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Showing papers on "Biochip published in 1999"


Journal ArticleDOI
TL;DR: Experiments demonstrate that specific multiplex detection of protein antigens arrayed on a glass substrate is feasible and the 96-well microarray format is compatible with automated robotic systems and supports a low-cost, highly parallel assay format.
Abstract: A new generation biochip is described a s capable of supporting high-throughput (HT) , multiplexed enzyme-linked immunosorben t assays (ELISAs). These biochips consist o f an optically flat, glass plate containing 96 wells formed by an enclosing hydrophobi c Teflon ® mask. The footprint dimensions o f

377 citations


Book
01 Jan 1999
TL;DR: This book is intended for genomics researchers investigating patterns of gene expression (and the relationship with disease) wanting to take advantage of this powerful new technology.
Abstract: DNA microarrays, or biochips, are small glass chips embedded with ordered rows of DNA and by providing a massive parallel platform for data gathering represent a fundamental technical advance in biomedical research. Such biochips enable the use of advanced fabrication, detection, and data mining technologies that allow data gathering at an unprecedented rate. The first chapter is an introduction to the technology of DNA microarrays, emphasizing the methodological fundamentals of biochips. The next two chapters describe the use of confocal scanning in microarray detection and techniques for the efficient cloning and screening of differentially expressed genes. Chapter 4 describes assay optimization for enzymatic assays and chapter 5 antisense scanning arrays. This is followed by a chapter on the manufacture of molecular arrays using ink-jet printing technology. Chapter 7 describes gene expression analysis from cDNA microarrays and then chapter 8 covers the use of expression data in bioinformatics. Chapter 9 describes the use of active microelectronic arrays for DNA hybridization analysis and the last chapter details the use of microarray technology in pharmacogenomics. This book is intended for genomics researchers investigating patterns of gene expression (and the relationship with disease) wanting to take advantage of this powerful new technology.

328 citations


Patent
17 Sep 1999
TL;DR: In this article, an electromagnetic biochip comprises an individually addressable micro-electromagnetic unit chip with ligand molecules immobilized on its surface, which can be used for directed manipulation, synthesis and release of biomolecules in order to increase sensitivity of biochemical or chemical analysis.
Abstract: This invention provides electromagnetic chips and electromagnetic biochips having arrays of individually addressable micro-electromagnetic units, as well as methods of utilizing these chips for directed manipulation of micro-particles and micro-structures such as biomolecules and chemical reagents. An electromagnetic biochip comprises an individually addressable micro-electromagnetic unit chip with ligand molecules immobilized on its surface. By controlling the electromagnetic field at each unit of the array and combining this control with magnetic modification of biomolecules, these chips can be used for directed manipulation, synthesis and release of biomolecules in order to increase sensitivity of biochemical or chemical analysis and reduce assay time. Other advantages with these chips include minimized damages to biological molecules and increased reproducibility of assay results.

205 citations


Journal ArticleDOI
TL;DR: Measurements of fluorescent-labeled DNA probe microarrays and hybridization experiments with a sequence-specific DNA probe for the human immunodeficiency virus 1 system on nitrocellulose substrates illustrate the usefulness and potential of the DNA biochip.
Abstract: This work describes the development of an integrated biosensor based on phototransistor integrated circuits (IC) for use in medical detection, DNA diagnostics, and gene mapping. The evaluation of various system components developed for an integrated biosensor microchip is discussed. Methods to develop a microarray of DNA probes on nitrocellulose substrate are discussed. The biochip device has sensors, amplifiers, discriminators, and logic circuitry on board. Integration of light-emitting diodes into the device is also possible. To achieve improved sensitivity, we have designed an IC system having each phototransistor sensing element composed of 220 phototransistor cells connected in parallel. Measurements of fluorescent-labeled DNA probe microarrays and hybridization experiments with a sequence-specific DNA probe for the human immunodeficiency virus 1 system on nitrocellulose substrates illustrate the usefulness and potential of the DNA biochip.

169 citations


Journal ArticleDOI
TL;DR: In this article, a parallel affinity sensor array (PASA) was implemented based on chemiluminescence labels (peroxidase/luminol) and CCD detection.

68 citations


Journal ArticleDOI
TL;DR: In this paper, a new development using a fully silicon active substrate and DNA probe electro-immobilisation was reported, which was used for the analysis of genes involved in Oncology.
Abstract: This paper reports a new development using a fully silicon active substrate and DNA probe electro-immobilisation. The DNA chip described is using CMOS 0.8 μm technology and an integrated multiplexer to address successively the electrode on which a specific DNA probe will be deposited. This approach is well adapted for low to medium range number of probes (50–1000) device. Applications targeted by this kind of device are wide, from specific kit of diagnosis to cancerology and agronomy. The final demonstrator is a 128 DNA probe chip which is used for the analysis of genes involved in Oncology.

54 citations


Patent
25 Aug 1999
TL;DR: In this paper, a charge coupled device (CCD) sensor, a broad spectrum light source, a lens, a light source filter, and a sensor filter are optimized and matched to each other.
Abstract: A biochip detection system detects and locates samples that are labeled with multiple fluorescent tags and are located on a biochip. This biochip detection system includes a charge coupled device (CCD) sensor, a broad spectrum light source, a lens, a light source filter, and a sensor filter. The CCD sensor comprises two dimensional CCD arrays to simultaneously detect light waves from at least a substantial portion of the biochip. The broad spectrum light source is optically coupled to the CCD sensor and is configured to be utilized with a variety of different fluorescent tags which have differing excitation wavelengths. The lens and the CCD sensor are optimized and matched to each other such that the sensor operates at or below the diffraction rating of the lens. Further, the resolution of the CCD sensor is matched to the samples on the biochip such that the CCD sensor oversamples each of the samples a sufficient number of times. Additionally, the lens is configured to frame at least a substantial portion of the biochip. The biochip detection system is optimized to provide a higher dynamic range, increased sensitivity, and faster throughput compared to system utilizing laser scanners. Further, the biochip detection system is capable of utilizing a same broad spectrum light source to excite samples labeled with a variety of fluorescent tags.

53 citations


Patent
04 Oct 1999
TL;DR: In this article, a device for reading a biochip including plural molecular recognition areas and plural optical positioning marks, associated with recognition areas, is presented, which includes an optical head capable of projecting excitation light onto the biochip.
Abstract: A device for reading a biochip including plural molecular recognition areas and plural optical positioning marks, associated with recognition areas. The device includes an optical head capable of projecting excitation light onto the biochip. A device is provided to effectuate relative displacement between the head and the biochip. A first optical analysis system is associated with the optical head to receive any light arriving from recognition areas. A second optical positioning system is associated with the optical head to receive any light from at least one guide track and/or optical positioning mark. A device is further provided for servocontrolling scanning by the optical head. Such a device may find particular application to biological and chemical analysis.

40 citations


Patent
19 Aug 1999
TL;DR: In this paper, a biochip capable of a centralized control of information and a method of using the biochip, wherein a storage medium (13) is added to a fixed substrate (11) such as glass on which bipolymer such as DNA and protein is spotted and information on spotted positions on the bio-chip and biopolymer spotted on each position are stored on the storage medium in association with each other.
Abstract: A biochip capable of a centralized control of information and a method of using the biochip, wherein a storage medium (13) is added to a fixed substrate (11) such as glass on which bipolymer (12) such as DNA and protein is spotted and information on spotted positions on the biochip (10) and information on biopolymer spotted on each position are stored on the storage medium (13) in association with each other.

40 citations


Patent
02 Aug 1999
TL;DR: In this paper, the authors describe a biochip with a small glass tube on the side of the substrate opposite the side to which the membrane is applied, so that an electrode can be introduced through the opening away from the substrate.
Abstract: Biochip, especially for investigating ion channels, has a substrate with opening(s) to receive a cell membrane with ion channel(s). Independent claims are also included for the following: (1) measuring probes comprising a biochip and a small glass tube on the side of the substrate opposite the side to which the membrane is applied, so that an electrode can be introduced through the opening away from the substrate; and (2) process for production of the biochip.

26 citations


Patent
15 Dec 1999
TL;DR: In this article, a method for making a biochip and a bio-chip consisting in particular of biological probes grafted on an conductive polymer was proposed, which consisted in the following steps: a) structuring a substrate so as to obtain on said substrate microwells comprising at their base a layer of a material capable of initiating and promoting adhesion thereon of a copolymer film of pyrrole, functionalised by electropolymerisation; b) collective electropolemerisation so asto form an electropolasticised film of a pyr
Abstract: The invention concerns a method for making a biochip and a biochip, said biochip consisting in particular of biological probes grafted on an conductive polymer. The inventive method comprises the following steps: a) structuring a substrate so as to obtain on said substrate microwells comprising at their base a layer of a material capable of initiating and promoting adhesion thereon of a copolymer film of pyrrole and pyrrole functionalised by electropolymerisation; b) collective electropolymerisation so as to form an electropolymerised film of a copolymer of pyrrole or functionalised pyrrole on the base of said microwells; c) directly or indirectly fixing functionalised oligonucleotides by micro-deposition or liquid jet printing process.

Journal ArticleDOI
23 Mar 1999-Langmuir
TL;DR: In this article, the surface of a novel biochip prototype, consisting of an array of gold microelectrodes on a gold microchip, was evaluated using ToF-SIMS.
Abstract: Time-of flight secondary ion mass spectrometry (ToF-SIMS) has been employed to characterize and evaluate the surface of a novel biochip prototype, consisting of an array of gold microelectrodes on ...

Journal ArticleDOI
TL;DR: The design of a “Flying Objective” epi-fluorescence microscope that is ideally suited to this application is described, and the performance of this novel instrument is compared with two other commercial epi -fluorescence microscopes designed to read DNA microarrays.
Abstract: DNA-based fluorescent microarrays (sometimes called “biochips”) are fast becoming the preferred tool for studying a variety of complex biochemical phenomena ranging from multiplex mutation detection, to gene mapping and expression monitoring, to high throughput screening for new drug candidates. Fluorescence is a low energy phenomenon. The need for rapid, high resolution, wide field imaging of fluorescent microarrays calls for a specialized microscope architecture. We now describe the design of a “Flying Objective” epi-fluorescence microscope that is ideally suited to this application, and compare the performance of this novel instrument with two other commercial epi-fluorescence microscopes designed to read DNA microarrays.

Patent
Hisanori Nasu1, Kenji c1, Noriko c
04 Mar 1999
TL;DR: A sample application method including the steps of: rotating a biochip including a plurality of regions bound with various probes; and dropping a sample onto generally a center of rotation of the rotating biochip so as to apply the sample to the plurality of region as discussed by the authors.
Abstract: A sample application method including the steps of: rotating a biochip including a plurality of regions bound with various probes; and dropping a sample onto generally a center of rotation of the rotating biochip so as to apply the sample to the plurality of regions.

Journal ArticleDOI
TL;DR: Biochips are computer-chip look-alikes intended to speedily, reliably, and inexpensively perform the sequential procedures that compose a medical test.
Abstract: The first biochips are already in use. They are computer-chip look-alikes intended to speedily, reliably, and inexpensively perform the sequential procedures that compose a medical test. Current applications lie chiefly in the analysis of genes. The devices may soon facilitate screening of potential drugs. Clinically, the immediate goal is to enable biochips to serve point-of-care diagnosis.

Patent
07 Sep 1999
TL;DR: In this paper, an analytical support (A), particularly a biochip, comprises many analytical sites (AS) that can be supplied with reagents and many resonant microcavities that can emit light and are associated with AS.
Abstract: Analytical support (A), particularly a biochip, comprises many analytical sites (AS) that can be supplied with reagents and many resonant microcavities (RMC) that can emit light and are associated with AS. An Independent claim is also included for an analytical system comprising (A), a source of pumping light for RMC and a detector for measuring fluorescence emitted from AS.

Patent
17 Dec 1999
TL;DR: In this article, a method for the photolithographic synthesis of biochips in which photolabile protective groups of the 2-(2-nitrophenyl-) ethyl type are used, whereby the irradiation step that is common in the photochemical synthesis of BioChips is carried out in the presence of a base, preferably in a secondary or tertiary base.
Abstract: The invention relates to a method for the photolithographic synthesis of biochips in which photolabile protective groups of the 2-(2-nitrophenyl-) ethyl type are used, whereby the irradiation step that is common in the photolithographic synthesis of biochips is carried out in the presence of a base, preferably in the presence of a secondary or tertiary base.

Patent
28 May 1999
TL;DR: In this article, the average value and standard deviation of readout values for probes at multiple positions on a biochip are calculated by a data processing device, and the reliability of the readout value can be evaluated by calculating the average values.
Abstract: PROBLEM TO BE SOLVED: To improve the reliability of readout by calculating the average value and standard deviation of readout values for probes at multiple positions on a biochip. SOLUTION: This biochip 12 is provided with probes of the same kind at multiple positions and a data processing means calculating the average value and standard deviation of readout values for the probes at multiple positions on the biochip 12. The probes of the same kind are allocated to multiple features 23 to constitute the biochip 12. The probes of the same kind are arranged at five positions, for example, however the number is not limited as far as it is multiple. The average value and standard deviation of readout values for the probes of the same kind are calculated by a data processing device. The reliable readout values can be obtained by calculating the average value. The distribution of the readout values is known by calculating the standard deviation, thus the reliability of the readout values can be evaluated.

Patent
15 Oct 1999
TL;DR: In this article, a sample is dropped and added from a sample nozzle 32 to nearly a rotation center of the rotated biochip, whereby a surface of the biochip is wet with the buffer solution.
Abstract: PROBLEM TO BE SOLVED: To uniformly add a sample of a small quantity to all features of a biochip. SOLUTION: A biochip 12 coupling a probe is rotated. A sample is dropped and added from a sample nozzle 32 to nearly a rotation center of the rotated biochip. The sample dropped to nearly the rotation center of the rotated biochip 12 is spread in a direction to the periphery of the biochip because of centrifugal force and uniformly added to all features of the biochip. A buffer solution is dropped from a buffer solution nozzle 31 before the sample is dropped, whereby a surface of the biochip is wet with the buffer solution.

Patent
19 Nov 1999
TL;DR: In this article, an inexpensive high performance biochip reading apparatus is constituted of an XY stage receiving a biochip 6 and performing two-dimensional scanning, a controller 4 thereof, a magnetic sensor 1 for reading the intensity of a magnetic field, a resistance meter 2 and a signal processing computer 5.
Abstract: PROBLEM TO BE SOLVED: To provide a biochip reading apparatus capable of reading a biochip by inexpensive apparatus constitution having sensitivity higher than that of a method using fluorescence. SOLUTION: An inexpensive high performance biochip reading apparatus is constituted of an XY stage 3 receiving a biochip 6 and performing two-dimensional scanning, a controller 4 thereof, a magnetic sensor 1 for reading the intensity of a magnetic field, a resistance meter 2 and a signal processing computer 5. In this apparatus, a magnetic sensor and a disk driving mechanism used in a hard disk driver generally are employed without using an expensive laser and an optical system.

Proceedings ArticleDOI
03 May 1999
TL;DR: In this paper, a 10 micrometer resolution optical scanner type high density device was proposed for detection of analytes based on arrays of proteins, DNA and high throughput screening targets for drug discovery.
Abstract: The choice of metal clusters as signal transducers of molecular binding events is based on their about 1000 times higher extinction coefficients compared to conjugated chromophores. Using cluster based assays it is possible to visualize the binding of biomolecules at a given surface by a bound layer of ligand-modified metal clusters. The success of cluster visualization was mainly based on the significant signal stability contrary to chromophores and especially fluorophores. Cluster probes are not only efficient direct markers but within the past years became the basis of new devices employing cluster resonance, cluster field enhancement, and cluster-cluster interactions. Multilayered highly resonant systems clearly exhibit strong reflection minima induced by the resonant behavior of the metal cluster layer. At least one narrow reflection minimum can be shifted to the red or infra red spectral range and therefore far away from spherical gold colloids to be ready by a 10 micrometer resolution optical scanner type high density device. Even without employing near-field optics spatial resolution is within 100 - 500 nm. The setup enabled us to replace conventional ELISA assays overcoming the various technological limits as there are e.g. multiple incubation steps and spatial resolution. The focus of the development was to provide an optical biochip which allows detection of analytes based on arrays of proteins, DNA and high throughput-screening targets for drug discovery.© (1999) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.



Journal ArticleDOI
TL;DR: In this article, the authors proposed Novel Magnetic Labeling (NLL) technology for high-throughput screening applications in clinical laboratories. But, the NLL technology is not suitable for biomedical applications.
Abstract: With the push to decrease the “cost per sample processed” in clinical laboratories comes the need to develop improved methods for increasing sample throughput. Biochips (which are used to analyze thousands of clinical samples on one square centimeter silicon substrates) are expected to eventually become the method of choice for many types of high-throughput screening applications. As biochip technology continue to find applications in clinical laboratories (1), refinements and innovations are occurring simultaneously that optimize the biochip technology itself for these applications. One of these innovations is Ericomp’s Novel Magnetic Labeling technology.

Proceedings ArticleDOI
11 Nov 1999
TL;DR: A brief introduction to the biochip technology in general is given, and the DNA micro-array technology is described as a specific example of this relatively new and burgeoning interdisciplinary research and development.
Abstract: Biotechnology has recently been regarded as the technology of the 21st century. One important advancement of the biotechnology is the biochip technology which integrates the conventional biotechnology with semiconductor processing, micro-electro-mechanical, optoelectronic, and digital signal and image acquisition and processing technologies. In this paper, we give a brief introduction to the biochip technology in general, and describe the DNA micro-array technology as a specific example of this relatively new and burgeoning interdisciplinary research and development.

Patent
30 Nov 1999
TL;DR: In this article, a biochip comprising probes spotted on a plate at a plurality of positions by using a binding agent for binding the probes to the plate, wherein the binding agent is locally spotted at positions where the probes are spotted.
Abstract: A biochip comprising probes spotted on a plate at a plurality of positions by using a binding agent for binding the probes to the plate, wherein the binding agent is locally spotted at positions where the probes are spotted.

Patent
11 Jun 1999
TL;DR: In this article, a device for reading a biochip comprising at least one line of discrete zones comprises a light source for illuminating the biochip and a detector for detecting the fluorescence emitted by the chip.
Abstract: Device for reading a biochip comprising at least one line of discrete zones comprises a light source for illuminating the biochip in the form of a strip covering at least one line of discrete zones and a detector for detecting the fluorescence emitted by the biochip. An Independent claim is also include for a biochip comprising: (a) at least one line of discrete zones, each containing a substance capable of emitting fluorescent light when the surface of the chip is illuminated; and (b) a series of synchronization zones permitting movement of the chip and fluorescence detection to be synchronized.