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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. 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. PMID:23851206

  4. 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.

  5. 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

  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. 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…

  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. PMID:24489484

  9. 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.

  10. 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…

  11. CMOS Monolithic Active Pixel Sensors (MAPS): Developments and future outlook

    NASA Astrophysics Data System (ADS)

    Turchetta, R.; Fant, A.; Gasiorek, P.; Esbrand, C.; Griffiths, J. A.; Metaxas, M. G.; Royle, G. J.; Speller, R.; Venanzi, C.; van der Stelt, P. F.; Verheij, H.; Li, G.; Theodoridis, S.; Georgiou, H.; Cavouras, D.; Hall, G.; Noy, M.; Jones, J.; Leaver, J.; Machin, D.; Greenwood, S.; Khaleeq, M.; Schulerud, H.; Østby, J. M.; Triantis, F.; Asimidis, A.; Bolanakis, D.; Manthos, N.; Longo, R.; Bergamaschi, A.

    2007-12-01

    Re-invented in the early 1990s, on both sides of the Atlantic, Monolithic Active Pixel Sensors (MAPS) in a CMOS technology are today the most sold solid-state imaging devices, overtaking the traditional technology of Charge-Coupled Devices (CCD). The slow uptake of CMOS MAPS started with low-end applications, for example web-cams, and is slowly pervading the high-end applications, for example in prosumer digital cameras. Higher specifications are required for scientific applications: very low noise, high speed, high dynamic range, large format and radiation hardness are some of these requirements. This paper will present a brief overview of the CMOS Image Sensor technology and of the requirements for scientific applications. As an example, a sensor for X-ray imaging will be presented. This sensor was developed within a European FP6 Consortium, intelligent imaging sensors (I-ImaS).

  12. Monolithic active pixel sensors (MAPS) in a VLSI CMOS technology

    NASA Astrophysics Data System (ADS)

    Turchetta, R.; French, M.; Manolopoulos, S.; Tyndel, M.; Allport, P.; Bates, R.; O'Shea, V.; Hall, G.; Raymond, M.

    2003-03-01

    Monolithic Active Pixel Sensors (MAPS) designed in a standard VLSI CMOS technology have recently been proposed as a compact pixel detector for the detection of high-energy charged particle in vertex/tracking applications. MAPS, also named CMOS sensors, are already extensively used in visible light applications. With respect to other competing imaging technologies, CMOS sensors have several potential advantages in terms of low cost, low power, lower noise at higher speed, random access of pixels which allows windowing of region of interest, ability to integrate several functions on the same chip. This brings altogether to the concept of 'camera-on-a-chip'. In this paper, we review the use of CMOS sensors for particle physics and we analyse their performances in term of the efficiency (fill factor), signal generation, noise, readout speed and sensor area. In most of high-energy physics applications, data reduction is needed in the sensor at an early stage of the data processing before transfer of the data to tape. Because of the large number of pixels, data reduction is needed on the sensor itself or just outside. This brings in stringent requirements on the temporal noise as well as to the sensor uniformity, expressed as a Fixed Pattern Noise (FPN). A pixel architecture with an additional transistor is proposed. This architecture, coupled to correlated double sampling of the signal will allow cancellation of the two dominant noise sources, namely the reset or kTC noise and the FPN. A prototype has been designed in a standard 0.25 μm CMOS technology. It has also a structure for electrical calibration of the sensor. The prototype is functional and detailed tests are under way.

  13. CMOS Imaging Device for Optical Imaging of Biological Activities

    NASA Astrophysics Data System (ADS)

    Shishido, Sanshiro; Oguro, Yasuhiro; Noda, Toshihiko; Sasagawa, Kiyotaka; Tokuda, Takashi; Ohta, Jun

    In this paper, we propose a CMOS image sensor device placed on the brain surface or cerebral sulcus (Fig. 1). The device has a photo detector array where a single optical detector is usually used. The proposed imaging device enables the analysis which reflects a surface blood pattern in the observed area. It is also possible to improve effective sensitivity by image processing and to simplify the measurement system by the CMOS sensor device with on-chip light source. We describe the design details and characterization of proposed device. We also demonstrate detection of hemoglobin oxygenation level with external light source, imaging capability of biological activities, and image processing for sensitivity improvement is also realized.

  14. 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

  15. CMOS Active Pixel Sensor (APS) Imager for Scientific Applications

    NASA Astrophysics Data System (ADS)

    Ay, Suat U.; Lesser, Michael P.; Fossum, Eric R.

    2002-12-01

    A 512×512 CMOS Active Pixel Sensor (APS) imager has been designed, fabricate, and tested for frontside illumination suitable for use in astronomy specifically in telescope guider systems as a replacement of CCD chips. The imager features a high-speed differential analog readout, 15 μm pixel pitch, 75 % fill factor (FF), 62 dB dynamic range, 315Ke- pixel capacity, less than 0.25% fixed pattern noise (FPN), 45 dB signal to noise ratio (SNR) and frame rate of up to 40 FPS. Design was implemented in a standard 0.5 μm CMOS process technology consuming less than 200mWatts on a single 5 Volt power supply. CMOS Active Pixel Sensor (APS) imager was developed with pixel structure suitable for both frontside and backside illumination holding large number of electron in relatively small pixel pitch of 15 μm. High-speed readout and signal processing circuits were designed to achieve low fixed pattern noise (FPN) and non-uniformity to provide CCD-like analog outputs. Target spectrum range of operation for the imager is in near ultraviolet (300-400 nm) with high quantum efficiency. This device is going to be used as a test vehicle to develop backside-thinning process.

  16. Transversal-readout CMOS active pixel image sensor

    NASA Astrophysics Data System (ADS)

    Miyatake, Shigehiro; Ishida, Kouichi; Morimoto, Takashi; Masaki, Yasuo; Tanabe, Hideki

    2001-05-01

    This paper presents a CMOS active pixel image sensor (APS) with a transversal readout architecture that eliminates the vertically striped fixed pattern noise (FPN). There are two kinds of FPNs for CMOS APSs. One originates form the pixel- to-pixel variation in dark current and source-follower threshold voltage, and the other from the column-to-column variation in column readout structures. The former may become invisible in the future due to process improvements. However, the latter, which result sin a vertically striped FPN, is and will be conspicuous without some subtraction because of the correlation in the vertical direction. The pixel consists of a photodiode, a row- and a column-reset transistor, a source follower input transistor, and a column-select transistor instead of the row-select transistor in conventional CMOS APSs. The column-select transistor is connected to a signal line, which runs horizontally instead of vertically. Every horizontal signal line is merged into a single vertical signal line via a row- select transistor, which can be made large enough to make its on-resistence variation negligible because of its low driving frequency. Therefore, the sensor has neither a vertical nor horizontal stripe FPN.

  17. 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.

  18. 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.

  19. 3D monolithically stacked CMOS Active Pixel Sensors for particle position and direction measurements

    NASA Astrophysics Data System (ADS)

    Servoli, L.; Passeri, D.; Morozzi, A.; Magalotti, D.; Piperku, L.

    2015-01-01

    In this work we propose a 3D monolithically stacked, multi-layer detectors based on CMOS Active Pixel Sensors (APS) layers which allows at the same time accurate estimation of the impact point and of the incidence angle an ionizing particle. The whole system features two fully-functional CMOS APS matrix detectors, including both sensing area and control/signal elaboration circuitry, stacked in a monolithic device by means of Through Silicon Via (TSV) connections thanks to the capabilities of the CMOS vertical scale integration (3D-IC) 130 nm Chartered/Tezzaron technology. In order to evaluate the suitability of the two layer monolithic active pixel sensor system to reconstruct particle tracks, tests with proton beams have been carried out at the INFN LABEC laboratories in Florence (Italy) with 3 MeV proton beam.

  20. 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.

  1. Diffractive micro-arrays for active spectroscopy and interconnect applications

    NASA Astrophysics Data System (ADS)

    Castracane, James; Xu, Bai; Gutin, Olga N.; Lavrijsen, Rein; Stollenwerk, Andrew

    2002-06-01

    The use of Micro-Electro-Mechanical Systems (MEMS) technology has opened the door for many applications. In particular, by exploiting the reconfigurability of optical surfaces fabricated with this technology, many sensor, communication and spectroscopic systems can benefit. The controlled re-direction of single or multiple optical input sources can lend itself to high throughput sample analysis or massively parallel optical connectivity. In addition, the change in a MEMS-based optical surface can result in a flexible spectral analysis of incoming radiation. We report on the recent advances in our projects which are focused on the design/simulation, materials processing and integration issues involved with the creation and optimized operation of such diffractive micro-arrays. In this presentation, the state of the art in such devices will be presented which will include the process flow associated with production, structural metrology, optical performance, and parallel switching capabilities of the systems. The use of numerous materials including polysilicon, silicon dioxide and selected polymers as structural layers has enabled the production of devices which can be tailored for specific, performance related applications. Examples to be presented include diffractive surfaces with substantial (1 cm x 1 cm) active areas as well as large arrays with sub-micron feature sizes. Functional integration of the prototype devices include optical interconnects, active spectroscopy and bio/chem diagnostic systems.

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

    PubMed

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

    2014-07-01

    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

  3. 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

  4. 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.

  5. Towards real-time VMAT verification using a prototype, high-speed CMOS active pixel sensor

    NASA Astrophysics Data System (ADS)

    Zin, Hafiz M.; Harris, Emma J.; Osmond, John P. F.; Allinson, Nigel M.; Evans, Philip M.

    2013-05-01

    This work investigates the feasibility of using a prototype complementary metal oxide semiconductor active pixel sensor (CMOS APS) for real-time verification of volumetric modulated arc therapy (VMAT) treatment. The prototype CMOS APS used region of interest read out on the chip to allow fast imaging of up to 403.6 frames per second (f/s). The sensor was made larger (5.4 cm × 5.4 cm) using recent advances in photolithographic technique but retains fast imaging speed with the sensor's regional read out. There is a paradigm shift in radiotherapy treatment verification with the advent of advanced treatment techniques such as VMAT. This work has demonstrated that the APS can track multi leaf collimator (MLC) leaves moving at 18 mm s-1 with an automatic edge tracking algorithm at accuracy better than 1.0 mm even at the fastest imaging speed. Evaluation of the measured fluence distribution for an example VMAT delivery sampled at 50.4 f/s was shown to agree well with the planned fluence distribution, with an average gamma pass rate of 96% at 3%/3 mm. The MLC leaves motion and linac pulse rate variation delivered throughout the VMAT treatment can also be measured. The results demonstrate the potential of CMOS APS technology as a real-time radiotherapy dosimeter for delivery of complex treatments such as VMAT.

  6. CMOS Active Pixel Sensors as energy-range detectors for proton Computed Tomography

    NASA Astrophysics Data System (ADS)

    Esposito, M.; Anaxagoras, T.; Evans, P. M.; Green, S.; Manolopoulos, S.; Nieto-Camero, J.; Parker, D. J.; Poludniowski, G.; Price, T.; Waltham, C.; Allinson, N. M.

    2015-06-01

    Since the first proof of concept in the early 70s, a number of technologies has been proposed to perform proton CT (pCT), as a means of mapping tissue stopping power for accurate treatment planning in proton therapy. Previous prototypes of energy-range detectors for pCT have been mainly based on the use of scintillator-based calorimeters, to measure proton residual energy after passing through the patient. However, such an approach is limited by the need for only a single proton passing through the energy-range detector in a read-out cycle. A novel approach to this problem could be the use of pixelated detectors, where the independent read-out of each pixel allows to measure simultaneously the residual energy of a number of protons in the same read-out cycle, facilitating a faster and more efficient pCT scan. This paper investigates the suitability of CMOS Active Pixel Sensors (APSs) to track individual protons as they go through a number of CMOS layers, forming an energy-range telescope. Measurements performed at the iThemba Laboratories will be presented and analysed in terms of correlation, to confirm capability of proton tracking for CMOS APSs.

  7. Assessing design activity in complex CMOS circuit design

    NASA Astrophysics Data System (ADS)

    Biswas, Gautam; Goldman, Susan R.; Fisher, Doug; Bhuva, Bharat; Glewwe, Grant

    1994-03-01

    This chapter characterizes human problem solving in digital circuit design. We analyze protocols of designers with varying degrees of training, identifying problem solving strategies used by these designers, discuss activity patterns that differentiate designers, and propose these as a tentative basis for assessing expertise in digital design. Throughout, we argue that a comprehensive model of human design should integrate a variety of strategies, which heretofore have been proposed as individually sufficient models of human design problem solving. We close by describing an automated tool for design and its assessment.

  8. 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.

  9. 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.

  10. Depleted Monolithic Active Pixel Sensors (DMAPS) implemented in LF-150 nm CMOS technology

    NASA Astrophysics Data System (ADS)

    Kishishita, T.; Hemperek, T.; Krüger, H.; Wermes, N.

    2015-03-01

    We present the recent development of Depleted Monolithic Active Pixel Sensors (DMAPS), implemented with an LFoundry (LF) 150 nm CMOS process. MAPS detectors based on an epi-layer have been matured in recent years and have attractive features in terms of reducing material budget and handling cost compared to conventional hybrid pixel detectors. However, the obtained signal is relatively small (~1000 e-) due to the thin epi-layer, and charge collection time is relatively slow, e.g., in the order of 100 ns, because charges are mainly collected by diffusion. Modern commercial CMOS technology, however, offers advanced process options to overcome such difficulties and enable truly monolithic devices as an alternative to hybrid pixel sensors and charge coupled devices. Unlike in the case of the standard MAPS technologies with epi-layers, the LF process provides a high-resistivity substrate that enables large signal and fast charge collection by drift in a ~50 μm thick depleted layer. Since this process also enables the use of deep n- and p-wells to isolate the collection electrode from the thin active device layer, PMOS and NMOS transistors are available for the readout electronics in each pixel cell. In order to evaluate the sensor and transistor characteristics, several collection electrodes variants and readout architectures have been implemented. In this report, we focus on its design aspect of the LF-DMAPS prototype chip.

  11. 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

  12. Towards monolithically integrated CMOS cameras for active imaging with 600 GHz radiation

    NASA Astrophysics Data System (ADS)

    Boppel, Sebastian; Lisauskas, Alvydas; Krozer, Viktor; Roskos, Hartmut G.

    2012-02-01

    We explore terahertz imaging with CMOS field-effect transistors exploiting their plasmonic detection capability and the advantages of CMOS technology for the fabrication of THz cameras with respect to process stability, array uniformity, ease of integration of additional functionality, scalability and cost-effectiveness. A 100×100-pixel camera with an active area of 20×20 mm² is physically simulated by scanning single detectors and groups of a few detectors in the image plane. Using detectors with a noise-equivalent power of 43 pW/√Hz, a distributed illumination of 432 μW at 591.4 GHz, and an integration time of 20 ms (for a possible frame rate of 17 fps), this virtual camera allows to obtain images with a dynamic range of at least 20 dB and a resolution approaching the diffraction limit. Imaging examples acquired in direct and heterodyne detection mode, and in transmission and reflection geometry, show the potential for real-time operation. It is demonstrated that heterodyning (i) improves the dynamic range substantially even if the radiation from the local oscillator is distributed over the camera area, and (ii) allows sensitive determination of object-induced phase changes, which promises the realization of coherent imaging systems.

  13. A Real-time Auto-detection Method for Random Telegraph Signal (RTS) Noise Detection in CMOS Active pixel sensors

    NASA Astrophysics Data System (ADS)

    Zheng, R.; Zhao, R.; Ma, Y.; Li, B.; Wei, X.; Wang, J.; Gao, W.; Wei, T.; Gao, D.; Hu, Y.

    2015-07-01

    CMOS Active pixel sensors (CMOS APS) are attractive for use in the innermost layers of charged particle trackers, due to their good tradeoffs among the key performances. However, CMOS APS can be greatly influenced by random telegraph signal (RTS) noise, which can cause particle tracking or energy calculation failures. In-depth research of pixels' RTS behavior stimulates the interest of the methods for RTS noise detection, reconstruction and parameters extraction. In this paper, a real-time auto-detection method is proposed, using real-time Gaussian noise standard deviation as the detection threshold. Experimental results show that, compared with current methods using signal standard deviation as the thresholds, the proposed method is more sensitive in multi-level RTS detection and more effective in the case of RTS noise degradation.

  14. 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. PMID:26842269

  15. 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.

  16. The Peptide Microarray-Based Resonance Light Scattering Assay for Sensitively Detecting Intracellular Kinase Activity.

    PubMed

    Li, Tao; Liu, Xia; Liu, Dianjun; Wang, Zhenxin

    2016-01-01

    The peptide microarray technology is a robust, reliable, and efficient technique for large-scale determination of enzyme activities, and high-throughput profiling of substrate/inhibitor specificities of enzymes. Here, the activities of cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) in different cell lysates have been detected by a peptide microarray-based resonance light scattering (RLS) assay with gold nanoparticle (GNP) probes. Highly sensitive detection of PKA activity in 0.1 μg total cell proteins of SHG-44 (human glioma cell) cell lysate (corresponding to 200 cells) is achieved by a selected peptide substrate. The experimental results also demonstrate that the RLS assay can be employed to evaluate the chemical regulation of intracellular kinase activity. PMID:26490469

  17. 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.

  18. Characterization of Depleted Monolithic Active Pixel detectors implemented with a high-resistive CMOS technology

    NASA Astrophysics Data System (ADS)

    Kishishita, T.; Hemperek, T.; Rymaszewski, P.; Hirono, T.; Krüger, H.; Wermes, N.

    2016-07-01

    We present the recent development of DMAPS (Depleted Monolithic Active Pixel Sensor), implemented with a Toshiba 130 nm CMOS process. Unlike in the case of standard MAPS technologies which are based on an epi-layer, this process provides a high-resistive substrate that enables larger signal and faster charge collection by drift in a 50 - 300 μm thick depleted layer. Since this process also enables the use of deep n-wells to isolate the collection electrodes from the thin active device layer, NMOS and PMOS transistors are available for the readout electronics in each pixel cell. In order to characterize the technology, we implemented a simple three transistor readout with a variety of pixel pitches and input FET sizes. This layout variety gives us a clue on sensor characteristics for future optimization, such as the input detector capacitance or leakage current. In the initial measurement, the radiation spectra were obtained from 55Fe with an energy resolution of 770 eV (FWHM) and 90Sr with the MVP of 4165 e-.

  19. Next-generation CMOS active pixel sensors for satellite hybrid optical communications/imaging sensor systems

    NASA Astrophysics Data System (ADS)

    Stirbl, Robert C.; Pain, Bedabrata; Cunningham, Thomas J.; Hancock, Bruce R.; McCarty, Kenneth P.

    1998-12-01

    Given the current choices of (1) an ever increasing population of large numbers of satellites in low-earth orbit (LEO) constellations for commercial and military global coverage systems, or (2) the alternative of smaller count geosynchronous satellite system constellations in high-earth (HEO), of higher cost and complexity, a number of commercial communications and military operations satellite systems designers are investigating the potential advantages and issues of operating in the mid-earth orbit altitudes (MEO) (between LEO and HEO). At these MEO altitudes both total dose and displacement damage can be traded against the system advantages of fewer satellites required. With growing demand for higher bandwidth communication for real-time earth observing satellite sensor systems, and NASA's interplanetary and deep space virtual unmanned exploration missions in stressing radiation environments, JPL is developing the next generation of smart sensors to address these new requirements of: low-cost, high bandwidth, miniaturization, ultra low-power and mission environment ruggedness. Radiation hardened/tolerant Active Pixel Sensor CMOS imagers that can be adaptively windowed with low power, on-chip control, timing, digital output and provide data-channel efficient on-chip compression, high bandwidth optical communications links are being designed and investigated to reduce size, weight and cost for common optics/hybrid architectures.

  20. Characterisation of a CMOS active pixel sensor for use in the TEAM microscope

    NASA Astrophysics Data System (ADS)

    Battaglia, Marco; Contarato, Devis; Denes, Peter; Doering, Dionisio; Duden, Thomas; Krieger, Brad; Giubilato, Piero; Gnani, Dario; Radmilovic, Velimir

    2010-10-01

    A 1M- and a 4M-pixel monolithic CMOS active pixel sensor with 9.5×9.5 μm2 pixels have been developed for direct imaging in transmission electron microscopy as part of the TEAM project. We present the design and a full characterisation of the detector. Data collected with electron beams at various energies of interest in electron microscopy are used to determine the detector response. Data are compared to predictions of simulation. The line spread function measured with 80 and 300 keV electrons is (12.1±0.7) and (7.4±0.6) μm, respectively, in good agreement with our simulation. We measure the detection quantum efficiency to be 0.78±0.04 at 80 keV and 0.74±0.03 at 300 keV. Using a new imaging technique, based on single electron reconstruction, the line spread function for 80 and 300 keV electrons becomes (6.7±0.3) and (2.4±0.2) μm, respectively. The radiation tolerance of the pixels has been tested up to 5 Mrad and the detector is still functional with a decrease of dynamic range by ≃30%, corresponding to a reduction in full-well depth from ˜39 to ˜27 primary 300 keV electrons, due to leakage current increase, but identical line spread function performance.

  1. 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

  2. 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.

  3. Microarray Analysis of Fluorescence Activated Cell Sorter-Derived Cells: Creating Harmony between Technologies

    PubMed Central

    Tighe, S.

    2011-01-01

    Although microarray technology is well-established in both the research and clinical fields, it continues to evolve into new areas that require new methods for the successful isolations of nucleic acid from non-traditional sources. Because RNA specifically is a labile molecule, special procedures and considerations must be implemented to avoid degradation from methods such as fluorescence activated cell sorting (FACS) and laser capture microdissection (LCM) to name a few. This presentation will discuss specific methodologies to maximize the success of nucleic acid recovery from these approaches including instrument preparation, extraction methods, and the use of special reagents to deal with problematic samples.

  4. 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

  5. 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.

  6. Screening of Pre-miRNA-155 Binding Peptides for Apoptosis Inducing Activity Using Peptide Microarrays.

    PubMed

    Pai, Jaeyoung; Hyun, Soonsil; Hyun, Ji Young; Park, Seong-Hyun; Kim, Won-Je; Bae, Sung-Hun; Kim, Nak-Kyoon; Yu, Jaehoon; Shin, Injae

    2016-01-27

    MicroRNA-155, one of the most potent miRNAs that suppress apoptosis in human cancer, is overexpressed in numerous cancers, and it displays oncogenic activity. Peptide microarrays, constructed by immobilizing 185 peptides containing the C-terminal hydrazide onto epoxide-derivatized glass slides, were employed to evaluate peptide binding properties of pre-miRNA-155 and to identify its binding peptides. Two peptides, which were identified based on the results of peptide microarray and in vitro Dicer inhibition studies, were found to inhibit generation of mature miRNA-155 catalyzed by Dicer and to enhance expression of miRNA-155 target genes in cells. In addition, the results of cell experiments indicate that peptide inhibitors promote apoptotic cell death via a caspase-dependent pathway. Finally, observations made in NMR and molecular modeling studies suggest that a peptide inhibitor preferentially binds to the upper bulge and apical stem-loop region of pre-miRNA-155, thereby suppressing Dicer-mediated miRNA-155 processing. PMID:26771315

  7. Non-linear responsivity characterisation of a CMOS Active Pixel Sensor for high resolution imaging of the Jovian system

    NASA Astrophysics Data System (ADS)

    Soman, M.; Stefanov, K.; Weatherill, D.; Holland, A.; Gow, J.; Leese, M.

    2015-02-01

    The Jovian system is the subject of study for the Jupiter Icy Moon Explorer (JUICE), an ESA mission which is planned to launch in 2022. The scientific payload is designed for both characterisation of the magnetosphere and radiation environment local to the spacecraft, as well as remote characterisation of Jupiter and its satellites. A key instrument on JUICE is the high resolution and wide angle camera, JANUS, whose main science goals include detailed characterisation and study phases of three of the Galilean satellites, Ganymede, Callisto and Europa, as well as studies of other moons, the ring system, and irregular satellites. The CIS115 is a CMOS Active Pixel Sensor from e2v technologies selected for the JANUS camera. It is fabricated using 0.18 μ m CMOS imaging sensor process, with an imaging area of 2000 × 1504 pixels, each 7 μ m square. A 4T pixel architecture allows for efficient correlated double sampling, improving the readout noise to better than 8 electrons rms, whilst the sensor is operated in a rolling shutter mode, sampling at up to 10 Mpixel/s at each of the four parallel outputs.A primary parameter to characterise for an imaging device is the relationship that converts the sensor's voltage output back to the corresponding number of electrons that were detected in a pixel, known as the Charge to Voltage Factor (CVF). In modern CMOS sensors with small feature sizes, the CVF is known to be non-linear with signal level, therefore a signal-dependent measurement of the CIS115's CVF has been undertaken and is presented here. The CVF is well modelled as a quadratic function leading to a measurement of the maximum charge handling capacity of the CIS115 to be 3.4 × 104 electrons. If the CIS115's response is assumed linear, its CVF is 21.1 electrons per mV (1/47.5 μ V per electron).

  8. 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.

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

    PubMed Central

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

    2015-01-01

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

  10. 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

    2015-04-01

    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.

  11. A data parallel digitizer for a time-based simulation of CMOS Monolithic Active Pixel Sensors with FairRoot

    NASA Astrophysics Data System (ADS)

    Sitzmann, P.; Amar-Youcef, S.; Doering, D.; Deveaux, M.; Fröhlich, I.; Koziel, M.; Krebs, E.; Linnik, B.; Michel, J.; Milanovic, B.; Müntz, C.; Li, Q.; Stroth, J.; Tischler, T.

    2014-06-01

    CMOS Monolithic Active Pixel Sensors (MAPS) demonstrated excellent performances in the field of charged particle tracking. They feature an excellent single point resolution of few μm, a light material budget of 0.05% Xo in combination with a good radiation tolerance and time resolution. This makes the sensors a valuable technology for micro vertex detectors (MVD) of various experiments in heavy ion and particle physics like STAR and CBM. State of the art MAPS are equipped with a rolling shutter readout. Therefore, the data of one individual event is typically found in more than one data train generated by the sensor. This paper presents a concept to introduce this feature in both simulation and data analysis, taking profit of the sensor topology of the MVD. This topology allows to use for massive parallel data streaming and handling strategies within the FairRoot framework.

  12. T Cell Dynamic Activation and Functional Analysis in Nanoliter Droplet Microarray

    PubMed Central

    Sarkar, Saheli; Motwani, Vinny; Sabhachandani, Pooja; Cohen, Noa; Konry, Tania

    2015-01-01

    Objective Characterization of the heterogeneity in immune reactions requires assessing dynamic single cell responses as well as interactions between the various immune cell subsets. Maturation and activation of effector cells is regulated by cell contact-dependent and soluble factor-mediated paracrine signalling. Currently there are few methods available that allow dynamic investigation of both processes simultaneously without physically constraining non-adherent cells and eliminating crosstalk from neighboring cell pairs. We describe here a microfluidic droplet microarray platform that permits rapid functional analysis of single cell responses and co-encapsulation of heterotypic cell pairs, thereby allowing us to evaluate the dynamic activation state of primary T cells. Methods The microfluidic droplet platform enables generation and docking of monodisperse nanoliter volume (0.523 nl) droplets, with the capacity of monitoring a thousand droplets per experiment. Single human T cells were encapsulated in droplets and stimulated on-chip with the calcium ionophore ionomycin. T cells were also co-encapsulated with dendritic cells activated by ovalbumin peptide, followed by dynamic calcium signal monitoring. Results Ionomycin-stimulated cells depicted fluctuation in calcium signalling compared to control. Both cell populations demonstrated marked heterogeneity in responses. Calcium signalling was observed in T cells immediately following contact with DCs, suggesting an early activation signal. T cells further showed non-contact mediated increase in calcium level, although this response was delayed compared to contact-mediated signals. Conclusions Our results suggest that this nanoliter droplet array-based microfluidic platform is a promising technique for assessment of heterogeneity in various types of cellular responses, detection of early/delayed signalling events and live cell phenotyping of immune cells. PMID:26613065

  13. Isolation of Microarray-Quality RNA from Primary Human Cells after Intracellular Immunostaining and Fluorescence-Activated Cell Sorting

    PubMed Central

    Iglesias-Ussel, Maria; Marchionni, Luigi; Romerio, Fabio

    2013-01-01

    Microarrays have made it possible to perform high-throughput, genome-wide analyses of RNA expression from an extremely wide range of sources. This technology relies on the ability to obtain RNA of sufficient quantity and quality for this type of application. While there are means to circumvent limitations in the former, recovery of RNA suitable for microarray analysis still represents a major issue when working with some biological samples, particularly those treated with and preserved in nucleic acid-modifying organic reagents. In the present report we describe a procedure for the isolation of RNA suitable for microarray analysis from cells purified by fluorescence-activated cell sorting after fixation, permeabilization and intracellular staining with fluorochrome-conjugated antibodies. We show that – although the RNA isolated from these samples presented some degradation – it performed remarkably well in microarray analysis. The method we describe here makes it available to genome-wide expression profiling a variety of biological samples that so far were confined to single-gene analysis. PMID:23434645

  14. 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

  15. Performance of a-Si:H photodiode technology-based advanced CMOS active pixel sensor imagers

    NASA Astrophysics Data System (ADS)

    Theil, Jeremy A.; Haddad, Homayoon; Snyder, Rick D.; Zelman, Mike; Hula, David; Lindahl, Kirk A.

    2001-12-01

    Amorphous silicon photodiode technology is a very attractive option for image array integrated circuits because it enables large die-size reduction and higher light collection efficiency than c-Si arrays. The concept behind the technology is to place the photosensing element directly above the rest of the circuit, thus eliminating the need to make areal tradeoffs between photodiode and pixel circuit. We have developed an photodiode array technology that is fully compatible with a 0.35 um CMOS process to produce image sensors arrays with 10-bit dynamic range that are 30% smaller than comparable c-Si photodiode arrays. The work presented here will discuss performance issues and solutions to lend itself to cost-effective high-volume manufacturing. The various methods of interconnection of the diode to the array and their advantages will be presented. The effect of doped layer thickness and concentration on quantum efficiency, and the effect of a-Si:H defect concentration on diode performance will be discussed. The photodiode dark leakage current density is about 80 pA/cm2, and its absolute quantum efficiency peaks about 85% at 550 nm. These sensors have 50% higher sensitivity, and 2x lower dark current when compared to bulk silicon sensors of the same design. The cell utilizes a 3 FET design, but allows for 100% photodiode area due to the elevated nature of the design. The VGA (640 X 480), array demonstrated here uses common intrinsic and p-type contact layers, and makes reliable contact to those layers by use of a monolithic transparent conductor strap tied to vias in the interconnect.

  16. Deubiquitylase, deSUMOylase, and deISGylase activity microarrays for assay of substrate preference and functional modifiers.

    PubMed

    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.

  17. 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.

  18. Surface-activated microtiter-plate microarray for simultaneous CRP quantification and viral antibody detection.

    PubMed

    Viitala, Sari M; Jääskeläinen, Anne J; Kelo, Eira; Sirola, Helena; Moilanen, Kirsi; Suni, Jukka; Vaheri, Antti; Vapalahti, Olli; Närvänen, Ale

    2013-02-01

    Microarrays are widely used in high-throughput DNA and RNA hybridization tests and recently adopted to protein and small molecule interaction studies in basic research and diagnostics. Parallel detection of serum antibodies and antigens has several potential applications in epidemiologic research, vaccine development, and in the diagnosis of allergies, autoimmunity, and infectious diseases. This study demonstrates an immobilization method for immunoassay-based microarray in conventional 96-well polystyrene plates for a serologic diagnostic method combined with quantitative C-reactive protein (CRP) assay. A synthetic peptide (HIV-1), a recombinant protein (Puumala hantavirus nucleocapsid), and purified virus preparations (Sindbis and adenoviruses) were used as antigens for virus-specific antibody detection and monoclonal anti-CRP antibody for antigen detection. The microarray was based on conventional enzyme immunoassays and densitometry from photographed results. Peptide and recombinant antigens functioned well, while whole virus antigens gave discrepant results in 1 out of 23 samples from the reference method, tested with human sera with various antibody responses. The CRP results were in concordance in the concentration range 0.5-150 mg/L with 2 commercially available CRP assays: ReaScan rapid test (R(2) = 0.9975) and Cobas 6000 analyzer (R(2) =0.9595). The results indicate that microtiter plates provide a promising platform for further development of microarrays for parallel antibody and antigen detection. PMID:23219230

  19. 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. PMID:25498332

  20. Functional Protein Microarray Technology

    PubMed Central

    Hu, Shaohui; Xie, Zhi; Qian, Jiang; Blackshaw, Seth; Zhu, Heng

    2010-01-01

    Functional protein microarrays are emerging as a promising new tool for large-scale and high-throughput studies. In this article, we will review their applications in basic proteomics research, where various types of assays have been developed to probe binding activities to other biomolecules, such as proteins, DNA, RNA, small molecules, and glycans. We will also report recent progress of using functional protein microarrays in profiling protein posttranslational modifications, including phosphorylation, ubiquitylation, acetylation, and nitrosylation. Finally, we will discuss potential of functional protein microarrays in biomarker identification and clinical diagnostics. We strongly believe that functional protein microarrays will soon become an indispensible and invaluable tool in proteomics research and systems biology. PMID:20872749

  1. A microarray of ubiquitylated proteins for profiling deubiquitylase activity reveals the critical roles of both chain and substrate.

    PubMed

    Loch, Christian M; Strickler, James E

    2012-11-01

    Substrate ubiquitylation is a reversible process critical to cellular homeostasis that is often dysregulated in many human pathologies including cancer and neurodegeneration. Elucidating the mechanistic details of this pathway could unlock a large store of information useful to the design of diagnostic and therapeutic interventions. Proteomic approaches to the questions at hand have generally utilized mass spectrometry (MS), which has been successful in identifying both ubiquitylation substrates and profiling pan-cellular chain linkages, but is generally unable to connect the two. Interacting partners of the deubiquitylating enzymes (DUBs) have also been reported by MS, although substrates of catalytically competent DUBs generally cannot be. Where they have been used towards the study of ubiquitylation, protein microarrays have usually functioned as platforms for the identification of substrates for specific E3 ubiquitin ligases. Here, we report on the first use of protein microarrays to identify substrates of DUBs, and in so doing demonstrate the first example of microarray proteomics involving multiple (i.e., distinct, sequential and opposing) enzymatic activities. This technique demonstrates the selectivity of DUBs for both substrate and type (mono- versus poly-) of ubiquitylation. This work shows that the vast majority of DUBs are monoubiquitylated in vitro, and are incapable of removing this modification from themselves. This work also underscores the critical role of utilizing both ubiquitin chains and substrates when attempting to characterize DUBs. This article is part of a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics.

  2. 50 μm pixel pitch wafer-scale CMOS active pixel sensor x-ray detector for digital breast tomosynthesis

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

    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.

  3. 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

    2015-12-01

    Wafer-scale CMOS active pixel sensors (APSs) have been developed recently for x-ray imaging applications. The small pixel pitch and low noise are very promising properties for medical imaging applications such as digital breast tomosynthesis (DBT). In this work, we evaluated experimentally and through modeling the imaging properties of a 50 μm pixel pitch CMOS APS x-ray detector named DynAMITe (Dynamic Range Adjustable for Medical Imaging Technology). A modified cascaded system model was developed for CMOS APS x-ray detectors by taking into account the device nonlinear signal and noise properties. The imaging properties such as modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) were extracted from both measurements and the nonlinear cascaded system analysis. The results show that the DynAMITe x-ray detector achieves a high spatial resolution of 10 mm(-1) and a DQE of around 0.5 at spatial frequencies  <1 mm(-1). In addition, the modeling results were used to calculate the image signal-to-noise ratio (SNRi) of microcalcifications at various mean glandular dose (MGD). For an average breast (5 cm thickness, 50% glandular fraction), 165 μm microcalcifications can be distinguished at a MGD of 27% lower than the clinical value (~1.3 mGy). To detect 100 μm microcalcifications, further optimizations of the CMOS APS x-ray detector, image aquisition geometry and image reconstruction techniques should be considered. PMID:26540090

  4. Protein Microarrays

    NASA Astrophysics Data System (ADS)

    Ricard-Blum, S.

    Proteins are key actors in the life of the cell, involved in many physiological and pathological processes. Since variations in the expression of messenger RNA are not systematically correlated with variations in the protein levels, the latter better reflect the way a cell functions. Protein microarrays thus supply complementary information to DNA chips. They are used in particular to analyse protein expression profiles, to detect proteins within complex biological media, and to study protein-protein interactions, which give information about the functions of those proteins [3-9]. They have the same advantages as DNA microarrays for high-throughput analysis, miniaturisation, and the possibility of automation. Section 18.1 gives a brief overview of proteins. Following this, Sect. 18.2 describes how protein microarrays can be made on flat supports, explaining how proteins can be produced and immobilised on a solid support, and discussing the different kinds of substrate and detection method. Section 18.3 discusses the particular format of protein microarrays in suspension. The diversity of protein microarrays and their applications are then reported in Sect. 18.4, with applications to therapeutics (protein-drug interactions) and diagnostics. The prospects for future developments of protein microarrays are then outlined in the conclusion. The bibliography provides an extensive list of reviews and detailed references for those readers who wish to go further in this area. Indeed, the aim of the present chapter is not to give an exhaustive or detailed analysis of the state of the art, but rather to provide the reader with the basic elements needed to understand how proteins are designed and used.

  5. CMOS Detector Technology

    NASA Astrophysics Data System (ADS)

    Hoffman, Alan; Loose, Markus; Suntharalingam, Vyshnavi

    2005-01-01

    An entry level overview of state-of-the-art CMOS detector technology is presented. Operating principles and system architecture are explained in comparison to the well-established CCD technology, followed by a discussion of important benefits of modern CMOS-based detector arrays. A number of unique CMOS features including different shutter modes and scanning concepts are described. In addition, sub-field stitching is presented as a technique for producing very large imagers. After a brief introduction to the concept of monolithic CMOS sensors, hybrid detectors technology is introduced. A comparison of noise reduction methods for CMOS hybrids is presented. The final sections review CMOS fabrication processes for monolithic and vertically integrated image sensors.

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

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

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

  7. Optical and electrical characterization of a back-thinned CMOS active pixel sensor

    NASA Astrophysics Data System (ADS)

    Blue, Andrew; Clark, A.; Houston, S.; Laing, A.; Maneuski, D.; Prydderch, M.; Turchetta, R.; O'Shea, V.

    2009-06-01

    This work will report on the first work on the characterization of a back-thinned Vanilla-a 512×512 (25 μm squared) active pixel sensor (APS). Characterization of the detectors was carried out through the analysis of photon transfer curves to yield a measurement of full well capacity, noise levels, gain constants and linearity. Spectral characterization of the sensors was also performed in the visible and UV regions. A full comparison against non-back-thinned front illuminated Vanilla sensors is included. Such measurements suggest that the Vanilla APS will be suitable for a wide range of applications, including particle physics and biomedical imaging.

  8. Tissue Microarrays.

    PubMed

    Dancau, Ana-Maria; Simon, Ronald; Mirlacher, Martina; Sauter, Guido

    2016-01-01

    Modern next-generation sequencing and microarray technologies allow for the simultaneous analysis of all human genes on the DNA, RNA, miRNA, and methylation RNA level. Studies using such techniques have lead to the identification of hundreds of genes with a potential role in cancer or other diseases. The validation of all of these candidate genes requires in situ analysis of high numbers of clinical tissues samples. The tissue microarray technology greatly facilitates such analysis. In this method minute tissue samples (typically 0.6 mm in diameter) from up to 1000 different tissues can be analyzed on one microscope glass slide. All in situ methods suitable for histological studies can be applied to TMAs without major changes of protocols, including immunohistochemistry, fluorescence in situ hybridization, or RNA in situ hybridization. Because all tissues are analyzed simultaneously with the same batch of reagents, TMA studies provide an unprecedented degree of standardization, speed, and cost efficiency.

  9. 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. PMID:27276104

  10. 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.

  11. Using a customized DNA microarray for expression profiling of the estrogen-responsive genes to evaluate estrogen activity among natural estrogens and industrial chemicals.

    PubMed Central

    Terasaka, Shunichi; Aita, Yukie; Inoue, Akio; Hayashi, Shinichi; Nishigaki, Michiko; Aoyagi, Kazuhiko; Sasaki, Hiroki; Wada-Kiyama, Yuko; Sakuma, Yasuo; Akaba, Shuichi; Tanaka, Junko; Sone, Hideko; Yonemoto, Junzo; Tanji, Masao; Kiyama, Ryoiti

    2004-01-01

    We developed a DNA microarray to evaluate the estrogen activity of natural estrogens and industrial chemicals. Using MCF-7 cells, we conducted a comprehensive analysis of estrogen-responsive genes among approximately 20,000 human genes. On the basis of reproducible and reliable responses of the genes to estrogen, we selected 172 genes to be used for developing a customized DNA microarray. Using this DNA microarray, we examined estrogen activity among natural estrogens (17beta-estradiol, estriol, estrone, genistein), industrial chemicals (diethylstilbestrol, bisphenol A, nonylphenol, methoxychlor), and dioxin. We obtained results identical to those for other bioassays that are used for detecting estrogen activity. On the basis of statistical correlations analysis, these bioassays have shown more sensitivity for dioxin and methoxychlor. PMID:15159206

  12. 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.

  13. 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. PMID:27410361

  14. Integrated CMOS amplifier for ENG signal recording.

    PubMed

    Uranga, A; Navarro, X; Barniol, N

    2004-12-01

    The development and in vivo test of a fully integrated differential CMOS amplifier, implemented with standard 0.7-microm CMOS technology (one poly, two metals, self aligned twin-well CMOS process) intended to record extracellular neural signals is described. In order to minimize the flicker noise generated by the CMOS circuitry, a chopper technique has been chosen. The fabricated amplifier has a gain of 74 dB, a bandwidth of 3 kHz, an input noise of 6.6 nV/(Hz)0.5, a power dissipation of 1.3 mW, and the active area is 2.7 mm2. An ac coupling has been used to adapt the electrode to the amplifier circuitry for the in vivo testing. Compound muscle action potentials, motor unit action potentials, and compound nerve action potentials have been recorded in acute experiments with rats, in order to validate the amplifier. PMID:15605867

  15. 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.

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

    PubMed

    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.

  17. A 70μm × 70μm CMOS digital active pixel sensor for digital mammography and X-ray imaging

    NASA Astrophysics Data System (ADS)

    Sabadell, J.; Figueras, R.; Margarit, J. M.; Martín, E.; Terès, L.; Serra-Graells, F.

    2011-03-01

    This work presents an architecture for CMOS active pixel sensors (APS) based on a novel lossless charge integration method, proposed for X-ray imagers in general but specifically optimized for full-field digital mammography. The objective is to provide all the required functionality inside the pixel, so to use full digital control and read-out signals only, therefore avoiding crosstalk between analog lines over large pixel arrays. It includes a novel lossless A/D conversion scheme besides a self-calibrating dark current cancellation circuit, a self-biasing circuitry, biphasic current sensing for the collection of electrons (e-) or holes (h+) and built-in test. Furthermore, FPN compensation is available by individually addressing the pixel's internal DAC controlling the gain. Implemented in a 0.18μm 1P6M CMOS technology with MiM capacitors, everything fits into a 70μm by 70μm due to the extensive reuse of available blocks and aggressive layout techniques. Also, thanks to the MOSFET subthreshold operation, the average power consumption is as low as 8μW/pixel.

  18. 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

  19. High-voltage CMOS detectors

    NASA Astrophysics Data System (ADS)

    Ehrler, F.; Blanco, R.; Leys, R.; Perić, I.

    2016-07-01

    High-voltage CMOS (HVCMOS) pixel sensors are depleted active pixel sensors implemented in standard commercial CMOS processes. The sensor element is the n-well/p-substrate diode. The sensor electronics are entirely placed inside the n-well which is at the same time used as the charge collection electrode. High voltage is used to deplete the part of the substrate around the n-well. HVCMOS sensors allow implementation of complex in-pixel electronics. This, together with fast signal collection, allows a good time resolution, which is required for particle tracking in high energy physics. HVCMOS sensors will be used in Mu3e experiment at PSI and are considered as an option for both ATLAS and CLIC (CERN). Radiation tolerance and time walk compensation have been tested and results are presented.

  20. DNA Microarrays

    NASA Astrophysics Data System (ADS)

    Nguyen, C.; Gidrol, X.

    Genomics has revolutionised biological and biomedical research. This revolution was predictable on the basis of its two driving forces: the ever increasing availability of genome sequences and the development of new technology able to exploit them. Up until now, technical limitations meant that molecular biology could only analyse one or two parameters per experiment, providing relatively little information compared with the great complexity of the systems under investigation. This gene by gene approach is inadequate to understand biological systems containing several thousand genes. It is essential to have an overall view of the DNA, RNA, and relevant proteins. A simple inventory of the genome is not sufficient to understand the functions of the genes, or indeed the way that cells and organisms work. For this purpose, functional studies based on whole genomes are needed. Among these new large-scale methods of molecular analysis, DNA microarrays provide a way of studying the genome and the transcriptome. The idea of integrating a large amount of data derived from a support with very small area has led biologists to call these chips, borrowing the term from the microelectronics industry. At the beginning of the 1990s, the development of DNA chips on nylon membranes [1, 2], then on glass [3] and silicon [4] supports, made it possible for the first time to carry out simultaneous measurements of the equilibrium concentration of all the messenger RNA (mRNA) or transcribed RNA in a cell. These microarrays offer a wide range of applications, in both fundamental and clinical research, providing a method for genome-wide characterisation of changes occurring within a cell or tissue, as for example in polymorphism studies, detection of mutations, and quantitative assays of gene copies. With regard to the transcriptome, it provides a way of characterising differentially expressed genes, profiling given biological states, and identifying regulatory channels.

  1. Microarray technology for use in molecular epidemiology.

    PubMed

    Vernon, Suzanne D; Whistler, Toni

    2007-01-01

    Microarrays are a powerful laboratory tool for the simultaneous assessment of the activity of thousands genes. Remarkable advances in biological sample collection, preparation and automation of hybridization have enabled the application of microarray technology to large, population-based studies. Now, microarrays have the potential to serve as screening tools for the detection of altered gene expression activity that might contribute to diseases in human populations. Reproducible and reliable microarray results depend on multiple factors. In this chapter, biological sample parameters are introduced that should be considered for any microarray experiment. Then, the microarray technology that we have successfully applied to limited biological sample from all our molecular epidemiology studies is detailed. This reproducible and reliable approach for using microarrays should be applicable to any biological questions asked.

  2. Microarray profiling of L1-overexpressing endothelial cells reveals STAT3 activation via IL-6/IL-6Rα axis.

    PubMed

    Magrini, Elena; Cavallaro, Ugo; Bianchi, Fabrizio

    2015-06-01

    We recently identified a novel role for the L1 transmembrane glycoprotein (also known as L1CAM or CD171) in the regulation of tumor angiogenesis and vessels stabilization. L1 overexpression in cultured endothelial cells of the lung (luECs) exerted a pleiotropic effect in that it regulated proliferation, migration, tubulogenesis, vascular permeability, and endothelial-to-mesenchymal transition (EndMT). In addition, we provided strong evidence that antibody-mediated targeting of L1 may be an effective strategy for vessel normalization with the potential to increase efficacy of chemotherapeutic agents. High-throughput microarray expression profile revealed that L1 modulates the expression of hundreds of genes mainly involved in cell cycle regulation, DNA replication, cellular assembly, migration, development and organization. By using a 'pathway-oriented' analysis strategy we were able to identify a network of 105 genes modulated by L1 through the predicted activation of five transcription factors: STAT1, STAT2, STAT3, IRF7, and ATF4. Indeed, L1 overexpression resulted in the strong induction of STAT3 phosphorylation which was abolished by antibody-mediated neutralization of IL-6Rα. These results indicated that L1 promoted STAT3 activation via the IL-6/IL-6Rα axis. PMID:26484199

  3. 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.

  4. Aptamer Microarrays

    SciTech Connect

    Angel-Syrett, Heather; Collett, Jim; Ellington, Andrew D.

    2009-01-02

    In vitro selection can yield specific, high-affinity aptamers. We and others have devised methods for the automated selection of aptamers, and have begun to use these reagents for the construction of arrays. Arrayed aptamers have proven to be almost as sensitive as their solution phase counterparts, and when ganged together can provide both specific and general diagnostic signals for proteins and other analytes. We describe here technical details regarding the production and processing of aptamer microarrays, including blocking, washing, drying, and scanning. We will also discuss the challenges involved in developing standardized and reproducible methods for binding and quantitating protein targets. While signals from fluorescent analytes or sandwiches are typically captured, it has proven possible for immobilized aptamers to be uniquely coupled to amplification methods not available to protein reagents, thus allowing for protein-binding signals to be greatly amplified. Into the future, many of the biosensor methods described in this book can potentially be adapted to array formats, thus further expanding the utility of and applications for aptamer arrays.

  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. 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

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

    PubMed

    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. PMID:20850466

  8. 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.

  9. 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.

  10. 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.

  11. Fluorescently Activated Cell Sorting Followed by Microarray Profiling of Helper T Cell Subtypes from Human Peripheral Blood

    PubMed Central

    Ono, Chiaki; Yu, Zhiqian; Kasahara, Yoshiyuki; Kikuchi, Yoshie; Ishii, Naoto; Tomita, Hiroaki

    2014-01-01

    Background Peripheral blood samples have been subjected to comprehensive gene expression profiling to identify biomarkers for a wide range of diseases. However, blood samples include red blood cells, white blood cells, and platelets. White blood cells comprise polymorphonuclear leukocytes, monocytes, and various types of lymphocytes. Blood is not distinguishable, irrespective of whether the expression profiles reflect alterations in (a) gene expression patterns in each cell type or (b) the proportion of cell types in blood. CD4+ Th cells are classified into two functionally distinct subclasses, namely Th1 and Th2 cells, on the basis of the unique characteristics of their secreted cytokines and their roles in the immune system. Th1 and Th2 cells play an important role not only in the pathogenesis of human inflammatory, allergic, and autoimmune diseases, but also in diseases that are not considered to be immune or inflammatory disorders. However, analyses of minor cellular components such as CD4+ cell subpopulations have not been performed, partly because of the limited number of these cells in collected samples. Methodology/Principal Findings We describe fluorescently activated cell sorting followed by microarray (FACS–array) technology as a useful experimental strategy for characterizing the expression profiles of specific immune cells in the circulation. We performed reproducible gene expression profiling of Th1 and Th2, respectively. Our data suggest that this procedure provides reliable information on the gene expression profiles of certain small immune cell populations. Moreover, our data suggest that GZMK, GZMH, EOMES, IGFBP3, and STOM may be novel markers for distinguishing Th1 cells from Th2 cells, whereas IL17RB and CNTNAP1 can be Th2-specific markers. Conclusions/Significance Our approach may help in identifying aberrations and novel therapeutic or diagnostic targets for diseases that affect Th1 or Th2 responses and elucidating the involvement of a

  12. Microarrays, Integrated Analytical Systems

    NASA Astrophysics Data System (ADS)

    Combinatorial chemistry is used to find materials that form sensor microarrays. This book discusses the fundamentals, and then proceeds to the many applications of microarrays, from measuring gene expression (DNA microarrays) to protein-protein interactions, peptide chemistry, carbodhydrate chemistry, electrochemical detection, and microfluidics.

  13. 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.

  14. 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.

  15. Manufacturing of microarrays.

    PubMed

    Petersen, David W; Kawasaki, Ernest S

    2007-01-01

    DNA microarray technology has become a powerful tool in the arsenal of the molecular biologist. Capitalizing on high precision robotics and the wealth of DNA sequences annotated from the genomes of a large number of organisms, the manufacture of microarrays is now possible for the average academic laboratory with the funds and motivation. Microarray production requires attention to both biological and physical resources, including DNA libraries, robotics, and qualified personnel. While the fabrication of microarrays is a very labor-intensive process, production of quality microarrays individually tailored on a project-by-project basis will help researchers shed light on future scientific questions.

  16. Peptide Microarrays for Real-Time Kinetic Profiling of Tyrosine Phosphatase Activity of Recombinant Phosphatases and Phosphatases in Lysates of Cells or Tissue Samples.

    PubMed

    Hovestad-Bijl, Liesbeth; van Ameijde, Jeroen; Pijnenburg, Dirk; Hilhorst, Riet; Liskamp, Rob; Ruijtenbeek, Rob

    2016-01-01

    A high-throughput method for the determination of the kinetics of protein tyrosine phosphatase (PTP) activity in a microarray format is presented, allowing real-time monitoring of the dephosphorylation of a 3-nitro-phosphotyrosine residue. The 3-nitro-phosphotyrosine residue is incorporated in potential PTP substrates. The peptide substrates are immobilized onto a porous surface in discrete spots. After dephosphorylation by a PTP, a 3-nitrotyrosine residue is formed that can be detected by a specific, sequence-independent antibody. The rate of dephosphorylation can be measured simultaneously on 12 microarrays, each comprising three concentrations of 48 clinically relevant peptides, using 1.0-5.0 μg of protein from a cell or tissue lysate or 0.1-2.0 μg of purified phosphatase. The data obtained compare well with solution phase assays involving the corresponding unmodified phosphotyrosine substrates. This technology, characterized by high-throughput (12 assays in less than 2 h), multiplexing and low sample requirements, facilitates convenient and unbiased investigation of the enzymatic activity of the PTP enzyme family, for instance by profiling of PTP substrate specificities, evaluation of PTP inhibitors and pinpointing changes in PTP activity in biological samples related to diseases. PMID:27514800

  17. Microarrays in hematology.

    PubMed

    Walker, Josef; Flower, Darren; Rigley, Kevin

    2002-01-01

    Microarrays are fast becoming routine tools for the high-throughput analysis of gene expression in a wide range of biologic systems, including hematology. Although a number of approaches can be taken when implementing microarray-based studies, all are capable of providing important insights into biologic function. Although some technical issues have not been resolved, microarrays will continue to make a significant impact on hematologically important research. PMID:11753074

  18. 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.

  19. 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.

  20. 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.

  1. Investigation of the relationship between protein-protein interaction and catalytic activity of a heme-regulated phosphodiesterase from Escherichia coli (Ec DOS) by protein microarray.

    PubMed

    Sasakura, Yukie; Kanda, Katsuhiro; Yoshimura-Suzuki, Tokiko; Matsui, Takuya; Fukuzono, Shinichi; Shimizu, Toru

    2005-07-19

    Ec DOS, a heme-regulated phosphodiesterase from Escherichia coli, is composed of an N-terminal heme-bound PAS domain and a C-terminal phosphodiesterase domain. The heme redox state in the PAS domain regulates Ec DOS phosphodiesterase activity. Interestingly, the isolated heme-bound PAS fragment enhances phosphodiesterase activity of full-length Ec DOS. The enhancement is also regulated by the heme redox state of the isolated PAS domain. In the present study, we used a newly developed protein microarray system to examine the relationship between catalytic activity and the interaction of full-length Ec DOS and the isolated PAS fragment. Adenosine 3',5'-cyclic monophosphate (cAMP), a substrate of the Ec DOS phosphodiesterase, was found to be indispensable for the interaction between Ec DOS and the PAS fragment, and two phosphodiesterase inhibitors, 3-isobutyl-methyl-xanthine and etazolate hydrochloride, hindered the interaction. In addition, an enzyme with a mutation in the putative cAMP-binding sites (H590 and H594) was unable to interact with Ec DOS and lacked enzymatic activity. These results strongly suggest a close relationship between Ec DOS phosphodiesterase activity and interaction with the isolated PAS fragment. Therefore, this study provides insights into the mechanism of how the isolated PAS domain activates Ec DOS, which has important implications for the general role of the isolated PAS domain in cells. Moreover, we found that multiple microscale analyses using the protein microarray system had several advantages over conventional affinity column methods, including the quantity of protein needed, the sensitivity, the variability of immobilized protein, and the time required for the experiment. PMID:16008345

  2. Microarray Analysis in Glioblastomas

    PubMed Central

    Bhawe, Kaumudi M.; Aghi, Manish K.

    2016-01-01

    Microarray analysis in glioblastomas is done using either cell lines or patient samples as starting material. A survey of the current literature points to transcript-based microarrays and immunohistochemistry (IHC)-based tissue microarrays as being the preferred methods of choice in cancers of neurological origin. Microarray analysis may be carried out for various purposes including the following: To correlate gene expression signatures of glioblastoma cell lines or tumors with response to chemotherapy (DeLay et al., Clin Cancer Res 18(10):2930–2942, 2012)To correlate gene expression patterns with biological features like proliferation or invasiveness of the glioblastoma cells (Jiang et al., PLoS One 8(6):e66008, 2013)To discover new tumor classificatory systems based on gene expression signature, and to correlate therapeutic response and prognosis with these signatures (Huse et al., Annu Rev Med 64(1):59–70, 2013; Verhaak et al., Cancer Cell 17(1):98–110, 2010) While investigators can sometimes use archived tumor gene expression data available from repositories such as the NCBI Gene Expression Omnibus to answer their questions, new arrays must often be run to adequately answer specific questions. Here, we provide a detailed description of microarray methodologies, how to select the appropriate methodology for a given question, and analytical strategies that can be used. Experimental methodology for protein microarrays is outside the scope of this chapter, but basic sample preparation techniques for transcript-based microarrays are included here. PMID:26113463

  3. Microarray Analysis in Glioblastomas.

    PubMed

    Bhawe, Kaumudi M; Aghi, Manish K

    2016-01-01

    Microarray analysis in glioblastomas is done using either cell lines or patient samples as starting material. A survey of the current literature points to transcript-based microarrays and immunohistochemistry (IHC)-based tissue microarrays as being the preferred methods of choice in cancers of neurological origin. Microarray analysis may be carried out for various purposes including the following: i. To correlate gene expression signatures of glioblastoma cell lines or tumors with response to chemotherapy (DeLay et al., Clin Cancer Res 18(10):2930-2942, 2012). ii. To correlate gene expression patterns with biological features like proliferation or invasiveness of the glioblastoma cells (Jiang et al., PLoS One 8(6):e66008, 2013). iii. To discover new tumor classificatory systems based on gene expression signature, and to correlate therapeutic response and prognosis with these signatures (Huse et al., Annu Rev Med 64(1):59-70, 2013; Verhaak et al., Cancer Cell 17(1):98-110, 2010). While investigators can sometimes use archived tumor gene expression data available from repositories such as the NCBI Gene Expression Omnibus to answer their questions, new arrays must often be run to adequately answer specific questions. Here, we provide a detailed description of microarray methodologies, how to select the appropriate methodology for a given question, and analytical strategies that can be used. Experimental methodology for protein microarrays is outside the scope of this chapter, but basic sample preparation techniques for transcript-based microarrays are included here. PMID:26113463

  4. Microarray analysis of Etrog citron (Citrus medica L.) reveals changes in chloroplast, cell wall, peroxidase and symporter activities in response to viroid infection.

    PubMed

    Rizza, Serena; Conesa, Ana; Juarez, José; Catara, Antonino; Navarro, Luis; Duran-Vila, Nuria; Ancillo, Gema

    2012-10-01

    Viroids are small (246-401 nucleotides), single-stranded, circular RNA molecules that infect several crop plants and can cause diseases of economic importance. Citrus are the hosts in which the largest number of viroids have been identified. Citrus exocortis viroid (CEVd), the causal agent of citrus exocortis disease, induces considerable losses in citrus crops. Changes in the gene expression profile during the early (pre-symptomatic) and late (post-symptomatic) stages of Etrog citron infected with CEVd were investigated using a citrus cDNA microarray. MaSigPro analysis was performed and, on the basis of gene expression profiles as a function of the time after infection, the differentially expressed genes were classified into five clusters. FatiScan analysis revealed significant enrichment of functional categories for each cluster, indicating that viroid infection triggers important changes in chloroplast, cell wall, peroxidase and symporter activities.

  5. 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.

  6. Microarrays in Glycoproteomics Research

    PubMed Central

    Yue, Tingting; Haab, Brian B.

    2009-01-01

    Microarrays have been extremely useful for investigating binding interactions among diverse types of molecular species, with the main advantage being the ability to examine many interactions using small amount of samples and reagents. Microarrays are increasingly being used to advance research in the field of glycobiology, which is the study of the nature and function and carbohydrates in health and disease. Several types of microarrays are being used in the study of glycans and proteins in glycobiology, including glycan arrays to study the recognition of carbohydrates, lectin arrays to determine carbohydrate expression on purified proteins or on cells, and antibody arrays to examine the variation in particular glycan structures on specific proteins. This review will cover the technology and applications of these types of microarrays, as well as their use for obtaining complementary information on various aspects of glycobiology. PMID:19389548

  7. 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.

  8. Reconfigurable RF CMOS Circuit for Cognitive Radio

    NASA Astrophysics Data System (ADS)

    Masu, Kazuya; Okada, Kenichi

    Cognitive radio and/or SDR (Software Defined Radio) inherently requires multi-band and multi standard wireless circuit. The circuit is implemented based on Si CMOS technology. In this article, the recent progress of Si RF CMOS is described and the reconfigurable RF CMOS circuit which was proposed by the authors is introduced. At the present and in the future, several kind of Si CMOS technology can be used for RF CMOS circuit implementation. The realistic RF CMOS circuit implementation toward cognitive and/or SDR is discussed.

  9. DNA microarrays in neuropsychopharmacology.

    PubMed

    Marcotte, E R; Srivastava, L K; Quirion, R

    2001-08-01

    Recent advances in experimental genomics, coupled with the wealth of sequence information available for a variety of organisms, have the potential to transform the way pharmacological research is performed. At present, high-density DNA microarrays allow researchers to quickly and accurately quantify gene-expression changes in a massively parallel manner. Although now well established in other biomedical fields, such as cancer and genetics research, DNA microarrays have only recently begun to make significant inroads into pharmacology. To date, the major focus in this field has been on the general application of DNA microarrays to toxicology and drug discovery and design. This review summarizes the major microarray findings of relevance to neuropsychopharmacology, as a prelude to the design and analysis of future basic and clinical microarray experiments. The ability of DNA microarrays to monitor gene expression simultaneously in a large-scale format is helping to usher in a post-genomic age, where simple constructs about the role of nature versus nurture are being replaced by a functional understanding of gene expression in living organisms. PMID:11479006

  10. 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

  11. 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

  12. 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.

  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. Development and characterization of CMOS avalanche photodiode arrays

    NASA Astrophysics Data System (ADS)

    Lawrence, William G.; Christian, James F.; Augustine, Frank L.; Squillante, Michael R.; Entine, Gerald

    2005-04-01

    Avalanche photodiode (APD) arrays fabricated by using complementary metal-oxide-semiconductor (CMOS) fabrication technology offer the possibility of combining these high sensitivity detectors with cost effective, on-board, complementary circuitry. Using CMOS techniques, Radiation Monitoring Devices has developed prototype pixels with active diameters ranging from 5 to 60 microns and with measured quantum efficiencies of up to 65%. The prototype CMOS APD pixel designs support both proportional and Geiger modes of photo-detection. When operating in Geiger mode, these APD"s act as single-optical-photon-counting detectors that can be used for time-resolved measurements under signal-starved conditions. We have also designed and fabricated CMOS chips that contain not only the APD pixels, but also associated circuitry for both actively and passively quenching the self-propagating Geiger avalanche. This report presents the noise and timing performance for the prototype CMOS APD pixels in both the proportional and Geiger modes of operation. It compares the quantum efficiency and dark-count rate of different pixel designs as a function of the applied bias and presents a discussion of the maximum count rates that is obtained with each of the two types of quenching circuits for operating the pixel in Geiger mode. Preliminary data on the application of the APD pixels to laser ranging and fluorescent lifetime measurement is also presented.

  15. Lectin microarrays for glycomic analysis.

    PubMed

    Gupta, Garima; Surolia, Avadhesha; Sampathkumar, Srinivasa-Gopalan

    2010-08-01

    Glycomics is the study of comprehensive structural elucidation and characterization of all glycoforms found in nature and their dynamic spatiotemporal changes that are associated with biological processes. Glycocalyx of mammalian cells actively participate in cell-cell, cell-matrix, and cell-pathogen interactions, which impact embryogenesis, growth and development, homeostasis, infection and immunity, signaling, malignancy, and metabolic disorders. Relative to genomics and proteomics, glycomics is just growing out of infancy with great potential in biomedicine for biomarker discovery, diagnosis, and treatment. However, the immense diversity and complexity of glycan structures and their multiple modes of interactions with proteins pose great challenges for development of analytical tools for delineating structure function relationships and understanding glyco-code. Several tools are being developed for glycan profiling based on chromatography, mass spectrometry, glycan microarrays, and glyco-informatics. Lectins, which have long been used in glyco-immunology, printed on a microarray provide a versatile platform for rapid high throughput analysis of glycoforms of biological samples. Herein, we summarize technological advances in lectin microarrays and critically review their impact on glycomics analysis. Challenges remain in terms of expansion to include nonplant derived lectins, standardization for routine clinical use, development of recombinant lectins, and exploration of plant kingdom for discovery of novel lectins. PMID:20726799

  16. Lectin microarrays for glycomic analysis.

    PubMed

    Gupta, Garima; Surolia, Avadhesha; Sampathkumar, Srinivasa-Gopalan

    2010-08-01

    Glycomics is the study of comprehensive structural elucidation and characterization of all glycoforms found in nature and their dynamic spatiotemporal changes that are associated with biological processes. Glycocalyx of mammalian cells actively participate in cell-cell, cell-matrix, and cell-pathogen interactions, which impact embryogenesis, growth and development, homeostasis, infection and immunity, signaling, malignancy, and metabolic disorders. Relative to genomics and proteomics, glycomics is just growing out of infancy with great potential in biomedicine for biomarker discovery, diagnosis, and treatment. However, the immense diversity and complexity of glycan structures and their multiple modes of interactions with proteins pose great challenges for development of analytical tools for delineating structure function relationships and understanding glyco-code. Several tools are being developed for glycan profiling based on chromatography, mass spectrometry, glycan microarrays, and glyco-informatics. Lectins, which have long been used in glyco-immunology, printed on a microarray provide a versatile platform for rapid high throughput analysis of glycoforms of biological samples. Herein, we summarize technological advances in lectin microarrays and critically review their impact on glycomics analysis. Challenges remain in terms of expansion to include nonplant derived lectins, standardization for routine clinical use, development of recombinant lectins, and exploration of plant kingdom for discovery of novel lectins.

  17. 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.

  18. Signalling networks associated with urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in breast cancer tissues: new insights from protein microarray analysis.

    PubMed

    Wolff, Claudia; Malinowsky, Katharina; Berg, Daniela; Schragner, Kerstin; Schuster, Tibor; Walch, Axel; Bronger, Holger; Höfler, Heinz; Becker, Karl-Friedrich

    2011-01-01

    The urokinase-type plasminogen activator (uPA) and the main uPA inhibitor PAI-1 play important roles in cell migration and invasion in both physiological and pathological contexts. Both factors are clinically applicable predictive markers in node-negative breast cancer patients that are used to stratify patients for adjuvant chemotherapy. In addition to their classical functions in plasmin regulation, both factors are key components in cancer-related cell signalling. Such signalling cascades are well described in cell culture systems, but a better understanding of uPA- and PAI-1-associated signalling networks in clinical tissues is needed. We examined the expression of uPA, PAI-1, and 21 signalling molecules in 201 primary breast cancer tissues using protein microarrays. Expression of uPA was significantly correlated with the expression of ERK and Stat3, while expression of PAI-1 was correlated with the uPA receptor and Akt activation, presumably via integrin and HER-receptor signalling. Analysis of uPA expression did not reveal any significant correlation with staging, grading or age of the patients. The PAI-1 expression was correlated with nodal stage. Network monitoring for uPA and PAI-1 in breast cancer reveals interactions with main signalling cascades and extends the findings from cell culture experiments. Our results reveal possible mechanisms underlying cancer development.

  19. 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. PMID:26039143

  20. 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.

  1. High gain CMOS image sensor design and fabrication on SOI and bulk technology

    NASA Astrophysics Data System (ADS)

    Zhang, Weiquan

    2000-12-01

    The CMOS imager is now competing with the CCD imager, which still dominates the electronic imaging market. By taking advantage of the mature CMOS technology, the CMOS imager can integrate AID converters, digital signal processing (DSP) and timing control circuits on the same chip. This low cost and high-density integration solution to the image capture is the strong driving force in industry. Silicon on insulator (SOI) is considered as the coming mainstream technology. It challenges the current bulk CMOS technology because of its reduced power consumption, high speed, radiation hardness etc. Moving the CMOS imager from the bulk to the SOI substrate will benefit from these intrinsic advantages. In addition, the blooming and the cross-talk between the pixels of the sensor array can be ideally eliminated, unlike those on the bulk technology. Though there are many advantages to integrate CMOS imager on SOI, the problem is that the top silicon film is very thin, such as 2000Å. Many photons can just pass through this layer without being absorbed. A good photo-detector on SOI is critical to integrate SOI CMOS imagers. In this thesis, several methods to make photo-detectors on SOI substrate are investigated. A floating gate MOSFET on SOI substrate, operating in its lateral bipolar mode, is photon sensitive. One step further, the SOI MOSFET gate and body can be tied together. The positive feedback between the body and gate enables this device have a high responsivity. A similar device can be found on the bulk CMOS technology: the gate-well tied PMOSFET. A 32 x 32 CMOS imager is designed and characterized using such a device as the light-sensing element. I also proposed the idea of building hybrid active pixels on SOI substrate. Such devices are fabricated and characterized. The work here represents my contribution on the CMOS imager, especially moving the CMOS imager onto the SOI substrate.

  2. 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

    2007-01-01

    In vitro antioxidant and antimutagenic activities of two polyphenols isolated from the fruits of Pistacia lentiscus was assessed. Antioxidant activity was determined by the ability of each compound to scavenge the free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH*), to inhibit xanthine oxidase and to inhibit the lipid peroxidation induced by H(2)O(2) in K562 cell line. Antimutagenic activity was assayed with SOS chromotest using Escherichia coli PQ37 as tester strain and Comet assay using K562 cell line. 1,2,3,4,6-Pentagalloylglucose was found to be more effective to scavenge DPPH* radical and protect against lipid peroxidation. Moreover, these two compounds induced an inhibitory activity against nifuroxazide and aflatoxin B1 mutagenicity. The protective effect exhibited by these molecules was also determined by analysis of gene expression as response to an oxidative stress. For this purpose, we used a cDNA-microarray containing 82 genes related to cell defense, essentially represented by antioxidant and DNA repair proteins. We found that 1,2,3,4,6-pentagalloylglucose induced a decrease in the expression of 11 transcripts related to antioxidant enzymes family (GPX1, TXN, AOE372, SHC1 and SEPW1) and DNA repair (POLD1, APEX, POLD2, MPG, PARP and XRCC5). The use of Gallic acid, induced expression of TXN, TXNRD1, AOE372, GSS (antioxidant enzymes) and LIG4, POLD2, MPG, GADD45A, PCNA, RPA2, DDIT3, HMOX2, XPA, TDG, ERCC1 and GTF2H1 (DNA repair) as well as the repression of GPX1, SEPW1, POLD1 and SHC1 gene expression. PMID:17129579

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

    PubMed

    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 degrees 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.

  4. 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…

  5. 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.

  6. 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.

  7. 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

  8. DNA microarray analyses in higher plants.

    PubMed

    Galbraith, David W

    2006-01-01

    DNA microarrays were originally devised and described as a convenient technology for the global analysis of plant gene expression. Over the past decade, their use has expanded enormously to cover all kingdoms of living organisms. At the same time, the scope of applications of microarrays has increased beyond expression analyses, with plant genomics playing a leadership role in the on-going development of this technology. As the field has matured, the rate-limiting step has moved from that of the technical process of data generation to that of data analysis. We currently face major problems in dealing with the accumulating datasets, not simply with respect to how to archive, access, and process the huge amounts of data that have been and are being produced, but also in determining the relative quality of the different datasets. A major recognized concern is the appropriate use of statistical design in microarray experiments, without which the datasets are rendered useless. A vigorous area of current research involves the development of novel statistical tools specifically for microarray experiments. This article describes, in a necessarily selective manner, the types of platforms currently employed in microarray research and provides an overview of recent activities using these platforms in plant biology.

  9. Advancing Microarray Assembly with Acoustic Dispensing Technology

    PubMed Central

    Wong, E. Y.; Diamond, S. L.

    2011-01-01

    In the assembly of microarrays and microarray-based chemical assays and enzymatic bioassays, most approaches use pins for contact spotting. Acoustic dispensing is a technology capable of nanoliter transfers by using acoustic energy to eject liquid sample from an open source well. Although typically used for well plate transfers, when applied to microarraying it avoids drawbacks of undesired physical contact with sample, difficulty in assembling multicomponent reactions on a chip by readdressing, a rigid mode of printing that lacks patterning capabilities, and time-consuming wash steps. We demonstrated the utility of acoustic dispensing by delivering human cathepsin L in a drop-on-drop fashion into individual 50-nanoliter, pre-spotted reaction volumes to activate enzyme reactions at targeted positions on a microarray. We generated variable-sized spots ranging from 200 to 750 μm (and higher), and handled the transfer of fluorescent bead suspensions with increasing source well concentrations of 0.1 to 10 ×108 beads/mL in a linear fashion. There are no tips that can clog and liquid dispensing CVs are generally below 5%. This platform expands the toolbox for generating analytical arrays and meets needs associated with spatially-addressed assembly of multicomponent microarrays on the nanoliter scale. PMID:19035650

  10. A Synthetic Kinome Microarray Data Generator

    PubMed Central

    Maleki, Farhad; Kusalik, Anthony

    2015-01-01

    Cellular pathways involve the phosphorylation and dephosphorylation of proteins. Peptide microarrays called kinome arrays facilitate the measurement of the phosphorylation activity of hundreds of proteins in a single experiment. Analyzing the data from kinome microarrays is a multi-step process. Typically, various techniques are possible for a particular step, and it is necessary to compare and evaluate them. Such evaluations require data for which correct analysis results are known. Unfortunately, such kinome data is not readily available in the community. Further, there are no established techniques for creating artificial kinome datasets with known results and with the same characteristics as real kinome datasets. In this paper, a methodology for generating synthetic kinome array data is proposed. The methodology relies on actual intensity measurements from kinome microarray experiments and preserves their subtle characteristics. The utility of the methodology is demonstrated by evaluating methods for eliminating heterogeneous variance in kinome microarray data. Phosphorylation intensities from kinome microarrays often exhibit such heterogeneous variance and its presence can negatively impact downstream statistical techniques that rely on homogeneity of variance. It is shown that using the output from the proposed synthetic data generator, it is possible to critically compare two variance stabilization methods. PMID:27600233

  11. Microarrays under the microscope

    PubMed Central

    Wildsmith, S E; Elcock, F J

    2001-01-01

    Microarray technology is a rapidly advancing area, which is gaining popularity in many biological disciplines from drug target identification to predictive toxicology. Over the past few years, there has been a dramatic increase in the number of methods and techniques available for carrying out this form of gene expression analysis. The techniques and associated peripherals, such as slide types, deposition methods, robotics, and scanning equipment, are undergoing constant improvement, helping to drive the technology forward in terms of robustness and ease of use. These rapid developments, combined with the number of options available and the associated hyperbole, can prove daunting for the new user. This review aims to guide the researcher through the various steps of conducting microarray experiments, from initial strategy to analysing the data, with critical examination of the benefits and disadvantages along the way. PMID:11212888

  12. Navigating public microarray databases.

    PubMed

    Penkett, Christopher J; Bähler, Jürg

    2004-01-01

    With the ever-escalating amount of data being produced by genome-wide microarray studies, it is of increasing importance that these data are captured in public databases so that researchers can use this information to complement and enhance their own studies. Many groups have set up databases of expression data, ranging from large repositories, which are designed to comprehensively capture all published data, through to more specialized databases. The public repositories, such as ArrayExpress at the European Bioinformatics Institute contain complete datasets in raw format in addition to processed data, whilst the specialist databases tend to provide downstream analysis of normalized data from more focused studies and data sources. Here we provide a guide to the use of these public microarray resources.

  13. 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.

  14. 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.

  15. Using CMOS image sensors to detect photons

    NASA Astrophysics Data System (ADS)

    Xu, Chenzhi; Tong, Xiaobo; Zhou, Xiang; Zheng, Xiaodong; Xu, Yunfei

    2010-05-01

    A research is carried out on the characteristics of CMOS (Complementary Metal-Oxide Semiconductor) image sensors. A CMOS image sensor is used to probe the fluorescence intensity of atoms or absorbed photons in order to measure the shape and atomicity density of Rb (Rubidium) cold-atom-cloud. A series of RGB data of images is obtained and the spectrum response curve of CMOS image sensor is deduced. After filtering out the noise of the pixel signals of CMOS image sensor, the number of photons received by every pixel of the CMOS image sensor is obtained. Compared with CCD camera, the CMOS image sensor has some advantages in measuring the properties of cold-atom-cloud,such as quick response, large sensory area, low cost, and so on.

  16. Fabrication of CMOS image sensors

    NASA Astrophysics Data System (ADS)

    Malinovich, Yacov; Koltin, Ephie; Choen, David; Shkuri, Moshe; Ben-Simon, Meir

    1999-04-01

    In order to provide its customers with sub-micron CMOS fabrication solutions for imaging applications, Tower Semiconductor initiated a project to characterize the optical parameters of Tower's 0.5-micron process. A special characterization test chip was processed using the TS50 process. The results confirmed a high quality process for optical applications. Perhaps the most important result is the process' very low dark current, of 30-50 pA/cm2, using the entire window of process. This very low dark current characteristic was confirmed for a variety of pixel architectures. Additionally, we have succeeded to reduce and virtually eliminate the white spots on large sensor arrays. As a foundry Tower needs to support fabrication of many different imaging products. Therefore we have developed a fabrication methodology that is adjusted to the special needs of optical applications. In order to establish in-line process monitoring of the optical parameters, Tower places a scribe line optical test chip that enables wafer level measurements of the most important parameters, ensuring the optical quality and repeatability of the process. We have developed complementary capabilities like in house deposition of color filter and fabrication of very large are dice using sub-micron CMOS technologies. Shellcase and Tower are currently developing a new CMOS image sensor optical package.

  17. 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.

  18. 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.

  19. Tiling Microarray Analysis Tools

    SciTech Connect

    Nix, Davis Austin

    2005-05-04

    TiMAT is a package of 23 command line Java applications for use in the analysis of Affymetrix tiled genomic microarray data. TiMAT enables: 1) Rebuilding the genome annotation for entire tiled arrays (repeat filtering, chromosomal coordinate assignment). 2) Post processing of oligo intensity values (quantile normalization, median scaling, PMMM transformation), 3) Significance testing (Wilcoxon rank sum and signed rank tests, intensity difference and ratio tests) and Interval refinement (filtering based on multiple statistics, overlap comparisons), 4) Data visualization (detailed thumbnail/zoomed view with Interval Plots and data export to Affymetrix's Integrated Genome Browser) and Data reports (spreadsheet summaries and detailed profiles)

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Profiling protein function with small molecule microarrays

    PubMed Central

    Winssinger, Nicolas; Ficarro, Scott; Schultz, Peter G.; Harris, Jennifer L.

    2002-01-01

    The regulation of protein function through posttranslational modification, local environment, and protein–protein interaction is critical to cellular function. The ability to analyze on a genome-wide scale protein functional activity rather than changes in protein abundance or structure would provide important new insights into complex biological processes. Herein, we report the application of a spatially addressable small molecule microarray to an activity-based profile of proteases in crude cell lysates. The potential of this small molecule-based profiling technology is demonstrated by the detection of caspase activation upon induction of apoptosis, characterization of the activated caspase, and inhibition of the caspase-executed apoptotic phenotype using the small molecule inhibitor identified in the microarray-based profile. PMID:12167675

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  7. Virulence Characterization of Salmonella enterica by a New Microarray: Detection and Evaluation of the Cytolethal Distending Toxin Gene Activity in the Unusual Host S. Typhimurium

    PubMed Central

    Figueiredo, Rui; Card, Roderick; Nunes, Carla; AbuOun, Manal; Bagnall, Mary C.; Nunez, Javier; Mendonça, Nuno; Anjum, Muna F.; da Silva, Gabriela Jorge

    2015-01-01

    Salmonella enterica is a zoonotic foodborne pathogen that causes acute gastroenteritis in humans. We assessed the virulence potential of one-hundred and six Salmonella strains isolated from food animals and products. A high through-put virulence genes microarray demonstrated Salmonella Pathogenicity Islands (SPI) and adherence genes were highly conserved, while prophages and virulence plasmid genes were variably present. Isolates were grouped by serotype, and virulence plasmids separated S. Typhimurium in two clusters. Atypical microarray results lead to whole genome sequencing (WGS) of S. Infantis Sal147, which identified deletion of thirty-eight SPI-1 genes. Sal147 was unable to invade HeLa cells and showed reduced mortality in Galleria mellonella infection model, in comparison to a SPI-1 harbouring S. Infantis. Microarray and WGS of S. Typhimurium Sal199, established for the first time in S. Typhimurium presence of cdtB and other Typhi-related genes. Characterization of Sal199 showed cdtB genes were upstream of transposase IS911, and co-expressed with other Typhi-related genes. Cell cycle arrest, cytoplasmic distension, and nuclear enlargement were detected in HeLa cells infected by Sal199, but not with S. Typhimurium LT2. Increased mortality of Galleria was detected on infection with Sal199 compared to LT2. Thus, Salmonella isolates were rapidly characterized using a high through-put microarray; helping to identify unusual virulence features which were corroborated by further characterisation. This work demonstrates that the use of suitable screening methods for Salmonella virulence can help assess the potential risk associated with certain Salmonella to humans. Incorporation of such methodology into surveillance could help reduce the risk of emergence of epidemic Salmonella strains. PMID:26244504

  8. Virulence Characterization of Salmonella enterica by a New Microarray: Detection and Evaluation of the Cytolethal Distending Toxin Gene Activity in the Unusual Host S. Typhimurium.

    PubMed

    Figueiredo, Rui; Card, Roderick; Nunes, Carla; AbuOun, Manal; Bagnall, Mary C; Nunez, Javier; Mendonça, Nuno; Anjum, Muna F; da Silva, Gabriela Jorge

    2015-01-01

    Salmonella enterica is a zoonotic foodborne pathogen that causes acute gastroenteritis in humans. We assessed the virulence potential of one-hundred and six Salmonella strains isolated from food animals and products. A high through-put virulence genes microarray demonstrated Salmonella Pathogenicity Islands (SPI) and adherence genes were highly conserved, while prophages and virulence plasmid genes were variably present. Isolates were grouped by serotype, and virulence plasmids separated S. Typhimurium in two clusters. Atypical microarray results lead to whole genome sequencing (WGS) of S. Infantis Sal147, which identified deletion of thirty-eight SPI-1 genes. Sal147 was unable to invade HeLa cells and showed reduced mortality in Galleria mellonella infection model, in comparison to a SPI-1 harbouring S. Infantis. Microarray and WGS of S. Typhimurium Sal199, established for the first time in S. Typhimurium presence of cdtB and other Typhi-related genes. Characterization of Sal199 showed cdtB genes were upstream of transposase IS911, and co-expressed with other Typhi-related genes. Cell cycle arrest, cytoplasmic distension, and nuclear enlargement were detected in HeLa cells infected by Sal199, but not with S. Typhimurium LT2. Increased mortality of Galleria was detected on infection with Sal199 compared to LT2. Thus, Salmonella isolates were rapidly characterized using a high through-put microarray; helping to identify unusual virulence features which were corroborated by further characterisation. This work demonstrates that the use of suitable screening methods for Salmonella virulence can help assess the potential risk associated with certain Salmonella to humans. Incorporation of such methodology into surveillance could help reduce the risk of emergence of epidemic Salmonella strains.

  9. 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.

  10. The Genopolis Microarray Database

    PubMed Central

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

    2007-01-01

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

  11. DNA Microarray-Based Diagnostics.

    PubMed

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

    2016-01-01

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

  12. Design and coupled-effect simulations of CMOS micro gas sensors built on SOI thin membranes

    NASA Astrophysics Data System (ADS)

    Lu, Chih-Cheng; Udrea, Florin; Gardner, Julian W.; Setiadi, D.; Dogaru, T.; Tsai, T. H.; Covington, James A.

    2001-04-01

    This paper describes coupled-effect simulations of smart micro gas-sensors based on standard BiCMOS technology. The smart sensor features very low power consumption, high sensitivity and potential low fabrication cost achieved through full CMOS integration. For the first time the micro heaters are made of active CMOS elements (i.e. MOSFET transistors) and embedded in a thin SOI membrane consisting of Si and SiO2 thin layers. Micro gas-sensors such as chemoresistive, microcalorimeteric and Pd/polymer gate FET sensors can be made using this technology. Full numerical analyses including 3D electro- thermo-mechanical simulations, in particular stress and deflection studies on the SOI membranes are presented. The transducer circuit design and the post-CMOS fabrication process, which includes single sided back-etching, are also reported.

  13. Living-Cell Microarrays

    PubMed Central

    Yarmush, Martin L.; King, Kevin R.

    2011-01-01

    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. PMID:19413510

  14. Tiling Microarray Analysis Tools

    2005-05-04

    TiMAT is a package of 23 command line Java applications for use in the analysis of Affymetrix tiled genomic microarray data. TiMAT enables: 1) Rebuilding the genome annotation for entire tiled arrays (repeat filtering, chromosomal coordinate assignment). 2) Post processing of oligo intensity values (quantile normalization, median scaling, PMMM transformation), 3) Significance testing (Wilcoxon rank sum and signed rank tests, intensity difference and ratio tests) and Interval refinement (filtering based on multiple statistics, overlap comparisons),more » 4) Data visualization (detailed thumbnail/zoomed view with Interval Plots and data export to Affymetrix's Integrated Genome Browser) and Data reports (spreadsheet summaries and detailed profiles)« less

  15. 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.

  16. 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. PMID:18563243

  17. 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.

  18. Microarray platform for omics analysis

    NASA Astrophysics Data System (ADS)

    Mecklenburg, Michael; Xie, Bin

    2001-09-01

    Microarray technology has revolutionized genetic analysis. However, limitations in genome analysis has lead to renewed interest in establishing 'omic' strategies. As we enter the post-genomic era, new microarray technologies are needed to address these new classes of 'omic' targets, such as proteins, as well as lipids and carbohydrates. We have developed a microarray platform that combines self- assembling monolayers with the biotin-streptavidin system to provide a robust, versatile immobilization scheme. A hydrophobic film is patterned on the surface creating an array of tension wells that eliminates evaporation effects thereby reducing the shear stress to which biomolecules are exposed to during immobilization. The streptavidin linker layer makes it possible to adapt and/or develop microarray based assays using virtually any class of biomolecules including: carbohydrates, peptides, antibodies, receptors, as well as them ore traditional DNA based arrays. Our microarray technology is designed to furnish seamless compatibility across the various 'omic' platforms by providing a common blueprint for fabricating and analyzing arrays. The prototype microarray uses a microscope slide footprint patterned with 2 by 96 flat wells. Data on the microarray platform will be presented.

  19. 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.

  20. 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.

  1. 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

  2. Silicon CMOS optical receiver circuits with integrated thin-film compound semiconductor detectors

    NASA Astrophysics Data System (ADS)

    Brooke, Martin A.; Lee, Myunghee; Jokerst, Nan Marie; Camperi-Ginestet, C.

    1995-04-01

    While many circuit designers have tackled the problem of CMOS digital communications receiver design, few have considered the problem of circuitry suitable for an all CMOS digital IC fabrication process. Faced with a high speed receiver design the circuit designer will soon conclude that a high speed analog-oriented fabrication process provides superior performance advantages to a digital CMOS process. However, for applications where there are overwhelming reasons to integrate the receivers on the same IC as large amounts of conventional digital circuitry, the low yield and high cost of the exotic analog-oriented fabrication is no longer an option. The issues that result from a requirement to use a digital CMOS IC process cut across all aspects of receiver design, and result in significant differences in circuit design philosophy and topology. Digital ICs are primarily designed to yield small, fast CMOS devices for digital logic gates, thus no effort is put into providing accurate or high speed resistances, or capacitors. This lack of any reliable resistance or capacitance has a significant impact on receiver design. Since resistance optimization is not a prerogative of the digital IC process engineer, the wisest option is thus to not use these elements, opting instead for active circuitry to replace the functions normally ascribed to resistance and capacitance. Depending on the application receiver noise may be a dominant design constraint. The noise performance of CMOS amplifiers is different than bipolar or GaAs MESFET circuits, shot noise is generally insignificant when compared to channel thermal noise. As a result the optimal input stage topology is significantly different for the different technologies. It is found that, at speeds of operation approaching the limits of the digital CMOS process, open loop designs have noise-power-gain-bandwidth tradeoff performance superior to feedback designs. Furthermore, the lack of good resisters and capacitors

  3. A CMOS microdisplay with integrated controller utilizing improved silicon hot carrier luminescent light sources

    NASA Astrophysics Data System (ADS)

    Venter, Petrus J.; Alberts, Antonie C.; du Plessis, Monuko; Joubert, Trudi-Heleen; Goosen, Marius E.; Janse van Rensburg, Christo; Rademeyer, Pieter; Fauré, Nicolaas M.

    2013-03-01

    Microdisplay technology, the miniaturization and integration of small displays for various applications, is predominantly based on OLED and LCoS technologies. Silicon light emission from hot carrier electroluminescence has been shown to emit light visibly perceptible without the aid of any additional intensification, although the electrical to optical conversion efficiency is not as high as the technologies mentioned above. For some applications, this drawback may be traded off against the major cost advantage and superior integration opportunities offered by CMOS microdisplays using integrated silicon light sources. This work introduces an improved version of our previously published microdisplay by making use of new efficiency enhanced CMOS light emitting structures and an increased display resolution. Silicon hot carrier luminescence is often created when reverse biased pn-junctions enter the breakdown regime where impact ionization results in carrier transport across the junction. Avalanche breakdown is typically unwanted in modern CMOS processes. Design rules and process design are generally tailored to prevent breakdown, while the voltages associated with breakdown are too high to directly interact with the rest of the CMOS standard library. This work shows that it is possible to lower the operating voltage of CMOS light sources without compromising the optical output power. This results in more efficient light sources with improved interaction with other standard library components. This work proves that it is possible to create a reasonably high resolution microdisplay while integrating the active matrix controller and drivers on the same integrated circuit die without additional modifications, in a standard CMOS process.

  4. Microarray Analysis of Microbial Weathering

    NASA Astrophysics Data System (ADS)

    Olsson-Francis, K.; van Houdt, R.; Leys, N.; Mergeay, M.; Cockell, C. S.

    2010-04-01

    Microarray analysis of the heavy metal resistant bacterium, Cupriavidus metallidurans CH34 was used to investigate the genes involved in the weathering. The results demonstrated that large porin and membrane transporter genes were unregulated.

  5. Characterization of an inexpensive, nontoxic, and highly sensitive microarray substrate.

    PubMed

    Dufva, Martin; Petronis, Sarunas; Jensen, Louise Bjerremann; Krag, Claudia; Christensen, Claus B V

    2004-08-01

    An agarose film has been proposed as an efficient substrate for producing microarrays. The original film preparation procedure was simplified significantly by grafting the agarose layer directly onto unmodified microscope glass slides instead of aminated glass slides, and the blocking procedure was replaced with a wash in 0.1x standard saline citrate (SSC) and 0.5% sodium dodecyl sulfate (SDS) without decreasing the performance of the produced microarrays. Characterization of the grafted agarose film using atomic force microscopy (AFM) and scanning electron microscopy (SEM) showed that the agarose film had a 10-fold increase in surface roughness compared to glass and that the interior of the agarose film was porous, with pore sizes between 100-500 nm. A comparison of hybridization on aldehyde-activated agarose-coated microarray slides and commercial amino-reactive microarray slides showed that aldehyde-activated agarose-coated slides had the highest signal-to-noise ratio of 850, suggesting that the aldehyde-activated agarose microarray slides are suitable in applications where analytes have a wide concentration range. By immobilizing the DNA probes using ultraviolet (UV) light, the signal-to-noise ratio was further increased to 3000 on the agarose microarray slides. The specificity of the UV cross-linked DNA probes was demonstrated using 21 and 25 bp long capture probes, enabling discrimination of target molecules differing in only one base.

  6. [Protein microarrays and personalized medicine].

    PubMed

    Yu, Xiabo; Schneiderhan-Marra, Nicole; Joos, Thomas O

    2011-01-01

    Over the last 10 years, DNA microarrays have achieved a robust analytical performance, enabling their use for analyzing the whole transcriptome or for screening thousands of single-nucleotide polymorphisms in a single experiment. DNA microarrays allow scientists to correlate gene expression signatures with disease progression, to screen for disease-specific mutations, and to treat patients according to their individual genetic profiles; however, the real key is proteins and their manifold functions. It is necessary to achieve a greater understanding of not only protein function and abundance but also their role in the development of diseases. Protein concentrations have been shown to reflect the physiological and pathologic state of an organ, tissue, or cells far more directly than DNA, and proteins can be profiled effectively with protein microarrays, which require only a small amount of sample material. Protein microarrays have become wellestablished tools in basic and applied research, and the first products have already entered the in vitro diagnostics market. This review focuses on protein microarray applications for biomarker discovery and validation, disease diagnosis, and use within the area of personalized medicine. Protein microarrays have proved to be reliable research tools in screening for a multitude of parameters with only a minimal quantity of sample and have enormous potential in applications for diagnostic and personalized medicine.

  7. Fully depleted, thick, monolithic CMOS pixels with high quantum efficiency

    NASA Astrophysics Data System (ADS)

    Clarke, A.; Stefanov, K.; Johnston, N.; Holland, A.

    2015-04-01

    The Centre for Electronic Imaging (CEI) has an active programme of evaluating and designing Complementary Metal-Oxide Semiconductor (CMOS) image sensors with high quantum efficiency, for applications in near-infrared and X-ray photon detection. This paper describes the performance characterisation of CMOS devices made on a high resistivity 50 μ m thick p-type substrate with a particular focus on determining the depletion depth and the quantum efficiency. The test devices contain 8 × 8 pixel arrays using CCD-style charge collection, which are manufactured in a low voltage CMOS process by ESPROS Photonics Corporation (EPC). Measurements include determining under which operating conditions the devices become fully depleted. By projecting a spot using a microscope optic and a LED and biasing the devices over a range of voltages, the depletion depth will change, causing the amount of charge collected in the projected spot to change. We determine if the device is fully depleted by measuring the signal collected from the projected spot. The analysis of spot size and shape is still under development.

  8. 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.

  9. 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.

  10. Future of nano CMOS technology

    NASA Astrophysics Data System (ADS)

    Iwai, Hiroshi

    2015-10-01

    Although Si MOS devices have dominated the integrated circuit applications over the four decades, it has been anticipated that the development of CMOS would reach its limits after the next decade because of the difficulties in the technologies for further downscaling and also because of some fundamental limits of MOSFETs. However, there have been no promising candidates yet, which can replace Si MOSFETs with better performance with low cost. Thus, for the moment, it seems that we have to stick to the Si MOSFET devices until their end. The downsizing is limited by the increase of off-leakage current between source and drain. In order to suppress the off-leakage current, multi-gate structures (FinFET, Tri-gate, and Si-nanowire MOSFETs) are replacing conventional planar MOSFETs, and continuous innovation of high-k/metal gate technologies has enabled EOT scaling down to 0.9 nm in production. However, it was found that the multi-gate structures have a future big problem of significant conduction reduction with decrease in fin width. Also it is not easy to further decrease EOT because of the mobility and reliability degradation. Furthermore, the development of EUV (Extremely Ultra-Violet) lithography, which is supposed to be essential for sub-10 nm lithography, delays significantly because of insufficient illumination intensity for production. Thus, it is now expected that the reduction rate of the gate length, which has a strong influence on the off-leakage current, will become slower in near future.

  11. 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.

  12. Profiling in situ microbial community structure with an amplification microarray.

    PubMed

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

    2013-02-01

    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 HCO(3)(-)) 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 NaHCO(3), 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.

  13. 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

  14. Protein microarrays: prospects and problems.

    PubMed

    Kodadek, T

    2001-02-01

    Protein microarrays are potentially powerful tools in biochemistry and molecular biology. Two types of protein microarrays are defined. One, termed a protein function array, will consist of thousands of native proteins immobilized in a defined pattern. Such arrays can be utilized for massively parallel testing of protein function, hence the name. The other type is termed a protein-detecting array. This will consist of large numbers of arrayed protein-binding agents. These arrays will allow for expression profiling to be done at the protein level. In this article, some of the major technological challenges to the development of protein arrays are discussed, along with potential solutions.

  15. Characterization and reliability of CMOS microstructures

    NASA Astrophysics Data System (ADS)

    Fedder, Gary K.; Blanton, Ronald D. S.

    1999-08-01

    This paper provides an overview of high-aspect-ratio CMOS micromachining, focusing on materials characterization, reliability, and fault analysis. Composite microstrutural beam widths and gaps down to 1.2 micrometers are etched out of conventional CMOS dielectric, aluminum, and gate-polysilicon thin films using post-CMOS dry etching for both structural sidewall definition and for release from the substrate. Differences in stress between the multiple metal and dielectric layers cause vertical stress gradients and curl, while misalignment between layers causes lateral stress gradients and curl. Cracking is induced in a resonant fatigue structures at 620 MPa of repetitive stress after over 50 million cycles. Beams have withstood over 1.3 billion cycles at 124 MPa stress levels induced by electrostatic actuation. Failures due to process defects are classified according to the geometrical features of the defective structures. Relative probability of occurrence of each defect type is extracted from the process simulation results.

  16. Nanopore-CMOS Interfaces for DNA Sequencing.

    PubMed

    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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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).

  4. 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.

  5. Microarray Developed on Plastic Substrates.

    PubMed

    Bañuls, María-José; Morais, Sergi B; Tortajada-Genaro, Luis A; Maquieira, Ángel

    2016-01-01

    There is a huge potential interest to use synthetic polymers as versatile solid supports for analytical microarraying. Chemical modification of polycarbonate (PC) for covalent immobilization of probes, micro-printing of protein or nucleic acid probes, development of indirect immunoassay, and development of hybridization protocols are described and discussed. PMID:26614067

  6. Microfluidic microarray systems and methods thereof

    SciTech Connect

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

    2009-04-28

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

  7. 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.

  8. 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,…

  9. Radiation Tolerance of 65nm CMOS Transistors

    DOE PAGES

    Krohn, M.; Bentele, B.; Christian, D. C.; Cumalat, J. P.; Deptuch, G.; Fahim, F.; Hoff, J.; Shenai, A.; Wagner, S. R.

    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.

  10. 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.

  11. 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.

  12. Fully CMOS-compatible titanium nitride nanoantennas

    NASA Astrophysics Data System (ADS)

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

    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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. CMOS MEMS capacitive absolute pressure sensor

    NASA Astrophysics Data System (ADS)

    Narducci, M.; Yu-Chia, L.; Fang, W.; Tsai, J.

    2013-05-01

    This paper presents the design, fabrication and characterization of a capacitive pressure sensor using a commercial 0.18 µm CMOS (complementary metal-oxide-semiconductor) process and postprocess. The pressure sensor is capacitive and the structure is formed by an Al top electrode enclosed in a suspended SiO2 membrane, which acts as a movable electrode against a bottom or stationary Al electrode fixed on the SiO2 substrate. Both the movable and fixed electrodes form a variable parallel plate capacitor, whose capacitance varies with the applied pressure on the surface. In order to release the membranes the CMOS layers need to be applied postprocess and this mainly consists of four steps: (1) deposition and patterning of PECVD (plasma-enhanced chemical vapor deposition) oxide to protect CMOS pads and to open the pressure sensor top surface, (2) etching of the sacrificial layer to release the suspended membrane, (3) deposition of PECVD oxide to seal the etching holes and creating vacuum inside the gap, and finally (4) etching of the passivation oxide to open the pads and allow electrical connections. This sensor design and fabrication is suitable to obey the design rules of a CMOS foundry and since it only uses low-temperature processes, it allows monolithic integration with other types of CMOS compatible sensors and IC (integrated circuit) interface on a single chip. Experimental results showed that the pressure sensor has a highly linear sensitivity of 0.14 fF kPa-1 in the pressure range of 0-300 kPa.

  1. Analysis-Driven Lossy Compression of DNA Microarray Images.

    PubMed

    Hernández-Cabronero, Miguel; Blanes, Ian; Pinho, Armando J; Marcellin, Michael W; Serra-Sagristà, Joan

    2016-02-01

    DNA microarrays are one of the fastest-growing new technologies in the field of genetic research, and DNA microarray images continue to grow in number and size. Since analysis techniques are under active and ongoing development, storage, transmission and sharing of DNA microarray images need be addressed, with compression playing a significant role. However, existing lossless coding algorithms yield only limited compression performance (compression ratios below 2:1), whereas lossy coding methods may introduce unacceptable distortions in the analysis process. This work introduces a novel Relative Quantizer (RQ), which employs non-uniform quantization intervals designed for improved compression while bounding the impact on the DNA microarray analysis. This quantizer constrains the maximum relative error introduced into quantized imagery, devoting higher precision to pixels critical to the analysis process. For suitable parameter choices, the resulting variations in the DNA microarray analysis are less than half of those inherent to the experimental variability. Experimental results reveal that appropriate analysis can still be performed for average compression ratios exceeding 4.5:1.

  2. Production of biomolecule microarrays through laser induced forward transfer

    NASA Astrophysics Data System (ADS)

    Fernandez-Pradas, Juan Marcos; Serra, Pere; Colina, Monica; Morenza, Jose-Luis

    2004-10-01

    Biomolecule microarrays are a kind of biosensors that consist in patterns of different biological molecules immobilized on a solid substrate and capable to bind specifically to their complementary targets. In particular, DNA and protein microarrays have been revealed to be very efficient devices for genen and protein identification, what has converted them in powerful tools for many applications, like clinical diagnose, drug discovery analysis, genomics and proteomics. The production of these devices requires the manipulation of tiny amounts of a liquid solution containing biomolecules without damaging them. In this work laser induced forward transfer (LIFT) has been used for spotting a biomolecule in order to check the viability of this technique for the production of microarrays. A pulsed Nd:YAG laser beam (355 nm wavelength) has been used to transfer droplets of a biomolecule containing solution onto a solid slide. Optical microscopy of the transferred material has been carried out to investigate the morphological characteristics of the droplets obtained under different irradiation conditions. Afterwards, a DNA microarray has been spotted. The viability of the transference has been tested by checking the biological activity of the biomolecule in front of its specific complementary target. This has revealed that, indeed, the LIFT technique is adequate for the production of DNA microarrays.

  3. 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. PMID:27076594

  4. Phenotypic MicroRNA Microarrays

    PubMed Central

    Kwon, Yong-Jun; Heo, Jin Yeong; Kim, Hi Chul; Kim, Jin Yeop; Liuzzi, Michel; Soloveva, Veronica

    2013-01-01

    Microarray technology has become a very popular approach in cases where multiple experiments need to be conducted repeatedly or done with a variety of samples. In our lab, we are applying our high density spots microarray approach to microscopy visualization of the effects of transiently introduced siRNA or cDNA on cellular morphology or phenotype. In this publication, we are discussing the possibility of using this micro-scale high throughput process to study the role of microRNAs in the biology of selected cellular models. After reverse-transfection of microRNAs and siRNA, the cellular phenotype generated by microRNAs regulated NF-κB expression comparably to the siRNA. The ability to print microRNA molecules for reverse transfection into cells is opening up the wide horizon for the phenotypic high content screening of microRNA libraries using cellular disease models.

  5. Self-Assembling Protein Microarrays

    NASA Astrophysics Data System (ADS)

    Ramachandran, Niroshan; Hainsworth, Eugenie; Bhullar, Bhupinder; Eisenstein, Samuel; Rosen, Benjamin; Lau, Albert Y.; C. Walter, Johannes; LaBaer, Joshua

    2004-07-01

    Protein microarrays provide a powerful tool for the study of protein function. However, they are not widely used, in part because of the challenges in producing proteins to spot on the arrays. We generated protein microarrays by printing complementary DNAs onto glass slides and then translating target proteins with mammalian reticulocyte lysate. Epitope tags fused to the proteins allowed them to be immobilized in situ. This obviated the need to purify proteins, avoided protein stability problems during storage, and captured sufficient protein for functional studies. We used the technology to map pairwise interactions among 29 human DNA replication initiation proteins, recapitulate the regulation of Cdt1 binding to select replication proteins, and map its geminin-binding domain.

  6. 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

  7. 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

  8. III-V/Ge channel MOS device technologies in nano CMOS era

    NASA Astrophysics Data System (ADS)

    Takagi, Shinichi; Zhang, Rui; Suh, Junkyo; Kim, Sang-Hyeon; Yokoyama, Masafumi; Nishi, Koichi; Takenaka, Mitsuru

    2015-06-01

    CMOS utilizing high-mobility III-V/Ge channels on Si substrates is expected to be one of the promising devices for high-performance and low power advanced LSIs in the future, because of its enhanced carrier transport properties. However, there are many critical issues and difficult challenges for realizing III-V/Ge-based CMOS on the Si platform such as (1) the formation of high-crystal-quality Ge/III-V films on Si substrates, (2) gate stack technologies to realize superior MOS/MIS interface quality, (3) the formation of a source/drain (S/D) with low resistivity and low leakage current, (4) process integration to realize ultrashort channel devices, and (5) total CMOS integration including Si CMOS. In this paper, we review the recent progress in III-V/Ge MOS devices and process technologies as viable approaches to solve the above critical problems on the basis of our recent research activities. The technologies include MOS gate stack formation, high-quality channel formation, low-resistance S/D formation, and CMOS integration. For the Ge device technologies, we focus on the gate stack technology and Ge channel formation on Si. Also, for the III-V MOS device technologies, we mainly address the gate stack technology, III-V channel formation on Si, the metal S/D technology, and implementation of these technologies into short-channel III-V-OI MOSFETs on Si substrates. On the basis of the present status of the achievements, we finally discuss the possibility of various CMOS structures using III-V/Ge channels.

  9. 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

  10. 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

  11. Enzyme Microarrays Assembled by Acoustic Dispensing Technology

    PubMed Central

    Wong, E. Y.; Diamond, S. L.

    2008-01-01

    Miniaturizing bioassays to the nanoliter scale for high-throughput screening reduces the consumption of reagents that are expensive or difficult to handle. Utilizing acoustic dispensing technology, nanodroplets containing 10 µM ATP (3 µCi/µL 32P) and reaction buffer in 10% glycerol were positionally dispensed to the surface of glass slides to form 40 nL compartments (100 droplets/slide) for Pim1 (Proviral integration site 1) kinase reactions. The reactions were activated by dispensing 4 nL of various levels of a pyridocarbazolo-cyclopentadienyl ruthenium-complex Pim1 inhibitor, followed by dispensing 4 nL of a Pim1 kinase and peptide substrate solution to achieve final concentrations of 150 nM enzyme and 10 µM substrate. The microarray was incubated at 30°C (97% Rh) for 1.5 hr. The spots were then blotted to phosphocellulose membranes to capture phosphorylated substrate. Using phosphor imaging to quantify the washed membranes, the assay showed that, for doses of inhibitor from 0.75 µM to 3 µM, Pim1 was increasingly inhibited. Signal-to-background ratios were as high as 165 and average coefficients of variation (CVs) for the assay were ~20%. CVs for dispensing typical working buffers were under 5%. Thus, microarrays assembled by acoustic dispensing are promising as cost-effective tools that can be used in protein assay development. PMID:18616925

  12. High-Q CMOS-integrated photonic crystal microcavity devices.

    PubMed

    Mehta, Karan K; Orcutt, Jason S; Tehar-Zahav, Ofer; Sternberg, Zvi; Bafrali, Reha; Meade, Roy; Ram, Rajeev J

    2014-01-01

    Integrated optical resonators are necessary or beneficial in realizations of various functions in scaled photonic platforms, including filtering, modulation, and detection in classical communication systems, optical sensing, as well as addressing and control of solid state emitters for quantum technologies. Although photonic crystal (PhC) microresonators can be advantageous to the more commonly used microring devices due to the former's low mode volumes, fabrication of PhC cavities has typically relied on electron-beam lithography, which precludes integration with large-scale and reproducible CMOS fabrication. Here, we demonstrate wavelength-scale polycrystalline silicon (pSi) PhC microresonators with Qs up to 60,000 fabricated within a bulk CMOS process. Quasi-1D resonators in lateral p-i-n structures allow for resonant defect-state photodetection in all-silicon devices, exhibiting voltage-dependent quantum efficiencies in the range of a few 10 s of %, few-GHz bandwidths, and low dark currents, in devices with loaded Qs in the range of 4,300-9,300; one device, for example, exhibited a loaded Q of 4,300, 25% quantum efficiency (corresponding to a responsivity of 0.31 A/W), 3 GHz bandwidth, and 30 nA dark current at a reverse bias of 30 V. This work demonstrates the possibility for practical integration of PhC microresonators with active electro-optic capability into large-scale silicon photonic systems.

  13. High-Q CMOS-integrated photonic crystal microcavity devices

    NASA Astrophysics Data System (ADS)

    Mehta, Karan K.; Orcutt, Jason S.; Tehar-Zahav, Ofer; Sternberg, Zvi; Bafrali, Reha; Meade, Roy; Ram, Rajeev J.

    2014-02-01

    Integrated optical resonators are necessary or beneficial in realizations of various functions in scaled photonic platforms, including filtering, modulation, and detection in classical communication systems, optical sensing, as well as addressing and control of solid state emitters for quantum technologies. Although photonic crystal (PhC) microresonators can be advantageous to the more commonly used microring devices due to the former's low mode volumes, fabrication of PhC cavities has typically relied on electron-beam lithography, which precludes integration with large-scale and reproducible CMOS fabrication. Here, we demonstrate wavelength-scale polycrystalline silicon (pSi) PhC microresonators with Qs up to 60,000 fabricated within a bulk CMOS process. Quasi-1D resonators in lateral p-i-n structures allow for resonant defect-state photodetection in all-silicon devices, exhibiting voltage-dependent quantum efficiencies in the range of a few 10 s of %, few-GHz bandwidths, and low dark currents, in devices with loaded Qs in the range of 4,300-9,300 one device, for example, exhibited a loaded Q of 4,300, 25% quantum efficiency (corresponding to a responsivity of 0.31 A/W), 3 GHz bandwidth, and 30 nA dark current at a reverse bias of 30 V. This work demonstrates the possibility for practical integration of PhC microresonators with active electro-optic capability into large-scale silicon photonic systems.

  14. 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.

  15. Advanced CMOS Radiation Effects Testing Analysis

    NASA Technical Reports Server (NTRS)

    Pellish, Jonathan Allen; Marshall, Paul W.; Rodbell, Kenneth P.; Gordon, Michael S.; LaBel, Kenneth A.; Schwank, James R.; Dodds, Nathaniel A.; Castaneda, Carlos M.; Berg, Melanie D.; Kim, Hak S.; Phan, Anthony M.; Seidleck, Christina M.

    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.

  16. Advanced CMOS Radiation Effects Testing and Analysis

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

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

  17. 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.

  18. 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.

  19. 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.

  20. Radiation characteristics of scintillator coupled CMOS APS for radiography conditions

    NASA Astrophysics Data System (ADS)

    Kim, Kwang Hyun; Kim, Soongpyung; Kang, Dong-Won; Kim, Dong-Kie

    2006-11-01

    Under industrial radiography conditions, we analyzed short-term radiation characteristics of scintillator coupled CMOS APS (hereinafter SC CMOS APS). By means of experimentation, the contribution of the transmitted X-ray through the scintillator to the properties of the CMOS APS and the afterimage, generated in the acquired image even at low dose condition, were investigated. To see the transmitted X-ray effects on the CMOS APS, Fein focus™ X-ray machine, two scintillators of Lanex™ Fine and Regular, and two CMOS APS array of RadEye™ were used under the conditions of 50 kV p/1 mAs and 100 kV p/1 mAs. By measuring the transmitted X-ray on signal and Noise Power Spectrum, we analytically examined the generation mechanism of the afterimage, based on dark signal or dark current increase in the sensor, and explained the afterimage in the SC CMOS APS.

  1. Integrated Amplification Microarrays for Infectious Disease Diagnostics

    PubMed Central

    Chandler, Darrell P.; Bryant, Lexi; Griesemer, Sara B.; Gu, Rui; Knickerbocker, Christopher; Kukhtin, Alexander; Parker, Jennifer; Zimmerman, Cynthia; George, Kirsten St.; Cooney, Christopher G.

    2012-01-01

    This overview describes microarray-based tests that combine solution-phase amplification chemistry and microarray hybridization within a single microfluidic chamber. The integrated biochemical approach improves microarray workflow for diagnostic applications by reducing the number of steps and minimizing the potential for sample or amplicon cross-contamination. Examples described herein illustrate a basic, integrated approach for DNA and RNA genomes, and a simple consumable architecture for incorporating wash steps while retaining an entirely closed system. It is anticipated that integrated microarray biochemistry will provide an opportunity to significantly reduce the complexity and cost of microarray consumables, equipment, and workflow, which in turn will enable a broader spectrum of users to exploit the intrinsic multiplexing power of microarrays for infectious disease diagnostics.

  2. Microarray data analysis and mining approaches.

    PubMed

    Cordero, Francesca; Botta, Marco; Calogero, Raffaele A

    2007-12-01

    Microarray based transcription profiling is now a consolidated methodology and has widespread use in areas such as pharmacogenomics, diagnostics and drug target identification. Large-scale microarray studies are also becoming crucial to a new way of conceiving experimental biology. A main issue in microarray transcription profiling is data analysis and mining. When microarrays became a methodology of general use, considerable effort was made to produce algorithms and methods for the identification of differentially expressed genes. More recently, the focus has switched to algorithms and database development for microarray data mining. Furthermore, the evolution of microarray technology is allowing researchers to grasp the regulative nature of transcription, integrating basic expression analysis with mRNA characteristics, i.e. exon-based arrays, and with DNA characteristics, i.e. comparative genomic hybridization, single nucleotide polymorphism, tiling and promoter structure. In this article, we will review approaches used to detect differentially expressed genes and to link differential expression to specific biological functions.

  3. 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.

  4. Surface free energy and microarray deposition technology.

    PubMed

    McHale, Glen

    2007-03-01

    Microarray techniques use a combinatorial approach to assess complex biochemical interactions. The fundamental goal is simultaneous, large-scale experimentation analogous to the automation achieved in the semiconductor industry. However, microarray deposition inherently involves liquids contacting solid substrates. Liquid droplet shapes are determined by surface and interfacial tension forces, and flows during drying. This article looks at how surface free energy and wetting considerations may influence the accuracy and reliability of spotted microarray experiments.

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

    PubMed

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

    2013-01-01

    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

  6. 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.

  7. 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.

  8. 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...

  9. Living Cell Microarrays: An Overview of Concepts.

    PubMed

    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

  10. 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

  11. 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.

  12. Highly parallel microbial diagnostics using oligonucleotide microarrays.

    PubMed

    Loy, Alexander; Bodrossy, Levente

    2006-01-01

    Oligonucleotide microarrays are highly parallel hybridization platforms, allowing rapid and simultaneous identification of many different microorganisms and viruses in a single assay. In the past few years, researchers have been confronted with a dramatic increase in the number of studies reporting development and/or improvement of oligonucleotide microarrays for microbial diagnostics, but use of the technology in routine diagnostics is still constrained by a variety of factors. Careful development of microarray essentials (such as oligonucleotide probes, protocols for target preparation and hybridization, etc.) combined with extensive performance testing are thus mandatory requirements for the maturation of diagnostic microarrays from fancy technological gimmicks to robust and routinely applicable tools.

  13. 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

  14. 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.

  15. 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

  16. 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

    2016-01-01

    In the present work, a portable and low-cost planar waveguide based resonance light scattering (RLS) scanner (termed as: PW-RLS scanner) has been developed for microarray detection. The PW-RLS scanner employs a 2 × 4 white light emitting diode array (WLEDA) as the excitation light source, a folded optical path with a complementary metal oxide semiconductor (CMOS) as the signal/image acquisition device and stepper motors with gear drives as the mechanical drive system. The biological binding/recognizing events on the microarray can be detected with an evanescent waveguide-directed illumination and light-scattering label (e.g., nanoparticles) while the microarray slide acts as an evanescent waveguide substrate. The performance of the as-developed PW-RLS scanner has been evaluated by analyzing type 2 diabetes mellitus (T2DM) risk genes. Highly selective and sensitive (less than 1% allele frequency at the attomole-level) T2DM risk gene detection is achieved using single-stranded DNA functionalized gold nanoparticles (ssDNA-GNPs) as detection probes. Additionally, the successful simultaneous analysis of 15 T2DM patient genotypes suggests that the device has great potential for the realization of a personalized diagnostic test for a given disease or patient follow-up. PMID:26567521

  17. 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...

  18. 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...

  19. 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. PMID:27102089

  20. 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. PMID:26922341

  1. Microactuateur electrothermique bistable: Etude d'implementation avec une technologie standard CMOS

    NASA Astrophysics Data System (ADS)

    Ressejac, Isabelle

    up to a hundred times higher than its thickness. This natural deflection results from the relaxation of internal stresses inside the thin films which are part of the microactuator. These internal stresses are intrinsics to the host CMOS process. We have developed a model of the microactuator's initial deflection using mechanical properties of thin films and dimensions of the structure. Actuation experiments were performed in order to characterize the deflection of the microactuator with respect to the heating of the bilayers (separately and together). We have developed a thermal actuation analytical model for an n-layers multimorph structure, which takes into account the initial deflection resulting from the relaxation of stresses as well as the deflection due to the temperature increase during the electrothermal activation of the bilayers. (Abstract shortened by UMI.)

  2. Studying bovine early embryo transcriptome by microarray.

    PubMed

    Dufort, Isabelle; Robert, Claude; Sirard, Marc-André

    2015-01-01

    Microarrays represent a significant advantage when studying gene expression in early embryo because they allow for a speedy study of a large number of genes even if the sample of interest contains small quantities of genetic material. Here we describe the protocols developed by the EmbryoGENE Network to study the bovine transcriptome in early embryo using a microarray experimental design.

  3. Application of microarray technology in pulmonary diseases

    PubMed Central

    Tzouvelekis, Argyris; Patlakas, George; Bouros, Demosthenes

    2004-01-01

    Microarrays are a powerful tool that have multiple applications both in clinical and cell biology arenas of common lung diseases. To exemplify how this tool can be useful, in this review, we will provide an overview of the application of microarray technology in research relevant to common lung diseases and present some of the future perspectives. PMID:15585067

  4. Sensing immune responses with customized peptide microarrays.

    PubMed

    Schirwitz, Christopher; Loeffler, Felix F; Felgenhauer, Thomas; Stadler, Volker; Breitling, Frank; Bischoff, F Ralf

    2012-12-01

    The intent to solve biological and biomedical questions in high-throughput led to an immense interest in microarray technologies. Nowadays, DNA microarrays are routinely used to screen for oligonucleotide interactions within a large variety of potential interaction partners. To study interactions on the protein level with the same efficiency, protein and peptide microarrays offer similar advantages, but their production is more demanding. A new technology to produce peptide microarrays with a laser printer provides access to affordable and highly complex peptide microarrays. Such a peptide microarray can contain up to 775 peptide spots per cm², whereby the position of each peptide spot and, thus, the amino acid sequence of the corresponding peptide, is exactly known. Compared to other techniques, such as the SPOT synthesis, more features per cm² at lower costs can be synthesized which paves the way for laser printed peptide microarrays to take on roles as efficient and affordable biomedical sensors. Here, we describe the laser printer-based synthesis of peptide microarrays and focus on an application involving the blood sera of tetanus immunized individuals, indicating the potential of peptide arrays to sense immune responses.

  5. Interferometric metrology of wafer nanotopography for advanced CMOS process integration

    NASA Astrophysics Data System (ADS)

    Valley, John F.; Koliopoulos, Chris L.; Tang, Shouhong

    2001-12-01

    According to industry standards (SEMI M43, Guide for Reporting Wafer Nanotopography), Nanotopography is the non- planar deviation of the whole front wafer surface within a spatial wavelength range of approximately 0.2 to 20 mm and within the fixed quality area (FQA). The need for precision metrology of wafer nanotopography is being actively addressed by interferometric technology. In this paper we present an approach to mapping the whole wafer front surface nanotopography using an engineered coherence interferometer. The interferometer acquires a whole wafer raw topography map. The raw map is then filtered to remove the long spatial wavelength, high amplitude shape contributions and reveal the nanotopography in the filtered map. Filtered maps can be quantitatively analyzed in a variety of ways to enable statistical process control (SPC) of nanotopography parameters. The importance of tracking these parameters for CMOS gate level processes at 180-nm critical dimension, and below, is examined.

  6. 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.

  7. CMOS cassette for digital upgrade of film-based mammography systems

    NASA Astrophysics Data System (ADS)

    Baysal, Mehmet A.; Toker, Emre

    2006-03-01

    While full-field digital mammography (FFDM) technology is gaining clinical acceptance, the overwhelming majority (96%) of the installed base of mammography systems are conventional film-screen (FSM) systems. A high performance, and economical digital cassette based product to conveniently upgrade FSM systems to FFDM would accelerate the adoption of FFDM, and make the clinical and technical advantages of FFDM available to a larger population of women. The planned FFDM cassette is based on our commercial Digital Radiography (DR) cassette for 10 cm x 10 cm field-of-view spot imaging and specimen radiography, utilizing a 150 micron columnar CsI(Tl) scintillator and 48 micron active-pixel CMOS sensor modules. Unlike a Computer Radiography (CR) cassette, which requires an external digitizer, our DR cassette transfers acquired images to a display workstation within approximately 5 seconds of exposure, greatly enhancing patient flow. We will present the physical performance of our prototype system against other FFDM systems in clinical use today, using established objective criteria such as the Modulation Transfer Function (MTF), Detective Quantum Efficiency (DQE), and subjective criteria, such as a contrast-detail (CD-MAM) observer performance study. Driven by the strong demand from the computer industry, CMOS technology is one of the lowest cost, and the most readily accessible technologies available for FFDM today. Recent popular use of CMOS imagers in high-end consumer cameras have also resulted in significant advances in the imaging performance of CMOS sensors against rivaling CCD sensors. This study promises to take advantage of these unique features to develop the first CMOS based FFDM upgrade cassette.

  8. Real-time DNA microarray analysis

    PubMed Central

    Hassibi, Arjang; Vikalo, Haris; Riechmann, José Luis; Hassibi, Babak

    2009-01-01

    We present a quantification method for affinity-based DNA microarrays which is based on the real-time measurements of hybridization kinetics. This method, i.e. real-time DNA microarrays, enhances the detection dynamic range of conventional systems by being impervious to probe saturation in the capturing spots, washing artifacts, microarray spot-to-spot variations, and other signal amplitude-affecting non-idealities. We demonstrate in both theory and practice that the time-constant of target capturing in microarrays, similar to all affinity-based biosensors, is inversely proportional to the concentration of the target analyte, which we subsequently use as the fundamental parameter to estimate the concentration of the analytes. Furthermore, to empirically validate the capabilities of this method in practical applications, we present a FRET-based assay which enables the real-time detection in gene expression DNA microarrays. PMID:19723688

  9. Real-time DNA microarray analysis.

    PubMed

    Hassibi, Arjang; Vikalo, Haris; Riechmann, José Luis; Hassibi, Babak

    2009-11-01

    We present a quantification method for affinity-based DNA microarrays which is based on the real-time measurements of hybridization kinetics. This method, i.e. real-time DNA microarrays, enhances the detection dynamic range of conventional systems by being impervious to probe saturation in the capturing spots, washing artifacts, microarray spot-to-spot variations, and other signal amplitude-affecting non-idealities. We demonstrate in both theory and practice that the time-constant of target capturing in microarrays, similar to all affinity-based biosensors, is inversely proportional to the concentration of the target analyte, which we subsequently use as the fundamental parameter to estimate the concentration of the analytes. Furthermore, to empirically validate the capabilities of this method in practical applications, we present a FRET-based assay which enables the real-time detection in gene expression DNA microarrays. PMID:19723688

  10. 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

  11. DNA Microarrays for Identifying Fishes

    PubMed Central

    Nölte, M.; Weber, H.; Silkenbeumer, N.; Hjörleifsdottir, S.; Hreggvidsson, G. O.; Marteinsson, V.; Kappel, K.; Planes, S.; Tinti, F.; Magoulas, A.; Garcia Vazquez, E.; Turan, C.; Hervet, C.; Campo Falgueras, D.; Antoniou, A.; Landi, M.; Blohm, D.

    2008-01-01

    In many cases marine organisms and especially their diverse developmental stages are difficult to identify by morphological characters. DNA-based identification methods offer an analytically powerful addition or even an alternative. In this study, a DNA microarray has been developed to be able to investigate its potential as a tool for the identification of fish species from European seas based on mitochondrial 16S rDNA sequences. Eleven commercially important fish species were selected for a first prototype. Oligonucleotide probes were designed based on the 16S rDNA sequences obtained from 230 individuals of 27 fish species. In addition, more than 1200 sequences of 380 species served as sequence background against which the specificity of the probes was tested in silico. Single target hybridisations with Cy5-labelled, PCR-amplified 16S rDNA fragments from each of the 11 species on microarrays containing the complete set of probes confirmed their suitability. True-positive, fluorescence signals obtained were at least one order of magnitude stronger than false-positive cross-hybridisations. Single nontarget hybridisations resulted in cross-hybridisation signals at approximately 27% of the cases tested, but all of them were at least one order of magnitude lower than true-positive signals. This study demonstrates that the 16S rDNA gene is suitable for designing oligonucleotide probes, which can be used to differentiate 11 fish species. These data are a solid basis for the second step to create a “Fish Chip” for approximately 50 fish species relevant in marine environmental and fisheries research, as well as control of fisheries products. PMID:18270778

  12. Failures of CMOS Circuits Irradiated At Low Rates

    NASA Technical Reports Server (NTRS)

    Goben, Charles A.; Price, William E.

    1990-01-01

    Report describes experiments on irradiation of SGS 4007 complementary metal oxide/semiconductor (CMOS) integrated inverter circuits by 60Co and 137Cs radioactive sources. Purpose of experiments to supplement previous observations that minimum radiation doses at which failure occurred in more-complicated CMOS parts were lower at lower dose rates.

  13. 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

  14. 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.

  15. 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

  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. Organic Field-Effect Transistors for CMOS Devices

    NASA Astrophysics Data System (ADS)

    Melzer, Christian; von Seggern, Heinz

    Organic field-effect transistors (OFETs) are the key elements of future low cost electronics such as radio frequency identification tags. In order to take full advantage of organic electronics, low power consumption is mandatory, requiring the use of a complementary metal oxide semiconductor (CMOS) like technique. To realize CMOS-devices p-type and n-type organic field-effect transistors on one substrate have to be provided. Here, the latest concepts to produce in a straightforward way complementary acting OFETs for CMOS-like elements are illustrated on basis of the inverter. Starting from a simple description of thin-film transistors, the basic design rules for the development of complementary OFETs are given and some realizations of CMOS-like inverters are discussed. A CMOS-like inverter based on two identical field-effect transistors disclosing almost unipolar p-type and n-type behavior is presented.

  18. 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.

  19. 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

  20. High-Q CMOS-integrated photonic crystal microcavity devices

    PubMed Central

    Mehta, Karan K.; Orcutt, Jason S.; Tehar-Zahav, Ofer; Sternberg, Zvi; Bafrali, Reha; Meade, Roy; Ram, Rajeev J.

    2014-01-01

    Integrated optical resonators are necessary or beneficial in realizations of various functions in scaled photonic platforms, including filtering, modulation, and detection in classical communication systems, optical sensing, as well as addressing and control of solid state emitters for quantum technologies. Although photonic crystal (PhC) microresonators can be advantageous to the more commonly used microring devices due to the former's low mode volumes, fabrication of PhC cavities has typically relied on electron-beam lithography, which precludes integration with large-scale and reproducible CMOS fabrication. Here, we demonstrate wavelength-scale polycrystalline silicon (pSi) PhC microresonators with Qs up to 60,000 fabricated within a bulk CMOS process. Quasi-1D resonators in lateral p-i-n structures allow for resonant defect-state photodetection in all-silicon devices, exhibiting voltage-dependent quantum efficiencies in the range of a few 10 s of %, few-GHz bandwidths, and low dark currents, in devices with loaded Qs in the range of 4,300–9,300; one device, for example, exhibited a loaded Q of 4,300, 25% quantum efficiency (corresponding to a responsivity of 0.31 A/W), 3 GHz bandwidth, and 30 nA dark current at a reverse bias of 30 V. This work demonstrates the possibility for practical integration of PhC microresonators with active electro-optic capability into large-scale silicon photonic systems. PMID:24518161

  1. 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. PMID:24682025

  2. Real-time reconfigurable subthreshold CMOS perceptron.

    PubMed

    Aunet, S; Oelmann, B; Norseng, P A; Berg, Y

    2008-04-01

    In this paper, a new, real-time reconfigurable perceptron circuit element is presented. A six-transistor version used as a threshold gate, having a fan-in of three, producing adequate outputs for threshold of T =1, 2 and 3 is demonstrated by chip measurements. Subthreshold operation for supply voltages in the range of 100-350 mV is shown. The circuit performs competitively with a standard static complimentary metal-oxide-semiconductor (CMOS) implementation when maximum speed and energy delay product are taken into account, when used in a ring oscillator. Functionality per transistor is, to our knowledge, the highest reported for a variety of comparable circuits not based on floating gate techniques. Statistical simulations predict probabilities for making working circuits under mismatch and process variations. The simulations, in 120-nm CMOS, also support discussions regarding lower limits to supply voltage and redundancy. A brief discussion on how the circuit may be exploited as a basic building block for future defect tolerant mixed signal circuits, as well as neural networks, exploiting redundancy, is included.

  3. 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. PMID:26500051

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. Detection of antibodies against avian influenza virus by protein microarray using nucleoprotein expressed in insect cells.

    PubMed

    Zhao, Yuhui; Wang, Xiurong; Chen, Pucheng; Zeng, Xianying; Bao, Hongmei; Wang, Yunhe; Xu, Xiaolong; Jiang, Yongping; Chen, Hualan; Li, Guangxing

    2015-04-01

    Avian influenza (AI) is an infectious disease caused by avian influenza viruses (AIVs) which belong to the influenza virus A group. AI causes tremendous economic losses in poultry industry and pose great threatens to human health. Active serologic surveillance is necessary to prevent and control the spread of AI. In this study, a protein microarray using nucleoprotein (NP) of H5N1 AIV expressed in insect cells was developed to detect antibodies against AIV NP protein. The protein microarray was used to test Newcastle disease virus (NDV), infectious bursal disease virus (IBDV), AIV positive and negative sera. The results indicated that the protein microarray could hybridize specifically with antibodies against AIV with strong signals and without cross-hybridization. Moreover, 76 field serum samples were detected by microarray, enzyme-linked immunosorbent assay (ELISA) and hemagglutination inhibition test (HI). The positive rate was 92.1% (70/76), 93.4% (71/76) and 89.4% (68/76) by protein microarray, ELISA and HI test, respectively. Compared with ELISA, the microarray showed 100% (20/20) agreement ratio in chicken and 98.2% (55/56) in ornamental bird. In conclusion, this method provides an alternative serological diagnosis for influenza antibody screening and will provide a basis for the development of protein microarrays that can be used to respectively detect antibodies of different AIV subtypes and other pathogens. PMID:25650059

  11. Microarray-Based Phospho-Proteomic Profiling of Complex Biological Systems12

    PubMed Central

    Goodwin, C. Rory; Woodard, Crystal L.; Zhou, Xin; Pan, Jianbo; Olivi, Alessandro; Xia, Shuli; Bettegowda, Chetan; Sciubba, Daniel M.; Pevsner, Jonathan; Zhu, Heng; Laterra, John

    2016-01-01

    Protein microarray technology has been successfully used for identifying substrates of purified activated kinases. We used protein microarrays to globally interrogate the effects of PTEN and Akt activity on the phospho-kinome of in vitro and in vivo glioma models and validated results in clinical pathological specimens. Whole cell lysates extracted from tumor samples can be applied to human kinome chip microarrays to profile the global kinase phosphorylation patterns in a high-throughput manner and identify novel substrates inherent to the tumor cell and the interactions with tumor microenvironment. Our findings identify a novel microarray-based method for assessing intracellular signaling events applicable to human oncogenesis and other pathophysiologic states. PMID:27084428

  12. Microarray-Based Phospho-Proteomic Profiling of Complex Biological Systems.

    PubMed

    Goodwin, C Rory; Woodard, Crystal L; Zhou, Xin; Pan, Jianbo; Olivi, Alessandro; Xia, Shuli; Bettegowda, Chetan; Sciubba, Daniel M; Pevsner, Jonathan; Zhu, Heng; Laterra, John

    2016-04-01

    Protein microarray technology has been successfully used for identifying substrates of purified activated kinases. We used protein microarrays to globally interrogate the effects of PTEN and Akt activity on the phospho-kinome of in vitro and in vivo glioma models and validated results in clinical pathological specimens. Whole cell lysates extracted from tumor samples can be applied to human kinome chip microarrays to profile the global kinase phosphorylation patterns in a high-throughput manner and identify novel substrates inherent to the tumor cell and the interactions with tumor microenvironment. Our findings identify a novel microarray-based method for assessing intracellular signaling events applicable to human oncogenesis and other pathophysiologic states. PMID:27084428

  13. 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.

  14. 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

  15. Comparison of microarray preprocessing methods.

    PubMed

    Shakya, K; Ruskin, H J; Kerr, G; Crane, M; Becker, J

    2010-01-01

    Data preprocessing in microarray technology is a crucial initial step before data analysis is performed. Many preprocessing methods have been proposed but none has proved to be ideal to date. Frequently, datasets are limited by laboratory constraints so that the need is for guidelines on quality and robustness, to inform further experimentation while data are yet restricted. In this paper, we compared the performance of four popular methods, namely MAS5, Li & Wong pmonly (LWPM), Li & Wong subtractMM (LWMM), and Robust Multichip Average (RMA). The comparison is based on the analysis carried out on sets of laboratory-generated data from the Bioinformatics Lab, National Institute of Cellular Biotechnology (NICB), Dublin City University, Ireland. These experiments were designed to examine the effect of Bromodeoxyuridine (5-bromo-2-deoxyuridine, BrdU) treatment in deep lamellar keratoplasty (DLKP) cells. The methodology employed is to assess dispersion across the replicates and analyze the false discovery rate. From the dispersion analysis, we found that variability is reduced more effectively by LWPM and RMA methods. From the false positive analysis, and for both parametric and nonparametric approaches, LWMM is found to perform best. Based on a complementary q-value analysis, LWMM approach again is the strongest candidate. The indications are that, while LWMM is marginally less effective than LWPM and RMA in terms of variance reduction, it has considerably improved discrimination overall.

  16. AMIC@: All MIcroarray Clusterings @ once.

    PubMed

    Geraci, Filippo; Pellegrini, Marco; Renda, M Elena

    2008-07-01

    The AMIC@ Web Server offers a light-weight multi-method clustering engine for microarray gene-expression data. AMIC@ is a highly interactive tool that stresses user-friendliness and robustness by adopting AJAX technology, thus allowing an effective interleaved execution of different clustering algorithms and inspection of results. Among the salient features AMIC@ offers, there are: (i) automatic file format detection, (ii) suggestions on the number of clusters using a variant of the stability-based method of Tibshirani et al. (iii) intuitive visual inspection of the data via heatmaps and (iv) measurements of the clustering quality using cluster homogeneity. Large data sets can be processed efficiently by selecting algorithms (such as FPF-SB and k-Boost), specifically designed for this purpose. In case of very large data sets, the user can opt for a batch-mode use of the system by means of the Clustering wizard that runs all algorithms at once and delivers the results via email. AMIC@ is freely available and open to all users with no login requirement at the following URL http://bioalgo.iit.cnr.it/amica.

  17. Quality Visualization of Microarray Datasets Using Circos

    PubMed Central

    Koch, Martin; Wiese, Michael

    2012-01-01

    Quality control and normalization is considered the most important step in the analysis of microarray data. At present there are various methods available for quality assessments of microarray datasets. However there seems to be no standard visualization routine, which also depicts individual microarray quality. Here we present a convenient method for visualizing the results of standard quality control tests using Circos plots. In these plots various quality measurements are drawn in a circular fashion, thus allowing for visualization of the quality and all outliers of each distinct array within a microarray dataset. The proposed method is intended for use with the Affymetrix Human Genome platform (i.e., GPL 96, GPL570 and GPL571). Circos quality measurement plots are a convenient way for the initial quality estimate of Affymetrix datasets that are stored in publicly available databases.

  18. 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.

  19. 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.

  20. Application of DNA microarray for screening metagenome library clones.

    PubMed

    Park, Soo-Je; Chae, Jong-Chan; Rhee, Sung-Keun

    2010-01-01

    Sequence-based screening tools of a metagenome library can expedite metagenome researches considering tremendous metagenome diversities. Several critical disadvantages of activity-based screening of metagenome libraries could be overcome by sequence-based screening approaches. DNA microarray technology widely used for monitoring environmental genes can be employed for screening environmental fosmid and BAC clones harboring target genes due to its high throughput nature. DNAs of fosmid clones are extracted and spotted on a glass slide and fluorescence-labeled probes are hybridized to the microarray. Specific hybridization signals can be obtained only for the fosmid clones that contain the target gene with high sensitivity (10 ng/μL of fosmid clone DNA) and quantitativeness. PMID:20830574

  1. PALM and STORM: Into large fields and high-throughput microscopy with sCMOS detectors.

    PubMed

    Almada, Pedro; Culley, Siân; Henriques, Ricardo

    2015-10-15

    Single Molecule Localization Microscopy (SMLM) techniques such as Photo-Activation Localization Microscopy (PALM) and Stochastic Optical Reconstruction Microscopy (STORM) enable fluorescence microscopy super-resolution: the overcoming of the resolution barrier imposed by the diffraction of light. These techniques are based on acquiring hundreds or thousands of images of single molecules, locating them and reconstructing a higher-resolution image from the high-precision localizations. These methods generally imply a considerable trade-off between imaging speed and resolution, limiting their applicability to high-throughput workflows. Recent advancements in scientific Complementary Metal-Oxide Semiconductor (sCMOS) camera sensors and localization algorithms reduce the temporal requirements for SMLM, pushing it toward high-throughput microscopy. Here we outline the decisions researchers face when considering how to adapt hardware on a new system for sCMOS sensors with high-throughput in mind. PMID:26079924

  2. Heterogeneous CMOS/memristor hardware neural networks for real-time target classification

    NASA Astrophysics Data System (ADS)

    Merkel, Cory; Kudithipudi, Dhireesha; Ptucha, Ray

    2014-05-01

    The advent of nanoscale metal-insulator-metal (MIM) structures with memristive properties has given birth to a new generation of hardware neural networks based on CMOS/memristor integration (CMHNNs). The advantage of the CMHNN paradigm compared to a pure CMOS approach lies in the multi-faceted functionality of memristive devices: They can efficiently store neural network configurations (weights and activation function parameters) via non-volatile, quasi-analog resistance states. They also provide high-density interconnects between neurons when integrated into 2-D and 3-D crossbar architectures. In this work, we explore the combination of CMHNN classifiers with manifold learning to reduce the dimensionality of CMHNN inputs. This allows the size of the CMHNN to be reduced significantly (by ≍ 97%). We tested the proposed system using the Caltech101 database and were able to achieve classification accuracies within ≍ 1:5% of those produced by a traditional support vector machine.

  3. Photon counting system based on intensified CMOS-APS: PC-IAPS

    NASA Astrophysics Data System (ADS)

    Bonanno, Giovanni; Belluso, Massimiliano; Cali, Antonio; Timpanaro, Maria C.; Uslenghi, Michela C.; Fiorini, Mauro; Modica, Angelo

    2001-12-01

    A progress report on the work, started ten months ago, aimed to evaluate the use of a new type of position sensor (Complementary Metal Oxide Semiconductor Active Pixel Sensor or CMOS-APS) as readout system in MCP-based intensified photon counting systems, is presented in this paper. The main differences respect to the more classical Photon Counting Intensified CCDs (PC-ICCD), the advantages and the disadvantages of their use as image photon counters, the adopted solutions to acquire the images and compute the photon event center, are described. The adopted optics and the designed mechanical assembly are also shown. The selected CMOS-APS, heart of the system, is treated in detail, as well as the electronics designed to drive the detector, to compute the center of the luminous spot on the MCP phosphor screen, and to send and receive data from a host computer. Finally we present preliminary results and achieved performances.

  4. CMOS On-Chip Optoelectronic Neural Interface Device with Integrated Light Source for Optogenetics

    NASA Astrophysics Data System (ADS)

    Sawadsaringkarn, Y.; Kimura, H.; Maezawa, Y.; Nakajima, A.; Kobayashi, T.; Sasagawa, K.; Noda, T.; Tokuda, T.; Ohta, J.

    2012-03-01

    A novel optoelectronic neural interface device is proposed for target applications in optogenetics for neural science. The device consists of a light emitting diode (LED) array implemented on a CMOS image sensor for on-chip local light stimulation. In this study, we designed a suitable CMOS image sensor equipped with on-chip electrodes to drive the LEDs, and developed a device structure and packaging process for LED integration. The prototype device produced an illumination intensity of approximately 1 mW with a driving current of 2.0 mA, which is expected to be sufficient to activate channelrhodopsin (ChR2). We also demonstrated the functions of light stimulation and on-chip imaging using a brain slice from a mouse as a target sample.

  5. 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…

  6. The Impact of Photobleaching on Microarray Analysis.

    PubMed

    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. Automated analytical microarrays: a critical review.

    PubMed

    Seidel, Michael; Niessner, Reinhard

    2008-07-01

    Microarrays provide a powerful analytical tool for the simultaneous detection of multiple analytes in a single experiment. The specific affinity reaction of nucleic acids (hybridization) and antibodies towards antigens is the most common bioanalytical method for generating multiplexed quantitative results. Nucleic acid-based analysis is restricted to the detection of cells and viruses. Antibodies are more universal biomolecular receptors that selectively bind small molecules such as pesticides, small toxins, and pharmaceuticals and to biopolymers (e.g. toxins, allergens) and complex biological structures like bacterial cells and viruses. By producing an appropriate antibody, the corresponding antigenic analyte can be detected on a multiplexed immunoanalytical microarray. Food and water analysis along with clinical diagnostics constitute potential application fields for multiplexed analysis. Diverse fluorescence, chemiluminescence, electrochemical, and label-free microarray readout systems have been developed in the last decade. Some of them are constructed as flow-through microarrays by combination with a fluidic system. Microarrays have the potential to become widely accepted as a system for analytical applications, provided that robust and validated results on fully automated platforms are successfully generated. This review gives an overview of the current research on microarrays with the focus on automated systems and quantitative multiplexed applications.

  8. 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

  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. Log polar image sensor in CMOS technology

    NASA Astrophysics Data System (ADS)

    Scheffer, Danny; Dierickx, Bart; Pardo, Fernando; Vlummens, Jan; Meynants, Guy; Hermans, Lou

    1996-08-01

    We report on the design, design issues, fabrication and performance of a log-polar CMOS image sensor. The sensor is developed for the use in a videophone system for deaf and hearing impaired people, who are not capable of communicating through a 'normal' telephone. The system allows 15 detailed images per second to be transmitted over existing telephone lines. This framerate is sufficient for conversations by means of sign language or lip reading. The pixel array of the sensor consists of 76 concentric circles with (up to) 128 pixels per circle, in total 8013 pixels. The interior pixels have a pitch of 14 micrometers, up to 250 micrometers at the border. The 8013-pixels image is mapped (log-polar transformation) in a X-Y addressable 76 by 128 array.

  11. 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.

  12. 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

  13. New technologies for fabricating biological microarrays

    NASA Astrophysics Data System (ADS)

    Larson, Bradley James

    This dissertation contains the description of two technologies that we have developed to reduce the cost and improve the quality of spotted biological microarrays. The first is a device, called a fluid microplotter, that uses ultrasonics to deposit spots with diameters of less than 5 microns. It consists of a dispenser, composed of a micropipette fastened to a piece of PZT piezoelectric, attached to a precision positioning system. A gentle pumping of fluid to the surface occurs when the micropipette is driven at specific frequencies. Spots or continuous lines can be deposited in this manner. The small fluid features conserve expensive and limited-quantity biological reagents. We characterize the performance of the microplotter in depositing fluid and examine the theoretical underpinnings of its operation. We present an analytical expression for the diameter of a deposited spot as a function of droplet volume and wettability of a surface and compare it with experimental results. We also examine the resonant properties of the piezoelectric element used to drive the dispenser and relate that to the frequencies at which pumping occurs. Finally, we propose a mechanism to explain the pumping behavior within the microplotter dispenser. The second technology we present is a process that uses a cold plasma and a subsequent in vacuo vapor-phase reaction to terminate a variety of oxide surfaces with epoxide chemical groups. These epoxide groups can react with amine-containing biomolecules to form strong covalent linkages between the biomolecules and the treated surface. The use of a plasma activation step followed by an in vacuo vapor-phase reaction allows for the precise control of surface functional groups, rather than the mixture of functionalities normally produced. This process modifies a range of different oxide surfaces, is fast, consumes a minimal amount of reagents, and produces attachment densities for bound biomolecules that are comparable to or better than

  14. A Liposome-Based Approach to the Integrated Multi-Component Antigen Microarrays

    PubMed Central

    Wang, Denong

    2015-01-01

    This report describes an experimental procedure for constructing integrated lipid, carbohydrate, and protein microarrays. In essence, it prints liposomes on nitrocellulose-coated micro-glass slides, a biochip substrate for spotting protein and carbohydrate microarrays, and the substances that can form liposomes (homo-liposomes) or can be incorporated into liposomes (hetero-liposomes) are suitable for microarray construction using existing microarray spotting devices. Importantly, this technology allows simultaneous detection of serum antibody activities among the three major classes of antigens, i.e., lipids, carbohydrates, and proteins. The potential of this technology is illustrated by its use in revealing a broad-spectrum of pre-existing anti-lipid antibodies in blood circulation and monitoring the epitope spreading of autoantibody reactivities among protein, carbohydrate, and lipid antigens in experimental autoimmune encephalomyelitis (EAE).

  15. 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.

  16. Analysis of protein tyrosine phosphatase interactions with microarrayed phosphopeptide substrates using imaging mass spectrometry

    PubMed Central

    McKee, Christopher J.; Hines, Harry B.; Ulrich, Robert G.

    2013-01-01

    Microarrays of peptide and recombinant protein libraries are routinely used for high-throughput studies of protein-protein interactions and enzymatic activities. Imaging mass spectrometry (IMS) is currently applied as a method to localize analytes on thin tissue sections and other surfaces. Here, we have applied IMS as a label-free means to analyze protein-peptide interactions in a microarray-based phosphatase assay. This IMS strategy visualizes the entire microarray in one composite image by collecting a pre-defined raster of MALDI-TOF MS spectra over the surface of the chip. Examining the bacterial tyrosine phosphatase YopH, we used IMS as a label-free means to visualize enzyme binding and activity with a microarrayed phosphopeptide library printed on chips coated with either gold or indium-tin oxide. Further, we demonstrate that microarray-based IMS can be coupled with surface plasmon resonance imaging to add kinetic analyses to measured binding interactions. The method described here is within the capabilities of many modern MALDI-TOF instruments and has general utility for the label-free analysis of microarray assays. PMID:23906642

  17. Depleted CMOS pixels for LHC proton-proton experiments

    NASA Astrophysics Data System (ADS)

    Wermes, N.

    2016-07-01

    While so far monolithic pixel detectors have remained in the realm of comparatively low rate and radiation applications outside LHC, new developments exploiting high resistivity substrates with three or four well CMOS process options allow reasonably large depletion depths and full CMOS circuitry in a monolithic structure. This opens up the possibility to target CMOS pixel detectors also for high radiation pp-experiments at the LHC upgrade, either in a hybrid-type fashion or even fully monolithic. Several pixel matrices have been prototyped with high ohmic substrates, high voltage options, and full CMOS electronics. They were characterized in the lab and in test beams. An overview of the necessary development steps and different approaches as well as prototype results are presented in this paper.

  18. Implementation of CMOS Millimeter-Wave Devices for Rotational Spectroscopy

    NASA Astrophysics Data System (ADS)

    Drouin, Brian; Tang, Adrian; Schlecht, Erich T.; Daly, Adam M.; Brageot, Emily; Gu, Qun Jane; Ye, Yu; Shu, Ran; Chang, M.-C. Frank; Kim, Rod M.

    2015-06-01

    The extension of radio-frequency CMOS circuitry into millimeter wavelengths promises the extension of spectroscopic techniques in compact, power efficient systems. We are now exploring the use of CMOS millimeter devices for low-mass, low-power instrumentation capable of remote or in-situ detection of gas composition during space missions. This effort focuses on the development of a semi-confocal Fabry-Perot cavity with mm-wavelength CMOS transmitter and receiver attached directly to a cavity coupler. Placement of the devices within the cavity structure bypasses problems encountered with signal injection and extraction in traditional cavity designs and simultaneously takes full advantage of the miniaturized form of the CMOS hardware. The presentation will provide an overview of the project and details of the accomplishments thus far, including the development and testing of a pulse modulated 83-98 GHz transmitter.

  19. Tests of commercial colour CMOS cameras for astronomical applications

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  20. 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.

  1. 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.

  2. 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.

  3. Chromosomal Microarray versus Karyotyping for Prenatal Diagnosis

    PubMed Central

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

    2013-01-01

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

  4. 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.

  5. Multiplexed protein profiling on microarrays by rolling-circle amplification

    PubMed Central

    Schweitzer, Barry; Roberts, Scott; Grimwade, Brian; Shao, Weiping; Wang, Minjuan; Fu, Qin; Shu, Quiping; Laroche, Isabelle; Zhou, Zhimin; Tchernev, Velizar T.; Christiansen, Jason; Velleca, Mark; Kingsmore, Stephen F.

    2010-01-01

    Fluorescent-sandwich immunoassays on microarrays hold appeal for proteomics studies, because equipment and antibodies are readily available, and assays are simple, scalable, and reproducible. The achievement of adequate sensitivity and specificity, however, requires a general method of immunoassay amplification. We describe coupling of isothermal rolling-circle amplification (RCA) to universal antibodies for this purpose. A total of 75 cytokines were measured simultaneously on glass arrays with signal amplification by RCA with high specificity, femtomolar sensitivity, 3 log quantitative range, and economy of sample consumption. A 51-feature RCA cytokine glass array was used to measure secretion from human dendritic cells (DCs) induced by lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α). As expected, LPS induced rapid secretion of inflammatory cytokines such as macrophage inflammatory protein (MIP)-1β, interleukin (IL)-8, and interferon-inducible protein (IP)-10. We found that eotaxin-2 and I-309 were induced by LPS; in addition, macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC), soluble interleukin 6 receptor (sIL-6R), and soluble tumor necrosis factor receptor I (sTNF-RI) were induced by TNF-α treatment. Because microarrays can accommodat ~1,000 sandwich immunoassays of this type, a relatively small number of RCA microarrays seem to offer a tractable approach for proteomic surveys. PMID:11923841

  6. 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.

  7. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2012-04-01

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

  9. Low-dose performance of wafer-scale CMOS-based X-ray detectors

    NASA Astrophysics Data System (ADS)

    Maes, Willem H.; Peters, Inge M.; Smit, Chiel; Kessener, Yves; Bosiers, Jan

    2015-03-01

    Compared to published amorphous-silicon (TFT) based X-ray detectors, crystalline silicon CMOS-based active-pixel detectors exploit the benefits of low noise, high speed, on-chip integration and featuring offered by CMOS technology. This presentation focuses on the specific advantage of high image quality at very low dose levels. The measurement of very low dose performance parameters like Detective Quantum Efficiency (DQE) and Noise Equivalent Dose (NED) is a challenge by itself. Second-order effects like defect pixel behavior, temporal and quantization noise effects, dose measurement accuracy and limitation of the x-ray source settings will influence the measurements at very low dose conditions. Using an analytical model to predict the low dose behavior of a detector from parameters extracted from shot-noise limited dose levels is presented. These models can also provide input for a simulation environment for optimizing the performance of future detectors. In this paper, models for predicting NED and the DQE at very low dose are compared to measurements on different CMOS detectors. Their validity for different sensor and optical stack combinations as well as for different x-ray beam conditions was validated.

  10. 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.

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

    SciTech Connect

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

    2011-07-01

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

  13. Low-noise CMOS SPAD arrays with in-pixel time-to-digital converters

    NASA Astrophysics Data System (ADS)

    Tosi, Alberto; Villa, Federica; Bronzi, Danilo; Zou, Yu; Lussana, Rudi; Tamborini, Davide; Tisa, Simone; Durini, Daniel; Weyers, Sascha; Pashen, Uwe; Brockherde, Werner; Zappa, Franco

    2014-05-01

    We present our latest results concerning CMOS Single-Photon Avalanche Diode (SPAD) arrays for high-throughput parallel single-photon counting. We exploited a high-voltage 0.35 μm CMOS technology in order to develop low-noise CMOS SPADs. The Dark Count Rate is 30 cps at room temperature for 30 μm devices, increases to 2 kcps for 100 μm SPADs and just to 100 kcps for 500 μm ones. Afterpulsing is less than 1% for hold-off time longer than 50 ns, thus allowing to reach high count rates. Photon Detection Efficiency is > 50% at 420 nm, > 40% below 500 nm and is still 5% at 850 nm. Timing jitter is less than 100 ps (FWHM) in SPADs with active area diameter up to 50 μm. We developed CMOS SPAD imagers with 150 μm pixel pitch and 30 μm SPADs. A 64×32 SPAD array is based on pixels including three 9-bit counters for smart phase-resolved photon counting up to 100 kfps. A 32x32 SPAD array includes 1024 10-bit Time-to-Digital Converters (TDC) with 300 ps resolution and 450 ps single-shot precision, for 3D ranging and FLIM. We developed also linear arrays with up to 60 pixels (with 100 μm SPAD, 150 μm pitch and in-pixel 250 ps TDC) for time-resolved parallel spectroscopy with high fill factor.

  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. 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.

  16. A new architecture of current-mode CMOS TDI Sensor

    NASA Astrophysics Data System (ADS)

    Ji, Cheng; Chen, Yongping

    2015-10-01

    Nowadays, CMOS sensors still suffer from the problem of low SNR, especially in the stage of low illumination and high relative scanning velocity. Lots of methods have been develop to overcome this problem. Among these researches, TDI (Time Delay Integration) architecture is a more natural choice, which is natively supported by CCD sensors. In this paper a new kind of proposed current-mode sensor is used to achieve TDI operation in analog domain. The circuit is composed of three main parts. At first, a current-type pixel is proposed, in which the active MOSFET is operated in the triode region to ensure the output current is linearly dependent on the gate voltage and avoid the reduction of threshold voltage in the traditional voltage mode pixels, such as 3T, 4T which use the source followers as its active part. Then a discrete double sampling (DDS) unit, which is operated in the form of currents is used to efficiently reduce the fixed pattern noise (FPN) and make the output is independent of reset voltage of pixels. For accumulation, an improved current mirror adder under controlled of timing circuits is proposed to overcome the problem of saturation suffered in voltage domain. Some main noise sources, especially come from analog sample and holds capacitors and switches is analyzed. Finally, simulation results with CSMC 0.5um technology and Cadence IC show that the proposed method is reasonable and efficient to improve the SNR.

  17. Oligonucleotide microarrays in constitutional genetic diagnosis.

    PubMed

    Keren, Boris; Le Caignec, Cedric

    2011-06-01

    Oligonucleotide microarrays such as comparative genomic hybridization arrays and SNP microarrays enable the identification of genomic imbalances - also termed copy-number variants - with increasing resolution. This article will focus on the most significant applications of high-throughput oligonucleotide microarrays, both in genetic diagnosis and research. In genetic diagnosis, the method is becoming a standard tool for investigating patients with unexplained developmental delay/intellectual disability, autism spectrum disorders and/or with multiple congenital anomalies. Oligonucleotide microarray have also been recently applied to the detection of genomic imbalances in prenatal diagnosis either to characterize a chromosomal rearrangement that has previously been identified by standard prenatal karyotyping or to detect a cryptic genomic imbalance in a fetus with ultrasound abnormalities and a normal standard prenatal karyotype. In research, oligonucleotide microarrays have been used for a wide range of applications, such as the identification of new genes responsible for monogenic disorders and the association of a copy-number variant as a predisposing factor to a common disease. Despite its widespread use, the interpretation of results is not always straightforward. We will discuss several unexpected results and ethical issues raised by these new methods.

  18. 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

  19. Protein microarrays for parasite antigen discovery.

    PubMed

    Driguez, Patrick; Doolan, Denise L; Molina, Douglas M; Loukas, Alex; Trieu, Angela; Felgner, Phil L; McManus, Donald P

    2015-01-01

    The host serological profile to a parasitic infection, such as schistosomiasis, can be used to define potential vaccine and diagnostic targets. Determining the host antibody response using traditional approaches is hindered by the large number of putative antigens in any parasite proteome. Parasite protein microarrays offer the potential for a high-throughput host antibody screen to simplify this task. In order to construct the array, parasite proteins are selected from available genomic sequence and protein databases using bioinformatic tools. Selected open reading frames are PCR amplified, incorporated into a vector for cell-free protein expression, and printed robotically onto glass slides. The protein microarrays can be probed with antisera from infected/immune animals or humans and the antibody reactivity measured with fluorophore labeled antibodies on a confocal laser microarray scanner to identify potential targets for diagnosis or therapeutic or prophylactic intervention. PMID:25388117

  20. Self-testable CMOS thermopile-based infrared imager

    NASA Astrophysics Data System (ADS)

    Charlot, Benoit; Parrain, F.; Mir, Salvador; Courtois, Bernard

    2001-04-01

    This paper describes a CMOS-compatible self-testable uncooled InfraRed (IR) imager that can be used in multiple applications such as overheating detection, night vision, and earth tracking for satellite positioning. The imager consists of an array of thermal pixels that sense an infrared radiation. Each pixel is implemented as a front-side bulk micromachined membrane suspended by four arms, each arm containing a thermopile made of Poly/Al thermocouples. The imager has a pixel self-test function that can be activated off-line in the field for validation and maintenance purposes, with an on-chip test signal generation that requires only slight modifications in the pixel design. The self-test of a pixel takes about 15 ms. The area overhead required by the test electronics does not imply any reduction of the pixel fill factor, since the electronics fits in the pixel silicon boundary. However, the additional self-test circuitry contributes to a small increase in the thermal conductance of a pixel due to the wiring of a heating resistor over the suspended arms. The self-test capability of the imager allows for a production test with a standard test equipment, without the need of special infrared sources and the associated optical equipment. A prototype with 8 X 8 pixels is currently in fabrication for validation of the self-test approach. In this prototype, each pixel occupies an area of 200 X 200 micrometer2, with a membrane size of 90 X 90 micrometer2 (fill factor of 0.2). Simulation results indicate a pixel thermal conductance of 22.6 (mu) W/K, giving a responsivity of 138 V/W, with a thermocouple Seebeck coefficient that has been measured at 248 (mu) V/K for the 0.6 micrometer CMOS technology used. The noise equivalent power (considering only Johnson noise in the thermopile) is calculated as 0.18 nW.H-1/2 with a detectivity of 5.03 X 107 cm.Hz1/2.W-1, in line with current state-of-the-art. Since the imager may need to measure irradiation intensities below 1(mu) W

  1. Hybridization and Selective Release of DNA Microarrays

    SciTech Connect

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

    2011-11-29

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

  2. Analysis of High-Throughput ELISA Microarray Data

    SciTech Connect

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

    2011-02-23

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

  3. 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.

  4. Photo-Generation of Carbohydrate Microarrays

    NASA Astrophysics Data System (ADS)

    Carroll, Gregory T.; Wang, Denong; Turro, Nicholas J.; Koberstein, Jeffrey T.

    The unparalleled structural diversity of carbohydrates among biological molecules has been recognized for decades. Recent studies have highlighted carbohydrate signaling roles in many important biological processes, such as fertilization, embryonic development, cell differentiation and cellȁ4cell communication, blood coagulation, inflammation, chemotaxis, as well as host recognition and immune responses to microbial pathogens. In this chapter, we summarize recent progress in the establishment of carbohydrate-based microarrays and the application of these technologies in exploring the biological information content in carbohydrates. A newly established photochemical platform of carbohydrate microarrays serves as a model for a focused discussion.

  5. Protein Microarrays for the Detection of Biothreats

    NASA Astrophysics Data System (ADS)

    Herr, Amy E.

    Although protein microarrays have proven to be an important tool in proteomics research, the technology is emerging as useful for public health and defense applications. Recent progress in the measurement and characterization of biothreat agents is reviewed in this chapter. Details concerning validation of various protein microarray formats, from contact-printed sandwich assays to supported lipid bilayers, are presented. The reviewed technologies have important implications for in vitro characterization of toxin-ligand interactions, serotyping of bacteria, screening of potential biothreat inhibitors, and as core components of biosensors, among others, research and engineering applications.

  6. Pineal Function: Impact of Microarray Analysis

    PubMed Central

    Klein, David C.; Bailey, Michael J.; Carter, David A.; Kim, Jong-so; Shi, Qiong; Ho, Anthony; Chik, Constance; Gaildrat, Pascaline; Morin, Fabrice; Ganguly, Surajit; Rath, Martin F.; Møller, Morten; Sugden, David; Rangel, Zoila G.; Munson, Peter J.; Weller, Joan L.; Coon, Steven L.

    2009-01-01

    Microarray analysis has provided a new understanding of pineal function by identifying genes that are highly expressed in this tissue relative to other tissues and also by identifying over 600 genes that are expressed on a 24-hour schedule. This effort has highlighted surprising similarity to the retina and has provided reason to explore new avenues of study including intracellular signaling, signal transduction, transcriptional cascades, thyroid/retinoic acid hormone signaling, metal biology, RNA splicing, and the role the pineal gland plays in the immune/inflammation response. The new foundation that microarray analysis has provided will broadly support future research on pineal function. PMID:19622385

  7. MicroRNA expression profiling using microarrays.

    PubMed

    Love, Cassandra; Dave, Sandeep

    2013-01-01

    MicroRNAs are small noncoding RNAs which are able to regulate gene expression at both the transcriptional and translational levels. There is a growing recognition of the role of microRNAs in nearly every tissue type and cellular process. Thus there is an increasing need for accurate quantitation of microRNA expression in a variety of tissues. Microarrays provide a robust method for the examination of microRNA expression. In this chapter, we describe detailed methods for the use of microarrays to measure microRNA expression and discuss methods for the analysis of microRNA expression data. PMID:23666707

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. A new method for gridding DNA microarrays.

    PubMed

    Charalambous, Christoforos C; Matsopoulos, George K

    2013-10-01

    In this paper, a new methodological scheme for the gridding of DNA microarrays is proposed. The scheme composes of a series of processes applied sequentially. Each DNA microarray image is pre-processed to remove any noise and the center of each spot is detected using a template matching algorithm. Then, an initial gridding is automatically placed on the DNA microarray image by 'building' rectangular pyramids around the detected spots' centers. The gridlines "move" between the pyramids, horizontally and vertically, forming this initial grid. Furthermore, a refinement process is applied composing of a five-step approach in order to correct gridding imperfections caused by its initial placement, both in non-spot cases and in more than one spot enclosure cases. The proposed gridding scheme is applied on DNA microarray images under known transformations and on real-world DNA data. Its performance is compared against the projection pursuit method, which is often used due to its speed and simplicity, as well as against a state-of-the-art method, the Optimal Multi-level Thresholding Gridding (OMTG). According to the obtained results, the proposed gridding scheme outperforms both methods, qualitatively and quantitatively.

  15. Diagnostic Oligonucleotide Microarray Fingerprinting of Bacillus Isolates

    SciTech Connect

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

    2006-01-01

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

  16. Data Analysis Strategies for Protein Microarrays

    PubMed Central

    Díez, Paula; Dasilva, Noelia; González-González, María; Matarraz, Sergio; Casado-Vela, Juan; Orfao, Alberto; Fuentes, Manuel

    2012-01-01

    Microarrays constitute a new platform which allows the discovery and characterization of proteins. According to different features, such as content, surface or detection system, there are many types of protein microarrays which can be applied for the identification of disease biomarkers and the characterization of protein expression patterns. However, the analysis and interpretation of the amount of information generated by microarrays remain a challenge. Further data analysis strategies are essential to obtain representative and reproducible results. Therefore, the experimental design is key, since the number of samples and dyes, among others aspects, would define the appropriate analysis method to be used. In this sense, several algorithms have been proposed so far to overcome analytical difficulties derived from fluorescence overlapping and/or background noise. Each kind of microarray is developed to fulfill a specific purpose. Therefore, the selection of appropriate analytical and data analysis strategies is crucial to achieve successful biological conclusions. In the present review, we focus on current algorithms and main strategies for data interpretation.

  17. Shrinkage covariance matrix approach for microarray data

    NASA Astrophysics Data System (ADS)

    Karjanto, Suryaefiza; Aripin, Rasimah

    2013-04-01

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

  18. Microarrays (DNA Chips) for the Classroom Laboratory

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  19. Data Analysis Strategies for Protein Microarrays

    PubMed Central

    Díez, Paula; Dasilva, Noelia; González-González, María; Matarraz, Sergio; Casado-Vela, Juan; Orfao, Alberto; Fuentes, Manuel

    2012-01-01

    Microarrays constitute a new platform which allows the discovery and characterization of proteins. According to different features, such as content, surface or detection system, there are many types of protein microarrays which can be applied for the identification of disease biomarkers and the characterization of protein expression patterns. However, the analysis and interpretation of the amount of information generated by microarrays remain a challenge. Further data analysis strategies are essential to obtain representative and reproducible results. Therefore, the experimental design is key, since the number of samples and dyes, among others aspects, would define the appropriate analysis method to be used. In this sense, several algorithms have been proposed so far to overcome analytical difficulties derived from fluorescence overlapping and/or background noise. Each kind of microarray is developed to fulfill a specific purpose. Therefore, the selection of appropriate analytical and data analysis strategies is crucial to achieve successful biological conclusions. In the present review, we focus on current algorithms and main strategies for data interpretation. PMID:27605336

  20. DISC-BASED IMMUNOASSAY MICROARRAYS. (R825433)

    EPA Science Inventory

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

  1. MICROARRAY DATA ANALYSIS USING MULTIPLE STATISTICAL MODELS

    EPA Science Inventory

    Microarray Data Analysis Using Multiple Statistical Models

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

  2. Raman-based microarray readout: a review.

    PubMed

    Haisch, Christoph

    2016-07-01

    For a quarter of a century, microarrays have been part of the routine analytical toolbox. Label-based fluorescence detection is still the commonest optical readout strategy. Since the 1990s, a continuously increasing number of label-based as well as label-free experiments on Raman-based microarray readout concepts have been reported. This review summarizes the possible concepts and methods and their advantages and challenges. A common label-based strategy is based on the binding of selective receptors as well as Raman reporter molecules to plasmonic nanoparticles in a sandwich immunoassay, which results in surface-enhanced Raman scattering signals of the reporter molecule. Alternatively, capture of the analytes can be performed by receptors on a microarray surface. Addition of plasmonic nanoparticles again leads to a surface-enhanced Raman scattering signal, not of a label but directly of the analyte. This approach is mostly proposed for bacteria and cell detection. However, although many promising readout strategies have been discussed in numerous publications, rarely have any of them made the step from proof of concept to a practical application, let alone routine use. Graphical Abstract Possible realization of a SERS (Surface-Enhanced Raman Scattering) system for microarray readout. PMID:26973235

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

    EPA Science Inventory

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

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

    SciTech Connect

    Rohde, Rachel M.; Timlin, Jerilyn Ann

    2005-11-01

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

  5. Identifying Fishes through DNA Barcodes and Microarrays

    PubMed Central

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

    2010-01-01

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

  6. Facilitating functional annotation of chicken microarray data

    PubMed Central

    2009-01-01

    Background Modeling results from chicken microarray studies is challenging for researchers due to little functional annotation associated with these arrays. The Affymetrix GenChip chicken genome array, one of the biggest arrays that serve as a key research tool for the study of chicken functional genomics, is among the few arrays that link gene products to Gene Ontology (GO). However the GO annotation data presented by Affymetrix is incomplete, for example, they do not show references linked to manually annotated functions. In addition, there is no tool that facilitates microarray researchers to directly retrieve functional annotations for their datasets from the annotated arrays. This costs researchers amount of time in searching multiple GO databases for functional information. Results We have improved the breadth of functional annotations of the gene products associated with probesets on the Affymetrix chicken genome array by 45% and the quality of annotation by 14%. We have also identified the most significant diseases and disorders, different types of genes, and known drug targets represented on Affymetrix chicken genome array. To facilitate functional annotation of other arrays and microarray experimental datasets we developed an Array GO Mapper (AGOM) tool to help researchers to quickly retrieve corresponding functional information for their dataset. Conclusion Results from this study will directly facilitate annotation of other chicken arrays and microarray experimental datasets. Researchers will be able to quickly model their microarray dataset into more reliable biological functional information by using AGOM tool. The disease, disorders, gene types and drug targets revealed in the study will allow researchers to learn more about how genes function in complex biological systems and may lead to new drug discovery and development of therapies. The GO annotation data generated will be available for public use via AgBase website and will be updated on regular

  7. Microarray analysis at single molecule resolution

    PubMed Central

    Mureşan, Leila; Jacak, Jarosław; Klement, Erich Peter; Hesse, Jan; Schütz, Gerhard J.

    2010-01-01

    Bioanalytical chip-based assays have been enormously improved in sensitivity in the recent years; detection of trace amounts of substances down to the level of individual fluorescent molecules has become state of the art technology. The impact of such detection methods, however, has yet not fully been exploited, mainly due to a lack in appropriate mathematical tools for robust data analysis. One particular example relates to the analysis of microarray data. While classical microarray analysis works at resolutions of two to 20 micrometers and quantifies the abundance of target molecules by determining average pixel intensities, a novel high resolution approach [1] directly visualizes individual bound molecules as diffraction limited peaks. The now possible quantification via counting is less susceptible to labeling artifacts and background noise. We have developed an approach for the analysis of high-resolution microarray images. It consists first of a single molecule detection step, based on undecimated wavelet transforms, and second, of a spot identification step via spatial statistics approach (corresponding to the segmentation step in the classical microarray analysis). The detection method was tested on simulated images with a concentration range of 0.001 to 0.5 molecules per square micron and signal-to-noise ratio (SNR) between 0.9 and 31.6. For SNR above 15 the false negatives relative error was below 15%. Separation of foreground/background proved reliable, in case foreground density exceeds background by a factor of 2. The method has also been applied to real data from high-resolution microarray measurements. PMID:20123580

  8. 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.

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

    PubMed

    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

  10. Design and characterization of avalanche photodiodes in submicron CMOS technologies

    NASA Astrophysics Data System (ADS)

    Pancheri, L.; Bendib, T.; Dalla Betta, G.-F.; Stoppa, D.

    2014-03-01

    The fabrication of Avalanche Photodiodes (APDs) in CMOS processes can be exploited in several application domains, including telecommunications, time-resolved optical detection and scintillation detection. CMOS integration allows the realization of systems with a high degree of parallelization which are competitive with hybrid solutions in terms of cost and complexity. In this work, we present a linear-mode APD fabricated in a 0.15μm process, and report its gain and noise characterization. The experimental observations can be accurately predicted using Hayat dead-space noise model. Device simulations based on dead-space model are then used to discuss the current status and the perspectives for the integration of high-performance low-noise devices in standard CMOS processes.

  11. Fabrication of the planar angular rotator using the CMOS process

    NASA Astrophysics Data System (ADS)

    Dai, Ching-Liang; Chang, Chien-Liu; Chen, Hung-Lin; Chang, Pei-Zen

    2002-05-01

    In this investigation we propose a novel planar angular rotator fabricated by the conventional complementary metal-oxide semiconductor (CMOS) process. Following the 0.6 μm single poly triple metal (SPTM) CMOS process, the device is completed by a simple maskless, post-process etching step. The rotor of the planar angular rotator rotates around its geometric center with electrostatic actuation. The proposed design adopts an intelligent mechanism including the slider-crank system to permit simultaneous motion. The CMOS planar angular rotator could be driven with driving voltages of around 40 V. The design proposed here has a shorter response time and longer life, without problems of friction and wear, compared to the more common planar angular micromotor.

  12. Scaling CMOS photonics transceivers beyond 100 Gb/s

    NASA Astrophysics Data System (ADS)

    Mekis, Attila; Abdalla, Sherif; De Dobbelaere, Peter M.; Foltz, Dennis; Gloeckner, Steffen; Hovey, Steven; Jackson, Steven; Liang, Yi; Mack, Michael; Masini, Gianlorenzo; Novais, Rafaela; Peterson, Mark; Pinguet, Thierry; Sahni, Subal; Schramm, Jeff; Sharp, Michael; Song, Daniel; Welch, Brian P.; Yokoyama, Kosei; Yu, Shuhuan

    2012-01-01

    We report on the performance of an integrated four-channel parallel optical transceiver built in a CMOS photonics process, operating at 28 Gb/s per channel. The optical engine of the transceiver comprises a single silicon die and a hybrid integrated DFB laser. The silicon die contains the all functionalities needed for an optical transceiver: transmitter and receiver optics, electrical driver, receiver and control circuits. We also describe the CMOS photonics platform used to build such transceiver device, which consists of: an optically enabled CMOS process, a photonic device library, and a design infrastructure that is modeled after standard circuit design tools. We discuss how this platform can scale to higher speeds and channel counts.

  13. High-speed polysilicon CMOS photodetector for telecom and datacom

    NASA Astrophysics Data System (ADS)

    Atabaki, Amir H.; Meng, Huaiyu; Alloatti, Luca; Mehta, Karan K.; Ram, Rajeev J.

    2016-09-01

    Absorption by mid-bandgap states in polysilicon or heavily implanted silicon has been previously utilized to implement guided-wave infrared photodetectors in CMOS compatible photonic platforms. Here, we demonstrate a resonant guided-wave photodetector based on the polysilicon layer that is used for the transistor gate in a microelectronic SOI CMOS process without any change to the foundry process flow ("zero-change" CMOS). Through a combination of doping mask layers, a lateral pn junction diode in the polysilicon is demonstrated with a strong electric field to enable efficient photo-carrier extraction and high-speed operation. This photodetector has a responsivity of more than 0.14 A/W from 1300 to 1600 nm, a 10 GHz bandwidth, and 80 nA dark current at 15 V reverse bias.

  14. 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.

  15. 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.

  16. 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

  17. 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...

  18. Measuring trunk orientation with a CMOS camera: feasibility and accuracy.

    PubMed

    Gissot, A-S; Barbieri, G; Iacobelis, M; Paindavoine, M; Pérennou, D

    2007-10-01

    The purpose of this study was to develop and validate a new tool to objectively quantify trunk orientation at the bedside, especially dedicated to the measurement of the lateropulsion in acute and subacute stroke patients. We developed software to analyze 2D movement with a CMOS camera (Logitech Quickcam Pro 4000) and to calculate the orientation of a segment defined by two color markers. First, the accuracy, reproducibility and noise when measuring segment orientations were evaluated with the CMOS camera placed in different positions, and second trunk orientation was measured in static and in dynamic conditions both with a CMOS camera and with a gold standard 3D video system (BTS SMART-e). Results showed that the measurement was accurate (mean error=0.05+/-0.12 degrees), reproducible (S.D. over five measurements=0.005 degrees ) and steady (noise signal=0.02 degrees ). The data obtained with the CMOS camera were highly correlated with those obtained with the 3D video system both in static and in dynamic conditions. However, the CMOS camera must be relatively well centered on the measured segment to avoid error due to image distortion. The parallax error was negligible. In conclusion, this could be an important step in the postural assessment of acute and subacute stroke patients. The CMOS camera, a simple, portable, compact, low-cost, commercially available apparatus is the first tool to objectively quantify lateropulsion at the bedside. This method could also support the development of a rehabilitation program for trunk orientation based on biofeedback using the real-time signal provided by the device.

  19. CMOS pixel sensors on high resistive substrate for high-rate, high-radiation environments

    NASA Astrophysics Data System (ADS)

    Hirono, Toko; Barbero, Marlon; Breugnon, Patrick; Godiot, Stephanie; Gonella, Laura; Hemperek, Tomasz; Hügging, Fabian; Krüger, Hans; Liu, Jian; Pangaud, Patrick; Peric, Ivan; Pohl, David-Leon; Rozanov, Alexandre; Rymaszewski, Piotr; Wang, Anqing; Wermes, Norbert

    2016-09-01

    A depleted CMOS active pixel sensor (DMAPS) has been developed on a substrate with high resistivity in a high voltage process. High radiation tolerance and high time resolution can be expected because of the charge collection by drift. A prototype of DMAPS was fabricated in a 150 nm process by LFoundry. Two variants of the pixel layout were tested, and the measured depletion depths of the variants are 166 μm and 80 μm. We report the results obtained with the prototype fabricated in this technology.

  20. 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

  1. Multi-purpose CMOS sensor interface for low-power applications

    NASA Astrophysics Data System (ADS)

    Wouters, P.; de Cooman, M.; Puers, R.

    1994-08-01

    A dedicated low-power CMOS transponder microchip is presented as part of a novel telemetry implant for biomedical applications. This mixed analog-digital circuit contains an identification code and collects information on physiological parameters, i.e., body temperature and physical activity, and on the status of the battery. To minimize the amount of data to be transmitted, a dedicated signal processing algorithm is embedded within its circuitry. All telemetry functions (encoding, modulation, generation of the carrier) are implemented on the integrated circuit. Emphasis is on a high degree of flexibility towards sensor inputs and internal data management, extreme miniaturization, and low-power consumption to allow a long implantation lifetime.

  2. Modifications in CMOS Dynamic Logic Style: A Review Paper

    NASA Astrophysics Data System (ADS)

    Meher, Preetisudha; Mahapatra, Kamalakanta

    2015-12-01

    Dynamic logic style is used in high performance circuit design because of its fast speed and less transistors requirement as compared to CMOS logic style. But it is not widely accepted for all types of circuit implementations due to its less noise tolerance and charge sharing problems. A small noise at the input of the dynamic logic can change the desired output. Domino logic uses one static CMOS inverter at the output of dynamic node which is more noise immune and consuming very less power as compared to other proposed circuit. In this paper, an overview and classification of these techniques are first presented and then compared according to their performance.

  3. 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.

  4. CMOS Compatible Integrated Thermoelectric Sensors Using Novel Frontside Micromachining

    NASA Astrophysics Data System (ADS)

    Socher, E.; Bochobza-Degani, O.; Nemirovsky, Y.

    2000-12-01

    CMOS compatible integrated thermoelectric sensors were designed and realized using a standard CMOS process and frontside RIE micromachining. The suspended structures were designed to have a spiral structure that enhances the thermal resistance and isolation of the sensor. Using dry RIE frontside micromachining for the release of the sensors allows better yield in realization of sensitive and smaller sensor pixels. Measured results of sensors used for IR detection show NEP's down to 0.4 nW/√Hz and response times down to 3 msec in 70*70 μm2 pixels.

  5. New Multiple-Times Programmable CMOS ROM Cell

    NASA Astrophysics Data System (ADS)

    Chung, In-Young; Jeong, Seong Yeol; Seo, Sung Min; Lee, Myungjin; Jang, Taesu; Cha, Seon-Yong; Park, Young June

    New concept of CMOS nonvolatile memory is presented with demonstration of cell implementations. The memory cell, which is a comparator basically, makes use of comparator offset for storage quantity and the FN stress phenomena for cell programming. We also propose the stress-packet operation which is the relevant programming method to finely control the offset of the memory cell. The memory cell is multiple-time programmable while it is implemented in a standard CMOS process. We fabricated the memory cell arrays of the latch comparator and demonstrated that it is rewritten several times. We also investigated the reliability of cell data retention by monitoring programmed offsets for several months.

  6. 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.

  7. A 0.5-GHz CMOS digital RF memory chip

    NASA Astrophysics Data System (ADS)

    Schnaitter, W. M.; Lewis, E. T.; Gordon, B. E.

    1986-10-01

    Digital RF memories (DRFM's) are key elements for modern radar jamming. An RF signal is sampled, stored in random access memory (RAM), and later recreated from the stored data. Here the first CMOS DRFM chip, integrating static RAM, control circuitry, and two channels of shift registers, on a single chip is described. The sample rate achieved was 0.5 GHz, VLSI density was made possible by the low-power dissipation of quiescent CMOS circuits. An 8K RAM prototype chip has been built and tested.

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

    NASA Astrophysics Data System (ADS)

    Ewart, Tom; Carmichael, Stuart; Lea, Peter

    2005-09-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2002-06-01

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

  10. Oxygen plasma treated interactive polycarbonate DNA microarraying platform.

    PubMed

    Tamarit-López, Jesús; Morais, Sergi; Puchades, Rosa; Maquieira, Angel

    2011-12-21

    A novel DNA microarrying platform based on oxygen plasma activation of polycarbonate surface of compact disks (DVD) is presented. Carboxylic acid groups are generated in few seconds on polycarbonate in an efficient, fast, and clean way. Following this surface activation strategy, amino-modified oligonucleotide probes were covalently attached, reaching an immobilization density of 2 pmol cm(-2). Atomic force microscopy imaging revealed the nondestructive character of this treatment when applied for short times, allowing for disk scanning in standard DVD drives. DNA assays performed on oxygen plasma treated disks resulted very efficient with maximum hybridization yield of 93% and reaching a low limit of detection (200 pM) for perfect match synthetic oligonucleotide targets when reading the disk with a standard drive as detector. The approach was also evaluated by scoring single nucleotide polymorphisms with a discrimination ratio of 12.8. As proof of concept, the oxygen plasma treated interactive polycarbonate DNA microarraying platform was applied to the detection of PCR products of Salmonella spp., reaching a detection limit of 2 nM that corresponds to a DNA concentration of only 1 c.f.u./mL. The results confirm the suitability of the microarray platform for analysis of biological samples with high sensitivity. PMID:22044406

  11. Immobilization strategies for single-chain antibody microarrays

    SciTech Connect

    Seurynck-Servoss, Shannon L.; Baird, Cheryl L.; Miller, Keith D.; Pefaur, Noah B.; Gonzalez, Rachel M.; Apiyo, David O.; Engelmann, Heather E.; Srinivastava, Sudhir; Kagan, Jacob; Rodland, Karin D.; Zangar, Richard C.

    2008-06-01

    Sandwich enzyme-linked immunosorbent assay (ELISA) microarrays have great potential for validating biomarkers of disease. ELISA relies on robust affinity reagents that retain activity when immobilized or when labeled for detection. Single-chain antibodies (scFv) are affinity reagents that have greater potential for high-throughput production than traditional immunoglobin G (IgG). Unfortunately, scFv are typically less stabile than IgG and not always suitable for use in sandwich ELISAs. We therefore investigated different immobilization strategies and scFv structural modifications to see if we could develop a more robust scFv reagent. Two promising strategies that emerged from these studies: 1) the precapture of epitope-tagged scFv using an anti-epitope antibody and 2) the direct printing of a thioredoxin/scFv fusion protein on glass slides. The use of either strategy improved the stability of immobilized scFv and increased the sensitivity of the scFv ELISA microarray assays, although the anti-epitope precapture method had a risk of reagent transfer. Using the direct printing method, we show that anti-PSA scFv are highly specific when tested against 21 different IgG-based assays. Finally, the scFv microarray PSA assay gave comparable results (R2 = 0.95) to a commercial 96-well ELISA when tested using serum samples. Overall, these results suggest that minor modifications of the scFv protein structure are sufficiently to produce reagents that are suitable for use in multiplex assay systems.

  12. Environmental microarray analyses of Antarctic soil microbial communities.

    PubMed

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

    2009-03-01

    Antarctic ecosystems are fascinating in their limited trophic complexity, with decomposition and nutrient cycling functions being dominated by microbial activities. Not only are Antarctic habitats exposed to extreme environmental conditions, the Antarctic Peninsula is also experiencing unequalled effects of global warming. Owing to their uniqueness and the potential impact of global warming on these pristine systems, there is considerable interest in determining the structure and function of microbial communities in the Antarctic. We therefore utilized a recently designed 16S rRNA gene microarray, the PhyloChip, which targets 8741 bacterial and archaeal taxa, to interrogate microbial communities inhabiting densely vegetated and bare fell-field soils along a latitudinal gradient ranging from 51 degrees S (Falkland Islands) to 72 degrees S (Coal Nunatak). Results indicated a clear decrease in diversity with increasing latitude, with the two southernmost sites harboring the most distinct Bacterial and Archaeal communities. The microarray approach proved more sensitive in detecting the breadth of microbial diversity than polymerase chain reaction-based bacterial 16S rRNA gene libraries of modest size ( approximately 190 clones per library). Furthermore, the relative signal intensities summed for phyla and families on the PhyloChip were significantly correlated with the relative occurrence of these taxa in clone libraries. PhyloChip data were also compared with functional gene microarray data obtained earlier, highlighting numerous significant relationships and providing evidence for a strong link between community composition and functional gene distribution in Antarctic soils. Integration of these PhyloChip data with other complementary methods provides an unprecedented understanding of the microbial diversity and community structure of terrestrial Antarctic habitats. PMID:19020556

  13. Environmental microarray analyses of Antarctic soil microbial communities.

    PubMed

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

    2009-03-01

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

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

    PubMed

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

    2015-01-01

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

  15. Advancing translational research with next-generation protein microarrays.

    PubMed

    Yu, Xiaobo; Petritis, Brianne; LaBaer, Joshua

    2016-04-01

    Protein microarrays are a high-throughput technology used increasingly in translational research, seeking to apply basic science findings to enhance human health. In addition to assessing protein levels, posttranslational modifications, and signaling pathways in patient samples, protein microarrays have aided in the identification of potential protein biomarkers of disease and infection. In this perspective, the different types of full-length protein microarrays that are used in translational research are reviewed. Specific studies employing these microarrays are presented to highlight their potential in finding solutions to real clinical problems. Finally, the criteria that should be considered when developing next-generation protein microarrays are provided. PMID:26749402

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

    PubMed Central

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

    2015-01-01

    Recurrent oral ulcer seriously threatens patients’ daily life and health. This study investigated potential genes and pathways that participate in the pathogenesis of recurrent oral ulcer by high throughput bioinformatic analysis. RT-PCR and Western blot were applied to further verify screened interleukins effect. Recurrent oral ulcer related genes were collected from websites and papers, and further found out from Human Genome 280 6.0 microarray data. Each pathway of recurrent oral ulcer related genes were got through chip hybridization. RT-PCR was applied to test four recurrent oral ulcer related genes to verify the microarray data. Data transformation, scatter plot, clustering analysis, and expression pattern analysis were used to analyze recurrent oral ulcer related gene expression changes. Recurrent oral ulcer gene microarray was successfully established. Microarray showed that 551 genes involved in recurrent oral ulcer activity and 196 genes were recurrent oral ulcer related genes. Of them, 76 genes up-regulated, 62 genes down-regulated, and 58 genes up-/down-regulated. Total expression level up-regulated 752 times (60%) and down-regulated 485 times (40%). IL-2 plays an important role in the occurrence, development and recurrence of recurrent oral ulcer on the mRNA and protein levels. Gene microarray can be used to analyze potential genes and pathways in recurrent oral ulcer. IL-2 may be involved in the pathogenesis of recurrent oral ulcer. PMID:26722428

  17. A tiling microarray for global analysis of chloroplast genome expression in cucumber and other plants

    PubMed Central

    2011-01-01

    Plastids are small organelles equipped with their own genomes (plastomes). Although these organelles are involved in numerous plant metabolic pathways, current knowledge about the transcriptional activity of plastomes is limited. To solve this problem, we constructed a plastid tiling microarray (PlasTi-microarray) consisting of 1629 oligonucleotide probes. The oligonucleotides were designed based on the cucumber chloroplast genomic sequence and targeted both strands of the plastome in a non-contiguous arrangement. Up to 4 specific probes were designed for each gene/exon, and the intergenic regions were covered regularly, with 70-nt intervals. We also developed a protocol for direct chemical labeling and hybridization of as little as 2 micrograms of chloroplast RNA. We used this protocol for profiling the expression of the cucumber chloroplast plastome on the PlasTi-microarray. Owing to the high sequence similarity of plant plastomes, the newly constructed microarray can be used to study plants other than cucumber. Comparative hybridization of chloroplast transcriptomes from cucumber, Arabidopsis, tomato and spinach showed that the PlasTi-microarray is highly versatile. PMID:21952044

  18. High-quality gene assembly directly from unpurified mixtures of microarray-synthesized oligonucleotides

    PubMed Central

    Borovkov, Alex Y.; Loskutov, Andrey V.; Robida, Mark D.; Day, Kristen M.; Cano, Jose A.; Le Olson, Tien; Patel, Hetal; Brown, Kevin; Hunter, Preston D.; Sykes, Kathryn F.

    2010-01-01

    To meet the growing demand for synthetic genes more robust, scalable and inexpensive gene assembly technologies must be developed. Here, we present a protocol for high-quality gene assembly directly from low-cost marginal-quality microarray-synthesized oligonucleotides. Significantly, we eliminated the time- and money-consuming oligonucleotide purification steps through the use of hybridization-based selection embedded in the assembly process. The protocol was tested on mixtures of up to 2000 oligonucleotides eluted directly from microarrays obtained from three different chip manufacturers. These mixtures containing <5% perfect oligos, and were used directly for assembly of 27 test genes of different sizes. Gene quality was assessed by sequencing, and their activity was tested in coupled in vitro transcription/translation reactions. Genes assembled from the microarray-eluted material using the new protocol matched the quality of the genes assembled from >95% pure column-synthesized oligonucleotides by the standard protocol. Both averaged only 2.7 errors/kb, and genes assembled from microarray-eluted material without clonal selection produced only 30% less protein than sequence-confirmed clones. This report represents the first demonstration of cost-efficient gene assembly from microarray-synthesized oligonucleotides. The overall cost of assembly by this method approaches 5¢ per base, making gene synthesis more affordable than traditional cloning. PMID:20693531

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Evans, Irene M.

    2010-01-01

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

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

    PubMed

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

    2016-01-27

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

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

    PubMed Central

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

    2016-01-01

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

  3. Statistical Considerations for Analysis of Microarray Experiments

    PubMed Central

    Owzar, Kouros; Barry, William T.; Jung, Sin-Ho

    2014-01-01

    Microarray technologies enable the simultaneous interrogation of expressions from thousands of genes from a biospecimen sample taken from a patient. This large set of expressions generate a genetic profile of the patient that may be used to identify potential prognostic or predictive genes or genetic models for clinical outcomes. The aim of this article is to provide a broad overview of some of the major statistical considerations for the design and analysis of microarrays experiments conducted as correlative science studies to clinical trials. An emphasis will be placed on how the lack of understanding and improper use of statistical concepts and methods will lead to noise discovery and misinterpretation of experimental results. PMID:22212230

  4. Plasmonically amplified fluorescence bioassay with microarray format

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  5. Microarrays: how many do you need?

    PubMed

    Zien, Alexander; Fluck, Juliane; Zimmer, Ralf; Lengauer, Thomas

    2003-01-01

    We estimate the number of microarrays that is required in order to gain reliable results from a common type of study: the pairwise comparison of different classes of samples. We show that current knowledge allows for the construction of models that look realistic with respect to searches for individual differentially expressed genes and derive prototypical parameters from real data sets. Such models allow investigation of the dependence of the required number of samples on the relevant parameters: the biological variability of the samples within each class, the fold changes in expression that are desired to be detected, the detection sensitivity of the microarrays, and the acceptable error rates of the results. We supply experimentalists with general conclusions as well as a freely accessible Java applet at www.scai.fhg.de/special/bio/howmanyarrays/ for fine tuning simulations to their particular settings. PMID:12935350

  6. A Flexible Microarray Data Simulation Model

    PubMed Central

    Dembélé, Doulaye

    2013-01-01

    Microarray technology allows monitoring of gene expression profiling at the genome level. This is useful in order to search for genes involved in a disease. The performances of the methods used to select interesting genes are most often judged after other analyzes (qPCR validation, search in databases...), which are also subject to error. A good evaluation of gene selection methods is possible with data whose characteristics are known, that is to say, synthetic data. We propose a model to simulate microarray data with similar characteristics to the data commonly produced by current platforms. The parameters used in this model are described to allow the user to generate data with varying characteristics. In order to show the flexibility of the proposed model, a commented example is given and illustrated. An R package is available for immediate use.

  7. Application of DNA Microarray to Clinical Diagnostics.

    PubMed

    Patel, Ankita; Cheung, Sau W

    2016-01-01

    Microarray-based technology to conduct array comparative genomic hybridization (aCGH) has made a significant impact on the diagnosis of human genetic diseases. Such diagnoses, previously undetectable by traditional G-banding chromosome analysis, are now achieved by identifying genomic copy number variants (CNVs) using the microarray. Not only can hundreds of well-characterized genetic syndromes be detected in a single assay, but new genomic disorders and disease-causing genes can also be discovered through the utilization of aCGH technology. Although other platforms such as single nucleotide polymorphism (SNP) arrays can be used for detecting CNVs, in this chapter we focus on describing the methods for performing aCGH using Agilent oligonucleotide arrays for both prenatal (e.g., amniotic fluid and chorionic villus sample) and postnatal samples (e.g., blood).

  8. Weighted analysis of general microarray experiments

    PubMed Central

    Sjögren, Anders; Kristiansson, Erik; Rudemo, Mats; Nerman, Olle

    2007-01-01

    Background In DNA microarray experiments, measurements from different biological samples are often assumed to be independent and to have identical variance. For many datasets these assumptions have been shown to be invalid and typically lead to too optimistic p-values. A method called WAME has been proposed where a variance is estimated for each sample and a covariance is estimated for each pair of samples. The current version of WAME is, however, limited to experiments with paired design, e.g. two-channel microarrays. Results The WAME procedure is extended to general microarray experiments, making it capable of handling both one- and two-channel datasets. Two public one-channel datasets are analysed and WAME detects both unequal variances and correlations. WAME is compared to other common methods: fold-change ranking, ordinary linear model with t-tests, LIMMA and weighted LIMMA. The p-value distributions are shown to differ greatly between the examined methods. In a resampling-based simulation study, the p-values generated by WAME are found to be substantially more correct than the alternatives when a relatively small proportion of the genes is regulated. WAME is also shown to have higher power than the other methods. WAME is available as an R-package. Conclusion The WAME procedure is generalized and the limitation to paired-design microarray datasets is removed. The examined other methods produce invalid p-values in many cases, while WAME is shown to produce essentially valid p-values when a relatively small proportion of genes is regulated. WAME is also shown to have higher power than the examined alternative methods. PMID:17937807

  9. Undetected sex chromosome aneuploidy by chromosomal microarray.

    PubMed

    Markus-Bustani, Keren; Yaron, Yuval; Goldstein, Myriam; Orr-Urtreger, Avi; Ben-Shachar, Shay

    2012-11-01

    We report on a case of a female fetus found to be mosaic for Turner syndrome (45,X) and trisomy X (47,XXX). Chromosomal microarray analysis (CMA) failed to detect the aneuploidy because of a normal average dosage of the X chromosome. This case represents an unusual instance in which CMA may not detect chromosomal aberrations. Such a possibility should be taken into consideration in similar cases where CMA is used in a clinical setting.

  10. Microarray analysis in gastric cancer: A review

    PubMed Central

    D’Angelo, Giovanna; Di Rienzo, Teresa; Ojetti, Veronica

    2014-01-01

    Gastric cancer is one of the most common tumors worldwide. Although several treatment options have been developed, the mortality rate is increasing. Lymph node involvement is considered the most reliable prognostic indicator in gastric cancer. Early diagnosis improves the survival rate of patients and increases the likelihood of successful treatment. The most reliable diagnostic method is endoscopic examination, however, it is expensive and not feasible in poorer countries. Therefore, many innovative techniques have been studied to develop a new non-invasive screening test and to identify specific serum biomarkers. DNA microarray analysis is one of the new technologies able to measure the expression levels of a large number of genes simultaneously. It is possible to define the gene expression profile of the tumor and to correlate it with the prognosis and metastasis formation. Several studies in the literature have been published on the role of microarray analysis in gastric cancer and the mechanisms of proliferation and metastasis formation. The aim of this review is to analyze the importance of microarray analysis and its clinical applications to better define the genetic characteristics of gastric cancer and its possible implications in a more decisive treatment. PMID:25232233

  11. Repeatability of published microarray gene expression analyses.

    PubMed

    Ioannidis, John P A; Allison, David B; Ball, Catherine A; Coulibaly, Issa; Cui, Xiangqin; Culhane, Aedín C; Falchi, Mario; Furlanello, Cesare; Game, Laurence; Jurman, Giuseppe; Mangion, Jon; Mehta, Tapan; Nitzberg, Michael; Page, Grier P; Petretto, Enrico; van Noort, Vera

    2009-02-01

    Given the complexity of microarray-based gene expression studies, guidelines encourage transparent design and public data availability. Several journals require public data deposition and several public databases exist. However, not all data are publicly available, and even when available, it is unknown whether the published results are reproducible by independent scientists. Here we evaluated the replication of data analyses in 18 articles on microarray-based gene expression profiling published in Nature Genetics in 2005-2006. One table or figure from each article was independently evaluated by two teams of analysts. We reproduced two analyses in principle and six partially or with some discrepancies; ten could not be reproduced. The main reason for failure to reproduce was data unavailability, and discrepancies were mostly due to incomplete data annotation or specification of data processing and analysis. Repeatability of published microarray studies is apparently limited. More strict publication rules enforcing public data availability and explicit description of data processing and analysis should be considered.

  12. An imputation approach for oligonucleotide microarrays.

    PubMed

    Li, Ming; Wen, Yalu; Lu, Qing; Fu, Wenjiang J

    2013-01-01

    Oligonucleotide microarrays are commonly adopted for detecting and qualifying the abundance of molecules in biological samples. Analysis of microarray data starts with recording and interpreting hybridization signals from CEL images. However, many CEL images may be blemished by noises from various sources, observed as "bright spots", "dark clouds", and "shadowy circles", etc. It is crucial that these image defects are correctly identified and properly processed. Existing approaches mainly focus on detecting defect areas and removing affected intensities. In this article, we propose to use a mixed effect model for imputing the affected intensities. The proposed imputation procedure is a single-array-based approach which does not require any biological replicate or between-array normalization. We further examine its performance by using Affymetrix high-density SNP arrays. The results show that this imputation procedure significantly reduces genotyping error rates. We also discuss the necessary adjustments for its potential extension to other oligonucleotide microarrays, such as gene expression profiling. The R source code for the implementation of approach is freely available upon request.

  13. High-Throughput Enzyme Kinetics Using Microarrays

    SciTech Connect

    Guoxin Lu; Edward S. Yeung

    2007-11-01

    We report a microanalytical method to study enzyme kinetics. The technique involves immobilizing horseradish peroxidase on a poly-L-lysine (PLL)- coated glass slide in a microarray format, followed by applying substrate solution onto the enzyme microarray. Enzyme molecules are immobilized on the PLL-coated glass slide through electrostatic interactions, and no further modification of the enzyme or glass slide is needed. In situ detection of the products generated on the enzyme spots is made possible by monitoring the light intensity of each spot using a scientific-grade charged-coupled device (CCD). Reactions of substrate solutions of various types and concentrations can be carried out sequentially on one enzyme microarray. To account for the loss of enzyme from washing in between runs, a standard substrate solution is used for calibration. Substantially reduced amounts of substrate solution are consumed for each reaction on each enzyme spot. The Michaelis constant K{sub m} obtained by using this method is comparable to the result for homogeneous solutions. Absorbance detection allows universal monitoring, and no chemical modification of the substrate is needed. High-throughput studies of native enzyme kinetics for multiple enzymes are therefore possible in a simple, rapid, and low-cost manner.

  14. Integrating data from heterogeneous DNA microarray platforms.

    PubMed

    Valente, Eduardo; Rocha, Miguel

    2015-01-01

    DNA microarrays are one of the most used technologies for gene expression measurement. However, there are several distinct microarray platforms, from different manufacturers, each with its own measurement protocol, resulting in data that can hardly be compared or directly integrated. Data integration from multiple sources aims to improve the assertiveness of statistical tests, reducing the data dimensionality problem. The integration of heterogeneous DNA microarray platforms comprehends a set of tasks that range from the re-annotation of the features used on gene expression, to data normalization and batch effect elimination. In this work, a complete methodology for gene expression data integration and application is proposed, which comprehends a transcript-based re-annotation process and several methods for batch effect attenuation. The integrated data will be used to select the best feature set and learning algorithm for a brain tumor classification case study. The integration will consider data from heterogeneous Agilent and Affymetrix platforms, collected from public gene expression databases, such as The Cancer Genome Atlas and Gene Expression Omnibus. PMID:26673932

  15. Development and Applications of the Lectin Microarray.

    PubMed

    Hirabayashi, Jun; Kuno, Atsushi; Tateno, Hiroaki

    2015-01-01

    The lectin microarray is an emerging technology for glycomics. It has already found maximum use in diverse fields of glycobiology by providing simple procedures for differential glycan profiling in a rapid and high-throughput manner. Since its first appearance in the literature in 2005, many application methods have been developed essentially on the same platform, comprising a series of glycan-binding proteins immobilized on an appropriate substrate such as a glass slide. Because the lectin microarray strategy does not require prior liberation of glycans from the core protein in glycoprotein analysis, it should encourage researchers not familiar with glycotechnology to use glycan analysis in future work. This feasibility should provide a broader range of experimental scientists with good opportunities to investigate novel aspects of glycoscience. Applications of the technology include not only basic sciences but also the growing fields of bio-industry. This chapter describes first the essence of glycan profiling and the basic fabrication of the lectin microarray for this purpose. In the latter part the focus is on diverse applications to both structural and functional glycomics, with emphasis on the wide applicability now available with this new technology. Finally, the importance of developing advanced lectin engineering is discussed.

  16. Metadata management and semantics in microarray repositories.

    PubMed

    Kocabaş, F; Can, T; Baykal, N

    2011-12-01

    The number of microarray and other high-throughput experiments on primary repositories keeps increasing as do the size and complexity of the results in response to biomedical investigations. Initiatives have been started on standardization of content, object model, exchange format and ontology. However, there are backlogs and inability to exchange data between microarray repositories, which indicate that there is a great need for a standard format and data management. We have introduced a metadata framework that includes a metadata card and semantic nets that make experimental results visible, understandable and usable. These are encoded in syntax encoding schemes and represented in RDF (Resource Description Frame-word), can be integrated with other metadata cards and semantic nets, and can be exchanged, shared and queried. We demonstrated the performance and potential benefits through a case study on a selected microarray repository. We concluded that the backlogs can be reduced and that exchange of information and asking of knowledge discovery questions can become possible with the use of this metadata framework. PMID:24052712

  17. Chicken sperm transcriptome profiling by microarray analysis.

    PubMed

    Singh, R P; Shafeeque, C M; Sharma, S K; Singh, R; Mohan, J; Sastry, K V H; Saxena, V K; Azeez, P A

    2016-03-01

    It has been confirmed that mammalian sperm contain thousands of functional RNAs, and some of them have vital roles in fertilization and early embryonic development. Therefore, we attempted to characterize transcriptome of the sperm of fertile chickens using microarray analysis. Spermatozoal RNA was pooled from 10 fertile males and used for RNA preparation. Prior to performing the microarray, RNA quality was assessed using a bioanalyzer, and gDNA and somatic cell RNA contamination was assessed by CD4 and PTPRC gene amplification. The chicken sperm transcriptome was cross-examined by analysing sperm and testes RNA on a 4 × 44K chicken array, and results were verified by RT-PCR. Microarray analysis identified 21,639 predominantly nuclear-encoded transcripts in chicken sperm. The majority (66.55%) of the sperm transcripts were shared with the testes, while surprisingly, 33.45% transcripts were detected (raw signal intensity greater than 50) only in the sperm and not in the testes. The greatest proportion of up-regulated transcripts were responsible for signal transduction (63.20%) followed by embryonic development (56.76%) and cell structure (56.25%). Of the 20 most abundant transcripts, 18 remain uncharacterized, whereas the least abundant genes were mostly associated with the ribosome. These findings lay a foundation for more detailed investigations on sperm RNAs in chickens to identify sperm-based biomarkers for fertility.

  18. [Genomic medicine. Polymorphisms and microarray applications].

    PubMed

    Spalvieri, Mónica P; Rotenberg, Rosa G

    2004-01-01

    This update shows new concepts related to the significance of DNA variations among individuals, as well as to their detection by using a new technology. The sequencing of the human genome is only the beginning of what will enable us to understand genetic diversity. The unit of DNA variability is the polymorphism of a single nucleotide (SNP). At present, studies on SNPs are restricted to basic research but the large number of papers on this subject makes feasible their entrance into clinical practice. We illustrate here the use of SNPs as molecular markers in ethnical genotyping, gene expression in some diseases and as potential targets in pharmacological response, and also introduce the technology of arrays. Microarrays experiments allow the quantification and comparison of gene expression on a large scale, at the same time, by using special chips and array designs. Conventional methods provide data from up to 20 genes, while a single microarray may provide information about thousands of them simultaneously, leading to a more rapid and accurate genotyping. Biotechnology improvements will facilitate our knowledge of each gene sequence, the frequency and exact location of SNPs and their influence on cellular behavior. Although experimental efficiency and validity of results from microarrays are still controversial, the knowledge and characterization of a patient's genetic profile will lead, undoubtedly, to advances in prevention, diagnosis, prognosis and treatment of human diseases. PMID:15637833

  19. Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus

    NASA Astrophysics Data System (ADS)

    Lee, Jung-Rok; Haddon, D. James; Wand, Hannah E.; Price, Jordan V.; Diep, Vivian K.; Hall, Drew A.; Petri, Michelle; Baechler, Emily C.; Balboni, Imelda M.; Utz, Paul J.; Wang, Shan X.

    2016-06-01

    High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides. We used the microarrays to analyze serum samples from SLE patients and found individuals with high chemokine scores had significantly greater reactivity to 13 autoantigens than individuals with low chemokine scores. Our findings demonstrate that multiple autoantibodies, including antibodies to U1-70K and modified histone H2B tails, are associated with IFN dysregulation in SLE. Further, they show the microarrays are capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice.

  20. The Potentials and Pitfalls of Microarrays in Neglected Tropical Diseases: A Focus on Human Filarial Infections.

    PubMed

    Kwarteng, Alexander; Ahuno, Samuel Terkper

    2016-01-01

    Data obtained from expression microarrays enables deeper understanding of the molecular signatures of infectious diseases. It provides rapid and accurate information on how infections affect the clustering of gene expression profiles, pathways and networks that are transcriptionally active during various infection states compared to conventional diagnostic methods, which primarily focus on single genes or proteins. Thus, microarray technologies offer advantages in understanding host-parasite interactions associated with filarial infections. More importantly, the use of these technologies can aid diagnostics and helps translate current genomic research into effective treatment and interventions for filarial infections. Studying immune responses via microarray following infection can yield insight into genetic pathways and networks that can have a profound influence on the development of anti-parasitic vaccines. PMID:27600086

  1. Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus

    PubMed Central

    Lee, Jung-Rok; Haddon, D. James; Wand, Hannah E.; Price, Jordan V.; Diep, Vivian K.; Hall, Drew A.; Petri, Michelle; Baechler, Emily C.; Balboni, Imelda M.; Utz, Paul J.; Wang, Shan X.

    2016-01-01

    High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides. We used the microarrays to analyze serum samples from SLE patients and found individuals with high chemokine scores had significantly greater reactivity to 13 autoantigens than individuals with low chemokine scores. Our findings demonstrate that multiple autoantibodies, including antibodies to U1-70K and modified histone H2B tails, are associated with IFN dysregulation in SLE. Further, they show the microarrays are capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice. PMID:27279139

  2. The Potentials and Pitfalls of Microarrays in Neglected Tropical Diseases: A Focus on Human Filarial Infections

    PubMed Central

    Kwarteng, Alexander; Ahuno, Samuel Terkper

    2016-01-01

    Data obtained from expression microarrays enables deeper understanding of the molecular signatures of infectious diseases. It provides rapid and accurate information on how infections affect the clustering of gene expression profiles, pathways and networks that are transcriptionally active during various infection states compared to conventional diagnostic methods, which primarily focus on single genes or proteins. Thus, microarray technologies offer advantages in understanding host-parasite interactions associated with filarial infections. More importantly, the use of these technologies can aid diagnostics and helps translate current genomic research into effective treatment and interventions for filarial infections. Studying immune responses via microarray following infection can yield insight into genetic pathways and networks that can have a profound influence on the development of anti-parasitic vaccines. PMID:27600086

  3. Single Event Upset Behavior of CMOS Static RAM Cells

    NASA Technical Reports Server (NTRS)

    Lieneweg, Udo; Jeppson, Kjell O.; Buehler, Martin G.

    1993-01-01

    An improved state-space analysis of the CMOS static RAM cell is presented. Introducing theconcept of the dividing line, the critical charge for heavy-ion-induced upset of memory cells can becalculated considering symmetrical as well as asymmetrical capacitive loads. From the criticalcharge, the upset-rate per bit-day for static RAMs can be estimated.

  4. CCD AND PIN-CMOS DEVELOPMENTS FOR LARGE OPTICAL TELESCOPE.

    SciTech Connect

    RADEKA, V.

    2006-04-03

    Higher quantum efficiency in near-IR, narrower point spread function and higher readout speed than with conventional sensors have been receiving increased emphasis in the development of CCDs and silicon PIN-CMOS sensors for use in large optical telescopes. Some key aspects in the development of such devices are reviewed.

  5. CMOS Ultra Low Power Radiation Tolerant (CULPRiT) Microelectronics

    NASA Technical Reports Server (NTRS)

    Yeh, Penshu; Maki, Gary

    2007-01-01

    Space Electronics needs Radiation Tolerance or hardness to withstand the harsh space environment: high-energy particles can change the state of the electronics or puncture transistors making them disfunctional. This viewgraph document reviews the use of CMOS Ultra Low Power Radiation Tolerant circuits for NASA's electronic requirements.

  6. Effects Of Dose Rates On Radiation Damage In CMOS Parts

    NASA Technical Reports Server (NTRS)

    Goben, Charles A.; Coss, James R.; Price, William E.

    1990-01-01

    Report describes measurements of effects of ionizing-radiation dose rate on consequent damage to complementary metal oxide/semiconductor (CMOS) electronic devices. Depending on irradiation time and degree of annealing, survivability of devices in outer space, or after explosion of nuclear weapons, enhanced. Annealing involving recovery beyond pre-irradiation conditions (rebound) detrimental. Damage more severe at lower dose rates.

  7. Characterisation of a CMOS charge transfer device for TDI imaging

    NASA Astrophysics Data System (ADS)

    Rushton, J.; Holland, A.; Stefanov, K.; Mayer, F.

    2015-03-01

    The performance of a prototype true charge transfer imaging sensor in CMOS is investigated. The finished device is destined for use in TDI applications, especially Earth-observation, and to this end radiation tolerance must be investigated. Before this, complete characterisation is required. This work starts by looking at charge transfer inefficiency and then investigates responsivity using mean-variance techniques.

  8. Fabrication and Characterization of CMOS-MEMS Thermoelectric Micro Generators

    PubMed Central

    Kao, Pin-Hsu; Shih, Po-Jen; Dai, Ching-Liang; Liu, Mao-Chen

    2010-01-01

    This work presents a thermoelectric micro generator fabricated by the commercial 0.35 μm complementary metal oxide semiconductor (CMOS) process and the post-CMOS process. The micro generator is composed of 24 thermocouples in series. Each thermocouple is constructed by p-type and n-type polysilicon strips. The output power of the generator depends on the temperature difference between the hot and cold parts in the thermocouples. In order to prevent heat-receiving in the cold part in the thermocouples, the cold part is covered with a silicon dioxide layer with low thermal conductivity to insulate the heat source. The hot part of the thermocouples is suspended and connected to an aluminum plate, to increases the heat-receiving area in the hot part. The generator requires a post-CMOS process to release the suspended structures. The post-CMOS process uses an anisotropic dry etching to remove the oxide sacrificial layer and an isotropic dry etching to etch the silicon substrate. Experimental results show that the micro generator has an output voltage of 67 μV at the temperature difference of 1 K. PMID:22205869

  9. CMOS VLSI Layout and Verification of a SIMD Computer

    NASA Technical Reports Server (NTRS)

    Zheng, Jianqing

    1996-01-01

    A CMOS VLSI layout and verification of a 3 x 3 processor parallel computer has been completed. The layout was done using the MAGIC tool and the verification using HSPICE. Suggestions for expanding the computer into a million processor network are presented. Many problems that might be encountered when implementing a massively parallel computer are discussed.

  10. CMOS-compatible LVOF-based visible microspectrometer

    NASA Astrophysics Data System (ADS)

    Emadi, Arvin; Wu, Huaiwen; de Graaf, Ger; Wolffenbuttel, Reinoud F.

    2010-04-01

    This paper reports on a CMOS-Compatible Linear Variable Optical Filter (LVOF) visible micro-spectrometer. The CMOS-compatible post process for fabrication of the LVOF has been used for integration of the LVOF with a CMOS chip containing a 128-element photodiode array and readout circuitry. Fabrication of LVOF involves a process for fabrication of very small taper angles, ranging from 0.001° to 0.1°, in SiO2. These layers can be fabricated flexibly in a resist layer by just one lithography step and a subsequent reflow process. The 3D pattern of the resist structures is subsequently transferred into SiO2 by appropriate etching. Complete LVOF fabrication involves CMOS-compatible deposition of a lower dielectric mirror using a stack of dielectrics on the wafer, tapered layer formation and deposition of the top dielectric mirror. The LVOF has been optimized for 580 nm - 720 nm spectral operating range and has also been mounted on a CCD camera for characterization. The design of LVOF micro-spectrometer, the fabrication and characterization results are presented.

  11. Optical and noise performance of CMOS solid-state photomultipliers

    NASA Astrophysics Data System (ADS)

    Chen, Xiao Jie; Johnson, Erik B.; Staples, Christopher J.; Chapman, Eric; Alberghini, Guy; Christian, James F.

    2010-08-01

    Solid-state photomultipliers (SSPM) are photodetectors composed of avalanche photodiode pixel arrays operating in Geiger mode (biased above diode breakdown voltage). They are built using CMOS technology and can be used in a variety of applications in high energy and nuclear physics, medical imaging and homeland security related areas. The high gain and low cost associated with the SSPM makes it an attractive alternative to existing photodetectors such as the photomultiplier tube (PMT). The capability of integrating CMOS on-chip readout circuitry on the same substrate as the SSPM also provides a compact and low-power-consumption solution to photodetector applications with stringent area and power requirements. The optical performance of the SSPM, specifically the detection and quantum efficiencies, can depend on the geometry and the doping profile associated with each photodiode pixel. The noise associated with the SSPM not only includes dark noise from each pixel, but also consists of excess noise terms due to after pulsing and inter-pixel cross talk. The magnitude of the excess noise terms can depend on biasing conditions, temperature, as well as pixel and inter-pixel dimensions. We present the optical and noise performance of SSPMs fabricated in a conventional CMOS process, and demonstrate the dependence of the SSPM performance on pixel/inter-pixel geometry, doping profile, temperature, as well as bias conditions. The continuing development of CMOS SSPM technology demonstrated here shows that low cost and high performance solid state photodetectors are viable solutions for many existing and future optical detection applications.

  12. Simulation toolkit with CMOS detector in the framework of hadrontherapy

    NASA Astrophysics Data System (ADS)

    Rescigno, R.; Finck, Ch.; Juliani, D.; Baudot, J.; Dauvergne, D.; Dedes, G.; Krimmer, J.; Ray, C.; Reithinger, V.; Rousseau, M.; Testa, E.; Winter, M.

    2014-03-01

    Proton imaging can be seen as a powerful technique for on-line monitoring of ion range during carbon ion therapy irradiation. The protons detection technique uses, as three-dimensional tracking system, a set of CMOS sensor planes. A simulation toolkit based on GEANT4 and ROOT is presented including detector response and reconstruction algorithm.

  13. Attributes and drawbacks of submicron CMOS for IR FPA readouts

    NASA Astrophysics Data System (ADS)

    Kozlowski, L. J.

    1998-09-01

    The availability of submicron CMOS has enabled the development of shingle-chip IR cameras having performance capabilities and on-chip functions which were previously impossible. Sensor designers are, however, encoutering and overcoming several challanges including steadily decreasing operating voltage.

  14. Performance of CMOS ternary full adder at liquid nitrogen temperature

    NASA Astrophysics Data System (ADS)

    Srivastava, A.; Venkatapathy, K.

    We have designed, implemented and studied the performance at liquid nitrogen temperature (77 K) of a CMOS ternary full adder and its building blocks, the simple ternary inverter (STI), positive ternary inverter (PTI) and negative ternary inverter (NTI), and compared the corresponding performance at room temperature (300 K). The ternary full adder has been fabricated in 2 μm, n-well CMOS through MOSIS. In a ternary full adder, the basic building blocks, the PTI and NTI, have been developed using combinations of a CMOS inverter and transmission gate(s). There is close agreement between the simulated and measured voltage transfer characteristics and noise margins of ternary-valued devices. The measured transient times for the NTI, PTI and ternary full adder at 77 K show an improvement by a factor of ≈1.5-2.5 over the corresponding values at 300 K. The present design does not use linear resistors and depletion-mode MOSFETs to implement the ternary full adder and its building blocks, and is fully compatible with current CMOS technology.

  15. Research-grade CMOS image sensors for remote sensing applications

    NASA Astrophysics Data System (ADS)

    Saint-Pe, Olivier; Tulet, Michel; Davancens, Robert; Larnaudie, Franck; Magnan, Pierre; Martin-Gonthier, Philippe; Corbiere, Franck; Belliot, Pierre; Estribeau, Magali

    2004-11-01

    Imaging detectors are key elements for optical instruments and sensors on board space missions dedicated to Earth observation (high resolution imaging, atmosphere spectroscopy...), Solar System exploration (micro cameras, guidance for autonomous vehicle...) and Universe observation (space telescope focal planes, guiding sensors...). This market has been dominated by CCD technology for long. Since the mid-90s, CMOS Image Sensors (CIS) have been competing with CCDs for consumer domains (webcams, cell phones, digital cameras...). Featuring significant advantages over CCD sensors for space applications (lower power consumption, smaller system size, better radiations behaviour...), CMOS technology is also expanding in this field, justifying specific R&D and development programs funded by national and European space agencies (mainly CNES, DGA and ESA). All along the 90s and thanks to their increasingly improving performances, CIS have started to be successfully used for more and more demanding space applications, from vision and control functions requiring low-level performances to guidance applications requiring medium-level performances. Recent technology improvements have made possible the manufacturing of research-grade CIS that are able to compete with CCDs in the high-performances arena. After an introduction outlining the growing interest of optical instruments designers for CMOS image sensors, this paper will present the existing and foreseen ways to reach high-level electro-optics performances for CIS. The developments and performances of CIS prototypes built using an imaging CMOS process will be presented in the corresponding section.

  16. Research-grade CMOS image sensors for demanding space applications

    NASA Astrophysics Data System (ADS)

    Saint-Pé, Olivier; Tulet, Michel; Davancens, Robert; Larnaudie, Franck; Magnan, Pierre; Corbière, Franck; Martin-Gonthier, Philippe; Belliot, Pierre

    2004-06-01

    Imaging detectors are key elements for optical instruments and sensors on board space missions dedicated to Earth observation (high resolution imaging, atmosphere spectroscopy...), Solar System exploration (micro cameras, guidance for autonomous vehicle...) and Universe observation (space telescope focal planes, guiding sensors...). This market has been dominated by CCD technology for long. Since the mid-90s, CMOS Image Sensors (CIS) have been competing with CCDs for more and more consumer domains (webcams, cell phones, digital cameras...). Featuring significant advantages over CCD sensors for space applications (lower power consumption, smaller system size, better radiations behaviour...), CMOS technology is also expanding in this field, justifying specific R&D and development programs funded by national and European space agencies (mainly CNES, DGA, and ESA). All along the 90s and thanks to their increasingly improving performances, CIS have started to be successfully used for more and more demanding applications, from vision and control functions requiring low-level performances to guidance applications requiring medium-level performances. Recent technology improvements have made possible the manufacturing of research-grade CIS that are able to compete with CCDs in the high-performances arena. After an introduction outlining the growing interest of optical instruments designers for CMOS image sensors, this talk will present the existing and foreseen ways to reach high-level electro-optics performances for CIS. The developments of CIS prototypes built using an imaging CMOS process and of devices based on improved designs will be presented.

  17. Direct readout of gaseous detectors with tiled CMOS circuits

    NASA Astrophysics Data System (ADS)

    Visschers, J. L.; Blanco Carballo, V.; Chefdeville, M.; Colas, P.; van der Graaf, H.; Schmitz, J.; Smits, S.; Timmermans, J.

    2007-03-01

    A coordinated design effort is underway, exploring the three-dimensional direct readout of gaseous detectors by an anode plate equipped with a tiled array of many CMOS pixel readout ASICs, having amplification grids integrated on their topsides and being contacted on their backside.

  18. Distinct development patterns of c-mos protooncogene expression in female and male mouse germ cells

    SciTech Connect

    Mutter, G.L.; Wolgemuth, D.J.

    1987-08-01

    The protooncogene c-mos is expressed in murine reproductive tissues, producing transcripts of 1.7 and 1.4 kilobases in testis and ovary, respectively. In situ hybridization analysis of c-mos expression in histological sections of mouse ovaries revealed that oocytes are the predominant if not exclusive source of c-mos transcripts. /sup 35/S- or /sup 32/P-labelled RNA probes were transcribed. c-mos transcripts accumulate in growing oocytes, increasing 40- to 90-fold during oocyte and follicular development. c-mos transcripts were also detected in male germ cells and are most abundant after the cells have entered the haploid stage of spermatogenesis. This developmentally regulated pattern of c-mos expression in oocytes and spermatogenic cells suggest that the c-mos gene product may have a function in normal germ-cell differentiation or early embryogenesis.

  19. Hybrid CMOS SiPIN detectors as astronomical imagers

    NASA Astrophysics Data System (ADS)

    Simms, Lance Michael

    Charge Coupled Devices (CCDs) have dominated optical and x-ray astronomy since their inception in 1969. Only recently, through improvements in design and fabrication methods, have imagers that use Complimentary Metal Oxide Semiconductor (CMOS) technology gained ground on CCDs in scientific imaging. We are now in the midst of an era where astronomers might begin to design optical telescope cameras that employ CMOS imagers. The first three chapters of this dissertation are primarily composed of introductory material. In them, we discuss the potential advantages that CMOS imagers offer over CCDs in astronomical applications. We compare the two technologies in terms of the standard metrics used to evaluate and compare scientific imagers: dark current, read noise, linearity, etc. We also discuss novel features of CMOS devices and the benefits they offer to astronomy. In particular, we focus on a specific kind of hybrid CMOS sensor that uses Silicon PIN photodiodes to detect optical light in order to overcome deficiencies of commercial CMOS sensors. The remaining four chapters focus on a specific type of hybrid CMOS Silicon PIN sensor: the Teledyne Hybrid Visible Silicon PIN Imager (HyViSI). In chapters four and five, results from testing HyViSI detectors in the laboratory and at the Kitt Peak 2.1m telescope are presented. We present our laboratory measurements of the standard detector metrics for a number of HyViSI devices, ranging from 1k×1k to 4k×4k format. We also include a description of the SIDECAR readout circuit that was used to control the detectors. We then show how they performed at the telescope in terms of photometry, astrometry, variability measurement, and telescope focusing and guiding. Lastly, in the final two chapters we present results on detector artifacts such as pixel crosstalk, electronic crosstalk, and image persistence. One form of pixel crosstalk that has not been discussed elsewhere in the literature, which we refer to as Interpixel Charge

  20. DNA Microarray for Detection of Gastrointestinal Viruses

    PubMed Central

    Martínez, Miguel A.; Soto-del Río, María de los Dolores; Gutiérrez, Rosa María; Chiu, Charles Y.; Greninger, Alexander L.; Contreras, Juan Francisco; López, Susana; Arias, Carlos F.

    2014-01-01

    Gastroenteritis is a clinical illness of humans and other animals that is characterized by vomiting and diarrhea and caused by a variety of pathogens, including viruses. An increasing number of viral species have been associated with gastroenteritis or have been found in stool samples as new molecular tools have been developed. In this work, a DNA microarray capable in theory of parallel detection of more than 100 viral species was developed and tested. Initial validation was done with 10 different virus species, and an additional 5 species were validated using clinical samples. Detection limits of 1 × 103 virus particles of Human adenovirus C (HAdV), Human astrovirus (HAstV), and group A Rotavirus (RV-A) were established. Furthermore, when exogenous RNA was added, the limit for RV-A detection decreased by one log. In a small group of clinical samples from children with gastroenteritis (n = 76), the microarray detected at least one viral species in 92% of the samples. Single infection was identified in 63 samples (83%), and coinfection with more than one virus was identified in 7 samples (9%). The most abundant virus species were RV-A (58%), followed by Anellovirus (15.8%), HAstV (6.6%), HAdV (5.3%), Norwalk virus (6.6%), Human enterovirus (HEV) (9.2%), Human parechovirus (1.3%), Sapporo virus (1.3%), and Human bocavirus (1.3%). To further test the specificity and sensitivity of the microarray, the results were verified by reverse transcription-PCR (RT-PCR) detection of 5 gastrointestinal viruses. The RT-PCR assay detected a virus in 59 samples (78%). The microarray showed good performance for detection of RV-A, HAstV, and calicivirus, while the sensitivity for HAdV and HEV was low. Furthermore, some discrepancies in detection of mixed infections were observed and were addressed by reverse transcription-quantitative PCR (RT-qPCR) of the viruses involved. It was observed that differences in the amount of genetic material favored the detection of the most abundant

  1. DNA microarray for detection of gastrointestinal viruses.

    PubMed

    Martínez, Miguel A; Soto-Del Río, María de Los Dolores; Gutiérrez, Rosa María; Chiu, Charles Y; Greninger, Alexander L; Contreras, Juan Francisco; López, Susana; Arias, Carlos F; Isa, Pavel

    2015-01-01

    Gastroenteritis is a clinical illness of humans and other animals that is characterized by vomiting and diarrhea and caused by a variety of pathogens, including viruses. An increasing number of viral species have been associated with gastroenteritis or have been found in stool samples as new molecular tools have been developed. In this work, a DNA microarray capable in theory of parallel detection of more than 100 viral species was developed and tested. Initial validation was done with 10 different virus species, and an additional 5 species were validated using clinical samples. Detection limits of 1 × 10(3) virus particles of Human adenovirus C (HAdV), Human astrovirus (HAstV), and group A Rotavirus (RV-A) were established. Furthermore, when exogenous RNA was added, the limit for RV-A detection decreased by one log. In a small group of clinical samples from children with gastroenteritis (n = 76), the microarray detected at least one viral species in 92% of the samples. Single infection was identified in 63 samples (83%), and coinfection with more than one virus was identified in 7 samples (9%). The most abundant virus species were RV-A (58%), followed by Anellovirus (15.8%), HAstV (6.6%), HAdV (5.3%), Norwalk virus (6.6%), Human enterovirus (HEV) (9.2%), Human parechovirus (1.3%), Sapporo virus (1.3%), and Human bocavirus (1.3%). To further test the specificity and sensitivity of the microarray, the results were verified by reverse transcription-PCR (RT-PCR) detection of 5 gastrointestinal viruses. The RT-PCR assay detected a virus in 59 samples (78%). The microarray showed good performance for detection of RV-A, HAstV, and calicivirus, while the sensitivity for HAdV and HEV was low. Furthermore, some discrepancies in detection of mixed infections were observed and were addressed by reverse transcription-quantitative PCR (RT-qPCR) of the viruses involved. It was observed that differences in the amount of genetic material favored the detection of the most abundant

  2. A microarray for assessing transcription from pelagic marine microbial taxa

    PubMed Central

    Shilova, Irina N; Robidart, Julie C; James Tripp, H; Turk-Kubo, Kendra; Wawrik, Boris; Post, Anton F; Thompson, Anne W; Ward, Bess; Hollibaugh, James T; Millard, Andy; Ostrowski, Martin; J Scanlan, David; Paerl, Ryan W; Stuart, Rhona; Zehr, Jonathan P

    2014-01-01

    Metagenomic approaches have revealed unprecedented genetic diversity within microbial communities across vast expanses of the world's oceans. Linking this genetic diversity with key metabolic and cellular activities of microbial assemblages is a fundamental challenge. Here we report on a collaborative effort to design MicroTOOLs (Microbiological Targets for Ocean Observing Laboratories), a high-density oligonucleotide microarray that targets functional genes of diverse taxa in pelagic and coastal marine microbial communities. MicroTOOLs integrates nucleotide sequence information from disparate data types: genomes, PCR-amplicons, metagenomes, and metatranscriptomes. It targets 19 400 unique sequences over 145 different genes that are relevant to stress responses and microbial metabolism across the three domains of life and viruses. MicroTOOLs was used in a proof-of-concept experiment that compared the functional responses of microbial communities following Fe and P enrichments of surface water samples from the North Pacific Subtropical Gyre. We detected transcription of 68% of the gene targets across major taxonomic groups, and the pattern of transcription indicated relief from Fe limitation and transition to N limitation in some taxa. Prochlorococcus (eHLI), Synechococcus (sub-cluster 5.3) and Alphaproteobacteria SAR11 clade (HIMB59) showed the strongest responses to the Fe enrichment. In addition, members of uncharacterized lineages also responded. The MicroTOOLs microarray provides a robust tool for comprehensive characterization of major functional groups of microbes in the open ocean, and the design can be easily amended for specific environments and research questions. PMID:24477198

  3. A microarray for assessing transcription from pelagic marine microbial taxa.

    PubMed

    Shilova, Irina N; Robidart, Julie C; James Tripp, H; Turk-Kubo, Kendra; Wawrik, Boris; Post, Anton F; Thompson, Anne W; Ward, Bess; Hollibaugh, James T; Millard, Andy; Ostrowski, Martin; Scanlan, David J; Paerl, Ryan W; Stuart, Rhona; Zehr, Jonathan P

    2014-07-01

    Metagenomic approaches have revealed unprecedented genetic diversity within microbial communities across vast expanses of the world's oceans. Linking this genetic diversity with key metabolic and cellular activities of microbial assemblages is a fundamental challenge. Here we report on a collaborative effort to design MicroTOOLs (Microbiological Targets for Ocean Observing Laboratories), a high-density oligonucleotide microarray that targets functional genes of diverse taxa in pelagic and coastal marine microbial communities. MicroTOOLs integrates nucleotide sequence information from disparate data types: genomes, PCR-amplicons, metagenomes, and metatranscriptomes. It targets 19 400 unique sequences over 145 different genes that are relevant to stress responses and microbial metabolism across the three domains of life and viruses. MicroTOOLs was used in a proof-of-concept experiment that compared the functional responses of microbial communities following Fe and P enrichments of surface water samples from the North Pacific Subtropical Gyre. We detected transcription of 68% of the gene targets across major taxonomic groups, and the pattern of transcription indicated relief from Fe limitation and transition to N limitation in some taxa. Prochlorococcus (eHLI), Synechococcus (sub-cluster 5.3) and Alphaproteobacteria SAR11 clade (HIMB59) showed the strongest responses to the Fe enrichment. In addition, members of uncharacterized lineages also responded. The MicroTOOLs microarray provides a robust tool for comprehensive characterization of major functional groups of microbes in the open ocean, and the design can be easily amended for specific environments and research questions. PMID:24477198

  4. A microarray for assessing transcription from pelagic marine microbial taxa.

    PubMed

    Shilova, Irina N; Robidart, Julie C; James Tripp, H; Turk-Kubo, Kendra; Wawrik, Boris; Post, Anton F; Thompson, Anne W; Ward, Bess; Hollibaugh, James T; Millard, Andy; Ostrowski, Martin; Scanlan, David J; Paerl, Ryan W; Stuart, Rhona; Zehr, Jonathan P

    2014-07-01

    Metagenomic approaches have revealed unprecedented genetic diversity within microbial communities across vast expanses of the world's oceans. Linking this genetic diversity with key metabolic and cellular activities of microbial assemblages is a fundamental challenge. Here we report on a collaborative effort to design MicroTOOLs (Microbiological Targets for Ocean Observing Laboratories), a high-density oligonucleotide microarray that targets functional genes of diverse taxa in pelagic and coastal marine microbial communities. MicroTOOLs integrates nucleotide sequence information from disparate data types: genomes, PCR-amplicons, metagenomes, and metatranscriptomes. It targets 19 400 unique sequences over 145 different genes that are relevant to stress responses and microbial metabolism across the three domains of life and viruses. MicroTOOLs was used in a proof-of-concept experiment that compared the functional responses of microbial communities following Fe and P enrichments of surface water samples from the North Pacific Subtropical Gyre. We detected transcription of 68% of the gene targets across major taxonomic groups, and the pattern of transcription indicated relief from Fe limitation and transition to N limitation in some taxa. Prochlorococcus (eHLI), Synechococcus (sub-cluster 5.3) and Alphaproteobacteria SAR11 clade (HIMB59) showed the strongest responses to the Fe enrichment. In addition, members of uncharacterized lineages also responded. The MicroTOOLs microarray provides a robust tool for comprehensive characterization of major functional groups of microbes in the open ocean, and the design can be easily amended for specific environments and research questions.

  5. A novel multi-actuation CMOS RF MEMS switch

    NASA Astrophysics Data System (ADS)

    Lee, Chiung-I.; Ko, Chih-Hsiang; Huang, Tsun-Che

    2008-12-01

    This paper demonstrates a capacitive shunt type RF MEMS switch, which is actuated by electro-thermal actuator and electrostatic actuator at the same time, and than latching the switching status by electrostatic force only. Since thermal actuators need relative low voltage compare to electrostatic actuators, and electrostatic force needs almost no power to maintain the switching status, the benefits of the mechanism are very low actuation voltage and low power consumption. Moreover, the RF MEMS switch has considered issues for integrated circuit compatible in design phase. So the switch is fabricated by a standard 0.35um 2P4M CMOS process and uses wet etching and dry etching technologies for postprocess. This compatible ability is important because the RF characteristics are not only related to the device itself. If a packaged RF switch and a packaged IC wired together, the parasitic capacitance will cause the problem for optimization. The structure of the switch consists of a set of CPW transmission lines and a suspended membrane. The CPW lines and the membrane are in metal layers of CMOS process. Besides, the electro-thermal actuators are designed by polysilicon layer of the CMOS process. So the RF switch is only CMOS process layers needed for both electro-thermal and electrostatic actuations in switch. The thermal actuator is composed of a three-dimensional membrane and two heaters. The membrane is a stacked step structure including two metal layers in CMOS process, and heat is generated by poly silicon resistors near the anchors of membrane. Measured results show that the actuation voltage of the switch is under 7V for electro-thermal added electrostatic actuation.

  6. Statistically designing microarrays and microarray experiments to enhance sensitivity and specificity.

    PubMed

    Hsu, Jason C; Chang, Jane; Wang, Tao; Steingrímsson, Eiríkur; Magnússon, Magnús Karl; Bergsteinsdottir, Kristin

    2007-01-01

    Gene expression signatures from microarray experiments promise to provide important prognostic tools for predicting disease outcome or response to treatment. A number of microarray studies in various cancers have reported such gene signatures. However, the overlap of gene signatures in the same disease has been limited so far, and some reported signatures have not been reproduced in other populations. Clearly, the methods used for verifying novel gene signatures need improvement. In this article, we describe an experiment in which microarrays and sample hybridization are designed according to the statistical principles of randomization, replication and blocking. Our results show that such designs provide unbiased estimation of differential expression levels as well as powerful tests for them.

  7. 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. PMID:24782680

  8. Design and characterization of high precision in-pixel discriminators for rolling shutter CMOS pixel sensors with full CMOS capability

    NASA Astrophysics Data System (ADS)

    Fu, Y.; Hu-Guo, C.; Dorokhov, A.; Pham, H.; Hu, Y.

    2013-07-01

    In order to exploit the ability to integrate a charge collecting electrode with analog and digital processing circuitry down to the pixel level, a new type of CMOS pixel sensors with full CMOS capability is presented in this paper. The pixel array is read out based on a column-parallel read-out architecture, where each pixel incorporates a diode, a preamplifier with a double sampling circuitry and a discriminator to completely eliminate analog read-out bottlenecks. The sensor featuring a pixel array of 8 rows and 32 columns with a pixel pitch of 80 μm×16 μm was fabricated in a 0.18 μm CMOS process. The behavior of each pixel-level discriminator isolated from the diode and the preamplifier was studied. The experimental results indicate that all in-pixel discriminators which are fully operational can provide significant improvements in the read-out speed and the power consumption of CMOS pixel sensors.

  9. A reliable ground bounce noise reduction technique for nanoscale CMOS circuits

    NASA Astrophysics Data System (ADS)

    Sharma, Vijay Kumar; Pattanaik, Manisha

    2015-11-01

    Power gating is the most effective method to reduce the standby leakage power by adding header/footer high-VTH sleep transistors between actual and virtual power/ground rails. When a power gating circuit transitions from sleep mode to active mode, a large instantaneous charge current flows through the sleep transistors. Ground bounce noise (GBN) is the high voltage fluctuation on real ground rail during sleep mode to active mode transitions of power gating circuits. GBN disturbs the logic states of internal nodes of circuits. A novel and reliable power gating structure is proposed in this article to reduce the problem of GBN. The proposed structure contains low-VTH transistors in place of high-VTH footer. The proposed power gating structure not only reduces the GBN but also improves other performance metrics. A large mitigation of leakage power in both modes eliminates the need of high-VTH transistors. A comprehensive and comparative evaluation of proposed technique is presented in this article for a chain of 5-CMOS inverters. The simulation results are compared to other well-known GBN reduction circuit techniques at 22 nm predictive technology model (PTM) bulk CMOS model using HSPICE tool. Robustness against process, voltage and temperature (PVT) variations is estimated through Monte-Carlo simulations.

  10. Comments on selected fundamental aspects of microarray analysis.

    PubMed

    Riva, Alessandra; Carpentier, Anne-Sophie; Torrésani, Bruno; Hénaut, Alain

    2005-10-01

    Microarrays are becoming a ubiquitous tool of research in life sciences. However, the working principles of microarray-based methodologies are often misunderstood or apparently ignored by the researchers who actually perform and interpret experiments. This in turn seems to lead to a common over-expectation regarding the explanatory and/or knowledge-generating power of microarray analyses. In this note we intend to explain basic principles of five (5) major groups of analytical techniques used in studies of microarray data and their interpretation: the principal component analysis (PCA), the independent component analysis (ICA), the t-test, the analysis of variance (ANOVA), and self organizing maps (SOM). We discuss answers to selected practical questions related to the analysis of microarray data. We also take a closer look at the experimental setup and the rules, which have to be observed in order to exploit microarrays efficiently. Finally, we discuss in detail the scope and limitations of microarray-based methods. We emphasize the fact that no amount of statistical analysis can compensate for (or replace) a well thought through experimental setup. We conclude that microarrays are indeed useful tools in life sciences but by no means should they be expected to generate complete answers to complex biological questions. We argue that even well posed questions, formulated within a microarray-specific terminology, cannot be completely answered with the use of microarray analyses alone.

  11. A low-power and small-area column-level ADC for high frame-rate CMOS pixel sensor

    NASA Astrophysics Data System (ADS)

    Zhang, L.; Morel, F.; Hu-Guo, C.; Hu, Y.

    2014-07-01

    CMOS pixel sensors (CPS) have demonstrated performances meeting the specifications of the International Linear Collider (ILC) vertex detector (VTX). This paper presents a low-power and small-area 4-bit column-level analog-to-digital converter (ADC) for CMOS pixel sensors. The ADC employs a self-timed trigger and completes the conversion by performing a multi-bit/step approximation. As in the outer layers of the ILC vertex detector hit density is of the order of a few per thousand, in order to reduce power consumption, the ADC is designed to work in two modes: active mode and idle mode. The ADC is fabricated in a 0.35 μm CMOS process with a pixel pitch of 35 μm. It is implemented with 48 columns in a sensor prototype. Each column ADC covers an area of 35 ×545 μm2. The measured temporal noise and Fixed Pattern Noise (FPN) are 0.96 mV and 0.40 mV, respectively. The power consumption, for a 3 V supply and 6.25 MS/s sampling rate, is 486 μW during idle time, which is by far the most frequently employed one. This value rises to 714 μW in the case of the active mode. The measured differential nonlinearity (DNL) and integral nonlinearity (INL) are 0.49/-0.28 LSB and 0.29/-0.20 LSB, respectively.

  12. Progress of science from microscopy to microarrays (part 1): diagnosis of parasitic diseases.

    PubMed

    Dey, Ayan; Singh, Sarman

    2009-01-01

    Even though description of the magnifying glass goes back to 1021 by an Arabic physicist in his book, Antony van Leeuwenhoek was the first man to improve the then simple microscope for viewing biological specimens in 1674. This suggests that every discovery has scope for improvement, be it physics or be it biology. In the field of biology, scientists have long studied gene expression as a hallmark of gene activities reflecting the current cell conditions and response to host immune defense systems. These studies have been cumbersome, technically demanding and time-consuming. Application of microarrays has revolutionized this field and help understand the simultaneous expression of thousands of genes in a single sample put onto a single solid support. It is also now possible to compare gene expression in two different cell types, different stages of life cycle or two tissue samples, such as in healthy and diseased ones. Thus microarrays are beginning to dominate other conventional and molecular diagnostic technologies. The microarrays consist of solid supports onto which the nucleic acid sequences from thousands of different genes are immobilized, or attached at fixed locations. These solid supports themselves are usually glass slides, silicon chips or nylon membranes. The nucleic acids are spotted or synthesized directly onto the support. Application of microarrays is new for parasites. Most of these applications are done for monitoring parasite gene expression, to predict the functions of uncharacterized genes, probe the physiologic adaptations made under various environmental conditions, identify virulence-associated genes and test the effects of drug targets. The best examples are vector-borne parasites, such as Plasmodium, Trypanosoma and Leishmania, in which genes expressed, during mammalian and insect host stages, have been elucidated. Microarrays have also been successfully applied to understand the factors responsible to induce transformation from

  13. High-throughput allogeneic antibody detection using protein microarrays.

    PubMed

    Paul, Jed; Sahaf, Bita; Perloff, Spenser; Schoenrock, Kelsi; Wu, Fang; Nakasone, Hideki; Coller, John; Miklos, David

    2016-05-01

    Enzyme-linked immunosorbent assays (ELISAs) have traditionally been used to detect alloantibodies in patient plasma samples post hematopoietic cell transplantation (HCT); however, protein microarrays have the potential to be multiplexed, more sensitive, and higher throughput than ELISAs. Here, we describe the development of a novel and sensitive microarray method for detection of allogeneic antibodies against minor histocompatibility antigens encoded on the Y chromosome, called HY antigens. Six microarray surfaces were tested for their ability to bind recombinant protein and peptide HY antigens. Significant allogeneic immune responses were determined in male patients with female donors by considering normal male donor responses as baseline. HY microarray results were also compared with our previous ELISA results. Our overall goal was to maximize antibody detection for both recombinant protein and peptide epitopes. For detection of HY antigens, the Epoxy (Schott) protein microarray surface was both most sensitive and reliable and has become the standard surface in our microarray platform. PMID:26902899

  14. Formation and characterization of DNA microarrays at silicon nitride substrates.

    PubMed

    Manning, Mary; Redmond, Gareth

    2005-01-01

    A versatile method for direct, covalent attachment of DNA microarrays at silicon nitride layers, previously deposited by chemical vapor deposition at silicon wafer substrates, is reported. Each microarray fabrication process step, from silicon nitride substrate deposition, surface cleaning, amino-silanation, and attachment of a homobifunctional cross-linking molecule to covalent immobilization of probe oligonucleotides, is defined, characterized, and optimized to yield consistent probe microarray quality, homogeneity, and probe-target hybridization performance. The developed microarray fabrication methodology provides excellent (high signal-to-background ratio) and reproducible responsivity to target oligonucleotide hybridization with a rugged chemical stability that permits exposure of arrays to stringent pre- and posthybridization wash conditions through many sustained cycles of reuse. Overall, the achieved performance features compare very favorably with those of more mature glass based microarrays. It is proposed that this DNA microarray fabrication strategy has the potential to provide a viable route toward the successful realization of future integrated DNA biochips.

  15. High-Voltage-Input Level Translator Using Standard CMOS

    NASA Technical Reports Server (NTRS)

    Yager, Jeremy A.; Mojarradi, Mohammad M.; Vo, Tuan A.; Blalock, Benjamin J.

    2011-01-01

    proposed integrated circuit would translate (1) a pair of input signals having a low differential potential and a possibly high common-mode potential into (2) a pair of output signals having the same low differential potential and a low common-mode potential. As used here, "low" and "high" refer to potentials that are, respectively, below or above the nominal supply potential (3.3 V) at which standard complementary metal oxide/semiconductor (CMOS) integrated circuits are designed to operate. The input common-mode potential could lie between 0 and 10 V; the output common-mode potential would be 2 V. This translation would make it possible to process the pair of signals by use of standard 3.3-V CMOS analog and/or mixed-signal (analog and digital) circuitry on the same integrated-circuit chip. A schematic of the circuit is shown in the figure. Standard 3.3-V CMOS circuitry cannot withstand input potentials greater than about 4 V. However, there are many applications that involve low-differential-potential, high-common-mode-potential input signal pairs and in which standard 3.3-V CMOS circuitry, which is relatively inexpensive, would be the most appropriate circuitry for performing other functions on the integrated-circuit chip that handles the high-potential input signals. Thus, there is a need to combine high-voltage input circuitry with standard low-voltage CMOS circuitry on the same integrated-circuit chip. The proposed circuit would satisfy this need. In the proposed circuit, the input signals would be coupled into both a level-shifting pair and a common-mode-sensing pair of CMOS transistors. The output of the level-shifting pair would be fed as input to a differential pair of transistors. The resulting differential current output would pass through six standoff transistors to be mirrored into an output branch by four heterojunction bipolar transistors. The mirrored differential current would be converted back to potential by a pair of diode-connected transistors

  16. ProMAT: protein microarray analysis tool

    SciTech Connect

    White, Amanda M.; Daly, Don S.; Varnum, Susan M.; Anderson, Kevin K.; Bollinger, Nikki; Zangar, Richard C.

    2006-04-04

    Summary: ProMAT is a software tool for statistically analyzing data from ELISA microarray experiments. The software estimates standard curves, sample protein concentrations and their uncertainties for multiple assays. ProMAT generates a set of comprehensive figures for assessing results and diagnosing process quality. The tool is available for Windows or Mac, and is distributed as open-source Java and R code. Availability: ProMAT is available at http://www.pnl.gov/statistics/ProMAT. ProMAT requires Java version 1.5.0 and R version 1.9.1 (or more recent versions) which are distributed with the tool.

  17. Protein Microarrays--Without a Trace

    SciTech Connect

    Camarero, J A

    2007-04-05

    Many experimental approaches in biology and biophysics, as well as applications in diagnosis and drug discovery, require proteins to be immobilized on solid supports. Protein microarrays, for example, provide a high-throughput format to study biomolecular interactions. The technique employed for protein immobilization is a key to the success of these applications. Recent biochemical developments are allowing, for the first time, the selective and traceless immobilization of proteins generated by cell-free systems without the need for purification and/or reconcentration prior to the immobilization step.

  18. Using a large area CMOS APS for direct chemiluminescence detection in Western blotting electrophoresis

    NASA Astrophysics Data System (ADS)

    Esposito, Michela; Newcombe, Jane; Anaxagoras, Thalis; Allinson, Nigel M.; Wells, Kevin

    2012-03-01

    Western blotting electrophoretic sequencing is an analytical technique widely used in Functional Proteomics to detect, recognize and quantify specific labelled proteins in biological samples. A commonly used label for western blotting is Enhanced ChemiLuminescence (ECL) reagents based on fluorescent light emission of Luminol at 425nm. Film emulsion is the conventional detection medium, but is characterized by non-linear response and limited dynamic range. Several western blotting digital imaging systems have being developed, mainly based on the use of cooled Charge Coupled Devices (CCDs) and single avalanche diodes that address these issues. Even so these systems present key drawbacks, such as a low frame rate and require operation at low temperature. Direct optical detection using Complementary Metal Oxide Semiconductor (CMOS) Active Pixel Sensors (APS)could represent a suitable digital alternative for this application. In this paper the authors demonstrate the viability of direct chemiluminescent light detection in western blotting electrophoresis using a CMOS APS at room temperature. Furthermore, in recent years, improvements in fabrication techniques have made available reliable processes for very large imagers, which can be now scaled up to wafer size, allowing direct contact imaging of full size western blotting samples. We propose using a novel wafer scale APS (12.8 cm×13.2 cm), with an array architecture using two different pixel geometries that can deliver an inherently low noise and high dynamic range image at the same time representing a dramatic improvement with respect to the current western blotting imaging systems.

  19. Proton-counting radiography for proton therapy: a proof of principle using CMOS APS technology.

    PubMed

    Poludniowski, G; Allinson, N M; Anaxagoras, T; Esposito, M; Green, S; Manolopoulos, S; Nieto-Camero, J; Parker, D J; Price, T; Evans, P M

    2014-06-01

    Despite the early recognition of the potential of proton imaging to assist proton therapy (Cormack 1963 J. Appl. Phys. 34 2722), the modality is still removed from clinical practice, with various approaches in development. For proton-counting radiography applications such as computed tomography (CT), the water-equivalent-path-length that each proton has travelled through an imaged object must be inferred. Typically, scintillator-based technology has been used in various energy/range telescope designs. Here we propose a very different alternative of using radiation-hard CMOS active pixel sensor technology. The ability of such a sensor to resolve the passage of individual protons in a therapy beam has not been previously shown. Here, such capability is demonstrated using a 36 MeV cyclotron beam (University of Birmingham Cyclotron, Birmingham, UK) and a 200 MeV clinical radiotherapy beam (iThemba LABS, Cape Town, SA). The feasibility of tracking individual protons through multiple CMOS layers is also demonstrated using a two-layer stack of sensors. The chief advantages of this solution are the spatial discrimination of events intrinsic to pixelated sensors, combined with the potential provision of information on both the range and residual energy of a proton. The challenges in developing a practical system are discussed.

  20. CMOS Amperometric ADC With High Sensitivity, Dynamic Range and Power Efficiency for Air Quality Monitoring.

    PubMed

    Li, Haitao; Boling, C Sam; Mason, Andrew J

    2016-08-01

    Airborne pollutants are a leading cause of illness and mortality globally. Electrochemical gas sensors show great promise for personal air quality monitoring to address this worldwide health crisis. However, implementing miniaturized arrays of such sensors demands high performance instrumentation circuits that simultaneously meet challenging power, area, sensitivity, noise and dynamic range goals. This paper presents a new multi-channel CMOS amperometric ADC featuring pixel-level architecture for gas sensor arrays. The circuit combines digital modulation of input currents and an incremental Σ∆ ADC to achieve wide dynamic range and high sensitivity with very high power efficiency and compact size. Fabricated in 0.5 [Formula: see text] CMOS, the circuit was measured to have 164 dB cross-scale dynamic range, 100 fA sensitivity while consuming only 241 [Formula: see text] and 0.157 [Formula: see text] active area per channel. Electrochemical experiments with liquid and gas targets demonstrate the circuit's real-time response to a wide range of analyte concentrations. PMID:27352395

  1. (Invited) Comprehensive Assessment of Oxide Memristors As Post-CMOS Memory and Logic Devices

    DOE PAGES

    Gao, X.; Mamaluy, D.; Cyr, E. C.; Marinella, M. J.

    2016-05-10

    As CMOS technology approaches the end of its scaling, oxide-based memristors have become one of the leading candidates for post-CMOS memory and logic devices. In orderTo facilitate the understanding of physical switching mechanisms and accelerate experimental development of memristors, we have developed a three-dimensional fully-coupled electrical and thermal transport model, which captures all the important processes that drive memristive switching and is applicable for simulating a wide range of memristors. Moreover, the model is applied to simulate the RESET and SET switching in a 3D filamentary TaOx memristor. Extensive simulations show that the switching dynamics of the bipolar device ismore » determined by thermally-activated field-dominant processes: with Joule heating, the raised temperature enables the movement of oxygen vacancies, and the field drift dominates the overall motion of vacancies. Simulated current-voltage hysteresis and device resistance profiles as a function of time and voltage during RESET and SET switching show good agreement with experimental measurement.« less

  2. Low-FPN high-gain capacitive transimpedance amplifier for low-noise CMOS image sensors

    NASA Astrophysics Data System (ADS)

    Fowler, Boyd A.; Balicki, Janusz; How, Dana; Godfrey, Michael

    2001-05-01

    In this paper we introduce a low fixed pattern noise (LFPN) capacitive transimpedance amplifier (CTIA) for active pixel CMOS image sensors (APS) with high switchable gain and low read noise. The LFPN CTIA APS uses a switched capacitor voltage divider feedback circuit to achieve high sensitivity, low gain FPN, and low read noise. This paper discusses the operation of the LFPN CTIA APS, and presents a theoretical analysis of its gain FPN and read noise. We do not analyze the effect of 1/f noise, since it is typically much smaller than the thermal and shot noise effects. Monte Carlo simulation of gain FPN and SPICE simulation of read noise are also presented. For a 0.35 micrometers CMOS LFPN CTIA at room temperature and an output data rate of 16Mpixel/sec, we show that the pixel amplifier gain FPN is less than 0.0064, where FPN is defined as the ratio of standard deviation to mean. The read noise and dynamic range are less than 3 electrons RMS and greater than 90dB respectively. We find that theory and simulated results match closely.

  3. Characterization of Si Hybrid CMOS Detectors for use in the Soft X-ray Band

    NASA Astrophysics Data System (ADS)

    Prieskorn, Zachary; Griffith, C.; Bongiorno, S.; Falcone, A.; Burrows, D. N.

    2014-01-01

    In a joint program between Penn State University and Teledyne Imaging Sensors a soft X-ray detector based on the HAWAII Hybrid Si CMOS detector (HCD) has been developed. HCDs could potentially be the optimum detectors for the next generation of X-ray missions, especially those with focused optics and/or large effective area. These innovative detectors are active pixel sensors (APS) which allow a pixel to be read through individual in-pixel electronics, without the need to transfer charge across many pixels, in contrast to a CCD. They are made by bonding a Si absorbing layer to a pixelated CMOS readout, allowing the two layers to be optimized independently. The advantages of this design compared to CCDs are high speed timing 100 μs in full imaging mode), a flexible windowed readout to reduce pile-up, dramatically improved radiation hardness and resistance to micrometeoroid damage, and reduced power requirements. We present recent measurements of energy resolution, read noise, inter-pixel crosstalk, quantum efficiency, and dark current for four of these devices.

  4. Use of carbon micro-particles for improved infrared temperature measurement of CMOS MEMS devices

    NASA Astrophysics Data System (ADS)

    Hopper, Richard H.; Haneef, Ibraheem; Zeeshan Ali, Syed; Udrea, Florin; Oxley, Christopher H.

    2010-04-01

    We report a technique which can be used to improve the accuracy of infrared (IR) surface temperature measurements made on micro-electro-mechanical systems (MEMS). In this work, a silicon-on-insulator (SOI) complementary metal oxide semiconductor (CMOS) MEMS thermal flow sensor was studied. The device consists of a meander-shaped resistive heater element that was fabricated using CMOS aluminum metallization and embedded in an SOI silicon oxide (SiO2) membrane. Conventional IR temperature measurements, made on the active device, were shown to give significant surface temperature errors—a consequence of the optical transparency of the SiO2 membrane and low emissivity of the metalized areas. Radiative carbon micro-particles were used to improve the measurement accuracy. By making IR measurements on carbon micro-particles placed in isothermal contact with parts of the MEMS sensor's structure, the accuracy of the surface temperature determination was significantly improved. The peak device operating temperatures measured using the 'IR micro-particle' technique were found to be in good agreement with those obtained from thermoelectric characterization. The work shows how wide area surface temperature profiles can be quickly built up by imaging multiple micro-particles using an IR charge-coupled device (CCD) detector array. The IR micro-particle technique removes the problems associated with coating MEMS sensors with a uniform high emissivity layer, which may cause damage to such devices and/or affect their thermal performance due to additional heat spreading.

  5. Proton-counting radiography for proton therapy: a proof of principle using CMOS APS technology

    PubMed Central

    Poludniowski, G; Allinson, N M; Anaxagoras, T; Esposito, M; Green, S; Manolopoulos, S; Nieto-Camero, J; Parker, D J; Price, T; Evans, P M

    2014-01-01

    Despite the early recognition of the potential of proton imaging to assist proton therapy the modality is still removed from clinical practice, with various approaches in development. For proton-counting radiography applications such as Computed Tomography (CT), the Water-Equivalent-Path-Length (WEPL) that each proton has travelled through an imaged object must be inferred. Typically, scintillator-based technology has been used in various energy/range telescope designs. Here we propose a very different alternative of using radiation-hard CMOS Active Pixel Sensor (APS) technology. The ability of such a sensor to resolve the passage of individual protons in a therapy beam has not been previously shown. Here, such capability is demonstrated using a 36 MeV cyclotron beam (University of Birmingham Cyclotron, Birmingham, UK) and a 200 MeV clinical radiotherapy beam (iThemba LABS, Cape Town, SA). The feasibility of tracking individual protons through multiple CMOS layers is also demonstrated using a two-layer stack of sensors. The chief advantages of this solution are the spatial discrimination of events intrinsic to pixelated sensors, combined with the potential provision of information on both the range and residual energy of a proton. The challenges in developing a practical system are discussed. PMID:24785680

  6. Applications of Functional Protein Microarrays in Basic and Clinical Research

    PubMed Central

    Zhu, Heng; Qian, Jiang

    2013-01-01

    The protein microarray technology provides a versatile platform for characterization of hundreds of thousands of proteins in a highly parallel and high-throughput manner. It is viewed as a new tool that overcomes the limitation of DNA microarrays. On the basis of its application, protein microarrays fall into two major classes: analytical and functional protein microarrays. In addition, tissue or cell lysates can also be directly spotted on a slide to form the so-called “reverse-phase” protein microarray. In the last decade, applications of functional protein microarrays in particular have flourished in studying protein function and construction of networks and pathways. In this chapter, we will review the recent advancements in the protein microarray technology, followed by presenting a series of examples to illustrate the power and versatility of protein microarrays in both basic and clinical research. 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:22989767

  7. Refractive index change detection based on porous silicon microarray

    NASA Astrophysics Data System (ADS)

    Chen, Weirong; Jia, Zhenhong; Li, Peng; Lv, Guodong; Lv, Xiaoyi

    2016-05-01

    By combining photolithography with the electrochemical anodization method, a microarray device of porous silicon (PS) photonic crystal was fabricated on the crystalline silicon substrate. The optical properties of the microarray were analyzed with the transfer matrix method. The relationship between refractive index and reflectivity of each array element of the microarray at 633 nm was also studied, and the array surface reflectivity changes were observed through digital imaging. By means of the reflectivity measurement method, reflectivity changes below 10-3 can be observed based on PS microarray. The results of this study can be applied to the detection of biosensor arrays.

  8. Re-Annotator: Annotation Pipeline for Microarray Probe Sequences.

    PubMed

    Arloth, Janine; Bader, Daniel M; Röh, Simone; Altmann, Andre

    2015-01-01

    Microarray technologies are established approaches for high throughput gene expression, methylation and genotyping analysis. An accurate mapping of the array probes is essential to generate reliable biological findings. However, manufacturers of the microarray platforms typically provide incomplete and outdated annotation tables, which often rely on older genome and transcriptome versions that differ substantially from up-to-date sequence databases. Here, we present the Re-Annotator, a re-annotation pipeline for microarray probe sequences. It is primarily designed for gene expression microarrays but can also be adapted to other types of microarrays. The Re-Annotator uses a custom-built mRNA reference database to identify the positions of gene expression array probe sequences. We applied Re-Annotator to the Illumina Human-HT12 v4 microarray platform and found that about one quarter (25%) of the probes differed from the manufacturer's annotation. In further computational experiments on experimental gene expression data, we compared Re-Annotator to another probe re-annotation tool, ReMOAT, and found that Re-Annotator provided an improved re-annotation of microarray probes. A thorough re-annotation of probe information is crucial to any microarray analysis. The Re-Annotator pipeline is freely available at http://sourceforge.net/projects/reannotator along with re-annotated files for Illumina microarrays HumanHT-12 v3/v4 and MouseRef-8 v2.

  9. Chemiluminescence microarrays in analytical chemistry: a critical review.

    PubMed

    Seidel, Michael; Niessner, Reinhard

    2014-09-01

    Multi-analyte immunoassays on microarrays and on multiplex DNA microarrays have been described for quantitative analysis of small organic molecules (e.g., antibiotics, drugs of abuse, small molecule toxins), proteins (e.g., antibodies or protein toxins), and microorganisms, viruses, and eukaryotic cells. In analytical chemistry, multi-analyte detection by use of analytical microarrays has become an innovative research topic because of the possibility of generating several sets of quantitative data for different analyte classes in a short time. Chemiluminescence (CL) microarrays are powerful tools for rapid multiplex analysis of complex matrices. A wide range of applications for CL microarrays is described in the literature dealing with analytical microarrays. The motivation for this review is to summarize the current state of CL-based analytical microarrays. Combining analysis of different compound classes on CL microarrays reduces analysis time, cost of reagents, and use of laboratory space. Applications are discussed, with examples from food safety, water safety, environmental monitoring, diagnostics, forensics, toxicology, and biosecurity. The potential and limitations of research on multiplex analysis by use of CL microarrays are discussed in this review.

  10. The use of antigen microarrays in antibody profiling.

    PubMed

    Papp, Krisztián; Prechl, József

    2012-01-01

    Technological advances in the field of microarray production and analysis lead to the development of protein microarrays. Of these, antigen microarrays are one particular format that allows the study of antigen-antibody interactions in a miniaturized and highly multiplexed fashion. Here, we describe the parallel detection of antibodies with different specificities in human serum, a procedure also called antibody profiling. Autoantigens printed on microarray slides are reacted with test sera and the bound antibodies are identified by fluorescently labeled secondary reagents. Reactivity patterns generated this way characterize individuals and can help design novel diagnostic tools.

  11. Combined reactor neutron beam and {sup 60}Co γ-ray radiation effects on CMOS APS image sensors

    SciTech Connect

    Wang, Zujun Chen, Wei; Sheng, Jiangkun; Liu, Yan; Xiao, Zhigang; Huang, Shaoyan; Liu, Minbo

    2015-02-15

    The combined reactor neutron beam and {sup 60}Co γ-ray radiation effects on complementary metal-oxide semiconductor (CMOS) active pixel sensors (APS) have been discussed and some new experimental phenomena are presented. The samples are manufactured in the standard 0.35-μm CMOS technology. Two samples were first exposed to {sup 60}Co γ-rays up to the total ionizing dose (TID) level of 200 krad(Si) at the dose rates of 50.0 and 0.2 rad(Si)/s, and then exposed to neutron fluence up to 1 × 10{sup 11} n/cm{sup 2} (1-MeV equivalent neutron fluence). One sample was first exposed to neutron fluence up to 1 × 10{sup 11} n/cm{sup 2} (1-MeV equivalent neutron fluence), and then exposed to {sup 60}Co γ-rays up to the TID level of 200 krad(Si) at the dose rate of 0.2 rad(Si)/s. The mean dark signal (K{sub D}), the dark signal non-uniformity (DSNU), and the noise (V{sub N}) versus the total dose and neutron fluence has been investigated. The degradation mechanisms of CMOS APS image sensors have been analyzed, especially for the interaction induced by neutron displacement damage and TID damage.

  12. Binary CMOS image sensor with a gate/body-tied MOSFET-type photodetector for high-speed operation

    NASA Astrophysics Data System (ADS)

    Choi, Byoung-Soo; Jo, Sung-Hyun; Bae, Myunghan; Kim, Sang-Hwan; Shin, Jang-Kyoo

    2016-05-01

    In this paper, a binary complementary metal oxide semiconductor (CMOS) image sensor with a gate/body-tied (GBT) metal oxide semiconductor field effect transistor (MOSFET)-type photodetector is presented. The sensitivity of the GBT MOSFET-type photodetector, which was fabricated using the standard CMOS 0.35-μm process, is higher than the sensitivity of the p-n junction photodiode, because the output signal of the photodetector is amplified by the MOSFET. A binary image sensor becomes more efficient when using this photodetector. Lower power consumptions and higher speeds of operation are possible, compared to the conventional image sensors using multi-bit analog to digital converters (ADCs). The frame rate of the proposed image sensor is over 2000 frames per second, which is higher than those of the conventional CMOS image sensors. The output signal of an active pixel sensor is applied to a comparator and compared with a reference level. The 1-bit output data of the binary process is determined by this level. To obtain a video signal, the 1-bit output data is stored in the memory and is read out by horizontal scanning. The proposed chip is composed of a GBT pixel array (144 × 100), binary-process circuit, vertical scanner, horizontal scanner, and readout circuit. The operation mode can be selected from between binary mode and multi-bit mode.

  13. Analyzing microarray data with transitive directed acyclic graphs.

    PubMed

    Phan, Vinhthuy; Olusegun George, E; Tran, Quynh T; Goodwin, Shirlean; Bodreddigari, Sridevi; Sutter, Thomas R

    2009-02-01

    Post hoc assignment of patterns determined by all pairwise comparisons in microarray experiments with multiple treatments has been proven to be useful in assessing treatment effects. We propose the usage of transitive directed acyclic graphs (tDAG) as the representation of these patterns and show that such representation can be useful in clustering treatment effects, annotating existing clustering methods, and analyzing sample sizes. Advantages of this approach include: (1) unique and descriptive meaning of each cluster in terms of how genes respond to all pairs of treatments; (2) insensitivity of the observed patterns to the number of genes analyzed; and (3) a combinatorial perspective to address the sample size problem by observing the rate of contractible tDAG as the number of replicates increases. The advantages and overall utility of the method in elaborating drug structure activity relationships are exemplified in a controlled study with real and simulated data. PMID:19226664

  14. CMOS active pixel sensor type imaging system on a chip

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R. (Inventor); Nixon, Robert (Inventor)

    2011-01-01

    A single chip camera which includes an .[.intergrated.]. .Iadd.integrated .Iaddend.image acquisition portion and control portion and which has double sampling/noise reduction capabilities thereon. Part of the .[.intergrated.]. .Iadd.integrated .Iaddend.structure reduces the noise that is picked up during imaging.

  15. CMOS RAM cosmic-ray-induced-error-rate analysis

    NASA Technical Reports Server (NTRS)

    Pickel, J. C.; Blandford, J. T., Jr.

    1981-01-01

    A significant number of spacecraft operational anomalies are believed to be associated with cosmic-ray-induced soft errors in the LSI memories. Test programs using a cyclotron to simulate cosmic rays have established conclusively that many common commercial memory types are vulnerable to heavy-ion upset. A description is given of the methodology and the results of a detailed analysis for predicting the bit-error rate in an assumed space environment for CMOS memory devices. Results are presented for three types of commercially available CMOS 1,024-bit RAMs. It was found that the HM6508 is susceptible to single-ion induced latchup from argon and krypton ions. The HS6508 and HS6508RH and the CDP1821 apparently are not susceptible to single-ion induced latchup.

  16. Fundamental performance differences between CMOS and CCD imagers: Part II

    NASA Astrophysics Data System (ADS)

    Janesick, James; Andrews, James; Tower, John; Grygon, Mark; Elliott, Tom; Cheng, John; Lesser, Michael; Pinter, Jeff

    2007-09-01

    A new class of CMOS imagers that compete with scientific CCDs is presented. The sensors are based on deep depletion backside illuminated technology to achieve high near infrared quantum efficiency and low pixel cross-talk. The imagers deliver very low read noise suitable for single photon counting - Fano-noise limited soft x-ray applications. Digital correlated double sampling signal processing necessary to achieve low read noise performance is analyzed and demonstrated for CMOS use. Detailed experimental data products generated by different pixel architectures (notably 3TPPD, 5TPPD and 6TPG designs) are presented including read noise, charge capacity, dynamic range, quantum efficiency, charge collection and transfer efficiency and dark current generation. Radiation damage data taken for the imagers is also reported.

  17. A CMOS integrated timing discriminator circuit for fast scintillation counters

    SciTech Connect

    Jochmann, M.W.

    1998-06-01

    Based on a zero-crossing discriminator using a CR differentiation network for pulse shaping, a new CMOS integrated timing discriminator circuit is proposed for fast (t{sub r} {ge} 2 ns) scintillation counters at the cooler synchrotron COSY-Juelich. By eliminating the input signal`s amplitude information by means of an analog continuous-time divider, a normalized pulse shape at the zero-crossing point is gained over a wide dynamic input amplitude range. In combination with an arming comparator and a monostable multivibrator this yields in a highly precise timing discriminator circuit, that is expected to be useful in different time measurement applications. First measurement results of a CMOS integrated logarithmic amplifier, which is part of the analog continuous-time divider, agree well with the corresponding simulations. Moreover, SPICE simulations of the integrated discriminator circuit promise a time walk well below 200 ps (FWHM) over a 40 dB input amplitude dynamic range.

  18. A back-illuminated megapixel CMOS image sensor

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata; Cunningham, Thomas; Nikzad, Shouleh; Hoenk, Michael; Jones, Todd; Wrigley, Chris; Hancock, Bruce

    2005-01-01

    In this paper, we present the test and characterization results for a back-illuminated megapixel CMOS imager. The imager pixel consists of a standard junction photodiode coupled to a three transistor-per-pixel switched source-follower readout [1]. The imager also consists of integrated timing and control and bias generation circuits, and provides analog output. The analog column-scan circuits were implemented in such a way that the imager could be configured to run in off-chip correlated double-sampling (CDS) mode. The imager was originally designed for normal front-illuminated operation, and was fabricated in a commercially available 0.5 pn triple-metal CMOS-imager compatible process. For backside illumination, the imager was thinned by etching away the substrate was etched away in a post-fabrication processing step.

  19. A CMOS image sensor dedicated to medical gamma camera application

    NASA Astrophysics Data System (ADS)

    Salahuddin, Nur S.; Paindavoine, Michel; Ginhac, Dominique; Parmentier, Michel; Tamda, Najia

    2005-03-01

    Generally, medical Gamma Camera are based on the Anger principle. These cameras use a scintillator block coupled to a bulky array of photomultiplier tube (PMT). To simplify this, we designed a new integrated CMOS image sensor in order to replace bulky PMT photodetetors. We studied several photodiodes sensors including current mirror amplifiers. These photodiodes have been fabricated using a CMOS 0.6 micrometers process from Austria Mikro Systeme (AMS). Each sensor pixel in the array occupies respectively, 1mm x 1mm area, 0.5mm x 0.5mm area and 0.2mm 0.2mm area with fill factor 98 % and total chip area is 2 square millimeters. The sensor pixels show a logarithmic response in illumination and are capable of detecting very low green light emitting diode (less than 0.5 lux) . These results allow to use our sensor in new Gamma Camera solid-state concept.

  20. CCD or CMOS camera calibration using point spread function

    NASA Astrophysics Data System (ADS)

    Abdelsalam, D. G.; Stanislas, M.; Coudert, S.

    2014-06-01

    We present a simple method based on the acquisition of a back-illuminated pinhole to estimate the point spread function (PSF) for CCD (or CMOS) sensor characterization. This method is used to measure the variations in sensitivity of the 2D-sensor array systems. The experimental results show that there is a variation in sensitivity for each position on the CCD of the calibrated camera and the pixel optical center error with respect to the geometrical center is in the range of 1/10th of a pixel. We claim that the pixel error comes most probably from the coherence of the laser light used, or eventually from possible defects in shape, surface quality, optical performance of micro-lenses, and the uniformity of the parameters across the wafer. This may have significant consequences for coherent light imaging using CCD (or CMOS) such as Particle Image Velocimetry.

  1. A Brief Discussion of Radiation Hardening of CMOS Microelectronics

    SciTech Connect

    Myers, D.R.

    1998-12-18

    Commercial microchips work well in their intended environments. However, generic microchips will not fimction correctly if exposed to sufficient amounts of ionizing radiation, the kind that satellites encounter in outer space. Modern CMOS circuits must overcome three specific concerns from ionizing radiation: total-dose, single-event, and dose-rate effects. Minority-carrier devices such as bipolar transistors, optical receivers, and solar cells must also deal with recombination-generation centers caused by displacement damage, which are not major concerns for majority-carrier CMOS devices. There are ways to make the chips themselves more resistant to radiation. This extra protection, called radiation hardening, has been called both a science and an art. Radiation hardening requires both changing the designs of the chips and altering the ways that the chips are manufactured.

  2. 324GHz CMOS VCO Using Linear Superimposition Technique

    NASA Technical Reports Server (NTRS)

    Daquan, Huang; LaRocca, Tim R.; Samoska, Lorene A; Fung, Andy; Chang, Frank

    2007-01-01

    Terahertz (frequencies ranged from 300GHz to 3THz) imaging and spectroscopic systems have drawn increasing attention recently due to their unique capabilities in detecting and possibly analyzing concealed objects. The generation of terahertz signals is nonetheless nontrivial and traditionally accomplished by using either free-electron radiation, optical lasers, Gunn diodes or fundamental oscillation by using III-V based HBT/HEMT technology[1-3]... We have substantially extended the operation range of deep-scaled CMOS by using a linear superimposition method, in which we have realized a 324GHz VCO in 90nm digital CMOS with 4GHz tuning range under 1V supply voltage. This may also pave the way for ultra-high data rate wireless communications beyond that of IEEE 802.15.3c and reach data rates comparable to that of fiber optical communications, such as OC768 (40Gbps) and beyond.

  3. TID Simulation of Advanced CMOS Devices for Space Applications

    NASA Astrophysics Data System (ADS)

    Sajid, Muhammad

    2016-07-01

    This paper focuses on Total Ionizing Dose (TID) effects caused by accumulation of charges at silicon dioxide, substrate/silicon dioxide interface, Shallow Trench Isolation (STI) for scaled CMOS bulk devices as well as at Buried Oxide (BOX) layer in devices based on Silicon-On-Insulator (SOI) technology to be operated in space radiation environment. The radiation induced leakage current and corresponding density/concentration electrons in leakage current path was presented/depicted for 180nm, 130nm and 65nm NMOS, PMOS transistors based on CMOS bulk as well as SOI process technologies on-board LEO and GEO satellites. On the basis of simulation results, the TID robustness analysis for advanced deep sub-micron technologies was accomplished up to 500 Krad. The correlation between the impact of technology scaling and magnitude of leakage current with corresponding total dose was established utilizing Visual TCAD Genius program.

  4. Smart CMOS image sensor for lightning detection and imaging.

    PubMed

    Rolando, Sébastien; Goiffon, Vincent; Magnan, Pierre; Corbière, Franck; Molina, Romain; Tulet, Michel; Bréart-de-Boisanger, Michel; Saint-Pé, Olivier; Guiry, Saïprasad; Larnaudie, Franck; Leone, Bruno; Perez-Cuevas, Leticia; Zayer, Igor

    2013-03-01

    We present a CMOS image sensor dedicated to lightning detection and imaging. The detector has been designed to evaluate the potentiality of an on-chip lightning detection solution based on a smart sensor. This evaluation is performed in the frame of the predevelopment phase of the lightning detector that will be implemented in the Meteosat Third Generation Imager satellite for the European Space Agency. The lightning detection process is performed by a smart detector combining an in-pixel frame-to-frame difference comparison with an adjustable threshold and on-chip digital processing allowing an efficient localization of a faint lightning pulse on the entire large format array at a frequency of 1 kHz. A CMOS prototype sensor with a 256×256 pixel array and a 60 μm pixel pitch has been fabricated using a 0.35 μm 2P 5M technology and tested to validate the selected detection approach.

  5. Segmentation of prostate cancer tissue microarray images

    NASA Astrophysics Data System (ADS)

    Cline, Harvey E.; Can, Ali; Padfield, Dirk

    2006-02-01

    Prostate cancer is diagnosed by histopathology interpretation of hematoxylin and eosin (H and E)-stained tissue sections. Gland and nuclei distributions vary with the disease grade. The morphological features vary with the advance of cancer where the epithelial regions grow into the stroma. An efficient pathology slide image analysis method involved using a tissue microarray with known disease stages. Digital 24-bit RGB images were acquired for each tissue element on the slide with both 10X and 40X objectives. Initial segmentation at low magnification was accomplished using prior spectral characteristics from a training tissue set composed of four tissue clusters; namely, glands, epithelia, stroma and nuclei. The segmentation method was automated by using the training RGB values as an initial guess and iterating the averaging process 10 times to find the four cluster centers. Labels were assigned to the nearest cluster center in red-blue spectral feature space. An automatic threshold algorithm separated the glands from the tissue. A visual pseudo color representation of 60 segmented tissue microarray image was generated where white, pink, red, blue colors represent glands, epithelia, stroma and nuclei, respectively. The higher magnification images provided refined nuclei morphology. The nuclei were detected with a RGB color space principle component analysis that resulted in a grey scale image. The shape metrics such as compactness, elongation, minimum and maximum diameters were calculated based on the eigenvalues of the best-fitting ellipses to the nuclei.

  6. Inferring genetic networks from microarray data.

    SciTech Connect

    May, Elebeoba Eni; Davidson, George S.; Martin, Shawn Bryan; Werner-Washburne, Margaret C.; Faulon, Jean-Loup Michel

    2004-06-01

    In theory, it should be possible to infer realistic genetic networks from time series microarray data. In practice, however, network discovery has proved problematic. The three major challenges are: (1) inferring the network; (2) estimating the stability of the inferred network; and (3) making the network visually accessible to the user. Here we describe a method, tested on publicly available time series microarray data, which addresses these concerns. The inference of genetic networks from genome-wide experimental data is an important biological problem which has received much attention. Approaches to this problem have typically included application of clustering algorithms [6]; the use of Boolean networks [12, 1, 10]; the use of Bayesian networks [8, 11]; and the use of continuous models [21, 14, 19]. Overviews of the problem and general approaches to network inference can be found in [4, 3]. Our approach to network inference is similar to earlier methods in that we use both clustering and Boolean network inference. However, we have attempted to extend the process to better serve the end-user, the biologist. In particular, we have incorporated a system to assess the reliability of our network, and we have developed tools which allow interactive visualization of the proposed network.

  7. Intensity-based segmentation of microarray images.

    PubMed

    Nagarajan, Radhakrishnan

    2003-07-01

    The underlying principle in microarray image analysis is that the spot intensity is a measure of the gene expression. This implicitly assumes the gene expression of a spot to be governed entirely by the distribution of the pixel intensities. Thus, a segmentation technique based on the distribution of the pixel intensities is appropriate for the current problem. In this paper, clustering-based segmentation is described to extract the target intensity of the spots. The approximate boundaries of the spots in the microarray are determined by manual adjustment of rectilinear grids. The distribution of the pixel intensity in a grid containing a spot is assumed to be the superposition of the foreground and the local background. The k-means clustering technique and the partitioning around medoids (PAM) were used to generate a binary partition of the pixel intensity distribution. The median (k-means) and the medoid (PAM) of the cluster members are chosen as the cluster representatives. The effectiveness of the clustering-based segmentation techniques was tested on publicly available arrays generated in a lipid metabolism experiment (Callow et al., 2000). The results are compared against those obtained using the region-growing approach (SPOT) (Yang et al., 2001). The effect of additive white Gaussian noise is also investigated. PMID:12906242

  8. Microarray analysis of the developing cortex.

    PubMed

    Semeralul, Mawahib O; Boutros, Paul C; Likhodi, Olga; Okey, Allan B; Van Tol, Hubert H M; Wong, Albert H C

    2006-12-01

    Abnormal development of the prefrontal cortex (PFC) is associated with a number of neuropsychiatric disorders that have an onset in childhood or adolescence. Although the basic laminar structure of the PFC is established in utero, extensive remodeling continues into adolescence. To map the overall pattern of changes in cortical gene transcripts during postnatal development, we made serial measurements of mRNA levels in mouse PFC using oligonucleotide microarrays. We observed changes in mRNA transcripts consistent with known postnatal morphological and biochemical events. Overall, most transcripts that changed significantly showed a progressive decrease in abundance after birth, with the majority of change between postnatal weeks 2 and 4. Genes with cell proliferative, cytoskeletal, extracellular matrix, plasma membrane lipid/transport, protein folding, and regulatory functions had decreases in mRNA levels. Quantitative PCR verified the microarray results for six selected genes: DNA methyltransferase 3A (Dnmt3a), procollagen, type III, alpha 1 (Col3a1), solute carrier family 16 (monocarboxylic acid transporters), member 1 (Slc16a1), MARCKS-like 1 (Marcksl1), nidogen 1 (Nid1) and 3-hydroxybutyrate dehydrogenase (heart, mitochondrial) (Bdh).

  9. Laser direct writing of biomolecule microarrays

    NASA Astrophysics Data System (ADS)

    Serra, P.; Fernández-Pradas, J. M.; Berthet, F. X.; Colina, M.; Elvira, J.; Morenza, J. L.

    Protein-based biosensors are highly efficient tools for protein detection and identification. The production of these devices requires the manipulation of tiny amounts of protein solutions in conditions preserving their biological properties. In this work, laser induced forward transfer (LIFT) was used for spotting an array of a purified bacterial antigen in order to check the viability of this technique for the production of protein microarrays. A pulsed Nd:YAG laser beam (355 nm wavelength, 10 ns pulse duration) was used to transfer droplets of a solution containing the Treponema pallidum 17 kDa protein antigen on a glass slide. Optical microscopy showed that a regular array of micrometric droplets could be precisely and uniformly spotted onto a solid substrate. Subsequently, it was proved that LIFT deposition of a T. pallidum 17 kDa antigen onto nylon-coated glass slides preserves its antigenic reactivity and diagnostic properties. These results support that LIFT is suitable for the production of protein microarrays and pave the way for future diagnostics applications.

  10. Label-free detection repeatability of protein microarrays by oblique-incidence reflectivity difference method

    NASA Astrophysics Data System (ADS)

    Dai, Jun; Li, Lin; Wang, JingYi; He, LiPing; Lu, HuiBin; Ruan, KangCheng; Jin, KuiJuan; Yang, GuoZhen

    2012-12-01

    We examine the repeatabilities of oblique-incidence reflectivity difference (OIRD) method for label-free detecting biological molecular interaction using protein microarrays. The experimental results show that the repeatabilities are the same in a given microarray or microarray-microarray and are consistent, indicating that OIRD is a promising label-free detection technique for biological microarrays.

  11. Attenuation of single event induced pulses in CMOS combinational logic

    SciTech Connect

    Baze, M.P.; Buchner, S.P.

    1997-12-01

    Results are presented of a study of SEU generated transient pulse attenuation in combinational logic structures built using common digital CMOS design practices. SPICE circuit analysis, heavy ion tests, and pulsed, focused laser simulations were used to examine the response characteristics of transient pulse behavior in long logic strings. Results show that while there is an observable effect, it cannot be generally assumed that attenuation will significantly reduce observed circuit bit error rates.

  12. Hardening of commercial CMOS PROMs with polysilicon fusible links

    NASA Technical Reports Server (NTRS)

    Newman, W. H.; Rauchfuss, J. E.

    1985-01-01

    The method by which a commercial 4K CMOS PROM with polysilicon fuses was hardened and the feasibility of applying this method to a 16K PROM are presented. A description of the process and the necessary minor modifications to the original layout are given. The PROM circuit and discrete device characteristics over radiation to 1000K rad-Si are summarized. The dose rate sensitivity of the 4K PROMs is also presented.

  13. Linear dynamic range enhancement in a CMOS imager

    NASA Technical Reports Server (NTRS)

    Pain, Bedabrata (Inventor)

    2008-01-01

    A CMOS imager with increased linear dynamic range but without degradation in noise, responsivity, linearity, fixed-pattern noise, or photometric calibration comprises a linear calibrated dual gain pixel in which the gain is reduced after a pre-defined threshold level by switching in an additional capacitance. The pixel may include a novel on-pixel latch circuit that is used to switch in the additional capacitance.

  14. A BiCMOS integrated charge to amplitude converter

    SciTech Connect

    Gallin-Martel, L.; Pouxe, J.; Rossetto, O.

    1996-12-31

    This paper describes a fast two channel gated charge to amplitude converter (QAC) which has been designed with the 1.2 {mu}m BiCMOS technology from AMS (Austria Mikro Systeme). It can integrate fast negative impulse currents up to 100 mA. Associated with an audio 18 bit low cost ADC, it can easily be used to make a 12 to 13 bit QDC. The problems of current to current conversion, pedestal and offset stability are discussed.

  15. CMOS Alcohol Sensor Employing ZnO Nanowire Sensing Films

    NASA Astrophysics Data System (ADS)

    Santra, S.; Ali, S. Z.; Guha, P. K.; Hiralal, P.; Unalan, H. E.; Dalal, S. H.; Covington, J. A.; Milne, W. I.; Gardner, J. W.; Udrea, F.

    2009-05-01

    This paper reports on the utilization of zinc oxide nanowires (ZnO NWs) on a silicon on insulator (SOI) CMOS micro-hotplate for use as an alcohol sensor. The device was designed in Cadence and fabricated in a 1.0 μm SOI CMOS process at XFAB (Germany). The basic resistive gas sensor comprises of a metal micro-heater (made of aluminum) embedded in an ultra-thin membrane. Gold plated aluminum electrodes, formed of the top metal, are used for contacting with the sensing material. This design allows high operating temperatures with low power consumption. The membrane was formed by using deep reactive ion etching. ZnO NWs were grown on SOI CMOS substrates by a simple and low-cost hydrothermal method. A few nanometer of ZnO seed layer was first sputtered on the chips, using a metal mask, and then the chips were dipped in a zinc nitrate hexahydrate and hexamethylenetramine solution at 90° C to grow ZnO NWs. The chemical sensitivity of the on-chip NWs were studied in the presence of ethanol (C2H5OH) vapour (with 10% relative humidity) at two different temperatures: 200 and 250° C (the corresponding power consumptions are only 18 and 22 mW). The concentrations of ethanol vapour were varied from 175-1484 ppm (pers per million) and the maximum response was observed 40% (change in resistance in %) at 786 ppm at 250° C. These preliminary measurements showed that the on-chip deposited ZnO NWs could be a promising material for a CMOS based ethanol sensor.

  16. CMOS integration of inkjet-printed graphene for humidity sensing

    NASA Astrophysics Data System (ADS)

    Santra, S.; Hu, G.; Howe, R. C. T.; de Luca, A.; Ali, S. Z.; Udrea, F.; Gardner, J. W.; Ray, S. K.; Guha, P. K.; Hasan, T.

    2015-11-01

    We report on the integration of inkjet-printed graphene with a CMOS micro-electro-mechanical-system (MEMS) microhotplate for humidity sensing. The graphene ink is produced via ultrasonic assisted liquid phase exfoliation in isopropyl alcohol (IPA) using polyvinyl pyrrolidone (PVP) polymer as the stabilizer. We formulate inks with different graphene concentrations, which are then deposited through inkjet printing over predefined interdigitated gold electrodes on a CMOS microhotplate. The graphene flakes form a percolating network to render the resultant graphene-PVP thin film conductive, which varies in presence of humidity due to swelling of the hygroscopic PVP host. When the sensors are exposed to relative humidity ranging from 10-80%, we observe significant changes in resistance with increasing sensitivity from the amount of graphene in the inks. Our sensors show excellent repeatability and stability, over a period of several weeks. The location specific deposition of functional graphene ink onto a low cost CMOS platform has the potential for high volume, economic manufacturing and application as a new generation of miniature, low power humidity sensors for the internet of things.

  17. CMOS integration of inkjet-printed graphene for humidity sensing.

    PubMed

    Santra, S; Hu, G; Howe, R C T; De Luca, A; Ali, S Z; Udrea, F; Gardner, J W; Ray, S K; Guha, P K; Hasan, T

    2015-11-30

    We report on the integration of inkjet-printed graphene with a CMOS micro-electro-mechanical-system (MEMS) microhotplate for humidity sensing. The graphene ink is produced via ultrasonic assisted liquid phase exfoliation in isopropyl alcohol (IPA) using polyvinyl pyrrolidone (PVP) polymer as the stabilizer. We formulate inks with different graphene concentrations, which are then deposited through inkjet printing over predefined interdigitated gold electrodes on a CMOS microhotplate. The graphene flakes form a percolating network to render the resultant graphene-PVP thin film conductive, which varies in presence of humidity due to swelling of the hygroscopic PVP host. When the sensors are exposed to relative humidity ranging from 10-80%, we observe significant changes in resistance with increasing sensitivity from the amount of graphene in the inks. Our sensors show excellent repeatability and stability, over a period of several weeks. The location specific deposition of functional graphene ink onto a low cost CMOS platform has the potential for high volume, economic manufacturing and application as a new generation of miniature, low power humidity sensors for the internet of things.

  18. Development of CMOS Imager Block for Capsule Endoscope

    NASA Astrophysics Data System (ADS)

    Shafie, S.; Fodzi, F. A. M.; Tung, L. Q.; Lioe, D. X.; Halin, I. A.; Hasan, W. Z. W.; Jaafar, H.

    2014-04-01

    This paper presents the development of imager block to be associated in a capsule endoscopy system. Since the capsule endoscope is used to diagnose gastrointestinal diseases, the imager block must be in small size which is comfortable for the patients to swallow. In this project, a small size 1.5V button battery is used as the power supply while the voltage supply requirements for other components such as microcontroller and CMOS image sensor are higher. Therefore, a voltage booster circuit is proposed to boost up the voltage supply from 1.5V to 3.3V. A low power microcontroller is used to generate control pulses for the CMOS image sensor and to convert the 8-bits parallel data output to serial data to be transmitted to the display panel. The results show that the voltage booster circuit was able to boost the voltage supply from 1.5V to 3.3V. The microcontroller precisely controls the CMOS image sensor to produce parallel data which is then serialized again by the microcontroller. The serial data is then successfully translated to 2fps image and displayed on computer.

  19. On-chip digital noise reduction for integrated CMOS Cameras

    NASA Astrophysics Data System (ADS)

    Rullmann, Markus; Schluessler, Jens-Uwe; Schueffny, Rene

    2003-06-01

    We propose an on-line noise reduction system especially designed for noisy CMOS image sensors. Image sequences from CMOS sensors in general are corrupted by two types of noise, temporal noise and fixed pattern noise (FPN). It is shown how the FPN component can be estimated from a sequence. We studied the theoretical performance of two different approaches called direct and indirect FPN estimation. We show that indirect estimation gives superior performance, both theoretically and by simulations. The FPN estimates can be used to improve the image quality by compensating it. We assess the quality of the estimates by the achievable SNR gains. Using those results a dedicated filtering scheme has been designed to accomplish both temporal noise reduction and FPN correction by applying a single noise filter. It allows signal gains of up to 12dB and provides a high visual quality of the results. We further analyzed and optimized the memory size and bandwidth requirements of our scheme and conclude that it is possible to implement it in hardware. The required memory size is 288kByte and the memory access rate is 70MHz. Our algorithm allows the integration of noisy CMOS sensors with digital noise reduction and other circuitry on a system-on-chip solution.

  20. Noise sources and noise suppression in CMOS imagers

    NASA Astrophysics Data System (ADS)

    Pain, Bedabrata; Cunningham, Thomas J.; Hancock, Bruce R.

    2004-01-01

    Mechanisms for noise coupling in CMOS imagers are complex, since unlike a CCD, a CMOS imager has to be considered as a full digital-system-on-a-chip, with a highly sensitive front-end. In this paper, we analyze the noise sources in a photodiode CMOS imager, and model their propagation through the signal chain to determine the nature and magnitude of noise coupling. We present methods for reduction of noise, and present measured data to show their viability. For temporal read noise reduction, we present pixel signal chain design techniques to achieve near 2 electrons read noise. We model the front-end reset noise both for conventional photodiode and CTIA type of pixels. For the suppression of reset noise, we present a column feedback-reset method to reduce reset noise below 6 electrons. For spatial noise reduction, we present the design of column signal chain that suppresses both spatial noise and power supply coupling noise. We conclude by identifying problems in low-noise design caused by dark current spatial distribution.

  1. An integrated CMOS detection system for optical short-pulse

    NASA Astrophysics Data System (ADS)

    Kim, Chang-Gun; Hong, Nam-Pyo; Choi, Young-Wan

    2014-03-01

    We present design of a front-end readout system consisting of charge sensitive amplifier (CSA) and pulse shaper for detection of stochastic and ultra-small semiconductor scintillator signal. The semiconductor scintillator is double sided silicon detector (DSSD) or avalanche photo detector (APD) for high resolution and peak signal reliability of γ-ray or X-ray spectroscopy. Such system commonly uses low noise multichannel CSA. Each CSA in multichannel includes continuous reset system based on tens of MΩ and charge-integrating capacitor in feedback loop. The high value feedback resistor requires large area and huge power consumption for integrated circuits. In this paper, we analyze these problems and propose a CMOS short pulse detection system with a novel CSA. The novel CSA is composed of continuous reset system with combination of diode connected PMOS and 100 fF. This structure has linearity with increased input charge quantity from tens of femto-coulomb to pico-coulomb. Also, the front-end readout system includes both slow and fast shapers for detecting CSA output and preventing pile-up distortion. Shaping times of fast and slow shapers are 150 ns and 1.4 μs, respectively. Simulation results of the CMOS detection system for optical short-pulse implemented in 0.18 μm CMOS technology are presented.

  2. Optimizing quantum efficiency in a stacked CMOS sensor

    NASA Astrophysics Data System (ADS)

    Hannebauer, Rob; Yoo, Sang Keun; Gilblom, David L.; Gilblom, Alexander D.

    2011-03-01

    Optimizing quantum efficiency of image sensors, whether CCD or CMOS, has usually required backside thinning to bring the photon receiving surface close to the charge generation elements. A new CMOS sensor architecture has been developed that permits high-fill-factor photodiodes to be placed at the silicon surface without the need for backside thinning. The photodiode access provided by this architecture permits application of highly-effective anti-reflection coatings on the input surface and construction of a mirror inside the silicon below the photodiodes to effectively double the optical thickness of the silicon charge generation volume. Secondary benefits of this architecture include prevention of light from reaching the CMOS circuitry under the photodiodes, improvement of near-infrared quantum efficiency, and reduction in optical artifacts caused by reflections from the sensor surface. Utilizing these techniques, a sensor is being constructed with 4096 x 4096 pixels 4.8 μm square with 95% fill factor backed by a mirror tuned to the 400-700 nm visible band and a front-surface anti-reflectance coating. The quantum efficiency is expected to exceed 80% through the visible and the global shutter extinction ratio should exceed 106:1. The sensors have been fabricated and first test data is due in February 2011.

  3. Optimization of precision localization microscopy using CMOS camera technology

    NASA Astrophysics Data System (ADS)

    Fullerton, Stephanie; Bennett, Keith; Toda, Eiji; Takahashi, Teruo

    2012-02-01

    Light microscopy imaging is being transformed by the application of computational methods that permit the detection of spatial features below the optical diffraction limit. Successful localization microscopy (STORM, dSTORM, PALM, PhILM, etc.) relies on the precise position detection of fluorescence emitted by single molecules using highly sensitive cameras with rapid acquisition speeds. Electron multiplying CCD (EM-CCD) cameras are the current standard detector for these applications. Here, we challenge the notion that EM-CCD cameras are the best choice for precision localization microscopy and demonstrate, through simulated and experimental data, that certain CMOS detector technology achieves better localization precision of single molecule fluorophores. It is well-established that localization precision is limited by system noise. Our findings show that the two overlooked noise sources relevant for precision localization microscopy are the shot noise of the background light in the sample and the excess noise from electron multiplication in EM-CCD cameras. At low light conditions (< 200 photons/fluorophore) with no optical background, EM-CCD cameras are the preferred detector. However, in practical applications, optical background noise is significant, creating conditions where CMOS performs better than EM-CCD. Furthermore, the excess noise of EM-CCD is equivalent to reducing the information content of each photon detected which, in localization microscopy, reduces the precision of the localization. Thus, new CMOS technology with 100fps, <1.3 e- read noise and high QE is the best detector choice for super resolution precision localization microscopy.

  4. CMOS integration of inkjet-printed graphene for humidity sensing

    PubMed Central

    Santra, S.; Hu, G.; Howe, R. C. T.; De Luca, A.; Ali, S. Z.; Udrea, F.; Gardner, J. W.; Ray, S. K.; Guha, P. K.; Hasan, T.

    2015-01-01

    We report on the integration of inkjet-printed graphene with a CMOS micro-electro-mechanical-system (MEMS) microhotplate for humidity sensing. The graphene ink is produced via ultrasonic assisted liquid phase exfoliation in isopropyl alcohol (IPA) using polyvinyl pyrrolidone (PVP) polymer as the stabilizer. We formulate inks with different graphene concentrations, which are then deposited through inkjet printing over predefined interdigitated gold electrodes on a CMOS microhotplate. The graphene flakes form a percolating network to render the resultant graphene-PVP thin film conductive, which varies in presence of humidity due to swelling of the hygroscopic PVP host. When the sensors are exposed to relative humidity ranging from 10–80%, we observe significant changes in resistance with increasing sensitivity from the amount of graphene in the inks. Our sensors show excellent repeatability and stability, over a period of several weeks. The location specific deposition of functional graphene ink onto a low cost CMOS platform has the potential for high volume, economic manufacturing and application as a new generation of miniature, low power humidity sensors for the internet of things. PMID:26616216

  5. Single photon detection and localization accuracy with an ebCMOS camera

    NASA Astrophysics Data System (ADS)

    Cajgfinger, T.; Dominjon, A.; Barbier, R.

    2015-07-01

    The CMOS sensor technologies evolve very fast and offer today very promising solutions to existing issues facing by imaging camera systems. CMOS sensors are very attractive for fast and sensitive imaging thanks to their low pixel noise (1e-) and their possibility of backside illumination. The ebCMOS group of IPNL has produced a camera system dedicated to Low Light Level detection and based on a 640 kPixels ebCMOS with its acquisition system. After reminding the principle of detection of an ebCMOS and the characteristics of our prototype, we confront our camera to other imaging systems. We compare the identification efficiency and the localization accuracy of a point source by four different photo-detection devices: the scientific CMOS (sCMOS), the Charge Coupled Device (CDD), the Electron Multiplying CCD (emCCD) and the Electron Bombarded CMOS (ebCMOS). Our ebCMOS camera is able to identify a single photon source in less than 10 ms with a localization accuracy better than 1 μm. We report as well efficiency measurement and the false positive identification of the ebCMOS camera by identifying more than hundreds of single photon sources in parallel. About 700 spots are identified with a detection efficiency higher than 90% and a false positive percentage lower than 5. With these measurements, we show that our target tracking algorithm can be implemented in real time at 500 frames per second under a photon flux of the order of 8000 photons per frame. These results demonstrate that the ebCMOS camera concept with its single photon detection and target tracking algorithm is one of the best devices for low light and fast applications such as bioluminescence imaging, quantum dots tracking or adaptive optics.

  6. CMOS Integrated Single Electron Transistor Electrometry (CMOS-SET) circuit design for nanosecond quantum-bit read-out.

    SciTech Connect

    Gurrieri, Thomas M.; Lilly, Michael Patrick; Carroll, Malcolm S.; Levy, James E.

    2008-08-01

    Novel single electron transistor (SET) read-out circuit designs are described. The circuits use a silicon SET interfaced to a CMOS voltage mode or current mode comparator to obtain a digital read-out of the state of the qubit. The design assumes standard submicron (0.35 um) CMOS SOI technology using room temperature SPICE models. Implications and uncertainties related to the temperature scaling of these models to 100mK operation are discussed. Using this technology, the simulations predict a read-out operation speed of approximately Ins and a power dissipation per cell as low as 2nW for single-shot read-out, which is a significant advantage over currently used radio frequency SET (RF-SET) approaches.

  7. Investigation of CMOS photodiodes integrated on an ASIC by a 0.5-µm analog CMOS process

    NASA Astrophysics Data System (ADS)

    Luo, H.; Ricklefs, U.; Hillmer, H.

    2010-04-01

    The characteristics of photodiodes integrated on CMOS ASICs depend on wavelength of radiation, structure of the photodiode itself and the parameters of the process of production. In this paper, the influence of the structure of integrated CMOS photodiodes produced in a standard 0.5 μm mixed signal CMOS process on the sensitivity is described. These photodiodes are used as image sensor elements arranged in an array for noncontact optoelectronic measurements. Models of integrated photodiodes distinguish the lateral and the vertical region of the photodiodes. The standard 0.5 μm CMOS process offers three types of pn-junctions: n+/p-substrate, p+/n-well and n-well/p-substrate. Based on our previous research and on the results from other authors the p+/n-well is chosen due to its better sensitivity and isolation against other structures. The local sensitivity is measured with a scanning setup by applying a diffraction limited spot spot of light on the surface of the diodes. Independent of the wavelength of radiation the charge carriers are generated mainly in the lateral region and not - as expected - in the vertical region. The maximum value of the local sensitivity is found in photodiodes with subdivided p+ regions showing a distance of 1.5 μm between these regions in the space between these two adjacent p+ regions. This local sensitivity is three times smaller than that of a reference PIN photodiode. According to this result, the new photodiodes will be constructed with optimized geometries. All examined structures of this type of photodiodes show a maximal spectral sensitivity in the range of 650 nm - 700 nm.

  8. VAMPIRE microarray suite: a web-based platform for the interpretation of gene expression data.

    PubMed

    Hsiao, Albert; Ideker, Trey; Olefsky, Jerrold M; Subramaniam, Shankar

    2005-07-01

    Microarrays are invaluable high-throughput tools used to snapshot the gene expression profiles of cells and tissues. Among the most basic and fundamental questions asked of microarray data is whether individual genes are significantly activated or repressed by a particular stimulus. We have previously presented two Bayesian statistical methods for this level of analysis, collectively known as variance-modeled posterior inference with regional exponentials (VAMPIRE). These methods each require a sophisticated modeling step followed by integration of a posterior probability density. We present here a publicly available, web-based platform that allows users to easily load data, associate related samples and identify differentially expressed features using the VAMPIRE statistical framework. In addition, this suite of tools seamlessly integrates a novel gene annotation tool, known as GOby, which identifies statistically overrepresented gene groups. Unlike other tools in this genre, GOby can localize enrichment while respecting the hierarchical structure of annotation systems like Gene Ontology (GO). By identifying statistically significant enrichment of GO terms, Kyoto Encyclopedia of Genes and Genomes pathways, and TRANSFAC transcription factor binding sites, users can gain substantial insight into the physiological significance of sets of differentially expressed genes. The VAMPIRE microarray suite can be accessed at http://genome.ucsd.edu/microarray.

  9. Non-contact protein microarray fabrication using a procedure based on liquid bridge formation.

    PubMed

    Hartmann, Michael; Sjödahl, Johan; Stjernström, Mårten; Redeby, Johan; Joos, Thomas; Roeraade, Johan

    2009-01-01

    Contemporary microarrayers of contact or non-contact format used in protein microarray fabrication still suffer from a number of problems, e.g. generation of satellite spots, inhomogeneous spots, misplaced or even absent spots, and sample carryover. In this paper, a new concept of non-contact sample deposition that reduces such problems is introduced. To show the potential and robustness of this pressure-assisted deposition technique, different sample solutions known to cause severe problems or to be even impossible to print with conventional microarrayers were accurately printed. The samples included 200 mg mL(-1) human serum albumin, highly concentrated sticky cell adhesion proteins, pure high-salt cell-lysis buffer, pure DMSO, and a suspension of 5-microm polystyrene beads. Additionally, a water-immiscible liquid fluorocarbon, which was shown not to affect the functionality of the capture molecules, was employed as a lid to reduce evaporation during microarray printing. The fluorocarbon liquid lid was shown to circumvent hydrolysis of water-sensitive activated surfaces during long-term deposition procedures. PMID:19023564

  10. Recognition of multiple imbalanced cancer types based on DNA microarray data using ensemble classifiers.

    PubMed

    Yu, Hualong; Hong, Shufang; Yang, Xibei; Ni, Jun; Dan, Yuanyuan; Qin, Bin

    2013-01-01

    DNA microarray technology can measure the activities of tens of thousands of genes simultaneously, which provides an efficient way to diagnose cancer at the molecular level. Although this strategy has attracted significant research attention, most studies neglect an important problem, namely, that most DNA microarray datasets are skewed, which causes traditional learning algorithms to produce inaccurate results. Some studies have considered this problem, yet they merely focus on binary-class problem. In this paper, we dealt with multiclass imbalanced classification problem, as encountered in cancer DNA microarray, by using ensemble learning. We utilized one-against-all coding strategy to transform multiclass to multiple binary classes, each of them carrying out feature subspace, which is an evolving version of random subspace that generates multiple diverse training subsets. Next, we introduced one of two different correction technologies, namely, decision threshold adjustment or random undersampling, into each training subset to alleviate the damage of class imbalance. Specifically, support vector machine was used as base classifier, and a novel voting rule called counter voting was presented for making a final decision. Experimental results on eight skewed multiclass cancer microarray datasets indicate that unlike many traditional classification approaches, our methods are insensitive to class imbalance. PMID:24078908

  11. Experimental Approaches to Microarray Analysis of Tumor Samples

    ERIC Educational Resources Information Center

    Furge, Laura Lowe; Winter, Michael B.; Meyers, Jacob I.; Furge, Kyle A.

    2008-01-01

    Comprehensive measurement of gene expression using high-density nucleic acid arrays (i.e. microarrays) has become an important tool for investigating the molecular differences in clinical and research samples. Consequently, inclusion of discussion in biochemistry, molecular biology, or other appropriate courses of microarray technologies has…

  12. Demonstrating a Multi-drug Resistant Mycobacterium tuberculosis Amplification Microarray

    PubMed Central

    Linger, Yvonne; Kukhtin, Alexander; Golova, Julia; Perov, Alexander; Qu, Peter; Knickerbocker, Christopher; Cooney, Christopher G.; Chandler, Darrell P.

    2014-01-01

    Simplifying microarray workflow is a necessary first step for creating MDR-TB microarray-based diagnostics that can be routinely used in lower-resource environments. An amplification microarray combines asymmetric PCR amplification, target size selection, target labeling, and microarray hybridization within a single solution and into a single microfluidic chamber. A batch processing method is demonstrated with a 9-plex asymmetric master mix and low-density gel element microarray for genotyping multi-drug resistant Mycobacterium tuberculosis (MDR-TB). The protocol described here can be completed in 6 hr and provide correct genotyping with at least 1,000 cell equivalents of genomic DNA. Incorporating on-chip wash steps is feasible, which will result in an entirely closed amplicon method and system. The extent of multiplexing with an amplification microarray is ultimately constrained by the number of primer pairs that can be combined into a single master mix and still achieve desired sensitivity and specificity performance metrics, rather than the number of probes that are immobilized on the array. Likewise, the total analysis time can be shortened or lengthened depending on the specific intended use, research question, and desired limits of detection. Nevertheless, the general approach significantly streamlines microarray workflow for the end user by reducing the number of manually intensive and time-consuming processing steps, and provides a simplified biochemical and microfluidic path for translating microarray-based diagnostics into routine clinical practice. PMID:24796567

  13. The Importance of Normalization on Large and Heterogeneous Microarray Datasets

    EPA Science Inventory

    DNA microarray technology is a powerful functional genomics tool increasingly used for investigating global gene expression in environmental studies. Microarrays can also be used in identifying biological networks, as they give insight on the complex gene-to-gene interactions, ne...

  14. Demonstrating a multi-drug resistant Mycobacterium tuberculosis amplification microarray.

    PubMed

    Linger, Yvonne; Kukhtin, Alexander; Golova, Julia; Perov, Alexander; Qu, Peter; Knickerbocker, Christopher; Cooney, Christopher G; Chandler, Darrell P

    2014-04-25

    Simplifying microarray workflow is a necessary first step for creating MDR-TB microarray-based diagnostics that can be routinely used in lower-resource environments. An amplification microarray combines asymmetric PCR amplification, target size selection, target labeling, and microarray hybridization within a single solution and into a single microfluidic chamber. A batch processing method is demonstrated with a 9-plex asymmetric master mix and low-density gel element microarray for genotyping multi-drug resistant Mycobacterium tuberculosis (MDR-TB). The protocol described here can be completed in 6 hr and provide correct genotyping with at least 1,000 cell equivalents of genomic DNA. Incorporating on-chip wash steps is feasible, which will result in an entirely closed amplicon method and system. The extent of multiplexing with an amplification microarray is ultimately constrained by the number of primer pairs that can be combined into a single master mix and still achieve desired sensitivity and specificity performance metrics, rather than the number of probes that are immobilized on the array. Likewise, the total analysis time can be shortened or lengthened depending on the specific intended use, research question, and desired limits of detection. Nevertheless, the general approach significantly streamlines microarray workflow for the end user by reducing the number of manually intensive and time-consuming processing steps, and provides a simplified biochemical and microfluidic path for translating microarray-based diagnostics into routine clinical practice.

  15. CMOS compatible thin-film ALD tungsten nanoelectromechanical devices

    NASA Astrophysics Data System (ADS)

    Davidson, Bradley Darren

    This research focuses on the development of a novel, low-temperature, CMOS compatible, atomic-layer-deposition (ALD) enabled NEMS fabrication process for the development of ALD Tungsten (WALD) NEMS devices. The devices are intended for use in CMOS/NEMS hybrid systems, and NEMS based micro-processors/controllers capable of reliable operation in harsh environments not accessible to standard CMOS technologies. The majority of NEMS switches/devices to date have been based on carbon-nano-tube (CNT) designs. The devices consume little power during actuation, and as expected, have demonstrated actuation voltages much smaller than MEMS switches. Unfortunately, NEMS CNT switches are not typically CMOS integrable due to the high temperatures required for their growth, and their fabrication typically results in extremely low and unpredictable yields. Thin-film NEMS devices offer great advantages over reported CNT devices for several reasons, including: higher fabrication yields, low-temperature (CMOS compatible) deposition techniques like ALD, and increased control over design parameters/device performance metrics, i.e., device geometry. Furthermore, top-down, thin-film, nano-fabrication techniques are better capable of producing complicated device geometries than CNT based processes, enabling the design and development of multi-terminal switches well-suited for low-power hybrid NEMS/CMOS systems as well as electromechanical transistors and logic devices for use in temperature/radiation hard computing architectures. In this work several novel, low-temperature, CMOS compatible fabrication technologies, employing WALD as a structural layer for MEMS or NEMS devices, were developed. The technologies developed are top-down nano-scale fabrication processes based on traditional micro-machining techniques commonly used in the fabrication of MEMS devices. Using these processes a variety of novel WALD NEMS devices have been successfully fabricated and characterized. Using two different

  16. Use and imaging performance of CMOS flat panel imager with LiF/ZnS(Ag) and Gadox scintillation screens for neutron radiography

    NASA Astrophysics Data System (ADS)

    Cha, B. K.; kim, J. Y.; Kim, T. J.; Sim, C.; Cho, G.; Lee, D. H.; Seo, C.-W.; Jeon, S.; Huh, Y.

    2011-01-01

    In digital neutron radiography system, a thermal neutron imaging detector based on neutron-sensitive scintillating screens with CMOS(complementary metal oxide semiconductor) flat panel imager is introduced for non-destructive testing (NDT) application. Recently, large area CMOS APS (active-pixel sensor) in conjunction with scintillation films has been widely used in many digital X-ray imaging applications. Instead of typical imaging detectors such as image plates, cooled-CCD cameras and amorphous silicon flat panel detectors in combination with scintillation screens, we tried to apply a scintillator-based CMOS APS to neutron imaging detection systems for high resolution neutron radiography. In this work, two major Gd2O2S:Tb and 6LiF/ZnS:Ag scintillation screens with various thickness were fabricated by a screen printing method. These neutron converter screens consist of a dispersion of Gd2O2S:Tb and 6LiF/ZnS:Ag scintillating particles in acrylic binder. These scintillating screens coupled-CMOS flat panel imager with 25x50mm2 active area and 48μm pixel pitch was used for neutron radiography. Thermal neutron flux with 6x106n/cm2/s was utilized at the NRF facility of HANARO in KAERI. The neutron imaging characterization of the used detector was investigated in terms of relative light output, linearity and spatial resolution in detail. The experimental results of scintillating screen-based CMOS flat panel detectors demonstrate possibility of high sensitive and high spatial resolution imaging in neutron radiography system.

  17. Genomic-Wide Analysis with Microarrays in Human Oncology

    PubMed Central

    Inaoka, Kenichi; Inokawa, Yoshikuni; Nomoto, Shuji

    2015-01-01

    DNA microarray technologies have advanced rapidly and had a profound impact on examining gene expression on a genomic scale in research. This review discusses the history and development of microarray and DNA chip devices, and specific microarrays are described along with their methods and applications. In particular, microarrays have detected many novel cancer-related genes by comparing cancer tissues and non-cancerous tissues in oncological research. Recently, new methods have been in development, such as the double-combination array and triple-combination array, which allow more effective analysis of gene expression and epigenetic changes. Analysis of gene expression alterations in precancerous regions compared with normal regions and array analysis in drug-resistance cancer tissues are also successfully performed. Compared with next-generation sequencing, a similar method of genome analysis, several important differences distinguish these techniques and their applications. Development of novel microarray technologies is expected to contribute to further cancer research.

  18. An ultralow background substrate for protein microarray technology.

    PubMed

    Feng, Hui; Zhang, Qingyang; Ma, Hongwei; Zheng, Bo

    2015-08-21

    We herein report an ultralow background substrate for protein microarrays. Conventional protein microarray substrates often suffer from non-specific protein adsorption and inhomogeneous spot morphology. Consequently, surface treatment and a suitable printing solution are required to improve the microarray performance. In the current work, we improved the situation by developing a new microarray substrate based on a fluorinated ethylene propylene (FEP) membrane. A polydopamine microspot array was fabricated on the FEP membrane, with proteins conjugated to the FEP surface through polydopamine. Uniform microspots were obtained on FEP without the application of a special printing solution. The modified FEP membrane demonstrated ultralow background signal and was applied in protein and peptide microarray analysis. PMID:26134063

  19. cDNA microarray screening in food safety.

    PubMed

    Roy, Sashwati; Sen, Chandan K

    2006-04-01

    The cDNA microarray technology and related bioinformatics tools presents a wide range of novel application opportunities. The technology may be productively applied to address food safety. In this mini-review article, we present an update highlighting the late breaking discoveries that demonstrate the vitality of cDNA microarray technology as a tool to analyze food safety with reference to microbial pathogens and genetically modified foods. In order to bring the microarray technology to mainstream food safety, it is important to develop robust user-friendly tools that may be applied in a field setting. In addition, there needs to be a standardized process for regulatory agencies to interpret and act upon microarray-based data. The cDNA microarray approach is an emergent technology in diagnostics. Its values lie in being able to provide complimentary molecular insight when employed in addition to traditional tests for food safety, as part of a more comprehensive battery of tests.

  20. Finding dominant sets in microarray data.

    PubMed

    Fu, Xuping; Teng, Li; Li, Yao; Chen, Wenbin; Mao, Yumin; Shen, I-Fan; Xie, Yi

    2005-01-01

    Clustering allows us to extract groups of genes that are tightly coexpressed from Microarray data. In this paper, a new method DSF_Clust is developed to find dominant sets (clusters). We have preformed DSF_Clust on several gene expression datasets and given the evaluation with some criteria. The results showed that this approach could cluster dominant sets of good quality compared to kmeans method. DSF_Clust deals with three issues that have bedeviled clustering, some dominant sets being statistically determined in a significance level, predefining cluster structure being not required, and the quality of a dominant set being ensured. We have also applied this approach to analyze published data of yeast cell cycle gene expression and found some biologically meaningful gene groups to be dug out. Furthermore, DSF_Clust is a potentially good tool to search for putative regulatory signals.