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Showing papers on "Biochip published in 2000"


Book
15 Apr 2000

420 citations


Journal ArticleDOI
TL;DR: Current trends and advances in protein biochip technologies that rely upon extraction and retention of target proteins from liquid media are presented with particular emphasis on selectivity, sensitivity, throughput and utility in the post-genome era.
Abstract: This article presents current trends and advances in protein biochip technologies that rely upon extraction and retention of target proteins from liquid media. Analytical strengths as well as technical challenges for these evolving platforms are presented with particular emphasis on selectivity, sensitivity, throughput and utility in the post-genome era. A general review of protein biochip technology is provided, which delineates approaches for protein biochip format and operation, as well as protein detection. A focused discussion of three protein biochip technologies, Biomolecular Interaction Analysis (Biacore, Uppsala, Sweden), Surface Enhanced Laser Desorption/Ionisation (SELDI) ProteinChip Arrays (Ciphergen Biosystems, Fremont, CA, USA) and Fluorescent Planar Wave Guide (Zeptosens, Witterswil, Switzerland), follows along with examples of relevant applications.

163 citations


Patent
25 Feb 2000
TL;DR: In this paper, a system for scanning biochip arrays includes a unique image array identifier recorded for each array, and a computer-stored record corresponding to each identifier and containing the parameters of the experiment in the array identified by the identifier.
Abstract: A system for scanning biochip arrays includes a unique image array identifier recorded for each array, and a computer-stored record corresponding to each identifier and containing the parameters of the experiment in the array identified by the identifier. The system further includes means for accessing a protocol library to retrieve the scanning protocols associated with the identified arrays and then scanning the arrays in accordance with the respective protocols. The resulting image maps generated by the scanners are stored in locations corresponding to the associated identifiers.

110 citations


Journal ArticleDOI
TL;DR: DNA chips will facilitate the integration of diagnosis and therapeutics, as well as the introduction of personalised medicines, and standardised procedures are essential for compatible data production, quality control and analysis.
Abstract: A DNA microarray system is usually comprised of DNA probes formatted on a microscale on a glass surface (chip), plus the instruments needed to handle samples (automated robotics), to read the reporter molecules (scanners) and analyse the data (bioinformatic tools). Biochips are formed by in situ (on chip) synthesis of oligonucleotides or peptide nucleic acids (PNAs) or spotting of DNA fragments. Hybridisation of RNA- or DNA-derived samples on chips allows the monitoring of expression of mRNAs or the occurrence of polymorphisms in genomic DNA. Basic types of DNA chips are the sequencing chip, the expression chip and chips for comparative genomic hybridisation. Advanced technologies used in automated microarray production are photolithography, mechanical microspotting and ink jets. Bioelectronic microchips contain numerous electronically active microelectrodes with specific DNA capture probes linked to the electrodes through molecular wires. Several biosensors have been used in combination with biochips. PN...

96 citations


Journal ArticleDOI
TL;DR: An electronically driven hybridization assay for an application in genetic identification that takes advantage of the large number of available assay locations is developed.
Abstract: We have developed a technology that brings together electronically active semiconductor chips with biomedical assays or tests. By creating an array of electrodes that can be individually addressed, it is possible to manipulate DNA and other biological molecules to perform bioassays in a number of different formats. Recently, we have fabricated and tested chips that support independent, electronically driven reactions at 400 or more sites. To control these sites, we have utilized a CMOS architecture which incorporates row and column addressing, and active current control and self-test at each site. We have developed an electronically driven hybridization assay for an application in genetic identification that takes advantage of the large number of available assay locations. To perform the assay, sample DNA is electrophoretically propelled and hybridized to an immobilized DNA probe on the chip and to a fluorophore-labeled DNA probe in solution. Detection of a positive assay result depends on light emitted by the fluorophore-labeled probe in a hybridization complex that also contains the immobilized capture probe and the sample DNA. The fluorophore is excited by light from a diode laser, which is coupled into the chip by a unique cartridge design that incorporates a polymer waveguide for dark field illumination. The light emitted by fluorophores is detected by a CCD camera. The present generation of chips will potentially enable a wide range of applications including genetic identification tests, detection of bacteria and other infectious agents, assays for genetic diseases, examination of the products of many genes and screening for potential drugs.

68 citations


Journal ArticleDOI
TL;DR: A new methodology for the preparation of addressed DNA matrices that allows discrimination between hybridization and nonspecific adsorption, and successfully applied to the genotyping of hepatitis C virus in blood samples is described.
Abstract: Biosensors based on electronic conducting polymers appear particularly well suited to the requirements of modern biological analysis—multiparametric assays, high information density, and miniaturization. We describe a new methodology for the preparation of addressed DNA matrices. The process includes an electrochemically directed copolymerization of pyrrole and oligonucleotides bearing on their 5′ end a pyrrole moiety. The resulting polymer film deposited on the addressed electrode consists of pyrrole chains bearing covalently linked oligonucleotides (ODN). An oligonucleotide array was constructed on a silicon device bearing a matrix of 48 addressable 50 × 50 µm gold microelectrodes. This technology was successfully applied to the genotyping of hepatitis C virus in blood samples. Fluorescence detection results show good sensitivity and a high degree of spatial resolution. In addition, gravimetric studies carried out by the quartz crystal microbalance technique provide quantitative data on the amount of surface-immobilized species. In the case of ODN, it allows discrimination between hybridization and nonspecific adsorption. The need for versatile processes for the immobilization of biological species on surfaces led us to extend our methodology. A biotinylated surface was obtained by coelectropolymerization of pyrrole and biotin-pyrrole monomers. The efficiency for recognition (and consequently immobilization) of R-phycoerythrin-avidin was demonstrated by fluorescence detection. Copolymerization of decreasing ratios of pyrrole-biotin over pyrrole allowed us to obtain a decreasing scale of fluorescence.

57 citations


Patent
Takeo Tanaami1
08 May 2000
TL;DR: In this paper, a biochip reader consisting of a light source for emitting excitation light, an objective lens for condensing this light reflected or transmitted by the dichroic mirror and an optical detector for detecting the fluorescent light was presented.
Abstract: The present invention provides a biochip reader, wherein light is irradiated at a biochip onto which multiple samples are arranged in spots or in linear arrays and image data according to the multiple samples is read using an optical detector. The biochip reader comprises means for arranging multiple pieces of spectroscopic information on the sample under analysis in spaces between images of the samples. The present invention further provides a biochip reader comprising a light source for emitting excitation light, a dichroic mirror for reflecting or transmitting this light, an objective lens for condensing this light reflected or transmitted by the dichroic mirror and projecting fluorescent light produced at the biochip onto the dichroic mirror, an optical detector for detecting the fluorescent light, and a lens for condensing the fluorescent light reflected or transmitted by the dichroic mirror onto the optical detector. The present invention further provides an electrophoresis system.

53 citations


Patent
14 Dec 2000
TL;DR: In this paper, a column-and-row-addressable high-density biochip array for electronic or electrochemical detection of molecular interactions between probe molecules bound to defined regions of the array and target molecules exposed to the array is presented.
Abstract: The present invention provides a method and apparatus (9) comprising a platform for a column-and-row-addressable high-density biochip array. The apparatus (9) can be used as a high-density biochip array for electronic or electrochemical detection of molecular interactions between probe molecules bound to defined regions of the array and target molecules exposed to the array.

39 citations


Patent
29 Feb 2000
TL;DR: In this paper, a biochip scanner 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.
Abstract: 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.

35 citations


Patent
27 Jun 2000
TL;DR: In this article, a biochip including a DNA chip and a protein chip is described and a method for patterning and measuring biomaterials of the same is disclosed, including a reflecting layer and an active layer on a substrate including the steps of rotating the biochip; successively irradiating pulse type laser beams to the rotating biochip to activate predetermined regions of the active layer; and fixing a biomaterial pattern on the activated predetermined regions.
Abstract: A biochip including a DNA chip and a protein chip and a method for patterning and measuring biomaterial of the same are disclosed. The method for patterning a biomaterial of the biochip including a reflecting layer and an active layer on a substrate includes the steps of: rotating the biochip; successively irradiating pulse type laser beams to the rotating biochip to activate predetermined regions of the active layer; and fixing a biomaterial pattern on the activated predetermined regions. A method for measuring the patterned biomaterial includes the steps of: reacting a biomaterial labeled with at least one dye material with the biochip; rotating the biochip reacted with at least one biomaterial; successively irradiating laser beams to the rotating biochip; and detecting and processing light derived from the biochip as a result of reaction of the biomaterial to measure the biomaterial. Thus, the biochip having reliability and high packing density can be fabricated at low cost and the biomaterial of the biochip can be measured at high speed without using expensive equipments.

34 citations


Journal ArticleDOI
TL;DR: In this article, the authors report on the fabrication of an affinity biochip with a matrix of 900 targets for detection with imaging ellipsometry, and two methods of fabrication of chips are shown: one based on wet etching of a silicon surface and the other on the preparation of tension wells on the silicon surface.
Abstract: In this paper we report on the fabrication of an affinity biochip with a matrix of 900 targets for detection with imaging ellipsometry. Two methods of fabrication of chips are shown: one based on wet etching of a silicon surface and the other on the preparation of so-called tension wells on the silicon surface. The dispensing of reagents and ligands was performed using a pipetting robot equipped with a micro-capillary, a syringe pump and micro-stepping motors. Measurements were performed on the chips in real time with carbohydrate model substances selected for six common lectins. Affinity binding was shown for three of the tested model substances.

Patent
27 Oct 2000
TL;DR: In this paper, a disk-type upper substrate is placed on the top surface of the biochip, a sample is put between the disk type upper substrate and the bio-chip, the reaction between the sample solution and the biomaterial is accelerated by rotating the bio chip, and the detection unit analyzes the biom material by receiving the light emitted from the biom materials.
Abstract: The present invention provides a biochip which includes: a substrate having a center hole at a central portion, an biomaterial region aranged at a circumferential portion of the top surface of the substrate; and an information region formed on the substrate between the biomaterial region and the center hole and having the information on the biomaterials. In the method for detecting biomaterials using the biochip, a disk-type upper substrate is placed on the top surface of the biochip, a sample is put between the disk-type upper substrate and the biochip, the reaction between the sample solution and the biomaterial of the biochip is accelerated by rotating the biochip, and the detection unit analyzes the biomaterial by receiving the light emitted from the biomaterials, thereby making it possible to analyze the biomaterial of the sample solution. Since the biochip of the present invention is constructed as a disk type, high-priced scanning equipment is not necessary for thereby reducing the cost for detecting biomaterials. Since the sample solution is stirred by rotating the biochip, the speed of binding reaction is increased for thereby decreasing the time for analysis. Since the information on the biomaterial and the analytical information of the biomaterial can be recorded in the biochip, the management of the information of the biomaterials is made easier.

Patent
29 Feb 2000
TL;DR: In this article, a portable biochip scanner device used to detect and acquire fluorescence signal data from biological microchips (biochips) is provided, which employs a laser for emitting an excitation beam.
Abstract: 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.

Patent
17 Jan 2000
TL;DR: In this article, a light source, a lens for turning output light from the light source into parallel light, an excitation filter for transmitting the output light of specific wavelengths and outputting it as excited light, a photo detecting element for detecting fluorescence generated from a sample by the excited light.
Abstract: PROBLEM TO BE SOLVED: To realize a device for reading a biochip, capable of enhancing S/N and reducing a cost. SOLUTION: This device for reading the biochip is equipped with a light source, a lens for turning output light from the light source into parallel light, an excitation filter for transmitting the output light of specific wavelengths and outputting it as excited light, a photo detecting element for detecting fluorescence generated from a sample by the excited light, and an objective lens for condensing the fluorescence generated at a biochip where the sample is disposed to the detecting element. The excited light comes into the biochip at an angle larger than a critical angle to the biochip substrate. COPYRIGHT: (C)2001,JPO

Proceedings ArticleDOI
12 Oct 2000
TL;DR: A micro liter PCR (polymerase chain reaction) biochip was designed and fabricated for DNA amplification as discussed by the authors, which was consist of a vessel, platinum thin film heater and a temperature sensor.
Abstract: A micro liter PCR (polymerase chain reaction) biochip was designed and fabricated for DNA amplification. It was consist of a vessel, platinum thin film heater and a temperature sensor. The heater and sensor were deposited on to the bottom of the vessel. Its advantage is rapid thermal cycling time constant. The PCR vessel is approximately 2 /spl mu/L, the maximal heating speed is over 15/spl deg/C/s and cooling speed 10/spl deg/C/s. This paper reports the PCR vessel's structure, chip package problems and solutions, its thermal uniformity analysis, DNA molecular testing results etc. The design of the thermal controller for the PCR biochip is described.

Journal ArticleDOI
TL;DR: A LOCI microscope is constructed and used to demonstrate sensitive detection of analytes in small volumes for three types of assays of potential interest in arrays: detection of a single-stranded DNA fragment, Detection of a double-Stranded DNA amplicon, and an immunoassay for a protein.
Abstract: Many of the emerging technologies in clinical chemistry and research require the ability to perform hundreds or thousands of measurements on a single sample such as amplified DNA, typically by contacting the sample with an array of different probes or other reagents. If these array approaches are to be practical, the underlying technology must be simple, robust, inexpensive, and amenable to automation. The Luminescent Oxygen Channeling Immunoassay (LOCITM) is a recently developed homogeneous assay method that should be suitable for arrays because of its simplicity. However, to perform large numbers of measurements on reasonable sample sizes (e.g., 500 different measurements on aliquots of a 50-μL volume), it must be possible to detect LOCI signals from very small volumes. Miniaturization has also become a central theme in other areas of clinical chemistry (1). Accordingly, we have constructed a LOCI microscope and used it to demonstrate sensitive detection of analytes in small volumes for three types of assays of potential interest in arrays: detection of a single-stranded DNA fragment, detection of a double-stranded DNA amplicon, and an immunoassay for a protein. LOCI is a sensitive (femtomolar) detection method that uses chemiluminescence to quantify latex agglutination (2). This technique utilizes one latex particle dyed with a photosensitizer and a second dyed with a chemiluminescent dye, both having binding ligands on their surfaces. Particle suspensions are mixed with the sample, and cross-linking by any analyte present leads to formation of bead pairs or higher aggregates. When the suspension is then illuminated, singlet oxygen is generated by the sensitizer particle, migrates to the chemiluminescent particle, and generates light. Nonspecific signals are low because singlet oxygen decays before it can reach unpaired particles. A small-volume LOCI reader was constructed by modifying a fluorescence microscope to allow sample illumination with a 678 nm laser and monitoring …

Patent
29 Mar 2000
TL;DR: In this paper, a new scheme of PCR microarray probe hybrid detection type biochip is proposed, which adopts gasor liquid reciprocating flow mode and multi-temperature zone PCR gene selective amplification and combines with solid-phase microprobe array technology to make gene diagnosis.
Abstract: The invented PCR microarray probe circulating detection type biochip relates to a new scheme of PCR microarray probe hybrid detection type biochip, specially it is a new type biochip which adopts gasor liquid reciprocating flow mode and multi-temperature zone PCR gene selective amplification and combines with solid-phase microprobe array technology to make gene diagnosis It is characterized by that PCR circulation process and probe hybrid detection are designed in a PCR microarray probe chip, and the four microreactors of denaturation, annealing, elongation and microarray probe hybridization of PCR are formed into a reciprocating or encircling circulating system, and the temperatures of denaturation, annealing, elongation and hybridization in the circulating system are independently andthermostaticly controlled Several PCR microarray probe type chip systems can be integrated on the same chip

Patent
26 Apr 2000
TL;DR: In this article, a method for preparing a hydrogel biochip where a plurality of biomolecular probes are bound to a prepolymer either prior to or simultaneously with polymerization of the prepolymers is presented.
Abstract: Methods for preparing a hydrogel biochip wherein a plurality of biomolecular probes are bound to a hydrogel prepolymer either prior to or simultaneously with polymerization of the prepolymer. While either hydrogel is polymerizing, it is microspotted onto a solid substrate to which the hydrogel becomes covalently bound in the form of a hydrogel microdroplet. Adjustment of the reactivity of the prepolymer and the polymerization conditions provides effective control of the density of biomolecular probe immobilization. Resulting biochips containing a plurality of such microdroplets having different biomolecules bound thereto are useful for gene discovery, gene characterization, functional gene analysis and related studies.

Patent
02 Aug 2000
TL;DR: In this paper, a detection and analysis plate of a microfluid biochip is composed of a chip plate and a cover plate, wherein, the chip plate is provided with micro flute passages which are connected with reaction sites; the transparent cover plate seals the chip surface, and the cover surface is provided by micro flutes.
Abstract: The utility model relates to a detection and analysis plate of a microfluid biochip and a detection method thereof, which applies the microfluid biochip to chemical or biologic analysis systems. The detection and analysis plate of a microfluid biochip is composed of a chip plate and a cover plate, wherein, the chip plate is provided with micro flute passages which are connected with reaction sites; the transparent cover plate seals the chip plate, or the chip plate is provided with the reaction sites, and the cover plate is provided with micro flutes. The detection method is that probes or marked object molecules of different types are respectively fixed on the reaction sites of the detection and analysis plate of a microfluid biochip, and each ingredient of the same test sample on the same chip is simultaneously analyzed.

Patent
10 Mar 2000
TL;DR: In this article, the problem of detecting and determining only a specific bond due to hybridization is solved by storing a plurality of images picked up by the image pickup means in a computer and analyzing them with respect to individual spots.
Abstract: PROBLEM TO BE SOLVED: To detect and determinate only a specific bond due to hybridization. SOLUTION: A biochip 10, on which a large number of probe biopolymers are spotted, is housed in a container 20 and a washing liquid is allowed to flow from an infusion device 23. The temperature of the biochip is controlled according to a predetermined time pattern by a heat block 31 and the image of the spotted surface of the biochip is picked up at a determined time interval by an image pickup means 55. A plurality of images picked up by the image pickup means are stored in a computer 40 and analyzed with respect to individual spots to detect hybridization with respect to all of spots with high reliability without receiving the effect of the optimum temperature of hybridization different at every spot corresponding to the kind of a probe. COPYRIGHT: (C)2001,JPO

Patent
29 Dec 2000
TL;DR: In this paper, biological assays using various constructions of biochips are disclosed to mirror in vivo situations, and an inverted microscope 65, digital camera 66 and recorder 67 are provided.
Abstract: Biological assays using various constructions of biochips are disclosed to mirror in vivo situations. The biochip 50 comprises a microchannel 51 having a liquid outlet port 1 , bubble release port 2 and a liquid outlet port 3 with an associated bubble release port 4 . A multiplicity of tests can be performed often by coating the bore of the microchannel 50 which various adhesion mediating proteins or the use of chemoattractants. The assay assembly 60 comprises a syringe pump feeding the biochip 50 . An inverted microscope 65 , digital camera 66 and recorder 67 are provided. A sample liquid containing cells in suspension is injected slowly through the biochip and the effect of the assay recorded over a long period.

Patent
05 Dec 2000
TL;DR: In this paper, a matrix biochip sensing system consisting of an LED matrix light source, a biochip clamping member, an optical information filter module, a single optical sensor, and a signal processing and control module is presented.
Abstract: The matrix biochip sensing system of this invention uses a low-cost LED (light emit diode) matrix as the light source for the sensing system. The matrix biochip sensing system comprises an LED matrix light source, a biochip clamping member, an optical information filter module, an optical lens array, an optical sensor and a signal processing and control module. The light spots of the LED matrix is turned on in sequence, such that the fluorescent spots of the biochip that are respectively corresponding to the light spots of the laser diodes matrix may be actuated in the same sequence. Fluorescent spots so actuated are focused to a single optical sensor through an optical lens. At each sensing cycle of the optical sensor, only one fluorescent spot may be actuated. The output of the optical sensor in combination of the time axis may be processed by the signal processing and control module to obtain the genetic signals of the biochip.

Patent
15 Mar 2000
TL;DR: In this article, reusable biochips for the detection of target analytes are described. The biochip comprises an array of ligands attached to a non-fluorescent acrylic that finds use in fluorescence detection and other methodologies.
Abstract: The invention relates to reusable biochips for the detection of target analytes. The biochips comprise an array of ligands attached to a non-fluorescent acrylic that finds use in fluorescence detection and other methodologies.

01 Jan 2000
TL;DR: These biochips, which were different from typical molecular microarrays such as DNA chip, were based on the microarray of various structures, and have successfully applied to analyze DNA mutations, polymorphisms and sequences, to separate mixtures and monitor biomolecular interactions.
Abstract: With the development of biochip techniques, several new types of biochip, such as bioelectronic chip, gel element microarray chip, drug controlled-release chip, capillary eletrophoretic or electrochromatographic chip, PCR chip and biosensor chip, had sprung up These biochips, which were different from typical molecular microarrays such as DNA chip, were based on the microarray of various structures, and have successfully applied to analyze DNA mutations, polymorphisms and sequences, to separate mixtures and monitor biomolecular interactions Because analyses on these chips have many advantages such as quick detection, high efficiency, little sample consumed and low cost, they will become novel tools in the field of life science and medicine

Book ChapterDOI
01 Jan 2000
TL;DR: This work focuses on miniaturization of DNA analysis on a single microfluidic chip and develops a complete biochemical intelligent microsystem for extraction, concentration, amplification, analysis, and processing of DNA.
Abstract: Recent developments in molecular biology and genetic analysis have inspired strong interests in miniaturization of DNA analysis on a single microfluidic chip. In the last few years there has been tremendous interest in developing a complete biochemical intelligent microsystem for extraction, concentration, amplification, analysis, and processing of DNA. Current biochips are being developed in a very conventional experimental trial and error manner with little computational design support.

Patent
20 Jun 2000
TL;DR: In this article, a system for performing molecular biological diagnosis, analysis and multistep and multiplex reactions utilizes a selfaddressable, selfassembling microelectronic system for actively carrying out controlled reactions in microscopic formats.
Abstract: A system for performing molecular biological diagnosis, analysis and multistep and multiplex reactions utilizes a selfaddressable, selfassembling microelectronic system for actively carrying out controlled reactions in microscopic formats. Preferably, a fluidic system flow a sample across an active area of the biochip, increasing diagnostic efficiency. Preferably, the fluidic system includes a flow cell having a window.

Patent
16 Dec 2000
TL;DR: In this article, a system for scanning the exposed smart biochip array includes a detector for detecting binding between probe molecules and target molecules in each test site and a reader for reading data from the smart circuit, including data identifying the type of probe molecules contained in each site.
Abstract: A smart biochip array comprises an array of test sites disposed on a substrate and a smart circuit operatively associated with the substrate. Each test site contains a distinct type of probe molecule, and the smart circuit includes a memory that stores data identifying which distinct type of molecule is stored in each test site. The test sites in the biochip array are exposed to a sample that may contain target molecules capable of binding with probe molecules contained in one or more test sites. A system for scanning the exposed smart biochip array includes a detector for detecting binding between probe molecules and target molecules in each test site and a reader for reading data from the smart circuit, including data identifying the type of probe molecules contained in each test site.

Proceedings ArticleDOI
01 Sep 2000
TL;DR: This paper presents a technique for segmenting spot-objects of possibly different sizes in images of biochip arrays as these images are taken after the biochips underwent a complex chemical process, they are subject to blur effects, distortions, and local intensity shifts.
Abstract: This paper presents a technique for segmenting spot-objects of possibly different sizes in images of biochip arrays. As these images are taken after the biochips underwent a complex chemical process, they are subject to blur effects, distortions, and local intensity shifts. Image segmentation is reduced to quantisation which in turn is reduced to function approximation. The approximation requires neither parametric assumptions nor parametric input and it iteratively optimizes an n-step histogram function by coarser step functions. Thus, a discrete "scale space" is created. The notion of so-called stable minima is used for finding good binarisation thresholds. Stability issues are combined with heuristic criteria tailored to segmenting biochip images. Finally, the complete approach is applied to a series of real biochip images.

Journal ArticleDOI
TL;DR: This article describes the development and production of DNA/RNA BioChip arrays for diagnostic applications emphasizing in particular quality controlled production processes with high reproducibility of each step.
Abstract: T he dramatic progress in the analysis of human, animal and plant genomes as well as parallel developments such as the human cancer gene anatomy project have created an enormous demand for low-cost high throughput technologies for DNA and RNA analysis. Chip-based molecular techniques if available in satisfactory quality for diagnostic applications will enable major analytical issues in health care such as predisposition, cancer, infectious diseases and others to be addressed. DNA micro-arrays have been predicted to become a key technology in molecular analysis for nearly one decade now. Although their proportion in the research market (e.g. expression profiling) has increased significantly they still play a minor role in clinical and medical diagnostic fields. Main drawbacks for the implementation of BioChips in clinical routine analysis are insufficient reproducibility, lack of standardization as well as expensive chips and detectors. With respect to BioChip production, industrial standards and uniform protocols have not yet been defined. Therefore different BioChip layouts and analytical performance cannot be compared. This article describes the development and production of DNA/RNA BioChip arrays for diagnostic applications emphasizing in particular quality controlled production processes with high reproducibility of each step. In order to achieve the required analytical performance, many of the currently used components and techniques such as substrate material, coupling chemistry, arraying, probe design, hybridization and high resolution scanning were reevaluated by IMNT and replaced by appropriate new approaches. In addition, TECAN has developed a novel nanopipetting solution based on GENESIS pipetting robot to dispense volumes as small as 0.5 nanoliters (nl).

Patent
15 Nov 2000
TL;DR: In this paper, a high performance inexpensive biochip reader comprising a magnetic sensor and a disc drive mechanism commonly employed in a hard disc drive without requiring any expensive laser or optical system is provided.
Abstract: A biochip reader reading a biochip with a higher sensitivity than that of a method employing fluorescence and having an inexpensive arrangement. The biochip reader comprises an X-Y stage (3) on which a biochip (6) is mounted to scan it two-dimensionally, a controller (4) therefor, a magnetic sensor (1) for measuring the strength of a magnetic field, a resistance meter (2), and a computer (5) for signal processing. Thus a high performance inexpensive biochip reader comprising a magnetic sensor and a disc drive mechanism commonly employed in a hard disc drive without requiring any expensive laser or optical system is provided.