System-level integration of active silicon photonic biosensors

NASA Astrophysics Data System (ADS)

Laplatine, L.; Al'Mrayat, O.; Luan, E.; Fang, C.; Rezaiezadeh, S.; Ratner, D. M.; Cheung, K.; Dattner, Y.; Chrostowski, L.

2017-02-01

Biosensors based on silicon photonic integrated circuits have attracted a growing interest in recent years. The use of sub-micron silicon waveguides to propagate near-infrared light allows for the drastic reduction of the optical system size, while increasing its complexity and sensitivity. Using silicon as the propagating medium also leverages the fabrication capabilities of CMOS foundries, which offer low-cost mass production. Researchers have deeply investigated photonic sensor devices, such as ring resonators, interferometers and photonic crystals, but the practical integration of silicon photonic biochips as part of a complete system has received less attention. Herein, we present a practical system-level architecture which can be employed to integrate the aforementioned photonic biosensors. We describe a system based on 1 mm2 dies that integrate germanium photodetectors and a single light coupling device. The die are embedded into a 16x16 mm2 epoxy package to enable microfluidic and electrical integration. First, we demonstrate a simple process to mimic Fan-Out Wafer-level-Packaging, which enables low-cost mass production. We then characterize the photodetectors in the photovoltaic mode, which exhibit high sensitivity at low optical power. Finally, we present a new grating coupler concept to relax the lateral alignment tolerance down to +/- 50 μm at 1-dB (80%) power penalty, which should permit non-experts to use the biochips in a"plug-and-play" style. The system-level integration demonstrated in this study paves the way towards the mass production of low-cost and highly sensitive biosensors, and can facilitate their wide adoption for biomedical and agro-environmental applications.

Spintronic microfluidic platform for biomedical and environmental applications

NASA Astrophysics Data System (ADS)

Cardoso, F. A.; Martins, V. C.; Fonseca, L. P.; Germano, J.; Sousa, L. A.; Piedade, M. S.; Freitas, P. P.

2010-09-01

Faster, more sensitive and easy to operate biosensing devices still are a need at important areas such as biomedical diagnostics, food control and environmental monitoring. Recently, spintronic-devices have emerged as a promising alternative to the existent technologies [1-3]. A number of advantages, namely high sensitivity, easy integration, miniaturization, scalability, robustness and low cost make these devices potentially capable of responding to the existent technological need. In parallel, the field of microfluidics has shown great advances [4]. Microfluidic systems allow the analysis of small sample volumes (from micro- down to pico-liters), often by automate sample processing with the ability to integrate several steps into a single device (analyte amplification, concentration, separation and/or labeling), all in a reduced assay time (minutes to hours) and affordable cost. The merging of these two technologies, magnetoresistive biochips and microfluidics, will enable the development of highly competitive devices. This work reports the integration of a magnetoresistive biochip with a microfluidic system inside a portable and autonomous electronic platform aiming for a fully integrated device. A microfluidic structure fabricated in polydimethylsiloxane with dimensions of W: 0.5mm, H: 0.1mm, L: 10mm, associated to a mechanical system to align and seal the channel by pressure is presented (Fig. 1) [5]. The goal is to perform sample loading and transportation over the chip and simultaneously control the stringency and uniformity of the wash-out process. The biochip output is acquired by an electronic microsystem incorporating the circuitry to control, address and read-out the 30 spin-valve sensors sequentially (Fig. 1) [2]. This platform is being applied to the detection of water-borne microbial pathogens (e.g. Salmonella and Escherichia coli) and genetic diseases diagnosis (e.g. cystic fibrosis) through DNA hybridization assays. Open chamber measurements were performed as described elsewhere [2]. Briefly, a 20 μl sample droplet is manually dispensed over the chip, limited by a polymeric frame. When using the microfluidic system for sample loading, a known volume of sample is introduced into the fluidic system through the help of a syringe pump at a controlled velocity.

Effect of Bio char on Plant Growth and Aluminium Form of Soil under Aluminium Stress

NASA Astrophysics Data System (ADS)

Qian, Lianwen; Li, Qingbiao; Sun, Jingwei; Feng, Ying

2018-01-01

Aluminium-enriched acid red soils in South China easily cause aluminium toxicity to plants, but biochip can improve soils and eliminate soil contaminations. In this project, biochip was used in potted plant control test to study the effect of biochip on plant growth in soil under acid aluminium stress and the migration and conversion of aluminium in plant-soil system. The fin dings show that the application of biochip increases the pH value of soil under aluminium stress significantly, changes the existing form of aluminium ion in soil, reduces the plants’ absorption of aluminium, and alleviates the aluminium toxicity to plants, but too much biochip may inhibit the growth of plants. In this case, further study should be carried out as regards the volume and way of biochip input in practical applications as well as the timeliness of aluminium toxicity removal.

OpenDrop: An Integrated Do-It-Yourself Platform for Personal Use of Biochips

PubMed Central

Alistar, Mirela; Gaudenz, Urs

2017-01-01

Biochips, or digital labs-on-chip, are developed with the purpose of being used by laboratory technicians or biologists in laboratories or clinics. In this article, we expand this vision with the goal of enabling everyone, regardless of their expertise, to use biochips for their own personal purposes. We developed OpenDrop, an integrated electromicrofluidic platform that allows users to develop and program their own bio-applications. We address the main challenges that users may encounter: accessibility, bio-protocol design and interaction with microfluidics. OpenDrop consists of a do-it-yourself biochip, an automated software tool with visual interface and a detailed technique for at-home operations of microfluidics. We report on two years of use of OpenDrop, released as an open-source platform. Our platform attracted a highly diverse user base with participants originating from maker communities, academia and industry. Our findings show that 47% of attempts to replicate OpenDrop were successful, the main challenge remaining the assembly of the device. In terms of usability, the users managed to operate their platforms at home and are working on designing their own bio-applications. Our work provides a step towards a future in which everyone will be able to create microfluidic devices for their personal applications, thereby democratizing parts of health care. PMID:28952524

Plastic-Based Structurally Programmable Microfluidic Biochips for Clinical Diagnostics

DTIC Science & Technology

2005-05-01

BIOCOMPATIBILITY CRITERIA OF SELECTED UV ADHESIVE LOCTITE 3211™......... 63 1 I. Executive Summary The objective of this project is to develop a smart...added into biochip design for improving the biocompatibility of entire biochip. Detailed problems include: • Design and development of structure... biocompatible biosensor array. 6 • Design and development of the sensor-to-circuit interface. Electronic Control System and Analyzer Design of the

A microfluidic system with integrated molecular imprinting polymer films for surface plasmon resonance detection

NASA Astrophysics Data System (ADS)

Huang, Shih-Chiang; Lee, Gwo-Bin; Chien, Fan-Ching; Chen, Shean-Jen; Chen, Wen-Janq; Yang, Ming-Chang

2006-07-01

This paper presents a novel microfluidic system with integrated molecular imprinting polymer (MIP) films designed for surface plasmon resonance (SPR) biosensing of multiple nanoscale biomolecules. The innovative microfluidic chip uses pneumatic microvalves and micropumps to transport a precise amount of the biosample through multiple microchannels to sensing regions containing the locally spin-coated MIP films. The signals of SPR biosensing are basically proportional to the number of molecules adsorbed on the MIP films. Hence, a precise control of flow rates inside microchannels is important to determine the adsorption amount of the molecules in the SPR/MIP chips. The integration of micropumps and microvalves can automate the sample introduction process and precisely control the amount of the sample injection to the microfluidic system. The proposed biochip enables the label-free biosensing of biomolecules in an automatic format, and provides a highly sensitive, highly specific and high-throughput detection performance. Three samples, i.e. progesterone, cholesterol and testosterone, are successfully detected using the developed system. The experimental results show that the proposed SPR/MIP microfluidic chip provides a comparable sensitivity to that of large-scale SPR techniques, but with reduced sample consumption and an automatic format. As such, the developed biochip has significant potential for a wide variety of nanoscale biosensing applications. The preliminary results of the current paper were presented at Transducers 2005, Seoul, Korea, 5-9 June 2005.

A portable cell-based impedance sensor for toxicity testing of drinking water.

PubMed

Curtis, Theresa M; Widder, Mark W; Brennan, Linda M; Schwager, Steven J; van der Schalie, William H; Fey, Julien; Salazar, Noe

2009-08-07

A major limitation to using mammalian cell-based biosensors for field testing of drinking water samples is the difficulty of maintaining cell viability and sterility without an on-site cell culture facility. This paper describes a portable automated bench-top mammalian cell-based toxicity sensor that incorporates enclosed fluidic biochips containing endothelial cells monitored by Electric Cell-substrate Impedance Sensing (ECIS) technology. Long-term maintenance of cells on the biochips is made possible by using a compact, self-contained disposable media delivery system. The toxicity sensor monitors changes in impedance of cell monolayers on the biochips after the introduction of water samples. The fluidic biochip includes an ECIS electronic layer and a polycarbonate channel layer, which together reduce initial impedance disturbances seen in commercially available open well ECIS chips caused by the mechanics of pipetting while maintaining the ability of the cells to respond to toxicants. A curve discrimination program was developed that compares impedance values over time between the control and treatment channels on the fluidic biochip and determines if they are significantly different. Toxicant responses of bovine pulmonary artery endothelial cells grown on fluidic biochips are similar to cells on commercially-available open well chips, and these cells can be maintained in the toxicity sensor device for at least nine days using an automated media delivery system. Longer-term cell storage is possible; bovine lung microvessel endothelial cells survive for up to four months on the fluidic biochips and remain responsive to a model toxicant. This is the first demonstration of a portable bench top system capable of both supporting cell health over extended periods of time and obtaining impedance measurements from endothelial cell monolayers after toxicant exposure.

Development towards compact nitrocellulose interferometric biochips for dry eye diagnosis based on MMP9, S100A6 and CST4 biomarkers using a Point-of-Care device

NASA Astrophysics Data System (ADS)

Santamaría, Beatriz; Laguna, María. Fe; López-Romero, David; López-Hernandez, A.; Sanza, F. J.; Lavín, A.; Casquel, R.; Maigler, M.; Holgado, M.

2018-02-01

A novel compact optical biochip based on a thin layer-sensing BICELL surface of nitrocellulose is used for in-situ labelfree detection of dry eye disease (DED). In this work the development of a compact biosensor that allows obtaining quantitative diagnosis with a limited volume of sample is reported. The designed sensors can be analyzed with an optical integrated Point-of-Care read-out system based on the "Increase Relative Optical Power" principle which enhances the performance and Limit of Detection. Several proteins involved with dry eye dysfunction have been validated as biomarkers. Presented biochip analyzes three of those biomarkers: MMP9, S100A6 and CST4. BICELLs based on nitrocellulose permit to immobilize antibodies for each biomarker recognition. The optical response obtained from the biosensor through the readout platform is capable to recognize specifically the desired proteins in the concentrations range for control eye (CE) and dry eye syndrome (DES). Preliminary results obtained will allow the development of a dry eye detection device useful in the area of ophthalmology and applicable to other possible diseases related to the eye dysfunction.

Bacteria Inside Semiconductors as Potential Sensor Elements: Biochip Progress

PubMed Central

Sah, Vasu R.; Baier, Robert E.

2014-01-01

It was discovered at the beginning of this Century that living bacteria—and specifically the extremophile Pseudomonas syzgii—could be captured inside growing crystals of pure water-corroding semiconductors—specifically germanium—and thereby initiated pursuit of truly functional “biochip-based” biosensors. This observation was first made at the inside ultraviolet-illuminated walls of ultrapure water-flowing semiconductor fabrication facilities (fabs) and has since been, not as perfectly, replicated in simpler flow cell systems for chip manufacture, described here. Recognizing the potential importance of these adducts as optical switches, for example, or probes of metabolic events, the influences of the fabs and their components on the crystal nucleation and growth phenomena now identified are reviewed and discussed with regard to further research needs. For example, optical beams of current photonic circuits can be more easily modulated by integral embedded cells into electrical signals on semiconductors. Such research responds to a recently published Grand Challenge in ceramic science, designing and synthesizing oxide electronics, surfaces, interfaces and nanoscale structures that can be tuned by biological stimuli, to reveal phenomena not otherwise possible with conventional semiconductor electronics. This short review addresses only the fabrication facilities' features at the time of first production of these potential biochips. PMID:24961215

Bacteria inside semiconductors as potential sensor elements: biochip progress.

PubMed

Sah, Vasu R; Baier, Robert E

2014-06-24

It was discovered at the beginning of this Century that living bacteria-and specifically the extremophile Pseudomonas syzgii-could be captured inside growing crystals of pure water-corroding semiconductors-specifically germanium-and thereby initiated pursuit of truly functional "biochip-based" biosensors. This observation was first made at the inside ultraviolet-illuminated walls of ultrapure water-flowing semiconductor fabrication facilities (fabs) and has since been, not as perfectly, replicated in simpler flow cell systems for chip manufacture, described here. Recognizing the potential importance of these adducts as optical switches, for example, or probes of metabolic events, the influences of the fabs and their components on the crystal nucleation and growth phenomena now identified are reviewed and discussed with regard to further research needs. For example, optical beams of current photonic circuits can be more easily modulated by integral embedded cells into electrical signals on semiconductors. Such research responds to a recently published Grand Challenge in ceramic science, designing and synthesizing oxide electronics, surfaces, interfaces and nanoscale structures that can be tuned by biological stimuli, to reveal phenomena not otherwise possible with conventional semiconductor electronics. This short review addresses only the fabrication facilities' features at the time of first production of these potential biochips.

Laser-assisted patterning of double-sided adhesive tapes for optofluidic chip integration

NASA Astrophysics Data System (ADS)

Zamora, Vanessa; Janeczka, Christian; Arndt-Staufenbiel, Norbert; Havlik, George; Queisser, Marco; Schröder, Henning

2018-02-01

Portable high-sensitivity biosensors exhibit a growing demand in healthcare, food industry and environmental monitoring sectors. Optical biosensors based on photonic integration platforms are attractive candidates due to their high sensitivity, compactness and multiplexing capabilities. However, they need a low-cost and reliable integration with the microfluidic system. Laser-micropatterned double-sided biocompatible adhesive tapes are promising bonding layers for hybrid integration of an optofluidic biochip. As a part of the EU-PHOCNOSIS project, double-sided adhesive tapes have been proposed to integrate the polymer microfluidic system with the optical integrated waveguide sensor chip. Here the adhesive tape should be patterned in a micrometer scale in order to create an interaction between the sample that flows through the polymer microchannel and the photonic sensing microstructure. Three laser-assisted structuring methods are investigated to transfer microchannel patterns to the adhesive tape. The test structure design consists of a single channel with 400 μm wide, 30 mm length and two circular receivers with 3 mm radius. The best structuring results are found by using the picosecond UV laser where smooth and straight channel cross-sections are obtained. Such patterned tapes are used to bond blank polymer substrates to blank silicon substrates. As a proof of concept, the hybrid integration is tested using colored DI-water. Structuring tests related to the reduction of channel widths are also considered in this work. The use of this technique enables a simple and rapid manufacturing of narrow channels (50-60 μm in width) in adhesive tapes, achieving a cheap and stable integration of the optofluidic biochip.

Research and development of biochip technologies in Taiwan

NASA Astrophysics Data System (ADS)

Ting, Solomon J.; Chiou, Arthur E. T.

2000-07-01

Recent advancements in several genome-sequencing projects have stimulated an enormous interest in microarray DNA chip technology, especially in the biomedical sciences and pharmaceutical industries. The DNA chips facilitated the miniaturization of conventional nucleic acid hybridizations, by either robotically spotting thousands of library cDNAs or in situ synthesis of high-density oligonucleotides onto solid supports. These innovations have found a wide range of applications in molecular biology, especially in studying gene expression and discovering new genes from the global view of genomic analysis. The research and development of this powerful tool has also received great attentions in Taiwan. In this paper, we report the current progresses of our DNA chip project, along with the current status of other biochip projects in Taiwan, such as protein chip, PCR chip, electrophoresis chip, olfactory chip, etc. The new development of biochip technologies integrates the biotechnology with the semiconductor processing, the micro- electro-mechanical, optoelectronic, and digital signal processing technologies. Most of these biochip technologies utilitze optical detection methods for data acquisition and analysis. The strengths and advantages of different approaches are compared and discussed in this report.

Whole-cell luminescence biosensor-based lab-on-chip integrated system for water toxicity analysis

NASA Astrophysics Data System (ADS)

Rabner, Arthur; Belkin, Shimshon; Rozen, Rachel; Shacham, Yosi

2006-01-01

A novel water chemical toxin sensor has been successfully developed and evaluated as a working portable laboratory prototype. This sensor relies on a disposable plastic biochip prepared with a 4x4 micro-laboratory (μLab) chambers array of Escherichia coli reporter cells and micro-fluidic channels for liquids translocation. Each bacterial strain has been genetically modified into a bioluminescent reporter that responds to a pre-determined class of chemical agents. When challenged with a water sample containing a toxic chemical, the sensor responds with an increased bioluminescent signal from the biochip that is monitored over time. The signal is received by a motorized photomultiplier-based analyzer and interpreted by signal processing software. We have performed several levels of analysis: (i) the change in the bioluminescent signal from the sensor bacteria serves as a rapid indication for the presence of toxic chemicals in the water sample; (ii) the intensity of the change indicates the toxin concentration level; and (iii) the pattern of the responses for the different members of the bacterial panel on the biochip characterizes the biological origin of the toxin. The analyzer contains housing mechanics, electro-optics for signal acquisition, motorized readout calibration accessories, hydro-pneumatics modules for water sample translocation into biochip micro laboratories, electronics for overall control and communication with the host computer. This prototype has a demonstrated sensitivity for broad classes of water-borne toxic chemicals including naladixic acid (a model genotoxic agent), botulinum and acetylcholine esterase inhibitors. This work has initiated an investigation of a novel handheld field-deployable Water Toxicity Analysis (WTA) device.

Development towards Compact Nitrocellulose-Based Interferometric Biochips for Dry Eye MMP9 Label-Free In-Situ Diagnosis

PubMed Central

Santamaría, Beatriz; Laguna, María F.; López-Romero, David; Hernandez, Ana L.; Sanza, Francisco J.; Lavín, Álvaro; Casquel, Rafael; Maigler, María V.; Espinosa, Rocío L.; Holgado, Miguel

2017-01-01

A novel compact optical biochip based on a thin layer-sensing surface of nitrocellulose is used for in-situ label-free detection of metalloproteinase (MMP9) related to dry eye disease. In this article, a new integrated chip with different interferometric transducers layout with an optimal sensing surface is reported for the first time. We demonstrate that specific antibodies can be immobilized onto these transducers with a very low volume of sample and with good orientation. Many sensing transducers constitute the presented biochip in order to yield statistical data and stability in the acquired measurements. As a result, we report the recognition curve for pure recombinant MMP9, tests of model tears with MMP9, and real tear performance from patients, with a promising limit of detection. PMID:28534808

Development of a biochip-based assay integrated in a global strategy for identification of fusion transcripts in acute myeloid leukemia: a work flow for acute myeloid leukemia diagnosis.

PubMed

Giusiano, S; Formisano-Tréziny, C; Benziane, A; Maroc, N; Picard, C; Hermitte, F; Taranger-Charpin, C; Gabert, J

2010-08-01

Three major types of rearrangements are involved in acute myeloid leukemias (AML): t(8;21)(q22;q22), inv(16)(p13q22), and 11q23/MLL abnormalities. Their precise identification becomes essential for diagnosis, prognosis, and therapeutic choices. Resulting fusion transcripts (FT) are also powerful markers for monitoring the efficacy of treatment, the minimal residual disease (MRD) and could become therapeutic targets. Today, the challenge is to propose an individual follow-up for each patient even for those with a rare fusion event. In this study, we propose a biochip-based assay integrated in a global strategy for identification of rare FT in AML, after fluorescence in situ hybridization detection, as described by the World Health Organization classification. Using cell lines, we developed and validated a biochip-based assay called the AMLFusionChip that identifies every FT of AML1-ETO, CBFbeta-MYH11 as well as MLL-AF9, MLL-ENL, MLL-AF6, and MLL-AF10. The original design of our AMLFusionChip.v01 enables the identification of these FT wherever the breakpoint on the partner gene may be. In case of biochip negative result, our 3'RACE amplification strategy enables to clone and then sequence the new translocation partner. This AMLFusionChip strategy fits into the concept of personalized medicine for the largest number of patients.

Intellectual property strategy in bioinformatics and biochips.

PubMed

Fernandez, Dennis; Chow, Mary

2005-07-15

Intellectual property rights are essential in today's technology-driven age. A strong intellectual property protection strategy is crucial in the bioinformatics and biochips technology spaces as monetary and temporal resources are tremendous in finding a blockbuster drug or gene therapy, as well as in deploying advanced biosensor and other medical systems. Current problems and intellectual property practice in the genomic space are presented and analyzed. Various strategy and solutions are proposed to guide bioinformatic and biochip companies in forming an aggressive strategy to protect one's intellectual property and competitive positioning.

Protein-diazonium adduct direct electrografting onto SPRi-biochip.

PubMed

Corgier, Benjamin P; Bellon, Sophie; Anger-Leroy, Marielle; Blum, Loïc J; Marquette, Christophe A

2009-08-18

A direct protein immobilization method for surface plasmon resonance imaging (SPRi) gold chip arraying is exposed. The biomolecule electroaddressing strategy, previously demonstrated by our team on carbon surfaces, is here valuably involved and adapted to create a straightforward and efficient protein immobilization process onto SPRi-biochips. The proteins, modified with an aryl-diazonium adduct, are addressed to the SPRi chip surface through the electroreduction of the aryl-diazonium. The biomolecule deposition was followed through SPRi live measurements during the electrografting process. A specially designed setup enabled us to directly observe the mass increasing at the sensor surface while the proteins were electrografted. A pin electrospotting method, allowing the achievement of distinct sensing layers on gold SPRi-biochips, was used to generate microarray biochips. The integrity of the immobilized proteins and the specificity of the detection, based on antigen/antibody interactions, were demonstrated for the detection of specific antibodies and ovalbumin. The SPRi detection limit of ovalbumin using the electroaddressing of anti-ovalbumin IgG was compared with two other immobilization procedures, cystamine-glutaraldehyde self-assembled monolayer and pyrrole, and was found to be a decade lower than these ones (100 ng/mL, i.e., 2 nM).

A microfluidic biochip platform for electrical quantification of proteins.

PubMed

Valera, Enrique; Berger, Jacob; Hassan, Umer; Ghonge, Tanmay; Liu, Julia; Rappleye, Michael; Winter, Jackson; Abboud, Daniel; Haidry, Zeeshan; Healey, Ryan; Hung, Na-Teng; Leung, Nathaniel; Mansury, Naif; Hasnain, Alexander; Lannon, Christine; Price, Zachary; White, Karen; Bashir, Rashid

2018-05-15

Sepsis, an adverse auto-immune response to an infection often causing life-threatening complications, results in the highest mortality and treatment cost of any illness in US hospitals. Several immune biomarker levels, including Interleukin 6 (IL-6), have shown a high correlation to the onset and progression of sepsis. Currently, no technology diagnoses and stratifies sepsis progression using biomarker levels. This paper reports a microfluidic biochip platform to detect proteins in undiluted human plasma samples. The device uses a differential enumeration platform that integrates Coulter counting principles, antigen specific capture chambers, and micro size bead based immunodetection to quantify cytokines. This microfluidic biochip was validated as a potential point of care technology by quantifying IL-6 from plasma samples (n = 29) with good correlation (R2 = 0.81) and agreement (Bland-Altman) compared to controls. In combination with previous applications, this point of care platform can potentially detect cell and protein biomarkers simultaneously for sepsis stratification.

Biochip scanner device

DOEpatents

Perov, Alexander; Belgovskiy, Alexander I.; Mirzabekov, Andrei D.

2001-01-01

A biochip scanner device used to detect and acquire fluorescence signal data from biological microchips or biochips and method of use are provided. The biochip scanner device includes a laser for emitting a laser beam. A modulator, such as an optical chopper modulates the laser beam. A scanning head receives the modulated laser beam and a scanning mechanics coupled to the scanning head moves the scanning head relative to the biochip. An optical fiber delivers the modulated laser beam to the scanning head. The scanning head collects the fluorescence light from the biochip, launches it into the same optical fiber, which delivers the fluorescence into a photodetector, such as a photodiode. The biochip scanner device is used in a row scanning method to scan selected rows of the biochip with the laser beam size matching the size of the immobilization site.

Portable biochip scanner device

DOEpatents

Perov, Alexander; Sharonov, Alexei; Mirzabekov, Andrei D.

2002-01-01

A portable biochip scanner device used to detect and acquire fluorescence signal data from biological microchips (biochips) is provided. The portable biochip scanner device employs a laser for emitting an excitation beam. An optical fiber delivers the laser beam to a portable biochip scanner. A lens collimates the laser beam, the collimated laser beam is deflected by a dichroic mirror and focused by an objective lens onto a biochip. The fluorescence light from the biochip is collected and collimated by the objective lens. The fluorescence light is delivered to a photomultiplier tube (PMT) via an emission filter and a focusing lens. The focusing lens focuses the fluorescence light into a pinhole. A signal output of the PMT is processed and displayed.

Single cell electroporation using proton beam fabricated biochips

NASA Astrophysics Data System (ADS)

Homhuan, S.; Zhang, B.; Sheu, F.-S.; Bettiol, A. A.; Watt, F.

2010-05-01

We report the design and fabrication of a novel single cell electroporation biochip fabricated by the Proton Beam Writing technique (PBW), a new technique capable of direct-writing high-aspect-ratio nano and microstructures. The biochip features nickel micro-electrodes with straight-side walls between which individual cells are positioned. By applying electrical impulses across the electrodes, SYTOX® Green nucleic acid stain is incorporated into mouse neuroblastoma (N2a) cells. When the stain binds with DNA inside the cell nucleus, green fluorescence is observed upon excitation from a halogen lamp. Three parameters; electric field strength, pulse duration, and the number of pulses have been considered and optimized for the single cell electroporation. The results show that our biochip gives successfully electroporated cells . This single cell electroporation system represents a promising method for investigating the introduction of a wide variety of fluorophores, nanoparticles, quantum dots, DNAs and proteins into cells.

A portable and integrated instrument for cell manipulation by dielectrophoresis.

PubMed

Burgarella, Sarah; Di Bari, Marco

2015-07-01

The physical manipulation of biological cells is a key point in the development of miniaturized systems for point-of-care analyses. Dielectrophoresis (DEP) has been reported by several laboratories as a promising method in biomedical research for label-free cell manipulation without physical contact, by exploiting the dielectric properties of cells suspended in a microfluidic sample, under the action of high-gradient electric fields. In view of a more extended use of DEP phenomena in lab-on-chip devices for point-of-care settings, we have developed a portable instrument, integrating on the same device the microfluidic biochip for cell manipulation and all the laboratory functions (i.e., DEP electric signal generation, microscopic observation of the biological sample under test and image acquisition) that are normally obtained by combining different nonportable standard laboratory instruments. The nonuniform electric field for cell manipulation on the biochip is generated by microelectrodes, patterned on the silicon substrate of microfluidic channels, using standard microfabrication techniques. Numerical modeling was performed to simulate the electric field distribution, quantify the DEP force, and optimize the geometry of the microelectrodes. The developed instrument includes an electronic board, which allows the control of the electric signal applied to electrodes necessary for DEP, and a miniaturized optical microscope system that allows visual inspection and eventually cell counting, as well as image and video recording. The system also includes the control software. The portable and integrated platform described in this work therefore represents a complete and innovative solution of applied research, suitable for many biological applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fabrication and characterization of semicircular detection electrodes for contactless conductivity detector - CE microchips.

PubMed

Lee, Chia-Yen; Chen, C M; Chang, Guan-Liang; Lin, Che-Hsin; Fu, Lung-Ming

2006-12-01

This study uses simple and reliable microfabrication techniques to fabricate CE biochips, integrating a novel contactless conductivity detector in a miniaturized detection system in a microfluidic biochip. The off-channel electrodes are deposited around side channels by Au sputtering and patterned using a standard "lift-off" process. A vacuum fusion bonding process is employed to seal the lower substrate containing the microchannels and the electrodes to an upper glass cover plate. The variations in the capacitance between the semicircular detection electrodes in the side channels are measured as different samples and ions pass through the detection region of the CE separation channel. Samples of Rhodamine B, commercial sports drinks, mineral waters, and a red wine, respectively, are mixed in different buffer solutions, separated, and successfully detected using the developed device. The semicircular detection electrodes for the contactless conductivity detector have microscale dimensions and provide a valuable contribution to the realization of the lab-on-a-chip concept.

Gold patterned biochips for on-chip immuno-MALDI-TOF MS: SPR imaging coupled multi-protein MS analysis.

PubMed

Kim, Young Eun; Yi, So Yeon; Lee, Chang-Soo; Jung, Yongwon; Chung, Bong Hyun

2012-01-21

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis of immuno-captured target protein efficiently complements conventional immunoassays by offering rich molecular information such as protein isoforms or modifications. Direct immobilization of antibodies on MALDI solid support enables both target enrichment and MS analysis on the same plate, allowing simplified and potentially multiplexing protein MS analysis. Reliable on-chip immuno-MALDI-TOF MS for multiple biomarkers requires successful adaptation of antibody array biochips, which also must accommodate consistent reaction conditions on antibody arrays during immuno-capture and MS analysis. Here we developed a facile fabrication process of versatile antibody array biochips for reliable on-chip MALDI-TOF-MS analysis of multiple immuno-captured proteins. Hydrophilic gold arrays surrounded by super-hydrophobic surfaces were formed on a gold patterned biochip via spontaneous chemical or protein layer deposition. From antibody immobilization to MALDI matrix treatment, this hydrophilic/phobic pattern allowed highly consistent surface reactions on each gold spot. Various antibodies were immobilized on these gold spots both by covalent coupling or protein G binding. Four different protein markers were successfully analyzed on the present immuno-MALDI biochip from complex protein mixtures including serum samples. Tryptic digests of captured PSA protein were also effectively detected by on-chip MALDI-TOF-MS. Moreover, the present MALDI biochip can be directly applied to the SPR imaging system, by which antibody and subsequent antigen immobilization were successfully monitored.

Compact handheld low-cost biosensor platform for remote health monitoring

NASA Astrophysics Data System (ADS)

Hastanin, J.; Lenaerts, C.; Gailly, P.; Jans, H.; Huang, C.; Lagae, L.; Kokkinos, D.; Fleury-Frenette, K.

2016-04-01

In this paper, we present an original concept of plasmonic-related instrumentation platform dedicated to diagnostic biosensing tests out of the laboratory. The developed instrumental platform includes both disposable one-use microfluidic affinity biochip and compact optical readout device for biochip monitoring involving mobile Internet devices for data processing and communication. The biochip includes both microfluidic and optical coupling structures formed into a single plastic slab. The microfluidic path of the biochip operates in passive capillary pumping mode. In the proof-of-concept prototype, we address specifically the sensing format involving Surface Plasmon Resonance phenomenon. The biochip is plugged in the readout device without the use of an index matching fluid. An essential advantage of the developed biochip is that its implementation involves conventional hot embossing and thin film deposition process, perfectly suited for mass production of low-cost microfluidic biochip for biochemical applications.

Advances in Testing Techniques for Digital Microfluidic Biochips

PubMed Central

Shukla, Vineeta; Hussin, Fawnizu Azmadi; Hamid, Nor Hisham; Zain Ali, Noohul Basheer

2017-01-01

With the advancement of digital microfluidics technology, applications such as on-chip DNA analysis, point of care diagnosis and automated drug discovery are common nowadays. The use of Digital Microfluidics Biochips (DMFBs) in disease assessment and recognition of target molecules had become popular during the past few years. The reliability of these DMFBs is crucial when they are used in various medical applications. Errors found in these biochips are mainly due to the defects developed during droplet manipulation, chip degradation and inaccuracies in the bio-assay experiments. The recently proposed Micro-electrode-dot Array (MEDA)-based DMFBs involve both fluidic and electronic domains in the micro-electrode cell. Thus, the testing techniques for these biochips should be revised in order to ensure proper functionality. This paper describes recent advances in the testing technologies for digital microfluidics biochips, which would serve as a useful platform for developing revised/new testing techniques for MEDA-based biochips. Therefore, the relevancy of these techniques with respect to testing of MEDA-based biochips is analyzed in order to exploit the full potential of these biochips. PMID:28749411

Advances in Testing Techniques for Digital Microfluidic Biochips.

PubMed

Shukla, Vineeta; Hussin, Fawnizu Azmadi; Hamid, Nor Hisham; Zain Ali, Noohul Basheer

2017-07-27

With the advancement of digital microfluidics technology, applications such as on-chip DNA analysis, point of care diagnosis and automated drug discovery are common nowadays. The use of Digital Microfluidics Biochips (DMFBs) in disease assessment and recognition of target molecules had become popular during the past few years. The reliability of these DMFBs is crucial when they are used in various medical applications. Errors found in these biochips are mainly due to the defects developed during droplet manipulation, chip degradation and inaccuracies in the bio-assay experiments. The recently proposed Micro-electrode-dot Array (MEDA)-based DMFBs involve both fluidic and electronic domains in the micro-electrode cell. Thus, the testing techniques for these biochips should be revised in order to ensure proper functionality. This paper describes recent advances in the testing technologies for digital microfluidics biochips, which would serve as a useful platform for developing revised/new testing techniques for MEDA-based biochips. Therefore, the relevancy of these techniques with respect to testing of MEDA-based biochips is analyzed in order to exploit the full potential of these biochips.

Multiplexed instrument-free meningitis diagnosis on a polymer/paper hybrid microfluidic biochip.

PubMed

Dou, Maowei; Sanjay, Sharma T; Dominguez, Delfina C; Liu, Peng; Xu, Feng; Li, XiuJun

2017-01-15

Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Haemophilus influenzae type b (Hib) are three most common pathogens accounting for most bacterial meningitis, a serious global infectious disease with high fatality, especially in developing nations. Because the treatment and antibiotics differ among each type, the identification of the exact bacteria causing the disease is vital. Herein, we report a polymer/paper hybrid microfluidic biochip integrated with loop-mediated isothermal amplification (LAMP) for multiplexed instrument-free diagnosis of these three major types of bacterial meningitis, with high sensitivity and specificity. Results can be visually observed by the naked eye or imaged by a smartphone camera under a portable UV light source. Without using any specialized laboratory instrument, the limits of detection of a few DNA copies per LAMP zone for N. meningitidis, S. pneumoniae and Hib were achieved within 1h. In addition, these three types of microorganisms spiked in artificial cerebrospinal fluid (ACSF) were directly detected simultaneously, avoiding cumbersome sample preparation procedures in conventional methods. Compared with the paper-free non-hybrid microfluidic biochip over a period of three months, the hybrid microfluidic biochip was found to have a much longer shelf life. Hence, this rapid, instrument-free and highly sensitive microfluidic approach has great potential for point-of-care (POC) diagnosis of multiple infectious diseases simultaneously, especially in resource-limited settings. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of an imaging method for quantifying a large digital PCR droplet

NASA Astrophysics Data System (ADS)

Huang, Jen-Yu; Lee, Shu-Sheng; Hsu, Yu-Hsiang

2017-02-01

Portable devices have been recognized as the future linkage between end-users and lab-on-a-chip devices. It has a user friendly interface and provides apps to interface headphones, cameras, and communication duct, etc. In particular, the digital resolution of cameras installed in smartphones or pads already has a high imaging resolution with a high number of pixels. This unique feature has triggered researches to integrate optical fixtures with smartphone to provide microscopic imaging capabilities. In this paper, we report our study on developing a portable diagnostic tool based on the imaging system of a smartphone and a digital PCR biochip. A computational algorithm is developed to processing optical images taken from a digital PCR biochip with a smartphone in a black box. Each reaction droplet is recorded in pixels and is analyzed in a sRGB (red, green, and blue) color space. Multistep filtering algorithm and auto-threshold algorithm are adopted to minimize background noise contributed from ccd cameras and rule out false positive droplets, respectively. Finally, a size-filtering method is applied to identify the number of positive droplets to quantify target's concentration. Statistical analysis is then performed for diagnostic purpose. This process can be integrated in an app and can provide a user friendly interface without professional training.

Microfluidic Biochip Design

NASA Technical Reports Server (NTRS)

Panzarella, Charles

2004-01-01

As humans prepare for the exploration of our solar system, there is a growing need for miniaturized medical and environmental diagnostic devices for use on spacecrafts, especially during long-duration space missions where size and power requirements are critical. In recent years, the biochip (or Lab-on-a- Chip) has emerged as a technology that might be able to satisfy this need. In generic terms, a biochip is a miniaturized microfluidic device analogous to the electronic microchip that ushered in the digital age. It consists of tiny microfluidic channels, pumps and valves that transport small amounts of sample fluids to biosensors that can perform a variety of tests on those fluids in near real time. It has the obvious advantages of being small, lightweight, requiring less sample fluids and reagents and being more sensitive and efficient than larger devices currently in use. Some of the desired space-based applications would be to provide smaller, more robust devices for analyzing blood, saliva and urine and for testing water and food supplies for the presence of harmful contaminants and microorganisms. Our group has undertaken the goal of adapting as well as improving upon current biochip technology for use in long-duration microgravity environments. In addition to developing computational models of the microfluidic channels, valves and pumps that form the basis of every biochip, we are also trying to identify potential problems that could arise in reduced gravity and develop solutions to these problems. One such problem is due to the prevalence of bubbly sample fluids in microgravity. A bubble trapped in a microfluidic channel could be detrimental to the operation of a biochip. Therefore, the process of bubble formation in microgravity needs to be studied, and a model of this process has been developed and used to understand how bubbles develop and move through biochip components. It is clear that some type of bubble filter would be necessary in Space, and several bubble filter designs are being evaluated.

Biochip-based instruments development for space exploration: influence of the antibody immobilization process on the biochip resistance to freeze-drying, temperature shifts and cosmic radiations

NASA Astrophysics Data System (ADS)

Coussot, G.; Moreau, T.; Faye, C.; Vigier, F.; Baqué, M.; Le Postollec, A.; Incerti, S.; Dobrijevic, M.; Vandenabeele-Trambouze, O.

2017-04-01

Due to the diversity of antibody (Ab)-based biochips chemistries available and the little knowledge about biochips resistance to space constraints, immobilization of Abs on the surface of the biochips dedicated to Solar System exploration is challenging. In the present paper, we have developed ten different biochip models including covalent or affinity immobilization with full-length Abs or Ab fragments. Ab immobilizations were carried out in oriented/non-oriented manner using commercial activated surfaces with N-hydroxysuccinic ester (NHS-surfaces) or homemade surfaces using three generations of dendrimers (dendrigraft of poly L-lysine (DGL) surfaces). The performances of the Ab -based surfaces were cross-compared on the following criteria: (i) analytical performances (expressed by both the surface density of immobilized Abs and the amount of antigens initially captured by the surface) and (ii) resistance of surfaces to preparation procedure (freeze-drying, storage) or spatial constraints (irradiation and temperature shifts) encountered during a space mission. The latter results have been expressed as percentage of surface binding capacity losses (or percentage of remaining active Abs). The highest amount of captured antigen was achieved with Ab surfaces having full-length Abs and DGL-surfaces that have much higher surface densities than commercial NHS-surface. After freeze-drying process, thermal shift and storage sample exposition, we found that more than 80% of surface binding sites remained active in this case. In addition, the resistance of Ab surfaces to irradiation with particles such as electron, carbon ions or protons depends not only on the chemistries (covalent/affinity linkages) and strategies (oriented/non-oriented) used to construct the biochip, but also on the type, energy and fluence of incident particles. Our results clearly indicate that full-length Ab immobilization on NHS-surfaces and DGL-surfaces should be preferred for potential use in instruments for planetary exploration.

Preparation and Testing of Impedance-based Fluidic Biochips with RTgill-W1 Cells for Rapid Evaluation of Drinking Water Samples for Toxicity

PubMed Central

Brennan, Linda M.; Widder, Mark W.; McAleer, Michael K.; Mayo, Michael W.; Greis, Alex P.; van der Schalie, William H.

2016-01-01

This manuscript describes how to prepare fluidic biochips with Rainbow trout gill epithelial (RTgill-W1) cells for use in a field portable water toxicity sensor. A monolayer of RTgill-W1 cells forms on the sensing electrodes enclosed within the biochips. The biochips are then used for testing in a field portable electric cell-substrate impedance sensing (ECIS) device designed for rapid toxicity testing of drinking water. The manuscript further describes how to run a toxicity test using the prepared biochips. A control water sample and the test water sample are mixed with pre-measured powdered media and injected into separate channels of the biochip. Impedance readings from the sensing electrodes in each of the biochip channels are measured and compared by an automated statistical software program. The screen on the ECIS instrument will indicate either "Contamination Detected" or "No Contamination Detected" within an hour of sample injection. Advantages are ease of use and rapid response to a broad spectrum of inorganic and organic chemicals at concentrations that are relevant to human health concerns, as well as the long-term stability of stored biochips in a ready state for testing. Limitations are the requirement for cold storage of the biochips and limited sensitivity to cholinesterase-inhibiting pesticides. Applications for this toxicity detector are for rapid field-portable testing of drinking water supplies by Army Preventative Medicine personnel or for use at municipal water treatment facilities. PMID:27023147

Preparation and Testing of Impedance-based Fluidic Biochips with RTgill-W1 Cells for Rapid Evaluation of Drinking Water Samples for Toxicity.

PubMed

Brennan, Linda M; Widder, Mark W; McAleer, Michael K; Mayo, Michael W; Greis, Alex P; van der Schalie, William H

2016-03-07

This manuscript describes how to prepare fluidic biochips with Rainbow trout gill epithelial (RTgill-W1) cells for use in a field portable water toxicity sensor. A monolayer of RTgill-W1 cells forms on the sensing electrodes enclosed within the biochips. The biochips are then used for testing in a field portable electric cell-substrate impedance sensing (ECIS) device designed for rapid toxicity testing of drinking water. The manuscript further describes how to run a toxicity test using the prepared biochips. A control water sample and the test water sample are mixed with pre-measured powdered media and injected into separate channels of the biochip. Impedance readings from the sensing electrodes in each of the biochip channels are measured and compared by an automated statistical software program. The screen on the ECIS instrument will indicate either "Contamination Detected" or "No Contamination Detected" within an hour of sample injection. Advantages are ease of use and rapid response to a broad spectrum of inorganic and organic chemicals at concentrations that are relevant to human health concerns, as well as the long-term stability of stored biochips in a ready state for testing. Limitations are the requirement for cold storage of the biochips and limited sensitivity to cholinesterase-inhibiting pesticides. Applications for this toxicity detector are for rapid field-portable testing of drinking water supplies by Army Preventative Medicine personnel or for use at municipal water treatment facilities.

Droplet Velocity Measurement Based on Dielectric Layer Thickness Variation Using Digital Microfluidic Devices.

PubMed

Zulkepli, Siti Noor Idora Syafinaz; Hamid, Nor Hisham; Shukla, Vineeta

2018-05-08

In recent years, the number of interdisciplinary research works related to the development of miniaturized systems with integrated chemical and biological analyses is increasing. Digital microfluidic biochips (DMFBs) are one kind of miniaturized systems designed for conducting inexpensive, fast, convenient and reliable biochemical assay procedures focusing on basic scientific research and medical diagnostics. The role of a dielectric layer in the digital microfluidic biochips is prominent as it helps in actuating microliter droplets based on the electrowetting-on-dielectric (EWOD) technique. The advantages of using three different material layers of dielectric such as parafilm, polytetrafluoroethylene (PTFE) and ethylene tetrafluoroethylene (ETFE) were reported in the current work. A simple fabrication process of a digital microfluidic device was performed and good results were obtained. The threshold of the actuation voltage was determined for all dielectric materials of varying thicknesses. Additionally, the OpenDrop device was tested by utilizing a single-plate system to transport microliter droplets for a bioassay operation. With the newly proposed fabrication methods, these dielectric materials showed changes in contact angle and droplet velocity when the actuation voltage was applied. The threshold actuation voltage for the dielectric layers of 10⁻13 μm was 190 V for the open plate DMFBs.

In vivo wireless biodiagnosis system for long-term bioactivity monitoring network

NASA Astrophysics Data System (ADS)

Chen, Chun-Kuang; Wu, Wen-Jong; Yu, Shih-An; Huang, Jhen-Gang; Lin, Yun-Han; Chen, Yih-Fan; Jin, Ming-Hui; Wen, Chih-Min; Kao, Cheng-Yan; Lin, Shi-Ming; Lu, Shey-Shi; Lin, Chii-Wann; Yen, Jia-Yush; Jaw, Fu-Shan; Chen, Chi-An; Liao, Fang-Jen; Chiu, Nan-Fu; Chien, Chia-Nan; Lee, Chih-Kung

2004-07-01

Attempts to develop a Wireless Health Advanced Mobile Bio-diagnostic System (abbreviated as WHAM-BioS) have arisen from the need to monitor the health status of patients under long-term care programs. The proposed WHAM-BioS as presented here was developed by integrating various technologies: nano/MEMS technology, biotechnology, network/communication technology, and information technology. The biochips proposed not only detect certain diseases but will also report any abnormal status readings on the patient to the medical personnel immediately through the network system. Since long-term home care is typically involved, the parameters monitored must be analyzed and traced continuously over a long period of time. To minimize the intrusion to the patients, a wireless sensor embedded within a wireless network is highly recommended. To facilitate the widest possible use of various biochips, a smart sensor node concept was implemented. More specifically, various technologies and components such as built-in micro power generators, energy storage devices, initialization processes, no-waste bio-detection methodologies, embedded controllers, wireless warning signal transmissions, and power/data management were merged and integrated to create this novel technology. The design methodologies and the implementation schemes are detailed. Potential expansions of this newly developed technology to other applications regimes will be presented as well.

Biochips: non-conventional strategies for biosensing elements immobilization.

PubMed

Marquette, Christophe A; Corgier, Benjamin P; Heyries, Kevin A; Blum, Loic J

2008-01-01

The present article draws a general picture of non-conventional methods for biomolecules immobilization. The technologies presented are based either on original solid supports or on innovative immobilization processes. Polydimethylsiloxane elastomer will be presented as a popular immobilization support within the biochip developer community. Electro-addressing of biomolecules at the surface of conducting biochips will appear to be an interesting alternative to immobilization processes based on surface functionalization. Finally, bead-assisted biomolecules immobilization will be presented as an open field of research for biochip developments.

Biochip-Based Detection of KRAS Mutation in Non-Small Cell Lung Cancer

PubMed Central

Kriegshäuser, Gernot; Fabjani, Gerhild; Ziegler, Barbara; Zöchbauer-Müller, Sabine; End, Adelheid; Zeillinger, Robert

2011-01-01

This study is aimed at evaluating the potential of a biochip assay to sensitively detect KRAS mutation in DNA from non-small cell lung cancer (NSCLC) tissue samples. The assay covers 10 mutations in codons 12 and 13 of the KRAS gene, and is based on mutant-enriched PCR followed by reverse-hybridization of biotinylated amplification products to an array of sequence-specific probes immobilized on the tip of a rectangular plastic stick (biochip). Biochip hybridization identified 17 (21%) samples to carry a KRAS mutation of which 16 (33%) were adenocarcinomas and 1 (3%) was a squamous cell carcinoma. All mutations were confirmed by DNA sequencing. Using 10 ng of starting DNA, the biochip assay demonstrated a detection limit of 1% mutant sequence in a background of wild-type DNA. Our results suggest that the biochip assay is a sensitive alternative to protocols currently in use for KRAS mutation testing on limited quantity samples. PMID:22272089

A new functional membrane protein microarray based on tethered phospholipid bilayers.

PubMed

Chadli, Meriem; Maniti, Ofelia; Marquette, Christophe; Tillier, Bruno; Cortès, Sandra; Girard-Egrot, Agnès

2018-04-30

A new prototype of a membrane protein biochip is presented in this article. This biochip was created by the combination of novel technologies of peptide-tethered bilayer lipid membrane (pep-tBLM) formation and solid support micropatterning. Pep-tBLMs integrating a membrane protein were obtained in the form of microarrays on a gold chip. The formation of the microspots was visualized in real-time by surface plasmon resonance imaging (SPRi) and the functionality of a GPCR (CXCR4), reinserted locally into microwells, was assessed by ligand binding studies. In brief, to achieve micropatterning, P19-4H, a 4 histidine-possessing peptide spacer, was spotted inside microwells obtained on polystyrene-coated gold, and Ni-chelating proteoliposomes were injected into the reaction chamber. Proteoliposome binding to the peptide was based on metal-chelate interaction. The peptide-tethered lipid bilayer was finally obtained by addition of a fusogenic peptide (AH peptide) to promote proteoliposome fusion. The CXCR4 pep-tBLM microarray was characterized by surface plasmon resonance imaging (SPRi) throughout the building-up process. This new generation of membrane protein biochip represents a promising method of developing a screening tool for drug discovery.

Microfluidic Biochip Design

NASA Technical Reports Server (NTRS)

Panzarella, Charles

2004-01-01

As humans prepare for the exploration of our solar system, there is a growing need for miniaturized medical and environmental diagnostic devices for use on spacecrafts, especially during long-duration space missions where size and power requirements are critical. In recent years, the biochip (or Lab-on-a-Chip) has emerged as a technology that might be able to satisfy this need. In generic terms, a biochip is a miniaturized microfluidic device analogous to the electronic microchip that ushered in the digital age. It consists of tiny microfluidic channels, pumps and valves that transport small amounts of sample fluids to biosensors that can perform a variety of tests on those fluids in near real time. It has the obvious advantages of being small, lightweight, requiring less sample fluids and reagents and being more sensitive and efficient than larger devices currently in use. Some of the desired space-based applications would be to provide smaller, more robust devices for analyzing blood, saliva and urine and for testing water and food supplies for the presence of harmful contaminants and microorganisms. Our group has undertaken the goal of adapting as well as improving upon current biochip technology for use in long-duration microgravity environments.

Sickle cell disease biochip: a functional red blood cell adhesion assay for monitoring sickle cell disease

PubMed Central

ALAPAN, YUNUS; KIM, CEONNE; ADHIKARI, ANIMA; GRAY, KAYLA E.; GURKAN-CAVUSOGLU, EVREN; LITTLE, JANE A.; GURKAN, UMUT A.

2016-01-01

Sickle cell disease (SCD) afflicts millions of people worldwide and is associated with considerable morbidity and mortality. Chronic and acute vaso-occlusion are the clinical hallmarks of SCD and can result in pain crisis, widespread organ damage, and early movtality. Even though the molecular underpinnings of SCD were identified more than 60 years ago, there are no molecular or biophysical markers of disease severity that are feasibly measured in the clinic. Abnormal cellular adhesion to vascular endothelium is at the root of vaso-occlusion. However, cellular adhesion is not currently evaluated clinically. Here, we present a clinically applicable microfluidic device (SCD biochip) that allows serial quantitative evaluation of red blood cell (RBC) adhesion to endothelium-associated protein-immobilized microchannels, in a closed and preprocessing-free system. With the SCD biochip, we have analyzed blood samples from more than 100 subjects and have shown associations between the measured RBC adhesion to endothelium-associated proteins (fibronectin and laminin) and individual RBC characteristics, including hemoglobin content, fetal hemoglobin concentration, plasma lactate dehydrogenase level, and reticulocyte count. The SCD biochip is a functional adhesion assay, reflecting quantitative evaluation of RBC adhesion, which could be used at baseline, during crises, relative to various long-term complications, and before and after therapeutic interventions. PMID:27063958

Frosted Slides Decorated with Silica Nanowires for Detecting Circulating Tumor Cells from Prostate Cancer Patients.

PubMed

Cui, Haijun; Wang, Binshuai; Wang, Wenshuo; Hao, Yuwei; Liu, Chuanyong; Song, Kai; Zhang, Shudong; Wang, Shutao

2018-06-13

Developing low-cost and highly efficient nanobiochips are important for liquid biopsies, real-time monitoring, and precision medicine. By in situ growth of silica nanowires on a commercial frosted slide, we develop a biochip for effective circulating tumor cells (CTCs) detection after modifying epithelial cell adhesion molecule antibody (anti-EpCAM). The biochip shows the specificity and high capture efficiency of 85.4 ± 8.3% for prostate cancer cell line (PC-3). The microsized frosted slides and silica nanowires allow enhanced efficiency in capture EpCAM positive cells by synergistic topographic interactions. And the capture efficiency of biochip increased with the increase of silica nanowires length on frosted slide. The biochip shows that micro/nanocomposite structures improve the capture efficiency of PC-3 more than 70% toward plain slide. Furthermore, the nanobiochip has been successfully applied to identify CTCs from whole blood specimens of prostate cancer patients. Thus, this frosted slide-based biochip may provide a cheap and effective way of clinical monitoring of CTCs.

A facile inhibitor screening of SARS coronavirus N protein using nanoparticle-based RNA oligonucleotide.

PubMed

Roh, Changhyun

2012-01-01

Hundreds of million people worldwide have been infected with severe acute respiratory syndrome (SARS), and the rate of global death from SARS has remarkably increased. Hence, the development of efficient drug treatments for the biological effects of SARS is highly needed. We have previously shown that quantum dots (QDs)-conjugated RNA oligonucleotide is sensitive to the specific recognition of the SARS-associated coronavirus (SARS-CoV) nucleocapsid (N) protein. In this study, we found that a designed biochip could analyze inhibitors of the SARS-CoV N protein using nanoparticle-based RNA oligonucleotide. Among the polyphenolic compounds examined, (-)-catechin gallate and (-)-gallocatechin gallate demonstrated a remarkable inhibition activity on SARS-CoV N protein. (-)-catechin gallate and (-)-gallocatechin gallate attenuated the binding affinity in a concentrated manner as evidenced by QDs-conjugated RNA oligonucleotide on a designed biochip. At a concentration of 0.05 μg mL(-1), (-)-catechin gallate and (-)-gallocatechin gallate showed more than 40% inhibition activity on a nanoparticle-based RNA oligonucleotide biochip system.

Microfluidically supported biochip design for culture of endothelial cell layers with improved perfusion conditions.

PubMed

Raasch, Martin; Rennert, Knut; Jahn, Tobias; Peters, Sven; Henkel, Thomas; Huber, Otmar; Schulz, Ingo; Becker, Holger; Lorkowski, Stefan; Funke, Harald; Mosig, Alexander

2015-03-02

Hemodynamic forces generated by the blood flow are of central importance for the function of endothelial cells (ECs), which form a biologically active cellular monolayer in blood vessels and serve as a selective barrier for macromolecular permeability. Mechanical stimulation of the endothelial monolayer induces morphological remodeling in its cytoskeleton. For in vitro studies on EC biology culture devices are desirable that simulate conditions of flow in blood vessels and allow flow-based adhesion/permeability assays under optimal perfusion conditions. With this aim we designed a biochip comprising a perfusable membrane that serves as cell culture platform multi-organ-tissue-flow (MOTiF biochip). This biochip allows an effective supply with nutrition medium, discharge of catabolic cell metabolites and defined application of shear stress to ECs under laminar flow conditions. To characterize EC layers cultured in the MOTiF biochip we investigated cell viability, expression of EC marker proteins and cell adhesion molecules of ECs dynamically cultured under low and high shear stress, and compared them with an endothelial culture in established two-dimensionally perfused flow chambers and under static conditions. We show that ECs cultured in the MOTiF biochip form a tight EC monolayer with increased cellular density, enhanced cell layer thickness, presumably as the result of a rapid and effective adaption to shear stress by remodeling of the cytoskeleton. Moreover, endothelial layers in the MOTiF biochip express higher amounts of EC marker proteins von-Willebrand-factor and PECAM-1. EC layers were highly responsive to stimulation with TNFα as detected at the level of ICAM-1, VCAM-1 and E-selectin expression and modulation of endothelial permeability in response to TNFα/IFNγ treatment under flow conditions. Compared to static and two-dimensionally perfused cell culture condition we consider MOTiF biochips as a valuable tool for studying EC biology in vitro under advanced culture conditions more closely resembling the in vivo situation.

Cell-free protein synthesis and assembly on a biochip

NASA Astrophysics Data System (ADS)

Heyman, Yael; Buxboim, Amnon; Wolf, Sharon G.; Daube, Shirley S.; Bar-Ziv, Roy H.

2012-06-01

Biologically active complexes such as ribosomes and bacteriophages are formed through the self-assembly of proteins and nucleic acids. Recapitulating these biological self-assembly processes in a cell-free environment offers a way to develop synthetic biodevices. To visualize and understand the assembly process, a platform is required that enables simultaneous synthesis, assembly and imaging at the nanoscale. Here, we show that a silicon dioxide grid, used to support samples in transmission electron microscopy, can be modified into a biochip to combine in situ protein synthesis, assembly and imaging. Light is used to pattern the biochip surface with genes that encode specific proteins, and antibody traps that bind and assemble the nascent proteins. Using transmission electron microscopy imaging we show that protein nanotubes synthesized on the biochip surface in the presence of antibody traps efficiently assembled on these traps, but pre-assembled nanotubes were not effectively captured. Moreover, synthesis of green fluorescent protein from its immobilized gene generated a gradient of captured proteins decreasing in concentration away from the gene source. This biochip could be used to create spatial patterns of proteins assembled on surfaces.

Hybrid inorganic/organic photonic crystal biochips for cancer biomarkers detection

NASA Astrophysics Data System (ADS)

Sinibaldi, Alberto; Danz, Norbert; Munzert, Peter; Michelotti, Francesco

2018-06-01

We report on hybrid inorganic/organic one-dimensional photonic crystal biochips sustaining Bloch surface waves. The biochips were used, together with an optical platform operating in a label-free and fluorescence configuration simultaneously, to detect the cancer biomarker Angiopoietin 2 in a protein base buffer. The hybrid photonic crystals embed in their geometry a thin functionalization poly-acrylic acid layer deposited by plasma polymerization, which is used to immobilize a monoclonal antibody for highly specific biological recognition. The fluorescence operation mode is described in detail, putting into evidence the role of field enhancement and localization at the photonic crystal surface in the shaping and intensification of the angular fluorescence pattern. In the fluorescence operation mode, the hybrid biochips can attain the limit of detection 6 ng/ml.

Microfluidics-Based Lab-on-Chip Systems in DNA-Based Biosensing: An Overview

PubMed Central

Dutse, Sabo Wada; Yusof, Nor Azah

2011-01-01

Microfluidics-based lab-on-chip (LOC) systems are an active research area that is revolutionising high-throughput sequencing for the fast, sensitive and accurate detection of a variety of pathogens. LOCs also serve as portable diagnostic tools. The devices provide optimum control of nanolitre volumes of fluids and integrate various bioassay operations that allow the devices to rapidly sense pathogenic threat agents for environmental monitoring. LOC systems, such as microfluidic biochips, offer advantages compared to conventional identification procedures that are tedious, expensive and time consuming. This paper aims to provide a broad overview of the need for devices that are easy to operate, sensitive, fast, portable and sufficiently reliable to be used as complementary tools for the control of pathogenic agents that damage the environment. PMID:22163925

Amperometric Immunosensors for screening of Polycyclic Aromatic Hydrocarbons in water

NASA Astrophysics Data System (ADS)

Ahmad, A.; Paschero, A.; Moore, E.

2011-08-01

An amperometric immunosensor with low limit detection was developed for the screening of polycyclic aromatic hydrocarbons (PAHs) in water. The system was based on detecting the specific substance using an immunological reaction by measuring the chemical responses to specific antibodies. An integrated biochip with a three electrode system was fabricated. Gold was used as the working electrode with platinum was used as the counter electrode. A modified Ag/AgCl reference electrode was employed to enhance the stability of the immunosensors. Indirect competition enzyme-linked immunosorbent assay (ELISA) was carried out within the electrode using alkaline phosphatase (AP) as the labelled-enzyme. The system shows acceptable reproducibility and good stability. The immunosensor exhibited a wide linear response to PAHs. A limit of detection for this sensor was in the range of 1 to 10 ng ml-1 in aqueous sample.

A Novel Cassette Method for Probe Evaluation in the Designed Biochips

PubMed Central

Zinkevich, Vitaly; Sapojnikova, Nelly; Mitchell, Julian; Kartvelishvili, Tamar; Asatiani, Nino; Alkhalil, Samia; Bogdarina, Irina; Al-Humam, Abdulmohsen A.

2014-01-01

A critical step in biochip design is the selection of probes with identical hybridisation characteristics. In this article we describe a novel method for evaluating DNA hybridisation probes, allowing the fine-tuning of biochips, that uses cassettes with multiple probes. Each cassette contains probes in equimolar proportions so that their hybridisation performance can be assessed in a single reaction. The model used to demonstrate this method was a series of probes developed to detect TORCH pathogens. DNA probes were designed for Toxoplasma gondii, Chlamidia trachomatis, Rubella, Cytomegalovirus, and Herpes virus and these were used to construct the DNA cassettes. Five cassettes were constructed to detect TORCH pathogens using a variety of genes coding for membrane proteins, viral matrix protein, an early expressed viral protein, viral DNA polymerase and the repetitive gene B1 of Toxoplasma gondii. All of these probes, except that for the B1 gene, exhibited similar profiles under the same hybridisation conditions. The failure of the B1 gene probe to hybridise was not due to a position effect, and this indicated that the probe was unsuitable for inclusion in the biochip. The redesigned probe for the B1 gene exhibited identical hybridisation properties to the other probes, suitable for inclusion in a biochip. PMID:24897111

Biochips: A fruitful product of solid state physics and molecular biology

NASA Astrophysics Data System (ADS)

Mendoza-Alvarez, Julio G.

1998-08-01

The application of the standard high resolution photolithography techniques used in the semiconductor device industry to the growth of a chain of nucleotides with a precise and well known sequence, has made possible the fabrication of a new kind of device, the so called biochips. At the National Polytechnic Institute in Mexico we have joined a multidisciplinary scientific group, and we are in the process of developing the technical capabilities in order to set up a processing lab to fabricate biochips focused to very specific applications in the area of cancer detection. We present here the main lines along which this project is being developed.

Existing and emerging detection technologies for DNA (Deoxyribonucleic Acid) finger printing, sequencing, bio- and analytical chips: a multidisciplinary development unifying molecular biology, chemical and electronics engineering.

PubMed

Kumar Khanna, Vinod

2007-01-01

The current status and research trends of detection techniques for DNA-based analysis such as DNA finger printing, sequencing, biochips and allied fields are examined. An overview of main detectors is presented vis-à-vis these DNA operations. The biochip method is explained, the role of micro- and nanoelectronic technologies in biochip realization is highlighted, various optical and electrical detection principles employed in biochips are indicated, and the operational mechanisms of these detection devices are described. Although a diversity of biochips for diagnostic and therapeutic applications has been demonstrated in research laboratories worldwide, only some of these chips have entered the clinical market, and more chips are awaiting commercialization. The necessity of tagging is eliminated in refractive-index change based devices, but the basic flaw of indirect nature of most detection methodologies can only be overcome by generic and/or reagentless DNA sensors such as the conductance-based approach and the DNA-single electron transistor (DNA-SET) structure. Devices of the electrical detection-based category are expected to pave the pathway for the next-generation DNA chips. The review provides a comprehensive coverage of the detection technologies for DNA finger printing, sequencing and related techniques, encompassing a variety of methods from the primitive art to the state-of-the-art scenario as well as promising methods for the future.

Design and fabrication of highly sensitive and stable biochip for glucose biosensing

NASA Astrophysics Data System (ADS)

Lu, Shi-Yu; Lu, Yao; Jin, Meng; Bao, Shu-Juan; Li, Wan-Yun; Yu, Ling

2017-11-01

Common producing steps for test strips is complex and fussy. In this work, we proposed a feasible binder-free test strips fabrication method to directly grow enzyme/manganese phosphate nanosheets hybrids on the screen-print electrodes (SPE). Combined with microfluidic packaging technology, the ready-made portable electrochemical biochip shows a wider linear range (1-40 mM, R2 = 0.9998) and excellent stability (maintained 98% response current after 20 days store and retained 75% response current after continuous 30 days determination) for the detection of glucose. Compared with commercial test strips, the biochip exhibits excellent sensitivity, stability and accuracy, which is indicative of its potential application in real samples.

The current status of alternatives to animal testing and predictive toxicology methods using liver microfluidic biochips.

PubMed

Prot, Jean Matthieu; Leclerc, Eric

2012-06-01

In this paper, we will consider new in vitro cell culture platforms and the progress made, based on the microfluidic liver biochips dedicated to pharmacological and toxicological studies. Particular emphasis will be given to recent developments in the microfluidic tools dedicated to cell culture (more particularly liver cell culture), in silico opportunities for Physiologically Based PharmacoKinetic (PBPK) modelling, the challenge of the mechanistic interpretations offered by the approaches resulting from "multi-omics" data (transcriptomics, proteomics, metabolomics, cytomics) and imaging microfluidic platforms. Finally, we will discuss the critical features regarding microfabrication, design and materials, and cell functionality as the key points for the future development of new microfluidic liver biochips.

Serial processing of biological reactions using flow-through microfluidic devices: coupled PCR/LDR for the detection of low-abundant DNA point mutations.

PubMed

Hashimoto, Masahiko; Barany, Francis; Xu, Feng; Soper, Steven A

2007-09-01

We have fabricated a flow-through biochip consisting of passive elements for the analysis of single base mutations in genomic DNA using polycarbonate (PC) as the substrate. The biochip was configured to carry out two processing steps on the input sample, a primary polymerase chain reaction (PCR) followed by an allele-specific ligation detection reaction (LDR) for scoring the presence of low abundant point mutations in genomic DNA. The operation of the device was demonstrated by detecting single nucleotide polymorphisms in gene fragments (K-ras) that carry high diagnostic value for colorectal cancers. The effect of carryover from the primary PCR on the subsequent LDR was investigated in terms of LDR yield and fidelity. We found that a post-PCR treatment step prior to the LDR phase of the assay was not essential. As a consequence, a thermal cycling microchip was used for a sequential PCR/LDR in a simple continuous-flow format, in which the following three steps were carried out: (1) exponential amplification of the gene fragments from genomic DNA; (2) mixing of the resultant PCR product(s) with an LDR cocktail via a Y-shaped passive micromixer; and (3) ligation of two primers (discriminating primer that carried the complement base to the mutation locus being interrogated and a common primer) only when the particular mutation was present in the genomic DNA. We successfully demonstrated the ability to detect one mutant DNA in 1000 normal sequences with the integrated microfluidic system. The PCR/LDR assay using the microchip performed the entire assay at a relatively fast processing speed: 18.7 min for 30 rounds of PCR, 4.1 min for 13 rounds of LDR (total processing time = ca. 22.8 min) and could screen multiple mutations simultaneously in a multiplexed format. In addition, the low cost of the biochip due to the fact that it was fabricated from polymers using replication technologies and consisted of passive elements makes the platform amenable to clinical diagnostics, where one-time use devices are required to eliminate false positives resulting from carryover contamination.

A comparison of DNA fragmentation methods - Applications for the biochip technology.

PubMed

Sapojnikova, Nelly; Asatiani, Nino; Kartvelishvili, Tamar; Asanishvili, Lali; Zinkevich, Vitaly; Bogdarina, Irina; Mitchell, Julian; Al-Humam, Abdulmohsen

2017-08-20

The efficiency of hybridization signal detection in a biochip is affected by the method used for test DNA preparation, such as fragmentation, amplification and fluorescent labelling. DNA fragmentation is the commonest methods used and it is recognised as a critical step in biochip analysis. Currently methods used for DNA fragmentation are based either on sonication or on the enzymatic digestion. In this study, we compared the effect of different types of enzymatic DNA fragmentations, using DNase I to generate ssDNA breaks, NEBNext dsDNA fragmentase and SaqAI restrictase, on DNA labelling. DNA from different Desulfovibrio species was used as a substrate for these enzymes. Of the methods used, DNA fragmented by NEBNext dsDNA Fragmentase digestion was subsequently labelled with the greatest efficiency. As a result of this, the use of this enzyme to fragment target DNA increases the sensitivity of biochip-based detection significantly, and this is an important consideration when determining the presence of targeted DNA in ecological and medical samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Exploiting Sub-threshold and above-threshold characteristics in a silver-enhanced gold nanoparticle based biochip.

PubMed

Liu, Yang; Alocilja, Evangelyn; Chakrabartty, Shantanu

2009-01-01

Silver-enhanced labeling is a technique used in immunochromatographic assays for improving the sensitivity of pathogen detection. In this paper, we employ the silver enhancement approach for constructing a biomolecular transistor that uses a high-density interdigitated electrode to detect rabbit IgG. We show that the response of the biomolecular transistor comprises of: (a) a sub-threshold region where the conductance change is an exponential function of the enhancement time and; (b) an above-threshold region where the conductance change is a linear function with respect to the enhancement time. By exploiting both these regions of operation, it is shown that the silver enhancing time is a reliable indicator of the IgG concentration. The method provides a relatively straightforward alternative to biomolecular signal amplification techniques. The measured results using a biochip prototype fabricated in silicon show that 240 pg/mL rabbit IgG can be detected at the silver enhancing time of 42 min. Also, the biomolecular transistor is compatible with silicon based processing making it ideal for designing integrated CMOS biosensors.

A biochip-based combined immunoassay for detection of serological status of Borrelia burgdorferi in Lyme borreliosis.

PubMed

Huang, Na-Li; Ye, Lei; Lv, Hui; Du, Yi-Xin; Schneider, Marion; Fan, Li-Bin; Du, Wei-Dong

2017-09-01

Dithiobis (succinimidyl undecanoate) modified gold surface biochip were used as a combined immunoassay platform for concurrently detecting immune responses to Borrelia burgdorferi (B. burgdorferi) sensu lato antigens, flagellin, outer surface protein C, variable major protein-like sequence proteins, and 3 VlsE protein IR 6 peptides. The peptides represented intrinsic Borrelia genospecies: B. burgdorferi sensu stricto, B. garinii, and B. afzelii, respectively. Fourier transform infrared spectroscopy was utilized to validate the surface chemical characteristics on the modified gold surface. The limits in detection of IgG antibody on the biochips were as little as 0.39μg/ml for anti-VlsE and 0.78μg/ml for anti-flagellin and anti-OspC, respectively. Samples from 56 neuroborreliosis (NB) patients and 114 healthy individuals were analyzed by the combined biochip. We found that the seroprevalences of IgM or IgG antibody against the 6 antigens were contributed to increased overall sensitivity by the multiplex immunobiochip assay. Serum combined positive rates of the 6 antigens in the patients were 92.86% for IgM antibody and 91.07% for IgG antibody. Part of the patients bore antibody responses against the 3 VlsE IR 6 variant peptides, indicating that Lyme borreliosis would attribute to consequence of multiple infections by one or more Borrelia burgdorferi strains. Concurrent assessment for both IgM and IgG antibodies against the protein antigens and B. burgdorferi IR 6 peptides in the sera of NB patients was beneficial from the biochip format, enabling detection of expanded serologic infection status and therapy strategy-making more efficiently. The combined biochip-based immunoassay, as a potential substitution of ELISA, provided a promising approach to extend the detection spectrum of infectious antibodies against a panel of Borrelia antigens. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficient droplet router for digital microfluidic biochip using particle swarm optimizer

NASA Astrophysics Data System (ADS)

Pan, Indrajit; Samanta, Tuhina

2013-01-01

Digital Microfluidic Biochip has emerged as a revolutionary finding in the field of micro-electromechanical research. Different complex bioassays and pathological analysis are being efficiently performed on this miniaturized chip with negligible amount of sample specimens. Initially biochip was invented on continuous-fluid-flow mechanism but later it has evolved with more efficient concept of digital-fluid-flow. These second generation biochips are capable of serving more complex bioassays. This operational change in biochip technology emerged with the requirement of high end computer aided design needs for physical design automation. The change also paved new avenues of research to assist the proficient design automation. Droplet routing is one of those major aspects where it necessarily requires minimization of both routing completion time and total electrode usage. This task involves optimization of multiple associated parameters. In this paper we have proposed a particle swarm optimization based approach for droplet outing. The process mainly operates in two phases where initially we perform clustering of state space and classification of nets into designated clusters. This helps us to reduce solution space by redefining local sub optimal target in the interleaved space between source and global target of a net. In the next phase we resolve the concurrent routing issues of every sub optimal situation to generate final routing schedule. The method was applied on some standard test benches and hard test sets. Comparative analysis of experimental results shows good improvement on the aspect of unit cell usage, routing completion time and execution time over some well existing methods.

How Can We Use Bioinformatics to Predict Which Agents Will Cause Birth Defects?

EPA Science Inventory

The availability of genomic sequences from a growing number of human and model organisms has provided an explosion of data, information, and knowledge regarding biological systems and disease processes. High-throughput technologies such as DNA and protein microarray biochips are ...

Toward the Development of an Artificial Brain on a Micropatterned and Material-Regulated Biochip by Guiding and Promoting the Differentiation and Neurite Outgrowth of Neural Stem/Progenitor Cells.

PubMed

Liu, Yung-Chiang; Lee, I-Chi; Lei, Kin Fong

2018-02-14

An in vitro model mimicking the in vivo environment of the brain must be developed to study neural communication and regeneration and to obtain an understanding of cellular and molecular responses. In this work, a multilayered neural network was successfully constructed on a biochip by guiding and promoting neural stem/progenitor cell differentiation and network formation. The biochip consisted of 3 × 3 arrays of cultured wells connected with channels. Neurospheroids were cultured on polyelectrolyte multilayer (PEM) films in the culture wells. Neurite outgrowth and neural differentiation were guided and promoted by the micropatterns and the PEM films. After 5 days in culture, a 3 × 3 neural network was constructed on the biochip. The function and the connections of the network were evaluated by immunocytochemistry and impedance measurements. Neurons were generated and produced functional and recyclable synaptic vesicles. Moreover, the electrical connections of the neural network were confirmed by measuring the impedance across the neurospheroids. The current work facilitates the development of an artificial brain on a chip for investigations of electrical stimulations and recordings of multilayered neural communication and regeneration.

Monte Carlo simulation of the radiation environment encountered by a biochip during a space mission to Mars.

PubMed

Le Postollec, A; Incerti, S; Dobrijevic, M; Desorgher, L; Santin, G; Moretto, P; Vandenabeele-Trambouze, O; Coussot, G; Dartnell, L; Nieminen, P

2009-04-01

Simulations with a Monte Carlo tool kit have been performed to determine the radiation environment a specific device, called a biochip, would face if it were placed into a rover bound to explore Mars' surface. A biochip is a miniaturized device that can be used to detect organic molecules in situ. Its specific detection part is constituted of proteins whose behavior under cosmic radiation is completely unknown and must be investigated to ensure a good functioning of the device under space conditions. The aim of this study is to define particle species and energy ranges that could be relevant to investigate during experiments on irradiation beam facilities. Several primary particles have been considered for galactic cosmic ray (GCR) and solar energetic particle (SEP) contributions. Ionizing doses accumulated in the biochip and differential fluxes of protons, alphas, neutrons, gammas, and electrons have been established for both the Earth-Mars transit and the journey at Mars' surface. Neutrons and gammas appear as dominant species on martian soil, whereas protons dominate during the interplanetary travel. Depending on solar event occurrence during the mission, an ionizing dose of around a few Grays (1 Gy = 100 rad) is expected.

Integrated Spintronic Platforms for Biomolecular Recognition Detection

NASA Astrophysics Data System (ADS)

Martins, V. C.; Cardoso, F. A.; Loureiro, J.; Mercier, M.; Germano, J.; Cardoso, S.; Ferreira, R.; Fonseca, L. P.; Sousa, L.; Piedade, M. S.; Freitas, P. P.

2008-06-01

This paper covers recent developments in magnetoresistive based biochip platforms fabricated at INESC-MN, and their application to the detection and quantification of pathogenic waterborn microorganisms in water samples for human consumption. Such platforms are intended to give response to the increasing concern related to microbial contaminated water sources. The presented results concern the development of biological active DNA chips and protein chips and the demonstration of the detection capability of the present platforms. Two platforms are described, one including spintronic sensors only (spin-valve based or magnetic tunnel junction based), and the other, a fully scalable platform where each probe site consists of a MTJ in series with a thin film diode (TFD). Two microfluidic systems are described, for cell separation and concentration, and finally, the read out and control integrated electronics are described, allowing the realization of bioassays with a portable point of care unit. The present platforms already allow the detection of complementary biomolecular target recognition with 1 pM concentration.

Microneedles for Transdermal Biosensing: Current Picture and Future Direction.

PubMed

Ventrelli, Letizia; Marsilio Strambini, Lucanos; Barillaro, Giuseppe

2015-12-09

A novel trend is rapidly emerging in the use of microneedles, which are a miniaturized replica of hypodermic needles with length-scales of hundreds of micrometers, aimed at the transdermal biosensing of analytes of clinical interest, e.g., glucose, biomarkers, and others. Transdermal biosensing via microneedles offers remarkable opportunities for moving biosensing technologies and biochips from research laboratories to real-field applications, and envisages easy-to-use point-of-care microdevices with pain-free, minimally invasive, and minimal-training features that are very attractive for both developed and emerging countries. In addition to this, microneedles for transdermal biosensing offer a unique possibility for the development of biochips provided with end-effectors for their interaction with the biological system under investigation. Direct and efficient collection of the biological sample to be analyzed will then become feasible in situ at the same length-scale of the other biochip components by minimally trained personnel and in a minimally invasive fashion. This would eliminate the need for blood extraction using hypodermic needles and reduce, in turn, related problems, such as patient infections, sample contaminations, analysis artifacts, etc. The aim here is to provide a thorough and critical analysis of state-of-the-art developments in this novel research trend, and to bridge the gap between microneedles and biosensors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High performance multichannel photonic biochip sensors for future point of care diagnostics: an overview on two EU-sponsored projects

NASA Astrophysics Data System (ADS)

Giannone, Domenico; Kazmierczak, Andrzej; Dortu, Fabian; Vivien, Laurent; Sohlström, Hans

2010-04-01

We present here research work on two optical biosensors which have been developed within two separate European projects (6th and 7th EU Framework Programmes). The biosensors are based on the idea of a disposable biochip, integrating photonics and microfluidics, optically interrogated by a multichannel interrogation platform. The objective is to develop versatile tools, suitable for performing screening tests at Point of Care or for example, at schools or in the field. The two projects explore different options in terms of optical design and different materials. While SABIO used Si3N4/SiO2 ring resonators structures, P3SENS aims at the use of photonic crystal devices based on polymers, potentially a much more economical option. We discuss both approaches to show how they enable high sensitivity and multiple channel detection. The medium term objective is to develop a new detection system that has low cost and is portable but at the same time offering high sensitivity, selectivity and multiparametric detection from a sample containing various components (e.g. blood, serum, saliva, etc.). Most biological sensing devices already present on the market suffer from limitations in multichannel operation capability (either the detection of multiple analytes indicating a given pathology or the simultaneous detection of multiple pathologies). In other words, the number of different analytes that can be detected on a single chip is very limited. This limitation is a main issue addressed by the two projects. The excessive cost per test of conventional bio sensing devices is a second issue that is addressed.

Differentiation and Monitoring of Cells Using a Biochip for Regenerative Medicine

NASA Astrophysics Data System (ADS)

Uchida, Tomoyuki; Arai, Fumihito; Suzuki, Osamu; Ichikawa, Akihiko; Fukuda, Toshio; Katagiri, Takenobu; Kamijo, Ryutaro; Nakamura, Masanori; Numata, Mamoru; Watanabe, Naruaki

A novel biochip is developed for culturing stem cells. Biochip is made of Polymer (PDMS), and cells can be loaded by gradient strains in one chip. They grow well on a hydrophilic membrane and differentiation is promoted by cyclic strains. In this paper, we propose the method for culturing and monitoring of stem cells such as bone marrow stromal cells (ST2 cells) and myoblasts (C2C12 cells), and the results of culture. First we analyzed strains on a membrane when an air hole is decompressed, and clarified their range. From experiment, bone marrow stromal cells grew well in a narrow range, and we quantified their ALP activity as a measure of differentiation. As myoblasts, the direction of their differentiation was perpendicular to a groove, that is, the same direction of uniaxial strains.

Modeling Hybridization Kinetics of Gene Probes in a DNA Biochip Using FEMLAB

PubMed Central

Munir, Ahsan; Waseem, Hassan; Williams, Maggie R.; Stedtfeld, Robert D.; Gulari, Erdogan; Tiedje, James M.; Hashsham, Syed A.

2017-01-01

Microfluidic DNA biochips capable of detecting specific DNA sequences are useful in medical diagnostics, drug discovery, food safety monitoring and agriculture. They are used as miniaturized platforms for analysis of nucleic acids-based biomarkers. Binding kinetics between immobilized single stranded DNA on the surface and its complementary strand present in the sample are of interest. To achieve optimal sensitivity with minimum sample size and rapid hybridization, ability to predict the kinetics of hybridization based on the thermodynamic characteristics of the probe is crucial. In this study, a computer aided numerical model for the design and optimization of a flow-through biochip was developed using a finite element technique packaged software tool (FEMLAB; package included in COMSOL Multiphysics) to simulate the transport of DNA through a microfluidic chamber to the reaction surface. The model accounts for fluid flow, convection and diffusion in the channel and on the reaction surface. Concentration, association rate constant, dissociation rate constant, recirculation flow rate, and temperature were key parameters affecting the rate of hybridization. The model predicted the kinetic profile and signal intensities of eighteen 20-mer probes targeting vancomycin resistance genes (VRGs). Predicted signal intensities and hybridization kinetics strongly correlated with experimental data in the biochip (R2 = 0.8131). PMID:28555058

Modeling Hybridization Kinetics of Gene Probes in a DNA Biochip Using FEMLAB.

PubMed

Munir, Ahsan; Waseem, Hassan; Williams, Maggie R; Stedtfeld, Robert D; Gulari, Erdogan; Tiedje, James M; Hashsham, Syed A

2017-05-29

Microfluidic DNA biochips capable of detecting specific DNA sequences are useful in medical diagnostics, drug discovery, food safety monitoring and agriculture. They are used as miniaturized platforms for analysis of nucleic acids-based biomarkers. Binding kinetics between immobilized single stranded DNA on the surface and its complementary strand present in the sample are of interest. To achieve optimal sensitivity with minimum sample size and rapid hybridization, ability to predict the kinetics of hybridization based on the thermodynamic characteristics of the probe is crucial. In this study, a computer aided numerical model for the design and optimization of a flow-through biochip was developed using a finite element technique packaged software tool (FEMLAB; package included in COMSOL Multiphysics) to simulate the transport of DNA through a microfluidic chamber to the reaction surface. The model accounts for fluid flow, convection and diffusion in the channel and on the reaction surface. Concentration, association rate constant, dissociation rate constant, recirculation flow rate, and temperature were key parameters affecting the rate of hybridization. The model predicted the kinetic profile and signal intensities of eighteen 20-mer probes targeting vancomycin resistance genes (VRGs). Predicted signal intensities and hybridization kinetics strongly correlated with experimental data in the biochip (R² = 0.8131).

Reusable and Mediator-Free Cholesterol Biosensor Based on Cholesterol Oxidase Immobilized onto TGA-SAM Modified Smart Bio-Chips

PubMed Central

Rahman, Mohammed M.

2014-01-01

A reusable and mediator-free cholesterol biosensor based on cholesterol oxidase (ChOx) was fabricated based on self-assembled monolayer (SAM) of thioglycolic acid (TGA) (covalent enzyme immobilization by dropping method) using bio-chips. Cholesterol was detected with modified bio-chip (Gold/Thioglycolic-acid/Cholesterol-oxidase i.e., Au/TGA/ChOx) by reliable cyclic voltammetric (CV) technique at room conditions. The Au/TGA/ChOx modified bio-chip sensor demonstrates good linearity (1.0 nM to 1.0 mM; R = 0.9935), low-detection limit (∼0.42 nM, SNR∼3), and higher sensitivity (∼74.3 µAµM−1cm−2), lowest-small sample volume (50.0 μL), good stability, and reproducibility. To the best of our knowledge, this is the first statement with a very high sensitivity, low-detection limit, and low-sample volumes are required for cholesterol biosensor using Au/TGA/ChOx-chips assembly. The result of this facile approach was investigated for the biomedical applications for real samples at room conditions with significant assembly (Au/TGA/ChOx) towards the development of selected cholesterol biosensors, which can offer analytical access to a large group of enzymes for wide range of biomedical applications in health-care fields. PMID:24949733

"Print-n-Shrink" technology for the rapid production of microfluidic chips and protein microarrays.

PubMed

Sollier, Kevin; Mandon, Céline A; Heyries, Kevin A; Blum, Loïc J; Marquette, Christophe A

2009-12-21

An innovative method for the production of microfluidic chips integrating protein spots is described. The technology, called "Print-n-Shrink", is based on the screen-printing of a microfluidic design (using a dielectric ink) onto Polyshrink polystyrene sheets. The initial print which has a minimum size of 15 microm (height) x 230 microm (width) is thermally treated (30 seconds, 163 degrees C) to shrink and generate features of 85 microm (height) x 100 microm (width). Concomitantly, proteins such as monoclonal antibodies or cellular adhesion proteins are spotted onto the Polyshrink sheets and shrunk together with the microfluidic design, creating a complete biochip integrating both complex microfluidic designs and protein spots for bioanalytical applications.

Biochip for Real-Time Monitoring of Hepatitis B Virus (HBV) by Combined Loop-Mediated Isothermal Amplification and Solution-Phase Electrochemical Detection

NASA Astrophysics Data System (ADS)

Tien, Bui Quang; Ngoc, Nguyen Thy; Loc, Nguyen Thai; Thu, Vu Thi; Lam, Tran Dai

2017-06-01

Accurate in situ diagnostic tests play a key role in patient management and control of most infectious diseases. To achieve this, use of handheld biochips that implement sample handling, sample analysis, and result readout together is an ideal approach. We present herein a fluid-handling biochip for real-time electrochemical monitoring of nucleic acid amplification based on loop-mediated isothermal amplification and real-time electrochemical detection on a microfluidic platform. Intercalation between amplifying DNA and free redox probe in solution phase was used to monitor the number of DNA copies. The whole diagnostic process is completed within 70 min. Our platform offers a fast and easy tool for quantification of viral pathogens in shorter time and with limited risk of all potential forms of cross-contamination. Such diagnostic tools have potential to make a huge difference to the lives of millions of people worldwide.

[Hydrogel microchip as a tool for studying exosomes in human serum].

PubMed

Butvilovskaya, V I; Tikhonov, A A; Savvateeva, E N; Ragimov, A A; Salimov, E L; Voloshin, S A; Sidorov, D V; Chernichenko, M A; Polyakov, A P; Filushin, M M; Tsybulskaya, M V; Rubina, A Yu

2017-01-01

Exosomes are cell-derived vesicles that are secreted by both normal and cancer cells. Over the last decade, a few studies have revealed that exosomes cross talk and/or influence major tumor-related pathways such as angiogenesis and metastasis involving many cell types within the tumor microenvironment. The protein composition of the membrane of an exosome reflects that of the membrane of the cell of origin. Because of this, tumor-derived exosomes differ from exosomes that are derived from normal cells. The detection of tumor exosomes and analysis of their molecular composition hold promise for diagnosis and prognosis of cancer. Here, we present hydrogel microarrays (biochips), which contain a panel of immobilized antibodies that recognize tetraspanins (CD9, CD63, CD81) and prognostic markers for colorectal cancer (A33, CD147). These biochips make it possible to analyze the surface proteins of either isolated exosomes or exosomes that are present in the serum samples without isolation. These biochips were successfully used to analyze the surface proteins of exosomes from serum that was collected from a colorectal cancer patient and healthy donor. Biochip-guided immunofluorescent analysis of the exosomes has made it possible for us to detect the A33 antigen and CD147 in the serum sample of the colorectal cancer patient with normal levels of CEA and CA19-9.

[Biochip for determination of genetic markers of sporadic Alzheimer's disease in the Russian Slavic population].

PubMed

Nizamutdinov, I I; Andreeva, T V; Stepanov, V A; Marusin, A V; Rogaev, E I; Zasedatelev, A S; Nasedkina, T V

2013-01-01

A biological microchip (biochip) for the genetic predis- position to sporadic form of Alzheimer's disease studying has been developed. The biochip allows determina- tion of ten genetic polymorphisms within APOE, TOMM40, APOJ, EXOC3L2, GAB2, A2M, CR1, BIN1 and PICALM genes. The genotyping assay includes the amplification of loci of interest and further allele-specific hybridization of the fluorescent labeled amplicons with oligonucleotides immobilized on a biochip. Based on the results of genotyping of 166 patients and 128 controls APOE epsilon4 allele was found to be significantly associated with Alzheimer's disease susceptibility (OR = 2.275, 95% CI = 1.045-4.954,p = 0.034). Additionally, protective effects for the APOE epsilon2 allele and CLUT-allele (rs11136000) were observed (OR = 0.215, 95% CI = 0.090-0.516, p = 0.001 and OR = 0.679, 95% CI = 0.47-0.99, p = 0.042, respectively). Gene-gene interaction revealed two genotype combinations associated with Alzheimer's disease: APOE E3/E4 GAB2 G/G (OR = 2.49; CI = 1.43-4.32, p = 0.001) and APOE epsilon4 GAB2 G/G (OR = 3.55, CI = 1.23-10.24,p = 0.015). Based on the results of the combined multivariate analysis the algorithm for identifying of individuals at increased risk of Alzheimer's disease was developed.

Integrated Microfluidic Devices for Automated Microarray-Based Gene Expression and Genotyping Analysis

NASA Astrophysics Data System (ADS)

Liu, Robin H.; Lodes, Mike; Fuji, H. Sho; Danley, David; McShea, Andrew

Microarray assays typically involve multistage sample processing and fluidic handling, which are generally labor-intensive and time-consuming. Automation of these processes would improve robustness, reduce run-to-run and operator-to-operator variation, and reduce costs. In this chapter, a fully integrated and self-contained microfluidic biochip device that has been developed to automate the fluidic handling steps for microarray-based gene expression or genotyping analysis is presented. The device consists of a semiconductor-based CustomArray® chip with 12,000 features and a microfluidic cartridge. The CustomArray was manufactured using a semiconductor-based in situ synthesis technology. The micro-fluidic cartridge consists of microfluidic pumps, mixers, valves, fluid channels, and reagent storage chambers. Microarray hybridization and subsequent fluidic handling and reactions (including a number of washing and labeling steps) were performed in this fully automated and miniature device before fluorescent image scanning of the microarray chip. Electrochemical micropumps were integrated in the cartridge to provide pumping of liquid solutions. A micromixing technique based on gas bubbling generated by electrochemical micropumps was developed. Low-cost check valves were implemented in the cartridge to prevent cross-talk of the stored reagents. Gene expression study of the human leukemia cell line (K562) and genotyping detection and sequencing of influenza A subtypes have been demonstrated using this integrated biochip platform. For gene expression assays, the microfluidic CustomArray device detected sample RNAs with a concentration as low as 0.375 pM. Detection was quantitative over more than three orders of magnitude. Experiment also showed that chip-to-chip variability was low indicating that the integrated microfluidic devices eliminate manual fluidic handling steps that can be a significant source of variability in genomic analysis. The genotyping results showed that the device identified influenza A hemagglutinin and neuraminidase subtypes and sequenced portions of both genes, demonstrating the potential of integrated microfluidic and microarray technology for multiple virus detection. The device provides a cost-effective solution to eliminate labor-intensive and time-consuming fluidic handling steps and allows microarray-based DNA analysis in a rapid and automated fashion.

Automated online optical biosensing system for continuous real-time determination of microcystin-LR with high sensitivity and specificity: early warning for cyanotoxin risk in drinking water sources.

PubMed

Shi, Han-Chang; Song, Bao-Dong; Long, Feng; Zhou, Xiao-Hong; He, Miao; Lv, Qing; Yang, Hai-Yang

2013-05-07

The accelerated eutrophication of surface water sources and climate change have led to an annual occurrence of cyanobacterial blooms in many drinking water resources. To minimize the health risks to the public, cyanotoxin detection methods that are rapid, sensitive, real time, and high frequency must be established. In this study, an innovative automated online optical biosensing system (AOBS) was developed for the rapid detection and early warning of microcystin-LR (MC-LR), one of the most toxic cyanotoxins and most frequently detected in environmental water. In this system, the capturing molecular MC-LR-ovalbumin (MC-LR-OVA) was covalently immobilized onto a biochip surface. By an indirect competitive detection mode, samples containing different concentrations of MC-LR were premixed with a certain concentration of fluorescence-labeled anti-MC-LR-mAb, which binds to MC-LR with high specificity. Then, the sample mixture was pumped onto the biochip surface, and a higher concentration of MC-LR led to less fluorescence-labeled antibody bound onto the biochip surface and thus to lower fluorescence signal. The quantification of MC-LR ranges from 0.2 to 4 μg/L, with a detection limit determined as 0.09 μg/L. The high specificity and selectivity of the sensor were evaluated in terms of its response to a number of potentially interfering cyanotoxins. Potential interference of the environmental sample matrix was assessed by spiked samples, and the recovery of MC-LR ranged from 90 to 120% with relative standard deviation values <8%. The immunoassay performance of the AOBS was validated with respect to that of conventional high-performance liquid chromatography, and the correlation between methods agreed well (R(2) = 0.9762). This system has successfully been applied to long-term, continuous determination and early warning for MC-LR in Lake Tai from June 2011 to May 2012. Thus, the AOBS paves the way for a vital routine online analysis that satisfies the high demand for ensuring the safety of drinking water sources. The AOBS can also serve as early warning system for accidental or intentional water pollution.

Biomaterials. New Chinese biochip center straddles business, academe.

PubMed

Yimin, D

2000-12-15

Last month, U.S.-trained entrepreneur and researcher Cheng Jing was named head of a new, two-pronged biochip venture here that will be highly unusual even for China, which has been experimenting with academic-industrial arrangements in recent years. One part is a for-profit company backed by $48 million from a combination of national and academic partners and overseas venture capital. The second piece is a nonprofit national center with nearly $10 million in research funding from the Ministry of Science and Technology.

New valve and bonding designs for microfluidic biochips containing proteins.

PubMed

Lu, Chunmeng; Xie, Yubing; Yang, Yong; Cheng, Mark M-C; Koh, Chee-Guan; Bai, Yunling; Lee, L James; Juang, Yi-Je

2007-02-01

Two major concerns in the design and fabrication of microfluidic biochips are protein binding on the channel surface and protein denaturing during device assembly. In this paper, we describe new methods to solve these problems. A "fishbone" microvalve design based on the concept of superhydrophobicity was developed to replace the capillary valve in applications where the chip surface requires protein blocking to prevent nonspecific binding. Our experimental results show that the valve functions well in a CD-like ELISA device. The packaging of biochips containing pre-loaded proteins is also a challenging task since conventional sealing methods often require the use of high temperatures, electric voltages, or organic solvents that are detrimental to the protein activity. Using CO2 gas to enhance the diffusion of polymer molecules near the device surface can result in good bonding at low temperatures and low pressure. This bonding method has little influence on the activity of the pre-loaded proteins after bonding.

Handheld analyzer with on-chip molecularly-imprinted biosensors for electrical detection of propofol in plasma samples.

PubMed

Hong, Chien-Chong; Lin, Chih-Chung; Hong, Chian-Lang; Lin, Zi-Xiang; Chung, Meng-Hua; Hsieh, Pei-Wen

2016-12-15

This paper proposes a novel handheld analyzer with disposable lab-on-a-chip technology for the electrical detection of the anesthetic propofol in human plasma samples for clinical diagnoses. The developed on-chip biosensors are based on the conduction of molecularly imprinted polymers (MIPs) that employ label-free electrical detection techniques. Propofol in total intravenous anesthesia is widely used with a target-controlled infusion system. At present, the methods employed for detecting blood propofol concentrations in hospitals comprise high-performance liquid chromatography and ion mobility spectrometry. These conventional instruments are bulky, expensive, and difficult to access. In this study, we developed a novel plastic microfluidic biochip with an on-chip anesthetic biosensor that was characterized for the rapid detection of propofol concentrations. The experimental results revealed that the response time of the developed propofol biosensors was 25s. The specific binding of an MIP to a nonimprinted polymer (NIP) reached up to 560%. Moreover, the detection limit of the biosensors was 0.1μg/mL, with a linear detection range of 0.1-30μg/mL. The proposed disposable microfluidic biochip with an on-chip anesthetic biosensor using MIPs exhibited excellent performance in the separation and sensing of propofol molecules in the human plasma samples. Compared with large-scale conventional instruments, the developed microfluidic biochips with on-chip MIP biosensors present the advantages of a compact size, high selectivity, low cost, rapid response, and single-step detection. Copyright © 2016 Elsevier B.V. All rights reserved.

Micro-hole array fluorescent sensor based on AC-Dielectrophoresis (DEP) for simultaneous analysis of nano-molecules

NASA Astrophysics Data System (ADS)

Kim, Hye Jin; Kang, Dong-Hoon; Lee, Eunji; Hwang, Kyo Seon; Shin, Hyun-Joon; Kim, Jinsik

2018-02-01

We propose a simple fluorescent bio-chip based on two types of alternative current-dielectrophoretic (AC-DEP) force, attractive (positive DEP) and repulsive (negative DEP) force, for simultaneous nano-molecules analysis. Various radius of micro-holes on the bio-chip are designed to apply the different AC-DEP forces, and the nano-molecules are concentrated inside the micro-hole arrays according to the intensity of the DEP force. The bio-chip was fabricated by Micro Electro Mechanical system (MEMS) technique, and was composed of two layers; a SiO2 layer and Ta/Pt layer were accomplished for an insulation layer and a top electrode with micro-hole arrays to apply electric fields for DEP force, respectively. Each SiO2 and Ta/Pt layers were deposited by thermal oxidation and sputtering, and micro-hole arrays were fabricated with Inductively Coupled Plasma (ICP) etching process. For generation of each positive and negative DEP at micro-holes, we applied two types of sine-wave AC voltage with different frequency range alternately. The intensity of the DEP force was controlled by the radius of the micro-hole and size of nano-molecule, and calculated with COMSOL multi-physics. Three types of nano-molecules labelled with different fluorescent dye were used and the intensity of nano-molecules was examined by the fluorescent optical analysis after applying the DEP force. By analyzing the fluorescent intensities of the nano-molecules, we verify the various nano-molecules in analyte are located successfully inside corresponding micro-holes with different radius according to their size.

Investigation of neutron radiation effects on polyclonal antibodies (IgG) and fluorescein dye for astrobiological applications.

PubMed

Le Postollec, A; Coussot, G; Baqué, M; Incerti, S; Desvignes, I; Moretto, P; Dobrijevic, M; Vandenabeele-Trambouze, O

2009-09-01

Detecting life in the Solar System is one of the great challenges of new upcoming space missions. Biochips have been proposed as a way to detect organic matter on extraterrestrial objects. A biochip is a miniaturized device composed of biologically sensitive systems, such as antibodies, which are immobilized on a slide. In the case of in situ measurements, the main concern is to ensure the survival of the antibodies under space radiation. Our recent computing simulation of cosmic ray interactions with the martian environment shows that neutrons are one of the dominant species at soil level. Therefore, we have chosen, in a first approach, to study antibody resistance to neutrons by performing irradiation experiments at the Applications Interdisciplinaires des Faisceaux d'Ions en Région Aquitaine (AIFIRA) platform, a French ion beam facility at the Centre d'Etudes Nucléaires de Bordeaux-Gradignan in Bordeaux. Antibodies and fluorescent dyes, freeze-dried and in buffer solution, were irradiated with 0.6 MeV and 6 MeV neutrons. Sample analyses demonstrated that, in the conditions tested, antibody recognition capability and fluorescence dye intensity are not affected by the neutrons.

Continuous Non-Destructive Monitoring of Cell Health Using Impedance Based Interdigitated Electrode Structured Sensors

NASA Astrophysics Data System (ADS)

Paschero, Anna; McLoughlin, Eve; Moore, Eric

2011-06-01

This article examines some preliminary tests which were performed in order to evaluate the best electrode configuration (width and spacing) for cell culture analyses. Biochips packaged with indium tin oxide (ITO) interdigitated electrodes (IDEs) were used to perform impedance measurements on A549 cells cultured on the surface of the biochip. Several tests were carried out using a 10 mM solution of Sodium Chloride (NaCl), cell medium and the cell culture itself to characterize some of the configurations already fabricated in the facilities at Tyndall National Institute.

Integrated multiple patch-clamp array chip via lateral cell trapping junctions

NASA Astrophysics Data System (ADS)

Seo, J.; Ionescu-Zanetti, C.; Diamond, J.; Lal, R.; Lee, L. P.

2004-03-01

We present an integrated multiple patch-clamp array chip by utilizing lateral cell trapping junctions. The intersectional design of a microfluidic network provides multiple cell addressing and manipulation sites for efficient electrophysiological measurements at a number of patch sites. The patch pores consist of openings in the sidewall of a main fluidic channel, and a membrane patch is drawn into a smaller horizontal channel. This device geometry not only minimizes capacitive coupling between the cell reservoir and the patch channel, but also allows simultaneous optical and electrical measurements of ion channel proteins. Evidence of the hydrodynamic placement of mammalian cells at the patch sites as well as measurements of patch sealing resistance is presented. Device fabrication is based on micromolding of polydimethylsiloxane, thus allowing inexpensive mass production of disposable high-throughput biochips.

Fluorescence-based bioassays for the detection and evaluation of food materials.

PubMed

Nishi, Kentaro; Isobe, Shin-Ichiro; Zhu, Yun; Kiyama, Ryoiti

2015-10-13

We summarize here the recent progress in fluorescence-based bioassays for the detection and evaluation of food materials by focusing on fluorescent dyes used in bioassays and applications of these assays for food safety, quality and efficacy. Fluorescent dyes have been used in various bioassays, such as biosensing, cell assay, energy transfer-based assay, probing, protein/immunological assay and microarray/biochip assay. Among the arrays used in microarray/biochip assay, fluorescence-based microarrays/biochips, such as antibody/protein microarrays, bead/suspension arrays, capillary/sensor arrays, DNA microarrays/polymerase chain reaction (PCR)-based arrays, glycan/lectin arrays, immunoassay/enzyme-linked immunosorbent assay (ELISA)-based arrays, microfluidic chips and tissue arrays, have been developed and used for the assessment of allergy/poisoning/toxicity, contamination and efficacy/mechanism, and quality control/safety. DNA microarray assays have been used widely for food safety and quality as well as searches for active components. DNA microarray-based gene expression profiling may be useful for such purposes due to its advantages in the evaluation of pathway-based intracellular signaling in response to food materials.

Fluorescence-Based Bioassays for the Detection and Evaluation of Food Materials

PubMed Central

Nishi, Kentaro; Isobe, Shin-Ichiro; Zhu, Yun; Kiyama, Ryoiti

2015-01-01

We summarize here the recent progress in fluorescence-based bioassays for the detection and evaluation of food materials by focusing on fluorescent dyes used in bioassays and applications of these assays for food safety, quality and efficacy. Fluorescent dyes have been used in various bioassays, such as biosensing, cell assay, energy transfer-based assay, probing, protein/immunological assay and microarray/biochip assay. Among the arrays used in microarray/biochip assay, fluorescence-based microarrays/biochips, such as antibody/protein microarrays, bead/suspension arrays, capillary/sensor arrays, DNA microarrays/polymerase chain reaction (PCR)-based arrays, glycan/lectin arrays, immunoassay/enzyme-linked immunosorbent assay (ELISA)-based arrays, microfluidic chips and tissue arrays, have been developed and used for the assessment of allergy/poisoning/toxicity, contamination and efficacy/mechanism, and quality control/safety. DNA microarray assays have been used widely for food safety and quality as well as searches for active components. DNA microarray-based gene expression profiling may be useful for such purposes due to its advantages in the evaluation of pathway-based intracellular signaling in response to food materials. PMID:26473869

Biochip microsystem for bioinformatics recognition and analysis

NASA Technical Reports Server (NTRS)

Lue, Jaw-Chyng (Inventor); Fang, Wai-Chi (Inventor)

2011-01-01

A system with applications in pattern recognition, or classification, of DNA assay samples. Because DNA reference and sample material in wells of an assay may be caused to fluoresce depending upon dye added to the material, the resulting light may be imaged onto an embodiment comprising an array of photodetectors and an adaptive neural network, with applications to DNA analysis. Other embodiments are described and claimed.

Development of a multilayered polymeric DNA biosensor using radio frequency technology with gold and magnetic nanoparticles.

PubMed

Yang, Cheng-Hao; Kuo, Long-Sheng; Chen, Ping-Hei; Yang, Chii-Rong; Tsai, Zuo-Min

2012-01-15

This study utilized the radio frequency (RF) technology to develop a multilayered polymeric DNA sensor with the help of gold and magnetic nanoparticles. The flexible polymeric materials, poly (p-xylylene) (Parylene) and polyethylene naphtholate (PEN), were used as substrates to replace the conventional rigid substrates such as glass and silicon wafers. The multilayered polymeric RF biosensor, including the two polymer layers and two copper transmission structure layers, was developed to reduce the total sensor size and further enhance the sensitivity of the biochip in the RF DNA detection. Thioglycolic acid (TGA) was used on the surface of the proposed biochip to form a thiolate-modified sensing surface for DNA hybridization. Gold nanoparticles (AuNPs) and magnetic nanoparticles (MNPs) were used to immobilize on the surface of the biosensor to enhance overall detection sensitivity. In addition to gold nanoparticles, the magnetic nanoparticles has been demonstrated the applicability for RF DNA detection. The performance of the proposed biosensor was evaluated by the shift of the center frequency of the RF biosensor because the electromagnetic characteristic of the biosensors can be altered by the immobilized multilayer nanoparticles on the biosensor. The experimental results show that the detection limit of the DNA concentration can reach as low as 10 pM, and the largest shift of the center frequency with triple-layer AuNPs and MNPs can approach 0.9 and 0.7 GHz, respectively. Such the achievement implies that the developed biosensor can offer an alternative inexpensive, disposable, and highly sensitive option for application in biomedicine diagnostic systems because the price and size of each biochip can be effectively reduced by using fully polymeric materials and multilayer-detecting structures. Copyright © 2011 Elsevier B.V. All rights reserved.

Ex situ bioremediation of oil-contaminated soil.

PubMed

Lin, Ta-Chen; Pan, Po-Tsen; Cheng, Sheng-Shung

2010-04-15

An innovative bioprocess method, Systematic Environmental Molecular Bioremediation Technology (SEMBT) that combines bioaugmentation and biostimulation with a molecular monitoring microarray biochip, was developed as an integrated bioremediation technology to treat S- and T-series biopiles by using the landfarming operation and reseeding process to enhance the bioremediation efficiency. After 28 days of the bioremediation process, diesel oil (TPH(C10-C28)) and fuel oil (TPH(C10-C40)) were degraded up to approximately 70% and 63% respectively in the S-series biopiles. When the bioaugmentation and biostimulation were applied in the beginning of bioremediation, the microbial concentration increased from approximately 10(5) to 10(6) CFU/g dry soil along with the TPH biodegradation. Analysis of microbial diversity in the contaminated soils by microarray biochips revealed that Acinetobacter sp. and Pseudomonas aeruginosa were the predominant groups in indigenous consortia, while the augmented consortia were Gordonia alkanivorans and Rhodococcus erythropolis in both series of biopiles during bioremediation. Microbial respiration as influenced by the microbial activity reflected directly the active microbial population and indirectly the biodegradation of TPH. Field experimental results showed that the residual TPH concentration in the complex biopile was reduced to less than 500 mg TPH/kg dry soil. The above results demonstrated that the SEMBT technology is a feasible alternative to bioremediate the oil-contaminated soil. Crown Copyright 2009. Published by Elsevier B.V. All rights reserved.

A matter of accuracy. Nanobiochips in diagnostics and in research: ethical issues as value trade-offs.

PubMed

Le Roux, Ronan

2015-04-01

The paper deals with the introduction of nanotechnology in biochips. Based on interviews and theoretical reflections, it explores blind spots left by technology assessment and ethical investigations. These have focused on possible consequences of increased diffusability of a diagnostic device, neglecting both the context of research as well as increased accuracy, despite it being a more essential feature of nanobiochip projects. Also, rather than one of many parallel aspects (technical, legal and social) in innovation processes, ethics is considered here as a ubiquitous system of choices between sometimes antagonistic values. Thus, the paper investigates what is at stake when accuracy is balanced with other practical values in different contexts. Dramatic nanotechnological increase of accuracy in biochips can raise ethical issues, since it is at odds with other values such as diffusability and reliability. But those issues will not be as revolutionary as is often claimed: neither in diagnostics, because accuracy of measurements is not accuracy of diagnostics; nor in research, because a boost in measurement accuracy is not sufficient to overcome significance-chasing malpractices. The conclusion extends to methodological recommendations.

Security Assessment of Cyberphysical Digital Microfluidic Biochips.

PubMed

Ali, Sk Subidh; Ibrahim, Mohamed; Sinanoglu, Ozgur; Chakrabarty, Krishnendu; Karri, Ramesh

2016-01-01

A digital microfluidic biochip (DMFB) is an emerging technology that enables miniaturized analysis systems for point-of-care clinical diagnostics, DNA sequencing, and environmental monitoring. A DMFB reduces the rate of sample and reagent consumption, and automates the analysis of assays. In this paper, we provide the first assessment of the security vulnerabilities of DMFBs. We identify result-manipulation attacks on a DMFB that maliciously alter the assay outcomes. Two practical result-manipulation attacks are shown on a DMFB platform performing enzymatic glucose assay on serum. In the first attack, the attacker adjusts the concentration of the glucose sample and thereby modifies the final result. In the second attack, the attacker tampers with the calibration curve of the assay operation. We then identify denial-of-service attacks, where the attacker can disrupt the assay operation by tampering either with the droplet-routing algorithm or with the actuation sequence. We demonstrate these attacks using a digital microfluidic synthesis simulator. The results show that the attacks are easy to implement and hard to detect. Therefore, this work highlights the need for effective protections against malicious modifications in DMFBs.

The molecular electronic device and the biochip computer: present status.

PubMed

Haddon, R C; Lamola, A A

1985-04-01

The idea that a single molecule might function as a self-contained electronic device has been of interest for some time. However, a fully integrated version--the biochip or the biocomputer, in which both production and assembly of molecular electronic components is achieved through biotechnology-is a relatively new concept that is currently attracting attention both within the scientific community and among the general public. In the present article we draw together some of the approaches being considered for the construction of such devices and delineate the revolutionary nature of the current proposals for molecular electronic devices (MEDs) and biochip computers (BCCs). With the silicon semiconductor conductor industry already in place and in view of the continuing successes of the lithographic process it seems appropriate to ask why the highly speculative MED or BCC has engendered such interest. In some respects the answer is paradigmatic as much as it is real. It is perhaps best stated as the promise of the realm of the molecular. Thus it is envisioned that devices will be constructed by assembly of individual molecular electronic components into arrays, thereby engineering from small upward rather than large downward as do current lithographic techniques. An important corollary of the construction technique is that the functional elements of such an array would be individual molecules rather than macroscopic ensembles. These two aspects of the MED/BCC--assembly of molecular arrays and individually accessible functional molecular units--are truly revolutionary. Both require scientific breakthroughs and the necessary principles, quite apart from the technology, remain essentially unknown. It is concluded that the advent of the MED/BCC still lies well before us. The twin criteria of utilization of individual molecules as functional elements and the assembly of such elements remains as elusive as ever. Biology engineers structures on the molecular scale but biomolecules do not seem to be imbued with useful electronic properties. Molecular beam epitaxy and thin-film techniques produce electronic devices but they "engineer down" and are currently unable to generate individual molecular units. The potential of the MED/BCC field is matched only by the obstacles that must be surmounted for its realization.

Surface engineered biosensors for the early detection of cancer

NASA Astrophysics Data System (ADS)

Islam, Muhymin

Cancer commences in the building block of human body which is cells and in most of the cases remains silent at early stage. Diseases are only expressed at molecular and cellular level at primary stages. Recognition of diseases at this micro and nano level might reduce the mortality rate of cancer significantly. This research work aimed to introduce novel electronic biosensors for for identification of cancer at cellular level. The dissertation study focuses on 1) Label-Free Isolation of Metastatic Tumor Cells Using Filter Based Microfluidic device; 2) Nanotextured Polymer Substrates for Enhanced Cancer Cell Isolation and Cell Growth; 3) Nanotextured Microfluidic Channel for Electrical Profiling and Detection of Tumor Cells from Blood; and 4) Single Biochip for the Detection of Tumor Cells by Electrical Profile and Surface Immobilized Aptamer. Standard silicon processing techniques were followed to fabricate all of the biosensors. Nantoextruing and surface functionalizon were also incorporated to elevate the efficiency of the devices. The first approach aimed to detect cancer cells from blood based on their mechanophysical properties. Cancer cells are larger than blood cells but highly elastic in nature. These cells can squeeze through small microchannels much smaller than their size. The cross sectional area of the microchannels was optimized to isolate tumor cells from blood. Nanotextured polymer substrates, a platform inspired from the natural basement membrane was used to enhance the isolation and growth of tumor cells. Micro reactive ion etching was performed to have better control on features of nantoxtured surfaces and did not require any template. Next, electrical measurement of ionic current was performed across single microchannel to detect tumor cells from blood. Later, nanotexturing enhanced the efficiency of the device by selectively altering the translocation profile of cancer cells. Eventually aptamer functionalized nanotextured polymer surface was integrated with current measurement facilities in a single biochip to discriminate tumor cells from blood with higher efficiency and selectivity. This biochip can be an implemented as a point-of-care device for the early detection of cancer at cellular level.

The molecular electronic device and the biochip computer: present status.

PubMed Central

Haddon, R C; Lamola, A A

1985-01-01

The idea that a single molecule might function as a self-contained electronic device has been of interest for some time. However, a fully integrated version--the biochip or the biocomputer, in which both production and assembly of molecular electronic components is achieved through biotechnology-is a relatively new concept that is currently attracting attention both within the scientific community and among the general public. In the present article we draw together some of the approaches being considered for the construction of such devices and delineate the revolutionary nature of the current proposals for molecular electronic devices (MEDs) and biochip computers (BCCs). With the silicon semiconductor conductor industry already in place and in view of the continuing successes of the lithographic process it seems appropriate to ask why the highly speculative MED or BCC has engendered such interest. In some respects the answer is paradigmatic as much as it is real. It is perhaps best stated as the promise of the realm of the molecular. Thus it is envisioned that devices will be constructed by assembly of individual molecular electronic components into arrays, thereby engineering from small upward rather than large downward as do current lithographic techniques. An important corollary of the construction technique is that the functional elements of such an array would be individual molecules rather than macroscopic ensembles. These two aspects of the MED/BCC--assembly of molecular arrays and individually accessible functional molecular units--are truly revolutionary. Both require scientific breakthroughs and the necessary principles, quite apart from the technology, remain essentially unknown. It is concluded that the advent of the MED/BCC still lies well before us. The twin criteria of utilization of individual molecules as functional elements and the assembly of such elements remains as elusive as ever. Biology engineers structures on the molecular scale but biomolecules do not seem to be imbued with useful electronic properties. Molecular beam epitaxy and thin-film techniques produce electronic devices but they "engineer down" and are currently unable to generate individual molecular units. The potential of the MED/BCC field is matched only by the obstacles that must be surmounted for its realization. PMID:3856865

Colloidal core-seeded semiconductor nanorods as fluorescent labels for in-vitro diagnostics (Conference Presentation)

NASA Astrophysics Data System (ADS)

Chan, YinThai

2016-03-01

Colloidal semiconductor nanocrystals are ideal fluorophores for clinical diagnostics, therapeutics, and highly sensitive biochip applications due to their high photostability, size-tunable color of emission and flexible surface chemistry. The relatively recent development of core-seeded semiconductor nanorods showed that the presence of a rod-like shell can confer even more advantageous physicochemical properties than their spherical counterparts, such as large multi-photon absorption cross-sections and facet-specific chemistry that can be exploited to deposit secondary nanoparticles. It may be envisaged that these highly fluorescent nanorods can be integrated with large scale integrated (LSI) microfluidic systems that allow miniaturization and integration of multiple biochemical processes in a single device at the nanoliter scale, resulting in a highly sensitive and automated detection platform. In this talk, I will describe a LSI microfluidic device that integrates RNA extraction, reverse transcription to cDNA, amplification and target pull-down to detect histidine decarboxylase (HDC) gene directly from human white blood cells samples. When anisotropic colloidal semiconductor nanorods (NRs) were used as the fluorescent readout, the detection limit was found to be 0.4 ng of total RNA, which was much lower than that obtained using spherical quantum dots (QDs) or organic dyes. This was attributed to the large action cross-section of NRs and their high probability of target capture in a pull-down detection scheme. The combination of large scale integrated microfluidics with highly fluorescent semiconductor NRs may find widespread utility in point-of-care devices and multi-target diagnostics.

The bacteriorhodopsin model membrane system as a prototype molecular computing element.

PubMed

Hong, F T

1986-01-01

The quest for more sophisticated integrated circuits to overcome the limitation of currently available silicon integrated circuits has led to the proposal of using biological molecules as computational elements by computer scientists and engineers. While the theoretical aspect of this possibility has been pursued by computer scientists, the research and development of experimental prototypes have not been pursued with an equal intensity. In this survey, we make an attempt to examine model membrane systems that incorporate the protein pigment bacteriorhodopsin which is found in Halobacterium halobium. This system was chosen for several reasons. The pigment/membrane system is sufficiently simple and stable for rigorous quantitative study, yet at the same time sufficiently complex in molecular structure to permit alteration of this structure in an attempt to manipulate the photosignal. Several methods of forming the pigment/membrane assembly are described and the potential application to biochip design is discussed. Experimental data using these membranes and measured by a tunable voltage clamp method are presented along with a theoretical analysis based on the Gouy-Chapman diffuse double layer theory to illustrate the usefulness of this approach. It is shown that detailed layouts of the pigment/membrane assembly as well as external loading conditions can modify the time course of the photosignal in a predictable manner. Some problems that may arise in the actual implementation and manufacturing, as well as the use of existing technology in protein chemistry, immunology, and recombinant DNA technology are discussed.

Soft Lithography for Oligonucleotide Arrays Fabrication

DTIC Science & Technology

2001-10-25

adenosine; Abbreviated T, C, G, A respectively), the other synthesis reagents and solvents except oxidation agent (seen in Table 1) were purchased...dried by cold blowing before hybridization. Oligonucleotide arrays were hybridized in 200 nM 3’-TCC TCC GAT TCA GAG AGT CC- HEX (PE Biosystems... citrate buffer), 0.1% SDS in 0.1xSSC respectively. The probe array was scanned on the Scanarray Microarray Systems (Packard Biochip Technologies, USA

Continuing evolution of in-vitro diagnostic instrumentation

NASA Astrophysics Data System (ADS)

Cohn, Gerald E.

2000-04-01

The synthesis of analytical instrumentation and analytical biochemistry technologies in modern in vitro diagnostic instrumentation continues to generate new systems with improved performance and expanded capability. Detection modalities have expanded to include multichip modes of fluorescence, scattering, luminescence and reflectance so as to accommodate increasingly sophisticated immunochemical and nucleic acid based reagent systems. The time line graph of system development now extends from the earliest automated clinical spectrophotometers through molecule recognition assays and biosensors to the new breakthroughs of biochip and DNA diagnostics. This brief review traces some of the major innovations in the evolution of system technologies and previews the conference program.

An electrical bio-chip to transfer and detect electromagnetic stimulation on the cells based on vertically aligned carbon nanotubes.

PubMed

Rafizadeh-Tafti, Saeed; Haqiqatkhah, Mohammad Hossein; Saviz, Mehrdad; Janmaleki, Mohsen; Faraji Dana, Reza; Zanganeh, Somayeh; Abdolahad, Mohammad

2017-01-01

A highly sensitive impedimetric bio-chip based on vertically aligned multiwall carbon nanotubes (VAMWCNTs), was applied in direct interaction with lung cancer cells. Our tool provided both inducing and monitoring the bioelectrical changes in the cells initiated by electromagnetic (EM) wave stimulation. EM wave of 940MHz frequency with different intensities was used. Here, wave ablation might accumulate electrical charge on the tips of nanotubes penetrated into cell's membrane. The charge might induce ionic exchanges into the cell and cause alterations in electrical states of the membrane. Transmembrane electrostatic/dynamic states would be strongly affected due to such exchanges. Our novel modality was that, the cells' vitality changes caused by charge inductions were electrically detected with the same nanotubes in the architecture of electrodes for impedance measurement. The responses of the sensor were confirmed by electron and florescent microscopy images as well as biological assays. In summation, our method provided an effective biochip for enhancing and detecting external EM stimulation on the cells useful for future diagnostic and therapeutic applications, such as wave-guided drug-resistance breakage. Copyright © 2016 Elsevier B.V. All rights reserved.

Pressure-Aware Control Layer Optimization for Flow-Based Microfluidic Biochips.

PubMed

Wang, Qin; Xu, Yue; Zuo, Shiliang; Yao, Hailong; Ho, Tsung-Yi; Li, Bing; Schlichtmann, Ulf; Cai, Yici

2017-12-01

Flow-based microfluidic biochips are attracting increasing attention with successful biomedical applications. One critical issue with flow-based microfluidic biochips is the large number of microvalves that require peripheral control pins. Even using the broadcasting addressing scheme, i.e., one control pin controls multiple microvalves simultaneously, thousands of microvalves would still require hundreds of control prins, which is unrealistic. To address this critical challenge in control scalability, the control-layer multiplexer is introduced to effectively reduce the number of control pins into log scale of the number of microvalves. There are two practical design issues with the control-layer multiplexer: (1) the reliability issue caused by the frequent control-valve switching, and (2) the pressure degradation problem caused by the control-valve switching without pressure refreshing from the pressure source. This paper addresses these two design issues by the proposed Hamming-distance-based switching sequence optimization method and the XOR-based pressure refreshing method. Simulation results demonstrate the effectiveness and efficiency of the proposed methods with an average 77.2% (maximum 89.6%) improvement in total pressure refreshing cost, and an average 88.5% (maximum 90.0%) improvement in pressure deviation.

Regenerable immuno-biochip for screening ochratoxin A in green coffee extract using an automated microarray chip reader with chemiluminescence detection.

PubMed

Sauceda-Friebe, Jimena C; Karsunke, Xaver Y Z; Vazac, Susanna; Biselli, Scarlett; Niessner, Reinhard; Knopp, Dietmar

2011-03-18

Ochratoxin A (OTA) can contaminate foodstuffs in the ppb to ppm range and once formed, it is difficult to remove. Because of its toxicity and potential risks to human health, the need exists for rapid, efficient detection methods that comply with legal maximum residual limits. In this work we have synthesized an OTA conjugate functionalized with a water-soluble peptide for covalent immobilization on a glass biochip by means of contact spotting. The chip was used for OTA determination with an indirect competitive immunoassay format with flow-through reagent addition and chemiluminescence detection, carried out with the stand-alone automated Munich Chip Reader 3 (MCR 3) platform. A buffer model and real green coffee extracts were used for this purpose. At the present, covalent conjugate immobilization allowed for at least 20 assay-regeneration cycles of the biochip surface. The total analysis time for a single sample, including measurement and surface regeneration, was 12 min and the LOQ of OTA in green coffee extract was 0.3 μg L(-1) which corresponds to 7 μg kg(-1). Copyright © 2011 Elsevier B.V. All rights reserved.

Self-calibrated dynamical optical biochip system using surface plasmon resonance imaging: application to genotyping

NASA Astrophysics Data System (ADS)

Hottin, Jérôme; Moreau, Julien; Spadavecchia, Jolanda; Bellemain, Alain; Lecerf, Laure; Goossens, Michel; Canva, Michael

2008-04-01

The present paper summarizes some of our work in the field of genetic diagnosis using Surface Plasmon Resonance Imaging. The optical setup and its capability are presented, as well as the gold surface functionalization used. Results obtained with oligonucleotides targets, specific to Cystic Fibrosis disease, in high and low concentration are shown. The self-calibration method we have developed to reduce data dispersion in genetic diagnosis applications is described.

Characterizing opto-electret based paper speakers by using a real-time projection Moiré metrology system

NASA Astrophysics Data System (ADS)

Chang, Ya-Ling; Hsu, Kuan-Yu; Lee, Chih-Kung

2016-03-01

Advancement of distributed piezo-electret sensors and actuators facilitates various smart systems development, which include paper speakers, opto-piezo/electret bio-chips, etc. The array-based loudspeaker system possess several advantages over conventional coil speakers, such as light-weightness, flexibility, low power consumption, directivity, etc. With the understanding that the performance of the large-area piezo-electret loudspeakers or even the microfluidic biochip transport behavior could be tailored by changing their dynamic behaviors, a full-field real-time high-resolution non-contact metrology system was developed. In this paper, influence of the resonance modes and the transient vibrations of an arraybased loudspeaker system on the acoustic effect were measured by using a real-time projection moiré metrology system and microphones. To make the paper speaker even more versatile, we combine the photosensitive material TiOPc into the original electret loudspeaker. The vibration of this newly developed opto-electret loudspeaker could be manipulated by illuminating different light-intensity patterns. Trying to facilitate the tailoring process of the opto-electret loudspeaker, projection moiré was adopted to measure its vibration. By recording the projected fringes which are modulated by the contours of the testing sample, the phase unwrapping algorithm can give us a continuous phase distribution which is proportional to the object height variations. With the aid of the projection moiré metrology system, the vibrations associated with each distinctive light pattern could be characterized. Therefore, we expect that the overall acoustic performance could be improved by finding the suitable illuminating patterns. In this manuscript, the system performance of the projection moiré and the optoelectret paper speakers were cross-examined and verified by the experimental results obtained.

Grafting of antibodies inside integrated microfluidic-microoptic devices by means of automated microcontact printing

PubMed Central

Bou Chakra, Elie; Hannes, Benjamin; Vieillard, Julien; Mansfield, Colin D.; Mazurczyk, Radoslav; Bouchard, Aude; Potempa, Jan; Krawczyk, Stanislas; Cabrera, Michel

2009-01-01

A novel approach to integrating biochip and microfluidic devices is reported in which microcontact printing is a key fabrication technique. The process is performed using an automated microcontact printer that has been developed as an application-specific tool. As proof-of-concept the instrument is used to consecutively and selectively graft patterns of antibodies at the bottom of a glass channel for use in microfluidic immunoassays. Importantly, feature collapse due to over compression of the PDMS stamp is avoided by fine control of the stamp’s compression during contact. The precise alignment of biomolecules at the intersection of microfluidic channel and integrated optical waveguides has been achieved, with antigen detection performed via fluorescence excitation. Thus, it has been demonstrated that this technology permits sequential microcontact printing of isolated features consisting of functional biomolecules at any position along a microfluidic channel and also that it is possible to precisely align these features with existing components. PMID:20161128

Interconnecting wearable devices with nano-biosensing implants through optical wireless communications

NASA Astrophysics Data System (ADS)

Johari, Pedram; Pandey, Honey; Jornet, Josep M.

2018-02-01

Major advancements in the fields of electronics, photonics and wireless communication have enabled the development of compact wearable devices, with applications in diverse domains such as fitness, wellness and medicine. In parallel, nanotechnology is enabling the development of miniature sensors that can detect events at the nanoscale with unprecedented accuracy. On this matter, in vivo implantable Surface Plasmon Resonance (SPR) nanosensors have been proposed to analyze circulating biomarkers in body fluids for the early diagnosis of a myriad of diseases, ranging from cardiovascular disorders to different types of cancer. In light of these results, in this paper, an architecture is proposed to bridge the gap between these two apparently disjoint paradigms, namely, the commercial wearable devices and the advanced nano-biosensing technologies. More specifically, this paper thoroughly assesses the feasibility of the wireless optical intercommunications of an SPR-based nanoplasmonic biochip -implanted subcutaneously in the wrist-, with a nanophotonic wearable smart band which is integrated by an array of nano-lasers and photon-detectors for distributed excitation and measurement of the nanoplasmonic biochip. This is done through a link budget analysis which captures the peculiarities of the intra-body optical channel at (sub) cellular level, the strength of the SPR nanosensor reflection, as well as the capabilities of the nanolasers (emission power, spectrum) and the nano photon-detectors (sensitivity and noise equivalent power). The proposed analysis guides the development of practical communication designs between the wearable devices and nano-biosensing implants, which paves the way through early-stage diagnosis of severe diseases.

Morphological investigations of cells that adhered to the irregular patterned polydimethylsiloxane (PDMS) surface without reagents.

PubMed

Chung, Sung Hee; Min, Junhong

2009-07-01

Polydimethylsiloxane (PDMS) surface consisting irregular pattern was investigated to develop cell-based biochip using PDMS. PDMS surface was modified with nano- and micro-combined patterns using surface deformation technology. Hydrophobicity of nano-patterned PDMS surface was sustained. Nevertheless it has irregular patterns consisting of micro- and nano-patterns. According to atomic force microscopy (AFM), scanning electron microscopy (SEM) and confocal microscopy results by immunostaining method, human mammary epithelial cells (HMEC) adhered well on irregularly patterned surface without any reagents such as gelatin and collagen, compared to commercial culture dish. It implies PDMS material can be utilized as template for cell-based biochip without any reagents.

Design and fabrication of label-free biochip using a guided mode resonance filter with nano grating structures by injection molding process.

PubMed

Cho, E; Kim, B; Choi, S; Han, J; Jin, J; Han, J; Lim, J; Heo, Y; Kim, S; Sung, G Y; Kang, S

2011-01-01

This paper introduces technology to fabricate a guided mode resonance filter biochip using injection molding. Of the various nanofabrication processes that exist, injection molding is the most suitable for the mass production of polymer nanostructures. Fabrication of a nanograting pattern for guided mode resonance filters by injection molding requires a durable metal stamp, because of the high injection temperature and pressure. Careful consideration of the optimized process parameters is also required to achieve uniform sub-wavelength gratings with high fidelity. In this study, a metallic nanostructure pattern to be used as the stamp for the injection molding process was fabricated using electron beam lithography, a UV nanoimprinting process, and an electroforming process. A one-dimensional nanograting substrate was replicated by injection molding, during which the process parameters were controlled. To evaluate the geometric quality of the injection molded nanograting patterns, the surface profile of the fabricated nanograting for different processing conditions was analyzed using an atomic force microscope and a scanning electron microscope. Finally, to demonstrate the feasibility of the proposed process for fabricating guided mode resonance filter biochips, a high-refractive-index material was deposited on the polymer nanograting and its guided mode resonance characteristics were analyzed.

Nanoplasmonic biochips for rapid label-free detection of imidacloprid pesticides with a smartphone.

PubMed

Lee, Kuang-Li; You, Meng-Lin; Tsai, Chia-Hsin; Lin, En-Hung; Hsieh, Shu-Yi; Ho, Ming-Hsun; Hsu, Ju-Chun; Wei, Pei-Kuen

2016-01-15

The widespread and intensive use of neonicotinoid insecticides induces negative cascading effects on ecosystems. It is desirable to develop a portable sensitive sensing platform for on-site screening of high-risk pesticides. We combined an indirect competitive immunoassay, highly sensitive surface plasmon resonance (SPR) biochip and a simple portable imaging setup for label-free detection of imidacloprid pesticides. The SPR biochip consists of several capped nanoslit arrays with different periods which form a spectral image on the chip. The qualitative and semiquantitative analyses of pesticides can be directly observed from the spot shift on the chip. The precise semiquantitative analyses can be further completed by using image processing in a smartphone. We demonstrate simultaneous detection of four different concentrations of imidacloprid pesticides. The visual detection limit is about 1ppb, which is well below the maximum residue concentration permitted by law (20ppb). Compared to the one-step strip assay, the proposed chip is capable of performing semiquantitative analyses and multiple detection. Compared to the enzyme-linked immunosorbent assay, our method is label-free and requires simple washing steps and short reaction time. In addition, the label-free chip has a comparable sensitivity but wider working range than those labeling techniques. Copyright © 2015 Elsevier B.V. All rights reserved.

A diagnostic biochip for the comprehensive analysis of MLL translocations in acute leukemia.

PubMed

Maroc, N; Morel, A; Beillard, E; De La Chapelle, A L; Fund, X; Mozziconacci, M-J; Dupont, M; Cayuela, J-M; Gabert, J; Koki, A; Fert, V; Hermitte, F

2004-09-01

Reciprocal rearrangements of the MLL gene are among the most common chromosomal abnormalities in both Acute Lymphoblastic and Myeloid Leukemia. The MLL gene, located on the 11q23 chromosomal band, is involved in more than 40 recurrent translocations. In the present study, we describe the development and validation of a biochip-based assay designed to provide a comprehensive molecular analysis of MLL rearrangements when used in a standard clinical pathology laboratory. A retrospective blind study was run with cell lines (n=5), and MLL positive and negative patient samples (n=31), to evaluate assay performance. The limits of detection determined on cell line data were 10(-1), and the precision studies yielded 100% repeatability and 98% reproducibility. The study shows that the device can detect frequent (AF4, AF6, AF10, ELL or ENL) as well as rare partner genes (AF17, MSF). The identified fusion transcripts can then be used as molecular phenotypic markers of disease for the precise evaluation of minimal residual disease by RQ-PCR. This biochip-based molecular diagnostic tool allows, in a single experiment, rapid and accurate identification of MLL gene rearrangements among 32 different fusion gene (FG) partners, precise breakpoint positioning and comprehensive screening of all currently characterized MLL FGs.

Red Blood Cell Agglutination for Blood Typing Within Passive Microfluidic Biochips.

PubMed

Huet, Maxime; Cubizolles, Myriam; Buhot, Arnaud

2018-04-19

Pre-transfusion bedside compatibility test is mandatory to check that the donor and the recipient present compatible groups before any transfusion is performed. Although blood typing devices are present on the market, they still suffer from various drawbacks, like results that are based on naked-eye observation or difficulties in blood handling and process automation. In this study, we addressed the development of a red blood cells (RBC) agglutination assay for point-of-care blood typing. An injection molded microfluidic chip that is designed to enhance capillary flow contained anti-A or anti-B dried reagents inside its microchannel. The only blood handling step in the assay protocol consisted in the deposit of a blood drop at the tip of the biochip, and imaging was then achieved. The embedded reagents were able to trigger RBC agglutination in situ, allowing for us to monitor in real time the whole process. An image processing algorithm was developed on diluted bloods to compute real-time agglutination indicator and was further validated on undiluted blood. Through this proof of concept, we achieved efficient, automated, real time, and quantitative measurement of agglutination inside a passive biochip for blood typing which could be further generalized to blood biomarker detection and quantification.

One-to-one neuron-electrode interfacing.

PubMed

Greenbaum, Alon; Anava, Sarit; Ayali, Amir; Shein, Mark; David-Pur, Moshe; Ben-Jacob, Eshel; Hanein, Yael

2009-09-15

The question of neuronal network development and organization is a principle one, which is closely related to aspects of neuronal and network form-function interactions. In-vitro two-dimensional neuronal cultures have proved to be an attractive and successful model for the study of these questions. Research is constraint however by the search for techniques aimed at culturing stable networks, whose electrical activity can be reliably and consistently monitored. A simple approach to form small interconnected neuronal circuits while achieving one-to-one neuron-electrode interfacing is presented. Locust neurons were cultured on a novel bio-chip consisting of carbon-nanotube multi-electrode-arrays. The cells self-organized to position themselves in close proximity to the bio-chip electrodes. The organization of the cells on the electrodes was analyzed using time lapse microscopy, fluorescence imaging and scanning electron microscopy. Electrical recordings from well identified cells is presented and discussed. The unique properties of the bio-chip and the specific neuron-nanotube interactions, together with the use of relatively large insect ganglion cells, allowed long-term stabilization (as long as 10 days) of predefined neural network topology as well as high fidelity electrical recording of individual neuron firing. This novel preparation opens ample opportunity for future investigation into key neurobiological questions and principles.

Optimization of a polydopamine (PD)-based coating method and polydimethylsiloxane (PDMS) substrates for improved mouse embryonic stem cell (ESC) pluripotency maintenance and cardiac differentiation.

PubMed

Fu, Jiayin; Chuah, Yon Jin; Ang, Wee Tong; Zheng, Nan; Wang, Dong-An

2017-05-30

Myocardiocyte derived from pluripotent stem cells, such as induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), is a promising cell source for cardiac tissue engineering. Combined with microfluidic technologies, a heart-on-a-chip is very likely to be developed and function as a platform for high throughput drug screening. Polydimethylsiloxane (PDMS) silicone elastomer is a widely-used biomaterial for the investigation of cell-substrate interactions and biochip fabrication. However, the intrinsic PDMS surface hydrophobicity inhibits cell adhesion on the PDMS surface, and PDMS surface modification is required for effective cell adhesion. Meanwhile, the formulation of PDMS also affects the behaviors of the cells. To fabricate PDMS-based biochips for ESC pluripotency maintenance and cardiac differentiation, PDMS surface modification and formulation were optimized in this study. We found that a polydopamine (PD) with gelatin coating greatly improved the ESC adhesion, proliferation and cardiac differentiation on its surface. In addition, different PDMS substrates varied in their surface properties, which had different impacts on ESCs, with the 40 : 1 PDMS substrate being more favorable for ESC adhesion and proliferation as well as embryoid body (EB) attachment than the other PDMS substrates. Moreover, the ESC pluripotency was best maintained on the 5 : 1 PDMS substrate, while the cardiac differentiation of the ESCs was optimal on the 40 : 1 PDMS substrate. Based on the optimized coating method and PDMS formulation, biochips with two different designs were fabricated and evaluated. Compared to the single channels, the multiple channels on the biochips could provide larger areas and accommodate more nutrients to support improved ESC pluripotency maintenance and cardiac differentiation. These results may contribute to the development of a real heart-on-a-chip for high-throughput drug screening in the future.

Fundamentals of Enzyme-Based Sensors

NASA Astrophysics Data System (ADS)

Moreno-Bondi, María C.; Benito-Peña, Elena

One of the mayor outbreaks in the development of analytical measurement techniques was the introduction, in the mid-twentieth century, of bioprobes for the analysis of chemical and biochemical compounds in real samples. The first devices, developed in the 1950's and 1960's by Clark et al. were based on electrochemical measurements and allowed the determination of oxygen and glucose in tissues and blood samples. Later on, in the 1970's, optical transduction was coupled to enzymatically-catalyzed reactions3 and since those early days the field of application of optical biosensors has broaden up considerably. According to the definition proposed by the International Union of Pure and Applied Chemistry (IUPAC): "A biosensor is a self-contained integrated device which is capable of providing specific quantitative or semi-quantitative analytical information using a biological recognition element (biochemical receptor) which is in direct spatial contact with a transducer element. A biosensor should be clearly distinguished from a bioanalytical system, which requires additional processing steps, such as reagent addition. Furthermore, a biosensor should be distinguished from a bioprobe which is either disposable after one measurement, i.e. single use, or unable to continuously monitor the analyte concentration". The general scheme of a biosensor configuration is shown in Figure 1. Biosensors that include transducers based on integrated circuit microchips are known as biochips.

Photosensitive biosensor array system using optical addressing without an addressing circuit on array biochips

NASA Astrophysics Data System (ADS)

Ahn, Chang-Geun; Ah, Chil Seong; Kim, Tae-Youb; Park, Chan Woo; Yang, Jong-Heon; Kim, Ansoon; Sung, Gun Yong

2010-09-01

This paper introduces a photosensitive biosensor array system with a simple photodiode array that detects photocurrent changes caused by reactions between probe and target molecules. Using optical addressing, the addressing circuit on the array chip is removed for low-cost application, and real cell addressing is achieved using an externally located computer-controllable light-emitting diode array module. The fabricated biosensor array chip shows a good dynamic range of 1-100 ng/mL under prostate-specific antigen detection, with an on-chip resolution of roughly 1 ng/mL.

Real time observation and automated measurement of red blood cells agglutination inside a passive microfluidic biochip containing embedded reagents.

PubMed

Huet, Maxime; Cubizolles, Myriam; Buhot, Arnaud

2017-07-15

The process of agglutination is commonly used for the detection of biomarkers like proteins or viruses. The multiple bindings between micrometer sized particles, either latex beads or red blood cells (RBCs), create aggregates that are easily detectable and give qualitative information about the presence of the biomarkers. In most cases, the detection is made by simple naked-eye observation of agglutinates without any access to the kinetics of agglutination. In this study, we address the development of a real-time time observation of RBCs agglutination. Using ABO blood typing as a proof-of-concept, we developed i) an integrated biological protocol suitable for further use as point-of-care (POC) analysis and ii) two dedicated image processing algorithms for the real-time and quantitative measurement of agglutination. Anti-A or anti-B typing reagents were dried inside the microchannel of a passive microfluidic chip designed to enhance capillary flow. A blood drop deposit at the tip of the biochip established a simple biological protocol. In situ agglutination of autologous RBCs was achieved by means of embedded reagents and real time agglutination process was monitored by video recording. Using a training set of 24 experiments, two real-time indicators based on correlation and variance of gray levels were optimized and then further confirmed on a validation set. 100% correct discrimination between positive and negative agglutinations was performed within less than 2min by measuring real-time evolution of both correlation and variance indicators. Copyright © 2016 Elsevier B.V. All rights reserved.

The design of a microfluidic biochip for the rapid, multiplexed detection of foodborne pathogens by surface plasmon resonance imaging

NASA Astrophysics Data System (ADS)

Zordan, Michael D.; Grafton, Meggie M. G.; Park, Kinam; Leary, James F.

2010-02-01

The rapid detection of foodborne pathogens is increasingly important due to the rising occurrence of contaminated food supplies. We have previously demonstrated the design of a hybrid optical device that has the capability to perform realtime surface plasmon resonance (SPR) and epi-fluorescence imaging. We now present the design of a microfluidic biochip consisting of a two-dimensional array of functionalized gold spots. The spots on the array have been functionalized with capture peptides that specifically bind E. coli O157:H7 or Salmonella enterica. This array is enclosed by a PDMS microfluidic flow cell. A magnetically pre-concentrated sample is injected into the biochip, and whole pathogens will bind to the capture array. The previously constructed optical device is being used to detect the presence and identity of captured pathogens using SPR imaging. This detection occurs in a label-free manner, and does not require the culture of bacterial samples. Molecular imaging can also be performed using the epi-fluorescence capabilities of the device to determine pathogen state, or to validate the identity of the captured pathogens using fluorescently labeled antibodies. We demonstrate the real-time screening of a sample for the presence of E. coli O157:H7 and Salmonella enterica. Additionally the mechanical properties of the microfluidic flow cell will be assessed. The effect of these properties on pathogen capture will be examined.

Evaluation and validation of a multi-residue method based on biochip technology for the simultaneous screening of six families of antibiotics in muscle and aquaculture products.

PubMed

Gaudin, Valérie; Hedou, Celine; Soumet, Christophe; Verdon, Eric

2016-01-01

The Evidence Investigator™ system (Randox, UK) is a biochip and semi-automated system. The microarray kit II (AM II) is capable of detecting several compounds belonging to different families of antibiotics: quinolones, ceftiofur, thiamphenicol, streptomycin, tylosin and tetracyclines. The performance of this innovative system was evaluated for the detection of antibiotic residues in new matrices, in muscle of different animal species and in aquaculture products. The method was validated according to the European Decision No. EC/2002/657 and the European guideline for the validation of screening methods, which represents a complete initial validation. The false-positive rate was equal to 0% in muscle and in aquaculture products. The detection capabilities CCβ for 12 validated antibiotics (enrofloxacin, difloxacin, ceftiofur, desfuroyl ceftiofur cysteine disulfide, thiamphenicol, florfenicol, tylosin, tilmicosin, streptomycin, dihydrostreptomycin, tetracycline, doxycycline) were all lower than the respective maximum residue limits (MRLs) in muscle from different animal origins (bovine, ovine, porcine, poultry). No cross-reactions were observed with other antibiotics, neither with the six detected families nor with other families of antibiotics. The AM II kit could be applied to aquaculture products but with higher detection capabilities from those in muscle. The detection capabilities CCβ in aquaculture products were respectively at 0.25, 0.10 and 0.5 of the respective MRL in aquaculture products for enrofloxacin, tylosin and oxytetracycline. The performance of the AM II kit has been compared with other screening methods and with the performance characteristics previously determined in honey.

Making the invisible visible: a microfluidic chip using a low refractive index polymer.

PubMed

Hanada, Yasutaka; Ogawa, Tatsuya; Koike, Kazuhiko; Sugioka, Koji

2016-07-07

Microfluidic frameworks known as micro-total-analysis-systems or lab-on-a-chip have become versatile tools in cell biology research, since functional biochips are able to streamline dynamic observations of various cells. Glass or polymers are generally used as the substrate due to their high transparency, chemical stability and cost-effectiveness. However, these materials are not well suited for the microscopic observation of cell migration at the fluid boundary due to the refractive index mismatch between the medium and the biochip material. For this reason, we have developed a new method of fabricating three-dimensional (3D) microfluidic chips made of the low refractive index fluoric polymer CYTOP. This novel fabrication procedure involves the use of a femtosecond laser for direct writing, followed by wet etching with a dilute fluorinated solvent and annealing, to create high-quality 3D microfluidic chips inside a polymer substrate. A microfluidic chip made in this manner enabled us to more clearly observe the flagellum motion of a Dinoflagellate moving in circles near the fluid surface compared to the observations possible using conventional microfluidic chips. We believe that CYTOP microfluidic chips made using this new method may allow more detailed analysis of various cell migrations near solid boundaries.

An ion-gated bipolar amplifier for ion sensing with enhanced signal and improved noise performance

NASA Astrophysics Data System (ADS)

Zhang, Da; Gao, Xindong; Chen, Si; Norström, Hans; Smith, Ulf; Solomon, Paul; Zhang, Shi-Li; Zhang, Zhen

2014-08-01

This work presents a proof-of-concept ion-sensitive device operating in electrolytes. The device, i.e., an ion-gated bipolar amplifier (IGBA), consists of a modified ion-sensitive field-effect transistor (ISFET) intimately integrated with a vertical bipolar junction transistor for immediate current amplification without introducing additional noise. With the current non-optimized design, the IGBA is already characterized by a 70-fold internal amplification of the ISFET output signal. This signal amplification is retained when the IGBA is used for monitoring pH variations. The tight integration significantly suppresses the interference of the IGBA signal by external noise, which leads to an improvement in signal-to-noise performance compared to its ISFET reference. The IGBA concept is especially suitable for biochips with millions of electric sensors that are connected to peripheral readout circuitry via extensive metallization which may in turn invite external interferences leading to contamination of the signal before it reaches the first external amplification stage.

Nano-Engineered Biomimetic Optical Sensors for Glucose Monitoring in Diabetes.

PubMed

Rauf, Sajid; Hayat Nawaz, Muhammad Azhar; Badea, Mihaela; Marty, Jean Louis; Hayat, Akhtar

2016-11-17

Diabetes is a rapidly growing disease that can be monitored at an individual level by controlling the blood glucose level, hence minimizing the negative impact of the disease. Significant research efforts have been focused on the design of novel and improved technologies to overcome the limitations of existing glucose analysis methods. In this context, nanotechnology has enabled the diagnosis at the single cell and molecular level with the possibility of incorporation in advanced molecular diagnostic biochips. Recent years have witnessed the exploration and synthesis of various types of nanomaterials with enzyme-like properties, with their subsequent integration into the design of biomimetic optical sensors for glucose monitoring. This review paper will provide insights on the type, nature and synthesis of different biomimetic nanomaterials. Moreover, recent developments in the integration of these nanomaterials for optical glucose biosensing will be highlighted, with a final discussion on the challenges that must be addressed for successful implementation of these nano-devices in the clinical applications is presented.

Nano-Engineered Biomimetic Optical Sensors for Glucose Monitoring in Diabetes

PubMed Central

Rauf, Sajid; Hayat Nawaz, Muhammad Azhar; Badea, Mihaela; Marty, Jean Louis; Hayat, Akhtar

2016-01-01

Diabetes is a rapidly growing disease that can be monitored at an individual level by controlling the blood glucose level, hence minimizing the negative impact of the disease. Significant research efforts have been focused on the design of novel and improved technologies to overcome the limitations of existing glucose analysis methods. In this context, nanotechnology has enabled the diagnosis at the single cell and molecular level with the possibility of incorporation in advanced molecular diagnostic biochips. Recent years have witnessed the exploration and synthesis of various types of nanomaterials with enzyme-like properties, with their subsequent integration into the design of biomimetic optical sensors for glucose monitoring. This review paper will provide insights on the type, nature and synthesis of different biomimetic nanomaterials. Moreover, recent developments in the integration of these nanomaterials for optical glucose biosensing will be highlighted, with a final discussion on the challenges that must be addressed for successful implementation of these nano-devices in the clinical applications is presented. PMID:27869658

Magnetically-focusing biochip structures for high-speed active biosensing with improved selectivity.

PubMed

Yoo, Haneul; Lee, Dong Jun; Kim, Daesan; Park, Juhun; Chen, Xing; Hong, Seunghun

2018-06-29

We report a magnetically-focusing biochip structure enabling a single layered magnetic trap-and-release cycle for biosensors with an improved detection speed and selectivity. Here, magnetic beads functionalized with specific receptor molecules were utilized to trap target molecules in a solution and transport actively to and away from the sensor surfaces to enhance the detection speed and reduce the non-specific bindings, respectively. Using our method, we demonstrated the high speed detection of IL-13 antigens with the improved detection speed by more than an order of magnitude. Furthermore, the release step in our method was found to reduce the non-specific bindings and improve the selectivity and sensitivity of biosensors. This method is a simple but powerful strategy and should open up various applications such as ultra-fast biosensors for point-of-care services.

Magnetically-focusing biochip structures for high-speed active biosensing with improved selectivity

NASA Astrophysics Data System (ADS)

Yoo, Haneul; Lee, Dong Jun; Kim, Daesan; Park, Juhun; Chen, Xing; Hong, Seunghun

2018-06-01

We report a magnetically-focusing biochip structure enabling a single layered magnetic trap-and-release cycle for biosensors with an improved detection speed and selectivity. Here, magnetic beads functionalized with specific receptor molecules were utilized to trap target molecules in a solution and transport actively to and away from the sensor surfaces to enhance the detection speed and reduce the non-specific bindings, respectively. Using our method, we demonstrated the high speed detection of IL-13 antigens with the improved detection speed by more than an order of magnitude. Furthermore, the release step in our method was found to reduce the non-specific bindings and improve the selectivity and sensitivity of biosensors. This method is a simple but powerful strategy and should open up various applications such as ultra-fast biosensors for point-of-care services.

Detection of BCG bacteria using a magnetoresistive biosensor: A step towards a fully electronic platform for tuberculosis point-of-care detection.

PubMed

Barroso, Teresa G; Martins, Rui C; Fernandes, Elisabete; Cardoso, Susana; Rivas, José; Freitas, Paulo P

2018-02-15

Tuberculosis is one of the major public health concerns. This highly contagious disease affects more than 10.4 million people, being a leading cause of morbidity by infection. Tuberculosis is diagnosed at the point-of-care by the Ziehl-Neelsen sputum smear microscopy test. Ziehl-Neelsen is laborious, prone to human error and infection risk, with a limit of detection of 10 4 cells/mL. In resource-poor nations, a more practical test, with lower detection limit, is paramount. This work uses a magnetoresistive biosensor to detect BCG bacteria for tuberculosis diagnosis. Herein we report: i) nanoparticle assembly method and specificity for tuberculosis detection; ii) demonstration of proportionality between BCG cell concentration and magnetoresistive voltage signal; iii) application of multiplicative signal correction for systematic effects removal; iv) investigation of calibration effectiveness using chemometrics methods; and v) comparison with state-of-the-art point-of-care tuberculosis biosensors. Results present a clear correspondence between voltage signal and cell concentration. Multiplicative signal correction removes baseline shifts within and between biochip sensors, allowing accurate and precise voltage signal between different biochips. The corrected signal was used for multivariate regression models, which significantly decreased the calibration standard error from 0.50 to 0.03log 10 (cells/mL). Results show that Ziehl-Neelsen detection limits and below are achievable with the magnetoresistive biochip, when pre-processing and chemometrics are used. Copyright © 2017 Elsevier B.V. All rights reserved.

Engineering of a novel Ca{sup 2+}-regulated kinesin molecular motor using a calmodulin dimer linker

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shishido, Hideki; Maruta, Shinsaku, E-mail: maruta@soka.ac.jp

Highlights: Black-Right-Pointing-Pointer Engineered kinesin-M13 and calmodulin involving single cysteine were prepared. Black-Right-Pointing-Pointer CaM mutant was cross-linked to dimer by bifunctional thiol reactive reagent. Black-Right-Pointing-Pointer Kinesin-M13 was dimerized via CaM dimer in the presence of calcium. Black-Right-Pointing-Pointer Function of the engineered kinesin was regulated by a Ca{sup 2+}-calmodulin dimer linker. -- Abstract: The kinesin-microtubule system holds great promise as a molecular shuttle device within biochips. However, one current barrier is that such shuttles do not have 'on-off' control of their movement. Here we report the development of a novel molecular motor powered by an accelerator and brake system, using a kinesinmore » monomer and a calmodulin (CaM) dimer. The kinesin monomer, K355, was fused with a CaM target peptide (M13 peptide) at the C-terminal part of the neck region (K355-M13). We also prepared CaM dimers using CaM mutants (Q3C), (R86C), or (A147C) and crosslinkers that react with cysteine residues. Following induction of K355-M13 dimerization with CaM dimers, we measured K355-M13 motility and found that it can be reversibly regulated in a Ca{sup 2+}-dependent manner. We also found that velocities of K355-M13 varied depending on the type and crosslink position of the CaM dimer used; crosslink length also had a moderate effect on motility. These results suggest Ca{sup 2+}-dependent dimerization of K355-M13 could be used as a novel molecular shuttle, equipped with an accelerator and brake system, for biochip applications.« less

Internal validation of the DNAscan/ANDE™ Rapid DNA Analysis™ platform and its associated PowerPlex® 16 high content DNA biochip cassette for use as an expert system with reference buccal swabs.

PubMed

Moreno, Lilliana I; Brown, Alice L; Callaghan, Thomas F

2017-07-01

Rapid DNA platforms are fully integrated systems capable of producing and analyzing short tandem repeat (STR) profiles from reference sample buccal swabs in less than two hours. The technology requires minimal user interaction and experience making it possible for high quality profiles to be generated outside an accredited laboratory. The automated production of point of collection reference STR profiles could eliminate the time delay for shipment and analysis of arrestee samples at centralized laboratories. Furthermore, point of collection analysis would allow searching against profiles from unsolved crimes during the normal booking process once the infrastructure to immediately search the Combined DNA Index System (CODIS) database from the booking station is established. The DNAscan/ANDE™ Rapid DNA Analysis™ System developed by Network Biosystems was evaluated for robustness and reliability in the production of high quality reference STR profiles for database enrollment and searching applications. A total of 193 reference samples were assessed for concordance of the CODIS 13 loci. Studies to evaluate contamination, reproducibility, precision, stutter, peak height ratio, noise and sensitivity were also performed. The system proved to be robust, consistent and dependable. Results indicated an overall success rate of 75% for the 13 CODIS core loci and more importantly no incorrect calls were identified. The DNAscan/ANDE™ could be confidently used without human interaction in both laboratory and non-laboratory settings to generate reference profiles. Published by Elsevier B.V.

Measurement of cell respiration and oxygenation in standard multichannel biochips using phosphorescent O2-sensitive probes.

PubMed

Kondrashina, Alina V; Papkovsky, Dmitri B; Dmitriev, Ruslan I

2013-09-07

Measurement of cell oxygenation and oxygen consumption is useful for studies of cell bioenergetics, metabolism, mitochondrial function, drug toxicity and common pathophysiological conditions. Here we present a new platform for such applications which uses commercial multichannel biochips (μ-slides, Ibidi) and phosphorescent O2 sensitive probes. This platform was evaluated with both extracellular and intracellular O2 probes, several different cell types and treatments including mitochondrial uncoupling and inhibition, depletion of extracellular Ca(2+) and inhibition of V-ATPase and histone deacetylases. The results show that compared to the standard microwell plates currently used, the μ-slide platform provides facile O2 measurements with both suspension and adherent cells, higher sensitivity and reproducibility, and faster measurement time. It also allows re-perfusion and multiple treatments of cells and multi-parametric analyses in conjunction with other probes. Optical measurements are conducted on standard fluorescence readers and microscopes.

Biochip Which Examines Hepatic Function by Employing Colorimetric Method

NASA Astrophysics Data System (ADS)

Oki, Akio; Ogawa, Hiroki; Takamura, Yuzuru; Horiike, Yasuhiro

2003-03-01

A biochip that is able to quickly analyze hepatic function from the bedside or at home was investigated. The chip essentially consisted of two chips, one that mixed the substrate buffer solution with serums using a centrifugal method and a chip that measured the amounts of γ-glutamyltranspeptidase (γ-GTP), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) in the serums employing a colorimetric method. The chip should be inexpensive and disposable. Therefore the mixing and measurement channels were fabricated by molding their reverse patterns onto a poly (ethylene terephthalate) (PET) plate. Furthermore, a hydrophobic treatment was performed on the inner wall of the measurement channel to efficiently propagate the light efficiently in the channel. Subsequently, calibration curves were obtained for γ-GTP, GOT and GPT activity levels based on an endpoint method for the γ-GTP and a rate assay for GOT and GPT.

Responsive etalon based on PNIPAM@SiO2 composite spacer with rapid response rate and excellent repeatability for sensing application

NASA Astrophysics Data System (ADS)

Wang, Tieqiang; Wang, Shuli; Zhang, Xun; Song, Guoshuai; Yu, Ye; Chen, Xinyang; Fu, Yu; Zhang, Junhu; Yang, Bai

2015-07-01

In this paper, we demonstrate a responsive etalon fabricated through combining colloidal lithography and surface-initiated atom-transfer radical polymerization (SI-ATRP). The responsive etalon is simply constructed with one responsive spacer sandwiched by two reflective layers, and the middle responsive spacer is constructed by grafting thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) brushes on a SiO2 nanosphere array. The etalon possesses one single interference peak in the visible region, and the interference peak changes sensitively against the concentration of the external stimulant (water vapor) or the temperature of the system, owing to the responsiveness of the PNIPAM brush. Importantly, the as-prepared etalon shows a rapid response rate and excellent stability, and it is also handy to realize the miniaturization and integration of the responsive etalon based on a conventional micro-fabrication method. These features all make the as-prepared responsive etalon an attractive candidate for future sensing applications. We believe such responsive etalons are promising for the fabrication of smart photonic materials and optical sensors that may be useful in tissue engineering, medical diagnosis, public security, and biochip areas.

Peptide Integrated Optics.

PubMed

Handelman, Amir; Lapshina, Nadezda; Apter, Boris; Rosenman, Gil

2018-02-01

Bio-nanophotonics is a wide field in which advanced optical materials, biomedicine, fundamental optics, and nanotechnology are combined and result in the development of biomedical optical chips. Silk fibers or synthetic bioabsorbable polymers are the main light-guiding components. In this work, an advanced concept of integrated bio-optics is proposed, which is based on bioinspired peptide optical materials exhibiting wide optical transparency, nonlinear and electrooptical properties, and effective passive and active waveguiding. Developed new technology combining bottom-up controlled deposition of peptide planar wafers of a large area and top-down focus ion beam lithography provides direct fabrication of peptide optical integrated circuits. Finding a deep modification of peptide optical properties by reconformation of biological secondary structure from native phase to β-sheet architecture is followed by the appearance of visible fluorescence and unexpected transition from a native passive optical waveguiding to an active one. Original biocompatibility, switchable regimes of waveguiding, and multifunctional nonlinear optical properties make these new peptide planar optical materials attractive for application in emerging technology of lab-on-biochips, combining biomedical photonic and electronic circuits toward medical diagnosis, light-activated therapy, and health monitoring. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DNA extraction on bio-chip: history and preeminence over conventional and solid-phase extraction methods.

PubMed

Ayoib, Adilah; Hashim, Uda; Gopinath, Subash C B; Md Arshad, M K

2017-11-01

This review covers a developmental progression on early to modern taxonomy at cellular level following the advent of electron microscopy and the advancement in deoxyribonucleic acid (DNA) extraction for expatiation of biological classification at DNA level. Here, we discuss the fundamental values of conventional chemical methods of DNA extraction using liquid/liquid extraction (LLE) followed by development of solid-phase extraction (SPE) methods, as well as recent advances in microfluidics device-based system for DNA extraction on-chip. We also discuss the importance of DNA extraction as well as the advantages over conventional chemical methods, and how Lab-on-a-Chip (LOC) system plays a crucial role for the future achievements.

Parallel confocal detection of single biomolecules using diffractive optics and integrated detector units.

PubMed

Blom, H; Gösch, M

2004-04-01

The past few years we have witnessed a tremendous surge of interest in so-called array-based miniaturised analytical systems due to their value as extremely powerful tools for high-throughput sequence analysis, drug discovery and development, and diagnostic tests in medicine (see articles in Issue 1). Terminologies that have been used to describe these array-based bioscience systems include (but are not limited to): DNA-chip, microarrays, microchip, biochip, DNA-microarrays and genome chip. Potential technological benefits of introducing these miniaturised analytical systems include improved accuracy, multiplexing, lower sample and reagent consumption, disposability, and decreased analysis times, just to mention a few examples. Among the many alternative principles of detection-analysis (e.g.chemiluminescence, electroluminescence and conductivity), fluorescence-based techniques are widely used, examples being fluorescence resonance energy transfer, fluorescence quenching, fluorescence polarisation, time-resolved fluorescence, and fluorescence fluctuation spectroscopy (see articles in Issue 11). Time-dependent fluctuations of fluorescent biomolecules with different molecular properties, like molecular weight, translational and rotational diffusion time, colour and lifetime, potentially provide all the kinetic and thermodynamic information required in analysing complex interactions. In this mini-review article, we present recent extensions aimed to implement parallel laser excitation and parallel fluorescence detection that can lead to even further increase in throughput in miniaturised array-based analytical systems. We also report on developments and characterisations of multiplexing extension that allow multifocal laser excitation together with matched parallel fluorescence detection for parallel confocal dynamical fluorescence fluctuation studies at the single biomolecule level.

DNA Photolithography with Cinnamate Crosslinkers

NASA Technical Reports Server (NTRS)

Feng, Lang (Inventor); Chaikin, Paul Michael (Inventor)

2016-01-01

The present invention relates generally to cinnamate crosslinkers. Specifically, the present invention relates to gels, biochips, and functionalized surfaces useful as probes, in assays, in gels, and for drug delivery, and methods of making the same using a newly-discovered crosslinking configuration.

[Advances of Molecular Diagnostic Techniques Application in Clinical Diagnosis.

PubMed

Ying, Bin-Wu

2016-11-01

Over the past 20 years,clinical molecular diagnostic technology has made rapid development,and became the most promising field in clinical laboratory medicine.In particular,with the development of genomics,clinical molecular diagnostic methods will reveal the nature of clinical diseases in a deeper level,thus guiding the clinical diagnosis and treatments.Many molecular diagnostic projects have been routinely applied in clinical works.This paper reviews the advances on application of clinical diagnostic techniques in infectious disease,tumor and genetic disorders,including nucleic acid amplification,biochip,next-generation sequencing,and automation molecular system,and so on.

Integrated microfluidic flowmeter based on a micro-FBG inscribed in Co²⁺-doped optical fiber.

PubMed

Liu, Zhengyong; Tse, Ming-Leung Vincent; Zhang, A Ping; Tam, Hwa-Yaw

2014-10-15

A novel microfluidic flowmeter integrated with microfiber Bragg grating (µFBG) is presented. Two glass capillaries and a short length of high-light-absorption Co²⁺-doped optical fiber were stacked inside a larger outer capillary tube. The stack was then drawn into a tapered device. Two microchannels with the diameter of ~50  μm were formed inside the capillaries for flowing of microfluidics. An FBG was inscribed in the tapered Co²⁺-doped fiber with waist diameter of ~70  μm, and acts as a flow-rate sensor. A pump laser with wavelength of 1480 nm was utilized to locally heat the µFBG, rendering the µFBG as miniature "hot-wire" flowmeter. The flow rate of the liquid in the microchannels is determined by the induced wavelength shift of the µFBG. The experimental results achieve a minimum detectable change of ~16  nL/s in flow rate, which is very promising in the use as part of biochips.

High-resolution liquid patterns via three-dimensional droplet shape control.

PubMed

Raj, Rishi; Adera, Solomon; Enright, Ryan; Wang, Evelyn N

2014-09-25

Understanding liquid dynamics on surfaces can provide insight into nature's design and enable fine manipulation capability in biological, manufacturing, microfluidic and thermal management applications. Of particular interest is the ability to control the shape of the droplet contact area on the surface, which is typically circular on a smooth homogeneous surface. Here, we show the ability to tailor various droplet contact area shapes ranging from squares, rectangles, hexagons, octagons, to dodecagons via the design of the structure or chemical heterogeneity on the surface. We simultaneously obtain the necessary physical insights to develop a universal model for the three-dimensional droplet shape by characterizing the droplet side and top profiles. Furthermore, arrays of droplets with controlled shapes and high spatial resolution can be achieved using this approach. This liquid-based patterning strategy promises low-cost fabrication of integrated circuits, conductive patterns and bio-microarrays for high-density information storage and miniaturized biochips and biosensors, among others.

Growing Embossed Nanostructures of Polymer Brushes on Wet-Etched Silicon Templated via Block Copolymers

PubMed Central

Lu, Xiaobin; Yan, Qin; Ma, Yinzhou; Guo, Xin; Xiao, Shou-Jun

2016-01-01

Block copolymer nanolithography has attracted enormous interest in chip technologies, such as integrated silicon chips and biochips, due to its large-scale and mass production of uniform patterns. We further modified this technology to grow embossed nanodots, nanorods, and nanofingerprints of polymer brushes on silicon from their corresponding wet-etched nanostructures covered with pendent SiHx (X = 1–3) species. Atomic force microscopy (AFM) was used to image the topomorphologies, and multiple transmission-reflection infrared spectroscopy (MTR-IR) was used to monitor the surface molecular films in each step for the sequential stepwise reactions. In addition, two layers of polymethacrylic acid (PMAA) brush nanodots were observed, which were attributed to the circumferential convergence growth and the diffusion-limited growth of the polymer brushes. The pH response of PMAA nanodots in the same region was investigated by AFM from pH 3.0 to 9.0. PMID:26841692

Growing Embossed Nanostructures of Polymer Brushes on Wet-Etched Silicon Templated via Block Copolymers

NASA Astrophysics Data System (ADS)

Lu, Xiaobin; Yan, Qin; Ma, Yinzhou; Guo, Xin; Xiao, Shou-Jun

2016-02-01

Block copolymer nanolithography has attracted enormous interest in chip technologies, such as integrated silicon chips and biochips, due to its large-scale and mass production of uniform patterns. We further modified this technology to grow embossed nanodots, nanorods, and nanofingerprints of polymer brushes on silicon from their corresponding wet-etched nanostructures covered with pendent SiHx (X = 1-3) species. Atomic force microscopy (AFM) was used to image the topomorphologies, and multiple transmission-reflection infrared spectroscopy (MTR-IR) was used to monitor the surface molecular films in each step for the sequential stepwise reactions. In addition, two layers of polymethacrylic acid (PMAA) brush nanodots were observed, which were attributed to the circumferential convergence growth and the diffusion-limited growth of the polymer brushes. The pH response of PMAA nanodots in the same region was investigated by AFM from pH 3.0 to 9.0.

Optically defined modal sensors incorporating spiropyran-doped liquid crystals with piezoelectric sensors.

PubMed

Chen, Kuan-Ting; Chang, Chin-Kai; Kuo, Hui-Lung; Lee, Chih-Kung

2011-01-01

We integrated a piezoelectric sensing layer lamina containing liquid crystals (LC) and spiropyran (SP) in a LC/SP mixture to create an optically reconfigurable modal sensor for a cantilever beam. The impedance of this LC/SP lamina was decreased by UV irradiation which constituted the underlying mechanism to modulate the voltage externally applied to the piezoelectric actuating layer. Illuminating a specific pattern onto the LC/SP lamina provided us with a way to spatially modulate the piezoelectric vibration signal. We showed that if an UV illuminated pattern matches the strain distribution of a specific mode, a piezoelectric modal sensor can be created. Since UV illumination can be changed in situ in real-time, our results confirm for the first time since the inception of smart sensors, that an optically tailored modal sensor can be created. Some potential applications of this type of sensor include energy harvesting devices, bio-chips, vibration sensing and actuating devices.

Role of Proteomics in the Development of Personalized Medicine.

PubMed

Jain, Kewal K

2016-01-01

Advances in proteomic technologies have made import contribution to the development of personalized medicine by facilitating detection of protein biomarkers, proteomics-based molecular diagnostics, as well as protein biochips and pharmacoproteomics. Application of nanobiotechnology in proteomics, nanoproteomics, has further enhanced applications in personalized medicine. Proteomics-based molecular diagnostics will have an important role in the diagnosis of certain conditions and understanding the pathomechanism of disease. Proteomics will be a good bridge between diagnostics and therapeutics; the integration of these will be important for advancing personalized medicine. Use of proteomic biomarkers and combination of pharmacoproteomics with pharmacogenomics will enable stratification of clinical trials and improve monitoring of patients for development of personalized therapies. Proteomics is an important component of several interacting technologies used for development of personalized medicine, which is depicted graphically. Finally, cancer is a good example of applications of proteomic technologies for personalized management of cancer. © 2016 Elsevier Inc. All rights reserved.

Microfluidic differential immunocapture biochip for specific leukocyte counting

PubMed Central

Hassan, Umer; Watkins, Nicholas N; Reddy, Bobby; Damhorst, Gregory; Bashir, Rashid

2016-01-01

Enumerating specific cell types from whole blood can be very useful for research and diagnostic purposes—e.g., for counting of cD4 and cD8 t cells in HIV/aIDs diagnostics. We have developed a biosensor based on a differential immunocapture technology to enumerate specific cells in 30 min using 10 µl of blood. this paper provides a comprehensive stepwise protocol to replicate our biosensor for cD4 and cD8 cell counts. the biochip can also be adapted to enumerate other specific cell types such as somatic cells or cells from tissue or liquid biopsies. capture of other specific cells requires immobilization of their corresponding antibodies within the capture chamber. therefore, this protocol is useful for research into areas surrounding immunocapture-based biosensor development. the biosensor production requires 24 h, a one-time cell capture optimization takes 6–9 h, and the final cell counting experiment in a laboratory environment requires 30 min to complete. PMID:26963632

Robust Bioinformatics Recognition with VLSI Biochip Microsystem

NASA Technical Reports Server (NTRS)

Lue, Jaw-Chyng L.; Fang, Wai-Chi

2006-01-01

A microsystem architecture for real-time, on-site, robust bioinformatic patterns recognition and analysis has been proposed. This system is compatible with on-chip DNA analysis means such as polymerase chain reaction (PCR)amplification. A corresponding novel artificial neural network (ANN) learning algorithm using new sigmoid-logarithmic transfer function based on error backpropagation (EBP) algorithm is invented. Our results show the trained new ANN can recognize low fluorescence patterns better than the conventional sigmoidal ANN does. A differential logarithmic imaging chip is designed for calculating logarithm of relative intensities of fluorescence signals. The single-rail logarithmic circuit and a prototype ANN chip are designed, fabricated and characterized.

Electrical chips for biological point-of-care detection

USDA-ARS?s Scientific Manuscript database

As the future of health care diagnostics moves toward more portable and personalized techniques, there is immense potential to harness the power of electrical signals for biological sensing and diagnostic applications at the point of care. Electrical biochips can be used to both manipulate and sense...

Frontiers of More than Moore in Bioelectronics and the Required Metrology Needs

NASA Astrophysics Data System (ADS)

Guiseppi-Elie, Anthony; Kotanen, Christian; Wilson, A. Nolan

2011-11-01

Silicon's intersection with biology is a premise inherent in Moore's prediction. Distinct from biologically inspired molecular logic and storage devices (more Moore) are the integration of solid state electronic devices with the soft condensed state of the body (more than Moore). Developments in biomolecular recognition events per sq. cm parallel those of Moore's Law. However, challenges continue in the area of "More than Moore". Two grand challenge problems must be addressed—the biocompatibility of synthetic materials with the myriad of tissue types within the human body and the interfacing of solid state micro- and nano-electronic devices with the electronics of biological systems. Electroconductive hydrogels have been developed as soft, condensed, biomimetic but otherwise inherently electronically conductive materials to address the challenge of interfacing solid state devices with the electronics of the body, which is predominantly ionic. Nano-templated interfaces via the oriented immobilization of single walled carbon nanotubes (SWCNTs) onto metallic electrodes have engendered reagentless, direct electron transfer between biological redox enzymes and solid state electrodes. In addressing these challenges, metrology needs and opportunities are found in such widely diverse areas as single molecule counting and addressing, sustainable power requirements such as the development of implantable biofuel cells for the deployment of implantable biochips, and new manufacturing paradigms to address plura-biology needs on solid state devices.

Irradiation effects on antibody performance in the frame of biochip-based instruments development for space exploration

NASA Astrophysics Data System (ADS)

Baqué, M.; Dobrijevic, M.; Le Postollec, A.; Moreau, T.; Faye, C.; Vigier, F.; Incerti, S.; Coussot, G.; Caron, J.; Vandenabeele-Trambouze, O.

2017-01-01

Several instruments based on immunoassay techniques have been proposed for life-detection experiments in the framework of planetary exploration but few experiments have been conducted so far to test the resistance of antibodies against cosmic ray particles. We present several irradiation experiments carried out on both grafted and free antibodies for different types of incident particles (protons, neutrons, electrons and 12C) at different energies (between 9 MeV and 50 MeV) and different fluences. No loss of antibodies activity was detected for the whole set of experiments except when considering protons with energy between 20 and 30 MeV (on free and grafted antibodies) and fluences much greater than expected for a typical planetary mission to Mars for instance. Our results on grafted antibodies suggest that biochip-based instruments must be carefully designed according to the expected radiation environment for a given mission. In particular, a surface density of antibodies much larger than the expected proton fluence would prevent significant loss of antibodies activity and thus assuring a successful detection.

System-Level Biochip for Impedance Sensing and Programmable Manipulation of Bladder Cancer Cells

PubMed Central

Chuang, Cheng-Hsin; Huang, Yao-Wei; Wu, Yao-Tung

2011-01-01

This paper develops a dielectrophoretic (DEP) chip with multi-layer electrodes and a micro-cavity array for programmable manipulations of cells and impedance measurement. The DEP chip consists of an ITO top electrode, flow chamber, middle electrode on an SU-8 surface, micro-cavity arrays of SU-8 and distributed electrodes at the bottom of the micro-cavity. Impedance sensing of single cells could be performed as follows: firstly, cells were trapped in a micro-cavity array by negative DEP force provided by top and middle electrodes; then, the impedance measurement for discrimination of different stage of bladder cancer cells was accomplished by the middle and bottom electrodes. After impedance sensing, the individual releasing of trapped cells was achieved by negative DEP force using the top and bottom electrodes in order to collect the identified cells once more. Both cell manipulations and impedance measurement had been integrated within a system controlled by a PC-based LabVIEW program. In the experiments, two different stages of bladder cancer cell lines (grade III: T24 and grade II: TSGH8301) were utilized for the demonstration of programmable manipulation and impedance sensing; as the results show, the lower-grade bladder cancer cells (TSGH8301) possess higher impedance than the higher-grade ones (T24). In general, the multi-step manipulations of cells can be easily programmed by controlling the electrical signal in our design, which provides an excellent platform technology for lab-on-a-chip (LOC) or a micro-total-analysis-system (Micro TAS). PMID:22346685

Development of a website and biobank database for the Nanosized Cancer Polymarker Biochip Project: a Multicenter Italian Experience.

PubMed

Leon, Antonette E; Fabricio, Aline S C; Benvegnù, Fabio; Michilin, Silvia; Secco, Annamaria; Spangaro, Omar; Meo, Sabrina; Gion, Massimo

2011-01-01

The Nanosized Cancer Polymarker Biochip Project (RBLA03S4SP) funded by an Italian MIUR-FIRB grant (Italian Ministry of University and Research - Investment Funds for Basic Research) has led to the creation of a free-access dynamic website, available at the web address https://serviziweb.ulss12.ve.it/firbabo, and of a centralized database with password-restricted access. The project network is composed of 9 research units (RUs) and has been active since 2005. The aim of the FIRB project was the design, production and validation of optoelectronic and chemoelectronic biosensors for the simultaneous detection of a novel class of cancer biomarkers associated with immunoglobulins of the M class (IgM) for early diagnosis of cancer. Biomarker immune complexes (BM-ICs) were assessed on samples of clinical cases and matched controls for breast, colorectal, liver, ovarian and prostate malignancies. This article describes in detail the architecture of the project website, the central database application, and the biobank developed for the FIRB Nanosized Cancer Polymarker Biochip Project. The article also illustrates many unique aspects that should be considered when developing a database within a multidisciplinary scenario. The main deliverables of the project were numerous, including the development of an online database which archived 1400 case report forms (700 cases and 700 matched controls) and more than 2700 experimental results relative to the BM-ICs assayed. The database also allowed for the traceability and retrieval of 21,000 aliquots archived in the centralized bank and stored as backup in the RUs, and for the development of a centralized biological bank in the coordinating unit with 6300 aliquots of serum. The constitution of the website and biobank database enabled optimal coordination of the RUs involved, highlighting the importance of sharing samples and scientific data in a multicenter setting for the achievement of the project goals.

Long-Term Storage and Impedance-Based Water Toxicity Testing Capabilities of Fluidic Biochips Seeded with RTgill-W1 Cells

DTIC Science & Technology

2012-03-24

Cell Line Microplate Cytotoxicity Test. In: Blaise, C., Férard, J.T. (Eds.), Small-scale Freshwater Toxicity Investigations, Vol 1. Springer, The...Eckert, M.L., Lee, L.E.J., Gallagher, E.P., 2008. Comparative oxygen radical formation and toxicity of BDE 47 in rainbow trout cell lines. Marine

Introduction to Special Issue on Games + Learning + Society

ERIC Educational Resources Information Center

Squire, Kurt; Gaydos, Matthew; DeVane, Ben

2016-01-01

Digital games for learning have quickly transitioned from a theoretical possibility, to a hyped technology, to an idea that almost seems quaint compared to advances in Biochips, Smart Robots, and self-driving cars. As a field, it is now better understand what games are good for, what they are not, and in what kinds of situations they can be…

Integrated active mixing and biosensing using low frequency vibrating mixer and Love-wave sensor for real time detection of antibody binding event

NASA Astrophysics Data System (ADS)

Kardous, F.; El Fissi, L.; Friedt, J.-M.; Bastien, F.; Boireau, W.; Yahiaoui, R.; Manceau, J.-F.; Ballandras, S.

2011-05-01

The development of lab-on-chip devices is expected to dramatically change biochemical analyses, allowing for a notable increase of processing quality and throughput, provided the induced chemical reactions are well controlled. In this work, we investigate the impact of local acoustic mixing to promote or accelerate such biochemical reactions, such as antibody grafting on activated surfaces. During microarray building, the spotting mode leads to low efficiency in the ligand grafting and heterogeneities which limits its performances. To improve the transfer rate, we induce a hydrodynamic flow in the spotted droplet to disrupt the steady state during antibody grafting. To prove that acoustic mixing increases the antibody transfer rate to the biochip surface, we have used a Love-wave sensor allowing for real-time monitoring of the biological reaction for different operating conditions (with or without mixing). An analysis of the impact of the proposed mixing on grafting kinetics is proposed and finally checked in the case of antibody-antigen combination.

A novel electrochemical biosensor based on dynamic polymerase-extending hybridization for E. coli O157:H7 DNA detection.

PubMed

Wang, Lijiang; Liu, Qingjun; Hu, Zhaoying; Zhang, Yuanfan; Wu, Chunsheng; Yang, Mo; Wang, Ping

2009-05-15

A novel biosensor based on single-stranded DNA (ssDNA) probe functionalized aluminum anodized oxide (AAO) nanopore membranes was demonstrated for Escherichia coli O157:H7 DNA detection. An original and dynamic polymerase-extending (PE) DNA hybridization procedure is proposed, where hybridization happens in the existence of Taq DNA polymerase and dNTPs under controlled reaction temperature. The probe strand would be extended as long as the target DNA strand, then the capability to block the ionic flow in the pores has been prominently enhanced by the double strand complex. We have investigated the variation of ionic conductivity during the fabrication of the film and the hybridization using cyclic voltammetry and impedance spectroscopy. The present approach provides low detection limit for DNA (a few hundreds of pmol), rapid label-free and easy-to-use bacteria detection, which holds the potential for future use in various ss-DNA analyses by integrated into a self-contained biochip.

Allergen extracts and recombinant proteins: comparison of efficiency of in vitro allergy diagnostics using multiplex assay on a biological microchip.

PubMed

Smoldovskaya, Olga; Feyzkhanova, Guzel; Arefieva, Alla; Voloshin, Sergei; Ivashkina, Olga; Reznikov, Yuriy; Rubina, Alla

2016-01-01

Immunological test systems for diagnostics of type I hypersensitivity involve the following types of antigens: whole allergen extracts, individual highly purified proteins and their recombinant analogues. The goal of this study was to compare the results obtained with whole allergen extracts (birch pollen, cat dander, and timothy grass pollen) and their respective recombinant proteins in biochip-based immunoassay. Multiplex fluorescent immunoassay of 139 patients' blood serum samples was carried out using biological microchips (biochips). sIgE concentrations for the chosen allergens and their recombinant components were measured. ROC analysis was used for comparison of the results and determination of diagnostic accuracy. The results for the birch pollen extract and its recombinant allergens have shown that the diagnostic accuracy of the methods utilizing the whole allergen extract, its major component Bet v 1 and the combination of major and minor components (Bet v 1 and Bet v 2) was the same. Values for diagnostic accuracy for the cat dander extract and its major recombinant component Fel d 1 were equal. In contrast with birch pollen and cat dander allergens, using of recombinant components of timothy grass pollen (Phl p 1, Phl p 5, Phl p 7 and Phl p 12) did not allow reaching the diagnostic accuracy of using natural extract. Multiplex analysis of samples obtained from patients with allergy to birch pollen and cat dander using biological microchips has shown that comparable accuracy was observed for the assay with natural extracts and recombinant allergens. In the case of timothy grass allergen, using the recombinant components may be insufficient.

Electrically biased GaAs/AlGaAs heterostructures for enhanced detection of bacteria

NASA Astrophysics Data System (ADS)

Aziziyan, Mohammad R.; Hassen, Walid M.; Dubowski, Jan J.

2016-03-01

We have examined the influence of electrical bias on immobilization of bacteria on the surface of GaAs/AlGaAs heterostructures, functionalized with an alkanethiol based architecture. A mixture of biotinylated polyethylene glycol (PEG) thiol and hexadecanethiol was applied to attach neutravidin and antibodies targeting specific immobilization of Legionella pneumophila. An electrochemical setup was designed to bias biofunctionalized samples with the potential measured versus silver/silver chloride reference electrode in a three electrode configuration system. The immobilization efficiency has been examined with fluorescence microscopy after tagging captured bacteria with fluorescein labeled antibodies. We demonstrate more than 2 times enhanced capture of Legionella pneumophila, suggesting the potential of electrically biased biochips to deliver enhanced sensitivity in detecting these bacteria.

Electrochemistry of Silicon: Instrumentation, Science, Materials and Applications

NASA Astrophysics Data System (ADS)

Lehmann, Volker

2002-04-01

Silicon has been and will most probably continue to be the dominant material in semiconductor technology. Although the defect-free silicon single crystal is one of the best understood systems in materails science, its electrochemistry to many people is still a kind of "alchemy". This view is partly due to the interdisciplinary aspects of the topic: Physics meets chemistry at the silicon-electrolyte interface. This book gives a comprehensive overview of this important aspect of silicon technology as well as examples of applications ranging from photonic crystals to biochips. It will serve materials scientists as well as engineers involved in silicon technology as a quick reference with its more than 150 technical tables and diagrams and ca. 1000 references cited for easy access of the original literature.

Automation of complex assays: pharmacogenetics of warfarin dosing.

PubMed

Wu, Whei-Kuo; Hujsak, Paul G; Kureshy, Fareed

2007-10-01

AutoGenomics, Inc. (Carlsbad, CA, USA) have developed a multiplex microarray assay for genotyping both VKORC1 and CYP2C9 using the INFINITI(™) Analyzer. Multiple alleles in each DNA sample are analyzed by polymerase chain reaction amplification, followed by detection primer extension using the INFINITI Analyzer. The INFINITI Analyzer performs single-nucleotide polymorphism (SNP) analysis using universal oligonucleotides immobilized on the biochip. To genotype broader ethnic groups, genomic DNA from whole blood was tested for nine SNPs for VKORC1 and six for CYP2C9 genotypes. Information related to all 15 SNPs is needed to determine dosing of population of diverse ethnic origin. The INFINITI system provides genotyping information for same day dosing of warfarin.

Using DNA chips for identification of tephritid pest species.

PubMed

Chen, Yen-Hou; Liu, Lu-Yan; Tsai, Wei-Huang; Haymer, David S; Lu, Kuang-Hui

2014-08-01

The ability correctly to identify species in a rapid and reliable manner is critical in many situations. For insects in particular, the primary tools for such identification rely on adult-stage morphological characters. For a number of reasons, however, there is a clear need for alternatives. This paper reports on the development of a new method employing DNA biochip technology for the identification of pest species within the family Tephritidae. The DNA biochip developed and tested here quickly and efficiently identifies and discriminates between several tephritid species, except for some that are members of a complex of closely related taxa and that may in fact not represent distinct biological species. The use of these chips offers a number of potential advantages over current methods. Results can be obtained in less than 5 h using material from any stage of the life cycle and with greater sensitivity than other methods currently available. This technology provides a novel tool for the rapid and reliable identification of several major pest species that may be intercepted in imported fruits or other commodities. The existing chips can also easily be expanded to incorporate additional markers and species as needed. © 2013 Society of Chemical Industry.

A microfluidically perfused three dimensional human liver model.

PubMed

Rennert, Knut; Steinborn, Sandra; Gröger, Marko; Ungerböck, Birgit; Jank, Anne-Marie; Ehgartner, Josef; Nietzsche, Sandor; Dinger, Julia; Kiehntopf, Michael; Funke, Harald; Peters, Frank T; Lupp, Amelie; Gärtner, Claudia; Mayr, Torsten; Bauer, Michael; Huber, Otmar; Mosig, Alexander S

2015-12-01

Within the liver, non-parenchymal cells (NPCs) are critically involved in the regulation of hepatocyte polarization and maintenance of metabolic function. We here report the establishment of a liver organoid that integrates NPCs in a vascular layer composed of endothelial cells and tissue macrophages and a hepatic layer comprising stellate cells co-cultured with hepatocytes. The three-dimensional liver organoid is embedded in a microfluidically perfused biochip that enables sufficient nutrition supply and resembles morphological aspects of the human liver sinusoid. It utilizes a suspended membrane as a cell substrate mimicking the space of Disse. Luminescence-based sensor spots were integrated into the chip to allow online measurement of cellular oxygen consumption. Application of microfluidic flow induces defined expression of ZO-1, transferrin, ASGPR-1 along with an increased expression of MRP-2 transporter protein within the liver organoids. Moreover, perfusion was accompanied by an increased hepatobiliary secretion of 5(6)-carboxy-2',7'-dichlorofluorescein and an enhanced formation of hepatocyte microvilli. From this we conclude that the perfused liver organoid shares relevant morphological and functional characteristics with the human liver and represents a new in vitro research tool to study human hepatocellular physiology at the cellular level under conditions close to the physiological situation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Novel 3D Culture Systems for Studies of Human Liver Function and Assessments of the Hepatotoxicity of Drugs and Drug Candidates.

PubMed

Lauschke, Volker M; Hendriks, Delilah F G; Bell, Catherine C; Andersson, Tommy B; Ingelman-Sundberg, Magnus

2016-12-19

The liver is an organ with critical importance for drug treatment as the disposition and response to a given drug is often determined by its hepatic metabolism. Patient-specific factors can entail increased susceptibility to drug-induced liver injury, which constitutes a major risk for drug development programs causing attrition of promising drug candidates or costly withdrawals in postmarketing stages. Hitherto, mainly animal studies and 2D hepatocyte systems have been used for the examination of human drug metabolism and toxicity. Yet, these models are far from satisfactory due to extensive species differences and because hepatocytes in 2D cultures rapidly dedifferentiate resulting in the loss of their hepatic phenotype and functionality. With the increasing comprehension that 3D cell culture systems more accurately reflect in vivo physiology, in the recent decade more and more research has focused on the development and optimization of various 3D culture strategies in an attempt to preserve liver properties in vitro. In this contribution, we critically review these developments, which have resulted in an arsenal of different static and perfused 3D models. These systems include sandwich-cultured hepatocytes, spheroid culture platforms, and various microfluidic liver or multiorgan biochips. Importantly, in many of these models hepatocytes maintain their phenotype for prolonged times, which allows probing the potential of newly developed chemical entities to cause chronic hepatotoxicity. Moreover, some platforms permit the investigation of drug action in specific genetic backgrounds or diseased hepatocytes, thereby significantly expanding the repertoire of tools to detect drug-induced liver injuries. It is concluded that the development of 3D liver models has hitherto been fruitful and that systems are now at hand whose sensitivity and specificity in detecting hepatotoxicity are superior to those of classical 2D culture systems. For the future, we highlight the need to develop more integrated coculture model systems to emulate immunotoxicities that arise due to complex interactions between hepatocytes and immune cells.

Performance evaluation for different sensing surface of BICELLs bio-transducers for dry eye biomarkers

NASA Astrophysics Data System (ADS)

Laguna, M. F.; Holgado, M.; Santamaría, B.; López, A.; Maigler, M.; Lavín, A.; de Vicente, J.; Soria, J.; Suarez, T.; Bardina, C.; Jara, M.; Sanza, F. J.; Casquel, R.; Otón, A.; Riesgo, T.

2015-03-01

Biophotonic Sensing Cells (BICELLs) are demonstrated to be an efficient technology for label-free biosensing and in concrete for evaluating dry eye diseases. The main advantage of BICELLs is its capability to be used by dropping directly a tear into the sensing surface without the need of complex microfluidics systems. Among this advantage, compact Point of Care read-out device is employed with the capability of evaluating different types of BICELLs packaged on Biochip-Kits that can be fabricated by using different sensing surfaces material. In this paper, we evaluate the performance of the combination of three sensing surface materials: (3-Glycidyloxypropyl) trimethoxysilane (GPTMS), SU-8 resist and Nitrocellulose (NC) for two different biomarkers relevant for dry eye diseases: PRDX-5 and ANXA-11.

Rapid Multi-Locus Sequence Typing Using Microfluidic Biochips

DTIC Science & Technology

2010-05-12

Sequence Types. The evolutionary history of all the B. cereus MLST concatenated Sequence Types (545 taxa, 2,394 nucleotide positions) was inferred using...the Neighbor-Joining method [28]. The bootstrap consensus tree inferred from 100 replicates was taken to represent the evolutionary history of the... Chlamydia (manuscript in preparation) and performed pilot studies on Staphylococcus aureus and Streptoccus pneumoniae (Data S4 and Text S2). Another potential

Micro Machining of Injection Mold Inserts for Fluidic Channel of Polymeric Biochips

PubMed Central

Jung, Woo-Chul; Heo, Young-Moo; Yoon, Gil-Sang; Shin, Kwang-Ho; Chang, Sung-Ho; Kim, Gun-Hee; Cho, Myeong-Woo

2007-01-01

Recently, the polymeric micro-fluidic biochip, often called LOC (lab-on-a-chip), has been focused as a cheap, rapid and simplified method to replace the existing biochemical laboratory works. It becomes possible to form miniaturized lab functionalities on a chip with the development of MEMS technologies. The micro-fluidic chips contain many micro-channels for the flow of sample and reagents, mixing, and detection tasks. Typical substrate materials for the chip are glass and polymers. Typical techniques for microfluidic chip fabrication are utilizing various micro pattern forming methods, such as wet-etching, micro-contact printing, and hot-embossing, micro injection molding, LIGA, and micro powder blasting processes, etc. In this study, to establish the basis of the micro pattern fabrication and mass production of polymeric micro-fluidic chips using injection molding process, micro machining method was applied to form micro-channels on the LOC molds. In the research, a series of machining experiments using micro end-mills were performed to determine optimum machining conditions to improve surface roughness and shape accuracy of designed simplified micro-channels. Obtained conditions were used to machine required mold inserts for micro-channels using micro end-mills. Test injection processes using machined molds and COC polymer were performed, and then the results were investigated.

A surface plasmon resonance based biochip for the detection of patulin toxin

NASA Astrophysics Data System (ADS)

Pennacchio, Anna; Ruggiero, Giuseppe; Staiano, Maria; Piccialli, Gennaro; Oliviero, Giorgia; Lewkowicz, Aneta; Synak, Anna; Bojarski, Piotr; D'Auria, Sabato

2014-08-01

Patulin is a toxic secondary metabolite of a number of fungal species belonging to the genera Penicillium and Aspergillus. One important aspect of the patulin toxicity in vivo is an injury of the gastrointestinal tract including ulceration and inflammation of the stomach and intestine. Recently, patulin has been shown to be genotoxic by causing oxidative damage to the DNA, and oxidative DNA base modifications have been considered to play a role in mutagenesis and cancer initiation. Conventional analytical methods for patulin detection involve chromatographic analyses, such as HPLC, GC, and, more recently, techniques such as LC/MS and GC/MS. All of these methods require the use of extensive protocols and the use of expensive analytical instrumentation. In this work, the conjugation of a new derivative of patulin to the bovine serum albumin for the production of polyclonal antibodies is described, and an innovative competitive immune-assay for detection of patulin is presented. Experimentally, an important part of the detection method is based on the optical technique called surface plasmon resonance (SPR). Laser beam induced interactions between probe and target molecules in the vicinity of gold surface of the biochip lead to the shift in resonance conditions and consequently to slight but easily detectable change of reflectivity.

Autonomous Magnetic Microrobots by Navigating Gates for Multiple Biomolecules Delivery.

PubMed

Hu, Xinghao; Lim, Byeonghwa; Torati, Sri Ramulu; Ding, Junjia; Novosad, Valentine; Im, Mi-Young; Reddy, Venu; Kim, Kunwoo; Jung, Eunjoo; Shawl, Asif Iqbal; Kim, Eunjoo; Kim, CheolGi

2018-05-08

The precise delivery of biofunctionalized matters is of great interest from the fundamental and applied viewpoints. In spite of significant progress achieved during the last decade, a parallel and automated isolation and manipulation of rare analyte, and their simultaneous on-chip separation and trapping, still remain challenging. Here, a universal micromagnet junction for self-navigating gates of microrobotic particles to deliver the biomolecules to specific sites using a remote magnetic field is described. In the proposed concept, the nonmagnetic gap between the lithographically defined donor and acceptor micromagnets creates a crucial energy barrier to restrict particle gating. It is shown that by carefully designing the geometry of the junctions, it becomes possible to deliver multiple protein-functionalized carriers in high resolution, as well as MCF-7 and THP-1 cells from the mixture, with high fidelity and trap them in individual apartments. Integration of such junctions with magnetophoretic circuitry elements could lead to novel platforms without retrieving for the synchronous digital manipulation of particles/biomolecules in microfluidic multiplex arrays for next-generation biochips. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Single Molecule Sensing by Nanopores and Nanopore Devices

PubMed Central

Gu, Li-Qun; Shim, Ji Wook

2010-01-01

Molecular-scale pore structures, called nanopores, can be assembled by protein ion channels through genetic engineering or be artificially fabricated on solid substrates using fashion nanotechnology. When target molecules interact with the functionalized lumen of a nanopore, they characteristically block the ion pathway. The resulting conductance changes allow for identification of single molecules and quantification of target species in the mixture. In this review, we first overview nanopore-based sensory techniques that have been created for the detection of myriad biomedical targets, from metal ions, drug compounds, and cellular second messengers to proteins and DNA. Then we introduce our recent discoveries in nanopore single molecule detection: (1) using the protein nanopore to study folding/unfolding of the G-quadruplex aptamer; (2) creating a portable and durable biochip that is integrated with a single-protein pore sensor (this chip is compared with recently developed protein pore sensors based on stabilized bilayers on glass nanopore membranes and droplet interface bilayer); and (3) creating a glass nanopore-terminated probe for single-molecule DNA detection, chiral enantiomer discrimination, and identification of the bioterrorist agent ricin with an aptamer-encoded nanopore. PMID:20174694

Planar MEMS bio-chip for recording ion-channel currents in biological cells

NASA Astrophysics Data System (ADS)

Pandey, Santosh; Ferdous, Zannatul; White, Marvin H.

2003-10-01

We describe a planar MEMS silicon structure to record ion-channel currents in biological cells. The conventional method of performing an electrophysiological experiment, 'patch-clamping,' employs a glass micropipette. Despite careful treatments of the micropipette tip, such as fire polishing and surface coating, the latter is a source of thermal noise because of its inherent, tapered, conical structure, which gives rise to a large pipette resistance. This pipette resistance, when coupled with the self-capacitance of the biological cell, limits the available bandwidth and processing of fast transient, ion channel current pulses. In this work, we reduce considerably the pipette resistance with a planar micropipette on a silicon chip to permit the resolution of sub-millisecond, ion-channel pulses. We discuss the design topology of the device, describe the fabrication sequence, and highlight important critical issues. The design of an integrated on-chip CMOS instrumentation amplifier is described, which has a low-noise front-end, input-offset cancellation, correlated double sampling (CDS), and an ultra-high gain in the order of 1012V/A.

PREFACE: E-MRS 2012 Spring Meeting, Symposium M: More than Moore: Novel materials approaches for functionalized Silicon based Microelectronics

NASA Astrophysics Data System (ADS)

Wenger, Christian; Fompeyrine, Jean; Vallée, Christophe; Locquet, Jean-Pierre

2012-12-01

More than Moore explores a new area of Silicon based microelectronics, which reaches beyond the boundaries of conventional semiconductor applications. Creating new functionality to semiconductor circuits, More than Moore focuses on motivating new technological possibilities. In the past decades, the main stream of microelectronics progresses was mainly powered by Moore's law, with two focused development arenas, namely, IC miniaturization down to nano scale, and SoC based system integration. While the microelectronics community continues to invent new solutions around the world to keep Moore's law alive, there is increasing momentum for the development of 'More than Moore' technologies which are based on silicon technologies but do not simply scale with Moore's law. Typical examples are RF, Power/HV, Passives, Sensor/Actuator/MEMS or Bio-chips. The More than Moore strategy is driven by the increasing social needs for high level heterogeneous system integration including non-digital functions, the necessity to speed up innovative product creation and to broaden the product portfolio of wafer fabs, and the limiting cost and time factors of advanced SoC development. It is believed that More than Moore will add value to society on top of and beyond advanced CMOS with fast increasing marketing potentials. Important key challenges for the realization of the 'More than Moore' strategy are: perspective materials for future THz devices materials systems for embedded sensors and actuators perspective materials for epitaxial approaches material systems for embedded innovative memory technologies development of new materials with customized characteristics The Hot topics covered by the symposium M (More than Moore: Novel materials approaches for functionalized Silicon based Microelectronics) at E-MRS 2012 Spring Meeting, 14-18 May 2012 have been: development of functional ceramics thin films New dielectric materials for advanced microelectronics bio- and CMOS compatible material systems piezoelectric films and nanostructures Atomic Layer Deposition (ALD) of oxides and nitrides characterization and metrology of very thin oxide layers We would like to take this opportunity to thank the Scientific Committee and Local Committee for bringing together a coherent and high quality Symposium at E-MRS 2012 Spring Meeting. Christian Wenger, Jean Fompeyrine, Christophe Vallée and Jean-Pierre Locquet Organizing Committee of Symposium M September 2012

Cambridge Healthtech Institute's Third Annual Conference on Lab-on-a-Chip and Microarrays. 22-24 January 2001, Zurich, Switzerland.

PubMed

Jain, K K

2001-02-01

Cambridge Healthtech Institute's Third Annual Conference on Lab-on-a-Chip and Microarray technology covered the latest advances in this technology and applications in life sciences. Highlights of the meetings are reported briefly with emphasis on applications in genomics, drug discovery and molecular diagnostics. There was an emphasis on microfluidics because of the wide applications in laboratory and drug discovery. The lab-on-a-chip provides the facilities of a complete laboratory in a hand-held miniature device. Several microarray systems have been used for hybridisation and detection techniques. Oligonucleotide scanning arrays provide a versatile tool for the analysis of nucleic acid interactions and provide a platform for improving the array-based methods for investigation of antisense therapeutics. A method for analysing combinatorial DNA arrays using oligonucleotide-modified gold nanoparticle probes and a conventional scanner has considerable potential in molecular diagnostics. Various applications of microarray technology for high-throughput screening in drug discovery and single nucleotide polymorphisms (SNP) analysis were discussed. Protein chips have important applications in proteomics. With the considerable amount of data generated by the different technologies using microarrays, it is obvious that the reading of the information and its interpretation and management through the use of bioinformatics is essential. Various techniques for data analysis were presented. Biochip and microarray technology has an essential role to play in the evolving trends in healthcare, which integrate diagnosis with prevention/treatment and emphasise personalised medicines.

Multifunctional microvalves control by optical illumination on nanoheaters and its application in centrifugal microfluidic devices.

PubMed

Park, Jong-Myeon; Cho, Yoon-Kyoung; Lee, Beom-Seok; Lee, Jeong-Gun; Ko, Christopher

2007-05-01

Valving is critical in microfluidic systems. Among many innovative microvalves used in lab-on-a-chip applications, phase change based microvalves using paraffin wax are particularly attractive for disposable biochip applications because they are simple to implement, cost-effective and biocompatible. However, previously reported paraffin-based valves require embedded microheaters and therefore multi-step operation of many microvalves was a difficult problem. Besides, the operation time was relatively long, 2-10 s. In this paper, we report a unique phase change based microvalve for rapid and versatile operation of multiple microvalves using a single laser diode. The valve is made of nanocomposite materials in which 10 nm-sized iron oxide nanoparticles are dispersed in paraffin wax and used as nanoheaters when excited by laser irradiation. Laser light of relatively weak intensity was able to melt the paraffin wax with the embedded iron oxide nanoparticles, whereas even a very intense laser beam does not melt wax alone. The microvalves are leak-free up to 403.0 +/- 7.6 kPa and the response times to operate both normally closed and normally opened microvalves are less than 0.5 s. Furthermore, a sequential operation of multiple microvalves on a centrifugal microfluidic device using a single laser diode was demonstrated. It showed that the optical control of multiple microvalves is fast, robust, simple to operate, and requires minimal chip space and thus is well suited for fully integrated lab-on-a-chip applications.

The facile fabrication of tunable plasmonic gold nanostructure arrays using microwave plasma

NASA Astrophysics Data System (ADS)

Hsu, Chuen-Yuan; Huang, Jing-Wen; Gwo, Shangjr; Lin, Kuan-Jiuh

2010-01-01

Fabrication of isolated noble metal nanoparticles embedded in transparent substrates is the fasting growing demand for innovative plasmonic technologies. Here we report a simple and effective methodology for the preparation of highly stable plasmonic nanoparticles embedded in a glass surface. Size-controllable (10-70 nm) Au nanoparticles were rapidly prepared when subjected to the home-microwave plasma. Accordingly, the optical extinction maximum of the localized surface plasmon resonance (LSPR) can be systematically tuned in the range 532-586 nm. We find that the plasmonic structures are exceedingly stable toward immersion in ethanol solvents and pass successfully the adhesive tape test, which makes our system highly promising for efficient transmission-LSPR nanosensors. Besides, the attractive features of substrate-bound plasmonic nanostructures include its low cost, versatility, robustness, reusability and a promising ability to make a multi-arrayed LSPR biochip.

[THE CONDITION AND TENDENCIES OF DEVELOPMENT OF CLINICAL AND SANITARY MICROBIOLOGY IN THE RUSSIAN FEDERATION AND PROBLEM OF IMPORT SUBSTITUTION].

PubMed

Dyatlov, I A; Mironov, A Yu; Shepelin, A P; Aleshkin, V A

2015-08-01

The import substitution becomes one of the strategic tasks of national economy as a result of prolongation of economic sanctions concerning the Russian Federation of part of the USA, EU countries, Japan and number of other countries. It is not proper to be limited in import substitution only by goods because in conditions ofsanctions when access toforeign technologies is complicated Russia is needed to substitute foreign technologies by national designs in faster manner One of directions of effective import substitution is localization of production of laboratory equipment and consumables for clinical and sanitary microbiology on the territory ofthe Russian Federation and countries of Customs union. In Russia, in the field ofdiagnostic of dangerous and socially significant infections, all components for import substitution to implement gene diagnostic, immune diagnostic. bio-sensory and biochip approaches, isolation and storage of live microbial cultures, implementation of high-tech methods of diagnostic are available. At the same time, national diagnostic instrument-making industry for microbiology is factually absent. The few devices of national production more than on 50% consist of import components. The microbiological laboratories are to be equipped only with import devices of open type for applying national components. The most perspective national designs to be implemented are multiplex polimerase chain reaction test-systems and biochips on the basis of national plotters and readers. The modern development of diagnostic equipment and diagnostic instruments requires supplement of national collections of bacterial and viral pathogens and working-through of organizational schemes of supplying collections with strains. The presented data concerning justification of nomenclature of laboratory equipment and consumables permits to satisfy in fill scope the needs of clinical and sanitary microbiology in devices, growth mediums, consumables of national production and to refuse import deliveries without decreasing quality of microbiological analysis. This approach will ensure appropriate response to occurring challenges and new biological dangers and maintenance of biosecurity of the Russian Federation at proper level.

CAD/CAM interface design of excimer laser micro-processing system

NASA Astrophysics Data System (ADS)

Jing, Liang; Chen, Tao; Zuo, Tiechuan

2005-12-01

Recently CAD/CAM technology has been gradually used in the field of laser processing. The excimer laser micro-processing system just identified G instruction before CAD/CAM interface was designed. However the course of designing a part with G instruction for users is too hard. The efficiency is low and probability of making errors is high. By secondary development technology of AutoCAD with Visual Basic, an application was developed to pick-up each entity's information in graph and convert them to each entity's processing parameters. Also an additional function was added into former controlling software to identify these processing parameters of each entity and realize continue processing of graphic. Based on the above CAD/CAM interface, Users can design a part in AutoCAD instead of using G instruction. The period of designing a part is sharply shortened. This new way of design greatly guarantees the processing parameters of the part is right and exclusive. The processing of complex novel bio-chip has been realized by this new function.

Building biochips: a protein production pipeline

NASA Astrophysics Data System (ADS)

de Carvalho-Kavanagh, Marianne G. S.; Albala, Joanna S.

2004-06-01

Protein arrays are emerging as a practical format in which to study proteins in high-throughput using many of the same techniques as that of the DNA microarray. The key advantage to array-based methods for protein study is the potential for parallel analysis of thousands of samples in an automated, high-throughput fashion. Building protein arrays capable of this analysis capacity requires a robust expression and purification system capable of generating hundreds to thousands of purified recombinant proteins. We have developed a method to utilize LLNL-I.M.A.G.E. cDNAs to generate recombinant protein libraries using a baculovirus-insect cell expression system. We have used this strategy to produce proteins for analysis of protein/DNA and protein/protein interactions using protein microarrays in order to understand the complex interactions of proteins involved in homologous recombination and DNA repair. Using protein array techniques, a novel interaction between the DNA repair protein, Rad51B, and histones has been identified.

Reversible nano-lithography for commercial approaches

NASA Astrophysics Data System (ADS)

Park, Jae Hong; Jang, Hyun Ik; Kim, Woo Choong; Yun, Hae S.; Park, Jun Yong; Jeon, Seok Woo; Kim, Hee Yeoun; Ahn, Chi Won

2016-04-01

The methodology suggested in this research provides the great possibility of creating nanostructures composed of various materials, such as soft polymer, hard polymer, and metal, as well as Si. Such nanostructures are required for a vast range of optical and display devices, photonic components, physical devices, energy devices including electrodes of secondary batteries, fuel cells, solar cells, and energy harvesters, biological devices including biochips, biomimetic or biosimilar structured devices, and mechanical devices including micro- or nano-scale sensors and actuators.

Deployable Laboratory Applications of Nano- and Bio-Technology (Applications de nanotechnologie et biotechnologie destinees a un laboratoire deployable)

DTIC Science & Technology

2014-10-01

applications of present nano-/ bio -technology include advanced health and fitness monitoring, high-resolution imaging, new environmental sensor platforms...others areas where nano-/ bio -technology development is needed: • Sensors : Diagnostic and detection kits (gene-chips, protein-chips, lab-on-chips, etc...studies on chemo- bio nano- sensors , ultra-sensitive biochips (“lab-on-a-chip” and “cells-on-chips” devices) have been prepared for routine medical

Evaluation and Refinement of a Field-Portable Drinking Water Toxicity Sensor Utilizing Electric Cell-Substrate Impedance Sensing and a Fluidic Biochip

DTIC Science & Technology

2014-01-01

Potential interferences tested were chlorine and chloramine (commonly used for drinking water disinfection ), geosmin and 2-methyl-isoborneol (MIB...Protection Agency maximum residual disinfectant level for chlorine and chloramine is set at 4 mg l1 under the Safe Drinking Water Act and thus would...Evaluation and refinement of a field-portable drinking water toxicity sensor utilizing electric cell–substrate impedance sensing and a fluidic

Fluorogenic Cell-Based Biosensors for Monitoring Microbes

NASA Technical Reports Server (NTRS)

Curtis, Theresa; Salazar, Noe; Tabb, Joel; Chase, Chris

2010-01-01

Fluorogenic cell-based sensor systems for detecting microbes (especially pathogenic ones) and some toxins and allergens are undergoing development. These systems harness the natural signaltransduction and amplification cascades that occur in mast cells upon activation with antigens. These systems include (1) fluidic biochips for automated containment of samples, reagents, and wastes and (2) sensitive, compact fluorometers for monitoring the fluorescent responses of mast cells engineered to contain fluorescent dyes. It should be possible to observe responses within minutes of adding immune complexes. The systems have been shown to work when utilizing either immunoglobulin E (IgE) antibodies or traditionally generated rat antibodies - a promising result in that it indicates that the systems could be developed to detect many target microbes. Chimeric IgE antibodies and rat immunoglobulin G (IgG) antibodies could be genetically engineered for recognizing biological and chemical warfare agents and airborne and food-borne allergens. Genetic engineering efforts thus far have yielded (1) CD14 chimeric antibodies that recognize both Grampositive and Gram-negative bacteria and bind to the surfaces of mast cells, eliciting a degranulation response and (2) rat IgG2a antibodies that act similarly in response to low levels of canine parvovirus.

Evaluation and refinement of a field-portable drinking water toxicity sensor utilizing electric cell-substrate impedance sensing and a fluidic biochip.

PubMed

Widder, Mark W; Brennan, Linda M; Hanft, Elizabeth A; Schrock, Mary E; James, Ryan R; van der Schalie, William H

2015-07-01

The US Army's need for a reliable and field-portable drinking water toxicity sensor was the catalyst for the development and evaluation of an electric cell-substrate impedance sensing (ECIS) device. Water testing technologies currently available to soldiers in the field are analyte-specific and have limited capabilities to detect broad-based water toxicity. The ECIS sensor described here uses rainbow trout gill epithelial cells seeded on fluidic biochips to measure changes in impedance for the detection of possible chemical contamination of drinking water supplies. Chemicals selected for testing were chosen as representatives of a broad spectrum of toxic industrial compounds. Results of a US Environmental Protection Agency (USEPA)-sponsored evaluation of the field portable device were similar to previously published US Army testing results of a laboratory-based version of the same technology. Twelve of the 18 chemicals tested following USEPA Technology Testing and Evaluation Program procedures were detected by the ECIS sensor within 1 h at USEPA-derived human lethal concentrations. To simplify field-testing methods further, elimination of a procedural step that acclimated cells to serum-free media streamlined the test process with only a slight loss of chemical sensitivity. For field use, the ECIS sensor will be used in conjunction with an enzyme-based sensor that is responsive to carbamate and organophosphorus pesticides. Copyright © 2014 John Wiley & Sons, Ltd.

[The association of polymorphisms in SLC18A1, TPH1 and RELN genes with risk of paranoid schizophrenia].

PubMed

Galaktionova, D Iu; Gareeva, A E; Khusnutdinova, E K; Nasedkina, T V

2014-01-01

We have developed a biochip for the analysis of polymorphisms in candidate genes for schizophrenia: DISC1, RELN, ZNF804A, PLXNA2, COMT, SLC18A41, CACNA1C, ANK3, TPH1, PLAA and SNAP-25. Using biochip the allele and genotype frequencies in 198 patients with schizophrenia and 192 healthy individuals have been obtained. For SLC18A1 polymorphism rs2270641 A>C, the frequencies of A allele (p = 0.007) and AA genotype (p = 0.002) were lower in patients compared with healthy individuals. A significant association was found between AA genotype (p = 0.036) of the TPH1 polymorphism rs1800532 C>A and schizophrenia. The C allele (p = 0.039) of the RELNpolymorphism rs7341475 C>T were lower in patients with schizophrenia compared with healthy individuals in a tatar population. Genotype AA of the TPH1 polymorphism rs1800532 C>A were more frequent in patients with schizophrenia compared with healthy individuals. Ithas been shown that the C allele (p = 0.0001) and GC (p = = 0.0001) genotype of the PLXNA2 polymorphism rs1327175 G>C are associated with the family history in patients with paranoid schizophrenia. The obtained data suggest that SLC18A1, TPH1 and RELN gene polymorphisms are associated with the risk of paranoid schizophrenia.

Development of a photodiode array biochip using a bipolar semiconductor and its application to detection of human papilloma virus.

PubMed

Baek, Taek Jin; Park, Pan Yun; Han, Kwi Nam; Kwon, Ho Taik; Seong, Gi Hun

2008-03-01

We describe a DNA microarray system using a bipolar integrated circuit photodiode array (PDA) chip as a new platform for DNA analysis. The PDA chip comprises an 8 x 6 array of photodiodes each with a diameter of 600 microm. Each photodiode element acts both as a support for an immobilizing probe DNA and as a two-dimensional photodetector. The usefulness of the PDA microarray platform is demonstrated by the detection of high-risk subtypes of human papilloma virus (HPV). The polymerase chain reaction (PCR)-amplified biotinylated HPV target DNA was hybridized with the immobilized probe DNA on the photodiode surface, and the chip was incubated in an anti-biotin antibody-conjugated gold nanoparticle solution. The silver enhancement by the gold nanoparticles bound to the biotin of the HPV target DNA precipitates silver metal particles at the chip surfaces, which block light irradiated from above. The resulting drop in output voltage depends on the amount of target DNA present in the sample solution, which allows the specific detection and the quantitative analysis of the complementary target DNA. The PDA chip showed high relative signal ratios of HPV probe DNA hybridized with complementary target DNA, indicating an excellent capability in discriminating HPV subtypes. The detection limit for the HPV target DNA analysis improved from 1.2 nM to 30 pM by changing the silver development time from 5 to 10 min. Moreover, the enhanced silver development promoted by the gold nanoparticles could be applied to a broader range of target DNA concentration by controlling the silver development time.

Microbial synthesis of poly(epsilon-lysine) and its various applications.

PubMed

Shih, Ing-Lung; Shen, Ming-Haw; Van, Yi-Tsong

2006-06-01

This review article deals with the microbial synthesis, physiochemical properties, and potential applications of poly-epsilon-lysine (epsilon-PL), which is a naturally occurring biomaterial that is water soluble, biodegradable, edible and non-toxic toward humans and the environment. The potential applications of epsilon-PL as food preservatives, emulsifying agent, dietary agent, biodegradable fibers, highly water absorbable hydrogels, drug carriers, anticancer agent enhancer, biochip coatings in the fields of food, medicine, agriculture and electronics are also discussed in this review.

UV waveguides light fabricated in fluoropolymer CYTOP by femtosecond laser direct writing.

PubMed

Hanada, Yasutaka; Sugioka, Koji; Midorikawa, Katsumi

2010-01-18

We have fabricated optical waveguides inside the UV-transparent polymer, CYTOP, by femtosecond laser direct writing for propagating UV light in biochip applications. Femtosecond laser irradiation is estimated to increase the refractive index of CYTOP by 1.7 x 10(-3) due to partial bond breaking in CYTOP. The waveguide in CYTOP has propagation losses of 0.49, 0.77, and 0.91 dB/cm at wavelengths of 632.8, 355, and 266 nm, respectively.

[The organization of scientific innovative laboratory complex of modern technologies].

PubMed

Totskaia, E G; Rozhnova, O M; Mamonova, E V

2013-01-01

The article discusses the actual issues of scientific innovative activity during the realization of principles of private-public partnership. The experience of development of model of scientific innovative complex is presented The possibilities to implement research achievements and their application in the area of cell technologies, technologies of regenerative medicine, biochip technologies are demonstrated. The opportunities to provide high level of diagnostic and treatment in practical health care increase of accessibility and quality of medical care and population health promotion are discussed.

Preparation and Testing of Impedance-based Fluidic Biochips with RTgill-W1 Cells for Rapid Evaluation of Drinking Water Samples for Toxicity

DTIC Science & Technology

2016-03-07

and rapid response to a broad spectrum of inorganic and organic chemicals at concentrations that are relevant to human health concerns, as well as the...broad spectrum of toxic industrial compounds rapidly (within an hour) at concentrations relevant to human health , that the device be field-portable...laboratory setting and was able to detect potential water contaminants at concentrations that are relevant to human health . The portability and

Double stranded nucleic acid biochips

DOEpatents

Chernov, Boris; Golova, Julia

2006-05-23

This invention describes a new method of constructing double-stranded DNA (dsDNA) microarrays based on the use of pre-synthesized or natural DNA duplexes without a stem-loop structure. The complementary oligonucleotide chains are bonded together by a novel connector that includes a linker for immobilization on a matrix. A non-enzymatic method for synthesizing double-stranded nucleic acids with this novel connector enables the construction of inexpensive and robust dsDNA/dsRNA microarrays. DNA-DNA and DNA-protein interactions are investigated using the microarrays.

Biomimetic interfaces based on S-layer proteins, lipid membranes and functional biomolecules

PubMed Central

Schuster, Bernhard; Sleytr, Uwe B.

2014-01-01

Designing and utilization of biomimetic membrane systems generated by bottom-up processes is a rapidly growing scientific and engineering field. Elucidation of the supramolecular construction principle of archaeal cell envelopes composed of S-layer stabilized lipid membranes led to new strategies for generating highly stable functional lipid membranes at meso- and macroscopic scale. In this review, we provide a state-of-the-art survey of how S-layer proteins, lipids and polymers may be used as basic building blocks for the assembly of S-layer-supported lipid membranes. These biomimetic membrane systems are distinguished by a nanopatterned fluidity, enhanced stability and longevity and, thus, provide a dedicated reconstitution matrix for membrane-active peptides and transmembrane proteins. Exciting areas in the (lab-on-a-) biochip technology are combining composite S-layer membrane systems involving specific membrane functions with the silicon world. Thus, it might become possible to create artificial noses or tongues, where many receptor proteins have to be exposed and read out simultaneously. Moreover, S-layer-coated liposomes and emulsomes copying virus envelopes constitute promising nanoformulations for the production of novel targeting, delivery, encapsulation and imaging systems. PMID:24812051

Nonlinear Dynamics of Formation of Drops of Non-Newtonian Liquids from Capillaries: Satellite Formation and Flow Transitions

NASA Astrophysics Data System (ADS)

Yildirim, Ozgur E.; Basaran, Osman A.

1999-11-01

Drop formation from capillaries, and the often undesired phenomenon of satellite generation, play a central role in diverse applications including ink-jet printing, biochip processors, and spray coating, where the working fluid is usually non-Newtonian. Although some work has been done in related areas, the phenomenon of formation of drops of non--Newtonian fluids from capillaries has remained largely unexplored. Here a theoretical approach is adopted to study the dripping of axisymmetric drops of non--Newtonian liquids from capillaries. The constitutive equation used accounts for both shear thinning and strain hardening. First, regular perturbation theory is utilized to reduce the spatial dimension of the governing equations to one. The computations rely on Galerkin/finite element analysis with adaptive finite differencing for time integration. The dynamics are followed beyond the first breakup to investigate conditions for occurrence of satellites. Effect of increasing flow rate is also studied to uncover transitions that occur as one moves from a regime of periodic drop formation to one of jetting.

Electroacoustic miniaturized DNA-biosensor.

PubMed

Gamby, Jean; Lazerges, Mathieu; Pernelle, Christine; Perrot, Hubert; Girault, Hubert H; Tribollet, Bernard

2007-11-01

A micrometer-sized electroacoustic DNA-biosensor was developed. The device included a thin semi-crystalline polyethylene terephthalate (PET) dielectric layer with two Ag microband electrodes on one side and a DNA thiol-labeled monolayer adsorbed on a gold surface on the other. A resonance wave was observed at 29 MHz with a network analyzer, upon AC voltage application between the two Ag electrodes, corresponding to electromechanical coupling induced by molecular dipoles of the PET polymer chain in the dielectric layer. It was found that the device size and geometry were well adapted to detect DNA hybridization, by measuring the capacity of the resonance response evolution: hybridization induced polarization of the dielectric material that affected the electromechanical coupling established in the dielectric layer. The 0.2 mm(2) sensor sensitive area allows detection in small volumes and still has higher detection levels for bioanalytical applications, the non-contact configuration adopted avoids electric faradic reactions that may damage biosensor sensitive layers, and finally, PET is a costless raw material, easy to process and well adapted for large scale production. The well-balanced technological and economic advantages of this kind of device make it a good candidate for biochip integration.

Research Results Ultra-fast Energy Transfer from Monomer to Dimer within a Trimeric Molecule New Progress in Heterogeneous Catalysis Research Key Progress in Research on Terrestrial Carbon Cycle in China A New Progress in Research on the Mechanism of Bio-Invasion New Findings in Anti-viral infection and Control of Inflammation Major Headway in Avian Origin Research New Progress in Gold-Nanoparticle-Based Biochips Topological Insulator Research Made Important Progress Major Progress in Biodiversity Achieved New Developments of Direct Methods in Protein Crystallography Major Progress in China-UK Collaboration on the Causal Relationship between Volcanic Activity and Biological Distinction News in Brief: NSFC set up "Research Fund for Young Foreign Scholars" How Often Does Human DNA Mutate? Research Progress on Colossal Anisotropic Magneto Resistive Effect

NASA Astrophysics Data System (ADS)

2009-01-01

Ultra-fast Energy Transfer from Monomer to Dimer within a Trimeric Molecule New Progress in Heterogeneous Catalysis Research Key Progress in Research on Terrestrial Carbon Cycle in China A New Progress in Research on the Mechanism of Bio-Invasion New Findings in Anti-viral infection and Control of Inflammation Major Headway in Avian Origin Research New Progress in Gold-Nanoparticle-Based Biochips Topological Insulator Research Made Important Progress Major Progress in Biodiversity Achieved New Developments of Direct Methods in Protein Crystallography Major Progress in China-UK Collaboration on the Causal Relationship between Volcanic Activity and Biological Distinction News in Brief: NSFC set up "Research Fund for Young Foreign Scholars" How Often Does Human DNA Mutate? Research Progress on Colossal Anisotropic Magneto Resistive Effect

3D microfluidic fabrication using a low refractive index polymer for clear microscopic observation at the fluid boundary

NASA Astrophysics Data System (ADS)

Hanada, Y.

2018-02-01

Microfluidic chips known as μ-TAS or LoC have become versatile tools in cell research, since functional biochips are able to streamline dynamic observations of various cells. Glass or polymers are generally used as the substrate due to their high transparency, chemical stability and cost-effectiveness. However, these materials are not well suited to the microscopic observation at the fluid boundary due to the refractive index mismatch between the medium and the biochip material. For this reason, we have developed a method of fabricating three-dimensional (3D) microfluidic chips made of a low refractive index fluoric polymer CYTOP. CYTOP has a refractive index of 1.34, a value that is almost equivalent to that of water. This optical property is very important for clear 3D microscopic observations of cell motion near the solid boundary, due to the minimal mismatch between the refractive index values of the medium and the CYTOP substrate. Therefore, CYTOP microfluidics are expected to allow the generation of clear images of unique cell migratory processes near the microfluidic sidewall. Therefore, we established the fabrication procedure involving the use of femtosecond laser direct writing, followed by wet etching and annealing, to create high-quality 3D microfluidics inside a polymer substrate. A microfluidic chip made in this manner enables us to more clearly observe areas near the fluid surface, compared to the observations possible using conventional microfluidic chips.

Advanced nano lithography via soft materials-derived and reversible nano-patterning methodology for molding of infrared nano lenses

NASA Astrophysics Data System (ADS)

Park, Jae Hong; Jang, Hyun Ik; Park, Jun Yong; Jeon, Seok Woo; Kim, Woo Choong; Kim, Hee Yeoun; Ahn, Chi Won

2015-03-01

The methodology suggested in this research provides the great possibility of creating nanostructures composed of various materials, such as soft polymer, hard polymer, and metal, as well as Si. Such nanostructures are required for a vast range of optical and display devices, photonic components, physical devices, energy devices including electrodes of secondary batteries, fuel cells, solar cells, and energy harvesters, biological devices including biochips, biomimetic or biosimilar structured devices, and mechanical devices including micro- or nano-scale sensors and actuators.

Electromechanical Coupling Factor of Breast Tissue as a Biomarker for Breast Cancer.

PubMed

Park, Kihan; Chen, Wenjin; Chekmareva, Marina A; Foran, David J; Desai, Jaydev P

2018-01-01

This research aims to validate a new biomarker of breast cancer by introducing electromechanical coupling factor of breast tissue samples as a possible additional indicator of breast cancer. Since collagen fibril exhibits a structural organization that gives rise to a piezoelectric effect, the difference in collagen density between normal and cancerous tissue can be captured by identifying the corresponding electromechanical coupling factor. The design of a portable diagnostic tool and a microelectromechanical systems (MEMS)-based biochip, which is integrated with a piezoresistive sensing layer for measuring the reaction force as well as a microheater for temperature control, is introduced. To verify that electromechanical coupling factor can be used as a biomarker for breast cancer, the piezoelectric model for breast tissue is described with preliminary experimental results on five sets of normal and invasive ductal carcinoma (IDC) samples in the 25-45 temperature range. While the stiffness of breast tissues can be captured as a representative mechanical signature which allows one to discriminate among tissue types especially in the higher strain region, the electromechanical coupling factor shows more distinct differences between the normal and IDC groups over the entire strain region than the mechanical signature. From the two-sample -test, the electromechanical coupling factor under compression shows statistically significant differences ( 0.0039) between the two groups. The increase in collagen density in breast tissue is an objective and reproducible characteristic of breast cancer. Although characterization of mechanical tissue property has been shown to be useful for differentiating cancerous tissue from normal tissue, using a single parameter may not be sufficient for practical usage due to inherent variation among biological samples. The portable breast cancer diagnostic tool reported in this manuscript shows the feasibility of measuring multiple parameters of breast tissue allowing for practical application.

Future of biosensors: a personal view.

PubMed

Scheller, Frieder W; Yarman, Aysu; Bachmann, Till; Hirsch, Thomas; Kubick, Stefan; Renneberg, Reinhard; Schumacher, Soeren; Wollenberger, Ulla; Teller, Carsten; Bier, Frank F

2014-01-01

Biosensors representing the technological counterpart of living senses have found routine application in amperometric enzyme electrodes for decentralized blood glucose measurement, interaction analysis by surface plasmon resonance in drug development, and to some extent DNA chips for expression analysis and enzyme polymorphisms. These technologies have already reached a highly advanced level and need minor improvement at most. The dream of the "100-dollar" personal genome may come true in the next few years provided that the technological hurdles of nanopore technology or of polymerase-based single molecule sequencing can be overcome. Tailor-made recognition elements for biosensors including membrane-bound enzymes and receptors will be prepared by cell-free protein synthesis. As alternatives for biological recognition elements, molecularly imprinted polymers (MIPs) have been created. They have the potential to substitute antibodies in biosensors and biochips for the measurement of low-molecular-weight substances, proteins, viruses, and living cells. They are more stable than proteins and can be produced in large amounts by chemical synthesis. Integration of nanomaterials, especially of graphene, could lead to new miniaturized biosensors with high sensitivity and ultrafast response. In the future individual therapy will include genetic profiling of isoenzymes and polymorphic forms of drug-metabolizing enzymes especially of the cytochrome P450 family. For defining the pharmacokinetics including the clearance of a given genotype enzyme electrodes will be a useful tool. For decentralized online patient control or the integration into everyday "consumables" such as drinking water, foods, hygienic articles, clothing, or for control of air conditioners in buildings and cars and swimming pools, a new generation of "autonomous" biosensors will emerge.

Multifunctional, inexpensive, and reusable nanoparticle-printed biochip for cell manipulation and diagnosis

PubMed Central

Esfandyarpour, Rahim; DiDonato, Matthew J.; Yang, Yuxin; Durmus, Naside Gozde; Harris, James S.; Davis, Ronald W.

2017-01-01

Isolation and characterization of rare cells and molecules from a heterogeneous population is of critical importance in diagnosis of common lethal diseases such as malaria, tuberculosis, HIV, and cancer. For the developing world, point-of-care (POC) diagnostics design must account for limited funds, modest public health infrastructure, and low power availability. To address these challenges, here we integrate microfluidics, electronics, and inkjet printing to build an ultra–low-cost, rapid, and miniaturized lab-on-a-chip (LOC) platform. This platform can perform label-free and rapid single-cell capture, efficient cellular manipulation, rare-cell isolation, selective analytical separation of biological species, sorting, concentration, positioning, enumeration, and characterization. The miniaturized format allows for small sample and reagent volumes. By keeping the electronics separate from microfluidic chips, the former can be reused and device lifetime is extended. Perhaps most notably, the device manufacturing is significantly less expensive, time-consuming, and complex than traditional LOC platforms, requiring only an inkjet printer rather than skilled personnel and clean-room facilities. Production only takes 20 min (vs. up to weeks) and $0.01—an unprecedented cost in clinical diagnostics. The platform works based on intrinsic physical characteristics of biomolecules (e.g., size and polarizability). We demonstrate biomedical applications and verify cell viability in our platform, whose multiplexing and integration of numerous steps and external analyses enhance its application in the clinic, including by nonspecialists. Through its massive cost reduction and usability we anticipate that our platform will enable greater access to diagnostic facilities in developed countries as well as POC diagnostics in resource-poor and developing countries. PMID:28167769

A microfluidic biochip for complete blood cell counts at the point-of-care

PubMed Central

Hassan, U.; Reddy, B.; Damhorst, G.; Sonoiki, O.; Ghonge, T.; Yang, C.; Bashir, R.

2016-01-01

Complete blood cell counts (CBCs) are one of the most commonly ordered and informative blood tests in hospitals. The results from a CBC, which typically include white blood cell (WBC) counts with differentials, red blood cell (RBC) counts, platelet counts and hemoglobin measurements, can have implications for the diagnosis and screening of hundreds of diseases and treatments. Bulky and expensive hematology analyzers are currently used as a gold standard for acquiring CBCs. For nearly all CBCs performed today, the patient must travel to either a hospital with a large laboratory or to a centralized lab testing facility. There is a tremendous need for an automated, portable point-of-care blood cell counter that could yield results in a matter of minutes from a drop of blood without any trained professionals to operate the instrument. We have developed microfluidic biochips capable of a partial CBC using only a drop of whole blood. Total leukocyte and their 3-part differential count are obtained from 10 μL of blood after on-chip lysing of the RBCs and counting of the leukocytes electrically using microfabricated platinum electrodes. For RBCs and platelets, 1 μL of whole blood is diluted with PBS on-chip and the cells are counted electrically. The total time for measurement is under 20 minutes. We demonstrate a high correlation of blood cell counts compared to results acquired with a commercial hematology analyzer. This technology could potentially have tremendous applications in hospitals at the bedside, private clinics, retail clinics and the developing world. PMID:26909365

A microfluidic biochip for complete blood cell counts at the point-of-care.

PubMed

Hassan, U; Reddy, B; Damhorst, G; Sonoiki, O; Ghonge, T; Yang, C; Bashir, R

2015-12-01

Complete blood cell counts (CBCs) are one of the most commonly ordered and informative blood tests in hospitals. The results from a CBC, which typically include white blood cell (WBC) counts with differentials, red blood cell (RBC) counts, platelet counts and hemoglobin measurements, can have implications for the diagnosis and screening of hundreds of diseases and treatments. Bulky and expensive hematology analyzers are currently used as a gold standard for acquiring CBCs. For nearly all CBCs performed today, the patient must travel to either a hospital with a large laboratory or to a centralized lab testing facility. There is a tremendous need for an automated, portable point-of-care blood cell counter that could yield results in a matter of minutes from a drop of blood without any trained professionals to operate the instrument. We have developed microfluidic biochips capable of a partial CBC using only a drop of whole blood. Total leukocyte and their 3-part differential count are obtained from 10 μL of blood after on-chip lysing of the RBCs and counting of the leukocytes electrically using microfabricated platinum electrodes. For RBCs and platelets, 1 μL of whole blood is diluted with PBS on-chip and the cells are counted electrically. The total time for measurement is under 20 minutes. We demonstrate a high correlation of blood cell counts compared to results acquired with a commercial hematology analyzer. This technology could potentially have tremendous applications in hospitals at the bedside, private clinics, retail clinics and the developing world.

An ultra-high-throughput spiral microfluidic biochip for the enrichment of circulating tumor cells.

PubMed

Warkiani, Majid Ebrahimi; Khoo, Bee Luan; Tan, Daniel Shao-Weng; Bhagat, Ali Asgar S; Lim, Wan-Teck; Yap, Yoon Sim; Lee, Soo Chin; Soo, Ross A; Han, Jongyoon; Lim, Chwee Teck

2014-07-07

The detection and characterization of rare circulating tumor cells (CTCs) from the blood of cancer patients can potentially provide critical insights into tumor biology and hold great promise for cancer management. The ability to collect a large number of viable CTCs for various downstream assays such as quantitative measurements of specific biomarkers or targeted somatic mutation analysis is increasingly important in medical oncology. Here, we present a simple yet reliable microfluidic device for the ultra-high-throughput, label-free, size-based isolation of CTCs from clinically relevant blood volumes. The fast processing time of the technique (7.5 mL blood in less than 10 min) and the ability to collect more CTCs from larger blood volumes lends itself to a broad range of potential genomic and transcriptomic applications. A critical advantage of this protocol is the ability to return all fractions of blood (i.e., plasma (centrifugation), CTCs and white blood cells (WBCs) (size-based sorting)) that can be utilized for diverse biomarker studies or time-sensitive molecular assays such as RT-PCR. The clinical use of this biochip was demonstrated by detecting CTCs from 100% (10/10) of blood samples collected from patients with advanced-stage metastatic breast and lung cancers. The CTC recovery rate ranged from 20 to 135 CTCs mL(-1) and obtained under high purity (of 1 CTC out of every 30-100 WBCs which gives ∼4 log depletion of WBCs). They were identified with immunofluorescence assays (pan-cytokeratin+/CD45-) and molecular probes such as HER2/neu.

INTRODUCTION: Wetting and dewetting in bio-related systems

NASA Astrophysics Data System (ADS)

Herminghaus, S.

2005-03-01

Research on such genuinely soft-matter related phenomena as wetting and dewetting would not be complete without reminiscence to biological systems. The recent stir around what has been known as the lotus effect, the amazing ultra-hydrophobic properties of many plants, has highlighted the interconnections of wetting with bio-systems. In the first paper of this section (Mock et al), a `biomimetic' system is conceived which imitates the properties of plant leaves with elastic hairs. The synthesis of such a system turns out to be tricky, but the progress is encouraging. The next three papers deal with surfactant layers, as they occur in many biological systems, such as the plasma membrane. Various experimental techniques, such as fluorescence microscopy (Tanaka et al), neutron reflectivity (Steitz et al), and x-ray scattering (Ahrens et al), are demonstrated as powerful tools for their investigation. The last paper (Heim et al) takes us back to where we started: the morphologies emerging upon dewetting of a liquid. This time, the full diversity of patterns is shown which appears in the deposited solute, once the liquid has evaporated. The motivation of this work is the morphology of deposition of DNA on bio-chips, which may affect the readout results of such devices. It is shown that although much can already be understood, a lot of work has still to be done, and many beautiful mechanisms may still be discovered.

Powerful actuation of magnetized microtools by focused magnetic field for particle sorting in a chip.

PubMed

Yamanishi, Yoko; Sakuma, Shinya; Onda, Kazuhisa; Arai, Fumihito

2010-08-01

This paper describes a novel powerful noncontact actuation of a magnetically driven microtool (MMT), achieved by magnetization of the MMT and focusing of the magnetic field in a microfluidic chip for particle sorting. The following are the highlights of this study: (1) an MMT was successfully fabricated from a mixture of neodymium powder and polydimethylsiloxane; the MMT was magnetized such that it acted as an elastic micromagnet with a magnetic flux density that increased by about 100 times after magnetization, and (2) a pair of sharp magnetic needles was fabricated adjacent to a microchannel in a chip by electroplating, in order to focus the magnetic flux density generated by the electromagnetic coils below the biochip; these needles contribute to miniaturization of an actuation module that would enable the integration of multiple functions in the limited area of a chip. FEM analysis of the magnetic flux density around the MMT showed that the magnetic flux density in the setup with the magnetic needles was around 8 times better than that in the setup without the needles. By magnetization, the drive frequency of the MMT improved by about 10 times--from 18 Hz to 180 Hz. We successfully demonstrated the separation of copolymer beads of a particular size in a chip by image sensing.

Technical Risk Prevention in the Workplace

NASA Astrophysics Data System (ADS)

Ricaud, Myriam

Nanotechnology has become a major economic and technological issue today. Indeed, nanometric dimensions give matter novel physical, chemical, and biological properties with a host of applications. Nanotechnology is thus having an increasing impact on new and emerging industries, such as computing, electronics, aerospace, and alternative energy supplies, but also on traditional forms of industry such as the automobile, aeronautics, food, pharmaceutical, and cosmetics sectors. In this way, nanotechnology has led to both gradual and radical innovation in many areas of industry: biochips, drug delivery, self-cleaning and antipollution concretes, antibacterial clothing, antiscratch paints, and the list continues [1, 2, 3].

MST development for medical applications: results of the German Research Programme on MST over ten years.

PubMed

Weiss, Christine

2007-01-01

Today microsystems are important for the prevention, diagnosis and therapy of diseases. Physicians use small endoscopes for minimally invasive surgery. Patients regain their mobility by high-tech prostheses equipped with several sensors and actuators. Intelligent implants such as pacemakers support existential functions. Cochlea-implants enable deaf persons to hear. Safe convalescence at home is possible by tele-monitoring devices. Point-of-care such as biochips supply quick diagnostic results. A number of these remarkable developments have been successfully supported by the German Federal Ministry of Education and Research (BMBF) since 1990.

Travel-associated infections caused by unusual serogroups of Legionella pneumophila identified using Legionella BIOCHIP slides in Turkey and Iraq.

PubMed

Kocazeybek, Bekir S; Yuksel, Pelin; Keskin, Dilek; Sheikh, Suhail; Habip, Zafer; Yavuzer, Serap Sahin; Caliskan, Reyhan; Altun, Yagız Meric; Kuskucu, Mert; Cengiz, Mahir; Dinc, Harika Oyku; Karakullukcu, Asiye; Ergin, Sevgi; Saribas, Suat; Yilmaz, Nail; Tokman, Hrisi Bahar

2016-01-01

Although Legionella pneumophila serogroup 1 is the common disease causing serogroup, rare serogroups can also may cause legionellosis. A 54-year-old male patient (index case) reported that he had been on a religious trip (for visiting, tomb of Ali, which is important for Shias) to Iraq with a large group (50 shia pilgrims from Kars city of Turkey) two weeks prior to admission. Due to civil war, the hotel where the patient stayed in Iraq lacked proper hygiene. A large number of people in the travel group were experiencing the same symptoms. Other five cases were 2 males (ages; 50, 45) and 3 females including the wife of the index case (ages; 50, 28, 27). The detection of L. pneumophila IgG and IgM was performed by anti-L. pneumophila Indirect Immunofluorescent IgM, IgG kit. Legionella 1 biochip/verification BIOCHIP slides were used for serogrouping in Euroimmun AG, Leubeck, Germany. In index case, L. pneumophila IgM was positive with a titer of 1/32 titer. IgG was negative with a 1/100 titer. Another case (28 year old female), had clinical symptoms identical to the index case. L. pneumophila IgM and IgG were positive with titers of 1/64 and 1/100, respectively. These two cases were diagnosed with Legionnaires' disease caused by L. pneumophila serogroup 12 (index case) and female (28-year-old) by serogroup 11. The other 4 cases were diagnosed with possible Pontiac fever caused by L. pneumophila serogroups 14 (wife of the index case), 4, and 6 whereas the serogroup of L. pneumophila detected in 27 years old female case could not be identified. A major limitation of this work is the absence of genotyping and the serogroup difference between index case and his wife who shared the same hotel. We suggest that this serogroup difference may be caused by (for men and women) sitting separately in Islamic rules. On the other hand, the movement of people in the context of mutual visits between countries or neighboring countries for tourism-related (i.e., for religious events or visits to holy sites) or immigration-related reasons, may cause some epidemic diseases. This study reemphasized that not only L. pneumophila serogroup 1, but other rare serogroups might cause also legionellosis which may increase in frequency and cause regional epidemics. We propose that increased financial resources for improving the hygiene conditions and performing routine legionella surveillance studies in touristic hotels would be useful measures for legionellosis prevention and control. Copyright © 2016 Elsevier Ltd. All rights reserved.

See what you eat--broad GMO screening with microarrays.

PubMed

von Götz, Franz

2010-03-01

Despite the controversy of whether genetically modified organisms (GMOs) are beneficial or harmful for humans, animals, and/or ecosystems, the number of cultivated GMOs is increasing every year. Many countries and federations have implemented safety and surveillance systems for GMOs. Potent testing technologies need to be developed and implemented to monitor the increasing number of GMOs. First, these GMO tests need to be comprehensive, i.e., should detect all, or at least the most important, GMOs on the market. This type of GMO screening requires a high degree of parallel tests or multiplexing. To date, DNA microarrays have the highest number of multiplexing capabilities when nucleic acids are analyzed. This trend article focuses on the evolution of DNA microarrays for GMO testing. Over the last 7 years, combinations of multiplex PCR detection and microarray detection have been developed to qualitatively assess the presence of GMOs. One example is the commercially available DualChip GMO (Eppendorf, Germany; http://www.eppendorf-biochip.com), which is the only GMO screening system successfully validated in a multicenter study. With use of innovative amplification techniques, promising steps have recently been taken to make GMO detection with microarrays quantitative.

The Use of Multi-Walled Carbon Nanotubes as Possible Carrier in Drug Delivery System for Aspirin

NASA Astrophysics Data System (ADS)

Yusof, Alias Mohd.; Buang, Nor Aziah; Yean, Lee Sze; Ibrahim, Mohd. Lokman

2009-06-01

Carbon nanotubes (CNTs) have raised great interest in a number of applications, including field emission, energy storage, molecular electronics, sensors, biochips and drug delivery systems. This is due to their remarkable mechanical properties, chemical stability and biofunctionalizability. This nanomaterial is low in weight, has high strength and a high aspect ratio (long length compared to a small diameter). This paper will present a brief overview of drugs adsorbed onto the surface of carbon nanotubes via sonication method. The surface area of carbon nanotubes was measured by methylene blue method, Carbon nanotubes synthesized by catalytic chemical vapor deposition (CCVD) method were purified and functionalized in a mixture of concentrated acids (H2SO4:HNO3 = 3:1) at room temperature (25° C) via sonication in water bath, yielding carboxylic acid group on the CNTs' surface. CNT was successfully loaded with 48 %(w/w) aspirin molecules by suspending CNTs in a solution of aspirin in alcohol. Analysis of loaded CNTs by Field Emission-Scanning Electron Microscope (FESEM), Fourier Transform Infrared Spectrum (FITR) and UV-visible Spectroscopy confirmed the loading of the drug onto the CNTs. The work presented is a prelude to the direction of using carbon nanotubes as a drug delivery system to desired sites in human body.

Altered proteomic polymorphisms in the caterpillar body and stroma of natural Cordyceps sinensis during maturation.

PubMed

Dong, Yun-Zi; Zhang, Li-Juan; Wu, Zi-Mei; Gao, Ling; Yao, Yi-Sang; Tan, Ning-Zhi; Wu, Jian-Yong; Ni, Luqun; Zhu, Jia-Shi

2014-01-01

To examine the maturational changes in proteomic polymorphisms resulting from differential expression by multiple intrinsic fungi in the caterpillar body and stroma of natural Cordyceps sinensis (Cs), an integrated micro-ecosystem. The surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) biochip technique was used to profile the altered protein compositions in the caterpillar body and stroma of Cs during its maturation. The MS chromatograms were analyzed using density-weighted algorithms to examine the similarities and cluster relationships among the proteomic polymorphisms of the Cs compartments and the mycelial products Hirsutella sinensis (Hs) and Paecilomyces hepiali (Ph). SELDI-TOF MS chromatograms displayed dynamic proteomic polymorphism alterations among samples from the different Cs compartments during maturation. More than 1,900 protein bands were analyzed using density-weighted ZUNIX similarity equations and clustering methods, revealing integral polymorphism similarities of 57.4% between the premature and mature stromata and 42.8% between the premature and mature caterpillar bodies. The across-compartment similarity was low, ranging from 10.0% to 18.4%. Consequently, each Cs compartment (i.e., the stroma and caterpillar body) formed a clustering clade, and the 2 clades formed a Cs cluster. The polymorphic similarities ranged from 0.51% to 1.04% between Hs and the Cs compartments and were 2.8- to 4.8-fold higher (1.92%-4.34%) between Ph and the Cs compartments. The Hs and Ph mycelial samples formed isolated clades outside of the Cs cluster. Proteomic polymorphisms in the caterpillar body and stroma of Cs change dynamically during maturation. The proteomic polymorphisms in Hs and Ph differ from those in Cs, suggesting the presence of multiple Cs-associated fungi and multiple Ophiocordyceps sinensis genotypes with altered differential protein expression in the Cs compartments during maturation. In conjunction with prior mycological and molecular observations, the findings from this proteomic study support the integrated micro-ecosystem hypothesis for natural Cs.

Altered Proteomic Polymorphisms in the Caterpillar Body and Stroma of Natural Cordyceps sinensis during Maturation

PubMed Central

Wu, Zi-Mei; Gao, Ling; Yao, Yi-Sang; Tan, Ning-Zhi; Wu, Jian-Yong; Ni, Luqun; Zhu, Jia-Shi

2014-01-01

Objective To examine the maturational changes in proteomic polymorphisms resulting from differential expression by multiple intrinsic fungi in the caterpillar body and stroma of natural Cordyceps sinensis (Cs), an integrated micro-ecosystem. Methods The surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) biochip technique was used to profile the altered protein compositions in the caterpillar body and stroma of Cs during its maturation. The MS chromatograms were analyzed using density-weighted algorithms to examine the similarities and cluster relationships among the proteomic polymorphisms of the Cs compartments and the mycelial products Hirsutella sinensis (Hs) and Paecilomyces hepiali (Ph). Results: SELDI-TOF MS chromatograms displayed dynamic proteomic polymorphism alterations among samples from the different Cs compartments during maturation. More than 1,900 protein bands were analyzed using density-weighted ZUNIX similarity equations and clustering methods, revealing integral polymorphism similarities of 57.4% between the premature and mature stromata and 42.8% between the premature and mature caterpillar bodies. The across-compartment similarity was low, ranging from 10.0% to 18.4%. Consequently, each Cs compartment (i.e., the stroma and caterpillar body) formed a clustering clade, and the 2 clades formed a Cs cluster. The polymorphic similarities ranged from 0.51% to 1.04% between Hs and the Cs compartments and were 2.8- to 4.8-fold higher (1.92%–4.34%) between Ph and the Cs compartments. The Hs and Ph mycelial samples formed isolated clades outside of the Cs cluster. Conclusion Proteomic polymorphisms in the caterpillar body and stroma of Cs change dynamically during maturation. The proteomic polymorphisms in Hs and Ph differ from those in Cs, suggesting the presence of multiple Cs-associated fungi and multiple Ophiocordyceps sinensis genotypes with altered differential protein expression in the Cs compartments during maturation. In conjunction with prior mycological and molecular observations, the findings from this proteomic study support the integrated micro-ecosystem hypothesis for natural Cs. PMID:25310818

Rapid Microarray Detection of DNA and Proteins in Microliter Volumes with SPR Imaging Measurements

PubMed Central

Seefeld, Ting Hu; Zhou, Wen-Juan; Corn, Robert M.

2011-01-01

A four chamber microfluidic biochip is fabricated for the rapid detection of multiple proteins and nucleic acids from microliter volume samples with the technique of surface plasmon resonance imaging (SPRI). The 18 mm × 18 mm biochip consists of four 3 μL microfluidic chambers attached to an SF10 glass substrate, each of which contains three individually addressable SPRI gold thin film microarray elements. The twelve element (4 × 3) SPRI microarray consists of gold thin film spots (1 mm2 area; 45 nm thickness) each in individually addressable 0.5 μL volume microchannels. Microarrays of single-stranded DNA and RNA (ssDNA and ssRNA respectively) are fabricated by either chemical and/or enzymatic attachment reactions in these microchannels; the SPRI microarrays are then used to detect femtomole amounts (nanomolar concentrations) of DNA and proteins (single stranded DNA binding protein and thrombin via aptamer-protein bioaffinity interactions). Microarrays of ssRNA microarray elements were also used for the ultrasensitive detection of zeptomole amounts (femtomolar concentrations) of DNA via the technique of RNase H-amplified SPRI. Enzymatic removal of ssRNA from the surface due to the hybridization adsorption of target ssDNA is detected as a reflectivity decrease in the SPR imaging measurements. The observed reflectivity loss was proportional to the log of the target ssDNA concentration with a detection limit of 10 fM or 30 zeptomoles (18,000 molecules). This enzymatic amplified ssDNA detection method is not limited by diffusion of ssDNA to the interface, and thus is extremely fast, requiring only 200 seconds in the microliter volume format. PMID:21488682

Electrochemical As(III) whole-cell based biochip sensor.

PubMed

Cortés-Salazar, Fernando; Beggah, Siham; van der Meer, Jan Roelof; Girault, Hubert H

2013-09-15

The development of a whole-cell based sensor for arsenite detection coupling biological engineering and electrochemical techniques is presented. This strategy takes advantage of the natural Escherichia coli resistance mechanism against toxic arsenic species, such as arsenite, which consists of the selective intracellular recognition of arsenite and its pumping out from the cell. A whole-cell based biosensor can be produced by coupling the intracellular recognition of arsenite to the generation of an electrochemical signal. Hereto, E. coli was equipped with a genetic circuit in which synthesis of beta-galactosidase is under control of the arsenite-derepressable arsR-promoter. The E. coli reporter strain was filled in a microchip containing 16 independent electrochemical cells (i.e. two-electrode cell), which was then employed for analysis of tap and groundwater samples. The developed arsenic-sensitive electrochemical biochip is easy to use and outperforms state-of-the-art bacterial bioreporters assays specifically in its simplicity and response time, while keeping a very good limit of detection in tap water, i.e. 0.8ppb. Additionally, a very good linear response in the ranges of concentration tested (0.94ppb to 3.75ppb, R(2)=0.9975 and 3.75 ppb to 30ppb, R(2)=0.9991) was obtained, complying perfectly with the acceptable arsenic concentration limits defined by the World Health Organization for drinking water samples (i.e. 10ppb). Therefore, the proposed assay provides a very good alternative for the portable quantification of As (III) in water as corroborated by the analysis of natural groundwater samples from Swiss mountains, which showed a very good agreement with the results obtained by atomic absorption spectroscopy. Copyright © 2013 Elsevier B.V. All rights reserved.

Cohort analysis of a single nucleotide polymorphism on DNA chips.

PubMed

Schwonbeck, Susanne; Krause-Griep, Andrea; Gajovic-Eichelmann, Nenad; Ehrentreich-Förster, Eva; Meinl, Walter; Glatt, Hansrüdi; Bier, Frank F

2004-11-15

A method has been developed to determine SNPs on DNA chips by applying a flow-through bioscanner. As a practical application we demonstrated the fast and simple SNP analysis of 24 genotypes in an array of 96 spots with a single hybridisation and dissociation experiment. The main advantage of this methodical concept is the parallel and fast analysis without any need of enzymatic digestion. Additionally, the DNA chip format used is appropriate for parallel analysis up to 400 spots. The polymorphism in the gene of the human phenol sulfotransferase SULT1A1 was studied as a model SNP. Biotinylated PCR products containing the SNP (The SNP summary web site: ) (mutant) and those containing no mutation (wild-type) were brought onto the chips coated with NeutrAvidin using non-contact spotting. This was followed by an analysis which was carried out in a flow-through biochip scanner while constantly rinsing with buffer. After removing the non-biotinylated strand a fluorescent probe was hybridised, which is complementary to the wild-type sequence. If this probe binds to a mutant sequence, then one single base is not fully matching. Thereby, the mismatched hybrid (mutant) is less stable than the full-matched hybrid (wild-type). The final step after hybridisation on the chip involves rinsing with a buffer to start dissociation of the fluorescent probe from the immobilised DNA strand. The online measurement of the fluorescence intensity by the biochip scanner provides the possibility to follow the kinetics of the hybridisation and dissociation processes. According to the different stability of the full-match and the mismatch, either visual discrimination or kinetic analysis is possible to distinguish SNP-containing sequence from the wild-type sequence.

Method for printing functional protein microarrays

NASA Technical Reports Server (NTRS)

Delehanty, James B.; Ligler, Frances S.

2003-01-01

Piezoelectric dispensing of proteins from borosilicate glass capillaries is a popular method of protein biochip fabrication that offers the advantages of sample recovery and noncontact with the printing substrate. However, little regard has been given to the quantitative aspects of dispensing minute volumes (1 nL or less) at the low protein concentrations (20 micrograms/mL or less) typically used in microprinting. Specifically, loss of protein sample due to nonspecific adsorption to the glass surface of the dispensing capillaries can limit the amount of protein delivered to the substrate. We demonstrate the benefits of a low ionic strength buffer containing the carrier protein BSA that effectively minimizes the ionic strength-dependent phenomenon of nonspecific protein adsorption to borosilicate glass. Over the concentration range of 20-2.5 micrograms/mL, the dispensing of a reference IgG in 10 mM PBS including 0.1% BSA resulted in the deposition of 3.6- to 44-fold more IgG compared to the deposition of IgG in standard 150 mM PBS in the absence of BSA. Furthermore, when the IgG was dispensed with carrier protein, the resulting spots exhibited a more uniform morphology. In a direct immunoassay for cholera toxin, capture antibody spots dispensed in 10 mM PBS containing 0.1% BSA produced fluorescent signals that were 2.8- to 4.3-fold more intense than antibody spots that were dispensed in 150 mM PBS without BSA. Interestingly, no differences were observed in the specific activities of the capture antibodies as a result of printing in the different buffers. The implications of these results on the future development of protein biochips are discussed.

Microfluidic dissolved oxygen gradient generator biochip as a useful tool in bacterial biofilm studies.

PubMed

Skolimowski, Maciej; Nielsen, Martin Weiss; Emnéus, Jenny; Molin, Søren; Taboryski, Rafael; Sternberg, Claus; Dufva, Martin; Geschke, Oliver

2010-08-21

A microfluidic chip for generation of gradients of dissolved oxygen was designed, fabricated and tested. The novel way of active oxygen depletion through a gas permeable membrane was applied. Numerical simulations for generation of O(2) gradients were correlated with measured oxygen concentrations. The developed microsystem was used to study growth patterns of the bacterium Pseudomonas aeruginosa in medium with different oxygen concentrations. The results showed that attachment of Pseudomonas aeruginosa to the substrate changed with oxygen concentration. This demonstrates that the device can be used for studies requiring controlled oxygen levels and for future studies of microaerobic and anaerobic conditions.

Novel wafer stepper with violet LED light source

NASA Astrophysics Data System (ADS)

Ting, Yung-Chiang; Shy, Shyi-Long

2014-03-01

Novel wafer stepper by using contact or proximity printing will be developed, using violet LED light source to replace Hg Arc. lamp or laser. Mirror, filter and condenser lens for Hg Arc. Lamp or laser and reduction lens for projection printing can be discarded. Reliability and manufacturing cost of wafer stepper can be improved. Exposure result by using IP3600 resist and wafer stepper with violet LED light source (wave-length 360nm to 410 nm) will be obtained. This novel wafer stepper can be used for 3DIC, MEMS and bio-chip lithography application by using thin and thick resist with sub-micron to 100 micron thickness.

A fluorescent immunoassay for the determination of procalcitonin and C-reactive protein

NASA Astrophysics Data System (ADS)

Baldini, F.; Bolzoni, L.; Giannetti, A.; Porro, G.; Senesi, F.; Trono, C.

2009-05-01

The discrimination of viral and bacterial sepsis is an important issue in intensive care patients. For this purpose, the simultaneous measurements of different analytes such as C-reactive protein (CRP), procalcitonin (PCT), myeloperoxidase, interleukines and neopterin, are necessary. A novel optical platform was designed and realised for the implementation of fluorescence-based immunoassays. The core of the optical platform is a plastic biochip, formed by a series of microchannels each of them devoted to the determination of a single analyte. Sandwich assays for CRP and PCT spiked in serum were performed in order to demonstrate the reliability of a multi-array device.

Complementary and partially complementary DNA duplexes tethered to a functionalized substrate: a molecular dynamics approach to biosensing.

PubMed

Monti, Susanna; Cacelli, Ivo; Ferretti, Alessandro; Prampolini, Giacomo; Barone, Vincenzo

2011-07-21

Molecular dynamics simulations (90 ns) of different DNA complexes attached to a functionalized substrate in solution were performed in order to clarify the behavior of mismatched DNA sequences captured by a tethered DNA probe (biochip). Examination of the trajectories revealed that the substrate influence and a series of cooperative events, including recognition, reorientation and reorganization of the bases, could induce the formation of stable duplexes having non-canonical arrangements. Major adjustment of the structures was observed when the mutated base was located in the end region of the chain close to the surface. This journal is © the Owner Societies 2011

Efficient Fluorescence Resonance Energy Transfer between Quantum Dots and Gold Nanoparticles Based on Porous Silicon Photonic Crystal for DNA Detection.

PubMed

Zhang, Hongyan; Lv, Jie; Jia, Zhenhong

2017-05-10

A novel assembled biosensor was prepared for detecting 16S rRNA, a small-size persistent specific for Actinobacteria. The mechanism of the porous silicon (PS) photonic crystal biosensor is based on the fluorescence resonance energy transfer (FRET) between quantum dots (QDs) and gold nanoparticles (AuNPs) through DNA hybridization, where QDs act as an emission donor and AuNPs serve as a fluorescence quencher. Results showed that the photoluminescence (PL) intensity of PS photonic crystal was drastically increased when the QDs-conjugated probe DNA was adhered to the PS layer by surface modification using a standard cross-link chemistry method. The PL intensity of QDs was decreased when the addition of AuNPs-conjugated complementary 16S rRNA was dropped onto QDs-conjugated PS. Based on the analysis of different target DNA concentration, it was found that the decrease of the PL intensity showed a good linear relationship with complementary DNA concentration in a range from 0.25 to 10 μM, and the detection limit was 328.7 nM. Such an optical FRET biosensor functions on PS-based photonic crystal for DNA detection that differs from the traditional FRET, which is used only in liquid. This method will benefit the development of a new optical FRET label-free biosensor on Si substrate and has great potential in biochips based on integrated optical devices.

Enhanced biofilm distribution and cell performance of microfluidic microbial fuel cells with multiple anolyte inlets.

PubMed

Yang, Yang; Ye, Dingding; Liao, Qiang; Zhang, Pengqing; Zhu, Xun; Li, Jun; Fu, Qian

2016-05-15

A laminar-flow controlled microfluidic microbial fuel cell (MMFC) is considered as a promising approach to be a bio-electrochemical system (BES). But poor bacterial colonization and low power generation are two severe bottlenecks to restrict its development. In this study, we reported a MMFC with multiple anolyte inlets (MMFC-MI) to enhance the biofilm formation and promote the power density of MMFCs. Voltage profiles during the inoculation process demonstrated MMFC-MI had a faster start-up process than the conventional microfluidic microbial fuel cell with one inlet (MMFC-OI). Meanwhile, benefited from the periodical replenishment of boundary layer near the electrode, a more densely-packed bacterial aggregation was observed along the flow direction and also the substantially low internal resistance for MMFC-MI. Most importantly, the output power density of MMFC-MI was the highest value among the reported µl-scale MFCs to our best knowledge. The presented MMFC-MI appears promising for bio-chip technology and extends the scope of microfluidic energy. Copyright © 2015 Elsevier B.V. All rights reserved.

A method to restrain the charging effect on an insulating substrate in high energy electron beam lithography

NASA Astrophysics Data System (ADS)

Mingyan, Yu; Shirui, Zhao; Yupeng, Jing; Yunbo, Shi; Baoqin, Chen

2014-12-01

Pattern distortions caused by the charging effect should be reduced while using the electron beam lithography process on an insulating substrate. We have developed a novel process by using the SX AR-PC 5000/90.1 solution as a spin-coated conductive layer, to help to fabricate nanoscale patterns of poly-methyl-methacrylate polymer resist on glass for phased array device application. This method can restrain the influence of the charging effect on the insulating substrate effectively. Experimental results show that the novel process can solve the problems of the distortion of resist patterns and electron beam main field stitching error, thus ensuring the accuracy of the stitching and overlay of the electron beam lithography system. The main characteristic of the novel process is that it is compatible to the multi-layer semiconductor process inside a clean room, and is a green process, quite simple, fast, and low cost. It can also provide a broad scope in the device development on insulating the substrate, such as high density biochips, flexible electronics and liquid crystal display screens.

A novel effective micromixer having horizontal and vertical weaving flow motion

NASA Astrophysics Data System (ADS)

Yoo, Won-Sul; Go, Jung Sang; Park, Seonghun; Park, Sang-Hu

2012-03-01

The need for small-scale product-related biotechnology (BT) is rapidly increasing. An important product among these is high-performance biochips. In these devices, many microchannels are used for separation, filtering and mixing of various materials; therefore, for compactness, these reactions should be carried out in the small space of microfluidic systems. However, there is no turbulence that can induce materials to be mixed or reacted in the microchannel, especially with low Reynolds number laminar flow. Hence, it is difficult to sufficiently mix different materials. To address this problem, we propose the HVW (horizontal and vertical weaving) micromixer having crossed barriers inside of a microchannel, for effective mixing and reacting different materials. From CFD analysis, we have evaluated the mixing mechanism and efficiency of the HVW mixer. In this work, it is shown that the HVW mixer has the maximum mixing efficiency of 89.9% with a short mixing distance of 450 µm at a Reynolds number of 5 with the barrier angle of 30°, when water and water combined with Rhodamine B figment were used as fluids.

3D Microfabrication Using Emulsion Mask Grayscale Photolithography Technique

NASA Astrophysics Data System (ADS)

Lee, Tze Pin; Mohamed, Khairudin

2016-02-01

Recently, the rapid development of technology such as biochips, microfluidic, micro-optical devices and micro-electromechanical-systems (MEMS) demands the capability to create complex design of three-dimensional (3D) microstructures. In order to create 3D microstructures, the traditional photolithography process often requires multiple photomasks to form 3D pattern from several stacked photoresist layers. This fabrication method is extremely time consuming, low throughput, costly and complicated to conduct for high volume manufacturing scale. On the other hand, next generation lithography such as electron beam lithography (EBL), focused ion beam lithography (FIB) and extreme ultraviolet lithography (EUV) are however too costly and the machines require expertise to setup. Therefore, the purpose of this study is to develop a simplified method in producing 3D microstructures using single grayscale emulsion mask technique. By using this grayscale fabrication method, microstructures of thickness as high as 500μm and as low as 20μm are obtained in a single photolithography exposure. Finally, the fabrication of 3D microfluidic channel has been demonstrated by using this grayscale photolithographic technique.

The Role of Paracrine and Autocrine Signaling in the Early Phase of Adipogenic Differentiation of Adipose-derived Stem Cells

PubMed Central

Hemmingsen, Mette; Vedel, Søren; Skafte-Pedersen, Peder; Sabourin, David; Collas, Philippe; Bruus, Henrik; Dufva, Martin

2013-01-01

Introduction High cell density is known to enhance adipogenic differentiation of mesenchymal stem cells, suggesting secretion of signaling factors or cell-contact-mediated signaling. By employing microfluidic biochip technology, we have been able to separate these two processes and study the secretion pathways. Methods and results Adipogenic differentiation of human adipose-derived stem cells (ASCs) cultured in a microfluidic system was investigated under perfusion conditions with an adipogenic medium or an adipogenic medium supplemented with supernatant from differentiating ASCs (conditioned medium). Conditioned medium increased adipogenic differentiation compared to adipogenic medium with respect to accumulation of lipid-filled vacuoles and gene expression of key adipogenic markers (C/EBPα, C/EBPβ, C/EBPδ, PPARγ, LPL and adiponectin). The positive effects of conditioned medium were observed early in the differentiation process. Conclusions Using different cell densities and microfluidic perfusion cell cultures to suppress the effects of cell-released factors, we have demonstrated the significant role played by auto- or paracrine signaling in adipocyte differentiation. The cell-released factor(s) were shown to act in the recruitment phase of the differentiation process. PMID:23723991

Application of nanostructured biochips for efficient cell transfection microarrays

NASA Astrophysics Data System (ADS)

Akkamsetty, Yamini; Hook, Andrew L.; Thissen, Helmut; Hayes, Jason P.; Voelcker, Nicolas H.

2007-01-01

Microarrays, high-throughput devices for genomic analysis, can be further improved by developing materials that are able to manipulate the interfacial behaviour of biomolecules. This is achieved both spatially and temporally by smart materials possessing both switchable and patterned surface properties. A system had been developed to spatially manipulate both DNA and cell growth based upon the surface modification of highly doped silicon by plasma polymerisation and polyethylene grafting followed by masked laser ablation for formation of a pattered surface with both bioactive and non-fouling regions. This platform has been successfully applied to transfected cell microarray applications with the parallel expression of genes by utilising its ability to direct and limit both DNA and cell attachment to specific sites. One of the greatest advantages of this system is its application to reverse transfection, whereupon by utilising the switchable adsorption and desorption of DNA using a voltage bias, the efficiency of cell transfection can be enhanced. However, it was shown that application of a voltage also reduces the viability of neuroblastoma cells grown on a plasma polymer surface, but not human embryonic kidney cells. This suggests that the application of a voltage may not only result in the desorption of bound DNA but may also affect attached cells. The characterisation of a DNA microarray by contact printing has also been investigated.

Giant magnetoresistive biosensors for molecular diagnosis: surface chemistry and assay development

NASA Astrophysics Data System (ADS)

Yu, Heng; Osterfeld, Sebastian J.; Xu, Liang; White, Robert L.; Pourmand, Nader; Wang, Shan X.

2008-08-01

Giant magnetoresistive (GMR) biochips using magnetic nanoparticle as labels were developed for molecular diagnosis. The sensor arrays consist of GMR sensing strips of 1.5 μm or 0.75 μm in width. GMR sensors are exquisitely sensitive yet very delicate, requiring ultrathin corrosion-resistive passivation and efficient surface chemistry for oligonucleotide probe immobilization. A mild and stable surface chemistry was first developed that is especially suitable for modifying delicate electronic device surfaces, and a practical application of our GMR biosensors was then demonstrated for detecting four most common human papillomavirus (HPV) subtypes in plasmids. We also showed that the DNA hybridization time could potentially be reduced from overnight to about ten minutes using microfluidics.

The significance of amperometric detection of alkaline phosphatase in colorectal cancer diagnostics

NASA Astrophysics Data System (ADS)

Belkin, Anton; Freynd, Genrietta; Katsnelson, Mikhail

2016-08-01

Colorectal cancer (CRC) is one of the most common cancers in the world; it takes the second place in oncological morbidity. The ALP activity of intestinal epithelial differentiation marker (ALP) was investigated in surgical material and colon biopsies of 47 patients with the electrochemical method using biosensors (biochips). The average current obtained in the studies of colorectal cancer tissues was lower than in the studies of intact colon mucosa. Histology of tumors matched the differentiation types/stages of adenocarcinomas. The study of ALP activity in the surgical material and biopsies of colon tumors can become one of the most useful methods for evaluating the functional atypia in tumor tissue.

AC electric field induced dipole-based on-chip 3D cell rotation.

PubMed

Benhal, Prateek; Chase, J Geoffrey; Gaynor, Paul; Oback, Björn; Wang, Wenhui

2014-08-07

The precise rotation of suspended cells is one of the many fundamental manipulations used in a wide range of biotechnological applications such as cell injection and enucleation in nuclear transfer (NT) cloning. Noticeably scarce among the existing rotation techniques is the three-dimensional (3D) rotation of cells on a single chip. Here we present an alternating current (ac) induced electric field-based biochip platform, which has an open-top sub-mm square chamber enclosed by four sidewall electrodes and two bottom electrodes, to achieve rotation about the two axes, thus 3D cell rotation. By applying an ac potential to the four sidewall electrodes, an in-plane (yaw) rotating electric field is generated and in-plane rotation is achieved. Similarly, by applying an ac potential to two opposite sidewall electrodes and the two bottom electrodes, an out-of-plane (pitch) rotating electric field is generated and rolling rotation is achieved. As a prompt proof-of-concept, bottom electrodes were constructed with transparent indium tin oxide (ITO) using the standard lift-off process and the sidewall electrodes were constructed using a low-cost micro-milling process and then assembled to form the chip. Through experiments, we demonstrate rotation of bovine oocytes of ~120 μm diameter about two axes, with the capability of controlling the rotation direction and the rate for each axis through control of the ac potential amplitude, frequency, and phase shift, and cell medium conductivity. The maximum observed rotation rate reached nearly 140° s⁻¹, while a consistent rotation rate reached up to 40° s⁻¹. Rotation rate spectra for zona pellucida-intact and zona pellucida-free oocytes were further compared and found to have no effective difference. This simple, transparent, cheap-to-manufacture, and open-top platform allows additional functional modules to be integrated to become a more powerful cell manipulation system.

Direct inhibition of excision/synthesis DNA repair activities by cadmium: analysis on dedicated biochips.

PubMed

Candéias, S; Pons, B; Viau, M; Caillat, S; Sauvaigo, S

2010-12-10

The well established toxicity of cadmium and cadmium compounds results from their additive effects on several key cellular processes, including DNA repair. Mammalian cells have evolved several biochemical pathways to repair DNA lesions and maintain genomic integrity. By interfering with the homeostasis of redox metals and antioxidant systems, cadmium promotes the development of an intracellular environment that results in oxidative DNA damage which can be mutagenic if unrepaired. Small base lesions are recognised by specialized glycosylases and excised from the DNA molecule. The resulting abasic sites are incised, and the correct sequences restored by DNA polymerases using the opposite strands as template. Bulky lesions are recognised by a different set of proteins and excised from DNA as part of an oligonucleotide. As in base repair, the resulting gaps are filled by DNA polymerases using the opposite strands as template. Thus, these two repair pathways consist in excision of the lesion followed by DNA synthesis. In this study, we analysed in vitro the direct effects of cadmium exposure on the functionality of base and nucleotide DNA repair pathways. To this end, we used recently described dedicated microarrays that allow the parallel monitoring in cell extracts of the repair activities directed against several model base and/or nucleotide lesions. Both base and nucleotide excision/repair pathways are inhibited by CdCl₂, with different sensitivities. The inhibitory effects of cadmium affect mainly the recognition and excision stages of these processes. Furthermore, our data indicate that the repair activities directed against different damaged bases also exhibit distinct sensitivities, and the direct comparison of cadmium effects on the excision of uracile in different sequences even allows us to propose a hierarchy of cadmium sensibility within the glycosylases removing U from DNA. These results indicate that, in our experimental conditions, cadmium is a very potent DNA repair poison. Copyright © 2010 Elsevier B.V. All rights reserved.

Validation of the Only Commercially Available Immunoassay for Synthetic Cathinones in Urine: Randox Drugs of Abuse V Biochip Array Technology

PubMed Central

Ellefsen, Kayla N.; Anizan, Sébastien; Castaneto, Marisol S.; Desrosiers, Nathalie A.; Martin, LTC Thomas M.; Klette, CAPT Kevin L.; Huestis, Marilyn A.

2014-01-01

Deterrence of synthetic cathinone abuse is hampered by the lack of a high-throughput immunoassay screen. The Randox Drugs of Abuse V biochip immunoassay (DOA-V) contains two synthetic cathinones antibodies: Bath Salt I (BSI) targets mephedrone/methcathinone and Bath Salt II (BSII) targets 3’,4’-methylenedioxypyrovalerone (MDPV)/3’,4’-methylenedioxy-α-pyrrolidinobutiophenone (MDPBP). We evaluated DOA-V synthetic cathinones performance and conducted a full validation on the original assay with calibrators reconstituted in water, and the new assay with calibrators prepared in lyophilized urine; both utilized the same antibodies and were run on the fully automated Evidence® Analyzer. 20,017 authentic military urine specimens were screened and confirmed by LC-MS/MS for 28 synthetic cathinones. Limits of detection (LOD) for the original and new assays were 0.35 and 0.18 (BSI), and 8.5 and 9.2µg/L (BSII), respectively. Linearity was acceptable (R2>0.98); however, a large negative bias was observed with in-house prepared calibrators. Intra-assay imprecision was <20% BSI-II, while inter-assay imprecision was 18–42% BSI and <22% BSII. Precision was acceptable for Randox controls. Cross-reactivities of many additional synthetic cathinones were determined. Authentic drug-free negative urine pH <4 produced false positive results for BSI (6.3µg/L) and BSII (473µg/L). Oxidizing agents reduced BSI and increased BSII results. Sensitivity, specificity, and efficiency of 100%, 52.1%, and 53.0% were obtained at manufacturer’s proposed cutoffs (BSI 5µg/L, BSII 30µg/L). Performance improved if cutoff concentrations increased (BSI 7.5µg/L, BSII 40µg/L); however, there were limited confirmed positive specimens. Currently, this is the first and only fully validated immunoassay for preliminary detection of synthetic cathinones in urine. PMID:24659527

Efficient Fluorescence Resonance Energy Transfer between Quantum Dots and Gold Nanoparticles Based on Porous Silicon Photonic Crystal for DNA Detection

PubMed Central

Zhang, Hongyan; Lv, Jie; Jia, Zhenhong

2017-01-01

A novel assembled biosensor was prepared for detecting 16S rRNA, a small-size persistent specific for Actinobacteria. The mechanism of the porous silicon (PS) photonic crystal biosensor is based on the fluorescence resonance energy transfer (FRET) between quantum dots (QDs) and gold nanoparticles (AuNPs) through DNA hybridization, where QDs act as an emission donor and AuNPs serve as a fluorescence quencher. Results showed that the photoluminescence (PL) intensity of PS photonic crystal was drastically increased when the QDs-conjugated probe DNA was adhered to the PS layer by surface modification using a standard cross-link chemistry method. The PL intensity of QDs was decreased when the addition of AuNPs-conjugated complementary 16S rRNA was dropped onto QDs-conjugated PS. Based on the analysis of different target DNA concentration, it was found that the decrease of the PL intensity showed a good linear relationship with complementary DNA concentration in a range from 0.25 to 10 μM, and the detection limit was 328.7 nM. Such an optical FRET biosensor functions on PS-based photonic crystal for DNA detection that differs from the traditional FRET, which is used only in liquid. This method will benefit the development of a new optical FRET label-free biosensor on Si substrate and has great potential in biochips based on integrated optical devices. PMID:28489033

Single molecule fluorescence microscopy for ultra-sensitive RNA expression profiling

NASA Astrophysics Data System (ADS)

Hesse, Jan; Jacak, Jaroslaw; Regl, Gerhard; Eichberger, Thomas; Aberger, Fritz; Schlapak, Robert; Howorka, Stefan; Muresan, Leila; Frischauf, Anna-Maria; Schütz, Gerhard J.

2007-02-01

We developed a microarray analysis platform for ultra-sensitive RNA expression profiling of minute samples. It utilizes a novel scanning system for single molecule fluorescence detection on cm2 size samples in combination with specialized biochips, optimized for low autofluorescence and weak unspecific adsorption. 20 μg total RNA was extracted from 10 6 cells of a human keratinocyte cell line (HaCaT) and reversely transcribed in the presence of Alexa647-aha-dUTP. 1% of the resulting labeled cDNA was used for complex hybridization to a custom-made oligonucleotide microarray representing a set of 125 different genes. For low abundant genes, individual cDNA molecules hybridized to the microarray spots could be resolved. Single cDNA molecules hybridized to the chip surface appeared as diffraction limited features in the fluorescence images. The à trous wavelet method was utilized for localization and counting of the separated cDNA signals. Subsequently, the degree of labeling of the localized cDNA molecules was determined by brightness analysis for the different genes. Variations by factors up to 6 were found, which in conventional microarray analysis would result in a misrepresentation of the relative abundance of mRNAs.

A Portable and Autonomous Magnetic Detection Platform for Biosensing

PubMed Central

Germano, José; Martins, Verónica C.; Cardoso, Filipe A.; Almeida, Teresa M.; Sousa, Leonel; Freitas, Paulo P.; Piedade, Moisés S.

2009-01-01

This paper presents a prototype of a platform for biomolecular recognition detection. The system is based on a magnetoresistive biochip that performs biorecognition assays by detecting magnetically tagged targets. All the electronic circuitry for addressing, driving and reading out signals from spin-valve or magnetic tunnel junctions sensors is implemented using off-the-shelf components. Taking advantage of digital signal processing techniques, the acquired signals are processed in real time and transmitted to a digital analyzer that enables the user to control and follow the experiment through a graphical user interface. The developed platform is portable and capable of operating autonomously for nearly eight hours. Experimental results show that the noise level of the described platform is one order of magnitude lower than the one presented by the previously used measurement set-up. Experimental results also show that this device is able to detect magnetic nanoparticles with a diameter of 250 nm at a concentration of about 40 fM. Finally, the biomolecular recognition detection capabilities of the platform are demonstrated by performing a hybridization assay using complementary and non-complementary probes and a magnetically tagged 20mer single stranded DNA target. PMID:22408516

Simultaneous detection of multiple lower genital tract pathogens by an impedimetric immunochip.

PubMed

Chiriacò, Maria Serena; Primiceri, Elisabetta; De Feo, Francesco; Montanaro, Alessandro; Monteduro, Anna Grazia; Tinelli, Andrea; Megha, Marcella; Carati, Davide; Maruccio, Giuseppe

2016-05-15

Lower genital tract infections caused by both sexually and not-sexually transmitted pathogens in women are a key public health priority worldwide, especially in developing countries. Since standard analyses are time-consuming, appropriate therapeutic intervention is often neglected or delayed. Lab-on-chips and biosensors open new perspectives and offer innovative tools to simplify the diagnosis by medical staff, especially in countries with inadequate resources. Here we report a biosensing platform based on Electrochemical Impedance Spectroscopy (EIS) that allows multiplexed detection of Candida albicans, Streptococcus agalactiae and Chlamydia trachomatis with a single biochip, enabling a quick screening thanks to the presence of different immobilized antibodies, each specific for one of the different target pathogens. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of bacteriophage-based bioluminescent bioreporters for monitoring of microbial pathogens

NASA Astrophysics Data System (ADS)

Ozen, Aysu; Montgomery, Kacey; Jegier, Pat; Patterson, Stacey; Daumer, Kathleen A.; Ripp, Steven A.; Garland, Jay L.; Sayler, Gary S.

2004-03-01

Microorganisms pose numerous problems when present in human occupied enclosed environments. Primary among these are health related hazards, manifested as infectious diseases related to contaminated drinking water, food, or air circulation systems or non-infectious allergy related complications associated with microbial metabolites (sick building syndrome). As a means towards rapid detection of microbial pathogens, we are attempting to harness the specificity of bacterial phage for their host with a modified quorum sensing amplification signal to produce quantifiable bioluminescent (lux) detection on a silicon microluminometer. The bacteriophage itself is metabolically inactive, only achieving replicative capabilities upon infection of its specific host bacterium. Bacteriophage bioluminescent bioreporters contain a genomically inserted luxI component. During an infection event, the phage genes and accompanying luxI construct are taken up by the host bacterium and transcribed, resulting in luxI expression and subsequent activation of a homoserine lactone inducible bioluminescent bioreporter. We constructed a vector carrying the luxI gene under the control of a strong E. coli promoter and cloned it into E. coli. We have shown that it can induce luminescence up to 14,000 counts per second when combined with the bioreporter strain. In their final embodiment, these sensors will be fully independent microelectronic monitors for microbial contamination, requiring only exposure of the biochip to the sample, with on-chip signal processing downloaded directly to the local area network of the environmental control system.

Polymer-based wireless implantable sensor and platform for systems biology study

NASA Astrophysics Data System (ADS)

Xue, Ning

Wireless implantable MEMS (microelectromechanical systems) devices have been developed over the past decade based on the combination of bio-MEMS and Radio frequency (RF) MEMS technology. These devices require the components of wireless telemetric antenna and the corresponding circuit. In the meanwhile, biocompatible material needs to be involved in the devices design. To supply maximum power upon the implantable device at given power supply from the external coil circuit, this dissertation theoretically analyzed the mutual inductance under the positions of variety of vertical distances, lateral displacements and angular misalignments between two coils in certain surgical coils misalignment situations. A planar spiral coil has been developed as the receiver coil of the coupling system. To get maximum induced voltage over the receiver circuit, different geometries of the power coil, system operation frequencies were investigated. An intraocular pressure (IOP) sensor has been developed consisting of only biocompatible matierials-SU-8 and gold. Its size is sufficiently small to be implanted in the eye. The measurement results showed that it has relatively linear pressure response, high resolution and relatively long working stability in saline environment. Finally, a simple and low cost micro-wells bio-chip has been developed with sole polydimethylsiloxane (PDMS) to be used for single cell or small group cells isolation. By performing atomic force microscopy (AFM), contact angle and x-ray photoelectron spectroscopy (XPS) measurements on the PDMS surfaces under various surface treatment conditions, the physical and chemical surface natures were thoroughly analyzed as the basis of study of cells attachment and isolation to the surfaces.

Design and application of fiber optic evanescent wave biosensor

NASA Astrophysics Data System (ADS)

Huang, Huijie; Zhai, Junhui; Zhao, Yongkai; Yang, Ruifu; Ren, Bingqiang; Cheng, Zhaogu; Du, Longlong; Lu, Dunwu

2003-12-01

A fiber-optic biosensor is developed based on the principle of evanescent wave while light propagates in optical fiber. The biosensor uses a red laser diode at 636.85 nm for exciting Cy5 fluorescent dye. Sensitivity limit of 0.01 nnmol/l is obtained from the detection of serial Cy5 solutions with various concentrations. In log-to-log plot, excellent linear response characteristic is seen in the Cy5 concentrations ranging from 0.01 nmlo/l to 100 nmol/l. And a good result of signal-to-noise ratio of 4.61 is obtained when the biosensor is used to measure Legionella pneumophila solution of 0.01 μmol/l. All the results are comparable with those that are obtained by a commercial biochip scanner GeneTAC 1000.

Brilliant molecular nanocrystals emerging from sol-gel thin films: towards a new generation of fluorescent biochips.

PubMed

Dubuisson, E; Monnier, V; Sanz-Menez, N; Boury, B; Usson, Y; Pansu, R B; Ibanez, A

2009-08-05

To develop highly sensitive biosensors, we made directly available to biological aqueous solutions organic nanocrystals previously grown in the pores of sol-gel films. Through the controlled dissolution of the sol-gel surface, we obtained emerging nanocrystals that remained strongly anchored to the sol-gel coating for good mechanical stability of the final sensing device. We demonstrated that in the presence of a solution of DNA functionalized with a molecular probe, the nanocrystal fluorescence is strongly quenched by Förster resonance energy transfer thus opening the way towards very sensitive fluorescent biosensors through biomolecules grafted onto fluorescent nanocrystals. Finally, this controlled dissolution, involving weak concentrated NaOH solution, is a generic process that can be used for the thinning of any kind of sol-gel layer.

Are biochips the new wave

NASA Astrophysics Data System (ADS)

Bussert, J.

1982-06-01

The possibility of microchip synthesis from molecular configurations is considered. A bistable memory element concept is described which can be independently written on and read, and which consists of a chain of transition metal atoms, a bulging ligand connecting the transition metal atoms, and two types of ligand attached to the transition metal atoms. The molecular emulation of switches, memory and interfaces is presently being investigated independently, although simultaneous synthesis of entire architectures is the ultimate goal of research. Molecular circuitry, which could incorporate 10,000 more gates into an IC chip than chemical techniques, would be of greatest immediate importance in avionics and other portable military electronics devices for which minimum size and weight are valuable. Attention is given to a computer-controlled method for the synthesis of molecular computers.

DNA hybridization detection on electrical microarrays using coulostatic pulse technique.

PubMed

Dharuman, V; Nebling, E; Grunwald, T; Albers, J; Blohm, L; Elsholz, B; Wörl, R; Hintsche, R

2006-12-15

We demonstrated a novel application of transient coulostatic pulse technique for the detection of label free DNA hybridization on nm-sized gold interdigitated ultramicroelectrode arrays (Au-IDA) made in silicon technology. The array consists of eight different positions with an Au-IDA pair at each position arranged on the Si-based Biochip. Immobilization of capture probes onto the Au-IDA was accomplished by self-assembling of thiol-modified oligonucleotides. Target hybridization was indicated by a change in the magnitude of the time dependant potential relaxation curve in presence of electroactive Fe(CN)(6)(3-) in the phosphate buffer solution. While complementary DNA hybridization showed 50% increase in the relaxation potential, the non-complementary DNA showed a negligible change. A constant behaviour was noted for all positions. The dsDNA specific intercalating molecule, methylene blue, was found to be enhancing the discrimination effect. The changes in the relaxation potential curves were further corroborated following the ELISA like experiments using ExtraAvidine alkaline phosphatase labelling and redox recycling of para-aminophenol phosphate at IDAs. The coulostatic pulse technique was shown to be useful for identifying DNA sequences from brain tumour gene CK20, human herpes simplex virus, cytomegalovirus, Epstein-Barr virus and M13 phage. Compared to the hybridization of short chain ONTs (27 mers), the hybridization of long chain M13 phage DNA showed three times higher increase in the relaxation curves. The method is fast enough to monitor hybridization interactions in milli or microsecond time scales and is well suitable for miniaturization and integration compared to the common impedance techniques for developing capacitative DNA sensors.

Versatile label free biochip for the detection of circulating tumor cells from peripheral blood in cancer patients.

PubMed

Tan, Swee Jin; Lakshmi, Rumkumar Lalitha; Chen, Pengfei; Lim, Wan-Teck; Yobas, Levent; Lim, Chwee Teck

2010-12-15

The isolation of circulating tumor cells (CTCs) using microfluidics is attractive as the flow conditions can be accurately manipulated to achieve an efficient separation. CTCs are rare events within the peripheral blood of metastatic cancer patients which makes them hard to detect. The presence of CTCs is likely to indicate the severity of the disease and increasing evidences show its use for prognostic and treatment monitoring purposes. We demonstrated an effective separation using a microfluidic device to utilize the unique differences in size and deformability of cancer cells to blood cells. Using physical structures placed in the path of blood specimens in a microchannel, CTCs which are generally larger and stiffer are retained while most blood constituents are removed. The placements of the structures are optimized by computational analysis to enhance the isolation efficiency. With blood specimens from metastatic lung cancer patients, we confirmed the successful detection of CTCs. The operations for processing blood are straightforward and permit multiplexing of the microdevices to concurrently work with different samples. The microfluidic device is optically transparent which makes it simple to be integrated to existing laboratory microscopes and immunofluorescence staining can be done in situ to distinguish cancer cells from hematopoietic cells. This also minimizes the use of expensive staining reagents, given the small size of the microdevice. Identification of CTCs will aid in the detection of malignancy and disease stage as well as understanding the phenotypic and genotypic expressions of cancer cells. Copyright © 2010 Elsevier B.V. All rights reserved.

Study on the SPR responses of various DNA probe concentrations by parallel scan spectral SPR imaging

NASA Astrophysics Data System (ADS)

Ma, Suihua; Liu, Le; Lu, Weiping; Zhang, Yaou; He, Yonghong; Guo, Jihua

2008-12-01

SPR sensors have become a high sensitive and label free method for characterizing and quantifying chemical and biochemical interactions. However, the relations between the SPR refractive index response and the property (such as concentrations) of biochemical probes are still lacking. In this paper, an experimental study on the SPR responses of varies concentrations of Legionella pneumophila mip DNA probes is presented. We developed a novel two-dimensional SPR sensing technique-parallel scan spectral SPR imaging-to detect an array of mip gene probes. This technique offers quantitative refractive index information with a high sensing throughput. By detecting mip DNA probes with different concentrations, we obtained the relations between the SPR refractive index response and the concentrations of mip DNA probes. These results are valuable for design and developing SPR based mip gene biochips.

A force-based protein biochip

NASA Astrophysics Data System (ADS)

Blank, K.; Mai, T.; Gilbert, I.; Schiffmann, S.; Rankl, J.; Zivin, R.; Tackney, C.; Nicolaus, T.; Spinnler, K.; Oesterhelt, F.; Benoit, M.; Clausen-Schaumann, H.; Gaub, H. E.

2003-09-01

A parallel assay for the quantification of single-molecule binding forces was developed based on differential unbinding force measurements where ligand-receptor interactions are compared with the unzipping forces of DNA hybrids. Using the DNA zippers as molecular force sensors, the efficient discrimination between specific and nonspecific interactions was demonstrated for small molecules binding to specific receptors, as well as for protein-protein interactions on protein arrays. Finally, an antibody sandwich assay with different capture antibodies on one chip surface and with the detection antibodies linked to a congruent surface via the DNA zippers was used to capture and quantify a recombinant hepatitis C antigen from solution. In this case, the DNA zippers enable not only discrimination between specific and nonspecific binding, but also allow for the local application of detection antibodies, thereby eliminating false-positive results caused by cross-reactive antibodies and nonspecific binding.

Two-step activation of paper batteries for high power generation: design and fabrication of biofluid- and water-activated paper batteries

NASA Astrophysics Data System (ADS)

Lee, Ki Bang

2006-11-01

Two-step activation of paper batteries has been successfully demonstrated to provide quick activation and to supply high power to credit card-sized biosystems on a plastic chip. A stack of a magnesium layer (an anode), a fluid guide (absorbent paper), a highly doped filter paper with copper chloride (a cathode) and a copper layer as a current collector is laminated between two transparent plastic films into a high power biofluid- and water-activated battery. The battery is activated by two-step activation: (1) after placing a drop of biofluid/water-based solution on the fluid inlet, the surface tension first drives the fluid to soak the fluid guide; (2) the fluid in the fluid guide then penetrates into the heavily doped filter paper with copper chloride to start the battery reaction. The fabricated half credit card-sized battery was activated by saliva, urine and tap water and delivered a maximum voltage of 1.56 V within 10 s after activation and a maximum power of 15.6 mW. When 10 kΩ and 1 KΩ loads are used, the service time with water, urine and saliva is measured as more than 2 h. An in-series battery of 3 V has been successfully tested to power two LEDs (light emitting diodes) and an electric driving circuit. As such, this high power paper battery could be integrated with on-demand credit card-sized biosystems such as healthcare test kits, biochips, lab-on-a-chip, DNA chips, protein chips or even test chips for water quality checking or chemical checking.

Top-down nanofabrication of silicon nanoribbon field effect transistor (Si-NR FET) for carcinoembryonic antigen detection.

PubMed

Bao, Zengtao; Sun, Jialin; Zhao, Xiaoqian; Li, Zengyao; Cui, Songkui; Meng, Qingyang; Zhang, Ye; Wang, Tong; Jiang, Yanfeng

2017-01-01

Sensitive and quantitative detection of tumor markers is highly required in the clinic for cancer diagnosis and consequent treatment. A field-effect transistor-based (FET-based) nanobiosensor emerges with characteristics of being label-free, real-time, having high sensitivity, and providing direct electrical readout for detection of biomarkers. In this paper, a top-down approach is proposed and implemented to fulfill a novel silicon nano-ribbon FET, which acts as biomarker sensor for future clinical application. Compared with the bottom-up approach, a top-down fabrication approach can confine width and length of the silicon FET precisely to control its electrical properties. The silicon nanoribbon (Si-NR) transistor is fabricated on a Silicon-on-Insulator (SOI) substrate by a top-down approach with complementary metal oxide semiconductor (CMOS)-compatible technology. After the preparation, the surface of Si-NR is functionalized with 3-aminopropyltriethoxysilane (APTES). Glutaraldehyde is utilized to bind the amino terminals of APTES and antibody on the surface. Finally, a microfluidic channel is integrated on the top of the device, acting as a flowing channel for the carcinoembryonic antigen (CEA) solution. The Si-NR FET is 120 nm in width and 25 nm in height, with ambipolar electrical characteristics. A logarithmic relationship between the changing ratio of the current and the CEA concentration is measured in the range of 0.1-100 ng/mL. The sensitivity of detection is measured as 10 pg/mL. The top-down fabricated biochip shows feasibility in direct detecting of CEA with the benefits of real-time, low cost, and high sensitivity as a promising biosensor for tumor early diagnosis.

Age-dependent atrophy and microgravity travel: what do they have in common?

PubMed

Wang, E

1999-01-01

Space travel and extending human lifespan are two of the many advances of the twentieth century. However, both of these scientific wonders exact a price for their gains; i.e. deleterious effects on normal physiological processes. For example, both old age and prolonged microgravity travel are associated with atrophy in heart, muscle, and bone. The underlying signal transduction pathways, the control mechanisms for the processes of proliferation, differentiation, and apoptosis, may prove to be similarly altered in both old age and microgravity travel. We suggest that the mechanical events involved in space travel provide a telescopic compression of lifespan changes in these tissues; if so, space travel provides an excellent opportunity to investigate how long-term degeneration occurs on Earth. With the aid of biochip technology for multi-factorial analysis, a platform can be generated to create therapeutic modalities to contain, retard, reduce, or prevent this tissue atrophy, either in space or on Earth.

A statistical nanomechanism of biomolecular patterning actuated by surface potential

NASA Astrophysics Data System (ADS)

Lin, Chih-Ting; Lin, Chih-Hao

2011-02-01

Biomolecular patterning on a nanoscale/microscale on chip surfaces is one of the most important techniques used in vitro biochip technologies. Here, we report upon a stochastic mechanics model we have developed for biomolecular patterning controlled by surface potential. The probabilistic biomolecular surface adsorption behavior can be modeled by considering the potential difference between the binding and nonbinding states. To verify our model, we experimentally implemented a method of electroactivated biomolecular patterning technology and the resulting fluorescence intensity matched the prediction of the developed model quite well. Based on this result, we also experimentally demonstrated the creation of a bovine serum albumin pattern with a width of 200 nm in 5 min operations. This submicron noncovalent-binding biomolecular pattern can be maintained for hours after removing the applied electrical voltage. These stochastic understandings and experimental results not only prove the feasibility of submicron biomolecular patterns on chips but also pave the way for nanoscale interfacial-bioelectrical engineering.

Directed formation of micro- and nanoscale patterns of functional light-harvesting LH2 complexes.

PubMed

Reynolds, Nicholas P; Janusz, Stefan; Escalante-Marun, Maryana; Timney, John; Ducker, Robert E; Olsen, John D; Otto, Cees; Subramaniam, Vinod; Leggett, Graham J; Hunter, C Neil

2007-11-28

The precision placement of the desired protein components on a suitable substrate is an essential prelude to any hybrid "biochip" device, but a second and equally important condition must also be met: the retention of full biological activity. Here we demonstrate the selective binding of an optically active membrane protein, the light-harvesting LH2 complex from Rhodobacter sphaeroides, to patterned self-assembled monolayers at the micron scale and the fabrication of nanometer-scale patterns of these molecules using near-field photolithographic methods. In contrast to plasma proteins, which are reversibly adsorbed on many surfaces, the LH2 complex is readily patterned simply by spatial control of surface polarity. Near-field photolithography has yielded rows of light-harvesting complexes only 98 nm wide. Retention of the native optical properties of patterned LH2 molecules was demonstrated using in situ fluorescence emission spectroscopy.

Development of Single-Stranded DNA Aptamers for Specific Bisphenol A Detection

PubMed Central

Jo, Minjoung; Ahn, Ji-Young; Lee, Joohyung; Lee, Seram; Hong, Sun Woo; Yoo, Jae-Wook; Kang, Jeehye; Dua, Pooja

2011-01-01

The development of reagents with high affinity and specificity to small molecules is crucial for the high-throughput detection of chemical compounds, such as toxicants or pollutants. Aptamers are short and single-stranded (ss) oligonucleotides able to recognize target molecules with high affinity. Here, we report the selection of ssDNA aptamers that bind to Bisphenol A (BPA), an environmental hormone. Using SELEX process, we isolated high affinity aptamers to BPA from a 1015 random library of 60 mer ssDNAs. The selected aptamers bound specifically to BPA, but not to structurally similar molecules, such as Bisphenol B with one methyl group difference, or 4,4′-Bisphenol with 2 methyl groups difference. Using these aptamers, we developed an aptamer-based sol–gel biochip and detected BPA dissolved in water. This novel BPA aptamer-based detection can be further applied to the universal and high-specificity detection of small molecules. PMID:21413891

Biosensor properties of SOI nanowire transistors with a PEALD Al{sub 2}O{sub 3} dielectric protective layer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popov, V. P., E-mail: popov@isp.nsc.ru; Ilnitskii, M. A.; Zhanaev, E. D.

2016-05-15

The properties of protective dielectric layers of aluminum oxide Al{sub 2}O{sub 3} applied to prefabricated silicon-nanowire transistor biochips by the plasma enhanced atomic layer deposition (PEALD) method before being housed are studied depending on the deposition and annealing modes. Coating the natural silicon oxide with a nanometer Al{sub 2}O{sub 3} layer insignificantly decreases the femtomole sensitivity of biosensors, but provides their stability in bioliquids. In deionized water, transistors with annealed aluminum oxide are closed due to the trapping of negative charges of <(1–10) × 10{sup 11} cm{sup −2} at surface states. The application of a positive potential to the substratemore » (V{sub sub} > 25 V) makes it possible to eliminate the negative charge and to perform multiple measurements in liquid at least for half a year.« less

NASA Tech Briefs, July 2008

NASA Technical Reports Server (NTRS)

2008-01-01

Topics covered include: Torque Sensor Based on Tunnel-Diode Oscillator; Shaft-Angle Sensor Based on Tunnel-Diode Oscillator; Ground Facility for Vicarious Calibration of Skyborne Sensors; Optical Pressure-Temperature Sensor for a Combustion Chamber; Impact-Locator Sensor Panels; Low-Loss Waveguides for Terahertz Frequencies; MEMS/ECD Method for Making Bi(2-x)Sb(x)Te3 Thermoelectric Devices; Low-Temperature Supercapacitors; Making a Back-Illuminated Imager with Back-Side Contact and Alignment Markers; Compact, Single-Stage MMIC InP HEMT Amplifier; Nb(x)Ti(1-x)N Superconducting-Nanowire Single-Photon Detectors; Improved Sand-Compaction Method for Lost-Foam Metal Casting; Improved Probe for Evaluating Compaction of Mold Sand; Polymer-Based Composite Catholytes for Li Thin-Film Cells; Using ALD To Bond CNTs to Substrates and Matrices; Alternating-Composition Layered Ceramic Barrier Coatings; Variable-Structure Control of a Model Glider Airplane; Axial Halbach Magnetic Bearings; Compact, Non-Pneumatic Rock-Powder Samplers; Biochips Containing Arrays of Carbon-Nanotube Electrodes; Nb(x)Ti(1-x)N Superconducting-Nanowire Single-Photon Detectors; Neon as a Buffer Gas for a Mercury-Ion Clock; Miniature Incandescent Lamps as Fiber-Optic Light Sources; Bidirectional Pressure-Regulator System; and Prism Window for Optical Alignment. Single-Grid-Pair Fourier Telescope for Imaging in Hard-X Rays and gamma Rays Range-Gated Metrology with Compact Optical Head Lossless, Multi-Spectral Data Compressor for Improved Compression for Pushbroom-Typetruments.

Biomonitoring and risk assessment on earth and during exploratory missions using AquaHab ®

NASA Astrophysics Data System (ADS)

Slenzka, K.; Dünne, M.; Jastorff, B.

2008-12-01

Bioregenerative closed ecological life support systems (CELSS) will be necessary in the exploration context revitalizing atmosphere, waste water and producing food for the human CELSS mates. During these long-term space travels and stays far away from Earth in an hostile environment as well as far for example from any hospital and surgery potential, it will be necessary to know much more about chemical and drug contamination in the special sense and by human's themselves in detail. Additionally, there is a strong need on Earth for more relevant standardized test systems including aquatic ones for the prospective risk assessment of chemicals and drugs in general on a laboratory scale. Current standardized test systems are mono species tests, and thus do not represent system aspects and have reduced environmental relevance. The experience gained during the last years in our research group lead to the development of a self-sustaining closed aquatic habitat/facility, called AquaHab ® which can serve regarding space exploration and Earth application. The AquaHab ® module can be the home of several fish species, snails, plants, amphipods and bacteria. The possibility to use different effect endpoints with certain beneficial characteristics is the basis for the application of AquaHab ® in different fields. Influence of drugs and chemicals can be tested on several trophic levels and ecosystem levels; guaranteeing a high relevance for aquatic systems in the real environment. Analyses of effect parameters of different complexity (e.g. general biological and water chemical parameters, activity of biotransforming enzymes) result in broad spectra of sensitivity. Combined with residual analyses (including all metabolites), this leads to an extended prospective risk assessment of a chemical on Earth and in a closed Life Support System. The possibility to measure also sensitive "online" parameters (e.g. behavior, respiration/photosynthetic activity) enables a quick and sensitive effect analysis of water contaminants in respective environments. AquaHab ® is currently under development to an early warning biomonitoring system using genetically modified fish and green algae. The implementation of biosensors/biochip in addition is also discussed.

Bio-Nanobattery Development and Characterization

NASA Technical Reports Server (NTRS)

King, Glen C.; Choi, Sang H.; Chu, Sang-Hyon; Kim, Jae-Woo; Watt, Gerald D.; Lillehei, Peter T.; Park, Yeonjoon; Elliott, James R.

2005-01-01

A bio-nanobattery is an electrical energy storage device that utilizes organic materials and processes on an atomic, or nanometer-scale. The bio-nanobattery under development at NASA s Langley Research Center provides new capabilities for electrical power generation, storage, and distribution as compared to conventional power storage systems. Most currently available electronic systems and devices rely on a single, centralized power source to supply electrical power to a specified location in the circuit. As electronic devices and associated components continue to shrink in size towards the nanometer-scale, a single centralized power source becomes impractical. Small systems, such as these, will require distributed power elements to reduce Joule heating, to minimize wiring quantities, and to allow autonomous operation of the various functions performed by the circuit. Our research involves the development and characterization of a bio-nanobattery using ferritins reconstituted with both an iron core (Fe-ferritin) and a cobalt core (Co-ferritin). Synthesis and characterization of the Co-ferritin and Fe-ferritin electrodes were performed, including reducing capability and the half-cell electrical potentials. Electrical output of nearly 0.5 V for the battery cell was measured. Ferritin utilizing other metallic cores were also considered to increase the overall electrical output. Two dimensional ferritin arrays were produced on various substrates to demonstrate the feasibility of a thin-film nano-scaled power storage system for distributed power storage applications. The bio-nanobattery will be ideal for nanometerscaled electronic applications, due to the small size, high energy density, and flexible thin-film structure. A five-cell demonstration article was produced for concept verification and bio-nanobattery characterization. Challenges to be addressed include the development of a multi-layered thin-film, increasing the energy density, dry-cell bionanobattery development, and selection of ferritin core materials to allow the broadest range of applications. The potential applications for the distributed power system include autonomously-operating intelligent chips, flexible thin-film electronic circuits, nanoelectromechanical systems (NEMS), ultra-high density data storage devices, nanoelectromagnetics, quantum electronic devices, biochips, nanorobots for medical applications and mechanical nano-fabrication, etc.

Organic solvent-free sugar-based transparency nanopatterning material derived from biomass for eco-friendly optical biochips using green lithography

NASA Astrophysics Data System (ADS)

Takei, Satoshi; Oshima, Akihiro; Oyama, Tomoko G.; Ito, Kenta; Sugahara, Kigenn; Kashiwakura, Miki; Kozawa, Takahiro; Tagawa, Seiichi

2014-05-01

An organic solvent-free sugar-based transparency nanopatterning material which had specific desired properties such as nanostructures of subwavelength grating and moth-eye antireflection, acceptable thermal stability of 160 °C, and low imaginary refractive index of less than 0.005 at 350-800 nm was proposed using electron beam lithography. The organic solvent-free sugar-based transparency nanopatterning material is expected for non-petroleum resources, environmental affair, safety, easiness of handling, and health of the working people, instead of the common developable process of tetramethylammonium hydroxide. 120 nm moth-eye antireflection nanopatterns images with exposure dose of 10 μC/cm2 were provided by specific process conditions of electron beam lithography. The developed sugar derivatives with hydroxyl groups and EB sensitive groups in the organic solvent-free sugar-based transparency nanopatterning material were applicable to future development of optical interface films of biology and electronics as a novel chemical design.

High-quality substrate for fluorescence enhancement using agarose-coated silica opal film.

PubMed

Xu, Ming; Li, Juan; Sun, Liguo; Zhao, Yuanjin; Xie, Zhuoying; Lv, Linli; Zhao, Xiangwei; Xiao, Pengfeng; Hu, Jing; Lv, Mei; Gu, Zhongze

2010-08-01

To improve the sensitivity of fluorescence detection in biochip, a new kind of substrates was developed by agarose coating on silica opal film. In this study, silica opal film was fabricated on glass substrate using the vertical deposition technique. It can provide stronger fluorescence signals and thus improve the detection sensitivity. After coating with agarose, the hybrid film could provide a 3D support for immobilizing sample. Comparing with agarose-coated glass substrate, the agarose-coated opal substrates could selectively enhance particular fluorescence signals with high sensitivity when the stop band of the silica opal film in the agarose-coated opal substrate overlapped the fluorescence emission wavelength. A DNA hybridization experiment demonstrated that fluorescence intensity of special type of agarose-coated opal substrates was about four times that of agarose-coated glass substrate. These results indicate that the optimized agarose-coated opal substrate can be used for improving the sensitivity of fluorescence detection with high quality and selectivity.

Biomaterials based on photosynthetic membranes as potential sensors for herbicides.

PubMed

Ventrella, Andrea; Catucci, Lucia; Placido, Tiziana; Longobardi, Francesco; Agostiano, Angela

2011-08-15

In this study, ultrathin film multilayers of Photosystem II-enriched photosynthetic membranes (BBY) were prepared and immobilized on quartz substrates by means of a Layer by Layer procedure exploiting electrostatic interactions with poly(ethylenimine) as polyelectrolyte. The biomaterials thus obtained were characterized by means of optical techniques and Atomic Force Microscopy, highlighting the fact that the Layer by Layer approach allowed the BBYs to be immobilized with satisfactory results. The activity of these hybrid materials was evaluated by means of optical assays based on the Hill Reaction, indicating that the biosamples, which preserved about 65% of their original activity even ten weeks after preparation, were both stable and active. Furthermore, an investigation of the biochips' sensitivity to the herbicide terbutryn, as a model analyte, gave interesting results: inhibition of photosynthetic activity was observed at terbutryn concentrations higher than 10(-7)M, thus evidencing the potential of such biomaterials in the environmental biosensor field. Copyright © 2011 Elsevier B.V. All rights reserved.

Rapid bio-patterning method based on the fabrication of PEG microstructures and layer-by-layer polymeric thin film

NASA Astrophysics Data System (ADS)

Shim, Hyun-Woo; Lee, Ji-Hye; Choi, Chang-Hyoung; Song, Hwan-Moon; Kim, Bo-Yeol; Kim, Dong-Pyo; Lee, Chang-Soo

2007-12-01

The patterning of biomolecules in well-defined microstructures is critical issue for the development of biosensors and biochips. However, the fabrication of microstructures with well-ordered and spatially discrete forms to provide the patterned surface for the immobilization of biomolecules is difficult because of the lack of distinct physical and chemical barriers separating patterns. This study present rapid biomolecule patterning using micromolding in capillaries (MIMIC), soft-lithographic fabrication of PEG microstructures for prevention of nonspecific binding as a biological barrier, and self assembled polymeric thin film for efficient immobilization of proteins or cells. For the proof of concept, protein (FITC-BSA), bacteria (E.coli BL21-pET23b-GFP) were used for biomolecules patterning on polyelectrolyte coated surface within PEG microstructures. The novel approach of MIMIC combined with LbL coating provides a general platform for patterning a broad range of materials because it can be easily applied to various substrates such as glass, silicon, silicon dioxide, and polymers.

G-Protein Coupled Receptors: Surface Display and Biosensor Technology

NASA Astrophysics Data System (ADS)

McMurchie, Edward; Leifert, Wayne

Signal transduction by G-protein coupled receptors (GPCRs) underpins a multitude of physiological processes. Ligand recognition by the receptor leads to the activation of a generic molecular switch involving heterotrimeric G-proteins and guanine nucleotides. With growing interest and commercial investment in GPCRs in areas such as drug targets, orphan receptors, high-throughput screening of drugs and biosensors, greater attention will focus on assay development to allow for miniaturization, ultrahigh-throughput and, eventually, microarray/biochip assay formats that will require nanotechnology-based approaches. Stable, robust, cell-free signaling assemblies comprising receptor and appropriate molecular switching components will form the basis of future GPCR/G-protein platforms, which should be able to be adapted to such applications as microarrays and biosensors. This chapter focuses on cell-free GPCR assay nanotechnologies and describes some molecular biological approaches for the construction of more sophisticated, surface-immobilized, homogeneous, functional GPCR sensors. The latter points should greatly extend the range of applications to which technologies based on GPCRs could be applied.

Current and Developing Technologies for Monitoring Agents of Bioterrorism and Biowarfare

PubMed Central

Lim, Daniel V.; Simpson, Joyce M.; Kearns, Elizabeth A.; Kramer, Marianne F.

2005-01-01

Recent events have made public health officials acutely aware of the importance of rapidly and accurately detecting acts of bioterrorism. Because bioterrorism is difficult to predict or prevent, reliable platforms to rapidly detect and identify biothreat agents are important to minimize the spread of these agents and to protect the public health. These platforms must not only be sensitive and specific, but must also be able to accurately detect a variety of pathogens, including modified or previously uncharacterized agents, directly from complex sample matrices. Various commercial tests utilizing biochemical, immunological, nucleic acid, and bioluminescence procedures are currently available to identify biological threat agents. Newer tests have also been developed to identify such agents using aptamers, biochips, evanescent wave biosensors, cantilevers, living cells, and other innovative technologies. This review describes these current and developing technologies and considers challenges to rapid, accurate detection of biothreat agents. Although there is no ideal platform, many of these technologies have proved invaluable for the detection and identification of biothreat agents. PMID:16223949

Characterizing Esophageal Cancerous Cells at Different Stages Using the Dielectrophoretic Impedance Measurement Method in a Microchip.

PubMed

Wang, Hsiang-Chen; Nguyen, Ngoc-Viet; Lin, Rui-Yi; Jen, Chun-Ping

2017-05-06

Analysis of cancerous cells allows us to provide useful information for the early diagnosis of cancer and to monitor treatment progress. An approach based on electrical principles has recently become an attractive technique. This study presents a microdevice that utilizes a dielectrophoretic impedance measurement method for the identification of cancerous cells. The proposed biochip consists of circle-on-line microelectrodes that are patterned using a standard microfabrication processes. A sample of various cell concentrations was introduced in an open-top microchamber. The target cells were collectively concentrated between the microelectrodes using dielectrophoresis manipulation, and their electrical impedance properties were also measured. Different stages of human esophageal squamous cell carcinoma lines could be distinguished. This result is consistent with findings using hyperspectral imaging technology. Moreover, it was observed that the distinguishing characteristics change in response to the progression of cancer cell invasiveness by Raman spectroscopy. The device enables highly efficient cell collection and provides rapid, sensitive, and label-free electrical measurements of cancerous cells.

Design, Fabrication and Characterization of an In Silico Cell Physiology lab for Bio Sensing Applications

NASA Astrophysics Data System (ADS)

Haque, A. ul; Rokkam, M.; DeCarlo, A. R.; Wereley, S. T.; Wells, H. W.; McLamb, W. T.; Roux, S. J.; Irazoqui, P. P.; Porterfield, D. M.

2006-04-01

In this paper, we report the design, fabrication and characterization of an In Silico cell physiology biochip for measuring Ca2+ ion concentrations and currents around single cells. This device has been designed around specific science objectives of measuring real time multidimensional calcium flux patterns around sixteen Ceratopteris richardii fern spores in microgravity flight experiments and ground studies. The sixteen microfluidic cell holding pores are 150 by 150 µm each and have 4 Ag/AgCl electrodes leading into them. An SU-8 structural layer is used for insulation and packaging purposes. The In Silico cell physiology lab is wire bonded on to a custom PCB for easy interface with a state of the art data acquisition system. The electrodes are coated with a Ca2+ ion selective membrane based on ETH-5234 ionophore and operated against an Ag/AgCl reference electrode. Initial characterization results have shown Nernst slopes of 30mv/decade that were stable over a number of measurement cycles. While this work is focused on technology to enable basic research on the Ceratopteris richardii spores, we anticipate that this type of cell physiology lab-on-a-chip will be broadly applied in biomedical and pharmacological research by making minor modifications to the electrode material and the measurement technique. Future applications include detection of glucose, hormones such as plant auxin, as well as multiple analyte detection on the same chip.

Genetic determination of the vascular reactions in humans in response to the diving reflex.

PubMed

Baranova, Tatiana I; Berlov, Dmitrii N; Glotov, Oleg S; Korf, Ekaterina A; Minigalin, Alexey D; Mitrofanova, Alla V; Ahmetov, Ildus I; Glotov, Andrey S

2017-03-01

The purpose of this study was to investigate the genetic mechanisms of the defense vascular reactions in response to the diving reflex in humans with polymorphisms in the genes ADBR2, ACE, AGTR1, BDKRB2 , and REN We hypothesized that protective vascular reactions, in response to the diving reflex, are genetically determined and are distinguished in humans with gene polymorphisms of the renin-angiotensin and kinin-bradykinin system. A total of 80 subjects (19 ± 1.4 yr) participated in the study. The intensity of the vascular response was estimated using photoplethysmogram. The I/D polymorphism (rs4340) of ACE was analyzed by PCR. REN (G/A, rs2368564), AGTR1 (A/C, rs5186), BDKRB2 (T/C, rs1799722), and ADBR2 (A/G, rs1042713) polymorphisms were examined using the two-step multiplex PCR followed by carrying allele hybridization on the biochip. Subjects with the BDKRB2 (C/C), ACE (D/D), and ADBR2 (G/G, G/A) genotypes exhibited the strongest peripheral vasoconstriction in response to diving. In subjects with a combination of the BDKRB2 (C/C) plus ACE (D/D) genotypes, we observed the lowest pulse wave amplitude and pulse transit time values and the highest arterial blood pressure during face immersion compared with the heterozygous individuals, suggesting that these subjects are more susceptible to diving hypoxia. This study observed that humans with gene polymorphisms of the renin-angiotensin and kinin-bradykinin systems demonstrate various expressions of protective vascular reactions in response to the diving reflex. The obtained results might be used in estimation of resistance to hypoxia of any origin in human beings or in a medical practice. NEW & NOTEWORTHY Our study demonstrates that the vascular reactions in response to the diving reflex are genetically determined and depend on gene polymorphisms of the kinin-bradykinin and the renin-angiotensin systems. Copyright © 2017 the American Physiological Society.

Preface: phys. stat. sol. (a) 203/4

NASA Astrophysics Data System (ADS)

Kittler, Martin; Yang, Deren

2006-03-01

This issue of physica status solidi (a) contains the majority of papers presented at the 2nd Sino-German Symposium The Silicon Age which was held at the Lindner Hotel Cottbus, Germany, 19-24 September 2005. This meeting followed the 1st Symposium Progress in Silicon Materials held in June 2002 in Hangzhou, P.R. China. 8 Chinese and 14 German scientists from universities, research institutes and industry were invited to present their views about different aspects of silicon.There was a continuous progress in silicon materials development during the last 40-50 years, driven by the need of the IC industry for better and larger monocrystalline silicon wafers. Moreover, low-cost crystalline silicon now dominates the world's production of solar cells in the photovoltaics industry. Furthermore, there are intensive research activities worldwide for on-chip integration of Si-based photonics in CMOS technology. In addition, new areas being connected with silicon are starting to appear, namely Si-based biochips and nanoelectronics. Silicon, one can reasonably argue, is already the most investigated of all materials. However, there is still a need for continuation of research and development regarding numerous aspects of Si and also SiGe, including related technologies, advanced diagnostics or the role of crystal defects, which are the working fields of many laboratories all over the world. This was also shown by the presentations at the symposium and can be found in the contributions contained in this issue.The organizers would like to thank the participants for their high level contributions and discussions during the symposium. This intensive and open communication allowed the participants to create synergies between the different fields of silicon research and also to build up relationships for cooperation between Chinese and German research groups.Finally, we would like to thank the Sino-German Science Center for the financial support of the symposium.

Bioactive surface modifications on inner walls of poly-tetra-fluoro-ethylene tubes using dielectric barrier discharge

NASA Astrophysics Data System (ADS)

Cho, Yong Ki; Park, Daewon; Kim, Hoonbae; Lee, Hyerim; Park, Heonyong; Kim, Hong Ja; Jung, Donggeun

2014-03-01

Bioactive surface modification can be used in a variety of medical polymeric materials in the fields of biochips and biosensors, artificial membranes, and vascular grafts. In this study, the surface modification of the inner walls of poly-tetra-fluoro-ethylene (PTFE) tubing was carried out to improve vascular grafts, which are made of biocompatible material for the human body in the medical field. Focus was centered on the cell attachment of the inner wall of the PTFE by sequential processes of hydrogen plasma treatment, hydrocarbon deposition, and reactive plasma treatment on the PFTE surface using micro plasma discharge. Micro plasma was generated by a medium-frequency alternating current high-voltage generator. The preliminary modification of PTFE was conducted by a plasma of hydrogen and argon gases. The hydrocarbon thin film was deposited on modified PTFE with a mixture of acetylene and argon gases. The reactive plasma treatment using oxygen plasma was done to give biocompatible functionality to the inner wall surface. The hydrophobic surface of bare PTFE is made hydrophilic by the reactive plasma treatment due to the formation of carbonyl groups on the surface. The reactive treatment could lead to improved attachment of smooth muscle cells (SMCs) on the modified PTFE tubing. Fourier transform infrared absorption spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and water contact angle measurement were used for the analysis of the surface modification. The SMC-attached PTFE tube developed will be applicable to in vitro human vasculature-mimetic model systems, and to medical vascular grafts.

Laser micromilling of convex microfluidic channels onto glassy carbon for glass molding dies

NASA Astrophysics Data System (ADS)

Tseng, Shih-Feng; Chen, Ming-Fei; Hsiao, Wen-Tse; Huang, Chien-Yao; Yang, Chung-Heng; Chen, Yu-Sheng

2014-06-01

This study reports the fabrication of convex microfluidic channels on glassy carbon using an ultraviolet laser processing system to produce glass molding dies. The laser processing parameters, including various laser fluences and scanning speeds of galvanometers, were adjusted to mill a convex microchannel on a glassy carbon substrate to identify the effects of material removal. The machined glassy carbon substrate was then applied as a glass molding die to fabricate a glass-based microfluidic biochip. The surface morphology, milled width and depth, and surface roughness of the microchannel die after laser micromilling were examined using a three-dimensional confocal laser scanning microscope. This study also investigates the transcription rate of microchannels after the glass molding process. To produce a 180 μm high microchannel on the GC substrate, the optimal number of milled cycles, laser fluence, and scanning speed were 25, 4.9 J/cm2, and 200 mm/s, respectively. The width, height, and surface roughness of milled convex microchannels were 119.6±0.217 μm, 180.26±0.01 μm, and 0.672±0.08 μm, respectively. These measured values were close to the predicted values and suitable for a glass molding die. After the glass molding process, a typical glass-based microchannel chip was formed at a molding temperature of 660 °C and the molding force of 0.45 kN. The transcription rates of the microchannel width and depth were 100% and 99.6%, respectively. Thus, the proposed approach is suitable for performing in chemical, biochemical, or medical reactions.

Microfabrication of through holes in polydimethylsiloxane (PDMS) sheets using a laser plasma EUV source (Conference Presentation)

NASA Astrophysics Data System (ADS)

Makimura, Tetsuya; Urai, Hikari; Niino, Hiroyuki

2017-03-01

Polydimethylsiloxane (PDMS) is a material used for cell culture substrates / bio-chips and micro total analysis systems / lab-on-chips due to its flexibility, chemical / thermo-dynamic stability, bio-compatibility, transparency and moldability. For further development, it is inevitable to develop a technique to fabricate precise three dimensional structures on micrometer-scale at high aspect ratio. In the previous works, we reported a technique for high-quality micromachining of PDMS without chemical modification, by means of photo direct machining using laser plasma EUV sources. In the present work, we have investigated fabrication of through holes. The EUV radiations around 10 nm were generated by irradiation of Ta targets with Nd:YAG laser light (10 ns, 500 mJ/pulse). The generated EUV radiations were focused using an ellipsoidal mirror. It has a narrower incident angle than those in the previous works in order to form a EUV beam with higher directivity, so that higher aspect structures can be fabricated. The focused EUV beam was incident on PDMS sheets with a thickness of 15 micrometers, through holes in a contact mask placed on top of them. Using a contact mask with holes with a diameter of three micrometers, complete through holes with a diameter of two micrometers are fabricated in the PDMS sheet. Using a contact mask with two micrometer holes, however, ablation holes almost reaches to the back side of the PDMS sheet. The fabricated structures can be explained in terms of geometrical optics. Thus, we have developed a technique for micromachining of PDMS sheets at high aspect ratios.

Microbial whole‐cell arrays

PubMed Central

Elad, Tal; Lee, Jin Hyung; Belkin, Shimshon; Gu, Man Bock

2008-01-01

Summary The coming of age of whole‐cell biosensors, combined with the continuing advances in array technologies, has prepared the ground for the next step in the evolution of both disciplines – the whole‐cell array. In the present review, we highlight the state‐of‐the‐art in the different disciplines essential for a functional bacterial array. These include the genetic engineering of the biological components, their immobilization in different polymers, technologies for live cell deposition and patterning on different types of solid surfaces, and cellular viability maintenance. Also reviewed are the types of signals emitted by the reporter cell arrays, some of the transduction methodologies for reading these signals and the mathematical approaches proposed for their analysis. Finally, we review some of the potential applications for bacterial cell arrays, and list the future needs for their maturation: a richer arsenal of high‐performance reporter strains, better methodologies for their incorporation into hardware platforms, design of appropriate detection circuits, the continuing development of dedicated algorithms for multiplex signal analysis and – most importantly – enhanced long‐term maintenance of viability and activity on the fabricated biochips. PMID:21261831

Optical heterogeneous bioassay for the detection of the inflammatory biomarker suPAR

NASA Astrophysics Data System (ADS)

Tombelli, S.; Trono, C.; Adinolfi, B.; Chiavaioli, F.; Giannetti, A.; Eugen-Olsen, J.; Bernini, R.; Grimaldi, I. A.; Persichetti, G.; Testa, G.; Baldini, F.

2015-03-01

Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory protein present in blood and a marker of disease presence, severity and prognosis. A heterogeneous sandwich assay is proposed for quantifying suPAR by employing a capture antibody from rat and a biotinylated detection antibody from mouse. Optical detection was achieved by a successive exposure of the biotinylated sandwich to streptavidin labelled with ATTO647N. The heterogeneous assay was implemented on a multichannel polymethylmetacrylate (PMMA) optical biochip, potentially capable of the simultaneous detection of more than one analyte. Capture antibody was immobilized on the PMMA surface of the microfluidic channel and the assay was performed with the following protocol: i) surface blocking with BSA, ii) incubation with suPAR or PBS, iii) incubation with biotinylated suPAR detection Ab and iv) incubation with streptavidin-ATTO647N. Promising preliminary results were obtained with this protocol. Moreover, an improved optical setup is proposed which avoids the mechanical scanning of the chip and consequently the in-series fluorescence excitation and read out, allowing the simultaneous measurement of the fluorescence on all the channels of the microfluidic chip.

Multi-walled carbon nanotubes and metallic nanoparticles and their application in biomedicine.

PubMed

Rojas-Chapana, Jose A; Giersig, Michael

2006-02-01

Interdisciplinary research has become a matter of paramount importance for novel applications of nanomaterials in biology and medicine. As such, many disciplines-physics, chemistry, microbiology, cell biology, and material science-all contribute to the design, synthesis and fabrication of functional and biocompatible devices at the nanometer scale. Since the most areas of cell biology and biomedicine deal with functional entities such as DNA and proteins, mimicry of these structures and function in the nanosize range offers exciting opportunities for the development of biosensors, biochips, and bioplatforms. In this report we highlight the potential benefits and challenges that arise in the manufacture of biocompatible nanoparticles and nano-networks that can be coupled with biological objects. Among the challenges facing us are those concerned with making the necessary advances in enabling affordability, innovation, and quality of manufactured nanodevices for rapid progress in the emerging field of bio-nanotechnology. The convergence of nanotechnology and biomedicine makes nanoscale research highly promising for new discoveries that can cost-effectively accelerate progress in moving from basic research to practical prototypes and products.

A silicon-based peptide biosensor for label-free detection of cancer cells

NASA Astrophysics Data System (ADS)

Martucci, Nicola M.; Rea, Ilaria; Ruggiero, Immacolata; Terracciano, Monica; De Stefano, Luca; Migliaccio, Nunzia; Dardano, Principia; Arcari, Paolo; Rendina, Ivo; Lamberti, Annalisa

2015-05-01

Sensitive and accurate detection of cancer cells plays a crucial role in diagnosis of cancer and minimal residual disease, so being one of the most hopeful approaches to reduce cancer death rates. In this paper, a strategy for highly selective and sensitive detection of lymphoma cells on planar silicon-based biosensor has been evaluated. In this setting an Idiotype peptide, able to specifically bind the B-cell receptor (BCR) of A20 cells in mice engrafted with A20 lymphoma, has been covalently linked to the sensor active surface and used as molecular probe. The biochip here presented showed a coverage efficiency of 85% with a detection efficiency of 8.5×10-3 cells/μm2. The results obtained suggested an efficient way for specific label-free cell detection by using a silicon-based peptide biosensor. In addition, the present recognition strategy, besides being useful for the development of sensing devices capable of monitoring minimal residual disease, could be used to find and characterize new specific receptor-ligand interactions through the screening of a recombinant phage library.

Simple detection of residual enrofloxacin in meat products using microparticles and biochips.

PubMed

Ha, Mi-Sun; Chung, Myung-Sub; Bae, Dong-Ho

2016-05-01

A simple and sensitive method for detecting enrofloxacin, a major veterinary fluoroquinolone, was developed. Monoclonal antibody specific for enrofloxacin was immobilised on a chip and fluorescent dye-labelled microparticles were covalently bound to the enrofloxacin molecules. Enrofloxacin in solution competes with the microparticle-immobilised enrofloxacin (enroMPs) to bind to the antibody on the chip. The presence of enrofloxacin was verified by detecting the fluorescence of enrofloxacin-bound microparticles. Under optimum conditions, a high dynamic range was achieved at enrofloxacin concentrations ranging from 1 to 1000 μg kg(-1). The limits of detection and quantification for standard solutions were 5 and 20 μg kg(-1) respectively, which are markedly lower than the maximum residue limit. Using simple extraction methods, recoveries from fortified beef, pork and chicken samples were 43.4-62.3%. This novel method also enabled approximate quantification of enrofloxacin concentration: the enroMP signal intensity decreased with increasing enrofloxacin concentration. Because of its sensitivity, specificity, simplicity and rapidity, the method described herein will facilitate the detection and approximate quantification of enrofloxacin residues in foods in a high-throughput manner.

Co-electrospinning of bacteria and viruses

NASA Astrophysics Data System (ADS)

Salalha, Wael; Kuhn, Jonathan; Chervinsky, Shmuel; Zussman, Eyal

2006-03-01

Co-electrospinning provides a novel and highly versatile approach towards composite fibers with diameters ranging from a few hundred nm down to 30 nm with embedded elements. In the present work, co-electrospinning of poly(vinyl alcohol) (PVA) and viruses (T7, T4, λ) or bacteria (Escherichia coli, Staphylococcus albus) was carried out. These preparations should have applications for tissue engineering, gene therapy, phage therapy and biosensing. The average diameter of the co-spun nanofibers was about 300 nm. We found that the encapsulated viruses and bacteria manage to survive the electrospinning process, its pressure buildup in the core of the fiber and the electrostatic field in the co-electrospinning process. Approximately 10% of the Escherichia coli and 20% of Staphylococcus albus cells are viable after spinning. Approximately 5% of the bacterial viruses were also viable after the electrospinning. It should be noted that the encapsulated cells and viruses remain stable for two months without a further decrease in number. These results demonstrate the potential of the co-electrospinning process for the encapsulation and immobilization of bio-objects and the possibility of adapting them to technical applications (e.g., bio-chips).

Reading disc-based bioassays with standard computer drives.

PubMed

Yu, Hua-Zhong; Li, Yunchao; Ou, Lily M-L

2013-02-19

Traditional methods of disease diagnosis are both time-consuming and labor-intensive, and many tests require expensive instrumentation and trained professionals, which restricts their use to biomedical laboratories. Because patients can wait several days (even weeks) for the results, the consequences of delayed treatment could be disastrous. Therefore, affordable and simple point-of-care (POC) biosensor devices could fill a diagnostic niche in the clinic or even at home, as personal glucose meters do for diabetics. These devices would allow patients to check their own health conditions and enable physicians to make prompt treatment decisions, which could improve the chances for rapid recovery and cure. Compact discs (CDs) provide inexpensive substrate materials for the preparation of microarray biochips, and conventional computer drives/disc players can be adapted as precise optical reading devices for signal processing. Researchers can employ the polycarbonate (PC) base of a CD as an alternative substrate to glass slides or silicon wafers for the preparation of microanalytical devices. Using the characteristic optical phenomena occurring on the metal layer of a CD, researchers can develop biosensors based on advanced spectroscopic readout (interferometry or surface plasmon resonance). If researchers integrate microfluidic functions with CD mechanics, they can control fluid transfer through the spinning motion of the disc, leading to "lab-on-a-CD" devices. Over the last decade, our laboratory has focused on the construction of POC biosensor devices from off-the-shelf CDs or DVDs and standard computer drives. Besides the initial studies of the suitability of CDs for surface and materials chemistry research (fabrication of self-assembled monolayers and oxide nanostructures), we have demonstrated that an ordinary optical drive, without modification of either the hardware or the software driver, can function as the signal transducing element for reading disc-based bioassays quantitatively. In this Account, we first provide a brief introduction to CD-related materials chemistry and microfluidics research. Then we describe the mild chemistry developed in our laboratory for the preparation of computer-readable biomolecular screening assays: photochemical activation of the polycarbonate (PC) disc surface and immobilization and delivery of probe and target biomolecules. We thoroughly discuss the analysis of the molecular recognition events: researchers can "read" these devices quantitatively with an unmodified optical drive of any personal computer. Finally, and critically, we illustrate our digitized molecular diagnosis approach with three trial systems: DNA hybridization, antibody-antigen binding, and ultrasensitive lead detection with a DNAzyme assay. These examples demonstrate the broad potential of this new analytical/diagnostic tool for medical screening, on-site food/water safety testing, and remote environmental monitoring.

[Autoimmune encephalitis: possibilities in the laboratory investigation].

PubMed

Böröcz, Katalin; Hayden, Zsófia; Mészáros, Viktória; Csizmadia, Zsuzsanna; Farkas, Kornélia; Kellermayer, Zoltán; Balogh, Péter; Nagy, Ferenc; Berki, Tímea

2018-01-01

The role of autoimmune responses against central nervous system (CNS) antigens in encephalitis presenting with non-classified neurologic or psychiatric symptoms has been appreciated in the past decade. Paraneoplastic limbic encephalitis has a poor prognosis and is most commonly associated with lung, ovarium, and testicular neoplasms, leading to immune reactions against intracellular antigens (anti-Hu/ANNA1, anti-Ri/ANNA2, anti-CV2/CRMP5 and anti-Ma2/Ta). In contrast, the recently described autoimmune encephalitis subtypes present with a broad spectrum of symptoms, respond to autoimmune therapies well and usually associate with autoantibodies against neuronal cell surface receptors (NMDAR, GABA B R, AMPAR) or synaptic proteins (LGI1, CASPR2). Our aim is to bring to awareness the increasing number of autoimmune encephalitis patients requiring neurologic, psychiatric and intensive care and to emphasize the significance of detecting various autoantibodies in diagnosing patients. In the past 6 years, our laboratory received 836 autoimmune encephalitis diagnostic test requests from a total of 717 patients. Serum and cerebrospinal fluid (CSF) samples were analysed with indirect immunofluorescence using a BIOCHIP consisting of cell lines transfected with 6 different receptor proteins. IgG autoantibodies against receptor proteins were present in 7.5% of patients. The frequency of positive samples was the following: NMDAR > LGI1 > GABA B R > CASPR2. Detecting autoantibodies facilitates the diagnosis of autoimmune encephalitis in an early stage. Patients diagnosed early can be effectively treated with plasmapheresis and immunosuppressive drugs. The efficiency of therapies can be monitored by autoantibody detection. Therefore, the diagnostic immune laboratory plays an important role in proper diagnosis and in the prevention of rapidly progressing symptoms. Orv Hetil. 2018; 159(3): 107-112.

A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics

PubMed Central

2013-01-01

Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing. MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT). Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology. PMID:24090398

A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics.

PubMed

Canonica, Giorgio Walter; Ansotegui, Ignacio J; Pawankar, Ruby; Schmid-Grendelmeier, Peter; van Hage, Marianne; Baena-Cagnani, Carlos E; Melioli, Giovanni; Nunes, Carlos; Passalacqua, Giovanni; Rosenwasser, Lanny; Sampson, Hugh; Sastre, Joaquin; Bousquet, Jean; Zuberbier, Torsten

2013-10-03

Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing.MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT).Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology.

Identifying Thoracic Malignancies Through Pleural Fluid Biomarkers: A Predictive Multivariate Model.

PubMed

Porcel, José M; Esquerda, Aureli; Martínez-Alonso, Montserrat; Bielsa, Silvia; Salud, Antonieta

2016-03-01

The diagnosis of malignant pleural effusions may be challenging when cytological examination of aspirated pleural fluid is equivocal or noncontributory. The purpose of this study was to identify protein candidate biomarkers differentially expressed in the pleural fluid of patients with mesothelioma, lung adenocarcinoma, lymphoma, and tuberculosis (TB).A multiplex protein biochip comprising 120 biomarkers was used to determine the pleural fluid protein profile of 29 mesotheliomas, 29 lung adenocarcinomas, 12 lymphomas, and 35 tuberculosis. The relative abundance of these predetermined biomarkers among groups served to establish the differential diagnosis of: malignant versus benign (TB) effusions, lung adenocarcinoma versus mesothelioma, and lymphoma versus TB. The selected putative markers were validated using widely available commercial techniques in an independent sample of 102 patients.Significant differences were found in the protein expressions of metalloproteinase-9 (MMP-9), cathepsin-B, C-reactive protein, and chondroitin sulfate between malignant and TB effusions. When integrated into a scoring model, these proteins yielded 85% sensitivity, 100% specificity, and an area under the curve (AUC) of 0.98 for labeling malignancy in the verification sample. For lung adenocarcinoma-mesothelioma discrimination, combining CA19-9, CA15-3, and kallikrein-12 had maximal discriminatory capacity (65% sensitivity, 100% specificity, AUC 0.94); figures which also refer to the validation set. Last, cathepsin-B in isolation was only moderately useful (sensitivity 89%, specificity 62%, AUC 0.75) in separating lymphomatous and TB effusions. However, this last differentiation improved significantly when cathepsin-B was used with respect to the patient's age (sensitivity 72%, specificity 100%, AUC 0.94).In conclusion, panels of 4 (i.e., MMP-9, cathepsin-B, C-reactive protein, chondroitin sulfate), or 3 (i.e., CA19-9, CA15-3, kallikrein-12) different protein biomarkers on pleural fluid samples are highly discriminative for signaling a malignant versus tuberculous effusion, or lung adenocarcinoma versus mesothelioma, respectively. Cathepsin-B could also be helpful in establishing the presence of a lymphomatous effusion versus that of TB, if the patient's age is simultaneously taken into consideration.

One-step fabrication of nanostructure-covered microstructures using selective aluminum anodization based on non-uniform electric field

NASA Astrophysics Data System (ADS)

Park, Yong Min; Kim, Byeong Hee; Seo, Young Ho

2016-06-01

This paper presents a selective aluminum anodization technique for the fabrication of microstructures covered by nanoscale dome structures. It is possible to fabricate bulging microstructures, utilizing the different growth rates of anodic aluminum oxide in non-uniform electric fields, because the growth rate of anodic aluminum oxide depends on the intensity of electric field, or current density. After anodizing under a non-uniform electric field, bulging microstructures covered by nanostructures were fabricated by removing the residual aluminum layer. The non-uniform electric field induced by insulative micropatterns was estimated by computational simulations and verified experimentally. Utilizing computational simulations, the intensity profile of the electric field was calculated according to the ratio of height and width of the insulative micropatterns. To compare computational simulation results and experimental results, insulative micropatterns were fabricated using SU-8 photoresist. The results verified that the shape of the bottom topology of anodic alumina was strongly dependent on the intensity profile of the applied electric field, or current density. The one-step fabrication of nanostructure-covered microstructures can be applied to various fields, such as nano-biochip and nano-optics, owing to its simplicity and cost effectiveness.

Use of radiation in biomaterials science

NASA Astrophysics Data System (ADS)

Benson, Roberto S.

2002-05-01

Radiation is widely used in the biomaterials science for surface modification, sterilization and to improve bulk properties. Radiation is also used to design of biochips, and in situ photopolymerizable of bioadhesives. The energy sources most commonly used in the irradiation of biomaterials are high-energy electrons, gamma radiation, ultraviolet (UV) and visible light. Surface modification involves placement of selective chemical moieties on the surface of a material by chemical reactions to improve biointeraction for cell adhesion and proliferation, hemocompatibility and water absorption. The exposure of a polymer to radiation, especially ionizing radiation, can lead to chain scission or crosslinking with changes in bulk and surface properties. Sterilization by irradiation is designed to inactivate most pathogens from the surface of biomedical devices. An overview of the use of gamma and UV radiation to improve surface tissue compatibility, bulk properties and surface properties for wear resistance, formation of hydrogels and curing dental sealants and bone adhesives is presented. Gamma and vacuum ultraviolet (VUV) irradiated ultrahigh molecular weight polyethylene (UHMWPE) exhibit improvement in surface modulus and hardness. The surface modulus and hardness of UHMWPE showed a dependence on type of radiation, dosage and processing. VUV surface modified e-PTFE vascular grafts exhibit increases in hydrophilicity and improvement towards adhesion of fibrin glue.

Silicon insulator-based dielectrophoresis devices for minimized heating effects.

PubMed

Zellner, Phillip; Agah, Masoud

2012-08-01

Concentration of biological specimens that are extremely dilute in a solution is of paramount importance for their detection. Microfluidic chips based on insulator-based DEP (iDEP) have been used to selectively concentrate bacteria and viruses. iDEP biochips are currently fabricated with glass or polymer substrates to allow for high electric fields within the channels. Joule heating is a well-known problem in these substrates and can lead to decreased throughput and even device failure. In this work, we present, for the first time, highly efficient trapping and separation of particles in DC iDEP devices that are fabricated on silicon using a single-etch-step three-dimensional microfabrication process with greatly improved heat dissipation properties. Fabrication in silicon allows for greater heat dissipation for identical geometries and operating conditions. The 3D fabrication allows for higher performance at lower applied potentials. Thermal measurements were performed on both the presented silicon chips and previously published PDMS devices comprised of microposts. Trapping and separation of 1 and 2 μm polystyrene particles was demonstrated. These results demonstrate the feasibility of high-performance silicon iDEP devices for the next generation of sorting and concentration microsystems. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Facile Fabrication of Hierarchically Thermoresponsive Binary Polymer Pattern for Controlled Cell Adhesion.

PubMed

Hou, Jianwen; Cui, Lele; Chen, Runhai; Xu, Xiaodong; Chen, Jiayue; Yin, Ligang; Liu, Jingchuan; Shi, Qiang; Yin, Jinghua

2018-03-01

A versatile platform allowing capture and detection of normal and dysfunctional cells on the same patterned surface is important for accessing the cellular mechanism, developing diagnostic assays, and implementing therapy. Here, an original and effective method for fabricating binary polymer brushes pattern is developed for controlled cell adhesion. The binary polymer brushes pattern, composed of poly(N-isopropylacrylamide) (PNIPAAm) and poly[poly(ethylene glycol) methyl ether methacrylate] (POEGMA) chains, is simply obtained via a combination of surface-initiated photopolymerization and surface-activated free radical polymerization. This method is unique in that it does not utilize any protecting groups or procedures of backfilling with immobilized initiator. It is demonstrated that the precise and well-defined binary polymer patterns with high resolution are fabricated using this facile method. PNIPAAm chains capture and release cells by thermoresponsiveness, while POEGMA chains possess high capability to capture dysfunctional cells specifically, inducing a switch of normal red blood cells (RBCs) arrays to hemolytic RBCs arrays on the pattern with temperature. This novel platform composed of binary polymer brush pattern is smart and versatile, which opens up pathways to potential applications as microsensors, biochips, and bioassays. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electro-induced protein deposition on low-fouling surfaces

NASA Astrophysics Data System (ADS)

Cole, M. A.; Voelcker, N. H.; Thissen, H.

2007-12-01

Control over protein adsorption is a key issue for numerous biomedical applications ranging from diagnostic microarrays to tissue-engineered medical devices. Here, we describe a method for creating surfaces that prevent non-specific protein adsorption, which upon application of an external trigger can be transformed into surfaces showing high protein adsorption on demand. Silicon wafers were used as substrate materials upon which thin functional coatings were constructed by the deposition of an allylamine plasma polymer followed by high-density grafting of poly(ethylene oxide) aldehyde, resulting in a low-fouling surface. When the underlying highly doped silicon substrate was used as an electrode, the resulting electrostatic attraction between the electrode and charged proteins in solution induced protein deposition at the low-fouling interface. X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) were used to characterize the surface modifications. Controlled protein adsorption experiments were carried out using horseradish peroxidase. The amount of protein deposited at the surface was then investigated by means of a colorimetric assay. It is expected that the concept described here will find use in a variety of biotechnological and biomedical applications, particularly in the area of biochips.

A highly efficient microfluidic nano biochip based on nanostructured nickel oxide.

PubMed

Ali, Md Azahar; Solanki, Pratima R; Patel, Manoj K; Dhayani, Hemant; Agrawal, Ved Varun; John, Renu; Malhotra, Bansi D

2013-04-07

We present results of the studies relating to fabrication of a microfluidic biosensor chip based on nickel oxide nanorods (NRs-NiO) that is capable of directly measuring the concentration of total cholesterol in human blood through electrochemical detection. Using this chip we demonstrate, with high reliability and in a time efficient manner, the detection of cholesterol present in buffer solutions at clinically relevant concentrations. The microfluidic channel has been fabricated onto a nickel oxide nanorod-based electrode co-immobilized with cholesterol esterase (ChEt) and cholesterol oxidase (ChOx) that serves as the working electrode. Bare indium tin oxide served as the counter electrode. A Ag/AgCl wire introduced to the outlet of the microchannel acts as a reference electrode. The fabricated NiO nanorod-based electrode has been characterized using X-ray diffraction, Raman spectroscopy, HR-TEM, FT-IR, UV-visible spectroscopy and electrochemical techniques. The presented NRs-NiO based microfluidic sensor exhibits linearity in the range of 1.5-10.3 mM, a high sensitivity of 0.12 mA mM(-1) cm(-2) and a low value of 0.16 mM of the Michaelis-Menten constant (Km).

[Genotyping of BRCA1, BRCA2 and CHEK2 germline mutations in Russian breast cancer patients using diagnostic biochips].

PubMed

Nasedkina, T V; Gromyko, O E; Emel'ianova, M A; Ignatova, E O; Kazubskaia, T P; Portnoĭ, S M; Zasedatelev, A S; Liubchenko, L N

2014-01-01

Germline mutations of BRCA1/2 genes cause the predisposition of their carriers to breast or/and ovary cancers (BC or/and OC) during the lifetime. Identification of these mutations is a basis of molecular diagnosis for BC susceptibility. Rapid genotyping technique using microarrays for identification of BRCA1 185delAG, 300T>G, 4153delA, 5382insC mutations and 4158 A>G sequence variant; BRCA2 695insT and 6174delT mutations; 1100delC mutation in CHEK2 gene was applied for 412 randomly collected breast cancer samples from the central region of European area of Russia. In 25 (6.0%) patients (6.0%) BC was associated with other tumours: OC, cervical cancer, colorectal cancer etc. BRCA1/2 and CHEK2 mutations were found in 33 (8.0%) BC patients. The most frequent mutation was BRCA1 5382insC, occurred in 16 (3.9%) BC patients, and CHEK2 1100delC, revealed in 7 (1.7%) BC patients. An application of diagnostic BC-microarray for genetic testing of BRCA1/2 and CHEK2 founder mutations has been discussed.

Systems Integration Challenges for a National Space Launch System

NASA Technical Reports Server (NTRS)

May, Todd A.

2011-01-01

System Integration was refined through the complexity and early failures experienced in rocket flight. System Integration encompasses many different viewpoints of the system development. System Integration must ensure consistency in development and operations activities. Human Space Flight tends toward large, complex systems. Understanding the system fs operational and use context is the guiding principle for System Integration: (1) Sizeable costs can be driven into systems by not fully understanding context (2). Adhering to the system context throughout the system fs life cycle is essential to maintaining efficient System Integration. System Integration exists within the System Architecture. Beautiful systems are simple in use and operation -- Block upgrades facilitate manageable steps in functionality evolution. Effective System Integration requires a stable system concept. Communication is essential to system simplicity

Energy Systems Integration Facility Control Room | Energy Systems

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Integration Facility | NREL Energy Systems Integration Facility Control Room Energy Systems Integration Facility Control Room The Energy Systems Integration Facility control room allows system engineers as the monitoring point for the facility's integrated safety and control systems. Photo of employees

What Is Energy Systems Integration? | Energy Systems Integration Facility |

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NREL What Is Energy Systems Integration? What Is Energy Systems Integration? Energy systems integration (ESI) is an approach to solving big energy challenges that explores ways for energy systems to Research Community NREL is a founding member of the International Institute for Energy Systems Integration

Subscribe to the Energy Systems Integration Newsletter | Energy Systems

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Integration Facility | NREL Subscribe to the Energy Systems Integration Newsletter Subscribe to the Energy Systems Integration Newsletter Subscribe to receive regular updates on what's happening at the Energy Systems Integration Facility and in energy systems integration research at NREL and around

Integration mechanisms and hospital efficiency in integrated health care delivery systems.

PubMed

Wan, Thomas T H; Lin, Blossom Yen-Ju; Ma, Allen

2002-04-01

This study analyzes integration mechanisms that affect system performances measured by indicators of efficiency in integrated delivery systems (IDSs) in the United States. The research question is, do integration mechanisms improve IDSs' efficiency in hospital care? American Hospital Association's Annual Survey (1998) and Dorenfest's Survey on Information Systems in Integrated Healthcare Delivery Systems (1998) were used to conduct the study, using IDS as the unit of analysis. A covariance structure equation model of the effects of system integration mechanisms on IDS performance was formulated and validated by an empirical examination of IDSs. The study sample includes 973 hospital-based integrated health care delivery systems operating in the United States, carried in the list of Dorenfests Survey on Information Systems in Integrated Health care Delivery Systems. The measurement indicators of system integration mechanisms are categorized into six related domains: informatic integration, case management, hybrid physician-hospital integration, forward integration, backward integration, and high tech medical services. The multivariate analysis reveals that integration mechanisms in system operation are positively correlated and positively affect IDSs' efficiency. The six domains of integration mechanisms account for 58.9% of the total variance in hospital performance. The service differentiation strategy such as having more high tech medical services have much stronger influences on efficiency than other integration mechanisms do. The beneficial effects of integration mechanisms have been realized in IDS performance. High efficiency in hospital care can be achieved by employing proper integration strategies in operations.

New Tethered Phospholipid Bilayers Integrating Functional G-Protein-Coupled Receptor Membrane Proteins.

PubMed

Chadli, Meriem; Rebaud, Samuel; Maniti, Ofelia; Tillier, Bruno; Cortès, Sandra; Girard-Egrot, Agnès

2017-10-03

Membrane proteins exhibiting extra- and intracellular domains require an adequate near-native lipid platform for their functional reconstitution. With this aim, we developed a new technology enabling the formation of a peptide-tethered bilayer lipid membrane (pep-tBLM), a lipid bilayer grafted onto peptide spacers, by way of a metal-chelate interaction. To this end, we designed an original peptide spacer derived from the natural α-laminin thiopeptide (P19) possessing a cysteine residue in the N-terminal extremity for grafting onto gold and a C-terminal extremity modified by four histidine residues (P19-4H). In the presence of nickel, the use of this anchor allowed us to bind liposomes of variable compositions containing a 2% molar ratio of a chelating lipid, 1,2-dioleoyl-sn-glycero-3-[(N-(5-amino-1-carboxypentyl)iminodiacetic acid)succinyl] so-called DOGS-NTA, and to form the planar bilayer by triggering liposome fusion by an α-helical (AH) peptide derived from the N-terminus of the hepatitis C virus NS5A protein. The formation of pep-tBLMs was characterized by surface plasmon resonance imaging (SPRi), and their continuity, fluidity, and homogeneity were demonstrated by fluorescence recovery after photobleaching (FRAP), with a diffusion coefficient of 2.5 × 10 -7 cm 2 /s, and atomic force microscopy (AFM). By using variable lipid compositions including phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol 4,5-bisphosphate (PIP 2 ), sphingomyelin (SM), phosphatidic acid (PA), and cholesterol (Chol) in various ratios, we show that the membrane can be formed independently from the lipid composition. We made the most of this advantage to reincorporate a transmembrane protein in an adapted complex lipid composition to ensure its functional reinsertion. For this purpose, a cell-free expression system was used to produce proteoliposomes expressing the functional C-X-C motif chemokine receptor 4 (CXCR4), a seven-transmembrane protein belonging to the large superfamily of G-protein-coupled receptors (GPCRs). We succeeded in reinserting CXCR4 in pep-tBLMs formed on P19-4H by the fusion of tethered proteoliposomes. AFM and FRAP characterization allowed us to show that pep-tBLMs inserting CXCR4 remained fluid, homogeneous, and continuous. The value of the diffusion coefficient determined in the presence of reinserted CXCR4 was 2 × 10 -7 cm 2 /s. Ligand binding assays using a synthetic CXCR4 antagonist, T22 ([Tyr5,12, Lys7]-polyphemusin II), revealed that CXCR4 can be reinserted in pep-tBLMs with functional folding and orientation. This new approach represents a method of choice for investigating membrane protein reincorporation and a promising way of creating a new generation of membrane biochips adapted for screening agonists or antagonists of transmembrane proteins.

Energy System Integration Facility Secure Data Center | Energy Systems

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Integration Facility | NREL Energy System Integration Facility Secure Data Center Energy System Integration Facility Secure Data Center The Energy Systems Integration Facility's Secure Data Center provides

Energy Systems Integration News | Energy Systems Integration Facility |

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NREL News Energy Systems Integration News A monthly recap of the latest happenings at the Energy Systems Integration Facility and developments in energy systems integration (ESI) research at NREL ; said Vahan Gevorgian, chief engineer with NREL's Power Systems Engineering Center. "Results of

Information integration in health care organizations: The case of a European health system.

PubMed

Calciolari, Stefano; Buccoliero, Luca

2010-01-01

Information system integration is an important dimension of a company's information system maturity and plays a relevant role in meeting information needs and accountability targets. However, no generalizable evidence exists about whether and how the main integrating technologies influence information system integration in health care organizations. This study examined how integrating technologies are adopted in public health care organizations and chief information officers' (CIOs) perceptions about their influence on information system integration. We used primary data on integrating technologies' adoption and CIOs' perception regarding information system integration in public health care organizations. Analysis of variance (ANOVA) and multinomial logistic regression were used to examine the relationship between CIOs' perception about information system integration and the adopted technologies. Data from 90 health care organizations were available for analyses. Integrating technologies are relatively diffused in public health care organizations, and CIOs seem to shape information system toward integrated architectures. There is a significant positive (although modest, .3) correlation between the number of integrating technologies adopted and the CIO's satisfaction with them. However, regression analysis suggests that organizations covering a broader spectrum of these technologies are less likely to have their CIO reporting main problems concerning integration in the administrative area of the information system compared with the clinical area and where the two areas overlap. Integrating technologies are associated with less perceived problems in the information system administrative area rather than in other areas. Because CIOs play the role of information resource allocators, by influencing information system toward integrated architecture, health care organization leaders should foster cooperation between CIOs and medical staff to enhance information system integration.

Data Entities and Information System Matrix for Integrated Agriculture Information System (IAIS)

NASA Astrophysics Data System (ADS)

Budi Santoso, Halim; Delima, Rosa

2018-03-01

Integrated Agriculture Information System is a system that is developed to process data, information, and knowledge in Agriculture sector. Integrated Agriculture Information System brings valuable information for farmers: (1) Fertilizer price; (2) Agriculture technique and practise; (3) Pest management; (4) Cultivation; (5) Irrigation; (6) Post harvest processing; (7) Innovation in agriculture processing. Integrated Agriculture Information System contains 9 subsystems. To bring an integrated information to the user and stakeholder, it needs an integrated database approach. Thus, researchers describes data entity and its matrix relate to subsystem in Integrated Agriculture Information System (IAIS). As a result, there are 47 data entities as entities in single and integrated database.

Energy Systems Integration Facility Videos | Energy Systems Integration

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Facility | NREL Energy Systems Integration Facility Videos Energy Systems Integration Facility Integration Facility NREL + SolarCity: Maximizing Solar Power on Electrical Grids Redefining What's Possible for Renewable Energy: Grid Integration Robot-Powered Reliability Testing at NREL's ESIF Microgrid

Systems Engineering and Integration for Advanced Life Support System and HST

NASA Technical Reports Server (NTRS)

Kamarani, Ali K.

2005-01-01

Systems engineering (SE) discipline has revolutionized the way engineers and managers think about solving issues related to design of complex systems: With continued development of state-of-the-art technologies, systems are becoming more complex and therefore, a systematic approach is essential to control and manage their integrated design and development. This complexity is driven from integration issues. In this case, subsystems must interact with one another in order to achieve integration objectives, and also achieve the overall system's required performance. Systems engineering process addresses these issues at multiple levels. It is a technology and management process dedicated to controlling all aspects of system life cycle to assure integration at all levels. The Advanced Integration Matrix (AIM) project serves as the systems engineering and integration function for the Human Support Technology (HST) program. AIM provides means for integrated test facilities and personnel for performance trade studies, analyses, integrated models, test results, and validated requirements of the integration of HST. The goal of AIM is to address systems-level integration issues for exploration missions. It will use an incremental systems integration approach to yield technologies, baselines for further development, and possible breakthrough concepts in the areas of technological and organizational interfaces, total information flow, system wide controls, technical synergism, mission operations protocols and procedures, and human-machine interfaces.

Integration of the TDWR and LLWAS wind shear detection system

NASA Technical Reports Server (NTRS)

Cornman, Larry

1991-01-01

Operational demonstrations of a prototype TDWR/LLWAS (Terminal Doppler Weather Radar/Low Level Wind shear Alarm System) integrated wind shear detection system were conducted. The integration of wind shear detection systems is needed to provide end-users with a single, consensus source of information. A properly implemented integrated system provides wind shear warnings of a higher quality than stand-alone LLWAS or TDWR systems. The algorithmic concept used to generate the TDWR/LLWAS integrated products and several case studies are discussed, indicating the viability and potential of integrated wind shear detection systems. Implications for integrating ground and airborne wind shear detection systems are briefly examined.

Cluster optical coding: from biochips to counterfeit security

NASA Astrophysics Data System (ADS)

Haglmueller, Jakob; Alguel, Yilmaz; Mayer, Christian; Matyushin, Viacheslav; Bauer, Georg; Pittner, Fritz; Leitner, Alfred; Aussenegg, Franz R.; Schalkhammer, Thomas G.

2004-07-01

Spatially tuned resonant nano-clusters allow high local field enhancement when exited by electromagnetic radiation. A number of phenomena had been described and subsequently applied to novel nano- and bionano-devices. Decisive for these types of devices and sensors is the precise nanometric assembly, coupling the local field surrounding a cluster to allow resonance with other elements interacting with this field. In particular, the distance cluster-mirror or cluster-fluorophore gives rise to a variety of enhancement phenomena. High throughput transducers using metal cluster resonance technology are based on surface-enhancement of metal cluster light absorption (SEA). The optical property for the analytical application of metal cluster films is the so-called anomalous absorption. At a well defined nanometric distance of a cluster to a mirror the reflected electromagnetic field has the same phase at the position of the absorbing cluster as the incident fields. This feedback mechanism strongly enhances the effective cluster absorption coefficient. The system is characterised by a narrow reflection minimum. Based on this SEA-phenomenon (licensed to and further developed and optimized by NovemberAG, Germany Erlangen) a number of commercial products have been constructed. Brandsealing(R) uses the patented SEA cluster technology to produce optical codings. Cluster SEA thin film systems show a characteristic color-flip effect and are extremely mechanically and thermally robust. This is the basis for its application as an unique security feature. The specific spectroscopic properties as e.g. narrow band multi-resonance of the cluster layers allow the authentication of the optical code which can be easily achieved with a mobile hand-held reader developed by november AG and Siemens AG. Thus, these features are machine-readable which makes them superior to comparable technologies. Cluster labels are available in two formats: as a label for tamper-proof product packaging, and as a direct label, where label and logo are permanently applied directly and unremovable to the product surface. Together with Infineon Technologies and HUECK FOLIEN, the SEA technology is currently developed as a direct label for e.g. SmartCards.

NEXT Single String Integration Test Results

NASA Technical Reports Server (NTRS)

Soulas, George C.; Patterson, Michael J.; Pinero, Luis; Herman, Daniel A.; Snyder, Steven John

2010-01-01

As a critical part of NASA's Evolutionary Xenon Thruster (NEXT) test validation process, a single string integration test was performed on the NEXT ion propulsion system. The objectives of this test were to verify that an integrated system of major NEXT ion propulsion system elements meets project requirements, to demonstrate that the integrated system is functional across the entire power processor and xenon propellant management system input ranges, and to demonstrate to potential users that the NEXT propulsion system is ready for transition to flight. Propulsion system elements included in this system integration test were an engineering model ion thruster, an engineering model propellant management system, an engineering model power processor unit, and a digital control interface unit simulator that acted as a test console. Project requirements that were verified during this system integration test included individual element requirements ; integrated system requirements, and fault handling. This paper will present the results of these tests, which include: integrated ion propulsion system demonstrations of performance, functionality and fault handling; a thruster re-performance acceptance test to establish baseline performance: a risk-reduction PMS-thruster integration test: and propellant management system calibration checks.

Choosing the Right Systems Integration

NASA Astrophysics Data System (ADS)

Péči, Matúš; Važan, Pavel

2014-12-01

The paper examines systems integration and its main levels at higher levels of control. At present, the systems integration is one of the main aspects participating in the consolidation processes and financial flows of a company. Systems Integration is a complicated emotionconsuming process and it is often a problem to choose the right approach and level of integration. The research focused on four levels of integration, while each of them is characterized by specific conditions. At each level, there is a summary of recommendations and practical experience. The paper also discusses systems integration between the information and MES levels. The main part includes user-level integration where we describe an example of such integration. Finally, we list recommendations and also possible predictions of the systems integration as one of the important factors in the future.

What Is Energy Systems Integration? (Text Version) | Energy Systems

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Integration Facility | NREL What Is Energy Systems Integration? (Text Version) What Is Energy Systems Integration? (Text Version) This is a text version of the video "What Is Energy Systems

Fuel Distribution Systems | Energy Systems Integration Facility | NREL

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Fuel Distribution Systems Fuel Distribution Systems The Energy Systems Integration Facility's integrated fuel distribution systems provide natural gas, hydrogen, and diesel throughout its laboratories in two laboratories: the Power Systems Integration Laboratory and the Energy Storage Laboratory. Each

Application of NMR Methods to Identify Detection Reagents for Use in the Development of Robust Nanosensors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cosman, M; Krishnan, V V; Balhorn, R

2004-04-29

Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful technique for studying bi-molecular interactions at the atomic scale. Our NMR lab is involved in the identification of small molecules, or ligands that bind to target protein receptors, such as tetanus (TeNT) and botulinum (BoNT) neurotoxins, anthrax proteins and HLA-DR10 receptors on non-Hodgkin's lymphoma cancer cells. Once low affinity binders are identified, they can be linked together to produce multidentate synthetic high affinity ligands (SHALs) that have very high specificity for their target protein receptors. An important nanotechnology application for SHALs is their use in the development of robust chemical sensors ormore » biochips for the detection of pathogen proteins in environmental samples or body fluids. Here, we describe a recently developed NMR competition assay based on transferred nuclear Overhauser effect spectroscopy (trNOESY) that enables the identification of sets of ligands that bind to the same site, or a different site, on the surface of TeNT fragment C (TetC) than a known ''marker'' ligand, doxorubicin. Using this assay, we can identify the optimal pairs of ligands to be linked together for creating detection reagents, as well as estimate the relative binding constants for ligands competing for the same site.« less

Patterned self-assembled monolayers of alkanethiols on copper nanomembranes by submerged laser ablation

NASA Astrophysics Data System (ADS)

Rhinow, Daniel; Hampp, Norbert A.

2012-06-01

Self-assembled monolayers (SAMs) of alkanethiols are major building blocks for nanotechnology. SAMs provide a functional interface between electrodes and biomolecules, which makes them attractive for biochip fabrication. Although gold has emerged as a standard, copper has several advantages, such as compatibility with semiconductors. However, as copper is easily oxidized in air, patterning SAMs on copper is a challenging task. In this work we demonstrate that submerged laser ablation (SLAB) is well-suited for this purpose, as thiols are exchanged in-situ, avoiding air exposition. Using different types of ω-substituted alkanethiols we show that alkanethiol SAMs on copper surfaces can be patterned using SLAB. The resulting patterns were analyzed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Both methods indicate that the intense laser beam promotes the exchange of thiols at the copper surface. Furthermore, we present a procedure for the production of free-standing copper nanomembranes, oxidation-protected by alkanethiol SAMs. Incubation of copper-coated mica in alkanethiol solutions leads to SAM formation on both surfaces of the copper film due to intercalation of the organic molecules. Corrosion-protected copper nanomembranes were floated onto water, transferred to electron microscopy grids, and subsequently analyzed by electron energy loss spectroscopy (EELS).

Biomedical informatics and the convergence of Nano-Bio-Info-Cogno (NBIC) technologies.

PubMed

Martin-Sanchez, F; Maojo, V

2009-01-01

To analyze the role that biomedical informatics could play in the application of the NBIC Converging Technologies in the medical field and raise awareness of these new areas throughout the Biomedical Informatics community. Review of the literature and analysis of the reference documents in this domain from the biomedical informatics perspective. Detailing existing developments showing that partial convergence of technologies have already yielded relevant results in biomedicine (such as bioinformatics or biochips). Input from current projects in which the authors are involved is also used. Information processing is a key issue in enabling the convergence of NBIC technologies. Researchers in biomedical informatics are in a privileged position to participate and actively develop this new scientific direction. The experience of biomedical informaticians in five decades of research in the medical area and their involvement in the completion of the Human and other genome projects will help them participate in a similar role for the development of applications of converging technologies -particularly in nanomedicine. The proposed convergence will bring bridges between traditional disciplines. Particular attention should be placed on the ethical, legal, and social issues raised by the NBIC convergence. These technologies provide new directions for research and education in Biomedical Informatics placing a greater emphasis in multidisciplinary approaches.

Novel calibration tools and validation concepts for microarray-based platforms used in molecular diagnostics and food safety control.

PubMed

Brunner, C; Hoffmann, K; Thiele, T; Schedler, U; Jehle, H; Resch-Genger, U

2015-04-01

Commercial platforms consisting of ready-to-use microarrays printed with target-specific DNA probes, a microarray scanner, and software for data analysis are available for different applications in medical diagnostics and food analysis, detecting, e.g., viral and bacteriological DNA sequences. The transfer of these tools from basic research to routine analysis, their broad acceptance in regulated areas, and their use in medical practice requires suitable calibration tools for regular control of instrument performance in addition to internal assay controls. Here, we present the development of a novel assay-adapted calibration slide for a commercialized DNA-based assay platform, consisting of precisely arranged fluorescent areas of various intensities obtained by incorporating different concentrations of a "green" dye and a "red" dye in a polymer matrix. These dyes present "Cy3" and "Cy5" analogues with improved photostability, chosen based upon their spectroscopic properties closely matching those of common labels for the green and red channel of microarray scanners. This simple tool allows to efficiently and regularly assess and control the performance of the microarray scanner provided with the biochip platform and to compare different scanners. It will be eventually used as fluorescence intensity scale for referencing of assays results and to enhance the overall comparability of diagnostic tests.

Portable Diagnostics Technology Assessment for Space Missions. Part 1; General Technology Capabilities for NASA Exploration Missions

NASA Technical Reports Server (NTRS)

Nelson, Emily S.; Chait, Arnon

2010-01-01

The changes in the scope of NASA s mission in the coming decade are profound and demand nimble, yet insightful, responses. On-board clinical and environmental diagnostics must be available for both mid-term lunar and long-term Mars exploration missions in an environment marked by scarce resources. Miniaturization has become an obvious focus. Despite solid achievements in lab-based devices, broad-based, robust tools for application in the field are not yet on the market. The confluence of rapid, wide-ranging technology evolution and internal planning needs are the impetus behind this work. This report presents an analytical tool for the ongoing evaluation of promising technology platforms based on mission- and application-specific attributes. It is not meant to assess specific devices, but rather to provide objective guidelines for a rational down-select of general categories of technology platforms. In this study, we have employed our expertise in the microgravity operation of fluidic devices, laboratory diagnostics for space applications, and terrestrial research in biochip development. A rating of the current state of technology development is presented using the present tool. Two mission scenarios are also investigated: a 30-day lunar mission using proven, tested technology in 5 years; and a 2- to 3-year mission to Mars in 10 to 15 years.

Correlation Analysis Between Expression Levels of Hepatic Growth Hormone Receptor, Janus Kinase 2, Insulin-Like Growth Factor-I Genes and Dwarfism Phenotype in Bama Minipig.

PubMed

Yang, Haowen; Jiang, Qinyang; Wu, Dan; Lan, Ganqiu; Fan, Jing; Guo, Yafen; Chen, Baojian; Yang, Xiurong; Jiang, Hesheng

2015-02-01

Animal growth and development are complex and sophisticated biological metabolic processes, in which genes plays an important role. In this paper, we employed real-time quantitative PCR (RT-qPCR) to analyze the expression levels of hepatic GHR, JAK2 and IGF-I genes in 1, 30, 180 day of Bama minipig and Landrace with attempt to verify the correlation between the expression of these growth-associated genes and the dwarfism phenotype of Bama minipig. The results showed that the expression levels of these 3 genes in Bama minipigs were down-regulated expressed from 1 day to 30 day, and which was up-regulated expressed in Landrace. The expression levels of the 3 genes on 1, 30, 180 day were prominently higher in Landrace than in Bama minipigs. The significant differences of the 3 genes expression levels on 1 day between this two breeds indicate that different expressions of these genes might occur before birth. It is speculated that the down-regulated expression of the 3 genes may have a close correlation with the dwarfism phenotype of Bama minipig. More investigations in depth of this study is under progress with the help of biochip nanotechnology.

Servo scanning 3D micro EDM for array micro cavities using on-machine fabricated tool electrodes

NASA Astrophysics Data System (ADS)

Tong, Hao; Li, Yong; Zhang, Long

2018-02-01

Array micro cavities are useful in many fields including in micro molds, optical devices, biochips and so on. Array servo scanning micro electro discharge machining (EDM), using array micro electrodes with simple cross-sectional shape, has the advantage of machining complex 3D micro cavities in batches. In this paper, the machining errors caused by offline-fabricated array micro electrodes are analyzed in particular, and then a machining process of array servo scanning micro EDM is proposed by using on-machine fabricated array micro electrodes. The array micro electrodes are fabricated on-machine by combined procedures including wire electro discharge grinding, array reverse copying and electrode end trimming. Nine-array tool electrodes with Φ80 µm diameter and 600 µm length are obtained. Furthermore, the proposed process is verified by several machining experiments for achieving nine-array hexagonal micro cavities with top side length of 300 µm, bottom side length of 150 µm, and depth of 112 µm or 120 µm. In the experiments, a chip hump accumulates on the electrode tips like the built-up edge in mechanical machining under the conditions of brass workpieces, copper electrodes and the dielectric of deionized water. The accumulated hump can be avoided by replacing the water dielectric by an oil dielectric.

One-step large-scale deposition of salt-free DNA origami nanostructures

PubMed Central

Linko, Veikko; Shen, Boxuan; Tapio, Kosti; Toppari, J. Jussi; Kostiainen, Mauri A.; Tuukkanen, Sampo

2015-01-01

DNA origami nanostructures have tremendous potential to serve as versatile platforms in self-assembly -based nanofabrication and in highly parallel nanoscale patterning. However, uniform deposition and reliable anchoring of DNA nanostructures often requires specific conditions, such as pre-treatment of the chosen substrate or a fine-tuned salt concentration for the deposition buffer. In addition, currently available deposition techniques are suitable merely for small scales. In this article, we exploit a spray-coating technique in order to resolve the aforementioned issues in the deposition of different 2D and 3D DNA origami nanostructures. We show that purified DNA origamis can be controllably deposited on silicon and glass substrates by the proposed method. The results are verified using either atomic force microscopy or fluorescence microscopy depending on the shape of the DNA origami. DNA origamis are successfully deposited onto untreated substrates with surface coverage of about 4 objects/mm2. Further, the DNA nanostructures maintain their shape even if the salt residues are removed from the DNA origami fabrication buffer after the folding procedure. We believe that the presented one-step spray-coating method will find use in various fields of material sciences, especially in the development of DNA biochips and in the fabrication of metamaterials and plasmonic devices through DNA metallisation. PMID:26492833

Detection of Pathological Changes in the Aorta during Thoracic Aortic Aneurysm Progression on Molecular Level

PubMed Central

Rabajdová, Miroslava; Špaková, Ivana; Panagiotis, Artemiou; Ferenčáková, Michaela; Rybár, Dušan; Bobrov, Nikita; Sabol, František

2017-01-01

The progression of thoracic aortic aneurysm depends on regulation of aortic wall homeostasis and on changes in the structural components of the extracellular matrix, which are affected by multiple molecular signalling pathways. We decided to correlate the diameter of ascending thoracic aneurysm with gene expression of inflammation markers (IL-6, CRP), cytokine receptors (IL-6R, TNFR1, and TNFR2), and extracellular matrix components (Emilin-1, MMP9, and TIMP) for detection of the degree of pathological process of TAA formation. The experimental group was divided into three groups according to the diameter of the aortic aneurysm. Whole blood and tissue samples were properly collected and used for nucleic acid, chromatin, and protein isolation. The mRNA levels were detected by qRT-PCR. For the detection of protein levels a Cytokine Array IV assay kit was used in combination with a biochip analyzer. In aortic tissue, significant positive correlations were found between increased mRNA levels of inflammatory cytokines (CRP and IL-6) on both mRNA levels in tissue and protein from the blood with maximum in stage 3. Changes of gene expression of selected genes can be used for the experimental study of the inflammatory receptor inhibitors during trials targeted on slowing down the progress of aortic wall aneurysm. PMID:29158612

Diazonium-protein adducts for graphite electrode microarrays modification: direct and addressed electrochemical immobilization.

PubMed

Corgier, Benjamin P; Marquette, Christophe A; Blum, Loïc J

2005-12-28

Diazonium cation electrodeposition was investigated for the direct and electro-addressed immobilization of proteins. For the first time, this reaction was triggered directly onto diazonium-modified proteins. Screen-printed (SP) graphite electrode microarrays were studied as active support for this immobilization. A 10-microelectrode (eight working electrodes, 0.2 mm2 each; one reference; and one auxiliary) setup was used to study the addressing possibilities of the method. These electrode microarrays were shown to be able to covalently graft diazonium cations through electrochemical reduction. Cyclic voltammetry and X-ray photoelectron spectroscopy were used to characterize the electrochemical grafting onto our SP graphite surface and suggested that a diazonium monolayer was deposited. Rabbit and human immunoglobulins (IgGs) were then chemically coupled to an aniline derivative (4-carboxymethylaniline), followed by diazotation to form an aryl diazonium function available for the electrodeposition. These modified proteins were both successfully electro-addressed at the surface of the graphite electrodes without cross-talk or interference. The immuno-biochip obtained using this novel approach enabled the specific detection of anti-rabbit IgG antibodies with a detection limit of 50 fmol of protein. A promising strategy to immobilize markedly different biological entities was then presented, providing an excellent spatial specificity of the electro-addressing.

Thermal Distribution System | Energy Systems Integration Facility | NREL

Science.gov Websites

Thermal Distribution System Thermal Distribution System The Energy Systems Integration Facility's integrated thermal distribution system consists of a thermal water loop connected to a research boiler and . Photo of the roof of the Energy Systems Integration Facility. The thermal distribution bus allows

The Structure and Effectiveness of Health Systems: Exploring the Impact of System Integration in Rural China.

PubMed

Wang, Xin; Birch, Stephen; Ma, Huifen; Zhu, Weiming; Meng, Qingyue

2016-08-12

Facing the challenges of aging populations, increasing chronic diseases prevalence and health system fragmentation, there have been several pilots of integrated health systems in China. But little is known about their structure, mechanism and effectiveness. The aim of this paper is to analyze health system integration and develop recommendations for achieving integration. Huangzhong and Hualong counties in Qinghai province were studied as study sites, with only Huangzhong having implemented health system integration. Questionnaires, interviews, and health insurance records were sources of data. Social network analysis was employed to analyze integration, through structure measurement and effectiveness evaluation. Health system integration in Huangzhong is higher than in Hualong, so is system effectiveness. The patient referral network in Hualong has more "leapfrog" referrals. The information sharing networks in both counties are larger than the other types of networks. The average distance in the joint training network of Huangzhong is less than in Hualong. Meanwhile, there are deficiencies common to both systems. Both county health systems have strengths and limitations regarding system integration. The use of medical consortia in Huangzhong has contributed to system effectiveness. Future research might consider alternative more context specific models of health system integration.

48 CFR 209.571-5 - Lead system integrators.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Lead system integrators... Consultant Conflicts of Interest 209.571-5 Lead system integrators. For limitations on contractors acting as lead systems integrators, see 209.570. [75 FR 81913, Dec. 29, 2010] ...

48 CFR 209.571-5 - Lead system integrators.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Lead system integrators... Consultant Conflicts of Interest 209.571-5 Lead system integrators. For limitations on contractors acting as lead systems integrators, see 209.570. [75 FR 81913, Dec. 29, 2010] ...

48 CFR 209.571-5 - Lead system integrators.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Lead system integrators... Consultant Conflicts of Interest 209.571-5 Lead system integrators. For limitations on contractors acting as lead systems integrators, see 209.570. [75 FR 81913, Dec. 29, 2010] ...

48 CFR 209.571-5 - Lead system integrators.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Lead system integrators... Consultant Conflicts of Interest 209.571-5 Lead system integrators. For limitations on contractors acting as lead systems integrators, see 209.570. [75 FR 81913, Dec. 29, 2010] ...

Thermalization threshold in models of 1D fermions

NASA Astrophysics Data System (ADS)

Mukerjee, Subroto; Modak, Ranjan; Ramswamy, Sriram

2013-03-01

The question of how isolated quantum systems thermalize is an interesting and open one. In this study we equate thermalization with non-integrability to try to answer this question. In particular, we study the effect of system size on the integrability of 1D systems of interacting fermions on a lattice. We find that for a finite-sized system, a non-zero value of an integrability breaking parameter is required to make an integrable system appear non-integrable. Using exact diagonalization and diagnostics such as energy level statistics and the Drude weight, we find that the threshold value of the integrability breaking parameter scales to zero as a power law with system size. We find the exponent to be the same for different models with its value depending on the random matrix ensemble describing the non-integrable system. We also study a simple analytical model of a non-integrable system with an integrable limit to better understand how a power law emerges.

4. Exterior view of Systems Integration Laboratory Building (T28), looking ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. Exterior view of Systems Integration Laboratory Building (T-28), looking northwest. - Air Force Plant PJKS, Systems Integration Laboratory, Systems Integration Laboratory Building, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

3. Exterior view of Systems Integration Laboratory Building (T28), looking ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. Exterior view of Systems Integration Laboratory Building (T-28), looking southeast. - Air Force Plant PJKS, Systems Integration Laboratory, Systems Integration Laboratory Building, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

46 CFR 111.105-5 - System integrity.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false System integrity. 111.105-5 Section 111.105-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Hazardous Locations § 111.105-5 System integrity. In order to maintain system integrity, each...

46 CFR 111.105-5 - System integrity.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false System integrity. 111.105-5 Section 111.105-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Hazardous Locations § 111.105-5 System integrity. In order to maintain system integrity, each...

46 CFR 111.105-5 - System integrity.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false System integrity. 111.105-5 Section 111.105-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Hazardous Locations § 111.105-5 System integrity. In order to maintain system integrity, each...

Completely integrable 2D Lagrangian systems and related integrable geodesic flows on various manifolds

NASA Astrophysics Data System (ADS)

Yehia, Hamad M.

2013-08-01

In this study we have formulated a theorem that generates deformations of the natural integrable conservative systems in the plane into integrable systems on Riemannian and other manifolds by introducing additional parameters into their structures. The relation of explicit solutions of the new and the original dynamics to the corresponding Jacobi (Maupertuis) geodesic flow is clarified. For illustration, we apply the result to three concrete examples of the many available integrable systems in the literature. Complementary integrals in those systems are polynomial in velocity with degrees 3, 4 and 6, respectively. As a special case of the first deformed system, a new several-parameter family of integrable mechanical systems (and geodesic flows) on S2 is constructed.

48 CFR 9.104-6 - Federal Awardee Performance and Integrity Information System.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Performance and Integrity Information System. 9.104-6 Section 9.104-6 Federal Acquisition Regulations System... Contractors 9.104-6 Federal Awardee Performance and Integrity Information System. (a) Before awarding a... Federal Awardee Performance and Integrity Information System (FAPIIS), (available at www.ppirs.gov, then...

48 CFR 9.104-6 - Federal Awardee Performance and Integrity Information System.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Performance and Integrity Information System. 9.104-6 Section 9.104-6 Federal Acquisition Regulations System... Contractors 9.104-6 Federal Awardee Performance and Integrity Information System. (a) Before awarding a... Federal Awardee Performance and Integrity Information System (FAPIIS), (available at www.ppirs.gov, then...

Man-systems integration and the man-machine interface

NASA Technical Reports Server (NTRS)

Hale, Joseph P.

1990-01-01

Viewgraphs on man-systems integration and the man-machine interface are presented. Man-systems integration applies the systems' approach to the integration of the user and the machine to form an effective, symbiotic Man-Machine System (MMS). A MMS is a combination of one or more human beings and one or more physical components that are integrated through the common purpose of achieving some objective. The human operator interacts with the system through the Man-Machine Interface (MMI).

Integrating Child Health Information Systems

PubMed Central

Hinman, Alan R.; Eichwald, John; Linzer, Deborah; Saarlas, Kristin N.

2005-01-01

The Health Resources and Services Administration and All Kids Count (a national technical assistance center fostering development of integrated child health information systems) have been working together to foster development of integrated child health information systems. Activities have included: identification of key elements for successful integration of systems; development of principles and core functions for the systems; a survey of state and local integration efforts; and a conference to develop a common vision for child health information systems to meet medical care and public health needs. We provide 1 state (Utah) as an example that is well on the way to development of integrated child health information systems. PMID:16195524

75 FR 66131 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-27

... Integration and Visualization System,'' JUSTICE/FBI-021, which describes the Data Integration and... Liberties Officer. JUSTICE/FBI-021 SYSTEM NAME: Data Integration and Visualization System. * * * * * SYSTEM...

Conceptualizing and measuring integration: findings from the health systems integration study.

PubMed

Gillies, R R; Shortell, S M; Anderson, D A; Mitchell, J B; Morgan, K L

1993-01-01

Given the pressures for health care reform, interest in the concept of integrated or organized delivery systems as a means to offer more coordinated cost-effective care is growing. This article has two primary objectives: (1) to clarify the different types of integration associated with the notion of an organized delivery system, and (2) to share the results from an ongoing study of 12 organized delivery systems. The findings indicate a moderate level of integration overall, particularly in the areas of culture, financial planning, and strategic planning. The study found that corporate staff respondents perceive their systems to be more integrated and effective than do operating unit managers, and that some functional integration areas are positively associated with both physician-system and clinical integration that, in turn, are positively related to each other. Overall, perceived integration was found to be positively associated with perceived effectiveness.

Reductions in finite-dimensional integrable systems and special points of classical r-matrices

NASA Astrophysics Data System (ADS)

Skrypnyk, T.

2016-12-01

For a given 𝔤 ⊗ 𝔤-valued non-skew-symmetric non-dynamical classical r-matrices r(u, v) with spectral parameters, we construct the general form of 𝔤-valued Lax matrices of finite-dimensional integrable systems satisfying linear r-matrix algebra. We show that the reduction in the corresponding finite-dimensional integrable systems is connected with "the special points" of the classical r-matrices in which they become degenerated. We also propose a systematic way of the construction of additional integrals of the Lax-integrable systems associated with the symmetries of the corresponding r-matrices. We consider examples of the Lax matrices and integrable systems that are obtained in the framework of the general scheme. Among them there are such physically important systems as generalized Gaudin systems in an external magnetic field, ultimate integrable generalization of Toda-type chains (including "modified" or "deformed" Toda chains), generalized integrable Jaynes-Cummings-Dicke models, integrable boson models generalizing Bose-Hubbard dimer models, etc.

48 CFR 1334.202 - Integrated baseline reviews.

Code of Federal Regulations, 2012 CFR

2012-10-01

... CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION Earned Value Management System 1334.202 Integrated baseline reviews. An Integrated Baseline Review shall be conducted when an Earned Value Management System... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Integrated baseline...

48 CFR 1334.202 - Integrated baseline reviews.

Code of Federal Regulations, 2011 CFR

2011-10-01

... CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION Earned Value Management System 1334.202 Integrated baseline reviews. An Integrated Baseline Review shall be conducted when an Earned Value Management System... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Integrated baseline...

48 CFR 1334.202 - Integrated baseline reviews.

Code of Federal Regulations, 2010 CFR

2010-10-01

... CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION Earned Value Management System 1334.202 Integrated baseline reviews. An Integrated Baseline Review shall be conducted when an Earned Value Management System... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Integrated baseline...

48 CFR 1334.202 - Integrated baseline reviews.

Code of Federal Regulations, 2014 CFR

2014-10-01

... CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION Earned Value Management System 1334.202 Integrated baseline reviews. An Integrated Baseline Review shall be conducted when an Earned Value Management System... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Integrated baseline...

48 CFR 1334.202 - Integrated baseline reviews.

Code of Federal Regulations, 2013 CFR

2013-10-01

... CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION Earned Value Management System 1334.202 Integrated baseline reviews. An Integrated Baseline Review shall be conducted when an Earned Value Management System... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Integrated baseline...

System integration case study : FAST-TRAC : preliminary IV deliverable : #2-systems integration case study

DOT National Transportation Integrated Search

1999-02-12

This report focuses on the system integration aspect of the Transportation Information Management System (TIMS), a component of the FAST-TRAC project. The TIMS functions as the center of a communications network which integrates advanced traffic cont...

NREL Leads Energy Systems Integration, Continuum Magazine: Issue 4 (Book)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

2013-04-01

Continuum Magazine showcases NREL's latest and most impactful clean energy innovations. This issue, 'NREL Leads Energy Systems Integration' explores the discipline of energy systems integration, in particular the role of the laboratory's new, one-of-a-kind Energy System Integration Facility. NREL scientists, engineers, and analysts deeply understand the fundamental science and technologies underpinning major energy producing and consuming systems, as well as the transmission infrastructure and communications and data networks required to integrate energy systems at all scales.

Integration of Systems with Varying Levels of Autonomy (Integration de Systemes a Niveau d’Autonomie Variable)

DTIC Science & Technology

2008-09-01

SCI-144 Integration of Systems with Varying Levels of Autonomy (Intégration de systèmes à niveau d’autonomie variable) This Report was...prepared by Task Group SCI-144 on “ System -Level Integration of Control plus Automation” and has been sponsored by the Systems Concepts and Integration... Systems with Varying Levels of Autonomy (Intégration de systèmes à niveau d’autonomie variable) This Report was prepared by Task Group SCI-144 on

Integration of Systems with Varying Levels of Autonomy (Integration de systemes a niveau d’autonomie variable)

DTIC Science & Technology

2008-09-01

SCI-144 Integration of Systems with Varying Levels of Autonomy (Intégration de systèmes à niveau d’autonomie variable) This Report was...prepared by Task Group SCI-144 on “ System -Level Integration of Control plus Automation” and has been sponsored by the Systems Concepts and Integration... Systems with Varying Levels of Autonomy (Intégration de systèmes à niveau d’autonomie variable) This Report was prepared by Task Group SCI-144 on

Highly Stable Bonding of Thiol Monolayers to Hydrogen-Terminated Si via Supercritical Carbon Dioxide: Toward a Super Hydrophobic and Bioresistant Surface.

PubMed

Bhartia, Bhavesh; Puniredd, Sreenivasa Reddy; Jayaraman, Sundaramurthy; Gandhimathi, Chinnasamy; Sharma, Mohit; Kuo, Yen-Chien; Chen, Chia-Hao; Reddy, Venugopal Jayarama; Troadec, Cedric; Srinivasan, Madapusi Palavedu

2016-09-21

Oxide-free silicon chemistry has been widely studied using wet-chemistry methods, but for emerging applications such as molecular electronics on silicon, nanowire-based sensors, and biochips, these methods may not be suitable as they can give rise to defects due to surface contamination, residual solvents, which in turn can affect the grafted monolayer devices for practical applications. Therefore, there is a need for a cleaner, reproducible, scalable, and environmentally benign monolayer grafting process. In this work, monolayers of alkylthiols were deposited on oxide-free semiconductor surfaces using supercritical carbon dioxide (SCCO2) as a carrier fluid owing to its favorable physical properties. The identity of grafted monolayers was monitored with Fourier transform infrared (FTIR) spectroscopy, high-resolution X-ray photoelectron spectroscopy (HRXPS), XPS, atomic force microscopy (AFM), contact angle measurements, and ellipsometry. Monolayers on oxide-free silicon were able to passivate the surface for more than 50 days (10 times than the conventional methods) without any oxide formation in ambient atmosphere. Application of the SCCO2 process was further extended by depositing alkylthiol monolayers on fragile and brittle 1D silicon nanowires (SiNWs) and 2D germanium substrates. With the recent interest in SiNWs for biological applications, the thiol-passivated oxide-free silicon nanowire surfaces were also studied for their biological response. Alkylthiol-functionalized SiNWs showed a significant decrease in cell proliferation owing to their superhydrophobicity combined with the rough surface morphology. Furthermore, tribological studies showed a sharp decrease in the coefficient of friction, which was found to be dependent on the alkyl chain length and surface bond. These studies can be used for the development of cost-effective and highly stable monolayers for practical applications such as solar cells, biosensors, molecular electronics, micro- and nano- electromechanical systems, antifouling agents, and drug delivery.

Toward a Digital Resilience (with a Dash of Location Enlightenment)

NASA Astrophysics Data System (ADS)

Wright, D. J.

2015-12-01

The AGU Earth and Space Science Informatics Focus Group addresses a compelling array of research questions and projects. This year's session topics range from large-scale data management within global cyberinfrastructures or virtual observatories, to intelligent systems theory, semantics, and handling of near-real-time data streams, to issues of "dark data," data transparency, reproducibility, and more. The aim of this lecture is to build in part on these themes but to consider more broadly how we might push the boundaries of informatics knowledge more along the lines of use-inspired science (responsive to the needs and perspectives of society while still being fundamental and cutting edge). To wit, as we contend with human impacts on the biosphere recent innovations in computational and data science are now facilitating community resilience to climate change (e.g., helping communities to monitoring air quality or drought, find available drinking water, determine habitat vulnerability, etc.). But not often discussed is a path toward digital resilience. If digital tools are to continue helping communities, it stands to reason that they must engender some resilience themselves. The capacity to deal effectively with change and threats, to recover quickly from challenges or difficulties, even to withstand stress and catastrophe, can apply to data too. As investments in digital data continue to rise, we find ourselves in new "digital world order" comprised of ubiquitous technologies from satellites to wristwatches to human biochip implants. And a significant proportion of these are geospatial, given the incredible power of maps to communicate, persuade, inspire, understand, and elicit action. Therefore, the lecture reviews and recommends seven fundamental digital research and communication practices. The aim is ensuring not only a modicum of resilience for our nascent discipline, but in prototyping and delivering repeatable solutions that all can use to help guide the planet towards a more resilient future.

48 CFR 3052.209-74 - Limitations on contractors acting as lead system integrators.

Code of Federal Regulations, 2010 CFR

2010-10-01

... acting as lead system integrators. 3052.209-74 Section 3052.209-74 Federal Acquisition Regulations System... contractors acting as lead system integrators. As prescribed in (HSAR) 48 CFR 3009.570-4(a), use the following provision: LIMITATIONS ON CONTRACTORS ACTING AS LEAD SYSTEM INTEGRATORS (JUL 2010) (a) Definitions. “Direct...

48 CFR 3052.209-74 - Limitations on contractors acting as lead system integrators.

Code of Federal Regulations, 2011 CFR

2011-10-01

... acting as lead system integrators. 3052.209-74 Section 3052.209-74 Federal Acquisition Regulations System... contractors acting as lead system integrators. As prescribed in (HSAR) 48 CFR 3009.570-4(a), use the following provision: LIMITATIONS ON CONTRACTORS ACTING AS LEAD SYSTEM INTEGRATORS (JUL 2010) (a) Definitions. “Direct...

Energy Systems Integration News | Energy Systems Integration Facility |

Science.gov Websites

-matter experts to develop cyber-physical systems security testing methodologies and resilience best the Energy Systems Integration Facility as part of NREL's work with SolarCity and the Hawaiian Electric Companies. Photo by Amy Glickson, NREL Welcome to Energy Systems Integration News, NREL's monthly

Ten key principles for successful health systems integration.

PubMed

Suter, Esther; Oelke, Nelly D; Adair, Carol E; Armitage, Gail D

2009-01-01

Integrated health systems are considered part of the solution to the challenge of sustaining Canada's healthcare system. This systematic literature review was undertaken to guide decision-makers and others to plan for and implement integrated health systems. This review identified 10 universal principles of successfully integrated healthcare systems that may be used by decision-makers to assist with integration efforts. These principles define key areas for restructuring and allow organizational flexibility and adaptation to local context. The literature does not contain a one-size-fits-all model or process for successful integration, nor is there a firm empirical foundation for specific integration strategies and processes.

Integrated Personnel and Pay System-Army Increment 2 (IPPS-A Inc 2)

DTIC Science & Technology

2016-03-01

2016 Major Automated Information System Annual Report Integrated Personnel and Pay System-Army Increment 2 (IPPS-A Inc 2) Defense Acquisition...703-325-3747 DSN Phone: 865-2915 DSN Fax: 221-3747 Date Assigned: May 2, 2014 Program Information Program Name Integrated Personnel and Pay System...Program Description The Integrated Personnel and Pay System-Army (IPPS-A) will provide the Army with an integrated, multi-Component (Active, National

Experience Of Implementing The Integrated Management System In Manufacturing Companies In Slovakia

NASA Astrophysics Data System (ADS)

Lestyánszka Škůrková, Katarína; Kučerová, Marta; Fidlerová, Helena

2015-06-01

In corporate practice, the term of Integrated Management System means a system the aim of which is to manage an organization regarding the quality, environment, health and safety at work. In the first phase of the VEGA project No. 1/0448/13 "Transformation of ergonomics program into the company management structure through interaction and utilization QMS, EMS, HSMS", we focused on obtaining information about the way or procedure of implementing the integrated management systems in manufacturing companies in Slovakia. The paper considers characteristics of integrated management system, specifies the possibilities for successive integration of the management systems and also describes the essential aspects of the practical implementation of integrated management systems in companies in Slovakia.

Is health systems integration being advanced through Local Health District planning?

PubMed

Saunders, Carla; Carter, David J

2017-05-01

Objective Delivering genuine integrated health care is one of three strategic directions in the New South Wales (NSW) Government State Health Plan: Towards 2021. This study investigated the current key health service plan of each NSW Local Health District (LHD) to evaluate the extent and nature of health systems integration strategies that are currently planned. Methods A scoping review was conducted to identify common key principles and practices for successful health systems integration to enable the development of an appraisal tool to content assess LHD strategic health service plans. Results The strategies that are planned for health systems integration across LHDs focus most often on improvements in coordination, health care access and care delivery for complex at-risk patients across the care continuum by both state- and commonwealth-funded systems, providers and agencies. The most common reasons given for integrated activities were to reduce avoidable hospitalisation, avoid inappropriate emergency department attendance and improve patient care. Conclusions Despite the importance of health systems integration and finding that all NSW LHDs have made some commitment towards integration in their current strategic health plans, this analysis suggests that health systems integration is in relatively early development across NSW. What is known about the topic? Effective approaches to managing complex chronic diseases have been found to involve health systems integration, which necessitates sound communication and connection between healthcare providers across community and hospital settings. Planning based on current health systems integration knowledge to ensure the efficient use of scarce resources is a responsibility of all health systems. What does this paper add? Appropriate planning and implementation of health systems integration is becoming an increasingly important expectation and requirement of effective health systems. The present study is the first of its kind to assess the planned activity in health systems integration in the NSW public health system. NSW health districts play a central role in health systems integration; each health service plan outlines the strategic directions for the development and delivery of all state-funded services across each district for the coming years, equating to hundreds of millions of dollars in health sector funding. The inclusion of effective health systems integration strategies allows Local Health Districts to lay the foundation for quality patient outcomes and long-term financial sustainability despite projected increases in demand for health services. What are the implications for practice? Establishing robust ongoing mechanisms for effective health systems integration is now a necessary part of health planning. The present study identifies several key areas and strategies that are wide in scope and indicative of efforts towards health systems integration, which may support Local Health Districts and other organisations in systematic planning and implementation.

Energy Systems Integration News | Energy Systems Integration Facility |

Science.gov Websites

DOE-funded research projects that are integrating cybersecurity controls with power systems principles Management, a hardware and software system that mimics the communications, power systems, and cybersecurity

Integrated control system for electron beam processes

NASA Astrophysics Data System (ADS)

Koleva, L.; Koleva, E.; Batchkova, I.; Mladenov, G.

2018-03-01

The ISO/IEC 62264 standard is widely used for integration of the business systems of a manufacturer with the corresponding manufacturing control systems based on hierarchical equipment models, functional data and manufacturing operations activity models. In order to achieve the integration of control systems, formal object communication models must be developed, together with manufacturing operations activity models, which coordinate the integration between different levels of control. In this article, the development of integrated control system for electron beam welding process is presented as part of a fully integrated control system of an electron beam plant, including also other additional processes: surface modification, electron beam evaporation, selective melting and electron beam diagnostics.

A large scale software system for simulation and design optimization of mechanical systems

NASA Technical Reports Server (NTRS)

Dopker, Bernhard; Haug, Edward J.

1989-01-01

The concept of an advanced integrated, networked simulation and design system is outlined. Such an advanced system can be developed utilizing existing codes without compromising the integrity and functionality of the system. An example has been used to demonstrate the applicability of the concept of the integrated system outlined here. The development of an integrated system can be done incrementally. Initial capabilities can be developed and implemented without having a detailed design of the global system. Only a conceptual global system must exist. For a fully integrated, user friendly design system, further research is needed in the areas of engineering data bases, distributed data bases, and advanced user interface design.

Meeting of Experts on NASA's Unmanned Aircraft System (UAS) Integration in the National Airspace Systems (NAS) Project

NASA Technical Reports Server (NTRS)

Wolfe, Jean; Bauer, Jeff; Bixby, C.J.; Lauderdale, Todd; Shively, Jay; Griner, James; Hayhurst, Kelly

2010-01-01

Topics discussed include: Aeronautics Research Mission Directorate Integrated Systems Research Program (ISRP) and UAS Integration in the NAS Project; UAS Integration into the NAS Project; Separation Assurance and Collision Avoidance; Pilot Aircraft Interface Objectives/Rationale; Communication; Certification; and Integrated Tests and Evaluations.

System Engineering of Photonic Systems for Space Application

NASA Technical Reports Server (NTRS)

Watson, Michael D.; Pryor, Jonathan E.

2014-01-01

The application of photonics in space systems requires tight integration with the spacecraft systems to ensure accurate operation. This requires some detailed and specific system engineering to properly incorporate the photonics into the spacecraft architecture and to guide the spacecraft architecture in supporting the photonics devices. Recent research in product focused, elegant system engineering has led to a system approach which provides a robust approach to this integration. Focusing on the mission application and the integration of the spacecraft system physics incorporation of the photonics can be efficiently and effectively accomplished. This requires a clear understanding of the driving physics properties of the photonics device to ensure proper integration with no unintended consequences. The driving physics considerations in terms of optical performance will be identified for their use in system integration. Keywords: System Engineering, Optical Transfer Function, Optical Physics, Photonics, Image Jitter, Launch Vehicle, System Integration, Organizational Interaction

Shared mental models of integrated care: aligning multiple stakeholder perspectives.

PubMed

Evans, Jenna M; Baker, G Ross

2012-01-01

Health service organizations and professionals are under increasing pressure to work together to deliver integrated patient care. A common understanding of integration strategies may facilitate the delivery of integrated care across inter-organizational and inter-professional boundaries. This paper aims to build a framework for exploring and potentially aligning multiple stakeholder perspectives of systems integration. The authors draw from the literature on shared mental models, strategic management and change, framing, stakeholder management, and systems theory to develop a new construct, Mental Models of Integrated Care (MMIC), which consists of three types of mental models, i.e. integration-task, system-role, and integration-belief. The MMIC construct encompasses many of the known barriers and enablers to integrating care while also providing a comprehensive, theory-based framework of psychological factors that may influence inter-organizational and inter-professional relations. While the existing literature on integration focuses on optimizing structures and processes, the MMIC construct emphasizes the convergence and divergence of stakeholders' knowledge and beliefs, and how these underlying cognitions influence interactions (or lack thereof) across the continuum of care. MMIC may help to: explain what differentiates effective from ineffective integration initiatives; determine system readiness to integrate; diagnose integration problems; and develop interventions for enhancing integrative processes and ultimately the delivery of integrated care. Global interest and ongoing challenges in integrating care underline the need for research on the mental models that characterize the behaviors of actors within health systems; the proposed framework offers a starting point for applying a cognitive perspective to health systems integration.

Extent of Integration of Priority Interventions into General Health Systems: A Case Study of Neglected Tropical Diseases Programme in the Western Region of Ghana.

PubMed

Mensah, Ernest O; Aikins, Moses K; Gyapong, Margaret; Anto, Francis; Bockarie, Moses J; Gyapong, John O

2016-05-01

The global health system has a large arsenal of interventions, medical products and technologies to address current global health challenges. However, identifying the most effective and efficient strategies to deliver these resources to where they are most needed has been a challenge. Targeted and integrated interventions have been the main delivery strategies. However, the health system discourse increasingly favours integrated strategies in the context of functionally merging targeted interventions with multifunctional health care delivery systems with a focus on strengthening country health systems to deliver needed interventions. Neglected Tropical Diseases (NTD) have been identified to promote and perpetuate poverty hence there has been global effort to combat these diseases. The Neglected Tropical Diseases Programme (NTDP) in Ghana has a national programme team and office, however, it depends on the multifunctional health delivery system at the regional and district level to implement interventions. The NTDP seeks further health system integration to accelerate achievement of coverage targets. The study estimated the extent of integration of the NTDP at the national, regional and district levels to provide evidence to guide further integration. The research design was a descriptive case study that interviewed key persons involved in the programme at the three levels of the health system as well as extensive document review. Integration was assessed on two planes-across health system functions-stewardship and governance, financing, planning, service delivery, monitoring and evaluation and demand generation; and across three administrative levels of the health system-national, regional and district. A composite measure of integration designated Cumulative Integration Index (CII) with a range of 0.00-1.00 was used to estimate extent of integration at the three levels of the health system. Service delivery was most integrated while financing and planning were least integrated. Extent of integration was partial at all levels of the health system with a CII of 0.48-0.68; however it was higher at the district compared to the national and regional levels. To ensure further integration of the NTDP, planning and finance management activities must be decentralized to involve regional and district levels of the health system. The study provides an empirical measure of extent of integration and indicators to guide further integration.

Enterprise Information System Integration Technology

NASA Astrophysics Data System (ADS)

Tanaka, Tetsuo; Yumoto, Masaki; Itsuki, Rei

In the current rapidly changing business environment, companies need to be efficient and agile to survive and thrive. That is why flexible systems integration is urgent and crucial concern for any enterprise. For the meanwhile, systems integration technology is getting more complicated, and middleware types are beginning blur for decades. We sort system integration into four different types, “Delayed Federation", “Real-time Federation", “Delayed Integration", and “Real-time Integration". We also outline appropriate technology and architecture for each type.

9. Exterior view, Test Cell 7, Systems Integration Laboratory Building ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

9. Exterior view, Test Cell 7, Systems Integration Laboratory Building (T-28), looking southwest. The enclosure discussed in CO-88-B-8 is at the right. - Air Force Plant PJKS, Systems Integration Laboratory, Systems Integration Laboratory Building, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

78 FR 7334 - Port Authority Access to Facility Vulnerability Assessments and the Integration of Security Systems

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-01

... to Facility Vulnerability Assessments and the Integration of Security Systems AGENCY: Coast Guard...-sharing measures. Security System Integration Alternatives Require each MTSA-regulated facility owner or... other forms of security system integration. Information Requested 1. We request comments on the...

Newly Branded Energy Systems Integration Group Joins International

Science.gov Websites

research fellow at NREL. Likewise, UVIG sees opportunity in partnering with iiESI. The international Group Joins International Institute for Energy Systems Integration Newly Branded Energy Systems Integration Group Joins International Institute for Energy Systems Integration March 22, 2018 The world of

1. Exterior view of Systems Integration Laboratory Building (T28), looking ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. Exterior view of Systems Integration Laboratory Building (T-28), looking northeast. The taller of the two gantries on the left houses Test Cell 6 (fuel), while the shorter gantry on the right houses Test Cell 7 (oxidizer). This structure serves as the functional center of the Systems Integration Laboratory complex for testing, handling, and storage of the Titan II's hydrazine - and nitrogen tetroxide-based fuel system propellants. - Air Force Plant PJKS, Systems Integration Laboratory, Systems Integration Laboratory Building, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

An Optimized Integrator Windup Protection Technique Applied to a Turbofan Engine Control

NASA Technical Reports Server (NTRS)

Watts, Stephen R.; Garg, Sanjay

1995-01-01

This paper introduces a new technique for providing memoryless integrator windup protection which utilizes readily available optimization software tools. This integrator windup protection synthesis provides a concise methodology for creating integrator windup protection for each actuation system loop independently while assuring both controller and closed loop system stability. The individual actuation system loops' integrator windup protection can then be combined to provide integrator windup protection for the entire system. This technique is applied to an H(exp infinity) based multivariable control designed for a linear model of an advanced afterburning turbofan engine. The resulting transient characteristics are examined for the integrated system while encountering single and multiple actuation limits.

Supervisory Control and Data Acquisition System | Energy Systems

Science.gov Websites

Integration Facility | NREL Supervisory Control and Data Acquisition System Supervisory Control supervisory control and data acquisition (SCADA) system monitors and controls safety systems and gathers real Energy Systems Integration Facility control room. The Energy Systems Integration Facility's SCADA system

Flight-determined benefits of integrated flight-propulsion control systems

NASA Technical Reports Server (NTRS)

Stewart, James F.; Burcham, Frank W., Jr.; Gatlin, Donald H.

1992-01-01

The fundamentals of control integration for propulsion are reviewed giving practical illustrations of its use to demonstrate the advantages of integration. Attention is given to the first integration propulsion-control systems (IPCSs) which was developed for the F-111E, and the integrated controller design is described that NASA developed for the YF-12C aircraft. The integrated control systems incorporate a range of aircraft components including the engine, inlet controls, autopilot, autothrottle, airdata, navigation, and/or stability-augmentation systems. Also described are emergency-control systems, onboard engine optimization, and thrust-vectoring control technologies developed for the F-18A and the F-15. Integrated flight-propulsion control systems are shown to enhance the thrust, range, and survivability of the aircraft while reducing fuel consumption and maintenance.

A service platform architecture design towards a light integration of heterogeneous systems in the wellbeing domain.

PubMed

Yang, Yaojin; Ahtinen, Aino; Lahteenmaki, Jaakko; Nyman, Petri; Paajanen, Henrik; Peltoniemi, Teijo; Quiroz, Carlos

2007-01-01

System integration is one of the major challenges for building wellbeing or healthcare related information systems. In this paper, we are going to share our experiences on how to design a service platform called Nuadu service platform, for providing integrated services in occupational health promotion and health risk management through two heterogeneous systems. Our design aims for a light integration covering the layers, from data through service up to presentation, while maintaining the integrity of the underlying systems.

Polarity management: the key challenge for integrated health systems.

PubMed

Burns, L R

1999-01-01

Integrated health systems are confronted with numerous dilemmas that must be managed. Many of these dilemmas are an inherent part of the system's structure, given that multiple competing hospitals, medical groups, and (sometimes) health plans are often under one organizational roof. This article presents an analysis of these dilemmas--referred to in the management literature as polarities--as they are found in six integrated health systems in Illinois. The nine polarities that must be managed include (1) hospital systems that want to be organizations of physicians; (2) system expansion by growing the physician component; (3) system centralization and physician decentralization; (4) centripetal and centrifugal forces involving physicians; (5) system objectives and physician interests; (6) system centralization and hospital decentralization; (7) primary care physicians and specialists; (8) physician autonomy via collectivization; and (9) vertical and virtual integration. The article identifies some of the solutions to the polarities that have been enacted by systems. In general, executives and physicians in integrated health systems must attend to the processes of integration as much as or more than the structures of integration.

Flight-determined benefits of integrated flight-propulsion control systems

NASA Technical Reports Server (NTRS)

Stewart, James F.; Burcham, Frank W., Jr.; Gatlin, Donald H.

1992-01-01

Over the last two decades, NASA has conducted several experiments in integrated flight-propulsion control. Benefits have included improved maneuverability; increased thrust, range, and survivability; reduced fuel consumption; and reduced maintenance. This paper presents the basic concepts for control integration, examples of implementation, and benefits. The F-111E experiment integrated the engine and inlet control systems. The YF-12C incorporated an integral control system involving the inlet, autopilot, autothrottle, airdata, navigation, and stability augmentation systems. The F-15 research involved integration of the engine, flight, and inlet control systems. Further extension of the integration included real-time, onboard optimization of engine, inlet, and flight control variables; a self-repairing flight control system; and an engines-only control concept for emergency control. The F-18A aircraft incorporated thrust vectoring integrated with the flight control system to provide enhanced maneuvering at high angles of attack. The flight research programs and the resulting benefits of each program are described.

Energy Systems Integration News | Energy Systems Integration Facility |

Science.gov Websites

Renewable Generation Integration Study (ERGIS), looks ahead to the year 2026 and examines how the Eastern accurately modeling the entire system at five-minute intervals for an entire year has never even been Integrated Network Testbed for Energy Grid Research and Technology Experimentation (INTEGRATE) project, up to

Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project Subcommittee Final

NASA Technical Reports Server (NTRS)

Johnson, Chuck; Griner, James H.; Hayhurst, Kelly J.; Shively, Robert J.; Consiglio, Maria; Muller, Eric; Murphy, James; Kim, Sam

2012-01-01

UAS Integration in the NAS Project overview with details from each of the subprojects. Subprojects include: Communications, Certification, Integrated Test and Evaluation, Human Systems Integration, and Separation Assurance/Sense and Avoid Interoperability.

Extent of Integration of Priority Interventions into General Health Systems: A Case Study of Neglected Tropical Diseases Programme in the Western Region of Ghana

PubMed Central

Mensah, Ernest O.; Aikins, Moses K.; Gyapong, Margaret; Anto, Francis; Bockarie, Moses J.; Gyapong, John O.

2016-01-01

Background The global health system has a large arsenal of interventions, medical products and technologies to address current global health challenges. However, identifying the most effective and efficient strategies to deliver these resources to where they are most needed has been a challenge. Targeted and integrated interventions have been the main delivery strategies. However, the health system discourse increasingly favours integrated strategies in the context of functionally merging targeted interventions with multifunctional health care delivery systems with a focus on strengthening country health systems to deliver needed interventions. Neglected Tropical Diseases (NTD) have been identified to promote and perpetuate poverty hence there has been global effort to combat these diseases. The Neglected Tropical Diseases Programme (NTDP) in Ghana has a national programme team and office, however, it depends on the multifunctional health delivery system at the regional and district level to implement interventions. The NTDP seeks further health system integration to accelerate achievement of coverage targets. The study estimated the extent of integration of the NTDP at the national, regional and district levels to provide evidence to guide further integration. Methodology/Principal Findings The research design was a descriptive case study that interviewed key persons involved in the programme at the three levels of the health system as well as extensive document review. Integration was assessed on two planes—across health system functions–stewardship and governance, financing, planning, service delivery, monitoring and evaluation and demand generation; and across three administrative levels of the health system–national, regional and district. A composite measure of integration designated Cumulative Integration Index (CII) with a range of 0.00–1.00 was used to estimate extent of integration at the three levels of the health system. Service delivery was most integrated while financing and planning were least integrated. Extent of integration was partial at all levels of the health system with a CII of 0.48–0.68; however it was higher at the district compared to the national and regional levels. Conclusions/Significance To ensure further integration of the NTDP, planning and finance management activities must be decentralized to involve regional and district levels of the health system. The study provides an empirical measure of extent of integration and indicators to guide further integration. PMID:27203854

Reframing the challenges to integrated care: a complex-adaptive systems perspective.

PubMed

Tsasis, Peter; Evans, Jenna M; Owen, Susan

2012-01-01

Despite over two decades of international experience and research on health systems integration, integrated care has not developed widely. We hypothesized that part of the problem may lie in how we conceptualize the integration process and the complex systems within which integrated care is enacted. This study aims to contribute to discourse regarding the relevance and utility of a complex-adaptive systems (CAS) perspective on integrated care. In the Canadian province of Ontario, government mandated the development of fourteen Local Health Integration Networks in 2006. Against the backdrop of these efforts to integrate care, we collected focus group data from a diverse sample of healthcare professionals in the Greater Toronto Area using convenience and snowball sampling. A semi-structured interview guide was used to elicit participant views and experiences of health systems integration. We use a CAS framework to describe and analyze the data, and to assess the theoretical fit of a CAS perspective with the dominant themes in participant responses. Our findings indicate that integration is challenged by system complexity, weak ties and poor alignment among professionals and organizations, a lack of funding incentives to support collaborative work, and a bureaucratic environment based on a command and control approach to management. Using a CAS framework, we identified several characteristics of CAS in our data, including diverse, interdependent and semi-autonomous actors; embedded co-evolutionary systems; emergent behaviours and non-linearity; and self-organizing capacity. One possible explanation for the lack of systems change towards integration is that we have failed to treat the healthcare system as complex-adaptive. The data suggest that future integration initiatives must be anchored in a CAS perspective, and focus on building the system's capacity to self-organize. We conclude that integrating care requires policies and management practices that promote system awareness, relationship-building and information-sharing, and that recognize change as an evolving learning process rather than a series of programmatic steps.

2. Exterior view of Systems Integration Laboratory Building (T28), looking ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. Exterior view of Systems Integration Laboratory Building (T-28), looking southwest. The low-lying concrete Signal Transfer Building (T-28A) is located in the immediate foreground. - Air Force Plant PJKS, Systems Integration Laboratory, Systems Integration Laboratory Building, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

48 CFR 252.209-7007 - Prohibited Financial Interests for Lead System Integrators.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Interests for Lead System Integrators. 252.209-7007 Section 252.209-7007 Federal Acquisition Regulations... for Lead System Integrators. As prescribed in 209.570-4(b), use the following clause: Prohibited Financial Interests for Lead System Integrators (JUL 2009) (a) Definitions. As used in this clause— (1) Lead...

48 CFR 3052.209-75 - Prohibited financial interests for lead system integrators.

Code of Federal Regulations, 2013 CFR

2013-10-01

... interests for lead system integrators. 3052.209-75 Section 3052.209-75 Federal Acquisition Regulations... interests for lead system integrators. As prescribed in (HSAR) 48 CFR 3009.570-4(b), use the following clause: Prohibited Financial Interests for Lead System Integrators (JUL 2010) (a) Definitions. As used in...

48 CFR 252.209-7007 - Prohibited Financial Interests for Lead System Integrators.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Interests for Lead System Integrators. 252.209-7007 Section 252.209-7007 Federal Acquisition Regulations... for Lead System Integrators. As prescribed in 209.570-4(b), use the following clause: Prohibited Financial Interests for Lead System Integrators (JUL 2009) (a) Definitions. As used in this clause— (1) Lead...

48 CFR 3052.209-75 - Prohibited financial interests for lead system integrators.

Code of Federal Regulations, 2014 CFR

2014-10-01

... interests for lead system integrators. 3052.209-75 Section 3052.209-75 Federal Acquisition Regulations... interests for lead system integrators. As prescribed in (HSAR) 48 CFR 3009.570-4(b), use the following clause: Prohibited Financial Interests for Lead System Integrators (JUL 2010) (a) Definitions. As used in...

48 CFR 252.209-7007 - Prohibited Financial Interests for Lead System Integrators.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Interests for Lead System Integrators. 252.209-7007 Section 252.209-7007 Federal Acquisition Regulations... for Lead System Integrators. As prescribed in 209.570-4(b), use the following clause: Prohibited Financial Interests for Lead System Integrators (JUL 2009) (a) Definitions. As used in this clause— (1) Lead...

48 CFR 3052.209-75 - Prohibited financial interests for lead system integrators.

Code of Federal Regulations, 2011 CFR

2011-10-01

... interests for lead system integrators. 3052.209-75 Section 3052.209-75 Federal Acquisition Regulations... interests for lead system integrators. As prescribed in (HSAR) 48 CFR 3009.570-4(b), use the following clause: PROHIBITED FINANCIAL INTERESTS FOR LEAD SYSTEM INTEGRATORS (JUL 2010) (a) Definitions. As used in...

48 CFR 252.209-7007 - Prohibited Financial Interests for Lead System Integrators.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Interests for Lead System Integrators. 252.209-7007 Section 252.209-7007 Federal Acquisition Regulations... for Lead System Integrators. As prescribed in 209.570-4(b), use the following clause: Prohibited Financial Interests for Lead System Integrators (JUL 2009) (a) Definitions. As used in this clause— (1) Lead...

48 CFR 3052.209-75 - Prohibited financial interests for lead system integrators.

Code of Federal Regulations, 2012 CFR

2012-10-01

... interests for lead system integrators. 3052.209-75 Section 3052.209-75 Federal Acquisition Regulations... interests for lead system integrators. As prescribed in (HSAR) 48 CFR 3009.570-4(b), use the following clause: Prohibited Financial Interests for Lead System Integrators (JUL 2010) (a) Definitions. As used in...

Process and information integration via hypermedia

NASA Technical Reports Server (NTRS)

Hammen, David G.; Labasse, Daniel L.; Myers, Robert M.

1990-01-01

Success stories for advanced automation prototypes abound in the literature but the deployments of practical large systems are few in number. There are several factors that militate against the maturation of such prototypes into products. Here, the integration of advanced automation software into large systems is discussed. Advanced automation systems tend to be specific applications that need to be integrated and aggregated into larger systems. Systems integration can be achieved by providing expert user-developers with verified tools to efficiently create small systems that interface to large systems through standard interfaces. The use of hypermedia as such a tool in the context of the ground control centers that support Shuttle and space station operations is explored. Hypermedia can be an integrating platform for data, conventional software, and advanced automation software, enabling data integration through the display of diverse types of information and through the creation of associative links between chunks of information. Further, hypermedia enables process integration through graphical invoking of system functions. Through analysis and examples, researchers illustrate how diverse information and processing paradigms can be integrated into a single software platform.

The MIST /MIUS Integration and Subsystems Test/ laboratory - A testbed for the MIUS /Modular Integrated Utility System/ program

NASA Technical Reports Server (NTRS)

Beckham, W. S., Jr.; Keune, F. A.

1974-01-01

The MIUS (Modular Integrated Utility System) concept is to be an energy-conserving, economically feasible, integrated community utility system to provide five necessary services: electricity generation, space heating and air conditioning, solid waste processing, liquid waste processing, and residential water purification. The MIST (MIUS Integration and Subsystem Test) integrated system testbed constructed at the Johnson Space Center in Houston includes subsystems for power generation, heating, ventilation, and air conditioning (HVAC), wastewater management, solid waste management, and control and monitoring. The key design issues under study include thermal integration and distribution techniques, thermal storage, integration of subsystems controls and displays, incinerator performance, effluent characteristics, and odor control.

[Development method of healthcare information system integration based on business collaboration model].

PubMed

Li, Shasha; Nie, Hongchao; Lu, Xudong; Duan, Huilong

2015-02-01

Integration of heterogeneous systems is the key to hospital information construction due to complexity of the healthcare environment. Currently, during the process of healthcare information system integration, people participating in integration project usually communicate by free-format document, which impairs the efficiency and adaptability of integration. A method utilizing business process model and notation (BPMN) to model integration requirement and automatically transforming it to executable integration configuration was proposed in this paper. Based on the method, a tool was developed to model integration requirement and transform it to integration configuration. In addition, an integration case in radiology scenario was used to verify the method.

Response of MDOF strongly nonlinear systems to fractional Gaussian noises.

PubMed

Deng, Mao-Lin; Zhu, Wei-Qiu

2016-08-01

In the present paper, multi-degree-of-freedom strongly nonlinear systems are modeled as quasi-Hamiltonian systems and the stochastic averaging method for quasi-Hamiltonian systems (including quasi-non-integrable, completely integrable and non-resonant, completely integrable and resonant, partially integrable and non-resonant, and partially integrable and resonant Hamiltonian systems) driven by fractional Gaussian noise is introduced. The averaged fractional stochastic differential equations (SDEs) are derived. The simulation results for some examples show that the averaged SDEs can be used to predict the response of the original systems and the simulation time for the averaged SDEs is less than that for the original systems.

Response of MDOF strongly nonlinear systems to fractional Gaussian noises

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng, Mao-Lin; Zhu, Wei-Qiu, E-mail: wqzhu@zju.edu.cn

2016-08-15

In the present paper, multi-degree-of-freedom strongly nonlinear systems are modeled as quasi-Hamiltonian systems and the stochastic averaging method for quasi-Hamiltonian systems (including quasi-non-integrable, completely integrable and non-resonant, completely integrable and resonant, partially integrable and non-resonant, and partially integrable and resonant Hamiltonian systems) driven by fractional Gaussian noise is introduced. The averaged fractional stochastic differential equations (SDEs) are derived. The simulation results for some examples show that the averaged SDEs can be used to predict the response of the original systems and the simulation time for the averaged SDEs is less than that for the original systems.

Information Security Management - Part Of The Integrated Management System

NASA Astrophysics Data System (ADS)

Manea, Constantin Adrian

2015-07-01

The international management standards allow their integrated approach, thereby combining aspects of particular importance to the activity of any organization, from the quality management systems or the environmental management of the information security systems or the business continuity management systems. Although there is no national or international regulation, nor a defined standard for the Integrated Management System, the need to implement an integrated system occurs within the organization, which feels the opportunity to integrate the management components into a cohesive system, in agreement with the purpose and mission publicly stated. The issues relating to information security in the organization, from the perspective of the management system, raise serious questions to any organization in the current context of electronic information, reason for which we consider not only appropriate but necessary to promote and implement an Integrated Management System Quality - Environment - Health and Operational Security - Information Security

The architecture of enterprise hospital information system.

PubMed

Lu, Xudong; Duan, Huilong; Li, Haomin; Zhao, Chenhui; An, Jiye

2005-01-01

Because of the complexity of the hospital environment, there exist a lot of medical information systems from different vendors with incompatible structures. In order to establish an enterprise hospital information system, the integration among these heterogeneous systems must be considered. Complete integration should cover three aspects: data integration, function integration and workflow integration. However most of the previous design of architecture did not accomplish such a complete integration. This article offers an architecture design of the enterprise hospital information system based on the concept of digital neural network system in hospital. It covers all three aspects of integration, and eventually achieves the target of one virtual data center with Enterprise Viewer for users of different roles. The initial implementation of the architecture in the 5-year Digital Hospital Project in Huzhou Central hospital of Zhejiang Province is also described.

Multi-viewer tracking integral imaging system and its viewing zone analysis.

PubMed

Park, Gilbae; Jung, Jae-Hyun; Hong, Keehoon; Kim, Yunhee; Kim, Young-Hoon; Min, Sung-Wook; Lee, Byoungho

2009-09-28

We propose a multi-viewer tracking integral imaging system for viewing angle and viewing zone improvement. In the tracking integral imaging system, the pickup angles in each elemental lens in the lens array are decided by the positions of viewers, which means the elemental image can be made for each viewer to provide wider viewing angle and larger viewing zone. Our tracking integral imaging system is implemented with an infrared camera and infrared light emitting diodes which can track the viewers' exact positions robustly. For multiple viewers to watch integrated three-dimensional images in the tracking integral imaging system, it is needed to formulate the relationship between the multiple viewers' positions and the elemental images. We analyzed the relationship and the conditions for the multiple viewers, and verified them by the implementation of two-viewer tracking integral imaging system.

Analysis of a Real-Time Separation Assurance System with Integrated Time-in-Trail Spacing

NASA Technical Reports Server (NTRS)

Aweiss, Arwa S.; Farrahi, Amir H.; Lauderdale, Todd A.; Thipphavong, Adam S.; Lee, Chu H.

2010-01-01

This paper describes the implementation and analysis of an integrated ground-based separation assurance and time-based metering prototype system into the Center-TRACON Automation System. The integration of this new capability accommodates constraints in four-dimensions: position (x-y), altitude, and meter-fix crossing time. Experiments were conducted to evaluate the performance of the integrated system and its ability to handle traffic levels up to twice that of today. Results suggest that the integrated system reduces the number and magnitude of time-in-trail spacing violations. This benefit was achieved without adversely affecting the resolution success rate of the system. Also, the data suggest that the integrated system is relatively insensitive to an increase in traffic of twice the current levels.

48 CFR 3009.570 - Limitations on contractors acting as lead system integrators.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Limitations on contractors acting as lead system integrators. 3009.570 Section 3009.570 Federal Acquisition Regulations System... contractors acting as lead system integrators. ...

On the integrability of some generalized Lotka-Volterra systems

NASA Astrophysics Data System (ADS)

Bier, M.; Hijmans, J.; Bountis, T. C.

1983-08-01

Several integrable systems of nonlinear ordinary differential equations of the Lotka-Volterra type are identified by the Painleveproperty and completely integrated. One such integrable case of N first order ode's is found, with N-2 free parameters and N arbitrary. The concept of integrability of a general dynamical system, not necessarily derived from a Hamiltonian, is also discussed.

Space station integrated propulsion and fluid systems study. Space station program fluid management systems databook

NASA Technical Reports Server (NTRS)

Bicknell, B.; Wilson, S.; Dennis, M.; Lydon, M.

1988-01-01

Commonality and integration of propulsion and fluid systems associated with the Space Station elements are being evaluated. The Space Station elements consist of the core station, which includes habitation and laboratory modules, nodes, airlocks, and trusswork; and associated vehicles, platforms, experiments, and payloads. The program is being performed as two discrete tasks. Task 1 investigated the components of the Space Station architecture to determine the feasibility and practicality of commonality and integration among the various propulsion elements. This task was completed. Task 2 is examining integration and commonality among fluid systems which were identified by the Phase B Space Station contractors as being part of the initial operating capability (IOC) and growth Space Station architectures. Requirements and descriptions for reference fluid systems were compiled from Space Station documentation and other sources. The fluid systems being examined are: an experiment gas supply system, an oxygen/hydrogen supply system, an integrated water system, the integrated nitrogen system, and the integrated waste fluids system. Definitions and descriptions of alternate systems were developed, along with analyses and discussions of their benefits and detriments. This databook includes fluid systems descriptions, requirements, schematic diagrams, component lists, and discussions of the fluid systems. In addition, cost comparison are used in some cases to determine the optimum system for a specific task.

A study of compositional verification based IMA integration method

NASA Astrophysics Data System (ADS)

Huang, Hui; Zhang, Guoquan; Xu, Wanmeng

2018-03-01

The rapid development of avionics systems is driving the application of integrated modular avionics (IMA) systems. But meanwhile it is improving avionics system integration, complexity of system test. Then we need simplify the method of IMA system test. The IMA system supports a module platform that runs multiple applications, and shares processing resources. Compared with federated avionics system, IMA system is difficult to isolate failure. Therefore, IMA system verification will face the critical problem is how to test shared resources of multiple application. For a simple avionics system, traditional test methods are easily realizing to test a whole system. But for a complex system, it is hard completed to totally test a huge and integrated avionics system. Then this paper provides using compositional-verification theory in IMA system test, so that reducing processes of test and improving efficiency, consequently economizing costs of IMA system integration.

Integrating an object system into CLIPS: Language design and implementation issues

NASA Technical Reports Server (NTRS)

Auburn, Mark

1990-01-01

This paper describes the reasons why an object system with integrated pattern-matching and object-oriented programming facilities is desirable for CLIPS and how it is possible to integrate such a system into CLIPS while maintaining the run-time performance and the low memory usage for which CLIPS is known. The requirements for an object system in CLIPS that includes object-oriented programming and integrated pattern-matching are discussed and various techniques for optimizing the object system and its integration with the pattern-matcher are presented.

Decentralized Multisensory Information Integration in Neural Systems.

PubMed

Zhang, Wen-Hao; Chen, Aihua; Rasch, Malte J; Wu, Si

2016-01-13

How multiple sensory cues are integrated in neural circuitry remains a challenge. The common hypothesis is that information integration might be accomplished in a dedicated multisensory integration area receiving feedforward inputs from the modalities. However, recent experimental evidence suggests that it is not a single multisensory brain area, but rather many multisensory brain areas that are simultaneously involved in the integration of information. Why many mutually connected areas should be needed for information integration is puzzling. Here, we investigated theoretically how information integration could be achieved in a distributed fashion within a network of interconnected multisensory areas. Using biologically realistic neural network models, we developed a decentralized information integration system that comprises multiple interconnected integration areas. Studying an example of combining visual and vestibular cues to infer heading direction, we show that such a decentralized system is in good agreement with anatomical evidence and experimental observations. In particular, we show that this decentralized system can integrate information optimally. The decentralized system predicts that optimally integrated information should emerge locally from the dynamics of the communication between brain areas and sheds new light on the interpretation of the connectivity between multisensory brain areas. To extract information reliably from ambiguous environments, the brain integrates multiple sensory cues, which provide different aspects of information about the same entity of interest. Here, we propose a decentralized architecture for multisensory integration. In such a system, no processor is in the center of the network topology and information integration is achieved in a distributed manner through reciprocally connected local processors. Through studying the inference of heading direction with visual and vestibular cues, we show that the decentralized system can integrate information optimally, with the reciprocal connections between processers determining the extent of cue integration. Our model reproduces known multisensory integration behaviors observed in experiments and sheds new light on our understanding of how information is integrated in the brain. Copyright © 2016 Zhang et al.

Decentralized Multisensory Information Integration in Neural Systems

PubMed Central

Zhang, Wen-hao; Chen, Aihua

2016-01-01

How multiple sensory cues are integrated in neural circuitry remains a challenge. The common hypothesis is that information integration might be accomplished in a dedicated multisensory integration area receiving feedforward inputs from the modalities. However, recent experimental evidence suggests that it is not a single multisensory brain area, but rather many multisensory brain areas that are simultaneously involved in the integration of information. Why many mutually connected areas should be needed for information integration is puzzling. Here, we investigated theoretically how information integration could be achieved in a distributed fashion within a network of interconnected multisensory areas. Using biologically realistic neural network models, we developed a decentralized information integration system that comprises multiple interconnected integration areas. Studying an example of combining visual and vestibular cues to infer heading direction, we show that such a decentralized system is in good agreement with anatomical evidence and experimental observations. In particular, we show that this decentralized system can integrate information optimally. The decentralized system predicts that optimally integrated information should emerge locally from the dynamics of the communication between brain areas and sheds new light on the interpretation of the connectivity between multisensory brain areas. SIGNIFICANCE STATEMENT To extract information reliably from ambiguous environments, the brain integrates multiple sensory cues, which provide different aspects of information about the same entity of interest. Here, we propose a decentralized architecture for multisensory integration. In such a system, no processor is in the center of the network topology and information integration is achieved in a distributed manner through reciprocally connected local processors. Through studying the inference of heading direction with visual and vestibular cues, we show that the decentralized system can integrate information optimally, with the reciprocal connections between processers determining the extent of cue integration. Our model reproduces known multisensory integration behaviors observed in experiments and sheds new light on our understanding of how information is integrated in the brain. PMID:26758843

Development and validation of the crew-station system-integration research facility

NASA Technical Reports Server (NTRS)

Nedell, B.; Hardy, G.; Lichtenstein, T.; Leong, G.; Thompson, D.

1986-01-01

The various issues associated with the use of integrated flight management systems in aircraft were discussed. To address these issues a fixed base integrated flight research (IFR) simulation of a helicopter was developed to support experiments that contribute to the understanding of design criteria for rotorcraft cockpits incorporating advanced integrated flight management systems. A validation experiment was conducted that demonstrates the main features of the facility and the capability to conduct crew/system integration research.

Contact Hamiltonian systems and complete integrability

NASA Astrophysics Data System (ADS)

Visinescu, Mihai

2017-12-01

We summarize recent results on the integrability of Hamiltonian systems on contact manifolds. We explain how to extend the classical formulation of action-angle variables to contact integrable systems. Using the Jacobi brackets defined on contact manifolds, we discuss the commutativity of first integrals for contact Hamiltonian systems and present the construction of generalized contact action-angle variables. We illustrate the integrability in the contact geometry on the five-dimensional Sasaki-Einstein spaces T1,1 and Yp,q.

Measuring primary care practice performance within an integrated delivery system: a case study.

PubMed

Stewart, Louis J; Greisler, David

2002-01-01

This article examines the use of an integrated performance measurement system to plan and control primary care service delivery within an integrated delivery system. We review a growing body of literature that focuses on the development and implementation of management reporting systems among healthcare providers. Our study extends the existing literature by examining the use of performance information generated by an integrated performance measurement system within a healthcare organization. We conduct our examination through a case study of the WMG Primary Care Medicine Group, the primary care medical group practice of WellSpan Health System. WellSpan Health System is an integrated delivery system that serves south central Pennsylvania and northern Maryland. Our study examines the linkage between WellSpan Health's strategic objectives and its primary care medicine group's integrated performance measurement system. The conceptual design of this integrated performance measurement system combines financial metrics with practice management and clinical operating metrics to provide a more complete picture of medical group performance. Our findings demonstrate that WellSpan Health was able to achieve superior financial results despite a weak linkage between its integrated performance measurement system and its strategic objectives. WellSpan Health achieved this objective for its primary care medicine group by linking clinical performance information to physician compensation and reporting practice management performance through the use of statistical process charts. They found that the combined mechanisms of integrated performance measurement and statistical process control charts improved organizational learning and communications between organizational stakeholders.

Human-Systems Integration (HSI) and the Network Integration Evaluations (NIEs), Part 3: Mitigating Cognitive Load in Network-Enabled Mission Command

DTIC Science & Technology

2016-06-01

ARL-TR-7698 ● JUNE 2016 US Army Research Laboratory Human -Systems Integration (HSI) and the Network Integration Evaluations...ARL-TR-7698 ● JUNE 2016 US Army Research Laboratory Human -Systems Integration (HSI) and the Network Integration Evaluations (NIEs), Part 3...Mitigating Cognitive Load in Network-Enabled Mission Command by John K Hawley Human Research and Engineering Directorate, ARL Michael W

Investigation on navigation patterns of inertial/celestial integrated systems

NASA Astrophysics Data System (ADS)

Luo, Dacheng; Liu, Yan; Liu, Zhiguo; Jiao, Wei; Wang, Qiuyan

2014-11-01

It is known that Strapdown Inertial Navigation System (SINS), Global Navigation Satellite System (GNSS) and Celestial Navigation System (CNS) can complement each other's advantages. The SINS/CNS integrated system, which has the characteristics of strong autonomy, high accuracy and good anti-jamming, is widely used in military and civilian applications. Similar to SINS/GNSS integrated system, the SINS/CNS integrated system can also be divided into three kinds according to the difference of integrating depth, i.e., loosely coupled pattern, tightly coupled pattern and deeply coupled pattern. In this paper, the principle and characteristics of each pattern of SINS/CNS system are analyzed. Based on the comparison of these patterns, a novel deeply coupled SINS/CNS integrated navigation scheme is proposed. The innovation of this scheme is that a new star pattern matching method aided by SINS information is put forward. Thus the complementary features of these two subsystems are reflected.

Automatic detection, tracking and sensor integration

NASA Astrophysics Data System (ADS)

Trunk, G. V.

1988-06-01

This report surveys the state of the art of automatic detection, tracking, and sensor integration. In the area of detection, various noncoherent integrators such as the moving window integrator, feedback integrator, two-pole filter, binary integrator, and batch processor are discussed. Next, the three techniques for controlling false alarms, adapting thresholds, nonparametric detectors, and clutter maps are presented. In the area of tracking, a general outline is given of a track-while-scan system, and then a discussion is presented of the file system, contact-entry logic, coordinate systems, tracking filters, maneuver-following logic, tracking initiating, track-drop logic, and correlation procedures. Finally, in the area of multisensor integration the problems of colocated-radar integration, multisite-radar integration, radar-IFF integration, and radar-DF bearing strobe integration are treated.

Suit study - The impact of VMS in subsystem integration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hill, B.; Watts, R.

1992-02-01

One of the thrusts of the Wright Laboratory/FIVE-sponsored Subsystem Integration Technology (SUIT) study is to investigate the impact of emerging vehicle management system (VMS) concepts on subsystem integration. This paper summarizes the issues relating to VMS/subsystem integration as examined during the Northrop SUIT study. Projected future weapon system requirements are identified and their impact on VMS and subsystem design interpreted. Integrated VMS/subsystem control and management functions are proposed. A candidate system VMS architecture satisfying the aforementioned weapon system requirements and providing the identified control and management functions is proposed. This architecture is used, together with the environmental control system, asmore » an illustrative subsystem example, to address the risks associated with the design, development, procurement, integration and testing of integrated VMS/subsystem concepts. The conclusion is that the development process requires an airframer to adopt the role of subsystem integrator, the consequences of which are discussed. 2 refs.« less

Guest editorial. Integrated healthcare information systems.

PubMed

Li, Ling; Ge, Ri-Li; Zhou, Shang-Ming; Valerdi, Ricardo

2012-07-01

The use of integrated information systems for healthcare has been started more than a decade ago. In recent years, rapid advances in information integration methods have spurred tremendous growth in the use of integrated information systems in healthcare delivery. Various techniques have been used for probing such integrated systems. These techniques include service-oriented architecture (SOA), EAI, workflow management, grid computing, and others. Many applications require a combination of these techniques, which gives rise to the emergence of enterprise systems in healthcare. Development of the techniques originated from different disciplines has the potential to significantly improve the performance of enterprise systems in healthcare. This editorial paper briefly introduces the enterprise systems in the perspective of healthcare informatics.

U.S. Space Shuttle GPS navigation capability for all mission phases

NASA Technical Reports Server (NTRS)

Kachmar, Peter; Chu, William; Montez, Moises

1993-01-01

Incorporating a GPS capability on the Space Shuttle presented unique system integration design considerations and has led to an integration concept that has minimum impact on the existing Shuttle hardware and software systems. This paper presents the Space Shuttle GPS integrated design and the concepts used in implementing this GPS capability. The major focus of the paper is on the modifications that will be made to the navigation systems in the Space Shuttle General Purpose Computers (GPC) and on the Operational Requirements of the integrated GPS/GPC system. Shuttle navigation system architecture, functions and operations are discussed for the current system and with the GPS integrated navigation capability. The GPS system integration design presented in this paper has been formally submitted to the Shuttle Avionics Software Control Board for implementation in the on-board GPC software.

A Survey of Applications and Research in Integrated Design Systems Technology

NASA Technical Reports Server (NTRS)

1998-01-01

The initial part of the study was begun with a combination of literature searches, World Wide Web searches, and contacts with individuals and companies who were known to members of our team to have an interest in topics that seemed to be related to our study. There is a long list of such topics, such as concurrent engineering, design for manufacture, life-cycle engineering, systems engineering, systems integration, systems design, design systems, integrated product and process approaches, enterprise integration, integrated product realization, and similar terms. These all capture, at least in part, the flavor of what we describe here as integrated design systems. An inhibiting factor in this inquiry was the absence of agreed terminology for the study of integrated design systems. It is common for the term to be applied to what are essentially augmented Computer-Aided Design (CAD) systems, which are integrated only to the extent that agreements have been reached to attach proprietary extensions to proprietary CAD programs. It is also common for some to use the term integrated design systems to mean a system that applies only, or mainly, to the design phase of a product life cycle. It is likewise common for many of the terms listed earlier to be used as synonyms for integrated design systems. We tried to avoid this ambiguity by adopting the definition of integrated design systems that is implied in the introductory notes that we provided to our contacts, cited earlier. We thus arrived at this definition: Integrated Design Systems refers to the integration of the different tools and processes that comprise the engineering, of complex systems. It takes a broad view of the engineering of systems, to include consideration of the entire product realization process and the product life cycle. An important aspect of integrated design systems is the extent to which they integrate existing, "islands of automation" into a comprehensive design and product realization environment. As the study progressed, we relied increasingly upon a networking approach to lead us to new information. The departure point for such searches often was a government-sponsored project or a company initiative. The advantage of this approach was that short conversations with knowledgeable persons would usually cut through confusion over differences of terminology, thereby somewhat reducing the search space of the study. Even so, it was not until late in our eight-month inquiry that we began to see signs of convergence of the search, in the sense that a number of the latest inquiries began to turn up references to earlier contacts. As suggested above, this convergence often occurred with respect to particular government or company projects.

CONFIG: Integrated engineering of systems and their operation

NASA Technical Reports Server (NTRS)

Malin, Jane T.; Ryan, Dan; Fleming, Land

1994-01-01

This article discusses CONFIG 3, a prototype software tool that supports integrated conceptual design evaluation from early in the product life cycle, by supporting isolated or integrated modeling, simulation, and analysis of the function, structure, behavior, failures and operations of system designs. Integration and reuse of models is supported in an object-oriented environment providing capabilities for graph analysis and discrete event simulation. CONFIG supports integration among diverse modeling approaches (component view, configuration or flow path view, and procedure view) and diverse simulation and analysis approaches. CONFIG is designed to support integrated engineering in diverse design domains, including mechanical and electro-mechanical systems, distributed computer systems, and chemical processing and transport systems.

Air Force Integrated Personnel and Pay System (AFIPPS)

DTIC Science & Technology

2016-03-01

2016 Major Automated Information System Annual Report Air Force Integrated Personnel and Pay System (AFIPPS) Defense Acquisition Management...DSN Fax: 665-1207 Date Assigned: February 1, 2016 Program Information Program Name Air Force Integrated Personnel and Pay System (AFIPPS) DoD...therefore, no Original Estimate has been established. AFIPPS 2016 MAR UNCLASSIFIED 4 Program Description Air Force Integrated Personnel and Pay

Integration of Schemas on the Pre-Design Level Using the KCPM-Approach

NASA Astrophysics Data System (ADS)

Vöhringer, Jürgen; Mayr, Heinrich C.

Integration is a central research and operational issue in information system design and development. It can be conducted on the system, schema, and view or data level. On the system level, integration deals with the progressive linking and testing of system components to merge their functional and technical characteristics and behavior into a comprehensive, interoperable system. Schema integration comprises the comparison and merging of two or more schemas, usually conceptual database schemas. The integration of data deals with merging the contents of multiple sources of related data. View integration is similar to schema integration, however focuses on views and queries on these instead of schemas. All these types of integration have in common, that two or more sources are merged and previously compared, in order to identify matches and mismatches as well as conflicts and inconsistencies. The sources may stem from heterogeneous companies, organizational units or projects. Integration enables the reuse and combined use of source components.

Grid Facilities | Grid Modernization | NREL

Science.gov Websites

groundbreaking innovations and collaboration in grid research. Photo of the Energy Systems Integration Facility Energy Systems Integration Facility The Energy Systems Integration Facility is the nation's premier user Located in Boulder, Colorado, the National Wind Technology Center (NWTC) offers similar integration

Invited Review Article: Review of centrifugal microfluidic and bio-optical disks

PubMed Central

Nolte, David D.

2009-01-01

Spinning biodisks have advantages that make them attractive for specialized biochip applications. The two main classes of spinning biodisks are microfluidic disks and bio-optical compact disks (BioCD). Microfluidic biodisks take advantage of noninertial pumping for lab-on-a-chip devices using noninertial valves and switches under centrifugal and Coriolis forces to distribute fluids about the disks. BioCDs use spinning-disk interferometry, under the condition of common-path phase quadrature, to perform interferometric label-free detection of molecular recognition and binding. The optical detection of bound molecules on a disk is facilitated by rapid spinning that enables high-speed repetitive sampling to eliminate 1∕f noise through common-mode rejection of intensity fluctuations and extensive signal averaging. Multiple quadrature classes have been developed, such as microdiffraction, in-line, phase contrast, and holographic adaptive optics. Thin molecular films are detected through the surface dipole density with a surface height sensitivity for the detection of protein spots that is approximately 1 pm. This sensitivity easily resolves a submonolayer of solid-support immobilized antibodies and their antigen targets. Fluorescence and light scattering provide additional optical detection techniques on spinning disks. Immunoassays have been applied to haptoglobin using protein A∕G immobilization of antibodies and to prostate specific antigen. Small protein spots enable scalability to many spots per disk for high-throughput and highly multiplexed immonoassays. PMID:19895047

An automated microreactor for semi-continuous biosensor measurements.

PubMed

Buffi, Nina; Beggah, Siham; Truffer, Frederic; Geiser, Martial; van Lintel, Harald; Renaud, Philippe; van der Meer, Jan Roelof

2016-04-21

Living bacteria or yeast cells are frequently used as bioreporters for the detection of specific chemical analytes or conditions of sample toxicity. In particular, bacteria or yeast equipped with synthetic gene circuitry that allows the production of a reliable non-cognate signal (e.g., fluorescent protein or bioluminescence) in response to a defined target make robust and flexible analytical platforms. We report here how bacterial cells expressing a fluorescence reporter ("bactosensors"), which are mostly used for batch sample analysis, can be deployed for automated semi-continuous target analysis in a single concise biochip. Escherichia coli-based bactosensor cells were continuously grown in a 13 or 50 nanoliter-volume reactor on a two-layered polydimethylsiloxane-on-glass microfluidic chip. Physiologically active cells were directed from the nl-reactor to a dedicated sample exposure area, where they were concentrated and reacted in 40 minutes with the target chemical by localized emission of the fluorescent reporter signal. We demonstrate the functioning of the bactosensor-chip by the automated detection of 50 μgarsenite-As l(-1) in water on consecutive days and after a one-week constant operation. Best induction of the bactosensors of 6-9-fold to 50 μg l(-1) was found at an apparent dilution rate of 0.12 h(-1) in the 50 nl microreactor. The bactosensor chip principle could be widely applicable to construct automated monitoring devices for a variety of targets in different environments.

Point of care optical device for sepsis diagnosis

NASA Astrophysics Data System (ADS)

Baldini, F.; Bolzoni, L.; Giannetti, A.; Porro, G.; Senesi, F.; Trono, C.

2009-10-01

The discrimination of viral and bacterial sepsis is an important issue in intensive care patients. For this purpose, the simultaneous measurements of different analytes are necessary. Among the possible candidates, C-reactive protein (CRP) and procalcitonin (PCT) are probably the most important ones. A novel optical platform was designed and realised for the implementation of fluorescence-based immunoassays. The core of the optical platform is a plastic biochip, constituted by 13 microchannels (50 μm high, 600 μm width, 10 mm long) through which the sample flows. The sensing layer, where the immunochemical reaction takes place, is located on the upper part of each microchannel. The chip is interrogated with a novel optoelectronic platform, based on fluorescence anisotropy. A line-shaped beam from a 635-nm laser-diode excites perpendicularly the sensing layer and great many of the emitted remains entrapped inside the chip. The particular shape of the top of the chip allows to guide the emitted fluorescence along the same direction of the microchannel. The fluorescence which comes out on the lateral side from the chip is collected by a single plastic optical fibre and sent to an amplified photodiode. The device was characterised by the implementation of the sandwich assay for CRP and PCT spiked in serum. Limit of quantifications of 4.5 and of 6 μg L-1 in serum solution were achieved for CRP and PCT, respectively.

Serum adipokines (adiponectin and resistin) correlation in developing gestational diabetes mellitus: pilot study.

PubMed

Siddiqui, Khalid; George, Teena P; Nawaz, Shaik Sarfaraz; Shehata, Nevene; El-Sayed, Amel Ahmed; Khanam, Latifa

2018-06-01

Adiponectin and resistin are adipose tissue-derived proteins with antagonistic actions; adiponectin has insulin sensitive properties while resistin is involved in the development of insulin resistance. We analyzed adiponectin and resistin levels in gestational diabetes mellitus (GDM) women to evaluate the association of these adipokines in a very high diabetes prevalence population. An age-matched case-control study of GDM and normal pregnant women in Saudi population. We recruited 90 pregnant women at 24-32 weeks of gestation. Glucose levels (fasting, 1, 2, and 3 h) and lipid parameters (cholesterol, triglyceride, HDL cholesterol, LDL cholesterol) were measured. Serum adiponectin and resistin levels were analyzed using Randox evidence biochip analyzer. Pearson's correlation coefficient was used to determine the association of adiponectin and resistin with GDM risk factors. GDM women showed significantly low adiponectin and high resistin levels when compared with control group. Pearson's correlation analysis of adiponectin and resistin in all the subjects with various GDM risk factors showed a negative association of adiponectin (r = -0.32, p = .05) and a positive correlation of resistin (r = 0.41, p = .01) with LDL cholesterol. This study analyzes adiponectin and resistin levels together, as accumulating evidences shows that these are involved in the pathophysiology of GDM. This is going to help to determine in conjunction with traditional risk factors the incremental value of circulating adiponectin and resistin in developing GDM.

Detecting Cancer Quickly and Accurately

NASA Astrophysics Data System (ADS)

Gourley, Paul; McDonald, Anthony; Hendricks, Judy; Copeland, Guild; Hunter, John; Akhil, Ohmar; Capps, Heather; Curry, Marc; Skirboll, Steve

2000-03-01

We present a new technique for high throughput screening of tumor cells in a sensitive nanodevice that has the potential to quickly identify a cell population that has begun the rapid protein synthesis and mitosis characteristic of cancer cell proliferation. Currently, pathologists rely on microscopic examination of cell morphology using century-old staining methods that are labor-intensive, time-consuming and frequently in error. New micro-analytical methods for automated, real time screening without chemical modification are critically needed to advance pathology and improve diagnoses. We have teamed scientists with physicians to create a microlaser biochip (based upon our R&D award winning bio-laser concept)1 which evaluates tumor cells by quantifying their growth kinetics. The key new discovery was demonstrating that the lasing spectra are sensitive to the biomolecular mass in the cell, which changes the speed of light in the laser microcavity. Initial results with normal and cancerous human brain cells show that only a few hundred cells -- the equivalent of a billionth of a liter -- are required to detect abnormal growth. The ability to detect cancer in such a minute tissue sample is crucial for resecting a tumor margin or grading highly localized tumor malignancy. 1. P. L. Gourley, NanoLasers, Scientific American, March 1998, pp. 56-61. This work supported under DOE contract DE-AC04-94AL85000 and the Office of Basic Energy Sciences.

Early-stage detection of VE-cadherin during endothelial differentiation of human mesenchymal stem cells using SPR biosensor.

PubMed

Fathi, Farzaneh; Rezabakhsh, Aysa; Rahbarghazi, Reza; Rashidi, Mohammad-Reza

2017-10-15

Surface plasmon resonance (SPR) biosensors are most commonly applied for real-time dynamic analysis and measurement of interactions in bio-molecular studies and cell-surface analysis without the need for labeling processes. Up to present, SPR application in stem cell biology and biomedical sciences was underused. Herein, a very simple and sensitive method was developed to evaluate human mesenchymal stem cells trans-differentiation to endothelial lineage of over a period of 14 days based on VE-cadherin biomarker. The SPR signals increased with the increase of the amount of VE-cadherin expression on the cell surface during cell differentiation process. The method was able to detect ≈27 cells permm 2 . No significant effect was observed on the cell viability during the cell attachment to the surface of immune-reactive biochips and during the SPR analysis. Using this highly sensitive SPR method, it was possible to sense the early stage of endothelial differentiation on day 3 in label-free form, whereas flow cytometry and fluorescent microscopy methods were found unable to detect the cell differentiation at the same time. Therefore, the proposed method can rapidly and accurately detect cell differentiation in live cells and label-free manner without any need of cell breakage and has great potential for both diagnostic and experimental approaches. Copyright © 2017. Published by Elsevier B.V.

Mechanical stability analysis of the protein L immunoglobulin-binding domain by full alanine screening using molecular dynamics simulations.

PubMed

Glyakina, Anna V; Likhachev, Ilya V; Balabaev, Nikolay K; Galzitskaya, Oxana V

2015-03-01

This article is the first to study the mechanical properties of the immunoglobulin-binding domain of protein L (referred to as protein L) and its mutants at the atomic level. In the structure of protein L, each amino acid residue (except for alanines and glycines) was replaced sequentially by alanine. Thus, 49 mutants of protein L were obtained. The proteins were stretched at their termini at constant velocity using molecular dynamics simulations in water, i.e. by forced unfolding. 19 out of 49 mutations resulted in a large decrease of mechanical protein stability. These amino acids were affecting either the secondary structure (11 mutations) or loop structures (8 mutations) of protein L. Analysis of mechanical unfolding of the generated protein that has the same topology as protein L but consists of only alanines and glycines allows us to suggest that the mechanical stability of proteins, and specifically protein L, is determined by interactions between certain amino acid residues, although the unfolding pathway depends on the protein topology. This insight can now be used to modulate the mechanical properties of proteins and their unfolding pathways in the desired direction for using them in various biochips, biosensors and biomaterials for medicine, industry, and household purposes. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Metal ion interaction with phosphorylated tyrosine analogue monolayers on gold.

PubMed

Petoral, Rodrigo M; Björefors, Fredrik; Uvdal, Kajsa

2006-11-23

Phosphorylated tyrosine analogue molecules (pTyr-PT) were assembled onto gold substrates, and the resulting monolayers were used for metal ion interaction studies. The monolayers were characterized by X-ray photoelectron spectroscopy (XPS), infrared reflection-absorption spectroscopy (IRAS), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS), both prior to and after exposure to metal ions. XPS verified the elemental composition of the molecular adsorbate and the presence of metal ions coordinated to the phosphate groups. Both the angle-dependent XPS and IRAS results were consistent with the change in the structural orientation of the pTyr-PT monolayer upon exposure to metal ions. The differential capacitance of the monolayers upon coordination of the metal ions was evaluated using EIS. These metal ions were found to significantly change the capacitance of the pTyr-PT monolayers in contrast to the nonphosphorylated tyrosine analogue (TPT). CV results showed reduced electrochemical blocking capabilities of the phosphorylated analogue monolayer when exposed to metal ions, supporting the change in the structure of the monolayer observed by XPS and IRAS. The largest change in the structure and interfacial capacitance was observed for aluminum ions, compared to calcium, magnesium, and chromium ions. This type of monolayer shows an excellent capability to coordinate metal ions and has a high potential for use as sensing layers in biochip applications to monitor the presence of metal ions.

Mastering multi-depth bio-chip patterns with DVD LBRs

NASA Astrophysics Data System (ADS)

Carson, Doug

2017-08-01

Bio chip and bio disc are rapidly growing technologies used in medical, health and other industries. While there are numerous unique designs and features, these products all rely on precise three-dimensional micro-fluidic channels or arrays to move, separate and combine samples under test. These bio chip and bio disc consumables are typically manufactured by molding these parts to a precise three-dimensional pattern on a negative metal stamper, or they can be made in smaller quantities using an appropriate curable resin and a negative mold/stamper. Stampers required for bio chips have been traditionally made using either micro machining or XY stepping lithography. Both of these technologies have their advantages as well as limitations when it comes to creating micro-fluidic patterns. Significant breakthroughs in continuous maskless lithography have enabled accurate and efficient manufacturing of micro-fluidic masters using LBRs (Laser Beam Recorders) and DRIE (Deep Reactive Ion Etching). The important advantages of LBR continuous lithography vs. XY stepping lithography and micro machining are speed and cost. LBR based continuous lithography is >100x faster than XY stepping lithography and more accurate than micro machining. Several innovations were required in order to create multi-depth patterns with sub micron accuracy. By combining proven industrial LBRs with DCA's G3-VIA pattern generator and DRIE, three-dimensional bio chip masters and stampers are being manufactured efficiently and accurately.

Energy Systems Integration: Demonstrating Distribution Feeder Voltage Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

2017-01-01

Overview fact sheet about the Smarter Grid Solutions Integrated Network Testbed for Energy Grid Research and Technology Experimentation (INTEGRATE) project at the Energy Systems Integration Facility. INTEGRATE is part of the U.S. Department of Energy's Grid Modernization Initiative.

Energy Systems Integration: Demonstrating Distributed Grid-Edge Control Hierarchy

DOE Office of Scientific and Technical Information (OSTI.GOV)

2017-01-01

Overview fact sheet about the OMNETRIC Group Integrated Network Testbed for Energy Grid Research and Technology Experimentation (INTEGRATE) project at the Energy Systems Integration Facility. INTEGRATE is part of the U.S. Department of Energy's Grid Modernization Initiative.

75 FR 53262 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-31

... a new Privacy Act system of records, JUSTICE/FBI- 021, the Data Integration and Visualization System... Act system of records, the Data Integration and Visualization System (DIVS), Justice/FBI-021. The... investigative mission by enabling access, search, integration, and analytics across multiple existing databases...

V-band integrated quadriphase modulator

NASA Technical Reports Server (NTRS)

Grote, A.; Chang, K.

1983-01-01

A V-band integrated circuit quadriphase shift keyed modulator/exciter for space communications systems was developed. Intersatellite communications systems require direct modulation at 60 GHz to enhance signal processing capability. For most systems, particularly space applications, small and lightweight components are essential to alleviate severe system design constraints. Thus to achieve wideband, high data rate systems, direct modulation techniques at millimeter waves using solid state integrated circuit technology are an integral part of the overall technology developments.

MEMS Technology for Space Applications

NASA Technical Reports Server (NTRS)

vandenBerg, A.; Spiering, V. L.; Lammerink, T. S. J.; Elwenspoek, M.; Bergveld, P.

1995-01-01

Micro-technology enables the manufacturing of all kinds of components for miniature systems or micro-systems, such as sensors, pumps, valves, and channels. The integration of these components into a micro-electro-mechanical system (MEMS) drastically decreases the total system volume and mass. These properties, combined with the increasing need for monitoring and control of small flows in (bio)chemical experiments, makes MEMS attractive for space applications. The level of integration and applied technology depends on the product demands and the market. The ultimate integration is process integration, which results in a one-chip system. An example of process integration is a dosing system of pump, flow sensor, micromixer, and hybrid feedback electronics to regulate the flow. However, for many applications, a hybrid integration of components is sufficient and offers the advantages of design flexibility and even the exchange of components in the case of a modular set up. Currently, we are working on hybrid integration of all kinds of sensors (physical and chemical) and flow system modules towards a modular system; the micro total analysis system (micro TAS). The substrate contains electrical connections as in a printed circuit board (PCB) as well as fluid channels for a circuit channel board (CCB) which, when integrated, form a mixed circuit board (MCB).

Grid Integration Studies: Advancing Clean Energy Planning and Deployment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katz, Jessica; Chernyakhovskiy, Ilya

2016-07-01

Integrating significant variable renewable energy (VRE) into the grid requires an evolution in power system planning and operation. To plan for this evolution, power system stakeholders can undertake grid integration studies. This Greening the Grid document reviews grid integration studies, common elements, questions, and guidance for system planners.

76 FR 69284 - Certain Integrated Solar Power Systems and Components Thereof: Notice of Institution of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-08

... the United States after importation of certain integrated solar power systems and components thereof... certain integrated solar power systems and components thereof that infringe one or more of claims 6 and 10... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-811] Certain Integrated Solar Power...

Take a Tour of Our Facility | Energy Systems Integration Facility | NREL

Science.gov Websites

Take a Tour of Our Facility Take a Tour of Our Facility The Energy Systems Integration Facility Optical Characterization Laboratory System Performance Laboratory Power Systems Integration Laboratory Control Room Energy Storage Laboratory Outdoor Testing Areas Outdoor Testing Areas Energy Systems

48 CFR 3007.106-70 - Limitations on Lead System Integrators.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Limitations on Lead System... Acquisition Plans 3007.106-70 Limitations on Lead System Integrators. See (HSAR) 48 CFR 3009.570 for policy applicable to acquisition strategies that consider the use of lead system integrators. ...

48 CFR 3007.106-70 - Limitations on Lead System Integrators.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Limitations on Lead System... Acquisition Plans 3007.106-70 Limitations on Lead System Integrators. See (HSAR) 48 CFR 3009.570 for policy applicable to acquisition strategies that consider the use of lead system integrators. ...

48 CFR 3007.106-70 - Limitations on Lead System Integrators.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Limitations on Lead System... Acquisition Plans 3007.106-70 Limitations on Lead System Integrators. See (HSAR) 48 CFR 3009.570 for policy applicable to acquisition strategies that consider the use of lead system integrators. ...

48 CFR 3007.106-70 - Limitations on Lead System Integrators.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Limitations on Lead System... Acquisition Plans 3007.106-70 Limitations on Lead System Integrators. See (HSAR) 48 CFR 3009.570 for policy applicable to acquisition strategies that consider the use of lead system integrators. ...

48 CFR 3007.106-70 - Limitations on Lead System Integrators.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Limitations on Lead System... Acquisition Plans 3007.106-70 Limitations on Lead System Integrators. See (HSAR) 48 CFR 3009.570 for policy applicable to acquisition strategies that consider the use of lead system integrators. ...

IEMIS (Integrated Emergency Management Information System) Floodplain Mapping Based on a Lidar Derived Data Set.

DTIC Science & Technology

1988-02-05

0-A193 971 IEMIS (INTEGRATED EMERGENCY MANAGEMENT INFORMATION SYSTEM ) FLOODPLRIN MAP.. (U) ARMY ENGINEER WATERWAYS EXPERIMENT STATION VICKSBURG HS J...illustrate the application of the automated mapping capabilities of the Integrated Emergency Management Information System (IEMIS) to FISs. Unclassified...mapping capabilities of the Integrated Emergency Management Information System (IEMIS) to FISs. II. BACKGROUND The concept of mounting laser ranging

Development of Spreadsheet-Based Integrated Transaction Processing Systems and Financial Reporting Systems

NASA Astrophysics Data System (ADS)

Ariana, I. M.; Bagiada, I. M.

2018-01-01

Development of spreadsheet-based integrated transaction processing systems and financial reporting systems is intended to optimize the capabilities of spreadsheet in accounting data processing. The purpose of this study are: 1) to describe the spreadsheet-based integrated transaction processing systems and financial reporting systems; 2) to test its technical and operational feasibility. This study type is research and development. The main steps of study are: 1) needs analysis (need assessment); 2) developing spreadsheet-based integrated transaction processing systems and financial reporting systems; and 3) testing the feasibility of spreadsheet-based integrated transaction processing systems and financial reporting systems. The technical feasibility include the ability of hardware and operating systems to respond the application of accounting, simplicity and ease of use. Operational feasibility include the ability of users using accounting applications, the ability of accounting applications to produce information, and control applications of the accounting applications. The instrument used to assess the technical and operational feasibility of the systems is the expert perception questionnaire. The instrument uses 4 Likert scale, from 1 (strongly disagree) to 4 (strongly agree). Data were analyzed using percentage analysis by comparing the number of answers within one (1) item by the number of ideal answer within one (1) item. Spreadsheet-based integrated transaction processing systems and financial reporting systems integrate sales, purchases, and cash transaction processing systems to produce financial reports (statement of profit or loss and other comprehensive income, statement of changes in equity, statement of financial position, and statement of cash flows) and other reports. Spreadsheet-based integrated transaction processing systems and financial reporting systems is feasible from the technical aspects (87.50%) and operational aspects (84.17%).

Integrated Main Propulsion System Performance Reconstruction Process/Models

NASA Technical Reports Server (NTRS)

Lopez, Eduardo; Elliott, Katie; Snell, Steven; Evans, Michael

2013-01-01

The Integrated Main Propulsion System (MPS) Performance Reconstruction process provides the MPS post-flight data files needed for postflight reporting to the project integration management and key customers to verify flight performance. This process/model was used as the baseline for the currently ongoing Space Launch System (SLS) work. The process utilizes several methodologies, including multiple software programs, to model integrated propulsion system performance through space shuttle ascent. It is used to evaluate integrated propulsion systems, including propellant tanks, feed systems, rocket engine, and pressurization systems performance throughout ascent based on flight pressure and temperature data. The latest revision incorporates new methods based on main engine power balance model updates to model higher mixture ratio operation at lower engine power levels.

Establishment of key grid-connected performance index system for integrated PV-ES system

NASA Astrophysics Data System (ADS)

Li, Q.; Yuan, X. D.; Qi, Q.; Liu, H. M.

2016-08-01

In order to further promote integrated optimization operation of distributed new energy/ energy storage/ active load, this paper studies the integrated photovoltaic-energy storage (PV-ES) system which is connected with the distribution network, and analyzes typical structure and configuration selection for integrated PV-ES generation system. By combining practical grid- connected characteristics requirements and technology standard specification of photovoltaic generation system, this paper takes full account of energy storage system, and then proposes several new grid-connected performance indexes such as paralleled current sharing characteristic, parallel response consistency, adjusting characteristic, virtual moment of inertia characteristic, on- grid/off-grid switch characteristic, and so on. A comprehensive and feasible grid-connected performance index system is then established to support grid-connected performance testing on integrated PV-ES system.

A SINS/SRS/GNS Autonomous Integrated Navigation System Based on Spectral Redshift Velocity Measurements.

PubMed

Wei, Wenhui; Gao, Zhaohui; Gao, Shesheng; Jia, Ke

2018-04-09

In order to meet the requirements of autonomy and reliability for the navigation system, combined with the method of measuring speed by using the spectral redshift information of the natural celestial bodies, a new scheme, consisting of Strapdown Inertial Navigation System (SINS)/Spectral Redshift (SRS)/Geomagnetic Navigation System (GNS), is designed for autonomous integrated navigation systems. The principle of this SINS/SRS/GNS autonomous integrated navigation system is explored, and the corresponding mathematical model is established. Furthermore, a robust adaptive central difference particle filtering algorithm is proposed for this autonomous integrated navigation system. The simulation experiments are conducted and the results show that the designed SINS/SRS/GNS autonomous integrated navigation system possesses good autonomy, strong robustness and high reliability, thus providing a new solution for autonomous navigation technology.

The Design and Implementation of an Integrated Financial Control System.

ERIC Educational Resources Information Center

Alexander, George D.

1978-01-01

The design and implementation of an integrated financial control system at Clemson University are described. The advantages of considering the integration of systems to meet university-wide objectives as design criteria are discussed as well as sub-system relationships. (Author/BH)

Energy Systems Integration: Demonstrating Distributed Resource Communications

DOE Office of Scientific and Technical Information (OSTI.GOV)

2017-01-01

Overview fact sheet about the Electric Power Research Institute (EPRI) and Schneider Electric Integrated Network Testbed for Energy Grid Research and Technology Experimentation (INTEGRATE) project at the Energy Systems Integration Facility. INTEGRATE is part of the U.S. Department of Energy's Grid Modernization Initiative.

Systems Engineering and Integration for Technology Programs

NASA Technical Reports Server (NTRS)

Kennedy, Kruss J.

2006-01-01

The Architecture, Habitability & Integration group (AH&I) is a system engineering and integration test team within the NASA Crew and Thermal Systems Division (CTSD) at Johnson Space Center. AH&I identifies and resolves system-level integration issues within the research and technology development community. The timely resolution of these integration issues is fundamental to the development of human system requirements and exploration capability. The integration of the many individual components necessary to construct an artificial environment is difficult. The necessary interactions between individual components and systems must be approached in a piece-wise fashion to achieve repeatable results. A formal systems engineering (SE) approach to define, develop, and integrate quality systems within the life support community has been developed. This approach will allow a Research & Technology Program to systematically approach the development, management, and quality of technology deliverables to the various exploration missions. A tiered system engineering structure has been proposed to implement best systems engineering practices across all development levels from basic research to working assemblies. These practices will be implemented through a management plan across all applicable programs, projects, elements and teams. While many of the engineering practices are common to other industries, the implementation is specific to technology development. An accounting of the systems engineering management philosophy will be discussed and the associated programmatic processes will be presented.

The Design of a Practical Enterprise Safety Management System

NASA Astrophysics Data System (ADS)

Gabbar, Hossam A.; Suzuki, Kazuhiko

This book presents design guidelines and implementation approaches for enterprise safety management system as integrated within enterprise integrated systems. It shows new model-based safety management where process design automation is integrated with enterprise business functions and components. It proposes new system engineering approach addressed to new generation chemical industry. It will help both the undergraduate and professional readers to build basic knowledge about issues and problems of designing practical enterprise safety management system, while presenting in clear way, the system and information engineering practices to design enterprise integrated solution.

Crop and cattle production responses to tillage and cover crop management in an integrated crop-livestock system in the southeastern USA

USDA-ARS?s Scientific Manuscript database

Integrated crop-livestock systems can help achieve greater environmental quality from disparate crop and livestock systems by recycling nutrients and taking advantage of synergies between systems. We investigated crop and animal production responses in integrated crop-livestock systems with two typ...

46 CFR 111.50-2 - Systems integration.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Systems integration. 111.50-2 Section 111.50-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Overcurrent Protection § 111.50-2 Systems integration. The electrical characteristics of each...

Energy System Basics and Distribution Integration Video Series | Energy

Science.gov Websites

renewablesparticularly solar photovoltaic (PV) technologiesonto the distribution grid. Solar Energy Technologies PV Integration Case Studies Integrating Photovoltaic Systems onto Secondary Network Distribution Systems Standards and Codes for U.S. Photovoltaic System Installation Network-Optimal Control of Photovoltaics on

Integrability of systems of two second-order ordinary differential equations admitting four-dimensional Lie algebras

PubMed Central

Gazizov, R. K.

2017-01-01

We suggest an algorithm for integrating systems of two second-order ordinary differential equations with four symmetries. In particular, if the admitted transformation group has two second-order differential invariants, the corresponding system can be integrated by quadratures using invariant representation and the operator of invariant differentiation. Otherwise, the systems reduce to partially uncoupled forms and can also be integrated by quadratures. PMID:28265184

Integrability of systems of two second-order ordinary differential equations admitting four-dimensional Lie algebras.

PubMed

Gainetdinova, A A; Gazizov, R K

2017-01-01

We suggest an algorithm for integrating systems of two second-order ordinary differential equations with four symmetries. In particular, if the admitted transformation group has two second-order differential invariants, the corresponding system can be integrated by quadratures using invariant representation and the operator of invariant differentiation. Otherwise, the systems reduce to partially uncoupled forms and can also be integrated by quadratures.

Super-integrable Calogero-type systems admit maximal number of Poisson structures

NASA Astrophysics Data System (ADS)

Gonera, C.; Nutku, Y.

2001-07-01

We present a general scheme for constructing the Poisson structure of super-integrable dynamical systems of which the rational Calogero-Moser system is the most interesting one. This dynamical system is 2 N-dimensional with 2 N-1 first integrals and our construction yields 2 N-1 degenerate Poisson tensors that each admit 2( N-1) Casimirs. Our results are quite generally applicable to all super-integrable systems and form an alternative to the traditional bi-Hamiltonian approach.

Avionics systems integration technology

NASA Technical Reports Server (NTRS)

Stech, George; Williams, James R.

1988-01-01

A very dramatic and continuing explosion in digital electronics technology has been taking place in the last decade. The prudent and timely application of this technology will provide Army aviation the capability to prevail against a numerically superior enemy threat. The Army and NASA have exploited this technology explosion in the development and application of avionics systems integration technology for new and future aviation systems. A few selected Army avionics integration technology base efforts are discussed. Also discussed is the Avionics Integration Research Laboratory (AIRLAB) that NASA has established at Langley for research into the integration and validation of avionics systems, and evaluation of advanced technology in a total systems context.

Health Systems Integration of Sexual and Reproductive Health and HIV Services in Sub-Saharan Africa: A Scoping Study

PubMed Central

Kendall, Tamil; Langer, Ana; Bärnighausen, Till

2014-01-01

Objective: Both sexual and reproductive health (SRH) services and HIV programs in sub-Saharan Africa are typically delivered vertically, operating parallel to national health systems. The objective of this study was to map the evidence on national and international strategies for integration of SRH and HIV services in sub-Saharan Africa and to develop a research agenda for future health systems integration. Methods: We examined the literature on national and international strategies to integrate SRH and HIV services using a scoping study methodology. Current policy frameworks, national HIV strategies and research, and gray literature on integration were mapped. Five countries in sub-Saharan Africa with experience of integrating SRH and HIV services were purposively sampled for detailed thematic analysis, according to the health systems functions of governance, policy and planning, financing, health workforce organization, service organization, and monitoring and evaluation. Results: The major international health policies and donor guidance now support integration. Most integration research has focused on linkages of SRH and HIV front-line services. Yet, the common problems with implementation are related to delayed or incomplete integration of higher level health systems functions: lack of coordinated leadership and unified national integration policies; separate financing streams for SRH and HIV services and inadequate health worker training, supervision and retention. Conclusions: Rigorous health systems research on the integration of SRH and HIV services is urgently needed. Priority research areas include integration impact, performance, and economic evaluation to inform the planning, financing, and coordination of integrated service delivery. PMID:25436826

Ceramic Integration Technologies for Aerospace and Energy Systems: Technical Challenges and Opportunities

NASA Technical Reports Server (NTRS)

Singh, Mrityunjay

2007-01-01

Ceramic integration technology has been recognized as an enabling technology for the implementation of advanced ceramic systems in a number of high-temperature applications in aerospace, power generation, nuclear, chemical, and electronic industries. Various ceramic integration technologies (joining, brazing, attachments, repair, etc.) play a role in fabrication and manufacturing of large and complex shaped parts of various functionalities. However, the development of robust and reliable integrated systems with optimum performance requires the understanding of many thermochemical and thermomechanical factors, particularly for high temperature applications. In this presentation, various challenges and opportunities in design, fabrication, and testing of integrated similar (ceramic-ceramic) and dissimilar (ceramic-metal) material systems will be discussed. Experimental results for bonding and integration of SiC based LDI fuel injector, high conductivity C/C composite based heat rejection system, solid oxide fuel cells system, ultra high temperature ceramics for leading edges, and ceramic composites for thermostructural applications will be presented. Potential opportunities and need for the development of innovative design philosophies, approaches, and integrated system testing under simulated application conditions will also be discussed.

Nonlinear integrable model of Frenkel-like excitations on a ribbon of triangular lattice

NASA Astrophysics Data System (ADS)

Vakhnenko, Oleksiy O.

2015-03-01

Following the considerable progress in nanoribbon technology, we propose to model the nonlinear Frenkel-like excitations on a triangular-lattice ribbon by the integrable nonlinear ladder system with the background-controlled intersite resonant coupling. The system of interest arises as a proper reduction of first general semidiscrete integrable system from an infinite hierarchy. The most significant local conservation laws related to the first general integrable system are found explicitly in the framework of generalized recursive approach. The obtained general local densities are equally applicable to any general semidiscrete integrable system from the respective infinite hierarchy. Using the recovered second densities, the Hamiltonian formulation of integrable nonlinear ladder system with background-controlled intersite resonant coupling is presented. In doing so, the relevant Poisson structure turns out to be essentially nontrivial. The Darboux transformation scheme as applied to the first general semidiscrete system is developed and the key role of Bäcklund transformation in justification of its self-consistency is pointed out. The spectral properties of Darboux matrix allow to restore the whole Darboux matrix thus ensuring generation one more soliton as compared with a priori known seed solution of integrable nonlinear system. The power of Darboux-dressing method is explicitly demonstrated in generating the multicomponent one-soliton solution to the integrable nonlinear ladder system with background-controlled intersite resonant coupling.

75 FR 53342 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-31

...), Federal Bureau of Investigation (FBI), proposes to establish a new system of records, the Data Integration and Visualization System, JUSTICE/FBI-021, to support and enhance data search, integration... to develop more efficient methods to analyze FBI data. The Data Integration and Visualization System...

Management/Technical Interaction in Integrated Information System Development.

ERIC Educational Resources Information Center

Bagley, Clarence H.; Gardner, Don E.

The integrated information system element of the management information system concept has practical applications for management in the areas of both information analysis and decision-model building. Four basic options for achieving integration in operational data systems are: a default option, the coordinated file option, the distributed…

A SINS/SRS/GNS Autonomous Integrated Navigation System Based on Spectral Redshift Velocity Measurements

PubMed Central

Wei, Wenhui; Gao, Zhaohui; Gao, Shesheng; Jia, Ke

2018-01-01

In order to meet the requirements of autonomy and reliability for the navigation system, combined with the method of measuring speed by using the spectral redshift information of the natural celestial bodies, a new scheme, consisting of Strapdown Inertial Navigation System (SINS)/Spectral Redshift (SRS)/Geomagnetic Navigation System (GNS), is designed for autonomous integrated navigation systems. The principle of this SINS/SRS/GNS autonomous integrated navigation system is explored, and the corresponding mathematical model is established. Furthermore, a robust adaptive central difference particle filtering algorithm is proposed for this autonomous integrated navigation system. The simulation experiments are conducted and the results show that the designed SINS/SRS/GNS autonomous integrated navigation system possesses good autonomy, strong robustness and high reliability, thus providing a new solution for autonomous navigation technology. PMID:29642549

“SLIMPLECTIC” INTEGRATORS: VARIATIONAL INTEGRATORS FOR GENERAL NONCONSERVATIVE SYSTEMS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsang, David; Turner, Alec; Galley, Chad R.

2015-08-10

Symplectic integrators are widely used for long-term integration of conservative astrophysical problems due to their ability to preserve the constants of motion; however, they cannot in general be applied in the presence of nonconservative interactions. In this Letter, we develop the “slimplectic” integrator, a new type of numerical integrator that shares many of the benefits of traditional symplectic integrators yet is applicable to general nonconservative systems. We utilize a fixed-time-step variational integrator formalism applied to the principle of stationary nonconservative action developed in Galley et al. As a result, the generalized momenta and energy (Noether current) evolutions are well-tracked. Wemore » discuss several example systems, including damped harmonic oscillators, Poynting–Robertson drag, and gravitational radiation reaction, by utilizing our new publicly available code to demonstrate the slimplectic integrator algorithm. Slimplectic integrators are well-suited for integrations of systems where nonconservative effects play an important role in the long-term dynamical evolution. As such they are particularly appropriate for cosmological or celestial N-body dynamics problems where nonconservative interactions, e.g., gas interactions or dissipative tides, can play an important role.« less

Information Systems Integration and Enterprise Application Integration (EAI) Adoption: A Case from Financial Services

ERIC Educational Resources Information Center

Lam, Wing

2007-01-01

Increasingly, organizations find that they need to integrate large number of information systems in order to support enterprise-wide business initiatives such as e-business, supply chain management and customer relationship management. To date, organizations have largely tended to address information systems (IS) integration in an ad-hoc manner.…

Automatic visual inspection system for microelectronics

NASA Technical Reports Server (NTRS)

Micka, E. Z. (Inventor)

1975-01-01

A system for automatically inspecting an integrated circuit was developed. A device for shining a scanning narrow light beam at an integrated circuit to be inspected and another light beam at an accepted integrated circuit was included. A pair of photodetectors that receive light reflected from these integrated circuits, and a comparing system compares the outputs of the photodetectors.

76 FR 57033 - Draft Toxicological Review of n-Butanol: In Support of Summary Information on the Integrated Risk...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-15

... Toxicological Review of n-Butanol: In Support of Summary Information on the Integrated Risk Information System..., ``Toxicological Review of n-Butanol: In Support of Summary Information on the Integrated Risk Information System...-Butanol: In Support of Summary Information on the Integrated Risk Information System (IRIS)'' is available...

What is a completely integrable nonholonomic dynamical system?

NASA Astrophysics Data System (ADS)

Bates, Larry; Cushman, Richard

1999-10-01

We compare the geometry of a toral fibration defined by the common level sets of the integrals of a Liouville integrable Hamiltonian system with a toral fibration coming from a completely integrable nonholonomic system. We illustrate their differences using the following examples: the nonholonomic oscillator, Chaplygin's skate, Routh's sphere and the rolling oblate ellipsoid of revolution.

NASA UAS Integration into the NAS Project: Human Systems Integration

NASA Technical Reports Server (NTRS)

Shively, Jay

2016-01-01

This presentation provides an overview of the work the Human Systems Integration (HSI) sub-project has done on detect and avoid (DAA) displays while working on the UAS (Unmanned Aircraft System) Integration into the NAS project. The most recent simulation on DAA interoperability with Traffic Collision Avoidance System (TCAS) is discussed in the most detail. The relationship of the work to the larger UAS community and next steps are also detailed.

Including safety-net providers in integrated delivery systems: issues and options for policymakers.

PubMed

Witgert, Katherine; Hess, Catherine

2012-08-01

Health care reform legislation has spurred efforts to develop integrated health care delivery systems that seek to coordinate the continuum of health services. These systems may be of particular benefit to patients who face barriers to accessing care or have multiple health conditions. But it remains to be seen how safety-net providers, including community health centers and public hospitals--which have long experience in caring for these vulnerable populations--will be included in integrated delivery systems. This issue brief explores key considerations for incorporating safety-net providers into integrated delivery systems and discusses the roles of state and federal agencies in sup­porting and testing models of integrated care delivery. The authors conclude that the most important principles in creating integrated delivery systems for vulnerable populations are: (1) an emphasis on primary care; (2) coordination of all care, including behavioral, social, and public health services; and (3) accountability for population health outcomes.

Integrated nuclear data utilisation system for innovative reactors.

PubMed

Yamano, N; Hasegawa, A; Kato, K; Igashira, M

2005-01-01

A five-year research and development project on an integrated nuclear data utilisation system was initiated in 2002, for developing innovative nuclear energy systems such as accelerator-driven systems. The integrated nuclear data utilisation system will be constructed as a modular code system, which consists of two sub-systems: the nuclear data search and plotting sub-system, and the nuclear data processing and utilisation sub-system. The system will be operated with a graphical user interface in order to enable easy utilisation through the Internet by both nuclear design engineers and nuclear data evaluators. This paper presents an overview of the integrated nuclear data utilisation system, describes the development of a prototype system to examine the operability of the user interface and discusses specifications of the two sub-systems.

What is Energy Systems Integration?

ScienceCinema

Kroposki, Ben; Lundstrom, Blake; Hannegan, Bryan; Symko-Davies, Martha

2018-06-12

To achieve the most efficient, flexible, and reliable energy system, NREL’s Energy Systems Integration researchers work with manufacturers, utilities, and other research organizations to find solutions to big energy challenges. This video describes the concept of energy systems integration, an approach that explores ways for energy systems to work more efficiently on their own and with each other.

What is Energy Systems Integration?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kroposki, Ben; Lundstrom, Blake; Hannegan, Bryan

2016-10-14

To achieve the most efficient, flexible, and reliable energy system, NREL’s Energy Systems Integration researchers work with manufacturers, utilities, and other research organizations to find solutions to big energy challenges. This video describes the concept of energy systems integration, an approach that explores ways for energy systems to work more efficiently on their own and with each other.

Highly integrated digital engine control system on an F-15 airplane

NASA Technical Reports Server (NTRS)

Burcham, F. W., Jr.; Haering, E. A., Jr.

1984-01-01

The Highly Integrated Digital Electronic Control (HIDEC) program will demonstrate and evaluate the improvements in performance and mission effectiveness that result from integrated engine/airframe control systems. This system is being used on the F-15 airplane. An integrated flightpath management mode and an integrated adaptive engine stall margin mode are implemented into the system. The adaptive stall margin mode is a highly integrated mode in which the airplane flight conditions, the resulting inlet distortion, and the engine stall margin are continuously computed; the excess stall margin is used to uptrim the engine for more thrust. The integrated flightpath management mode optimizes the flightpath and throttle setting to reach a desired flight condition. The increase in thrust and the improvement in airplane performance is discussed.

Integrated inertial stellar attitude sensor

NASA Technical Reports Server (NTRS)

Brady, Tye M. (Inventor); Kourepenis, Anthony S. (Inventor); Wyman, Jr., William F. (Inventor)

2007-01-01

An integrated inertial stellar attitude sensor for an aerospace vehicle includes a star camera system, a gyroscope system, a controller system for synchronously integrating an output of said star camera system and an output of said gyroscope system into a stream of data, and a flight computer responsive to said stream of data for determining from the star camera system output and the gyroscope system output the attitude of the aerospace vehicle.

Integrating PV in Distributed Grids: Solutions and Technologies Workshop |

Science.gov Websites

Energy Systems Integration Facility | NREL Integrating PV in Distributed Grids: Solutions and Technologies Workshop Integrating PV in Distributed Grids: Solutions and Technologies Workshop In October 2015 (PV) onto the grid. The workshop was held at the Energy Systems Integration Facility. Presenters from

Energy Systems Integration: Demonstrating the Grid Benefits of Connected Devices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Overview fact sheet about the Electric Power Research Institute (EPRI) and the University of Delaware Integrated Network Testbed for Energy Grid Research and Technology Experimentation (INTEGRATE) project at the Energy Systems Integration Facility. INTEGRATE is part of the U.S. Department of Energy's Grid Modernization Initiative.

Scrapping Patched Computer Systems: Integrated Data Processing for Information Management.

ERIC Educational Resources Information Center

Martinson, Linda

1991-01-01

Colleges and universities must find a way to streamline and integrate information management processes across the organization. The Georgia Institute of Technology responded to an acute problem of dissimilar operating systems with a campus-wide integrated administrative system using a machine independent relational database management system. (MSE)

77 FR 48984 - Privacy Act of 1974; System of Records Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-15

... General (OSG), Division of Systems Integration (DSI), Tower Oaks Building, Plaza Level 100, 1101 Wootton... Integration, at 240-453- 6085. FOR FURTHER INFORMATION CONTACT: For system 09-40-0006, contact CAPT Eric Shih, Office of the Surgeon General (OSG), Division of Systems Integration (DSI) Tower Oaks Building, Plaza...

Synthesis of an integrated cockpit management system

NASA Technical Reports Server (NTRS)

Dasaro, J. A.; Elliott, C. T.

1982-01-01

The process used in the synthesis of an integrated cockpit management system was discussed. Areas covered included flight displays, subsystem management, checklists, and procedures (both normal and emergency). The process of evolving from the unintegrated conventional system to the integrated system is examined and a brief description of the results presented.

Systems Analysis and Integration Publications | Transportation Research |

Science.gov Websites

data Vehicle analysis Vehicle energy Vehicle modeling Vehicle simulation Wireless power transfer The NREL Systems Analysis and Integration Publications Systems Analysis and Integration Publications NREL publishes technical reports, fact sheets, and other documents about its systems analysis and

Integrable and superintegrable Hamiltonian systems with four dimensional real Lie algebras as symmetry of the systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abedi-Fardad, J., E-mail: j.abedifardad@bonabu.ac.ir; Rezaei-Aghdam, A., E-mail: rezaei-a@azaruniv.edu; Haghighatdoost, Gh., E-mail: gorbanali@azaruniv.edu

2014-05-15

We construct integrable and superintegrable Hamiltonian systems using the realizations of four dimensional real Lie algebras as a symmetry of the system with the phase space R{sup 4} and R{sup 6}. Furthermore, we construct some integrable and superintegrable Hamiltonian systems for which the symmetry Lie group is also the phase space of the system.

Identifying Challenges to the Integration of Computer-Based Surveillance Information Systems in a Large City Health Department: A Case Study.

PubMed

Jennings, Jacky M; Stover, Jeffrey A; Bair-Merritt, Megan H; Fichtenberg, Caroline; Munoz, Mary Grace; Maziad, Rafiq; Ketemepi, Sherry Johnson; Zenilman, Jonathan

2009-01-01

Integrated infectious disease surveillance information systems have the potential to provide important new surveillance capacities and business efficiencies for local health departments. We conducted a case study at a large city health department of the primary computer-based infectious disease surveillance information systems during a 10-year period to identify the major challenges for information integration across the systems. The assessment included key informant interviews and evaluations of the computer-based surveillance information systems used for acute communicable diseases, human immunodeficiency virus/acquired immunodeficiency syndrome, sexually transmitted diseases, and tuberculosis. Assessments were conducted in 1998 with a follow-up in 2008. Assessments specifically identified and described the primary computer-based surveillance information system, any duplicative information systems, and selected variables collected. Persistent challenges to information integration across the information systems included the existence of duplicative data systems, differences in the variables used to collect similar information, and differences in basic architecture. The assessments identified a number of challenges for information integration across the infectious disease surveillance information systems at this city health department. The results suggest that local disease control programs use computer-based surveillance information systems that were not designed for data integration. To the extent that integration provides important new surveillance capacities and business efficiencies, we recommend that patient-centric information systems be designed that provide all the epidemiologic, clinical, and research needs in one system. In addition, the systems should include a standard system of elements and fields across similar surveillance systems.

Assuring structural integrity in Army systems

NASA Technical Reports Server (NTRS)

1985-01-01

The object of this study was to recommend possible improvements in the manner in which structural integrity of Army systems is assured. The elements of a structural integrity program are described, and relevant practices used in various industries and government organizations are reviewed. Some case histories of Army weapon systems are examined. The mandatory imposition of a structural integrity program patterned after the Air Force Aircraft Structural Integrity Program is recommended and the benefits of such an action are identified.

The Vanguard of Community-based Integrated Care in Japan: The Effect of a Rural Town on National Policy

PubMed Central

Matsumoto, Masatoshi; Okita, Mitsuaki; Inoue, Kazuo; Takeuchi, Keisuke; Tsutsui, Takako; Nishimura, Shuhei; Hayashi, Takuo

2017-01-01

Introduction: Japan has the largest percentage of elderly people in the world. In 2012 the government implemented a community-based integrated care system which provides seamless community healthcare resources for elderly people with chronic diseases and disabilities. Methods: This paper describes the challenges of establishing a community-based integrated care system in 1974 in Mitsugi, a rural town of Japan. This system has influenced the government and become the model for the nationwide system. Results: In the 1970s, Mitsugi’s aging population was growing faster than Japan’s, but elder care was fragmented among a variety of service sections. A community-based integrated care system evolved because of the small but aging population size and the initiative of some local leaders of medical care and politics. After the system took effect, the proportion of bedridden people and medical care costs for the elderly dropped in Mitsugi while it continued to rise everywhere else in Japan. Mitsugi’s community-based integrated care system is now shaping national policy. Conclusion: Mitsugi is in the vanguard of Japan’s community-based integrated care system. The case showed the community-based integrated care system can diffuse from rural to urban areas. PMID:28970743

A Strapdown Interial Navigation System/Beidou/Doppler Velocity Log Integrated Navigation Algorithm Based on a Cubature Kalman Filter

PubMed Central

Gao, Wei; Zhang, Ya; Wang, Jianguo

2014-01-01

The integrated navigation system with strapdown inertial navigation system (SINS), Beidou (BD) receiver and Doppler velocity log (DVL) can be used in marine applications owing to the fact that the redundant and complementary information from different sensors can markedly improve the system accuracy. However, the existence of multisensor asynchrony will introduce errors into the system. In order to deal with the problem, conventionally the sampling interval is subdivided, which increases the computational complexity. In this paper, an innovative integrated navigation algorithm based on a Cubature Kalman filter (CKF) is proposed correspondingly. A nonlinear system model and observation model for the SINS/BD/DVL integrated system are established to more accurately describe the system. By taking multi-sensor asynchronization into account, a new sampling principle is proposed to make the best use of each sensor's information. Further, CKF is introduced in this new algorithm to enable the improvement of the filtering accuracy. The performance of this new algorithm has been examined through numerical simulations. The results have shown that the positional error can be effectively reduced with the new integrated navigation algorithm. Compared with the traditional algorithm based on EKF, the accuracy of the SINS/BD/DVL integrated navigation system is improved, making the proposed nonlinear integrated navigation algorithm feasible and efficient. PMID:24434842

System Engineering and Integration of Controls for Advanced Life Support

NASA Technical Reports Server (NTRS)

Overland, David; Hoo, Karlene; Ciskowski, Marvin

2006-01-01

The Advanced Integration Matrix (AIM) project at the Johnson Space Center (JSC) was chartered to study and solve systems-level integration issues for exploration missions. One of the first issues identified was an inability to conduct trade studies on control system architectures due to the absence of mature evaluation criteria. Such architectures are necessary to enable integration of regenerative life support systems. A team was formed to address issues concerning software and hardware architectures and system controls.. The team has investigated what is required to integrate controls for the types of non-linear dynamic systems encountered in advanced life support. To this end, a water processing bioreactor testbed is being developed which will enable prototyping and testing of integration strategies and technologies. Although systems such as the water bioreactors exhibit the complexities of interactions between control schemes most vividly, it is apparent that this behavior and its attendant risks will manifest itself among any set of interdependent autonomous control systems. A methodology for developing integration requirements for interdependent and autonomous systems is a goal of this team and this testbed. This paper is a high-level summary of the current status of the investigation, the issues encountered, some tentative conclusions, and the direction expected for further research.

Comparative health systems research among Kaiser Permanente and other integrated delivery systems: a systematic literature review.

PubMed

Maeda, Jared Lane K; Lee, Karen M; Horberg, Michael

2014-01-01

Because of rising health care costs, wide variations in quality, and increased patient complexity, the US health care system is undergoing rapid changes that include payment reform and movement toward integrated delivery systems. Well-established integrated delivery systems, such as Kaiser Permanente (KP), should work to identify the specific system-level factors that result in superior patient outcomes in response to policymakers' concerns. Comparative health systems research can provide insights into which particular aspects of the integrated delivery system result in improved care delivery. To provide a baseline understanding of comparative health systems research related to integrated delivery systems and KP. Systematic literature review. We conducted a literature search on PubMed and the KP Publications Library. Studies that compared KP as a system or organization with other health care systems or across KP facilities internally were included. The literature search identified 1605 articles, of which 65 met the study inclusion criteria and were examined by 3 reviewers. Most comparative health systems studies focused on intra-KP comparisons (n = 42). Fewer studies compared KP with other US (n = 15) or international (n = 12) health care systems. Several themes emerged from the literature as possible factors that may contribute to improved care delivery in integrated delivery systems. Of all studies published by or about KP, only a small proportion of articles (4%) was identified as being comparative health systems research. Additional empirical studies that compare the specific factors of the integrated delivery system model with other systems of care are needed to better understand the "system-level" factors that result in improved and/or diminished care delivery.

Modular Architecture for Integrated Model-Based Decision Support.

PubMed

Gaebel, Jan; Schreiber, Erik; Oeser, Alexander; Oeltze-Jafra, Steffen

2018-01-01

Model-based decision support systems promise to be a valuable addition to oncological treatments and the implementation of personalized therapies. For the integration and sharing of decision models, the involved systems must be able to communicate with each other. In this paper, we propose a modularized architecture of dedicated systems for the integration of probabilistic decision models into existing hospital environments. These systems interconnect via web services and provide model sharing and processing capabilities for clinical information systems. Along the lines of IHE integration profiles from other disciplines and the meaningful reuse of routinely recorded patient data, our approach aims for the seamless integration of decision models into hospital infrastructure and the physicians' daily work.

Design distributed simulation platform for vehicle management system

NASA Astrophysics Data System (ADS)

Wen, Zhaodong; Wang, Zhanlin; Qiu, Lihua

2006-11-01

Next generation military aircraft requires the airborne management system high performance. General modules, data integration, high speed data bus and so on are needed to share and manage information of the subsystems efficiently. The subsystems include flight control system, propulsion system, hydraulic power system, environmental control system, fuel management system, electrical power system and so on. The unattached or mixed architecture is changed to integrated architecture. That means the whole airborne system is regarded into one system to manage. So the physical devices are distributed but the system information is integrated and shared. The process function of each subsystem are integrated (including general process modules, dynamic reconfiguration), furthermore, the sensors and the signal processing functions are shared. On the other hand, it is a foundation for power shared. Establish a distributed vehicle management system using 1553B bus and distributed processors which can provide a validation platform for the research of airborne system integrated management. This paper establishes the Vehicle Management System (VMS) simulation platform. Discuss the software and hardware configuration and analyze the communication and fault-tolerant method.

Chip-scale sensor system integration for portable health monitoring.

PubMed

Jokerst, Nan M; Brooke, Martin A; Cho, Sang-Yeon; Shang, Allan B

2007-12-01

The revolution in integrated circuits over the past 50 yr has produced inexpensive computing and communications systems that are powerful and portable. The technologies for these integrated chip-scale sensing systems, which will be miniature, lightweight, and portable, are emerging with the integration of sensors with electronics, optical systems, micromachines, microfluidics, and the integration of chemical and biological materials (soft/wet material integration with traditional dry/hard semiconductor materials). Hence, we stand at a threshold for health monitoring technology that promises to provide wearable biochemical sensing systems that are comfortable, inauspicious, wireless, and battery-operated, yet that continuously monitor health status, and can transmit compressed data signals at regular intervals, or alarm conditions immediately. In this paper, we explore recent results in chip-scale sensor integration technology for health monitoring. The development of inexpensive chip-scale biochemical optical sensors, such as microresonators, that are customizable for high sensitivity coupled with rapid prototyping will be discussed. Ground-breaking work in the integration of chip-scale optical systems to support these optical sensors will be highlighted, and the development of inexpensive Si complementary metal-oxide semiconductor circuitry (which makes up the vast majority of computational systems today) for signal processing and wireless communication with local receivers that lie directly on the chip-scale sensor head itself will be examined.

Role of IAC in large space systems thermal analysis

NASA Technical Reports Server (NTRS)

Jones, G. K.; Skladany, J. T.; Young, J. P.

1982-01-01

Computer analysis programs to evaluate critical coupling effects that can significantly influence spacecraft system performance are described. These coupling effects arise from the varied parameters of the spacecraft systems, environments, and forcing functions associated with disciplines such as thermal, structures, and controls. Adverse effects can be expected to significantly impact system design aspects such as structural integrity, controllability, and mission performance. One such needed design analysis capability is a software system that can integrate individual discipline computer codes into a highly user-oriented/interactive-graphics-based analysis capability. The integrated analysis capability (IAC) system can be viewed as: a core framework system which serves as an integrating base whereby users can readily add desired analysis modules and as a self-contained interdisciplinary system analysis capability having a specific set of fully integrated multidisciplinary analysis programs that deal with the coupling of thermal, structures, controls, antenna radiation performance, and instrument optical performance disciplines.

Introducing WISDEM:An Integrated System Modeling for Wind Turbines and Plant (Presentation)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dykes, K.; Graf, P.; Scott, G.

2015-01-01

The National Wind Technology Center wind energy systems engineering initiative has developed an analysis platform to leverage its research capabilities toward integrating wind energy engineering and cost models across wind plants. This Wind-Plant Integrated System Design & Engineering Model (WISDEM) platform captures the important interactions between various subsystems to achieve a better National Wind Technology Center wind energy systems engineering initiative has developed an analysis platform to leverage its research capabilities toward integrating wind energy engineering and cost models across wind plants. This Wind-Plant Integrated System Design & Engineering Model (WISDEM) platform captures the important interactions between various subsystems tomore » achieve a better understanding of how to improve system-level performance and achieve system-level cost reductions. This work illustrates a few case studies with WISDEM that focus on the design and analysis of wind turbines and plants at different system levels.« less

Comprehensive Anti-error Study on Power Grid Dispatching Based on Regional Regulation and Integration

NASA Astrophysics Data System (ADS)

Zhang, Yunju; Chen, Zhongyi; Guo, Ming; Lin, Shunsheng; Yan, Yinyang

2018-01-01

With the large capacity of the power system, the development trend of the large unit and the high voltage, the scheduling operation is becoming more frequent and complicated, and the probability of operation error increases. This paper aims at the problem of the lack of anti-error function, single scheduling function and low working efficiency for technical support system in regional regulation and integration, the integrated construction of the error prevention of the integrated architecture of the system of dispatching anti - error of dispatching anti - error of power network based on cloud computing has been proposed. Integrated system of error prevention of Energy Management System, EMS, and Operation Management System, OMS have been constructed either. The system architecture has good scalability and adaptability, which can improve the computational efficiency, reduce the cost of system operation and maintenance, enhance the ability of regional regulation and anti-error checking with broad development prospects.

Copernicus Architecture, Phase I: Requirements Definition

DTIC Science & Technology

1991-08-01

control primarily over maritime patrol aircraft (MPA) and Integrated Undersea Surveillance System (IUSS) units; however, surface ships and other units...Intermediate System Integrated Services Digital Network Integrated Tactical-Stategic Data Network Integrated Undersea Surveillance System Joint Army Navy... TTE Technical Training Equipment TTY Teletype UFO UHF Follow On UHF Ultra High Frequency USA/USAF U. S. Army/U.S. Air Force USCINC U. S

76 FR 71029 - Draft Toxicological Review of n-Butanol: In Support of Summary Information on the Integrated Risk...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-16

... Toxicological Review of n-Butanol: In Support of Summary Information on the Integrated Risk Information System... Information on the Integrated Risk Information System (IRIS)'' (EPA/635/R-11/081A). On September 15, 2011, the... ``Toxicological Review of n-Butanol: In Support of Summary Information on the Integrated Risk Information System...

Ship to Shore Data Communication and Prioritization

DTIC Science & Technology

2011-12-01

First Out FTP File Transfer Protocol GCCS-M Global Command and Control System Maritime HAIPE High Assurance Internet Protocol Encryptor HTTP Hypertext...Transfer Protocol (world wide web protocol ) IBS Integrated Bar Code System IDEF0 Integration Definition IER Information Exchange Requirements...INTEL Intelligence IP Internet Protocol IPT Integrated Product Team ISEA In-Service Engineering Agent ISNS Integrated Shipboard Network System IT