consider a hierarchical Bayes approach to meta-analysis using different types of information from different studies: the full data matrix, summary statistics, or ranks. The model uses an informative prior for the parameter of interest to aid the detection of differentially expressed genes. Simulations show that the new approach can give substantial power gains compared with classical meta-analysis and list aggregation methods. A meta-analysis of 11 published studies with different data types identifies genes known to be involved in ovarian cancer and shows significant enrichment.

  18. Software and tools for microarray data analysis.

    PubMed

    Mehta, Jai Prakash; Rani, Sweta

    2011-01-01

    A typical microarray experiment results in series of images, depending on the experimental design and number of samples. Software analyses the images to obtain the intensity at each spot and quantify the expression for each transcript. This is followed by normalization, and then various data analysis techniques are applied on the data. The whole analysis pipeline requires a large number of software to accurately handle the massive amount of data. Fortunately, there are large number of freely available and commercial software to churn the massive amount of data to manageable sets of differentially expressed genes, functions, and pathways. This chapter describes the software and tools which can be used to analyze the gene expression data right from the image analysis to gene list, ontology, and pathways.

  19. Protein microarray applications: Autoantibody detection and posttranslational modification.

    PubMed

    Atak, Apurva; Mukherjee, Shuvolina; Jain, Rekha; Gupta, Shabarni; Singh, Vedita Anand; Gahoi, Nikita; K P, Manubhai; Srivastava, Sanjeeva

    2016-10-01

    The discovery of DNA microarrays was a major milestone in genomics; however, it could not adequately predict the structure or dynamics of underlying protein entities, which are the ultimate effector molecules in a cell. Protein microarrays allow simultaneous study of thousands of proteins/peptides, and various advancements in array technologies have made this platform suitable for several diagnostic and functional studies. Antibody arrays enable researchers to quantify the abundance of target proteins in biological fluids and assess PTMs by using the antibodies. Protein microarrays have been used to assess protein-protein interactions, protein-ligand interactions, and autoantibody profiling in various disease conditions. Here, we summarize different microarray platforms with focus on its biological and clinical applications in autoantibody profiling and PTM studies. We also enumerate the potential of tissue microarrays to validate findings from protein arrays as well as other approaches, highlighting their significance in proteomics.

  20. DNA microarray-based mutation discovery and genotyping.

    PubMed

    Gresham, David

    2011-01-01

    DNA microarrays provide an efficient means of identifying single-nucleotide polymorphisms (SNPs) in DNA samples and characterizing their frequencies in individual and mixed samples. We have studied the parameters that determine the sensitivity of DNA probes to SNPs and found that the melting temperature (T (m)) of the probe is the primary determinant of probe sensitivity. An isothermal-melting temperature DNA microarray design, in which the T (m) of all probes is tightly distributed, can be implemented by varying the length of DNA probes within a single DNA microarray. I describe guidelines for designing isothermal-melting temperature DNA microarrays and protocols for labeling and hybridizing DNA samples to DNA microarrays for SNP discovery, genotyping, and quantitative determination of allele frequencies in mixed samples.

  1. Image microarrays (IMA): Digital pathology's missing tool

    PubMed Central

    Hipp, Jason; Cheng, Jerome; Pantanowitz, Liron; Hewitt, Stephen; Yagi, Yukako; Monaco, James; Madabhushi, Anant; Rodriguez-canales, Jaime; Hanson, Jeffrey; Roy-Chowdhuri, Sinchita; Filie, Armando C.; Feldman, Michael D.; Tomaszewski, John E.; Shih, Natalie NC.; Brodsky, Victor; Giaccone, Giuseppe; Emmert-Buck, Michael R.; Balis, Ulysses J.

    2011-01-01

    Introduction: The increasing availability of whole slide imaging (WSI) data sets (digital slides) from glass slides offers new opportunities for the development of computer-aided diagnostic (CAD) algorithms. With the all-digital pathology workflow that these data sets will enable in the near future, literally millions of digital slides will be generated and stored. Consequently, the field in general and pathologists, specifically, will need tools to help extract actionable information from this new and vast collective repository. Methods: To address this limitation, we designed and implemented a tool (dCORE) to enable the systematic capture of image tiles with constrained size and resolution that contain desired histopathologic features. Results: In this communication, we describe a user-friendly tool that will enable pathologists to mine digital slides archives to create image microarrays (IMAs). IMAs are to digital slides as tissue microarrays (TMAs) are to cell blocks. Thus, a single digital slide could be transformed into an array of hundreds to thousands of high quality digital images, with each containing key diagnostic morphologies and appropriate controls. Current manual digital image cut-and-paste methods that allow for the creation of a grid of images (such as an IMA) of matching resolutions are tedious. Conclusion: The ability to create IMAs representing hundreds to thousands of vetted morphologic features has numerous applications in education, proficiency testing, consensus case review, and research. Lastly, in a manner analogous to the way conventional TMA technology has significantly accelerated in situ studies of tissue specimens use of IMAs has similar potential to significantly accelerate CAD algorithm development. PMID:22200030

  2. Fluorescence detection in (sub-)nanoliter microarrays

    NASA Astrophysics Data System (ADS)

    van den Doel, L. Richard; Vellekoop, Michael J.; Sarro, Pasqualina M.; Picioreanu, S.; Moerman, R.; Frank, J.; van Dedem, G. W. K.; Hjelt, Kari H.; van Vliet, Lucas J.; Young, Ian T.

    1999-06-01

    The goal of our TU Delft interfaculty research program is to develop intelligent molecular diagnostic systems (IMDS) that can analyze liquid samples that contain a variety of biochemical compounds such as those associated with fermentation processes. One specific project within the IMDS program focuses on photon sensors. In order to analyze the liquid samples we use dedicated microarrays. At this stage, these are basically miniaturized micro titre plates. Typical dimensions of a vial are 200 X 200 X 20 micrometer3. These dimensions may be varied and the shape of the vials can be modified with a result that the volume of the vials varies from 0.5 to 1.6 nl. For all experiments, we have used vials with the shape of a truncated pyramid. These vials are fabricated in silicon by a wet etching process. For testing purposes the vials are filled with rhodamine solutions of various concentrations. To avoid evaporation glycerol-water (1:1, v/v) with a viscosity of 8.3 times the viscosity of water is used as solvent. We aim at wide field-of-view imaging at the expense of absolute sensitivity: the field-of-view increases quadratically with decreasing magnification. Small magnification, however, implies low Numerical Aperture (NA). The ability of a microscope objective to collect photons is proportional to the square of the NA. To image the entire microarray we have used an epi-illumination fluorescence microscope equipped with a low magnification (2.5 X/0.075) objective and a scientific CCD camera to integrate the photons emitted from the fluorescing particles in the solutions in the vials. From these experiments we found that for this setup the detection limit is on the order of micromolar concentrations of fluorescing particles. This translates to 108 molecules per vial.

  3. Lipid Microarray Biosensor for Biotoxin Detection.

    SciTech Connect

    Singh, Anup K.; Throckmorton, Daniel J.; Moran-Mirabal, Jose C.; Edel, Joshua B.; Meyer, Grant D.; Craighead, Harold G.

    2006-05-01

    We present the use of micron-sized lipid domains, patterned onto planar substrates and within microfluidic channels, to assay the binding of bacterial toxins via total internal reflection fluorescence microscopy (TIRFM). The lipid domains were patterned using a polymer lift-off technique and consisted of ganglioside-populated DSPC:cholesterol supported lipid bilayers (SLBs). Lipid patterns were formed on the substrates by vesicle fusion followed by polymer lift-off, which revealed micron-sized SLBs containing either ganglioside GT1b or GM1. The ganglioside-populated SLB arrays were then exposed to either Cholera toxin subunit B (CTB) or Tetanus toxin fragment C (TTC). Binding was assayed on planar substrates by TIRFM down to 1 nM concentration for CTB and 100 nM for TTC. Apparent binding constants extracted from three different models applied to the binding curves suggest that binding of a protein to a lipid-based receptor is strongly affected by the lipid composition of the SLB and by the substrate on which the bilayer is formed. Patterning of SLBs inside microfluidic channels also allowed the preparation of lipid domains with different compositions on a single device. Arrays within microfluidic channels were used to achieve segregation and selective binding from a binary mixture of the toxin fragments in one device. The binding and segregation within the microfluidic channels was assayed with epifluorescence as proof of concept. We propose that the method used for patterning the lipid microarrays on planar substrates and within microfluidic channels can be easily adapted to proteins or nucleic acids and can be used for biosensor applications and cell stimulation assays under different flow conditions. KEYWORDS. Microarray, ganglioside, polymer lift-off, cholera toxin, tetanus toxin, TIRFM, binding constant.4

  4. CMOS floating-point vector-arithmetic unit

    NASA Astrophysics Data System (ADS)

    Timmermann, D.; Rix, B.; Hahn, H.; Hosticka, B. J.

    1994-05-01

    This work describes a floating-point arithmetic unit based on the CORDIC algorithm. The unit computes a full set of high level arithmetic and elementary functions: multiplication, division, (co)sine, hyperbolic (co)sine, square root, natural logarithm, inverse (hyperbolic) tangent, vector norm, and phase. The chip has been integrated in 1.6 micron double-metal n-well CMOS technology and achieves a normalized peak performance of 220 MFLOPS.

  5. Hybrid CMOS/Nanodevice Integrated Circuits Design and Fabrication

    DTIC Science & Technology

    2008-08-25

    This approach combines a semiconductor transistor system with a nanowire crossbar, with simple two-terminal nanodevices self-assembled at each...hybrid CMOS/nanodevice integrated circuits [10-12]. Such circuit combines a semiconductor transistors system with a nanowire crossbar, with simple two...both with and without embedded metallic clusters), self-assembled molecular monolayers, and thin chalcogenide and crystalline perovskite layers [20

  6. CMOS Alcohol Sensor Employing ZnO Nanowire Sensing Films

    NASA Astrophysics Data System (ADS)

    Santra, S.; Ali, S. Z.; Guha, P. K.; Hiralal, P.; Unalan, H. E.; Dalal, S. H.; Covington, J. A.; Milne, W. I.; Gardner, J. W.; Udrea, F.

    2009-05-01

    This paper reports on the utilization of zinc oxide nanowires (ZnO NWs) on a silicon on insulator (SOI) CMOS micro-hotplate for use as an alcohol sensor. The device was designed in Cadence and fabricated in a 1.0 μm SOI CMOS process at XFAB (Germany). The basic resistive gas sensor comprises of a metal micro-heater (made of aluminum) embedded in an ultra-thin membrane. Gold plated aluminum electrodes, formed of the top metal, are used for contacting with the sensing material. This design allows high operating temperatures with low power consumption. The membrane was formed by using deep reactive ion etching. ZnO NWs were grown on SOI CMOS substrates by a simple and low-cost hydrothermal method. A few nanometer of ZnO seed layer was first sputtered on the chips, using a metal mask, and then the chips were dipped in a zinc nitrate hexahydrate and hexamethylenetramine solution at 90° C to grow ZnO NWs. The chemical sensitivity of the on-chip NWs were studied in the presence of ethanol (C2H5OH) vapour (with 10% relative humidity) at two different temperatures: 200 and 250° C (the corresponding power consumptions are only 18 and 22 mW). The concentrations of ethanol vapour were varied from 175-1484 ppm (pers per million) and the maximum response was observed 40% (change in resistance in %) at 786 ppm at 250° C. These preliminary measurements showed that the on-chip deposited ZnO NWs could be a promising material for a CMOS based ethanol sensor.

  7. Integrated CMOS transceiver for indoor optical wireless links

    NASA Astrophysics Data System (ADS)

    Holburn, David M.; Lalithambika, Vinod A.; Joyner, Valencia M.; Samsudin, Rina J.; Mears, Robert J.

    2001-11-01

    The purpose of this work is to develop integrated CMOS designs for optical transceivers at 1.55um wavelength that both meet the current system specification of 155Mb/s and provide a viable upgrade path to higher bit-rates. We present the design and implementation of an integrated multi-channel CMOS transceiver for use in a cellular 155Mb/s Manchester-coded optical wireless link. The receiver is an angle-diversity design and consists of multiple sectors with relatively small field of view; each driving an individual pre-amplifier channel. An on-chip selector selects signals to be passed to the combiner depending on the signal level and external control signals. The outputs of all the selected channels are combined using a current summing junction, implemented using a transconductance-transimpedance approach. In order to achieve a receiver design that will be robust in the face of process variations, an on-chip circuit is provided to maintain the operating point of the amplifier chain. The design has been optimized to achieve -30dBm sensitivity at a BER of 10-9. The CMOS transmitter circuit is tailored to match the electro-optic response of the resonant cavity LEDs being used. The transmitter driver incorporates current-peaking and charge-extraction circuitry using a novel timing generator, and has been designed to achieve rise and fall times of better than 0.2ns. Considerable effort is being directed towards the development of integrated designs which do not require significant numbers of discrete components. The prototype designs are being realised in a 0.7μm commodity mixed-signal CMOS process by Alcatel Microelectronics. We report results from the first prototype multi-channel demonstrator system and discuss future research directions.

  8. Performance Analysis of Visible Light Communication Using CMOS Sensors.

    PubMed

    Do, Trong-Hop; Yoo, Myungsik

    2016-02-29

    This paper elucidates the fundamentals of visible light communication systems that use the rolling shutter mechanism of CMOS sensors. All related information involving different subjects, such as photometry, camera operation, photography and image processing, are studied in tandem to explain the system. Then, the system performance is analyzed with respect to signal quality and data rate. To this end, a measure of signal quality, the signal to interference plus noise ratio (SINR), is formulated. Finally, a simulation is conducted to verify the analysis.

  9. Hardening of commercial CMOS PROMs with polysilicon fusible links

    NASA Technical Reports Server (NTRS)

    Newman, W. H.; Rauchfuss, J. E.

    1985-01-01

    The method by which a commercial 4K CMOS PROM with polysilicon fuses was hardened and the feasibility of applying this method to a 16K PROM are presented. A description of the process and the necessary minor modifications to the original layout are given. The PROM circuit and discrete device characteristics over radiation to 1000K rad-Si are summarized. The dose rate sensitivity of the 4K PROMs is also presented.

  10. Linear dynamic range enhancement in a CMOS imager

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata (Inventor)

    2008-01-01

    A CMOS imager with increased linear dynamic range but without degradation in noise, responsivity, linearity, fixed-pattern noise, or photometric calibration comprises a linear calibrated dual gain pixel in which the gain is reduced after a pre-defined threshold level by switching in an additional capacitance. The pixel may include a novel on-pixel latch circuit that is used to switch in the additional capacitance.

  11. CMOS integration of inkjet-printed graphene for humidity sensing

    PubMed Central

    Santra, S.; Hu, G.; Howe, R. C. T.; De Luca, A.; Ali, S. Z.; Udrea, F.; Gardner, J. W.; Ray, S. K.; Guha, P. K.; Hasan, T.

    2015-01-01

    We report on the integration of inkjet-printed graphene with a CMOS micro-electro-mechanical-system (MEMS) microhotplate for humidity sensing. The graphene ink is produced via ultrasonic assisted liquid phase exfoliation in isopropyl alcohol (IPA) using polyvinyl pyrrolidone (PVP) polymer as the stabilizer. We formulate inks with different graphene concentrations, which are then deposited through inkjet printing over predefined interdigitated gold electrodes on a CMOS microhotplate. The graphene flakes form a percolating network to render the resultant graphene-PVP thin film conductive, which varies in presence of humidity due to swelling of the hygroscopic PVP host. When the sensors are exposed to relative humidity ranging from 10–80%, we observe significant changes in resistance with increasing sensitivity from the amount of graphene in the inks. Our sensors show excellent repeatability and stability, over a period of several weeks. The location specific deposition of functional graphene ink onto a low cost CMOS platform has the potential for high volume, economic manufacturing and application as a new generation of miniature, low power humidity sensors for the internet of things. PMID:26616216

  12. Low voltage electron multiplying CCD in a CMOS process

    NASA Astrophysics Data System (ADS)

    Dunford, Alice; Stefanov, Konstantin; Holland, Andrew

    2016-07-01

    Low light level and high-speed image sensors as required for space applications can suffer from a decrease in the signal to noise ratio (SNR) due to the photon-starved environment and limitations of the sensor's readout noise. The SNR can be increased by the implementation of Time Delay Integration (TDI) as it allows photoelectrons from multiple exposures to be summed in the charge domain with no added noise. Electron Multiplication (EM) can further improve the SNR and lead to an increase in device performance. However, both techniques have traditionally been confined to Charge Coupled Devices (CCD) due to the efficient charge transfer required. With the increase in demand for CMOS sensors with equivalent or superior functionality and performance, this paper presents findings from the characterisation of a low voltage EMCCD in a CMOS process using advanced design features to increase the electron multiplying gain. By using the CMOS process, it is possible to increase chip integration and functionality and achieve higher readout speeds and reduced pixel size. The presented characterisation results include analysis of the photon transfer curve, the dark current, the electron multiplying gain and analysis of the parameters' dependence on temperature and operating voltage.

  13. Multi-target electrochemical biosensing enabled by integrated CMOS electronics

    NASA Astrophysics Data System (ADS)

    Rothe, J.; Lewandowska, M. K.; Heer, F.; Frey, O.; Hierlemann, A.

    2011-05-01

    An integrated electrochemical measurement system, based on CMOS technology, is presented, which allows the detection of several analytes in parallel (multi-analyte) and enables simultaneous monitoring at different locations (multi-site). The system comprises a 576-electrode CMOS sensor chip, an FPGA module for chip control and data processing, and the measurement laptop. The advantages of the highly versatile system are demonstrated by two applications. First, a label-free, hybridization-based DNA sensor is enabled by the possibility of large-scale integration in CMOS technology. Second, the detection of the neurotransmitter choline is presented by assembling the chip with biosensor microprobe arrays. The low noise level enables a limit of detection of, e.g., 0.3 µM choline. The fully integrated system is self-contained: it features cleaning, functionalization and measurement functions without the need for additional electrical equipment. With the power supplied by the laptop, the system is very suitable for on-site measurements.

  14. Polycrystalline Mercuric Iodide Films on CMOS Readout Arrays

    PubMed Central

    Hartsough, Neal E.; Iwanczyk, Jan S.; Nygard, Einar; Malakhov, Nail; Barber, William C.; Gandhi, Thulasidharan

    2009-01-01

    We have created high-resolution x-ray imaging devices using polycrystalline mercuric iodide (HgI2) films grown directly onto CMOS readout chips using a thermal vapor transport process. Images from prototype 400×400 pixel HgI2-coated CMOS readout chips are presented, where the pixel grid is 30 μm × 30 μm. The devices exhibited sensitivity of 6.2 μC/Rcm2 with corresponding dark current of ∼2.7 nA/cm2, and a 80 μm FWHM planar image response to a 50 μm slit aperture. X-ray CT images demonstrate a point spread function sufficient to obtain a 50 μm spatial resolution in reconstructed CT images at a substantially reduced dose compared to phosphor-coated readouts. The use of CMOS technology allows for small pixels (30 μm), fast readout speeds (8 fps for a 3200×3200 pixel array), and future design flexibility due to the use of well-developed fabrication processes. PMID:20161098

  15. Seamless integration of CMOS and microfluidics using flip chip bonding

    NASA Astrophysics Data System (ADS)

    Welch, David; Blain Christen, Jennifer

    2013-03-01

    We demonstrate the microassembly of PDMS (polydimethylsiloxane) microfluidics with integrated circuits made in complementary metal-oxide-semiconductor (CMOS) processes. CMOS-sized chips are flip chip bonded to a flexible polyimide printed circuit board (PCB) with commercially available solder paste patterned using a SU-8 epoxy. The average resistance of each flip chip bond is negligible and all connections are electrically isolated. PDMS is attached to the flexible polyimide PCB using a combination of oxygen plasma treatment and chemical bonding with 3-aminopropyltriethoxysilane. The total device has a burst pressure of 175 kPA which is limited by the strength of the flip chip attachment. This technique allows the sensor area of the die to act as the bottom of the microfluidic channel. The SU-8 provides a barrier between the pad ring (electrical interface) and the fluids; post-processing is not required on the CMOS die. This assembly method shows great promise for developing analytic systems which combine the strengths of microelectronics and microfluidics into one device.

  16. From vertex detectors to inner trackers with CMOS pixel sensors

    NASA Astrophysics Data System (ADS)

    Besson, A.; Pérez, A. Pérez; Spiriti, E.; Baudot, J.; Claus, G.; Goffe, M.; Winter, M.

    2017-02-01

    The use of CMOS Pixel Sensors (CPS) for high resolution and low material vertex detectors has been validated with the 2014 and 2015 physics runs of the STAR-PXL detector at RHIC/BNL. This opens the door to the use of CPS for inner tracking devices, with 10-100 times larger sensitive area, which require therefore a sensor design privileging power saving, response uniformity and robustness. The 350 nm CMOS technology used for the STAR-PXL sensors was considered as too poorly suited to upcoming applications like the upgraded ALICE Inner Tracking System (ITS), which requires sensors with one order of magnitude improvement on readout speed and improved radiation tolerance. This triggered the exploration of a deeper sub-micron CMOS technology, Tower-Jazz 180 nm, for the design of a CPS well adapted for the new ALICE-ITS running conditions. This paper reports the R & D results for the conception of a CPS well adapted for the ALICE-ITS.

  17. Aluminum nitride on titanium for CMOS compatible piezoelectric transducers

    PubMed Central

    Doll, Joseph C; Petzold, Bryan C; Ninan, Biju; Mullapudi, Ravi; Pruitt, Beth L

    2010-01-01

    Piezoelectric materials are widely used for microscale sensors and actuators but can pose material compatibility challenges. This paper reports a post-CMOS compatible fabrication process for piezoelectric sensors and actuators on silicon using only standard CMOS metals. The piezoelectric properties of aluminum nitride (AlN) deposited on titanium (Ti) by reactive sputtering are characterized and microcantilever actuators are demonstrated. The film texture of the polycrystalline Ti and AlN films is improved by removing the native oxide from the silicon substrate in situ and sequentially depositing the films under vacuum to provide a uniform growth surface. The piezoelectric properties for several AlN film thicknesses are measured using laser doppler vibrometry on unpatterned wafers and released cantilever beams. The film structure and properties are shown to vary with thickness, with values of d33f, d31 and d33 of up to 2.9, −1.9 and 6.5 pm V−1, respectively. These values are comparable with AlN deposited on a Pt metal electrode, but with the benefit of a fabrication process that uses only standard CMOS metals. PMID:20333316

  18. CCD/CMOS hybrid FPA for low light level imaging

    NASA Astrophysics Data System (ADS)

    Liu, Xinqiao; Fowler, Boyd A.; Onishi, Steve K.; Vu, Paul; Wen, David D.; Do, Hung; Horn, Stuart

    2005-08-01

    We present a CCD / CMOS hybrid focal plane array (FPA) for low light level imaging applications. The hybrid approach combines the best of CCD imaging characteristics (e.g. high quantum efficiency, low dark current, excellent uniformity, and low pixel cross talk) with the high speed, low power and ultra-low read noise of CMOS readout technology. The FPA is comprised of two CMOS readout integrated circuits (ROIC) that are bump bonded to a CCD imaging substrate. Each ROIC is an array of Capacitive Transimpedence Amplifiers (CTIA) that connect to the CCD columns via indium bumps. The proposed column parallel readout architecture eliminates the slow speed, high noise, and high power limitations of a conventional CCD. This results in a compact, low power, ultra-sensitive solid-state FPA that can be used in low light level applications such as live-cell microscopy and security cameras at room temperature operation. The prototype FPA has a 1280×1024 format with 12-um square pixels. Measured dark current is less than 5.8 pA/cm2 at room temperature and the overall read noise is as low as 2.9e at 30 frames/sec.

  19. Development of CMOS Imager Block for Capsule Endoscope

    NASA Astrophysics Data System (ADS)

    Shafie, S.; Fodzi, F. A. M.; Tung, L. Q.; Lioe, D. X.; Halin, I. A.; Hasan, W. Z. W.; Jaafar, H.

    2014-04-01

    This paper presents the development of imager block to be associated in a capsule endoscopy system. Since the capsule endoscope is used to diagnose gastrointestinal diseases, the imager block must be in small size which is comfortable for the patients to swallow. In this project, a small size 1.5V button battery is used as the power supply while the voltage supply requirements for other components such as microcontroller and CMOS image sensor are higher. Therefore, a voltage booster circuit is proposed to boost up the voltage supply from 1.5V to 3.3V. A low power microcontroller is used to generate control pulses for the CMOS image sensor and to convert the 8-bits parallel data output to serial data to be transmitted to the display panel. The results show that the voltage booster circuit was able to boost the voltage supply from 1.5V to 3.3V. The microcontroller precisely controls the CMOS image sensor to produce parallel data which is then serialized again by the microcontroller. The serial data is then successfully translated to 2fps image and displayed on computer.

  20. Cryogenic CMOS circuits for single charge digital readout.

    SciTech Connect

    Gurrieri, Thomas M.; Longoria, Erin Michelle; Eng, Kevin; Carroll, Malcolm S.; Hamlet, Jason R.; Young, Ralph Watson

    2010-03-01

    The readout of a solid state qubit often relies on single charge sensitive electrometry. However the combination of fast and accurate measurements is non trivial due to large RC time constants due to the electrometers resistance and shunt capacitance from wires between the cold stage and room temperature. Currently fast sensitive measurements are accomplished through rf reflectrometry. I will present an alternative single charge readout technique based on cryogenic CMOS circuits in hopes to improve speed, signal-to-noise, power consumption and simplicity in implementation. The readout circuit is based on a current comparator where changes in current from an electrometer will trigger a digital output. These circuits were fabricated using Sandia's 0.35 {micro}m CMOS foundry process. Initial measurements of comparators with an addition a current amplifier have displayed current sensitivities of < 1nA at 4.2K, switching speeds up to {approx}120ns, while consuming {approx}10 {micro}W. I will also discuss an investigation of noise characterization of our CMOS process in hopes to obtain a better understanding of the ultimate limit in signal to noise performance.