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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. JPL CMOS Active Pixel Sensor Technology

    NASA Technical Reports Server (NTRS)

    Fossum, E. R.

    1995-01-01

    This paper will present the JPL-developed complementary metal- oxide-semiconductor (CMOS) active pixel sensor (APS) technology. The CMOS APS has achieved performance comparable to charge coupled devices, yet features ultra low power operation, random access readout, on-chip timing and control, and on-chip analog to digital conversion. Previously published open literature will be reviewed.

  4. 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

  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. 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

  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. 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…

  10. 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…

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Thin Film on CMOS Active Pixel Sensor for Space Applications.

    PubMed

    Schulze Spuentrup, Jan Dirk; Burghartz, Joachim N; Graf, Heinz-Gerd; Harendt, Christine; Hutter, Franz; Nicke, Markus; Schmidt, Uwe; Schubert, Markus; Sterzel, Juergen

    2008-10-13

    A 664 x 664 element Active Pixel image Sensor (APS) with integrated analog signal processing, full frame synchronous shutter and random access for applications in star sensors is presented and discussed. A thick vertical diode array in Thin Film on CMOS (TFC) technology is explored to achieve radiation hardness and maximum fill factor.

  16. 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…

  17. 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…

  18. 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

  19. A 128 x 128 CMOS Active Pixel Image Sensor for Highly Integrated Imaging Systems

    NASA Technical Reports Server (NTRS)

    Mendis, Sunetra K.; Kemeny, Sabrina E.; Fossum, Eric R.

    1993-01-01

    A new CMOS-based image sensor that is intrinsically compatible with on-chip CMOS circuitry is reported. The new CMOS active pixel image sensor achieves low noise, high sensitivity, X-Y addressability, and has simple timing requirements. The image sensor was fabricated using a 2 micrometer p-well CMOS process, and consists of a 128 x 128 array of 40 micrometer x 40 micrometer pixels. The CMOS image sensor technology enables highly integrated smart image sensors, and makes the design, incorporation and fabrication of such sensors widely accessible to the integrated circuit community.

  20. A CMOS active pixel sensor for retinal stimulation

    NASA Astrophysics Data System (ADS)

    Prydderch, Mark L.; French, Marcus J.; Mathieson, Keith; Adams, Christopher; Gunning, Deborah; Laudanski, Jonathan; Morrison, James D.; Moodie, Alan R.; Sinclair, James

    2006-02-01

    Degenerative photoreceptor diseases, such as age-related macular degeneration and retinitis pigmentosa, are the most common causes of blindness in the western world. A potential cure is to use a microelectronic retinal prosthesis to provide electrical stimulation to the remaining healthy retinal cells. We describe a prototype CMOS Active Pixel Sensor capable of detecting a visual scene and translating it into a train of electrical pulses for stimulation of the retina. The sensor consists of a 10 x 10 array of 100 micron square pixels fabricated on a 0.35 micron CMOS process. Light incident upon each pixel is converted into output current pulse trains with a frequency related to the light intensity. These outputs are connected to a biocompatible microelectrode array for contact to the retinal cells. The flexible design allows experimentation with signal amplitudes and frequencies in order to determine the most appropriate stimulus for the retina. Neural processing in the retina can be studied by using the sensor in conjunction with a Field Programmable Gate Array (FPGA) programmed to behave as a neural network. The sensor has been integrated into a test system designed for studying retinal response. We present the most recent results obtained from this sensor.

  1. CMOS monolithic active pixel sensors for high energy physics

    NASA Astrophysics Data System (ADS)

    Snoeys, W.

    2014-11-01

    Monolithic pixel detectors integrating sensor matrix and readout in one piece of silicon are only now starting to make their way into high energy physics. Two major requirements are radiation tolerance and low power consumption. For the most extreme radiation levels, signal charge has to be collected by drift from a depletion layer onto a designated collection electrode without losing the signal charge elsewhere in the in-pixel circuit. Low power consumption requires an optimization of Q/C, the ratio of the collected signal charge over the input capacitance [1]. Some solutions to combine sufficient Q/C and collection by drift require exotic fabrication steps. More conventional solutions up to now require a simple in-pixel readout circuit. Both high voltage CMOS technologies and Monolithic Active Pixel Sensors (MAPS) technologies with high resistivity epitaxial layers offer high voltage diodes. The choice between the two is not fundamental but more a question of how much depletion can be reached and also of availability and cost. This paper tries to give an overview.

  2. 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.

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

    PubMed

    Seco, Joao; Depauw, Nicolas

    2011-02-01

    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). 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. 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. 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 CMOS detector for protons. The

  4. 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

  5. Development of radiation hard CMOS active pixel sensors for HL-LHC

    NASA Astrophysics Data System (ADS)

    Pernegger, Heinz

    2016-07-01

    New pixel detectors, based on commercial high voltage and/or high resistivity full CMOS processes, hold promise as next-generation active pixel sensors for inner and intermediate layers of the upgraded ATLAS tracker. The use of commercial CMOS processes allow cost-effective detector construction and simpler hybridisation techniques. The paper gives an overview of the results obtained on AMS-produced CMOS sensors coupled to the ATLAS Pixel FE-I4 readout chips. The SOI (silicon-on-insulator) produced sensors by XFAB hold great promise as radiation hard SOI-CMOS sensors due to their combination of partially depleted SOI transistors reducing back-gate effects. The test results include pre-/post-irradiation comparison, measurements of charge collection regions as well as test beam results.

  6. 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.

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

    PubMed Central

    Cooper, John; Yazvenko, Nina; Peyvan, Kia; Maurer, Karl; Taitt, Chris R.; Lyon, Wanda; Danley, David L.

    2010-01-01

    Background The CombiMatrix ElectraSense® microarray is a highly multiplex, complementary metal oxide semiconductor with 12,544 electrodes that are individually addressable. This platform is commercially available as a custom DNA microarray; and, in this configuration, it has also been used to tether antibodies (Abs) specifically on electrodes using complementary DNA sequences conjugated to the Abs. Methodology/Principal Findings An empirical method is described for developing and optimizing immunoassays on the CombiMatrix ElectraSense® microarray based upon targeted deposition of polypyrrole (Ppy) and capture Ab. This process was automated using instrumentation that can selectively apply a potential or current to individual electrodes and also measure current generated at the electrodes by an enzyme-enhanced electrochemical (ECD) reaction. By designating groups of electrodes on the array for different Ppy deposition conditions, we determined that the sensitivity and specificity of a sandwich immunoassay for staphylococcal enterotoxin B (SEB) is influenced by the application of different voltages or currents and the application time. The 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 detection were different. Conclusions/Significance Using Ppy deposition conditions for optimum results, the lower limit of detection for SEB using the ECD assay was between 0.003 and 0.01 pg/ml, which represents an order of magnitude improvement over a conventional enzyme-linked immunosorbant assay. In the absence of understanding the variables and complexities that affect assay performance, this highly multiplexed electrode array provided a rapid, high throughput, and empirical approach for developing a sensitive immunoassay. PMID:20333309

  8. 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.

  9. Low Power Camera-on-a-Chip Using CMOS Active Pixel Sensor Technology

    NASA Technical Reports Server (NTRS)

    Fossum, E. R.

    1995-01-01

    A second generation image sensor technology has been developed at the NASA Jet Propulsion Laboratory as a result of the continuing need to miniaturize space science imaging instruments. Implemented using standard CMOS, the active pixel sensor (APS) technology permits the integration of the detector array with on-chip timing, control and signal chain electronics, including analog-to-digital conversion.

  10. 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.

  11. Geant4-based simulations of charge collection in CMOS Active Pixel Sensors

    NASA Astrophysics Data System (ADS)

    Esposito, M.; Price, T.; Anaxagoras, T.; Allinson, N. M.

    2017-03-01

    Geant4 is an object-oriented toolkit for the simulation of the interaction of particles and radiation with matter. It provides a snapshot of the state of a simulated particle in time, as it travels through a specified geometry. One important area of application is the modelling of radiation detector systems. Here, we extend the abilities of such modelling to include charge transport and sharing in pixelated CMOS Active Pixel Sensors (APSs); though similar effects occur in other pixel detectors. The CMOS APSs discussed were developed in the framework of the PRaVDA consortium to assist the design of custom sensors to be used in an energy-range detector for proton Computed Tomography (pCT). The development of ad-hoc classes, providing a charge transport model for a CMOS APS and its integration into the standard Geant4 toolkit, is described. The proposed charge transport model includes, charge generation, diffusion, collection, and sharing across adjacent pixels, as well as the full electronic chain for a CMOS APS. The proposed model is validated against experimental data acquired with protons in an energy range relevant for pCT.

  12. 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.

  13. 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

  14. 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

  15. High-speed camera based on a CMOS active pixel sensor

    NASA Astrophysics Data System (ADS)

    Bloss, Hans S.; Ernst, Juergen D.; Firla, Heidrun; Schmoelz, Sybille C.; Gick, Stephan K.; Lauxtermann, Stefan C.

    2000-02-01

    Standard CMOS technologies offer great flexibility in the design of image sensors, which is a big advantage especially for high framerate system. For this application we have integrated an active pixel sensor with 256 X 256 pixel using a standard 0.5 micrometers CMOS technologies. With 16 analog outputs and a clockrate of 25-30 MHz per output, a continuous framerate of more than 50000 Hz is achieved. A global synchronous shutter is provided, but it required a more complex pixel circuit of five transistors and a special pixel layout to get a good optical fill factor. The active area of the photodiode is 9 X 9 micrometers . These square diodes are arranged in a chess pattern, while the remaining space is used for the electronic circuit. FIll factor is nearly 50 percent. The sensor is embedded in a high-speed camera system with 16 ADCs, 256Mbyte dynamic RAM, FPGAs for high-speed real time image processing, and a PC for user interface, data archive and network operation. Fixed pattern noise, which is always a problem of CMOS sensor, and the mismatching of the 16 analog channels is removed by a pixelwise gain-offset correction. After this, the chess pattern requires a reconstruction of all the 'missing' pixels, which can be done by a special edge sensitive algorithm. So a high quality 512 X 256 image with low remaining noise can be displayed. Sensor, architecture and processing are also suitable for color imaging.

  16. 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…

  17. 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.

  18. 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.

  19. 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.; hide

    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.

  20. 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.

  1. 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.

  2. HYBRID SILICON-ON-SAPPHIRE/SCALED CMOS INTERFERENCE MITIGATION FRONT END BASED ON SIMULTANEOUS NOISE CANCELLATION, ACTIVE-INTERFERENCE CANCELLATION AND N-PATH-MIXER FILTERING

    DTIC Science & Technology

    2017-04-01

    non-recurring engineering cost for the upgrading and maintenance of DoD receiver systems . 15. SUBJECT TERMS interference mitigation technology...maintenance of DoD receiver systems . Figure 1: Proposed Hybrid SOS/Scaled-CMOS Noise-Cancelling, Active-Interference- Cancelling, N-Path-Mixer Filtering...receiver sub- system (RSS). The second IC uses a scaled complementary metal-oxide-semiconductor (CMOS) technology (namely 45nm SOI CMOS) to implement a

  3. Radiation damage caused by cold neutrons in boron doped CMOS active pixel sensors

    NASA Astrophysics Data System (ADS)

    Linnik, B.; Bus, T.; Deveaux, M.; Doering, D.; Kudejova, P.; Wagner, F. M.; Yazgili, A.; Stroth, J.

    2017-05-01

    CMOS Monolithic Active Pixel Sensors (MAPS) are considered as an emerging technology in the field of charged particle tracking. They will be used in the vertex detectors of experiments like STAR, CBM and ALICE and are considered for the ILC and the tracker of ATLAS. In those applications, the sensors are exposed to sizeable radiation doses. While the tolerance of MAPS to ionizing radiation and fast hadrons is well known, the damage caused by low energy neutrons was not studied so far. Those slow neutrons may initiate nuclear fission of 10B dopants found in the B-doped silicon active medium of MAPS. This effect was expected to create an unknown amount of radiation damage beyond the predictions of the NIEL (Non Ionizing Energy Loss) model for pure silicon. We estimate the impact of this effect by calculating the additional NIEL created by this fission. Moreover, we show first measured data for CMOS sensors which were irradiated with cold neutrons. The empirical results contradict the prediction of the updated NIEL model both, qualitatively and quantitatively: the sensors irradiated with slow neutrons show an unexpected and strong acceptor removal, which is not observed in sensors irradiated with MeV neutrons.

  4. 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.

  5. 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.

  6. Use of a Multiplexed CMOS Microarray to Optimize and Compare Oligonucleotide Binding to DNA Probes Synthesized or Immobilized on Individual Electrodes

    PubMed Central

    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. PMID:22163607

  7. 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.

  8. 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.

  9. 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

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

    2016-04-01

    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-labeled antibody/laser scanner system. To do this, duplicate proteome microarrays of Vaccinia virus, Brucella melitensis and Plasmodium falciparum were probed with identical samples of immune sera, and IgG, IgA, and IgM profiles visualized using biotinylated secondary antibodies followed by a tertiary reagent of streptavidin coupled to either P3 (an organic cyanine dye typically used for microarrays) or Q800 (Qdot). The data show excellent correlation for all samples tested (R > 0.8) with no significant change of antibody reactivity profiles. We conclude that Qdot detection provides data equivalent to that obtained using conventional organic dye detection. The portable imager offers an economical, more robust, and deployable alternative to conventional laser array scanners. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  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. 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.

  12. Development and application of the active surveillance of pathogens microarray to monitor bacterial gene flux

    PubMed Central

    Stabler, Richard A; Dawson, Lisa F; Oyston, Petra CF; Titball, Richard W; Wade, Jim; Hinds, Jason; Witney, Adam A; Wren, Brendan W

    2008-01-01

    Background Human and animal health is constantly under threat by emerging pathogens that have recently acquired genetic determinants that enhance their survival, transmissibility and virulence. We describe the construction and development of an Active Surveillance of Pathogens (ASP) oligonucleotide microarray, designed to 'actively survey' the genome of a given bacterial pathogen for virulence-associated genes. Results The microarray consists of 4958 reporters from 151 bacterial species and include genes for the identification of individual bacterial species as well as mobile genetic elements (transposons, plasmid and phage), virulence genes and antibiotic resistance genes. The ASP microarray was validated with nineteen bacterial pathogens species, including Francisella tularensis, Clostridium difficile, Staphylococcus aureus, Enterococcus faecium and Stenotrophomonas maltophilia. The ASP microarray identified these bacteria, and provided information on potential antibiotic resistance (eg sufamethoxazole resistance and sulfonamide resistance) and virulence determinants including genes likely to be acquired by horizontal gene transfer (e.g. an alpha-haemolysin). Conclusion The ASP microarray has potential in the clinic as a diagnostic tool, as a research tool for both known and emerging pathogens, and as an early warning system for pathogenic bacteria that have been recently modified either naturally or deliberately. PMID:18844996

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. Active High Power Conversion Efficiency Rectifier With Built-In Dual-Mode Back Telemetry in Standard CMOS Technology.

    PubMed

    Bawa, G; Ghovanloo, M

    2008-09-01

    In this paper, we present an active rectifier with high power conversion efficiency (PCE) implemented in a 0.5- mum 5 V standard CMOS technology with two modes of built-in back telemetry; short- and open-circuit. As a rectifier, it ensures a PCE > 80%, taking advantage of active synchronous rectification technique in the frequency range of 0.125-1 MHz. The built-in complementary back telemetry feature can be utilized in implantable microelectronic devices (IMD), wireless sensors, and radio frequency identification (RFID) applications to reduce the silicon area, increase the data rate, and improve the reading range and robustness in load shift keying (LSK).

  1. 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

  2. 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.

  3. 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

  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. 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

  6. 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.

  7. 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.

  8. First tests of a novel radiation hard CMOS sensor process for Depleted Monolithic Active Pixel Sensors

    NASA Astrophysics Data System (ADS)

    Pernegger, H.; Bates, R.; Buttar, C.; Dalla, M.; van Hoorne, J. W.; Kugathasan, T.; Maneuski, D.; Musa, L.; Riedler, P.; Riegel, C.; Sbarra, C.; Schaefer, D.; Schioppa, E. J.; Snoeys, W.

    2017-06-01

    The upgrade of the ATLAS [1] tracking detector for the High-Luminosity Large Hadron Collider (LHC) at CERN requires novel radiation hard silicon sensor technologies. Significant effort has been put into the development of monolithic CMOS sensors but it has been a challenge to combine a low capacitance of the sensing node with full depletion of the sensitive layer. Low capacitance brings low analog power. Depletion of the sensitive layer causes the signal charge to be collected by drift sufficiently fast to separate hits from consecutive bunch crossings (25 ns at the LHC) and to avoid losing the charge by trapping. This paper focuses on the characterization of charge collection properties and detection efficiency of prototype sensors originally designed in the framework of the ALICE Inner Tracking System (ITS) upgrade [2]. The prototypes are fabricated both in the standard TowerJazz 180nm CMOS imager process [3] and in an innovative modification of this process developed in collaboration with the foundry, aimed to fully deplete the sensitive epitaxial layer and enhance the tolerance to non-ionizing energy loss. Sensors fabricated in standard and modified process variants were characterized using radioactive sources, focused X-ray beam and test beams before and after irradiation. Contrary to sensors manufactured in the standard process, sensors from the modified process remain fully functional even after a dose of 1015neq/cm2, which is the the expected NIEL radiation fluence for the outer pixel layers in the future ATLAS Inner Tracker (ITk) [4].

  9. 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.

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

    SciTech Connect

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

    2009-01-15

    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 {mu}C/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.

  11. Autoantigen microarrays reveal autoantibodies associated with proliferative nephritis and active disease in pediatric systemic lupus erythematosus.

    PubMed

    Haddon, D James; Diep, Vivian K; Price, Jordan V; Limb, Cindy; Utz, Paul J; Balboni, Imelda

    2015-06-17

    Pediatric systemic lupus erythematosus (pSLE) patients often initially present with more active and severe disease than adults, including a higher frequency of lupus nephritis. Specific autoantibodies, including anti-C1q, anti-DNA and anti-alpha-actinin, have been associated with kidney involvement in SLE, and DNA antibodies are capable of initiating early-stage lupus nephritis in severe combined immunodeficiency (SCID) mice. Over 100 different autoantibodies have been described in SLE patients, highlighting the need for comprehensive autoantibody profiling. Knowledge of the antibodies associated with pSLE and proliferative nephritis will increase the understanding of SLE pathogenesis, and may aid in monitoring patients for renal flare. We used autoantigen microarrays composed of 140 recombinant or purified antigens to compare the serum autoantibody profiles of new-onset pSLE patients (n = 45) to healthy controls (n = 17). We also compared pSLE patients with biopsy-confirmed class III or IV proliferative nephritis (n = 23) and without significant renal involvement (n = 18). We performed ELISA with selected autoantigens to validate the microarray findings. We created a multiple logistic regression model, based on the ELISA and clinical information, to predict whether a patient had proliferative nephritis, and used a validation cohort (n = 23) and longitudinal samples (88 patient visits) to test its accuracy. Fifty autoantibodies were at significantly higher levels in the sera of pSLE patients compared to healthy controls, including anti-B cell-activating factor (BAFF). High levels of anti-BAFF were associated with active disease. Thirteen serum autoantibodies were present at significantly higher levels in pSLE patients with proliferative nephritis than those without, and we confirmed five autoantigens (dsDNA, C1q, collagens IV and X and aggrecan) by ELISA. Our model, based on ELISA measurements and clinical variables, correctly identified patients with proliferative

  12. 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

  13. A CMOS active pixel sensor system for laboratory- based x-ray diffraction studies of biological tissue

    NASA Astrophysics Data System (ADS)

    Bohndiek, Sarah E.; Cook, Emily J.; Arvanitis, Costas D.; Olivo, Alessandro; Royle, Gary J.; Clark, Andy T.; Prydderch, Mark L.; Turchetta, Renato; Speller, Robert D.

    2008-02-01

    X-ray diffraction studies give material-specific information about biological tissue. Ideally, a large area, low noise, wide dynamic range digital x-ray detector is required for laboratory-based x-ray diffraction studies. The goal of this work is to introduce a novel imaging technology, the CMOS active pixel sensor (APS) that has the potential to fulfil all these requirements, and demonstrate its feasibility for coherent scatter imaging. A prototype CMOS APS has been included in an x-ray diffraction demonstration system. An industrial x-ray source with appropriate beam filtration is used to perform angle dispersive x-ray diffraction (ADXRD). Optimization of the experimental set-up is detailed including collimator options and detector operating parameters. Scatter signatures are measured for 11 different materials, covering three medical applications: breast cancer diagnosis, kidney stone identification and bone mineral density calculations. Scatter signatures are also recorded for three mixed samples of known composition. Results are verified using two independent models for predicting the APS scatter signature: (1) a linear systems model of the APS and (2) a linear superposition integral combining known monochromatic scatter signatures with the input polychromatic spectrum used in this case. Cross validation of experimental, modelled and literature results proves that APS are able to record biologically relevant scatter signatures. Coherent scatter signatures are sensitive to multiple materials present in a sample and provide a means to quantify composition. In the future, production of a bespoke APS imager for x-ray diffraction studies could enable simultaneous collection of the transmitted beam and scattered radiation in a laboratory-based coherent scatter system, making clinical transfer of the technique attainable.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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).

  19. 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.

  20. 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.

  1. 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

  2. Large area CMOS image sensors

    NASA Astrophysics Data System (ADS)

    Turchetta, R.; Guerrini, N.; Sedgwick, I.

    2011-01-01

    CMOS image sensors, also known as CMOS Active Pixel Sensors (APS) or Monolithic Active Pixel Sensors (MAPS), are today the dominant imaging devices. They are omnipresent in our daily life, as image sensors in cellular phones, web cams, digital cameras, ... In these applications, the pixels can be very small, in the micron range, and the sensors themselves tend to be limited in size. However, many scientific applications, like particle or X-ray detection, require large format, often with large pixels, as well as other specific performance, like low noise, radiation hardness or very fast readout. The sensors are also required to be sensitive to a broad spectrum of radiation: photons from the silicon cut-off in the IR down to UV and X- and gamma-rays through the visible spectrum as well as charged particles. This requirement calls for modifications to the substrate to be introduced to provide optimized sensitivity. This paper will review existing CMOS image sensors, whose size can be as large as a single CMOS wafer, and analyse the technical requirements and specific challenges of large format CMOS image sensors.

  3. Inferring transcription factor activity from microarray data reveals novel targets for toxicological investigations.

    PubMed

    Souza, T M; van den Beucken, T; Kleinjans, J C S; Jennen, D G J

    2017-08-15

    Transcription factors (TFs) are important modulators of the inducible portion of the transcriptome, and therefore relevant in the context of exposure to exogenous compounds. Current approaches to predict the activity of TFs in biological systems are usually restricted to a few entities at a time due to low-throughput techniques targeting a limited fraction of annotated human TFs. Therefore, high-throughput alternatives may help to identify new targets of mechanistic and predictive value in toxicological investigations. In this study, we inferred the activity multiple TFs using publicly available microarray data from primary human hepatocytes exposed to hundreds of chemicals and evaluated these molecular profiles using multiple correspondence analysis. Our results demonstrate that the lowest dose and latest exposure time (24h) in a subset of chemicals generates a signature indicative of carcinogenicity possibly due to DNA-damaging properties. Furthermore, profiles from the earliest exposure time (2h) and highest dose creates clusters of chemicals implicated in the development of diverse forms of drug-induced liver injury (DILI). Both approaches yielded a number of TFs with similar activity across groups of chemicals, including TFs known in toxicological responses such as AhR, NFE2L2 (Nrf2), NF-κB and PPARG. FOXM1, IRF1 and E2F4 were some of the TFs identified that may be relevant in genotoxic carcinogenesis. SMADs (SMAD1, SMAD2, SMAD5) and KLF5 were identified as some of potentially new TFs whose inferred activities were linked to acute and progressive outcomes in DILI. In conclusion this study offers a novel mechanistic approach targeting TF activity during chemical exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. 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. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  5. Tissue microarray methodology identifies complement pathway activation and dysregulation in progressive multiple sclerosis.

    PubMed

    Loveless, Sam; Neal, James W; Howell, Owain W; Harding, Katharine E; Sarkies, Patrick; Evans, Rhian; Bevan, Ryan J; Hakobyan, Svetlana; Harris, Claire L; Robertson, Neil P; Morgan, Bryan Paul

    2017-07-14

    The complement pathway has potential contributions to both white (WM) and grey matter (GM) pathology in Multiple Sclerosis (MS). A quantitative assessment of complement involvement is lacking. Here we describe the use of Tissue MicroArray (TMA) methodology in conjunction with immunohistochemistry to investigate the localization of complement pathway proteins in progressive MS cortical GM and subcortical WM. Antibodies targeting complement proteins C1q, C3b, regulatory proteins C1 inhibitor (C1INH, complement receptor 1 (CR1), clusterin, factor H (FH) and the C5a anaphylatoxin receptor (C5aR) were utilised alongside standard markers of tissue pathology. All stained slides were digitised for quantitative analysis. We found that numbers of cells immunolabelled for HLA-DR, GFAP, C5aR, C1q and C3b were increased in WM lesions (WML) and GM lesions (GML) compared to normal appearing WM (NAWM) and GM (NAGM), respectively. The complement regulators C1INH, CR1, FH and clusterin were more abundant in WM lesions, while the number of C1q+ neurons were increased and the number of C1INH+, clusterin+, FH+ and CR1+ neurons decreased in GM lesions. The number of complement component positive cells (C1q, C3b) correlated with complement regulator expression in WM, but there was no statistical association between complement activation and regulator expression in the GM. We conclude that TMA methodology and quantitative analysis provides evidence of complement dysregulation in MS GML, including an association of the numerical density of C1q+ cells with tissue lesions. Our work confirms that complement activation and dysregulation occur in all cases of progressive MS and suggest that complement may provide potential biomarkers of the disease. © 2017 International Society of Neuropathology.

  6. Micro-earthquakes monitoring at the Irpinia active fault zone by micro-arrays

    NASA Astrophysics Data System (ADS)

    Adinolfi, Guido Maria; Picozzi, Matteo; Zollo, Aldo; Parolai, Stefano

    2017-04-01

    The micro-seismicity monitoring requires the use of local dense network with an optimum azimuthal coverage. In the case of natural seismicity, different stations should be employed around a fault structure in order to characterize at first sights its dimensions, geometry and seismic activity. For induced seismicity, it is necessary to monitor the spatio-temporal evolution of earthquakes in order to follow the fluid migration and the fracture pattern of the reservoir. We propose the use of seismic arrays as alternative solution to dense and expensive seismic network to monitor and study the micro-seismicity. We designed a field experiment in the Irpinia region (Southern Italy) with seismic micro-arrays and tested its performance to record natural micro-seismicity. In particular, the experiment consisted of three seismic arrays at few tens of kilometers distance installed around one segment activated during the Ms 6.9 Irpinia earthquake in 1980. Each array is made up of seven stations, with three components sensor, small aperture (few hundred meters) and irregular geometries. Natural seismicity of the area, arranged occasionally in small seismic sequences, was recorded with magnitude (Ml) ranging between 0.5 and 1.6. Through the f-k analysis on three components, we derive for each earthquake apparent velocity and back-azimuth at each array of the incoming wavefront and, combining the information of the three arrays, we try to triangulate the ipocenter for a better estimate of the earthquake location. The results of the experiment are compared with the earthquake locations derived by ISNet, the local operating network that monitors the Irpinia faults system. We discuss our preliminary results and the seismic arrays performance to monitor the micro-seismicity, as valid and alternative tool to study natural or induced seismicity.

  7. 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

  8. Deubiquitylase, DeSUMOylase, and DeISGylase Activity Microarrays for Assay of Substrate Preference and Functional Modifiers*

    PubMed Central

    Loch, Christian M.; Cuccherini, Charles L.; Leach, Craig A.; Strickler, James E.

    2011-01-01

    Microarray-based proteomics expanded the information potential of DNA arrays to the level of protein translation and interaction, but so far, not much beyond. Although enzymatic activity from immobilized proteins has been reliably studied using surface plasmon resonance, a microarray of catalytically competent enzymes would facilitate high throughput, parallel study of their function. The ability to localize activity from soluble substrates has frustrated development of such an array. Here, we report the novel use of previously developed, highly specific suicide substrates for three families of enzymes: deubiquitylases, deSUMOylases, and deISGylases. We show specificity of each family to its cognate substrate, and demonstrate utility of the array in a secondary screen of small molecule inhibitors. PMID:20956615

  9. Biomarker genes used to predict AhR activity; accession numbers of microarray datasets used in the study

    EPA Pesticide Factsheets

    Biomarker genes used to predict AhR activity; accession numbers of microarray datasets used in the studyThis dataset is associated with the following publication:Oshida, K., N. Vasani, W. Ward , R. Thomas , D. Applegate, F. Gonzalez, L. Aleksunes, C. Klaassen, and C. Corton. Screening a mouse liver gene expression Compendium Identifies Effectors of the Aryl Hydrocarbon reeptors (AhR). TOXICOLOGICAL SCIENCES. Society of Toxicology, 336: 99-112, (2015).

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. A 13.56 MHz CMOS Active Rectifier With Switched-Offset and Compensated Biasing for Biomedical Wireless Power Transfer Systems.

    PubMed

    Yan Lu; Wing-Hung Ki

    2014-06-01

    A full-wave active rectifier switching at 13.56 MHz with compensated bias current for a wide input range for wirelessly powered high-current biomedical implants is presented. The four diodes of a conventional passive rectifier are replaced by two cross-coupled PMOS transistors and two comparator- controlled NMOS switches to eliminate diode voltage drops such that high voltage conversion ratio and power conversion efficiency could be achieved even at low AC input amplitude |VAC|. The comparators are implemented with switched-offset biasing to compensate for the delays of active diodes and to eliminate multiple pulsing and reverse current. The proposed rectifier uses a modified CMOS peaking current source with bias current that is quasi-inversely proportional to the supply voltage to better control the reverse current over a wide AC input range (1.5 to 4 V). The rectifier was fabricated in a standard 0.35 μm CMOS N-well process with active area of 0.0651 mm(2). For the proposed rectifier measured at |VAC| = 3.0 V, the voltage conversion ratios are 0.89 and 0.93 for RL=500 Ω and 5 kΩ, respectively, and the measured power conversion efficiencies are 82.2% to 90.1% with |VAC| ranges from 1.5 to 4 V for RL=500 Ω.

  16. 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.

  17. 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.

  18. Use of Microarray Datasets to generate Caco-2-dedicated Networks and to identify Reporter Genes of Specific Pathway Activity.

    PubMed

    Venkatasubramanian, Prashanna Balaji; Toydemir, Gamze; de Wit, Nicole; Saccenti, Edoardo; Martins Dos Santos, Vitor A P; van Baarlen, Peter; Wells, Jerry M; Suarez-Diez, Maria; Mes, Jurriaan J

    2017-07-28

    Intestinal epithelial cells, like Caco-2, are commonly used to study the interaction between food, other luminal factors and the host, often supported by microarray analysis to study the changes in gene expression as a result of the exposure. However, no compiled dataset for Caco-2 has ever been initiated and Caco-2-dedicated gene expression networks are barely available. Here, 341 Caco-2-specific microarray samples were collected from public databases and from in-house experiments pertaining to Caco-2 cells exposed to pathogens, probiotics and several food compounds. Using these datasets, a gene functional association network specific for Caco-2 was generated containing 8937 nodes 129711 edges. Two in silico methods, a modified version of biclustering and the new Differential Expression Correlation Analysis, were developed to identify Caco-2-specific gene targets within a pathway of interest. These methods were subsequently applied to the AhR and Nrf2 signalling pathways and altered expression of the predicted target genes was validated by qPCR in Caco-2 cells exposed to coffee extracts, known to activate both AhR and Nrf2 pathways. The datasets and in silico method(s) to identify and predict responsive target genes can be used to more efficiently design experiments to study Caco-2/intestinal epithelial-relevant biological processes.

  19. Fluorescent Activated Cell Sorting (FACS) Combined with Gene Expression Microarrays for Transcription Enrichment Profiling of Zebrafish Lateral Line Cells

    PubMed Central

    Gallardo, Viviana E; Behra, Martine

    2013-01-01

    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. PMID:23791746

  20. 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. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Functional GPCR microarrays.

    PubMed

    Hong, Yulong; Webb, Brian L; Su, Hui; Mozdy, Eric J; Fang, Ye; Wu, Qi; Liu, Li; Beck, Jonathan; Ferrie, Ann M; Raghavan, Srikanth; Mauro, John; Carre, Alain; Müeller, Dirk; Lai, Fang; Rasnow, Brian; Johnson, Michael; Min, Hosung; Salon, John; Lahiri, Joydeep

    2005-11-09

    This paper describes G-protein-coupled receptor (GPCR) microarrays on porous glass substrates and functional assays based on the binding of a europium-labeled GTP analogue. The porous glass slides were made by casting a glass frit on impermeable glass slides and then coating with gamma-aminopropyl silane (GAPS). The emitted fluorescence was captured on an imager with a time-gated intensified CCD detector. Microarrays of the neurotensin receptor 1, the cholinergic receptor muscarinic 2, the opioid receptor mu, and the cannabinoid receptor 1 were fabricated by pin printing. The selective agonism of each of the receptors was observed. The screening of potential antagonists was demonstrated using a cocktail of agonists. The amount of activation observed was sufficient to permit determinations of EC50 and IC50. Such microarrays could potentially streamline drug discovery by helping integrate primary screening with selectivity and safety screening without compromising the essential functional information obtainable from cellular assays.

  2. Empirical electro-optical and x-ray performance evaluation of CMOS active pixels sensor for low dose, high resolution x-ray medical imaging.

    PubMed

    Arvanitis, C D; Bohndiek, S E; Royle, G; Blue, A; Liang, H X; Clark, A; Prydderch, M; Turchetta, R; Speller, R

    2007-12-01

    Monolithic complementary metal oxide semiconductor (CMOS) active pixel sensors with high performance have gained attention in the last few years in many scientific and space applications. In order to evaluate the increasing capabilities of this technology, in particular where low dose high resolution x-ray medical imaging is required, critical electro-optical and physical x-ray performance evaluation was determined. The electro-optical performance includes read noise, full well capacity, interacting quantum efficiency, and pixels cross talk. The x-ray performance, including x-ray sensitivity, modulation transfer function, noise power spectrum, and detection quantum efficiency, has been evaluated in the mammographic energy range. The sensor is a 525 x 525 standard three transistor CMOS active pixel sensor array with more than 75% fill factor and 25 x 25 microm pixel pitch. Reading at 10 f/s, it is found that the sensor has 114 electrons total additive noise, 10(5) electrons full well capacity with shot noise limited operation, and 34% interacting quantum efficiency at 530 nm. Two different structured CsI:Tl phosphors with thickness 95 and 115 microm, respectively, have been optically coupled via a fiber optic plate to the array resulting in two different system configurations. The sensitivity of the two different system configurations was 43 and 47 electrons per x-ray incident on the sensor. The MTF at 10% of the two different system configurations was 9.5 and 9 cycles/mm with detective quantum efficiency of 0.45 and 0.48, respectively, close to zero frequency at approximately 0.44 microC/kg (1.72 mR) detector entrance exposure. The detector was quantum limited at low spatial frequencies and its performance was comparable with high resolution a: Si and charge coupled device based x-ray imagers. The detector also demonstrates almost an order of magnitude lower noise than active matrix flat panel imagers. The results suggest that CMOS active pixel sensors when coupled

  3. 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.

  4. 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.

  5. 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.

  6. Performance of capacitively coupled active pixel sensors in 180 nm HV-CMOS technology after irradiation to HL-LHC fluences

    NASA Astrophysics Data System (ADS)

    Feigl, S.

    2014-03-01

    In this ATLAS upgrade R&D project, we explore the concept of using a deep-submicron HV-CMOS process to produce a drop-in replacement for traditional radiation-hard silicon sensors. Such active sensors contain simple circuits, e.g. amplifiers and discriminators, but still require a traditional (pixel or strip) readout chip. This approach yields most advantages of MAPS (improved resolution, reduced cost and material budget, etc.), without the complication of full integration on a single chip. After outlining the basic design of the HV2FEI4 test ASIC, results after irradiation with X-rays to 862 Mrad and neutrons up to 1016(1 MeV neq)/cm2 will be presented. Finally, a brief outlook on further development plans is given.

  7. 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

  8. 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.

  9. Application of a novel functional gene microarray to probe the functional ecology of ammonia oxidation in nitrifying activated sludge.

    PubMed

    Short, Michael D; Abell, Guy C J; Bodrossy, Levente; van den Akker, Ben

    2013-01-01

    We report on the first study trialling a newly-developed, functional gene microarray (FGA) for characterising bacterial and archaeal ammonia oxidisers in activated sludge. Mixed liquor (ML) and media biofilm samples from a full-scale integrated fixed-film activated sludge (IFAS) plant were analysed with the FGA to profile the diversity and relative abundance of ammonia-oxidising archaea and bacteria (AOA and AOB respectively). FGA analyses of AOA and AOB communities revealed ubiquitous distribution of AOA across all samples - an important finding for these newly-discovered and poorly characterised organisms. Results also revealed striking differences in the functional ecology of attached versus suspended communities within the IFAS reactor. Quantitative assessment of AOB and AOA functional gene abundance revealed a dominance of AOB in the ML and approximately equal distribution of AOA and AOB in the media-attached biofilm. Subsequent correlations of functional gene abundance data with key water quality parameters suggested an important functional role for media-attached AOB in particular for IFAS reactor nitrification performance and indicate possible functional redundancy in some IFAS ammonia oxidiser communities. Results from this investigation demonstrate the capacity of the FGA to resolve subtle ecological shifts in key microbial communities in nitrifying activated sludge and indicate its value as a tool for better understanding the linkages between the ecology and performance of these engineered systems.

  10. Application of a Novel Functional Gene Microarray to Probe the Functional Ecology of Ammonia Oxidation in Nitrifying Activated Sludge

    PubMed Central

    Short, Michael D.; Abell, Guy C. J.; Bodrossy, Levente; van den Akker, Ben

    2013-01-01

    We report on the first study trialling a newly-developed, functional gene microarray (FGA) for characterising bacterial and archaeal ammonia oxidisers in activated sludge. Mixed liquor (ML) and media biofilm samples from a full-scale integrated fixed-film activated sludge (IFAS) plant were analysed with the FGA to profile the diversity and relative abundance of ammonia-oxidising archaea and bacteria (AOA and AOB respectively). FGA analyses of AOA and AOB communities revealed ubiquitous distribution of AOA across all samples – an important finding for these newly-discovered and poorly characterised organisms. Results also revealed striking differences in the functional ecology of attached versus suspended communities within the IFAS reactor. Quantitative assessment of AOB and AOA functional gene abundance revealed a dominance of AOB in the ML and approximately equal distribution of AOA and AOB in the media-attached biofilm. Subsequent correlations of functional gene abundance data with key water quality parameters suggested an important functional role for media-attached AOB in particular for IFAS reactor nitrification performance and indicate possible functional redundancy in some IFAS ammonia oxidiser communities. Results from this investigation demonstrate the capacity of the FGA to resolve subtle ecological shifts in key microbial communities in nitrifying activated sludge and indicate its value as a tool for better understanding the linkages between the ecology and performance of these engineered systems. PMID:24155925

  11. Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study

    PubMed Central

    2012-01-01

    Background This study undertakes a systematic and comprehensive analysis of brain gene expression profiles of immune/inflammation-related genes in aging and Alzheimer’s disease (AD). Methods In a well-powered microarray study of young (20 to 59 years), aged (60 to 99 years), and AD (74 to 95 years) cases, gene responses were assessed in the hippocampus, entorhinal cortex, superior frontal gyrus, and post-central gyrus. Results Several novel concepts emerge. First, immune/inflammation-related genes showed major changes in gene expression over the course of cognitively normal aging, with the extent of gene response far greater in aging than in AD. Of the 759 immune-related probesets interrogated on the microarray, approximately 40% were significantly altered in the SFG, PCG and HC with increasing age, with the majority upregulated (64 to 86%). In contrast, far fewer immune/inflammation genes were significantly changed in the transition to AD (approximately 6% of immune-related probesets), with gene responses primarily restricted to the SFG and HC. Second, relatively few significant changes in immune/inflammation genes were detected in the EC either in aging or AD, although many genes in the EC showed similar trends in responses as in the other brain regions. Third, immune/inflammation genes undergo gender-specific patterns of response in aging and AD, with the most pronounced differences emerging in aging. Finally, there was widespread upregulation of genes reflecting activation of microglia and perivascular macrophages in the aging brain, coupled with a downregulation of select factors (TOLLIP, fractalkine) that when present curtail microglial/macrophage activation. Notably, essentially all pathways of the innate immune system were upregulated in aging, including numerous complement components, genes involved in toll-like receptor signaling and inflammasome signaling, as well as genes coding for immunoglobulin (Fc) receptors and human leukocyte antigens I

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. Expression profiling of peroxisome proliferator-activated receptor-delta (PPAR-delta) in mouse tissues using tissue microarray.

    PubMed

    Higashiyama, Hiroyuki; Billin, Andrew N; Okamoto, Yuji; Kinoshita, Mine; Asano, Satoshi

    2007-05-01

    Peroxisome proliferator-activated receptor-delta (PPAR-delta) is known as a transcription factor involved in the regulation of fatty acid oxidation and mitochondrial biogenesis in several tissues, such as skeletal muscle, liver and adipose tissues. In this study, to elucidate systemic physiological functions of PPAR-delta, we examined the tissue distribution and localization of PPAR-delta in adult mouse tissues using tissue microarray (TMA)-based immunohistochemistry. PPAR-delta positive signals were observed on variety of tissues/cells in multiple systems including cardiovascular, urinary, respiratory, digestive, endocrine, nervous, hematopoietic, immune, musculoskeletal, sensory and reproductive organ systems. In these organs, PPAR-delta immunoreactivity was generally localized on the nucleus, although cytoplasmic localization was observed on several cell types including neurons in the nervous system and cells of the islet of Langerhans. These expression profiling data implicate various physiological roles of PPAR-delta in multiple organ systems. TMA-based immunohistochemistry enables to profile comprehensive protein localization and distribution in a high-throughput manner.

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

    PubMed

    Rajandram, Retnagowri; Razack, Azad H A; Ng, Keng Lim; Gobe, Glenda C

    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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  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. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. Dual activation of pathways regulated by steroid receptors and peptide growth factors in primary prostate cancer revealed by Factor Analysis of microarray data

    PubMed Central

    Lozano, Juan Jose; Soler, Marta; Bermudo, Raquel; Abia, David; Fernandez, Pedro L; Thomson, Timothy M; Ortiz, Angel R

    2005-01-01

    Background We use an approach based on Factor Analysis to analyze datasets generated for transcriptional profiling. The method groups samples into biologically relevant categories, and enables the identification of genes and pathways most significantly associated to each phenotypic group, while allowing for the participation of a given gene in more than one cluster. Genes assigned to each cluster are used for the detection of pathways predominantly activated in that cluster by finding statistically significant associated GO terms. We tested the approach with a published dataset of microarray experiments in yeast. Upon validation with the yeast dataset, we applied the technique to a prostate cancer dataset. Results Two major pathways are shown to be activated in organ-confined, non-metastatic prostate cancer: those regulated by the androgen receptor and by receptor tyrosine kinases. A number of gene markers (HER3, IQGAP2 and POR1) highlighted by the software and related to the later pathway have been validated experimentally a posteriori on independent samples. Conclusion Using a new microarray analysis tool followed by a posteriori experimental validation of the results, we have confirmed several putative markers of malignancy associated with peptide growth factor signalling in prostate cancer and revealed others, most notably ERRB3 (HER3). Our study suggest that, in primary prostate cancer, HER3, together or not with HER4, rather than in receptor complexes involving HER2, could play an important role in the biology of these tumors. These results provide new evidence for the role of receptor tyrosine kinases in the establishment and progression of prostate cancer. PMID:16107210

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Reverse Phase Protein Microarrays.

    PubMed

    Baldelli, Elisa; Calvert, Valerie; Hodge, Alex; VanMeter, Amy; Petricoin, Emanuel F; Pierobon, Mariaelena

    2017-01-01

    While genes and RNA encode information about cellular status, proteins are considered the engine of the cellular machine, as they are the effective elements that drive all cellular functions including proliferation, migration, differentiation, and apoptosis. Consequently, investigations of the cellular protein network are considered a fundamental tool for understanding cellular functions.Alteration of the cellular homeostasis driven by elaborate intra- and extracellular interactions has become one of the most studied fields in the era of personalized medicine and targeted therapy. Increasing interest has been focused on developing and improving proteomic technologies that are suitable for analysis of clinical samples. In this context, reverse-phase protein microarrays (RPPA) is a sensitive, quantitative, high-throughput immunoassay for protein analyses of tissue samples, cells, and body fluids.RPPA is well suited for broad proteomic profiling and is capable of capturing protein activation as well as biochemical reactions such as phosphorylation, glycosylation, ubiquitination, protein cleavage, and conformational alterations across hundreds of samples using a limited amount of biological material. For these reasons, RPPA represents a valid tool for protein analyses and generates data that help elucidate the functional signaling architecture through protein-protein interaction and protein activation mapping for the identification of critical nodes for individualized or combinatorial targeted therapy.

  2. 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.

  3. DNA Microarray Technology

    SciTech Connect

    WERNER-WASHBURNE, MARGARET; DAVIDSON, GEORGE S.

    2002-01-01

    Collaboration between Sandia National Laboratories and the University of New Mexico Biology Department resulted in the capability to train students in microarray techniques and the interpretation of data from microarray experiments. These studies provide for a better understanding of the role of stationary phase and the gene regulation involved in exit from stationary phase, which may eventually have important clinical implications. Importantly, this research trained numerous students and is the basis for three new Ph.D. projects.

  4. The acquisition of resistance to TNFα in breast cancer cells is associated with constitutive activation of autophagy as revealed by a transcriptome analysis using a custom microarray.

    PubMed

    Moussay, Etienne; Kaoma, Tony; Baginska, Joanna; Muller, Arnaud; Van Moer, Kris; Nicot, Nathalie; Nazarov, Petr V; Vallar, Laurent; Chouaib, Salem; Berchem, Guy; Janji, Bassam

    2011-07-01

    While the autophagic process is mainly regulated at the post-translational level, a growing body of evidence suggests that autophagy might also be regulated at the transcriptional level. The identification of transcription factors involved in the regulation of autophagy genes has provided compelling evidence for such regulation. In this context, a powerful high throughput analysis tool to simultaneously monitor the expression level of autophagy genes is urgently needed. Here we describe setting up the first comprehensive human autophagy database (HADb, available at www.autophagy.lu) and the development of a companion Human Autophagy-dedicated cDNA Microarray which comprises 234 genes involved in or related to autophagy. The autophagy microarray tool used on breast adenocarcinoma MCF-7 cell line allowed the identification of 47 differentially expressed autophagy genes associated with the acquisition of resistance to the cytotoxic effect of TNFα. The autophagy-core machinery genes DRAM (Damage-Regulated Autophagy Modulator), BNIP3L (BCL2/adenovirus E1B 19 kDa interacting protein 3-like), BECN1 (Beclin 1), GABARAP (Gamma-AminoButyric Acid Receptor-Associated Protein) and UVRAG (UV radiation resistance associated gene) were found upregulated in TNF-resistant cells, suggesting a constitutive activation of the autophagy machinery in these cells. More interestingly, we identified NPC1 as the most upregulated genes in TNF-resistant compared to TNF-sensitive MCF-7 cells, suggesting a relation between the intracellular transport of cholesterol, the regulation of autophagy and NPC1 expression in TNF-resistant tumor cells. In conclusion, we describe here new tools that may help investigating autophagy gene regulation in various cellular models and diseases.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Evaluation of Surface Chemistries for Antibody Microarrays

    SciTech Connect

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

    2007-12-01

    Antibody microarrays are an emerging technology that promises to be a powerful tool for the detection of disease biomarkers. The current technology for protein microarrays has been primarily derived from DNA microarrays and is not fully characterized for use with proteins. For example, there are a myriad of surface chemistries that are commercially available for antibody microarrays, but no rigorous studies that compare these different surfaces. Therefore, we have used an enzyme-linked immunosorbent assay (ELISA) microarray platform to analyze 16 different commercially available slide types. Full standard curves were generated for 24 different assays. We found that this approach provides a rigorous and quantitative system for comparing the different slide types based on spot size and morphology, slide noise, spot background, lower limit of detection, and reproducibility. These studies demonstrate that the properties of the slide surface affect the activity of immobilized antibodies and the quality of data produced. Although many slide types can produce useful data, glass slides coated with poly-L-lysine or aminosilane, with or without activation with a crosslinker, consistently produce superior results in the ELISA microarray analyses we performed.

  11. 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.

  12. Large Format CMOS-based Detectors for Diffraction Studies

    NASA Astrophysics Data System (ADS)

    Thompson, A. C.; Nix, J. C.; Achterkirchen, T. G.; Westbrook, E. M.

    2013-03-01

    Complementary Metal Oxide Semiconductor (CMOS) devices are rapidly replacing CCD devices in many commercial and medical applications. Recent developments in CMOS fabrication have improved their radiation hardness, device linearity, readout noise and thermal noise, making them suitable for x-ray crystallography detectors. Large-format (e.g. 10 cm × 15 cm) CMOS devices with a pixel size of 100 μm × 100 μm are now becoming available that can be butted together on three sides so that very large area detector can be made with no dead regions. Like CCD systems our CMOS systems use a GdOS:Tb scintillator plate to convert stopping x-rays into visible light which is then transferred with a fiber-optic plate to the sensitive surface of the CMOS sensor. The amount of light per x-ray on the sensor is much higher in the CMOS system than a CCD system because the fiber optic plate is only 3 mm thick while on a CCD system it is highly tapered and much longer. A CMOS sensor is an active pixel matrix such that every pixel is controlled and readout independently of all other pixels. This allows these devices to be readout while the sensor is collecting charge in all the other pixels. For x-ray diffraction detectors this is a major advantage since image frames can be collected continuously at up 20 Hz while the crystal is rotated. A complete diffraction dataset can be collected over five times faster than with CCD systems with lower radiation exposure to the crystal. In addition, since the data is taken fine-phi slice mode the 3D angular position of diffraction peaks is improved. We have developed a cooled 6 sensor CMOS detector with an active area of 28.2 × 29.5 cm with 100 μm × 100 μm pixels and a readout rate of 20 Hz. The detective quantum efficiency exceeds 60% over the range 8-12 keV. One, two and twelve sensor systems are also being developed for a variety of scientific applications. Since the sensors are butt able on three sides, even larger systems could be built at

  13. Nanotechnologies in protein microarrays.

    PubMed

    Krizkova, Sona; Heger, Zbynek; Zalewska, Marta; Moulick, Amitava; Adam, Vojtech; Kizek, Rene

    2015-01-01

    Protein microarray technology became an important research tool for study and detection of proteins, protein-protein interactions and a number of other applications. The utilization of nanoparticle-based materials and nanotechnology-based techniques for immobilization allows us not only to extend the surface for biomolecule immobilization resulting in enhanced substrate binding properties, decreased background signals and enhanced reporter systems for more sensitive assays. Generally in contemporarily developed microarray systems, multiple nanotechnology-based techniques are combined. In this review, applications of nanoparticles and nanotechnologies in creating protein microarrays, proteins immobilization and detection are summarized. We anticipate that advanced nanotechnologies can be exploited to expand promising fields of proteins identification, monitoring of protein-protein or drug-protein interactions, or proteins structures.

  14. 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.

  15. Metrology Of Silicide Contacts For Future CMOS

    NASA Astrophysics Data System (ADS)

    Zollner, Stefan; Gregory, Richard B.; Kottke, M. L.; Vartanian, Victor; Wang, Xiang-Dong; Theodore, David; Fejes, P. L.; Conner, J. R.; Raymond, Mark; Zhu, Xiaoyan; Denning, Dean; Bolton, Scott; Chang, Kyuhwan; Noble, Ross; Jahanbani, Mohamad; Rossow, Marc; Goedeke, Darren; Filipiak, Stan; Garcia, Ricardo; Jawarani, Dharmesh; Taylor, Bill; Nguyen, Bich-Yen; Crabtree, P. E.; Thean, Aaron

    2007-09-01

    Silicide materials (NiSi, CoSi2, TiSi2, etc) are used to form low-resistance contacts between the back-end (W plugs and Cu interconnects) and front-end portions (silicon source, drain, and gate regions) of integrated CMOS circuits. At the 65 nm node, a transition from CoSi2 to NiSi was necessary because of the unique capability of NiSi to form narrow silicide nanowires on active (monocrystalline) and gate (polycrystalline) lines. Like its predecessors TiSi2 and CoSi2, NiSi is a mid-gap silicide, i.e., the Fermi level of the NiSi metal is pinned half-way between the conduction and valence band edges in silicon. This leads to a Schottky barrier between the silicide and silicon source-drain regions, which creates undesirable parasitic resistances. For future CMOS generations, band-edge silicides, such as PtSi for contacts to p-type or rare earth silicides for contacts to n-type Si will be needed. This paper reviews metrology and characterization techniques for NiSi process control for development and manufacturing, with special emphasis on x-ray reflectance and x-ray fluorescence. We also report measurement methods useful for development of a PtSi PMOS module.

  16. 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.

  17. 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.

  18. 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.

  19. Portable design rules for bulk CMOS

    NASA Technical Reports Server (NTRS)

    Griswold, T. W.

    1982-01-01

    It is pointed out that for the past several years, one school of IC designers has used a simplified set of nMOS geometric design rules (GDR) which is 'portable', in that it can be used by many different nMOS manufacturers. The present investigation is concerned with a preliminary set of design rules for bulk CMOS which has been verified for simple test structures. The GDR are defined in terms of Caltech Intermediate Form (CIF), which is a geometry-description language that defines simple geometrical objects in layers. The layers are abstractions of physical mask layers. The design rules do not presume the existence of any particular design methodology. Attention is given to p-well and n-well CMOS processes, bulk CMOS and CMOS-SOS, CMOS geometric rules, and a description of the advantages of CMOS technology.

  20. 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.

  1. 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.

  2. Apoptotic activity of genistein on human lung adenocarcinoma SPC-A-1 cells and preliminary exploration of its mechanisms using microarray.

    PubMed

    Zou, Huafei; Zhan, Shuxuan; Cao, Kaiming

    2008-11-01

    Soy isoflavone genistein is active against certain solid malignancies, but its direct effect on lung adenocarcinoma and its mechanisms of action remain to be elucidated. In the present study, using the human lung adenocarcinoma cell line SPC-A-1, we found that genistein decreased SPC-A-1 cell viability in both a dose and time dependent manner. Flow cytometry analysis revealed that genistein significantly induced arrest of SPC-A-1 cells at the G2/M phase of the cell cycle. Furthermore, through DNA fragmentation and TUNEL assays, we demonstrated that the addition of genistein led to SPC-A-1 apoptosis in both a dose and time dependent manner. Finally, the apoptosis pathway-related gene expression profile affected by genistein was investigated using the oligonucleotide microarray method. The result showed that the expression profile of 20 genes (ratio of genistein group/control group >2 or <0.5) related to the apoptotic pathways changed. These genes, mainly consisting of the Bcl-2 family and TNF ligand and receptor family, are involved in regulation of the apoptosis process.

  3. Microarray analysis of tick-infested skin in resistant and susceptible cattle confirms the role of inflammatory pathways in immune activation and larval rejection.

    PubMed

    Carvalho, Wanessa Araújo; Domingues, Robert; de Azevedo Prata, Marcia Cristina; da Silva, Marcos Vinícius G B; de Oliveira, Guilherme Corrêa; Guimarães, Simone Eliza Facioni; Machado, Marco Antônio

    2014-09-15

    Tick bites promote activation of an inflammatory process that is influenced by bovine genetic composition and its history of previous exposure. Taurine and indicine breeds are known to differ on its immune response development against Rhipicephalus microplus. Nevertheless, further investigation about the complex molecular pathways involved in the development of immune response to tick infestation in cattle presenting the same genetic background is mandatory. The aim of this work was to access the early immune response triggered by R. microplus larvae attachment in previously selected resistant and susceptible animals in a bovine F2 population derived from Gyr (Bos indicus)×Holstein (Bos taurus) crosses. Microarray data analysis of RNA samples from tick infested skin was used to evaluate the gene expression at 0, 24 and 48h after R. microplus larvae attachment. Our experimental design allowed us to deeply explore the immune response related to R. microplus infestation avoiding the innate differences between these breeds. The differentially expressed genes found reveal networks and pathways that suggest a key role of lipid metabolism in inflammation control and impairment of tick infestation in resistant animals. Acute phase response also seems to be impaired in susceptible animals. These results provide new insights about early immune response against ticks and raise the possibility of using immunomodulation processes to improve and develop novel tools for tick control. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. 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

  5. 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…

  6. 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

  7. 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…

  8. 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.

  9. 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.

  10. INDEP approach for leakage reduction in nanoscale CMOS circuits

    NASA Astrophysics Data System (ADS)

    Sharma, Vijay Kumar; Pattanaik, Manisha; Raj, Balwinder

    2015-02-01

    Complementary metal oxide semiconductor (CMOS) technology scaling for improving speed and functionality turns leakage power one of the major concerns for nanoscale circuits design. The minimization of leakage power is a rising challenge for the design of the existing and future nanoscale CMOS circuits. This paper presents a novel, input-dependent, transistor-level, low leakage and reliable INput DEPendent (INDEP) approach for nanoscale CMOS circuits. INDEP approach is based on Boolean logic calculations for the input signals of the extra inserted transistors within the logic circuit. The gate terminals of extra inserted transistors depend on the primary input combinations of the logic circuits. The appropriate selection of input gate voltages of INDEP transistors are reducing the leakage current efficiently along with rail to rail output voltage swing. The important characteristic of INDEP approach is that it works well in both active as well as standby modes of the circuits. This approach overcomes the limitations created by the prevalent current leakage reduction techniques. The simulation results indicate that INDEP approach mitigates 41.6% and 35% leakage power for 1-bit full adder and ISCAS-85 c17 benchmark circuit, respectively, at 32 nm bulk CMOS technology node.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Biolog phenotype microarrays.

    PubMed

    Shea, April; Wolcott, Mark; Daefler, Simon; Rozak, David A

    2012-01-01

    Phenotype microarrays nicely complement traditional genomic, transcriptomic, and proteomic analysis by offering opportunities for researchers to ground microbial systems analysis and modeling in a broad yet quantitative assessment of the organism's physiological response to different metabolites and environments. Biolog phenotype assays achieve this by coupling tetrazolium dyes with minimally defined nutrients to measure the impact of hundreds of carbon, nitrogen, phosphorous, and sulfur sources on redox reactions that result from compound-induced effects on the electron transport chain. Over the years, we have used Biolog's reproducible and highly sensitive assays to distinguish closely related bacterial isolates, to understand their metabolic differences, and to model their metabolic behavior using flux balance analysis. This chapter describes Biolog phenotype microarray system components, reagents, and methods, particularly as they apply to bacterial identification, characterization, and metabolic analysis.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Microarray Data Analysis and Mining Tools

    PubMed Central

    Selvaraj, Saravanakumar; Natarajan, Jeyakumar

    2011-01-01

    Microarrays are one of the latest breakthroughs in experimental molecular biology that allow monitoring the expression levels of tens of thousands of genes simultaneously. Arrays have been applied to studies in gene expression, genome mapping, SNP discrimination, transcription factor activity, toxicity, pathogen identification and many other applications. In this paper we concentrate on discussing various bioinformatics tools used for microarray data mining tasks with its underlying algorithms, web resources and relevant reference. We emphasize this paper mainly for digital biologists to get an aware about the plethora of tools and programs available for microarray data analysis. First, we report the common data mining applications such as selecting differentially expressed genes, clustering, and classification. Next, we focused on gene expression based knowledge discovery studies such as transcription factor binding site analysis, pathway analysis, protein- protein interaction network analysis and gene enrichment analysis. PMID:21584183

  4. Microarray data analysis and mining tools.

    PubMed

    Selvaraj, Saravanakumar; Natarajan, Jeyakumar

    2011-04-22

    Microarrays are one of the latest breakthroughs in experimental molecular biology that allow monitoring the expression levels of tens of thousands of genes simultaneously. Arrays have been applied to studies in gene expression, genome mapping, SNP discrimination, transcription factor activity, toxicity, pathogen identification and many other applications. In this paper we concentrate on discussing various bioinformatics tools used for microarray data mining tasks with its underlying algorithms, web resources and relevant reference. We emphasize this paper mainly for digital biologists to get an aware about the plethora of tools and programs available for microarray data analysis. First, we report the common data mining applications such as selecting differentially expressed genes, clustering, and classification. Next, we focused on gene expression based knowledge discovery studies such as transcription factor binding site analysis, pathway analysis, protein- protein interaction network analysis and gene enrichment analysis.

  5. 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.

  6. Hybrid CMOS/Molecular Integrated Circuits

    NASA Astrophysics Data System (ADS)

    Stan, M. R.; Rose, G. S.; Ziegler, M. M.

    CMOS silicon technologies are likely to run out of steam in the next 10-15 years despite revolutionary advances in the past few decades. Molecular and other nanoscale technologies show significant promise but it is unlikely that they will completely replace CMOS, at least in the near term. This chapter explores opportunities for using CMOS and nanotechnology to enhance and complement each other in hybrid circuits. As an example of such a hybrid CMOS/nano system, a nanoscale programmable logic array (PLA) based on majority logic is described along with its supplemental CMOS circuitry. It is believed that such systems will be able to sustain the historical advances in the semiconductor industry while addressing manufacturability, yield, power, cost, and performance challenges.

  7. Implantable optogenetic device with CMOS IC technology for simultaneous optical measurement and stimulation

    NASA Astrophysics Data System (ADS)

    Haruta, Makito; Kamiyama, Naoya; Nakajima, Shun; Motoyama, Mayumi; Kawahara, Mamiko; Ohta, Yasumi; Yamasaki, Atsushi; Takehara, Hiroaki; Noda, Toshihiko; Sasagawa, Kiyotaka; Ishikawa, Yasuyuki; Tokuda, Takashi; Hashimoto, Hitoshi; Ohta, Jun

    2017-05-01

    In this study, we have developed an implantable optogenetic device that can measure and stimulate neurons by an optical method based on CMOS IC technology. The device consist of a blue LED array for optically patterned stimulation, a CMOS image sensor for acquiring brain surface image, and eight green LEDs surrounding the CMOS image sensor for illumination. The blue LED array is placed on the CMOS image sensor. We implanted the device in the brain of a genetically modified mouse and successfully demonstrated the stimulation of neurons optically and simultaneously acquire intrinsic optical images of the brain surface using the image sensor. The integrated device can be used for simultaneously measuring and controlling neuronal activities in a living animal, which is important for the artificial control of brain functions.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. Light-emitting polymer on CMOS: a new photonic technology?

    NASA Astrophysics Data System (ADS)

    Underwood, Ian; Gourlay, James

    2003-11-01

    A new hybrid optoelectronic technology has been developed which utilizes a very thin layer of light emitting polymer material on a CMOS silicon active-matrix substrate to create a 2-D array of independently programmable optical emitters. The technology has been developed thus far primarily for its use as a microdisplay. Here we detail aspects of device design and characterization. We consider the relevance of the new technology to optical and photonic systems other than displays.

  13. 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.

  14. 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

  15. Ecotoxicogenomics: Microarray interlaboratory comparability.

    PubMed

    Vidal-Dorsch, Doris E; Bay, Steven M; Moore, Shelly; Layton, Blythe; Mehinto, Alvine C; Vulpe, Chris D; Brown-Augustine, Marianna; Loguinov, Alex; Poynton, Helen; Garcia-Reyero, Natàlia; Perkins, Edward J; Escalon, Lynn; Denslow, Nancy D; Cristina, Colli-Dula R; Doan, Tri; Shukradas, Shweta; Bruno, Joy; Brown, Lorraine; Van Agglen, Graham; Jackman, Paula; Bauer, Megan

    2016-02-01

    Transcriptomic analysis can complement traditional ecotoxicology data by providing mechanistic insight, and by identifying sub-lethal organismal responses and contaminant classes underlying observed toxicity. Before transcriptomic information can be used in monitoring and risk assessment, it is necessary to determine its reproducibility and detect key steps impacting the reliable identification of differentially expressed genes. A custom 15K-probe microarray was used to conduct transcriptomics analyses across six laboratories with estuarine amphipods exposed to cyfluthrin-spiked or control sediments (10 days). Two sample types were generated, one consisted of total RNA extracts (Ex) from exposed and control samples (extracted by one laboratory) and the other consisted of exposed and control whole body amphipods (WB) from which each laboratory extracted RNA. Our findings indicate that gene expression microarray results are repeatable. Differentially expressed data had a higher degree of repeatability across all laboratories in samples with similar RNA quality (Ex) when compared to WB samples with more variable RNA quality. Despite such variability a subset of genes were consistently identified as differentially expressed across all laboratories and sample types. We found that the differences among the individual laboratory results can be attributed to several factors including RNA quality and technical expertise, but the overall results can be improved by following consistent protocols and with appropriate training. Published by Elsevier Ltd.

  16. 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.

  17. 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.

  18. Bridging faults in BiCMOS circuits

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

    Combining the advantages of CMOS and bipolar, BiCMOS is emerging as a major technology for many high performance digital and mixed signal applications. Recent investigations revealed that bridging faults can be a major failure mode in IC's. Effects of bridging faults in BiCMOS circuits are presented. Bridging faults between logical units without feedback and logical units with feedback are considered. Several bridging faults can be detected by monitoring the power supply current (I(sub DDQ) monitoring). Effects of bridging faults and bridging resistance on output logic levels were examined along with their effects on noise immunity.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. A fully integrated CMOS inverse sine circuit for computational systems

    NASA Astrophysics Data System (ADS)

    Seon, Jong-Kug

    2010-08-01

    An inverse trigonometric function generator using CMOS technology is presented and implemented. The development and synthesis of inverse trigonometric functional circuits based on the simple approximation equations are also introduced. The proposed inverse sine function generator has the infinite input range and can be used in many measurement and instrumentation systems. The nonlinearity of less than 2.8% for the entire input range of 0.5 Vp-p with a small-signal bandwidth of 3.2 MHz is achieved. The chip implemented in 0.25 μm CMOS process operates from a single 1.8 V supply. The measured power consumption and the active chip area of the inverse sine function circuit are 350 μW and 0.15 mm2, respectively.

  5. 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.

  6. 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

  7. CMOS-sensors for energy-resolved X-ray imaging

    NASA Astrophysics Data System (ADS)

    Doering, D.; Amar-Youcef, S.; Baudot, J.; Deveaux, M.; Dulinski, W.; Kachel, M.; Linnik, B.; Müntz, C.; Stroth, Joachim

    2016-01-01

    Due to their low noise, CMOS Monolithic Active Pixel Sensors are suited to sense X-rays with a few keV quantum energy, which is of interest for high resolution X-ray imaging. Moreover, the good energy resolution of the silicon sensors might be used to measure this quantum energy. Combining both features with the good spatial resolution of CMOS sensors opens the potential to build ``color sensitive" X-ray cameras. Taking such colored images is hampered by the need to operate the CMOS sensors in a single photon counting mode, which restricts the photon flux capability of the sensors. More importantly, the charge sharing between the pixels smears the potentially good energy resolution of the sensors. Based on our experience with CMOS sensors for charged particle tracking, we studied techniques to overcome the latter by means of an offline processing of the data obtained from a CMOS sensor prototype. We found that the energy resolution of the pixels can be recovered at the expense of reduced quantum efficiency. We will introduce the results of our study and discuss the feasibility of taking colored X-ray pictures with CMOS sensors.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. Silicon-gate CMOS/SOS processing

    NASA Technical Reports Server (NTRS)

    Ramondetta, P.

    1979-01-01

    Major silicon-gate CMOS/SOS processes are described. Sapphire substrate preparation is also discussed, as well as the following process variations: (1) the double epi process; and (2) ion implantation.

  13. Methods in molecular cardiology: microarray technology

    PubMed Central

    van den Bosch, B.; Doevendans, P.A.; Lips, D.; Smeets, H.J.M.

    2003-01-01

    It has become more and more evident that changes in expression levels of genes can play an important role in cardiovascular diseases. Specific gene expression profiles may explain, for example, the pathophysiology of myocardial hypertrophy and pump failure and may provide clues for therapeutic interventions. Knowledge of gene expression patterns can also be applied for diagnostic and prognostic purposes, in which differences in gene activity can be used for classification. DNA microarray technology has become the method of choice to simultaneously study the expression of many different genes in a single assay. Each microarray contains many thousands of different DNA sequences attached to a glass slide. The amount of messenger RNA, which is a measure of gene activity, is compared for each gene on the microarray by labelling the mRNA with different fluorescently labelled nucleotides (Cy3 or Cy5) for the test and reference samples. After hybridisation to the microarray the relative amounts of a particular gene transcript in the two samples can be determined by measuring the signal intensities for the fluorescent groups (Cy3 and Cy5) and calculating signal ratios. This paper describes the development of in-house microarray technology, using commercially available cDNA collections. Several technical approaches will be compared and an overview of the pitfalls and possibilities will be presented. The technology will be explained in the context of our project to determine gene expression differences between normal, hypertrophic and failing heart. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 9 PMID:25696214

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. CMOS SiPM with integrated amplifier

    NASA Astrophysics Data System (ADS)

    Schwinger, Alexander; Brockherde, Werner; Hosticka, Bedrich J.; Vogt, Holger

    2017-02-01

    The integration of silicon photomultiplier (SiPM) and frontend electronics in a suitable optoelectronic CMOS process is a promising approach to increase the versatility of single-photon avalanche diode (SPAD)-based singlephoton detectors. By integrating readout amplifiers, the device output capacitance can be reduced to minimize the waveform tail, which is especially important for large area detectors (>10 × 10mm2). Possible architectures include a single readout amplifier for the whole detector, which reduces the output capacitance to 1:1 pF at minimal reduction in detector active area. On the other hand, including a readout amplifier in every SiPM cell would greatly improve the total output capacitance by minimizing the influence of metal routing parasitic capacitance, but requiring a prohibitive amount of detector area. As tradeoff, the proposed detector features one readout amplifier for each column of the detector matrix to allow for a moderate reduction in output capacitance while allowing the electronics to be placed in the periphery of the active detector area. The presented detector with a total size of 1.7 ♢ 1.0mm2 features 400 cells with a 50 μm pitch, where the signal of each column of 20 SiPM cells is summed in a readout channel. The 20 readout channels are subsequently summed into one output channel, to allow the device to be used as a drop-in replacement for commonly used analog SiPMs.

  19. 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.

  20. Flexible packaging and integration of CMOS IC with elastomeric microfluidics

    NASA Astrophysics Data System (ADS)

    Zhang, Bowei; Dong, Quan; Korman, Can E.; Li, Zhenyu; Zaghloul, Mona E.

    2013-05-01

    We have demonstrated flexible packaging and integration of CMOS IC chips with PDMS microfluidics. Microfluidic channels are used to deliver both liquid samples and liquid metals to the CMOS die. The liquid metals are used to realize electrical interconnects to the CMOS chip. As a demonstration we integrated a CMOS magnetic sensor die and matched PDMS microfluidic channels in a flexible package. The packaged system is fully functional under 3cm bending radius. The flexible integration of CMOS ICs with microfluidics enables previously unavailable flexible CMOS electronic systems with fluidic manipulation capabilities, which hold great potential for wearable health monitoring, point-of-care diagnostics and environmental sensing.

  1. 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.

  2. 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.

  3. 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.

  4. New package for CMOS sensors

    NASA Astrophysics Data System (ADS)

    Diot, Jean-Luc; Loo, Kum Weng; Moscicki, Jean-Pierre; Ng, Hun Shen; Tee, Tong Yan; Teysseyre, Jerome; Yap, Daniel

    2004-02-01

    Cost is the main drawback of existing packages for C-MOS sensors (mainly CLCC family). Alternative packages are thus developed world-wide. And in particular, S.T.Microelectronics has studied a low cost alternative packages based on QFN structure, still with a cavity. Intensive work was done to optimize the over-molding operation forming the cavity onto a metallic lead-frame (metallic lead-frame is a low cost substrate allowing very good mechanical definition of the final package). Material selection (thermo-set resin and glue for glass sealing) was done through standard reliability tests for cavity packages (Moisture Sensitivity Level 3 followed by temperature cycling, humidity storage and high temperature storage). As this package concept is new (without leads protruding the molded cavity), the effect of variation of package dimensions, as well as board lay-out design, are simulated on package life time (during temperature cycling, thermal mismatch between board and package leads to thermal fatigue of solder joints). These simulations are correlated with an experimental temperature cycling test with daisy-chain packages.

  5. 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.

  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. 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.

  8. Wavelength dependence of silicon avalanche photodiode fabricated by CMOS process

    NASA Astrophysics Data System (ADS)

    Mohammed Napiah, Zul Atfyi Fauzan; Hishiki, Takuya; Iiyama, Koichi

    2017-07-01

    Avalanche photodiodes fabricated by CMOS process (CMOS-APDs) have features of high avalanche gain below 10 V, wide bandwidth over 5 GHz, and easy integration with electronic circuits. In CMOS-APDs, guard ring structure is introduced for high-speed operation by canceling photo-generated carriers in the substrate at the sacrifice of the responsivity. We describe here wavelength dependence of the responsivity and the bandwidth of the CMOS-APDs with shorted and opened guard ring structure.

  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. 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

  11. 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.

  12. 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.

  13. 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.

  14. Characterisation of novel prototypes of monolithic HV-CMOS pixel detectors for high energy physics experiments

    NASA Astrophysics Data System (ADS)

    Terzo, S.; Cavallaro, E.; Casanova, R.; Di Bello, F.; Förster, F.; Grinstein, S.; Períc, I.; Puigdengoles, C.; Ristić, B.; Barrero Pinto, M. Vicente; Vilella, E.

    2017-06-01

    An upgrade of the ATLAS experiment for the High Luminosity phase of LHC is planned for 2024 and foresees the replacement of the present Inner Detector (ID) with a new Inner Tracker (ITk) completely made of silicon devices. Depleted active pixel sensors built with the High Voltage CMOS (HV-CMOS) technology are investigated as an option to cover large areas in the outermost layers of the pixel detector and are especially interesting for the development of monolithic devices which will reduce the production costs and the material budget with respect to the present hybrid assemblies. For this purpose the H35DEMO, a large area HV-CMOS demonstrator chip, was designed by KIT, IFAE and University of Liverpool, and produced in AMS 350 nm CMOS technology. It consists of four pixel matrices and additional test structures. Two of the matrices include amplifiers and discriminator stages and are thus designed to be operated as monolithic detectors. In these devices the signal is mainly produced by charge drift in a small depleted volume obtained by applying a bias voltage of the order of 100V. Moreover, to enhance the radiation hardness of the chip, this technology allows to enclose the electronics in the same deep N-WELLs which are also used as collecting electrodes. In this contribution the characterisation of H35DEMO chips and results of the very first beam test measurements of the monolithic CMOS matrices with high energetic pions at CERN SPS will be presented.

  15. 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.

  16. 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.

  17. 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).

  18. 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.

  19. Simple BiCMOS CCCTA design and resistorless analog function realization.

    PubMed

    Tangsrirat, Worapong

    2014-01-01

    The simple realization of the current-controlled conveyor transconductance amplifier (CCCTA) in BiCMOS technology is introduced. The proposed BiCMOS CCCTA realization is based on the use of differential pair and basic current mirror, which results in simple structure. Its characteristics, that is, parasitic resistance (R x) and current transfer (i o/i z), are also tunable electronically by external bias currents. The realized circuit is suitable for fabrication using standard 0.35 μm BiCMOS technology. Some simple and compact resistorless applications employing the proposed CCCTA as active elements are also suggested, which show that their circuit characteristics with electronic controllability are obtained. PSPICE simulation results demonstrating the circuit behaviors and confirming the theoretical analysis are performed.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Time-course microarrays reveal early activation of the immune transcriptome in a choline-deficient mouse model of liver injury.

    PubMed

    Mitsumoto, Koji; Watanabe, Rina; Nakao, Katsuki; Yonenaka, Hisaki; Hashimoto, Takao; Kato, Norihisa; Kumrungsee, Thanutchaporn; Yanaka, Noriyuki

    2017-09-01

    Choline-deficient diet is extensively used as a model of nonalcoholic fatty liver disease (NAFLD). In this study, we explored genes in the liver for which the expression changed in response to the choline-deficient (CD) diet. Male CD-1 mice were divided into two groups and fed a CD diet with or without 0.2% choline bitartrate for one or three weeks. Hepatic levels of choline metabolites were analyzed by using liquid chromatography mass spectrometry and hepatic gene expression profiles were examined by DNA microarray analysis. The CD diet lowered liver choline metabolites after one week and exacerbated fatty liver between one and three weeks. We identified >300 genes whose expression was significantly altered in the livers of mice after consumption of this CD diet for one week and showed that liver gene expression profiles could be classified into six distinct groups. This study showed that STAT1 and interferon-regulated genes was up-regulated after the CD diet consumption and that the Stat1 mRNA level was negatively correlated with liver phosphatidylcholine level. Stat1 mRNA expression was actually up-regulated in isolated hepatocytes from the mouse liver with the CD diet. This study provides insight into the genomic effects of the CD diet through the Stat1 expression, which might be involved in NAFLD development. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. CMOS and sCMOS imaging performance comparison by digital holographic interferometry

    NASA Astrophysics Data System (ADS)

    Flores-Moreno, Jorge Mauricio; De la Torre Ibarra, Manuel H.; del Socorro Hernández-Montes, María; Perez Lopez, Carlos; Santoyo, Fernando Mendoza

    2016-12-01

    We use a digital holographic interferometric setup to assess, as a proof of concept, two state-of-the-art sensors (CMOS and sCMOS cameras) that are widely used in nondestructive testing (NDT). This interferometric study is intended to evaluate the image quality recorded by any camera used in NDT. The assessing relies on the quantification of the optical phase information recovered by the cameras used for this study. For this, we calculate the signal-to-noise ratio, correlation coefficient, and quality index (Q-index) as main figures-of-merit. As far as we know, the Q-index has not been used for evaluation of the optical phase coming from image holograms. The CMOS and sCMOS sensors used record the same deformation event under the same experimental conditions. The experiment involves the inspection of a large sample (>1 m2 of area) which implies low illumination conditions for the imaging sensors. The retrieved CMOS optical phase shows artifacts that are not observed in the sCMOS. An analysis of these two groups of interferometric images is presented and discussed. The methodology set forth here can be applied to evaluate other sensors such as CCDs and EM-CCDs.

  7. On the integration of ultrananocrystalline diamond (UNCD) with CMOS chip

    DOE PAGES

    Mi, Hongyi; Yuan, Hao -Chih; Seo, Jung -Hun; ...

    2017-03-27

    A low temperature deposition of high quality ultrananocrystalline diamond (UNCD) film onto a finished Si-based CMOS chip was performed to investigate the compatibility of the UNCD deposition process with CMOS devices for monolithic integration of MEMS on Si CMOS platform. DC and radio-frequency performances of the individual PMOS and NMOS devices on the CMOS chip before and after the UNCD deposition were characterized. Electrical characteristics of CMOS after deposition of the UNCD film remained within the acceptable ranges, namely showing small variations in threshold voltage Vth, transconductance gm, cut-off frequency fT and maximum oscillation frequency fmax. Finally, the results suggestmore » that low temperature UNCD deposition is compatible with CMOS to realize monolithically integrated CMOS-driven MEMS/NEMS based on UNCD.« less

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Low power SEU immune CMOS memory circuits

    NASA Technical Reports Server (NTRS)

    Liu, M. N.; Whitaker, Sterling

    1992-01-01

    The authors report a design improvement for CMOS static memory circuits hardened against single event upset (SEU) using a recently proposed logic/circuit design technique. This improvement drastically reduces static power consumption, reduces the number of transistors required in a D flip-flop design, and eliminates the possibility of capturing an upset state in the slave section during a clock transition.

  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. 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.

  15. A fail-safe CMOS logic gate

    NASA Technical Reports Server (NTRS)

    Bobin, V.; Whitaker, S.

    1990-01-01

    This paper reports a design technique to make Complex CMOS Gates fail-safe for a class of faults. Two classes of faults are defined. The fail-safe design presented has limited fault-tolerance capability. Multiple faults are also covered.

  16. 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.

  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. Profiling In Situ Microbial Community Structure with an Amplification Microarray

    PubMed Central

    Knickerbocker, Christopher; Bryant, Lexi; Golova, Julia; Wiles, Cory; Williams, Kenneth H.; Peacock, Aaron D.; Long, Philip E.

    2013-01-01

    The objectives of this study were to unify amplification, labeling, and microarray hybridization chemistries within a single, closed microfluidic chamber (an amplification microarray) and verify technology performance on a series of groundwater samples from an in situ field experiment designed to compare U(VI) mobility under conditions of various alkalinities (as HCO3−) during stimulated microbial activity accompanying acetate amendment. Analytical limits of detection were between 2 and 200 cell equivalents of purified DNA. Amplification microarray signatures were well correlated with 16S rRNA-targeted quantitative PCR results and hybridization microarray signatures. The succession of the microbial community was evident with and consistent between the two microarray platforms. Amplification microarray analysis of acetate-treated groundwater showed elevated levels of iron-reducing bacteria (Flexibacter, Geobacter, Rhodoferax, and Shewanella) relative to the average background profile, as expected. Identical molecular signatures were evident in the transect treated with acetate plus NaHCO3, but at much lower signal intensities and with a much more rapid decline (to nondetection). Azoarcus, Thaurea, and Methylobacterium were responsive in the acetate-only transect but not in the presence of bicarbonate. Observed differences in microbial community composition or response to bicarbonate amendment likely had an effect on measured rates of U reduction, with higher rates probable in the part of the field experiment that was amended with bicarbonate. The simplification in microarray-based work flow is a significant technological advance toward entirely closed-amplicon microarray-based tests and is generally extensible to any number of environmental monitoring applications. PMID:23160129

  19. 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

  20. 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.

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

    PubMed Central

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

    2013-01-01

    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. PMID:23590861

  3. 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

    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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. DNA microarray integromics analysis platform.

    PubMed

    Waller, Tomasz; Gubała, Tomasz; Sarapata, Krzysztof; Piwowar, Monika; Jurkowski, Wiktor

    2015-01-01

    The study of interactions between molecules belonging to different biochemical families (such as lipids and nucleic acids) requires specialized data analysis methods. This article describes the DNA Microarray Integromics Analysis Platform, a unique web application that focuses on computational integration and analysis of "multi-omics" data. Our tool supports a range of complex analyses, including - among others - low- and high-level analyses of DNA microarray data, integrated analysis of transcriptomics and lipidomics data and the ability to infer miRNA-mRNA interactions. We demonstrate the characteristics and benefits of the DNA Microarray Integromics Analysis Platform using two different test cases. The first test case involves the analysis of the nutrimouse dataset, which contains measurements of the expression of genes involved in nutritional problems and the concentrations of hepatic fatty acids. The second test case involves the analysis of miRNA-mRNA interactions in polysaccharide-stimulated human dermal fibroblasts infected with porcine endogenous retroviruses. The DNA Microarray Integromics Analysis Platform is a web-based graphical user interface for "multi-omics" data management and analysis. Its intuitive nature and wide range of available workflows make it an effective tool for molecular biology research. The platform is hosted at https://lifescience.plgrid.pl/.

  9. 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.

  10. Construction and validation of a Bovine Innate Immune Microarray

    PubMed Central

    Donaldson, Laurelea; Vuocolo, Tony; Gray, Christian; Strandberg, Ylva; Reverter, Antonio; McWilliam, Sean; Wang, YongHong; Byrne, Keren; Tellam, Ross

    2005-01-01

    Background Microarray transcript profiling has the potential to illuminate the molecular processes that are involved in the responses of cattle to disease challenges. This knowledge may allow the development of strategies that exploit these genes to enhance resistance to disease in an individual or animal population. Results The Bovine Innate Immune Microarray developed in this study consists of 1480 characterised genes identified by literature searches, 31 positive and negative control elements and 5376 cDNAs derived from subtracted and normalised libraries. The cDNA libraries were produced from 'challenged' bovine epithelial and leukocyte cells. The microarray was found to have a limit of detection of 1 pg/μg of total RNA and a mean slide-to-slide correlation co-efficient of 0.88. The profiles of differentially expressed genes from Concanavalin A (ConA) stimulated bovine peripheral blood lymphocytes were determined. Three distinct profiles highlighted 19 genes that were rapidly up-regulated within 30 minutes and returned to basal levels by 24 h; 76 genes that were up-regulated between 2–8 hours and sustained high levels of expression until 24 h and 10 genes that were down-regulated. Quantitative real-time RT-PCR on selected genes was used to confirm the results from the microarray analysis. The results indicate that there is a dynamic process involving gene activation and regulatory mechanisms re-establishing homeostasis in the ConA activated lymphocytes. The Bovine Innate Immune Microarray was also used to determine the cross-species hybridisation capabilities of an ovine PBL sample. Conclusion The Bovine Innate Immune Microarray has been developed which contains a set of well-characterised genes and anonymous cDNAs from a number of different bovine cell types. The microarray can be used to determine the gene expression profiles underlying innate immune responses in cattle and sheep. PMID:16176586

  11. 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.

  12. 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.

  13. Microfluidic microarray systems and methods thereof

    DOEpatents

    West, Jay A. A. [Castro Valley, CA; Hukari, Kyle W [San Ramon, CA; Hux, Gary A [Tracy, CA

    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.

  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. 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.

  16. 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,…

  17. 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,…

  18. Post-CMOS selective electroplating technique for the improvement of CMOS-MEMS accelerometers

    NASA Astrophysics Data System (ADS)

    Liu, Yu-Chia; Tsai, Ming-Han; Tang, Tsung-Lin; Fang, Weileun

    2011-10-01

    This study presents a simple approach to improve the performance of the CMOS-MEMS capacitive accelerometer by means of the post-CMOS metal electroplating process. The metal layer can be selectively electroplated on the MEMS structures at low temperature and the thickness of the metal layer can be easily adjusted by this process. Thus the performance of the capacitive accelerometer (i.e. sensitivity, noise floor and the minimum detectable signal) can be improved. In application, the proposed accelerometers have been implemented using (1) the standard CMOS 0.35 µm 2P4M process by CMOS foundry, (2) Ti/Au seed layers deposition/patterning by MEMS foundry and (3) in-house post-CMOS electroplating and releasing processes. Measurements indicate that the sensitivity is improved 2.85-fold, noise is decreased near 1.7-fold and the minimum detectable signal is improved from 1 to 0.2 G after nickel electroplating. Moreover, unwanted structure deformation due to the temperature variation is significantly suppressed by electroplated nickel.

  19. 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.

  20. Cmos spdt switch for wlan applications

    NASA Astrophysics Data System (ADS)

    Bhuiyan, M. A. S.; Reaz, M. B. I.; Rahman, L. F.; Minhad, K. N.

    2015-04-01

    WLAN has become an essential part of our today's life. The advancement of CMOS technology let the researchers contribute low power, size and cost effective WLAN devices. This paper proposes a single pole double through transmit/receive (T/R) switch for WLAN applications in 0.13 μm CMOS technology. The proposed switch exhibit 1.36 dB insertion loss, 25.3 dB isolation and 24.3 dBm power handling capacity. Moreover, it only dissipates 786.7 nW power per cycle. The switch utilizes only transistor aspect ratio optimization and resistive body floating technique to achieve such desired performance. In this design the use of bulky inductor and capacitor is avoided to evade imposition of unwanted nonlinearities to the communication signal.

  1. Submicrometer polysilicon gate CMOS/SOS technology

    NASA Astrophysics Data System (ADS)

    Ipri, A. C.; Sokoloski, J. C.; Flatley, D. W.

    1980-07-01

    A process is described for the fabrication of CMOS/SOS submicrometer devices and integrated circuits. The process utilizes the lateral diffusion of boron into polycrystalline silicon and a subsequent anisotropic etchant to define the narrow poly gates. Devices with channel lengths as small as 0.3 micron have been fabricated and characterized. Both avalanche and tunnel injection of carriers into the gate dielectric have been measured and both can have an impact on the limit of voltage operation. At present, these mechanisms appear to place an upper limit of about 8 V on the operating voltage of dynamic circuits containing 0.5-micron channel length devices. The propagation delay of 0.5-micron channel length CMOS/SOS inverters is about 200 ps at 5 V and dynamic binary counters will operate with a maximum input frequency of 550 MHz and 8 V while dissipating 130 mW.

  2. 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.

  3. 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.

  4. 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.; hide

    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.

  5. 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.

  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. 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.

  8. 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.

  9. 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.

  10. 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).

  11. 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

  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. 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.

  14. 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.

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

    PubMed Central

    2013-01-01

    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. PMID:24180626

  16. MEMS capacitive pressure sensor monolithically integrated with CMOS readout circuit by using post CMOS processes

    NASA Astrophysics Data System (ADS)

    Jang, Munseon; Yun, Kwang-Seok

    2017-12-01

    In this paper, we presents a MEMS pressure sensor integrated with a readout circuit on a chip for an on-chip signal processing. The capacitive pressure sensor is formed on a CMOS chip by using a post-CMOS MEMS processes. The proposed device consists of a sensing capacitor that is square in shape, a reference capacitor and a readout circuitry based on a switched-capacitor scheme to detect capacitance change at various environmental pressures. The readout circuit was implemented by using a commercial 0.35 μm CMOS process with 2 polysilicon and 4 metal layers. Then, the pressure sensor was formed by wet etching of metal 2 layer through via hole structures. Experimental results show that the MEMS pressure sensor has a sensitivity of 11 mV/100 kPa at the pressure range of 100-400 kPa.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  9. 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

  10. Current-mode CMOS hybrid image sensor

    NASA Astrophysics Data System (ADS)

    Benyhesan, Mohammad Kassim

    Digital imaging is growing rapidly making Complimentary Metal-Oxide-Semi conductor (CMOS) image sensor-based cameras indispensable in many modern life devices like cell phones, surveillance devices, personal computers, and tablets. For various purposes wireless portable image systems are widely deployed in many indoor and outdoor places such as hospitals, urban areas, streets, highways, forests, mountains, and towers. However, the increased demand on high-resolution image sensors and improved processing features is expected to increase the power consumption of the CMOS sensor-based camera systems. Increased power consumption translates into a reduced battery life-time. The increased power consumption might not be a problem if there is access to a nearby charging station. On the other hand, the problem arises if the image sensor is located in widely spread areas, unfavorable to human intervention, and difficult to reach. Given the limitation of energy sources available for wireless CMOS image sensor, an energy harvesting technique presents a viable solution to extend the sensor life-time. Energy can be harvested from the sun light or the artificial light surrounding the sensor itself. In this thesis, we propose a current-mode CMOS hybrid image sensor capable of energy harvesting and image capture. The proposed sensor is based on a hybrid pixel that can be programmed to perform the task of an image sensor and the task of a solar cell to harvest energy. The basic idea is to design a pixel that can be configured to exploit its internal photodiode to perform two functions: image sensing and energy harvesting. As a proof of concept a 40 x 40 array of hybrid pixels has been designed and fabricated in a standard 0.5 microm CMOS process. Measurement results show that up to 39 microW of power can be harvested from the array under 130 Klux condition with an energy efficiency of 220 nJ /pixel /frame. The proposed image sensor is a current-mode image sensor which has several

  11. 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

  12. X-ray characterization of CMOS imaging detector with high resolution for fluoroscopic imaging application

    NASA Astrophysics Data System (ADS)

    Cha, Bo Kyung; Kim, Cho Rong; Jeon, Seongchae; Kim, Ryun Kyung; Seo, Chang-Woo; Yang, Keedong; Heo, Duchang; Lee, Tae-Bum; Shin, Min-Seok; Kim, Jong-Boo; Kwon, Oh-Kyung

    2013-12-01

    This paper introduces complementary metal-oxide semiconductor (CMOS) active pixel sensor (APS)-based X-ray imaging detectors with high spatial resolution for medical imaging application. In this study, our proposed X-ray CMOS imaging sensor has been fabricated by using a 0.35 μm 1 Poly 4 Metal CMOS process. The pixel size is 100 μm×100 μm and the pixel array format is 24×96 pixels, which provide a field-of-view (FOV) of 9.6 mm×2.4 mm. The 14.3-bit extend counting analog-to digital converter (ADC) with built-in binning mode was used to reduce the area and simultaneously improve the image resolution. Both thallium-doped CsI (CsI:Tl) and Gd2O2S:Tb scintillator screens were used as converters for incident X-rays to visible light photons. The optical property and X-ray imaging characterization such as X-ray to light response as a function of incident X-ray exposure dose, spatial resolution and X-ray images of objects were measured under different X-ray energy conditions. The measured results suggest that our developed CMOS-based X-ray imaging detector has the potential for fluoroscopic imaging and cone-beam computed tomography (CBCT) imaging applications.

  13. 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.

  14. Comparison of hydroxylated print additives on antibody microarray performance

    PubMed Central

    Wu, Peng; Grainger, David W.

    2008-01-01

    Various hydroxylated additives were added to antibody print buffers at different concentrations to stabilize printed antibodies during normal array spot desiccation on commercial polymer-coated microarray slides. Polyvinyl alcohol addition to print buffers produced the most regular spot morphologies, homogenous intra-spot antibody distribution, uniform fluorescence intensity, and improved analyte capture activity, maintained up to 1 month at 4°C for capturing model analytes, anti-human IL-1β, IL-4 and TNFα, on these microarraying slides. PMID:17081047

  15. Cellular Moloney murine sarcoma (c-mos) sequences are hypermethylated and transcriptionally silent in normal and transformed rodent cells

    SciTech Connect

    Gattoni, S.; Kirschmeier, P.; Weinstein, I.B.; Escobedo, J.; Dina, D.

    1982-01-01

    Moloney murine sarcoma virus carries an oncogenic sequence (v-mos) which is homologous to a single copy gene (c-mos) present in the normal cells of several vertebrate species. Because of the possible significance of c-mos sequences in normal development and malignant transformation induced by physical or chemical agents, the authors examined the state of integration, methylation, and transcriptional activity of c-mos sequences in a variety of normal rodent tissues, normal cell lines, or cell lines transformed by radiation or chemical carcinogens. DNA-DNA hybridization, utilizing the Southern blotting technique and a plasmid-derived DNA probe representing the v-mos sequence, gave no evidence for rearrangements of the c-mos sequence in the DNAs obtained from these diverse cell types. Parallel studies employing the restriction enzyme isoschizomers HpaII and MspI indicated that in all of these cell types the c-mos sequences were heavily methylated. In addition, analysis of cellular RNAs by blot hybridization with the v-mos probe failed to detect evidence of transcription of the c-mos sequences in any of these cell types. This was in contrast to a Moloney sarcoma virus-transformed cell line in which they found that the integrated v-mos sequence was both undermethylated and extensively transcribed. Thus, it would appear that c-mos sequences do not play a role in the transformation of rodent cells by chemical or physical agents, although the possible role of other endogenous onc sequences remains to be determined.

  16. Microarray analysis of papillary thyroid cancers in Korean.

    PubMed

    Kim, Hyun Sook; Kim, Do Hyung; Kim, Ji Yeon; Jeoung, Nam Ho; Lee, In Kyu; Bong, Jin Gu; Jung, Eui Dal

    2010-12-01

    Papillary thyroid cancer (PTC) is the most common malignancy of the thyroid gland. It involves several molecular mechanisms. The BRAF V600E mutation has been identified as the most common genetic abnormality in PTC. Moreover, it is known to be more prevalent in Korean PTC patients than in patients from other countries. We investigated distinct genetic profiles in Korean PTC through cDNA microarray analysis. Transcriptional profiles of five PTC samples and five paired normal thyroid tissue samples were generated using cDNA microarrays. The tumors were genotyped for BRAF mutations. The results of the cDNA microarray gene expression analysis were confirmed by real-time PCR and immunohistochemistry analysis of 35 PTC patients. Four of the five patients whose PTC tissues were subjected to microarray analysis were found to carry the BRAF V600E mutation. Microarrays analysis of the five PTC tissue samples showed the expression of 96 genes to be increased and that of 16 genes decreased. Real-time reverse transcription-polymerase chain reaction (RT-PCR) confirmed increased expression of SLC34A2, TM7SF4, COMP, KLK7, and KCNJ2 and decreased expression of FOXA2, SLC4A4, LYVE-1, and TFCP2L1 in PTC compared with normal tissue. Of these genes, TFCP2L1, LYVE-1, and KLK7 were previously unidentified in PTC microarray analysis. Notably, Foxa2 activity in PTC was reduced, as shown by its cytoplasmic localization, in immunohistochemical analyses. These findings demonstrate both similarities and differences between our results and previous reports. In Korean cases of PTC, Foxa2 activity was reduced with its cytoplasmic accumulation. Further studies are needed to confirm the relationship between FOXA2 and BRAF mutations in Korean cases of PTC.

  17. Microarray Inspector: tissue cross contamination detection tool for microarray data.

    PubMed

    Stępniak, Piotr; Maycock, Matthew; Wojdan, Konrad; Markowska, Monika; Perun, Serhiy; Srivastava, Aashish; Wyrwicz, Lucjan S; Świrski, Konrad

    2013-01-01

    Microarray technology changed the landscape of contemporary life sciences by providing vast amounts of expression data. Researchers are building up repositories of experiment results with various conditions and samples which serve the scientific community as a precious resource. Ensuring that the sample is of high quality is of utmost importance to this effort. The task is complicated by the fact that in many cases datasets lack information concerning pre-experimental quality assessment. Transcription profiling of tissue samples may be invalidated by an error caused by heterogeneity of the material. The risk of tissue cross contamination is especially high in oncological studies, where it is often difficult to extract the sample. Therefore, there is a need of developing a method detecting tissue contamination in a post-experimental phase. We propose Microarray Inspector: customizable, user-friendly software that enables easy detection of samples containing mixed tissue types. The advantage of the tool is that it uses raw expression data files and analyses each array independently. In addition, the system allows the user to adjust the criteria of the analysis to conform to individual needs and research requirements. The final output of the program contains comfortable to read reports about tissue contamination assessment with detailed information about the test parameters and results. Microarray Inspector provides a list of contaminant biomarkers needed in the analysis of adipose tissue contamination. Using real data (datasets from public repositories) and our tool, we confirmed high specificity of the software in detecting contamination. The results indicated the presence of adipose tissue admixture in a range from approximately 4% to 13% in several tested surgical samples.

  18. 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.

  19. 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

  20. 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

  1. A CMOS imager using focal-plane pinhole effect for confocal multibeam scanning microscopy

    NASA Astrophysics Data System (ADS)

    Seo, Min-Woong; Wang, An; Li, Zhuo; Yasutomi, Keita; Kagawa, Keiichiro; Kawahito, Shoji

    2012-03-01

    A CMOS imager for confocal multi-beam scanning microscopy, where the pixel itself works as a pinhole, is proposed. This CMOS imager is suitable for building compact, low-power, and confocal microscopes because the complex Nipkow disk with a precisely aligned pinhole array can be omitted. The CMOS imager is composed of an array of sub-imagers, and can detect multiple beams at the same time. To achieve a focal-plane pinhole effect, only one pixel in each subimager, which is at the conjugate position of a light spot, accumulates the photocurrent, and the other pixels are unread. This operation is achieved by 2-dimensional vertical and horizontal shift registers. The proposed CMOS imager for the confocal multi-beam scanning microscope system was fabricated in 0.18-μm standard CMOS technology with a pinned photodiode option. The total area of the chip is 5.0mm × 5.0mm. The number of effective pixels is 256(Horizontal) × 256(Vertical). The pixel array consists of 32(H) × 32(V) sub-imagers each of which has 8(H) × 8(V) pixels. The pixel is an ordinary 4-transistor active pixel sensor using a pinned photodiode and the pixel size is 7.5μm × 7.5μm with a fillfactor of 45%. The basic operations such as normal image acquisition and selective pixel readout were experimentally confirmed. The sensitivity and the pixel conversion gain were 25.9 ke-/lx•sec and 70 μV/e- respectively.

  2. 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.

  3. Accelerated life testing effects on CMOS microcircuit characteristics

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Modifications and additions to the present process of making CMOS microcircuits which are designed to provide protective layers on the chip to guard against moisture and contaminants were investigated. High and low temperature Si3N4 protective layers were tested on the CMOS microcircuits and no conclusive improvements in device reliability characteristics were evidenced.

  4. 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.

  5. Protein microarrays identify disease-specific anti-cytokine autoantibody profiles in the landscape of immunodeficiency

    PubMed Central

    Rosenberg, Jacob M.; Price, Jordan V.; Barcenas-Morales, Gabriela; Ceron-Gutierrez, Lourdes; Davies, Sophie; Kumararatne, Dinakantha S.; Döffinger, Rainer; Utz, Paul J.

    2015-01-01

    Background Anti-cytokine autoantibodies (ACAAs) are pathogenic in a handful of rare immunodeficiencies. However, the prevalence and significance of other ACAAs across immunodeficiencies have not yet been described. Objective We sought to profile ACAAs in a diverse cohort of serum samples from patients with immunodeficiency and assess the sensitivity and specificity of protein microarrays for ACAA identification and discovery. Methods Highly multiplexed protein microarrays were designed and fabricated. Blinded serum samples from a cohort of 58 patients with immunodeficiency and healthy control subjects were used to probe microarrays. Unsupervised hierarchical clustering was used to identify clusters of reactivity, and after unblinding, significance analysis of microarrays was used to identify disease-specific autoantibodies. A bead-based assay was used to validate protein microarray results. Blocking activity of serum containing ACAAs was measured in vitro. Results Protein microarrays were highly sensitive and specific for the detection of ACAAs in patients with autoimmune polyendocrine syndrome type I and pulmonary alveolar proteinosis, detecting ACAA levels consistent with those in the published literature. Protein microarray results were validated by using an independent bead-based assay. To confirm the functional significance of these ACAAs, we tested and confirmed the blocking activity of select ACAAs in vitro. Conclusion Protein microarrays are a powerful tool for ACAA detection and discovery, and they hold promise as a diagnostic for the evaluation and monitoring of clinical immunodeficiency. PMID:26365387

  6. 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

  7. 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.

  8. A CMOS field-programmable analog array

    NASA Astrophysics Data System (ADS)

    Lee, Edward K. F.; Gulak, P. G.

    1991-12-01

    The design details and test results of a field-programmable analog array (FPAA) prototype chip in 1.2-micron CMOS are presented. The analog array is based on subthreshold circuit techniques and consists of a collection of a homogeneous configurable analog blocks (CABs) and an interconnection network. Interconnections between CABs and the analog functions to be implemented in each block are defined by a set of configuration bits loaded serially into an onboard shift register by the user. Macromodels are developed for the analog functions in order to simulate various neural network applications on the field-programmable analog array.

  9. 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.

  10. 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.

  11. CMOS current controlled fully balanced current conveyor

    NASA Astrophysics Data System (ADS)

    Chunhua, Wang; Qiujing, Zhang; Haiguang, Liu

    2009-07-01

    This paper presents a current controlled fully balanced second-generation current conveyor circuit (CF-BCCII). The proposed circuit has the traits of fully balanced architecture, and its X-Y terminals are current controllable. Based on the CFBCCII, two biquadratic universal filters are also proposed as its applications. The CFBCCII circuits and the two filters were fabricated with chartered 0.35-μm CMOS technology; with ±1.65 V power supply voltage, the total power consumption of the CFBCCII circuit is 3.6 mW. Comparisons between measured and HSpice simulation results are also given.

  12. 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

  13. Color recognition sensor in standard CMOS technology

    NASA Astrophysics Data System (ADS)

    Batistell, Graciele; Zhang, Vincent Chi; Sturm, Johannes

    2014-12-01

    Two integrated color detectors are presented as a solution for low cost color sensing applications. The color detection is based on lateral carrier diffusion and wavelength-dependent absorption-depth. The proposed detectors are implemented in a standard 130 nm CMOS technology without process modification or color filters. Three independent output signals are obtained with spectral responsivities optimized to short, middle and long wavelengths. R, G, B or X, Y, Z standard color representation can be realized by a linear transformation of the output signals.

  14. 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.

  15. Spotting effect in microarray experiments

    PubMed Central

    Mary-Huard, Tristan; Daudin, Jean-Jacques; Robin, Stéphane; Bitton, Frédérique; Cabannes, Eric; Hilson, Pierre

    2004-01-01

    Background Microarray data must be normalized because they suffer from multiple biases. We have identified a source of spatial experimental variability that significantly affects data obtained with Cy3/Cy5 spotted glass arrays. It yields a periodic pattern altering both signal (Cy3/Cy5 ratio) and intensity across the array. Results Using the variogram, a geostatistical tool, we characterized the observed variability, called here the spotting effect because it most probably arises during steps in the array printing procedure. Conclusions The spotting effect is not appropriately corrected by current normalization methods, even by those addressing spatial variability. Importantly, the spotting effect may alter differential and clustering analysis. PMID:15151695

  16. 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.

  17. Broadband image sensor array based on graphene-CMOS integration

    NASA Astrophysics Data System (ADS)

    Goossens, Stijn; Navickaite, Gabriele; Monasterio, Carles; Gupta, Shuchi; Piqueras, Juan José; Pérez, Raúl; Burwell, Gregory; Nikitskiy, Ivan; Lasanta, Tania; Galán, Teresa; Puma, Eric; Centeno, Alba; Pesquera, Amaia; Zurutuza, Amaia; Konstantatos, Gerasimos; Koppens, Frank

    2017-06-01

    Integrated circuits based on complementary metal-oxide-semiconductors (CMOS) are at the heart of the technological revolution of the past 40 years, enabling compact and low-cost microelectronic circuits and imaging systems. However, the diversification of this platform into applications other than microcircuits and visible-light cameras has been impeded by the difficulty to combine semiconductors other than silicon with CMOS. Here, we report the monolithic integration of a CMOS integrated circuit with graphene, operating as a high-mobility phototransistor. We demonstrate a high-resolution, broadband image sensor and operate it as a digital camera that is sensitive to ultraviolet, visible and infrared light (300-2,000 nm). The demonstrated graphene-CMOS integration is pivotal for incorporating 2D materials into the next-generation microelectronics, sensor arrays, low-power integrated photonics and CMOS imaging systems covering visible, infrared and terahertz frequencies.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  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. 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...

  4. 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...

  5. 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.

  6. 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

  7. 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).

  8. Antibody microarrays for label-free cell-based applications.

    PubMed

    Milgram, Sarah; Bombera, Radoslaw; Livache, Thierry; Roupioz, Yoann

    2012-02-01

    The recent advances in microtechnologies have shown the interest of developing microarrays dedicated to cell analysis. In this way, miniaturized cell analyzing platforms use several detection techniques requiring specific solid supports for microarray read-out (colorimetric, fluorescent, electrochemical, acoustic, optical…). Real-time and label-free techniques, such as Surface Plasmon Resonance imaging (SPRi), arouse increasing interest for applications in miniaturized formats. Thus, we focused our study on chemical methods for antibody-based microarray fabrication dedicated to the SPRi analysis of cells or cellular activity. Three different approaches were designed and developed for specific applications. In the first case, a polypyrrole-based chemistry was used to array antibody-microarray for specific capture of whole living cells. In the second case, the polypyrrole-based chemistry was complexified in a three molecular level assembly using DNA and antibody conjugates to allow the specific release of cells after their capture. Finally, in the third case, a thiol-based chemistry was developed for long incubation times of biological samples of high complexity. This last approach was focused on the simultaneous study of both cell type characterization and secretory activity (detection of proteins secreted by cells). This paper describes three original methods allowing a rapid and efficient analysis of cellular sample on-chip using immunoaffinity-based assays. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    DOE PAGES

    Kanisauskas, K.; Affolder, A.; Arndt, K.; ...

    2017-02-15

    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 twomore » active pixels on the test chip. As a result, 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.« less

  10. 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.

  11. "Harshlighting" small blemishes on microarrays

    PubMed Central

    Suárez-Fariñas, Mayte; Haider, Asifa; Wittkowski, Knut M

    2005-01-01

    Background Microscopists are familiar with many blemishes that fluorescence images can have due to dust and debris, glass flaws, uneven distribution of fluids or surface coatings, etc. Microarray scans show similar artefacts, which affect the analysis, particularly when one tries to detect subtle changes. However, most blemishes are hard to find by the unaided eye, particularly in high-density oligonucleotide arrays (HDONAs). Results We present a method that harnesses the statistical power provided by having several HDONAs available, which are obtained under similar conditions except for the experimental factor. This method "harshlights" blemishes and renders them evident. We find empirically that about 25% of our chips are blemished, and we analyze the impact of masking them on screening for differentially expressed genes. Conclusion Experiments attempting to assess subtle expression changes should be carefully screened for blemishes on the chips. The proposed method provides investigators with a novel robust approach to improve the sensitivity of microarray analyses. By utilizing topological information to identify and mask blemishes prior to model based analyses, the method prevents artefacts from confounding the process of background correction, normalization, and summarization. PMID:15784152

  12. "Harshlighting" small blemishes on microarrays.

    PubMed

    Suárez-Fariñas, Mayte; Haider, Asifa; Wittkowski, Knut M

    2005-03-22

    Microscopists are familiar with many blemishes that fluorescence images can have due to dust and debris, glass flaws, uneven distribution of fluids or surface coatings, etc. Microarray scans show similar artefacts, which affect the analysis, particularly when one tries to detect subtle changes. However, most blemishes are hard to find by the unaided eye, particularly in high-density oligonucleotide arrays (HDONAs). We present a method that harnesses the statistical power provided by having several HDONAs available, which are obtained under similar conditions except for the experimental factor. This method "harshlights" blemishes and renders them evident. We find empirically that about 25% of our chips are blemished, and we analyze the impact of masking them on screening for differentially expressed genes. Experiments attempting to assess subtle expression changes should be carefully screened for blemishes on the chips. The proposed method provides investigators with a novel robust approach to improve the sensitivity of microarray analyses. By utilizing topological information to identify and mask blemishes prior to model based analyses, the method prevents artefacts from confounding the process of background correction, normalization, and summarization.

  13. 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

  14. Centroid measurement error of CMOS detector in the presence of detector noise for inter-satellite optical communications

    NASA Astrophysics Data System (ADS)

    Li, Xin; Zhou, Shihong; Ma, Jing; Tan, Liying; Shen, Tao

    2013-08-01

    CMOS is a good candidate tracking detector for satellite optical communications systems with outstanding feature of sub-window for the development of APS (Active Pixel Sensor) technology. For inter-satellite optical communications it is critical to estimate the direction of incident laser beam precisely by measuring the centroid position of incident beam spot. The presence of detector noise results in measurement error, which degrades the tracking performance of systems. In this research, the measurement error of CMOS is derived taking consideration of detector noise. It is shown that the measurement error depends on pixel noise, size of the tracking sub-window (pixels number), intensity of incident laser beam, relative size of beam spot. The influences of these factors are analyzed by numerical simulation. We hope the results obtained in this research will be helpful in the design of CMOS detector satellite optical communications systems.

  15. 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.

  16. A CMOS Neural Interface for a Multichannel Vestibular Prosthesis.

    PubMed

    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

    2016-04-01

    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=0.34), suggesting that the MVP2A achieves performance at least as good as the larger MVP2.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Polymer microarray technology for stem cell engineering.

    PubMed

    Coyle, Robert; Jia, Jia; Mei, Ying

    2016-04-01

    Stem cells hold remarkable promise for applications in tissue engineering and disease modeling. During the past decade, significant progress has been made in developing soluble factors (e.g., small molecules and growth factors) to direct stem cells into a desired phenotype. However, the current lack of suitable synthetic materials to regulate stem cell activity has limited the realization of the enormous potential of stem cells. This can be attributed to a large number of materials properties (e.g., chemical structures and physical properties of materials) that can affect stem cell fate. This makes it challenging to design biomaterials to direct stem cell behavior. To address this, polymer microarray technology has been developed to rapidly identify materials for a variety of stem cell applications. In this article, we summarize recent developments in polymer array technology and their applications in stem cell engineering. Stem cells hold remarkable promise for applications in tissue engineering and disease modeling. In the last decade, significant progress has been made in developing chemically defined media to direct stem cells into a desired phenotype. However, the current lack of the suitable synthetic materials to regulate stem cell activities has been limiting the realization of the potential of stem cells. This can be attributed to the number of variables in material properties (e.g., chemical structures and physical properties) that can affect stem cells. Polymer microarray technology has shown to be a powerful tool to rapidly identify materials for a variety of stem cell applications. Here we summarize recent developments in polymer array technology and their applications in stem cell engineering. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. 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.

  4. 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...

  5. 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...

  6. 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...

  7. 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

  8. 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

  9. 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.

  10. Functional assessment of time course microarray data

    PubMed Central

    Nueda, María José; Sebastián, Patricia; Tarazona, Sonia; García-García, Francisco; Dopazo, Joaquín; Ferrer, Alberto; Conesa, Ana

    2009-01-01

    Motivation Time-course microarray experiments study the progress of gene expression along time across one or several experimental conditions. Most developed analysis methods focus on the clustering or the differential expression analysis of genes and do not integrate functional information. The assessment of the functional aspects of time-course transcriptomics data requires the use of approaches that exploit the activation dynamics of the functional categories to where genes are annotated. Methods We present three novel methodologies for the functional assessment of time-course microarray data. i) maSigFun derives from the maSigPro method, a regression-based strategy to model time-dependent expression patterns and identify genes with differences across series. maSigFun fits a regression model for groups of genes labeled by a functional class and selects those categories which have a significant model. ii) PCA-maSigFun fits a PCA model of each functional class-defined expression matrix to extract orthogonal patterns of expression change, which are then assessed for their fit to a time-dependent regression model. iii) ASCA-functional uses the ASCA model to rank genes according to their correlation to principal time expression patterns and assess functional enrichment on a GSA fashion. We used simulated and experimental datasets to study these novel approaches. Results were compared to alternative methodologies. Results Synthetic and experimental data showed that the different methods are able to capture different aspects of the relationship between genes, functions and co-expression that are biologically meaningful. The methods should not be considered as competitive but they provide different insights into the molecular and functional dynamic events taking place within the biological system under study. PMID:19534758

  11. Functional assessment of time course microarray data.

    PubMed

    Nueda, María José; Sebastián, Patricia; Tarazona, Sonia; García-García, Francisco; Dopazo, Joaquín; Ferrer, Alberto; Conesa, Ana

    2009-06-16

    Time-course microarray experiments study the progress of gene expression along time across one or several experimental conditions. Most developed analysis methods focus on the clustering or the differential expression analysis of genes and do not integrate functional information. The assessment of the functional aspects of time-course transcriptomics data requires the use of approaches that exploit the activation dynamics of the functional categories to where genes are annotated. We present three novel methodologies for the functional assessment of time-course microarray data. i) maSigFun derives from the maSigPro method, a regression-based strategy to model time-dependent expression patterns and identify genes with differences across series. maSigFun fits a regression model for groups of genes labeled by a functional class and selects those categories which have a significant model. ii) PCA-maSigFun fits a PCA model of each functional class-defined expression matrix to extract orthogonal patterns of expression change, which are then assessed for their fit to a time-dependent regression model. iii) ASCA-functional uses the ASCA model to rank genes according to their correlation to principal time expression patterns and assess functional enrichment on a GSA fashion. We used simulated and experimental datasets to study these novel approaches. Results were compared to alternative methodologies. Synthetic and experimental data showed that the different methods are able to capture different aspects of the relationship between genes, functions and co-expression that are biologically meaningful. The methods should not be considered as competitive but they provide different insights into the molecular and functional dynamic events taking place within the biological system under study.

  12. Picoliter-scale protein microarrays by laser direct write.

    PubMed

    Ringeisen, B R; Wu, P K; Kim, H; Piqué, A; Auyeung, R Y C; Young, H D; Chrisey, D B; Krizman, D B

    2002-01-01

    We demonstrate the accurate picoliter-scale dispensing of active proteins using a novel laser transfer technique. Droplets of protein solution are dispensed onto functionalized glass slides and into plastic microwells, activating as small as 50-microm diameter areas on these surfaces. Protein microarrays fabricated by laser transfer were assayed using standard fluorescent labeling techniques to demonstrate successful protein and antigen binding. These results indicate that laser transfer does not damage the active site of the dispensed protein and that this technique can be used to successfully fabricate a functioning protein microarray. Also, as a result of the efficient nature of the process, material usage is reduced by two to four orders of magnitude compared to conventional pin dispensing methods for protein spotting.

  13. Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease – a combined tissue microarray, in vitro and in vivo study

    PubMed Central

    2013-01-01

    Background Targeting signaling pathways is an attractive approach in many malignancies. The PI3K/Akt/mTOR pathway is activated in a number of human neoplasms, accompanied by lower overall and/or disease free survival. mTOR kinase inhibitors have been introduced in the therapy of renal cell carcinoma and mantle cell lymphoma, and several trials are currently underway. However, the pathological characterization of mTOR activity in lymphomas is still incomplete. Methods mTOR activity and the elements of mTOR complexes were investigated by immunohistochemistry on tissue microarrays representing different human non-Hodgkin-lymphomas (81 cases) and Hodgkin-lymphomas (87 cases). The expression of phospho-mTOR, phospho-4EBP1, phospho-p70S6K, phospho-S6, Rictor, Raptor and Bcl-2, Bcl-xL, Survivin and NF-kappaB-p50 were evaluated, and mTOR activity was statistically analyzed along with 5-year survival data. The in vitro and in vivo effect of the mTOR inhibitor rapamycin was also examined in human Hodgkin-lymphoma cell lines. Results The majority (>50%) of mantle cell lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, anaplastic large-cell lymphoma and Hodgkin-lymphoma cases showed higher mTOR activity compared to normal lymphoid tissues. Hodgkin-lymphoma was characterized by high mTOR activity in 93% of the cases, and Bcl-xL and NF-kappaB expression correlated with this mTOR activity. High mTOR activity was observed in the case of both favorable and unfavorable clinical response. Low mTOR activity was accompanied by complete remission and at least 5-year disease free survival in Hodgkin-lymphoma patients. However, statistical analysis did not identify correlation beetween mTOR activity and different clinical data of HL patients, such as survival. We also found that Rictor (mTORC2) was not overexpressed in Hodgkin-lymphoma biopsies and cell lines. Rapamycin inhibited proliferation and induced apoptosis in Hodgkin-lymphoma cells both in vitro and in vivo, moreover, it

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. CMOS Devices and Beyond — A Process Integration Perspective

    NASA Astrophysics Data System (ADS)

    Hutchby, James A.; Zhirnov, Victor; Cavin, Ralph; Bourianoff, George

    2003-09-01

    Development of CMOS technology is approaching severe technological limits in the next 10 - 15 years. Overcoming these limits will demand introduction of new manufacturable materials and device structures to extend the speed of silicon integrated circuits at the historical rate of 17 % per year to the end of the 2001 International Technology Roadmap for Semiconductors (2016). Following a brief discussion of these limits, this paper will review the most promising approaches to new materials, device structures and issues related to their integration in advanced CMOS structures. The paper will conclude with some brief observations and issues regarding extension of CMOS-like FET structures via new nano-scale materials.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Radiation hardness of two CMOS prototypes for the ATLAS HL-LHC upgrade project.

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

    The LHC luminosity upgrade, known as the High Luminosity LHC (HL-LHC), will require the replacement of the existing silicon strip tracker and the transistion radiation tracker. Although a baseline design for this tracker exists the ATLAS collaboration and other non-ATLAS groups are exploring the feasibility of using CMOS Monolithic Active Pixel Sensors (MAPS) which would be arranged in a strip-like fashion and would take advantage of the service and support structure already being developed for the upgrade. Two test devices made with the AMS H35 process (a High voltage or HV CMOS process) have been subjected to various radiation environments and have performed well. The results of these tests are presented in this paper.

  4. 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.

  5. 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

  6. 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).

  7. 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.

  8. 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.

  9. 1984 Joint Congress: CGU and CMOS

    NASA Astrophysics Data System (ADS)

    Camfield, P. A.

    The Canadian Geophysical Union (CGU) had a very successful joint meeting with the Canadian Meteorological and Oceanographic Society (CMOS) at Dalhousie University in Halifax, Nova Scotia, May 29 to June 1, 1984. Thirty-five scientific sessions were held in the 4-day meeting period.The invited speaker for CGU at the plenary session, David Simpson of Lamont-Doherty Geological Observatory, spoke about the Halifax Explosion of 1917 in terms of a seismic event. The 2.6-kt explosion was the largest man-made explosion prior to the detonation of the first atomic bombs. The effective seismic magnitude of the event may have been m, = 2.5-3.0.

  10. The CMOS integration of a power inverter

    NASA Astrophysics Data System (ADS)

    Mannarino, Eric Francis

    Due to their falling costs, the use of renewable energy systems is expanding around the world. These systems require the conversion of DC power into grid-synchronous AC power. Currently, the inverters that carry out this task are built using discrete transistors. TowerJazz Semiconductor Corp. has created a commercial CMOS process that allows for blocking voltages of up to 700 V, effectively removing the barrier to integrating power inverters onto a single chip. This thesis explores this process using two topologies. The first is a cell-based switched-capacitor topology first presented by Ke Zou. The second is a novel topology that explores the advantage of using a bused input-output system, as in digital electronics. Simulations run on both topologies confirm the high-efficiency demonstrated in Zou’s process as well as the advantage the bus-based system has in output voltage levels.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. CMOS image sensor with contour enhancement

    NASA Astrophysics Data System (ADS)

    Meng, Liya; Lai, Xiaofeng; Chen, Kun; Yuan, Xianghui

    2010-10-01

    Imitating the signal acquisition and processing of vertebrate retina, a CMOS image sensor with bionic pre-processing circuit is designed. Integration of signal-process circuit on-chip can reduce the requirement of bandwidth and precision of the subsequent interface circuit, and simplify the design of the computer-vision system. This signal pre-processing circuit consists of adaptive photoreceptor, spatial filtering resistive network and Op-Amp calculation circuit. The adaptive photoreceptor unit with a dynamic range of approximately 100 dB has a good self-adaptability for the transient changes in light intensity instead of intensity level itself. Spatial low-pass filtering resistive network used to mimic the function of horizontal cell, is composed of the horizontal resistor (HRES) circuit and OTA (Operational Transconductance Amplifier) circuit. HRES circuit, imitating dendrite of the neuron cell, comprises of two series MOS transistors operated in weak inversion region. Appending two diode-connected n-channel transistors to a simple transconductance amplifier forms the OTA Op-Amp circuit, which provides stable bias voltage for the gate of MOS transistors in HRES circuit, while serves as an OTA voltage follower to provide input voltage for the network nodes. The Op-Amp calculation circuit with a simple two-stage Op-Amp achieves the image contour enhancing. By adjusting the bias voltage of the resistive network, the smoothing effect can be tuned to change the effect of image's contour enhancement. Simulations of cell circuit and 16×16 2D circuit array are implemented using CSMC 0.5μm DPTM CMOS process.

  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. 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

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

    PubMed

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

    2016-12-01

    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. 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. 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). 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 bone formation.Cite this article: J. J

  19. 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.

  20. Novel R Pipeline for Analyzing Biolog Phenotypic Microarray Data

    PubMed Central

    Vehkala, Minna; Shubin, Mikhail; Connor, Thomas R; Thomson, Nicholas R; Corander, Jukka

    2015-01-01

    Data produced by Biolog Phenotype MicroArrays are longitudinal measurements of cells’ respiration on distinct substrates. We introduce a three-step pipeline to analyze phenotypic microarray data with novel procedures for grouping, normalization and effect identification. Grouping and normalization are standard problems in the analysis of phenotype microarrays defined as categorizing bacterial responses into active and non-active, and removing systematic errors from the experimental data, respectively. We expand existing solutions by introducing an important assumption that active and non-active bacteria manifest completely different metabolism and thus should be treated separately. Effect identification, in turn, provides new insights into detecting differing respiration patterns between experimental conditions, e.g. between different combinations of strains and temperatures, as not only the main effects but also their interactions can be evaluated. In the effect identification, the multilevel data are effectively processed by a hierarchical model in the Bayesian framework. The pipeline is tested on a data set of 12 phenotypic plates with bacterium Yersinia enterocolitica. Our pipeline is implemented in R language on the top of opm R package and is freely available for research purposes. PMID:25786143

  1. 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

  2. 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

  3. Electronics and photonics convergence on Si CMOS platform

    NASA Astrophysics Data System (ADS)

    Wada, Kazumi

    2004-07-01

    The present paper describes Si microphotonics and its current status of electronics and photonics convergence on Si platform based on monolithic integration using CMOS (Complementary Metal Oxide Semiconductor) technologies. The Si CMOS platform is advantageous over III-V semiconductor based platform because of a short time-lag between basic research and commercialization in terms of the standardized materials and processes. To implement photonic devices on the Si CMOS platform, it is important to reduce materials diversity in current photonics devices. Low loss SiNx waveguides with sharp bends, high performance strained Ge photodetectors for C+L band, and demultiplexer/multiplexer for WDM (wavelength division multiplexing) have been successfully implemented on the Si CMOS platform. The current targets are cost-effective OADMs (optical add-drop multiplexers) for optical communication and optical clocking for Si LSIs beyond Cu-low k technologies.

  4. 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.

  5. Monolithic integration of a plasmonic sensor with CMOS technology

    NASA Astrophysics Data System (ADS)

    Shakoor, Abdul; Cheah, Boon C.; Hao, Danni; Al-Rawhani, Mohammed; Nagy, Bence; Grant, James; Dale, Carl; Keegan, Neil; McNeil, Calum; Cumming, David R. S.

    2017-02-01

    Monolithic integration of nanophotonic sensors with CMOS detectors can transform the laboratory based nanophotonic sensors into practical devices with a range of applications in everyday life. In this work, by monolithically integrating an array of gold nanodiscs with the CMOS photodiode we have developed a compact and miniaturized nanophotonic sensor system having direct electrical read out. Doing so eliminates the need of expensive and bulky laboratory based optical spectrum analyzers used currently for measurements of nanophotonic sensor chips. The experimental optical sensitivity of the gold nanodiscs is measured to be 275 nm/RIU which translates to an electrical sensitivity of 5.4 V/RIU. This integration of nanophotonic sensors with the CMOS electronics has the potential to revolutionize personalized medical diagnostics similar to the way in which the CMOS technology has revolutionized the electronics industry.

  6. 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.

  7. Failures Of CMOS Devices At Low Radiation-Dose Rates

    NASA Technical Reports Server (NTRS)

    Goben, Charles A.; Price, William E.

    1990-01-01

    Method for obtaining approximate failure-versus-dose-rate curves derived from experiments on failures of SGS 4007 complementary metal oxide/semiconductor (CMOS) integrated circuits irradiated by Co60 and Cs137 radioactive sources.

  8. 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.

  9. A safety monitoring system for taxi based on CMOS imager

    NASA Astrophysics Data System (ADS)

    Liu, Zhi

    2005-01-01

    CMOS image sensors now become increasingly competitive with respect to their CCD counterparts, while adding advantages such as no blooming, simpler driving requirements and the potential of on-chip integration of sensor, analogue circuitry, and digital processing functions. A safety monitoring system for taxi based on cmos imager that can record field situation when unusual circumstance happened is described in this paper. The monitoring system is based on a CMOS imager (OV7120), which can output digital image data through parallel pixel data port. The system consists of a CMOS image sensor, a large capacity NAND FLASH ROM, a USB interface chip and a micro controller (AT90S8515). The structure of whole system and the test data is discussed and analyzed in detail.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Improved CMOS field isolation using Germaniun/Boron implantation

    SciTech Connect

    Pfiester, J.R.; Alvis, J.R. )

    1988-08-01

    A novel germanium/boron implantation technique for improving the electrical field isolation for high-density CMOS circuits is demonstrated. Germanium implantation causes a reduction in dopant diffusion and segregation during field oxidation and is shown to increase the p-well field threshold voltage by as much as 40 percent with no significant degradation to junction or device performance. Selective germanium implantation with a blanket boron field implant can also improve the electrical field isolation behavior for CMOS circuits.

  15. 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.

  16. 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.

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

    PubMed

    Koia, Jonni H; Moyle, Richard L; Botella, Jose R

    2012-12-18

    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. 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. 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 molecular basis of pineapple fruit

  18. 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

  19. 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

  20. Metric learning for DNA microarray data analysis

    NASA Astrophysics Data System (ADS)

    Takeuchi, Ichiro; Nakagawa, Masao; Seto, Masao

    2009-12-01

    In many microarray studies, gene set selection is an important preliminary step for subsequent main task such as tumor classification, cancer subtype identification, etc. In this paper, we investigate the possibility of using metric learning as an alternative to gene set selection. We develop a simple metric learning algorithm aiming to use it for microarray data analysis. Exploiting a property of the algorithm, we introduce a novel approach for extending the metric learning to be adaptive. We apply the algorithm to previously studied microarray data on malignant lymphoma subtype identification.

  1. 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

  2. Modeling and simulation of TDI CMOS image sensors

    NASA Astrophysics Data System (ADS)

    Nie, Kai-ming; Yao, Su-ying; Xu, Jiang-tao; Gao, Jing

    2013-09-01

    In this paper, a mathematical model of TDI CMOS image sensors was established in behavioral level through MATLAB based on the principle of a TDI CMOS image sensor using temporal oversampling rolling shutter in the along-track direction. The geometric perspective and light energy transmission relationships between the scene and the image on the sensor are included in the proposed model. A graphical user interface (GUI) of the model was also established. A high resolution satellitic picture was used to model the virtual scene being photographed. The effectiveness of the proposed model was verified by computer simulations based on the satellitic picture. In order to guide the design of TDI CMOS image sensors, the impacts of some parameters of TDI CMOS image sensors including pixel pitch, pixel photosensitive size, and integration time on the performance of the sensors were researched through the proposed model. The impacts of the above parameters on the sensors were quantified by sensor's modulation transfer function (MTF) of the along-track direction, which was calculated by slanted-edge method. The simulation results indicated that the TDI CMOS image sensor can get a better performance with smaller pixel photosensitive size and shorter integration time. The proposed model is useful in the process of researching and developing a TDI CMOS image sensor.

  3. 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.

  4. 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.

  5. 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).

  6. 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.

  7. 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)

  8. 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.

  9. 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.

  10. Experimental observation of the improvement in MTF from backthinning a CMOS direct electron detector

    PubMed Central

    McMullan, G.; Faruqi, A.R.; Henderson, R.; Guerrini, N.; Turchetta, R.; Jacobs, A.; van Hoften, G.

    2009-01-01

    The advantages of backthinning monolithic active pixel sensors (MAPS) based on complementary metal oxide semiconductor (CMOS) direct electron detectors for electron microscopy have been discussed previously; they include better spatial resolution (modulation transfer function or MTF) and efficiency at all spatial frequencies (detective quantum efficiency or DQE). It was suggested that a ‘thin’ CMOS detector would have the most outstanding properties [1–3] because of a reduction in the proportion of backscattered electrons. In this paper we show, theoretically (using Monte Carlo simulations of electron trajectories) and experimentally that this is indeed the case. The modulation transfer functions of prototype backthinned CMOS direct electron detectors have been measured at 300 keV. At zero spatial frequency, in non-backthinned 700-μm-thick detectors, the backscattered component makes up over 40% of the total signal but, by backthinning to 100, 50 or 35 μm, this can be reduced to 25%, 15% and 10%, respectively. For the 35 μm backthinned detector, this reduction in backscatter increases the MTF by 40% for spatial frequencies between 0.1 and 1.0 Nyquist. As discussed in the main text, reducing backscattering in backthinned detectors should also improve DQE. PMID:19541421

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. Demystified...tissue microarray technology.

    PubMed

    Packeisen, J; Korsching, E; Herbst, H; Boecker, W; Buerger, H

    2003-08-01

    Several "high throughput methods" have been introduced into research and routine laboratories during the past decade. Providing a new approach to the analysis of genomic alterations and RNA or protein expression patterns, these new techniques generate a plethora of new data in a relatively short time, and promise to deliver clues to the diagnosis and treatment of human cancer. Along with these revolutionary developments, new tools for the interpretation of these large sets of data became necessary and are now widely available. Tissue microarray (TMA) technology is one of these new tools. It is based on the idea of applying miniaturisation and a high throughput approach to the analysis of intact tissues. The potential and the scientific value of TMAs in modern research have been demonstrated in a logarithmically increasing number of studies. The spectrum for additional applications is widening rapidly, and comprises quality control in histotechnology, longterm tissue banking, and the continuing education of pathologists. This review covers the basic technical aspects of TMA production and discusses the current and potential future applications of TMA technology.

  17. 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.

  18. 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

  19. 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.

  20. [DNA microarrays in parasitology and medical sciences].

    PubMed

    Jaros, Sławomir

    2006-01-01

    The article presents the current knowledge on the microarray technique and its applications in medical sciences and parasitology. The first part of the article is focused on the technical aspects (microarray preparation, different microarray platforms, probes preparation, hybridization and signal detection). The article also describes possible ways of proceeding during laboratory work on organism of which the genome sequence is not known or has been only partially sequenced. The second part of the review describes how microarray technique have been, or possibly will be, used for better understanding parasite life cycles and development, host-parasite relationship, comparative genomics of virulent organisms, develpoment vaccines against the most virulent parasites and host responses to infection.

  1. 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.

  2. Multiband CMOS sensor simplify FPA design

    NASA Astrophysics Data System (ADS)

    Wang, Weng Lyang B.; Ling, Jer

    2015-10-01

    Push broom multi-band Focal Plane Array (FPA) design needs to consider optics, image sensor, electronic, mechanic as well as thermal. Conventional FPA use two or several CCD device as an image sensor. The CCD image sensor requires several high speed, high voltage and high current clock drivers as well as analog video processors to support their operation. Signal needs to digitize using external sample / hold and digitized circuit. These support circuits are bulky, consume a lot of power, must be shielded and placed in close to the CCD to minimize the introduction of unwanted noise. The CCD also needs to consider how to dissipate power. The end result is a very complicated FPA and hard to make due to more weighs and draws more power requiring complex heat transfer mechanisms. In this paper, we integrate microelectronic technology and multi-layer soft / hard Printed Circuit Board (PCB) technology to design electronic portion. Since its simplicity and integration, the optics, mechanic, structure and thermal design will become very simple. The whole FPA assembly and dis-assembly reduced to a few days. A multi-band CMOS Sensor (dedicated as C468) was used for this design. The CMOS Sensor, allow for the incorporation of clock drivers, timing generators, signal processing and digitization onto the same Integrated Circuit (IC) as the image sensor arrays. This keeps noise to a minimum while providing high functionality at reasonable power levels. The C468 is a first Multiple System-On-Chip (MSOC) IC. This device used our proprietary wafer butting technology and MSOC technology to combine five long sensor arrays into a size of 120 mm x 23.2 mm and 155 mm x 60 mm for chip and package, respectively. The device composed of one Panchromatic (PAN) and four different Multi- Spectral (MS) sensors. Due to its integration on the electronic design, a lot of room is clear for the thermal design. The optical and mechanical design is become very straight forward. The flight model FPA

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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…

  8. 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…

  9. Integration of room temperature single electron transistor with CMOS subsystem

    NASA Astrophysics Data System (ADS)

    Cheam, Daw Don

    The single electron transistor (SET) is a charge-based device that may complement the dominant metal-oxide-semiconductor field effect transistor (MOSFET) technology. As the cost of scaling MOSFET to smaller dimensions are rising and the the basic functionality of MOSFET is encountering numerous challenges at dimensions smaller than 10nm, the SET has shown the potential to become the next generation device which operates based on the tunneling of electrons. Since the electron transfer mechanism of a SET device is based on the non-dissipative electron tunneling effect, the power consumption of a SET device is extremely low, estimated to be on the order of 10--18 J. The objectives of this research are to demonstrate technologies that would enable the mass produce of SET devices that are operational at room temperature and to integrate these devices on top of an active complementary-MOSFET (CMOS) substrate. To achieve these goals, two fabrication techniques are considered in this work. The Focus Ion Beam (FIB) technique is used to fabricate the islands and the tunnel junctions of the SET device. A Ultra-Violet (UV) light based Nano-Imprint Lithography (NIL) call Step-and-Flash-Imprint Lithography (SFIL) is used to fabricate the interconnections of the SET devices. Combining these two techniques, a full array of SET devices are fabricated on a planar substrate. Test and characterization of the SET devices has shown consistent Coulomb blockade effect, an important single electron characteristic. To realize a room temperature operational SET device that function as a logic device to work along CMOS, it is important to know the device behavior at different temperatures. Based on the theory developed for a single island SET device, a thermal analysis is carried out on the multi-island SET device and the observation of changes in Coulomb blockade effect is presented. The results show that the multi-island SET device operation highly depends on temperature. The important

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. CMOS Integration of Single-Molecule Field-Effect Transistors

    NASA Astrophysics Data System (ADS)

    Warren, Steven Benjamin

    Point functionalized carbon nanotubes have recently demonstrated the ability to serve as single-molecule biosensors. Operating as single-molecule Field-Effect Transistors (smFET), the sensors have been used to explore activity ranging in scope from DNA hybridization kinetics to DNA polymerase functionality. High signal levels and an all-electronic label-free transduction mechanism make the smFET an attractive candidate for next-generation medical diagnostics platforms and high-bandwidth basic science research studies. In this work, carbon nanotubes are integrated onto a custom designed CMOS chip. Integration enables arraying many devices for measurement, providing the requisite scale-up for any commercial application of smFETs. Integration also provides substantial benefits towards achieving high bandwidths through the reduction of electrical parasitics. In a first exploitation of these high-bandwidth measurement capabilities, integrated devices are electrically characterized over a 1-MHz bandwidth. Functionalization through electrochemical oxidation of the devices is observed with microsecond temporal resolution, revealing complex reaction pathways with resolvable scattering signatures. High rate random telegraph noise (RTN) is observed in certain oxidized devices, further illustrating the temporal resolution of the integrated sensing platform.

  17. 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.

  18. A versatile approach to high-throughput microarrays using thiol-ene chemistry

    NASA Astrophysics Data System (ADS)

    Gupta, Nalini; Lin, Brian F.; Campos, Luis M.; Dimitriou, Michael D.; Hikita, Sherry T.; Treat, Neil D.; Tirrell, Matthew V.; Clegg, Dennis O.; Kramer, Edward J.; Hawker, Craig J.

    2010-02-01

    Microarray technology has become extremely useful in expediting the investigation of large libraries of materials in a variety of biomedical applications, such as in DNA chips, protein and cellular microarrays. In the development of cellular microarrays, traditional high-throughput printing strategies on stiff, glass substrates and non-covalent attachment methods are limiting. We have developed a facile strategy to fabricate multifunctional high-throughput microarrays embedded at the surface of a hydrogel substrate using thiol-ene chemistry. This user-friendly method provides a platform for the immobilization of a combination of bioactive and diagnostic molecules, such as peptides and dyes, at the surface of poly(ethylene glycol)-based hydrogels. The robust and orthogonal nature of thiol-ene chemistry allows for a range of covalent attachment strategies in a fast and reliable manner, and two complementary strategies for the attachment of active molecules are demonstrated.

  19. 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

  20. Chromosomal microarray versus karyotyping for prenatal diagnosis.

    PubMed

    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

    2012-12-06

    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. 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. 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. 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.).

  1. High-speed CMOS optical communication using silicon light emitters

    NASA Astrophysics Data System (ADS)

    Goosen, Marius E.; Venter, Petrus J.; du Plessis, Monuko; Nell, Ilse J.; Bogalecki, Alfons W.; Rademeyer, Pieter

    2011-01-01

    The idea of moving CMOS into the mainstream optical domain remains an attractive one. In this paper we discuss our recent advances towards a complete silicon optical communication solution. We prove that transmission of baseband data at multiples of megabits per second rates are possible using improved silicon light sources in a completely native standard CMOS process with no post processing. The CMOS die is aligned to a fiber end and the light sources are directly modulated. An optical signal is generated and transmitted to a silicon Avalanche Photodiode (APD) module, received and recovered. Signal detectability is proven through eye diagram measurements. The results show an improvement of more than tenfold over our previous results, also demonstrating the fastest optical communication from standard CMOS light sources. This paper presents an all silicon optical data link capable of 2 Mb/s at a bit error rate of 10-10, or alternatively 1 Mb/s at a bit error rate of 10-14. As the devices are not operating at their intrinsic switching speed limit, we believe that even higher transmission rates are possible with complete integration of all components in CMOS.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 77 FR 74513 - Certain CMOS Image Sensors and Products Containing Same; Investigations: Terminations...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-14

    ... From the Federal Register Online via the Government Publishing Office INTERNATIONAL TRADE COMMISSION Certain CMOS Image Sensors and Products Containing Same; Investigations: Terminations... importation, and the sale within the United States after importation of certain CMOS image sensors and...

  9. 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.

  10. 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.

  11. Universal ligation-detection-reaction microarray applied for compost microbes

    PubMed Central

    Hultman, Jenni; Ritari, Jarmo; Romantschuk, Martin; Paulin, Lars; Auvinen, Petri

    2008-01-01

    Background Composting is one of the methods utilised in recycling organic communal waste. The composting process is dependent on aerobic microbial activity and proceeds through a succession of different phases each dominated by certain microorganisms. In this study, a ligation-detection-reaction (LDR) based microarray method was adapted for species-level detection of compost microbes characteristic of each stage of the composting process. LDR utilises the specificity of the ligase enzyme to covalently join two adjacently hybridised probes. A zip-oligo is attached to the 3'-end of one probe and fluorescent label to the 5'-end of the other probe. Upon ligation, the probes are combined in the same molecule and can be detected in a specific location on a universal microarray with complementary zip-oligos enabling equivalent hybridisation conditions for all probes. The method was applied to samples from Nordic composting facilities after testing and optimisation with fungal pure cultures and environmental clones. Results Probes targeted for fungi were able to detect 0.1 fmol of target ribosomal PCR product in an artificial reaction mixture containing 100 ng competing fungal ribosomal internal transcribed spacer (ITS) area or herring sperm DNA. The detection level was therefore approximately 0.04% of total DNA. Clone libraries were constructed from eight compost samples. The LDR microarray results were in concordance with the clone library sequencing results. In addition a control probe was used to monitor the per-spot hybridisation efficiency on the array. Conclusion This study demonstrates that the LDR microarray method is capable of sensitive and accurate species-level detection from a complex microbial community. The method can detect key species from compost samples, making it a basis for a tool for compost process monitoring in industrial facilities. PMID:19116002

  12. Robust integration schemes for junction-based modulators in a 200mm CMOS compatible silicon photonic platform (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Szelag, Bertrand; Abraham, Alexis; Brision, Stéphane; Gindre, Paul; Blampey, Benjamin; Myko, André; Olivier, Segolene; Kopp, Christophe

    2017-05-01

    Silicon photonic is becoming a reality for next generation communication system addressing the increasing needs of HPC (High Performance Computing) systems and datacenters. CMOS compatible photonic platforms are developed in many foundries integrating passive and active devices. The use of existing and qualified microelectronics process guarantees cost efficient and mature photonic technologies. Meanwhile, photonic devices have their own fabrication constraints, not similar to those of cmos devices, which can affect their performances. In this paper, we are addressing the integration of PN junction Mach Zehnder modulator in a 200mm CMOS compatible photonic platform. Implantation based device characteristics are impacted by many process variations among which screening layer thickness, dopant diffusion, implantation mask overlay. CMOS devices are generally quite robust with respect to these processes thanks to dedicated design rules. For photonic devices, the situation is different since, most of the time, doped areas must be carefully located within waveguides and CMOS solutions like self-alignment to the gate cannot be applied. In this work, we present different robust integration solutions for junction-based modulators. A simulation setup has been built in order to optimize of the process conditions. It consist in a Mathlab interface coupling process and device electro-optic simulators in order to run many iterations. Illustrations of modulator characteristic variations with process parameters are done using this simulation setup. Parameters under study are, for instance, X and Y direction lithography shifts, screening oxide and slab thicknesses. A robust process and design approach leading to a pn junction Mach Zehnder modulator insensitive to lithography misalignment is then proposed. Simulation results are compared with experimental datas. Indeed, various modulators have been fabricated with different process conditions and integration schemes. Extensive

  13. Performing custom microRNA microarray experiments.

    PubMed

    Zhang, Xiaoxiao; Zeng, Yan

    2011-10-28

    microRNAs (miRNAs) are a large family of ˜ 22 nucleotides (nt) long RNA molecules that are widely expressed in eukaryotes (1). Complex genomes encode at least hundreds of miRNAs, which primarily inhibit the expression of a vast number of target genes post-transcriptionally (2, 3). miRNAs control a broad range of biological processes (1). In addition, altered miRNA expression has been associated with human diseases such as cancers, and miRNAs may serve as biomarkers for diseases and prognosis (4, 5). It is important, therefore, to understand the expression and functions of miRNAs under many different conditions. Three major approaches have been employed to profile miRNA expression: real-time PCR, microarray, and deep sequencing. The technique of miRNA microarray has the advantage of being high-throughput, generally less expensive, and most of the experimental and analysis steps can be carried out in a molecular biology laboratory at most universities, medical schools and associated hospitals. Here, we describe a method for performing custom miRNA microarray experiments. A miRNA probe set will be printed on glass slides to produce miRNA microarrays. RNA is isolated using a method or reagent that preserves small RNA species, and then labeled with a fluorescence dye. As a control, reference DNA oligonucleotides corresponding to a subset of miRNAs are also labeled with a different fluorescence dye. The reference DNA will serve to demonstrate the quality of the slide and hybridization and will also be used for data normalization. The RNA and DNA are mixed and hybridized to a microarray slide containing probes for most of the miRNAs in the database. After washing, the slide is scanned to obtain images, and intensities of the individual spots quantified. These raw signals will be further processed and analyzed as the expression data of the corresponding miRNAs. Microarray slides can be stripped and regenerated to reduce the cost of microarrays and to enhance the

  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. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Radiation imaging with a new scintillator and a CMOS camera

    NASA Astrophysics Data System (ADS)

    Kurosawa, S.; Shoji, Y.; Pejchal, J.; Yokota, Y.; Yoshikawa, A.

    2014-07-01

    A new imaging system consisting of a high-sensitivity complementary metal-oxide semiconductor (CMOS) sensor, a microscope and a new scintillator, Ce-doped Gd3(Al,Ga)5O12 (Ce:GAGG) grown by the Czochralski process, has been developed. The noise, the dark current and the sensitivity of the CMOS camera (ORCA-Flash4.0, Hamamatsu) was revised and compared to a conventional CMOS, whose sensitivity is at the same level as that of a charge coupled device (CCD) camera. Without the scintillator, this system had a good position resolution of 2.1 ± 0.4 μm and we succeeded in obtaining the alpha-ray images using 1-mm thick Ce:GAGG crystal. This system can be applied for example to high energy X-ray beam profile monitor, etc.

  20. 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

  1. 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.

  2. Equalizing Si photodetectors fabricated in standard CMOS processes

    NASA Astrophysics Data System (ADS)

    Guerrero, E.; Aguirre, J.; Sánchez-Azqueta, C.; Royo, G.; Gimeno, C.; Celma, S.

    2017-05-01

    This work presents a new continuous-time equalization approach to overcome the limited bandwidth of integrated CMOS photodetectors. It is based on a split-path topology that features completely decoupled controls for boosting and gain; this capability allows a better tuning of the equalizer in comparison with other architectures based on the degenerated differential pair, which is particularly helpful to achieve a proper calibration of the system. The equalizer is intended to enhance the bandwidth of CMOS standard n-well/p-bulk differential photodiodes (DPDs), which falls below 10MHz representing a bottleneck in fully integrated optoelectronic interfaces to fulfill the low-cost requirements of modern smart sensors. The proposed equalizer has been simulated in a 65nm CMOS process and biased with a single supply voltage of 1V, where the bandwidth of the DPD has been increased up to 3 GHz.

  3. 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.

  4. 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.

  5. Architectures for Low-noise CMOS Electronic Imaging

    NASA Astrophysics Data System (ADS)

    Kawahito, Shoji

    This chapter discusses various types of signal readout architectures for CMOS image sensors, implementing ultra-low-noise conversion of photo-generated charge packets into digital output values. It is based on a detailed analysis of the different noise sources in a CMOS imager, the noise responses of column noise cancelling circuits using correlated double sampling (CDS) and correlated multiple sampling (CMS) techniques and a noiseless signal readout technique using a precise digitizer. Finally, a practical example for the design of a CMOS image sensor with single-photon resolution is presented, and the technological requirements for meeting the condition for room-temperature readout noise of significantly less than 1 electron are discussed.

  6. 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.

  7. 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.

  8. Complementary Metal-Oxide-Silicon (CMOS)-Memristor Hybrid Nanoelectronics for Advanced Encryption Standard (AES) Encryption

    DTIC Science & Technology

    2016-04-01

    nanodevices may be limited. High- performance CMOS technology will remain as the primary driver for the integrated circuit (IC) industry and non-conventional...memristor hybrid nanoelectronic circuits . Specifically, memristor nanodevices optimized for performance and reliability were developed and integrated with...materials, integrated memristors with CMOS devices, designed and simulated CMOS-memristor hybrid circuits , and performed reliability assessments on

  9. 77 FR 26787 - Certain CMOS Image Sensors and Products Containing Same; Notice of Receipt of Complaint...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-07

    ... COMMISSION Certain CMOS Image Sensors and Products Containing Same; Notice of Receipt of Complaint... complaint entitled Certain CMOS Image Sensors and Products Containing Same, DN 2895; the Commission is... importation of certain CMOS image sensors and products containing same. The complaint names as...

  10. 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.

  11. Use of a bacterial antimicrobial resistance gene microarray for the identification of resistant Staphylococcus aureus.

    PubMed

    Garneau, P; Labrecque, O; Maynard, C; Messier, S; Masson, L; Archambault, M; Harel, J

    2010-11-01

    As diagnostic and surveillance activities are vital to determine measures needed to control antimicrobial resistance (AMR), new and rapid laboratory methods are necessary to facilitate this important effort. DNA microarray technology allows the detection of a large number of genes in a single reaction. This technology is simple, specific and high-throughput. We have developed a bacterial antimicrobial resistance gene DNA microarray that will allow rapid antimicrobial resistance gene screening for all Gram-positive and Gram-negative bacteria. A prototype microarray was designed using a 70-mer based oligonucleotide set targeting AMR genes of Gram-negative and Gram-positive bacteria. In the present version, the microarray consists of 182 oligonucleotides corresponding to 166 different acquired AMR gene targets, covering most of the resistance genes found in both Gram-negative and -positive bacteria. A test study was performed on a collection of Staphylococcus aureus isolates from milk samples from dairy farms in Québec, Canada. The reproducibility of the hybridizations was determined, and the microarray results were compared with those obtained by phenotypic resistance tests (either MIC or Kirby-Bauer). The microarray genotyping demonstrated a correlation between penicillin, tetracycline and erythromycin resistance phenotypes with the corresponding acquired resistance genes. The hybridizations showed that the 38 antimicrobial resistant S. aureus isolates possessed at least one AMR gene. © 2010 Blackwell Verlag GmbH.

  12. 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.

  13. Designing microarray phantoms for hyperspectral imaging validation

    PubMed Central

    Clarke, Matthew L.; Lee, Ji Youn; Samarov, Daniel V.; Allen, David W.; Litorja, Maritoni; Nossal, Ralph; Hwang, Jeeseong

    2012-01-01

    The design and fabrication of custom-tailored microarrays for use as phantoms in the characterization of hyperspectral imaging systems is described. Corresponding analysis methods for biologically relevant samples are also discussed. An image-based phantom design was used to program a microarrayer robot to print prescribed mixtures of dyes onto microscope slides. The resulting arrays were imaged by a hyperspectral imaging microscope. The shape of the spots results in significant scattering signals, which can be used to test image analysis algorithms. Separation of the scattering signals allowed elucidation of individual dye spectra. In addition, spectral fitting of the absorbance spectra of complex dye mixtures was performed in order to determine local dye concentrations. Such microarray phantoms provide a robust testing platform for comparisons of hyperspectral imaging acquisition and analysis methods. PMID:22741076

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. Digital architectures for hybrid CMOS/nanodevice circuits

    NASA Astrophysics Data System (ADS)

    Strukov, Dmitri B.

    This dissertation describes architectures of digital memories and reconfigurable Boolean logic circuits for the prospective hybrid CMOS/nanowire/nanodevice ("CMOL") technology. The basic idea of CMOL circuits is to combine the advantages of CMOS technology (including its flexibility and high fabrication yield) with those of molecular-scale nanodevices. Two-terminal nanodevices would be naturally incorporated into nanowire crossbar fabric, enabling very high function density at acceptable fabrication costs. In order to overcome the CMOS/nanodevice interface problem, in CMOL circuits the interface is provided by sharp-tipped pins that are distributed all over the circuit area, on top of the CMOS stack. The most straightforward possible application of CMOL circuits is terabit-scale "resistive" memories, in which nanodevices (e.g., single molecules) would be used as single-bit, memory cells, while the semiconductor subsystem would perform all the peripheral (input/output, coding/decoding, line driving, and sense amplification) functions. Using bad-bit exclusion and error-correcting codes synergistically we show that CMOL memories with a nano/CMOS pitch ratio close to 1/3 may overcome purely semiconductor memories in useful density if the fraction of bad nanodevices is below ˜ 15%, even for the 30 ns upper bound on the total access time. As the nanotechnology matures, and the pitch ratio approaches an order of magnitude, the CMOL memories may be far superior to the densest semiconductor memories by providing, e.g., 1 Tbit/cm2 density even for the plausible defect fraction of 2%. Even greater defect tolerance (about 20% for 99% circuit yield) can be achieved in uniform a cell-FPGA-like CMOL circuits. In such circuits, two-terminal nanodevices provide programmable diode functionality for logic circuit operation, and allow circuit mapping and reconfiguration around defective nanodevices, while CMOS subsystem is used for signal restoration and latching. The cell

  20. 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.