Showing papers on "Biochip published in 2001"

Devices and methods for biochip multiplexing

Abstract: The invention is directed to devices that allow for simultaneous multiple biochip analysis. In particular, the devices are configured to hold multiple cartridges comprising biochips comprising arrays such as nucleic acid arrays, and allow for high throughput analysis of samples.

Nanosensors and biochips: frontiers in biomolecular diagnostics

Abstract: In the past two decades, the biotechnology and medical fields have seen great advances in the development of novel technologies that open new horizons for identifying and quantifying biomolecules, and diagnosing diseases. This manuscript provides an overview of two of those important technologies, nanosensors and biochips. We describe various types of nanosensors and biochips that have been developed for biological and medical applications, along with significant advances achieved over the last several years in these technologies. Some applications of nanosensors, developed in our laboratory for single-cell analysis, and applications of biochips for biological sensing of pathogenic agents and medical diagnostics are described to illustrate the usefulness and potential of these technologies.

Microfluidic Biochip for Impedance Spectroscopy of Biological Species

Abstract: This paper describes the fabrication and characterization of a microelectronic device for the electrical interrogation and impedance spectroscopy of biological species. Key features of the device include an all top-side processing for the formation of fluidic channels, planar fluidic interface ports, integrated metal electrodes for impedance measurements, and a glass cover sealing the non-planar topography of the chip using spin-on-glass as an intermediate bonding layer. The total fluidic path volume in the device is on the order of 30 nl. Flow fields in the closed chip were mapped by particle image velocimetry. Electrical impedance measurements of suspensions of the live microorganism Listeria innocua injected into the chip demonstrate an easy method for detecting the viability of a few bacterial cells. By-products of the bacterial metabolism modify the ionic strength of a low conductivity suspension medium, significantly altering its electrical characteristics.

A flexible light-directed DNA chip synthesis gated by deprotection using solution photogenerated acids

Abstract: Oligonucleotide microarrays or oDNA chips are effective decoding and analytical tools for genomic sequences and are useful for a broad range of applications. Therefore, it is desirable to have synthesis methods of DNA chips that are highly flexible in sequence design and provide high quality and general adoptability. We report herein, DNA microarray synthesis based on a flexible biochip method. Our method simply uses photogenerated acid (PGA) in solution to trigger deprotection of the 5′-OH group in conventional nucleotide phosphoramidite monomers (i.e. PGA-gated deprotection), with the rest of the reactions in the synthesis cycle the same as those used for routine synthesis of oligonucleotides. The complete DNA chip synthesis process is accomplished on a regular DNA synthesizer that is coupled with a UV-VIS projection display unit for performing digital photolithography. Using this method, oDNA chips containing probes of newly discovered genes can be quickly and easily synthesized at high yields in a conventional laboratory setting. Furthermore, the PGA-gated chemistry should be applicable to microarray syntheses of a variety of combinatorial molecules, such as peptides and organic molecules.

Chemiluminescence detection for hybridization assays on the flow-thru chip, a three-dimensional microchannel biochip.

Abstract: Chemiluminescence (CL) detection is seldom used in two-dimensional solid support microarray platforms because adequate sensitivity and spatial resolution is difficult to achieve. The three-dimensional ordered microchannels of the Flow-thru Chip increase both the sensitivity and spatial resolution required for quantitative CL measurements on microarrays. Enzyme-catalyzed CL reactions for the detection of hybridizations on microchannel glass were imaged using a CCD camera. Signal uniformity, sensitivity, and dynamic range of the detection method were determined. The relative standard deviation of signal intensities across an array of 64 spots was 8.1%. A detection limit of 250 amol of target with a linear dynamic range of 3 orders of magnitude was obtained for a 3-h assay. Similar to two-color fluorescence measurements, multiple enzyme labels were employed to demonstrate two-channel chemiluminescence. A unique method for measuring the relaxation time of a chemiluminescent species is also described.

High density column and row addressable electrode arrays

Abstract: This invention relates to the detection of biomolecules. Specifically, the invention relates to electronic or electrochemical detection of biomolecules using biochip arrays. In particular, the invention provides an apparatus comprising a platform for a column-and-row addressable, high-density, enhanced-sensitivity biochip array, and methods of use thereof. The devices and methods of the invention can be used to detect molecular interactions such as nucleic acid hybridization or protein binding.

Chemiluminescence-based microfluidic biochip

Abstract: The disclosure describes how to use luminescence detection mechanism, move microfluid, and control multiple-step biochemical reactions in closed confined microfluidic biochip platform. More particularly, a self-contained disposable biochip with patterned microchannels and compartments having storage means for storing a plurality of samples, reagents, and luminescent substrates. At least one external microactuator in the biochip system produces positive pressure and automates multiple-step reactions in microfluidic platforms for clinical chemistry, cell biology, immunoassay and nucleic acid analysis. The method comprises the steps of transferring sequentially at least one of samples, reagents, and then luminescent substrate from compartments through microchannels to reaction sites. The luminescent substrates react with probes to form a probe complex resulting into luminescence, which is detected by an optical detector.

An integrated biochip system for sample preparation and analysis

Abstract: The invention includes a composition that is an integrated biochip system for processing and analyzing samples using sequential tasks that take place on one or more chips. The system preferably comprises one or more active chips, and can be automated. The invention also includes methods of using an integrated biochip for processing and analyzing samples. The methods include the application of a sample to the system and performing at least two sequential tasks on at least one chip surface. The method includes the use of physical forces, such as dielectrophoretic and electromagnetic forces to process and analyze samples, and includes the use of microparticles that can be coupled to sample components to be manipulated by dielectrophoretic and electromagnetic forces.

Individually addressable micro-electromagnetic unit array chips in horizontal configurations

Abstract: The present 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.

Detection of E. coli using a microfluidics-based antibody biochip detection system.

Abstract: This work demonstrates the detection of E. coli using a 2-dimensional photosensor array biochip which is efficiently equipped with a microfluidics sample/reagent delivery system for on-chip monitoring of bioassays. The biochip features a 4 x 4 array of independently operating photodiodes that are integrated along with amplifiers, discriminators and logic circuitry on a single platform. The microfluidics system includes a single 0.4 mL reaction chamber which houses a sampling platform that selectively captures detection probes from a sample through the use of immobilized bioreceptors. The independently operating photodiodes allow simultaneous monitoring of multiple samples. In this study the sampling platform is a cellulosic membrane that is exposed to E. coli organisms and subsequently analyzed using a sandwich immunoassay involving a Cy5-labeled antibody probe. The combined effectiveness of the integrated circuit (IC) biochip and the immunoassay is evaluated for assays performed both by conventional laboratory means followed by detection with the IC biochip, and through the use of the microfluidics system for on-chip detection. Highlights of the studies show that the biochip has a linear dynamic range of three orders of magnitude observed for conventional assays, and can detect 20 E. coli organisms. Selective detection of E. coli in a complex medium, milk diluent, is also reported for both off-chip and on-chip assays.

Integrated electro-luminescent biochip

Abstract: A biochip includes a plurality of sensors. Each sensor contains one or more light sources and one or more optical detectors.

Interactive transparent individual cells biochip processor

Abstract: An Interactive Transparent Individual Cells Biochip Processor (ITICBP) device is described, which is useful for assessing a single, individual living cell at identifiable location or assessing group of cells each at identifiable location.

Evaluation of three-dimensional microchannel glass biochips for multiplexed nucleic acid fluorescence hybridization assays.

Abstract: Three-dimensional, flow-through microchannel glass substrates have a potential for enhanced performance, including increased sensitivity and dynamic range, over traditional planar substrates used in medium-density microarray platforms. This paper presents a methodology for the implementation of multiplexed nucleic acid hybridization fluorescence assays on microchannel glass substrates. Fluorescence detection was achieved, in a first instance, using conventional low-magnification microscope objective lenses, as imaging optics whose depth-of-field characteristics match the thickness of the microchannel glass chip. The optical properties of microchannel glass were shown, through experimental results and simulations, to be compatible with the quantitative detection of heterogeneous hybridization events taking place along the microchannel sidewalls, with detection limits for oligonucleotide targets in the low-attomole range.

Microarray sampling-platform fabrication using bubble-jet technology for a biochip system.

Abstract: The fabrication of microarrays containing PCR-amplified genomic DNA extracts from mice tumors on a Zetaprobe membrane using a modified thermal ink-jet printer is described. A simple and cost-effective procedure for the fabrication of microarrays containing biological samples using a modified bubble-jet printing system is presented. Because of their mass-produced design, ink-jet printers are a much cheaper alternative to conventional spotting techniques. The usefulness of the biochip microarray platform is illustrated by the detection of human fragile histidine triad (FHIT), a tumor suppressor gene. Subcutaneous carcinomas were induced with MKN/FHIT and MKN/E4 cell lines in immunodeficient mice. Several weeks into their development, the tumors from both groups of mice were removed and subjected to DNA extraction by lysis of tissue samples. The extracted DNA samples were amplified by PCR (30 cycles) using the primers corresponding to nucleotides 2 to 18 of the FHIT sequence. The resulting solution was transferred to the individual reservoirs of a three-color cartridge from a conventional thermal ink-jet printer (HP 694C), and arrays were printed on to a Zetaprobe membrane. After spotting, these membranes were used in a hybridization assay, using fluorescent probes, and detected with a biochip.

Biochip technologies in cancer research.

Abstract: Development of high-throughput 'biochip' technologies has dramatically enhanced our ability to study biology and explore the molecular basis of disease. Biochips enable massively parallel molecular analyses to be carried out in a miniaturized format with a very high throughput. This review will highlight applications of the various biochip technologies in cancer research, including analysis of 1) disease predisposition by using single-nucleotide polymorphism (SNP) microarrays, 2) global gene expression patterns by cDNA microarrays, 3) concentrations, functional activities or interactions of proteins with proteomic biochips, and 4) cell types or tissues as well as clinical endpoints associated with molecular targets by using tissue microarrays. One can predict that individual cancer risks can, in the future, be estimated accurately by a microarray profile of multiple SNPs in critical genes. Diagnostics of cancer will be facilitated by biochip readout of activity levels of thousands of genes and proteins. Biochip diagnostics coupled with informatics solutions will form the basis of individualized treatment decisions for cancer patients.

Feature-size limitations of microarray technology--a critical review.

Abstract: The appeal of microarray technology is the possibility of large-scale parallel determination of a variety of variables simultaneously. Hence, microarray technologies attract the interest of both the scientific and business worlds alike. High-throughput screening has been the major focus of the utilization of microarray technologies in recent years, and has provided the strong driving force for developments in this field. DNA chip and biochip technologies have been developed as a consequence of worldwide activity in genome research. This review focuses on microarray-based analysis and emphasizes some of its principal constraints, especially detection limits.

Biochips for Gene Spotting

Abstract: Biochips containing microarrays of genetic information promise to be important research tools in the postgenomic era. Because DNA microarray can contain many thousands of samples, each representing a single gene, it is possible to design a single chip containing the complete gene set of a complex organism (30,000 to 60,000 genes). DNA microarrays provide a powerful way to simultaneously analyze the expression of thousands of genes. This article describes the design and uses of microarrays of DNA.

Compositions and methods for array-based nucleic acid hybridization

Abstract: The invention provides compositions and methods for generating a molecular profile of genomic DNA by hybridization of labeled nucleic acid representing the genomic DNA to immobilized nucleic acid probes, e.g., arrays or biochips.

Method of fabricating microchannel array structure embedded in silicon substrate

Abstract: The present invention is disclosed a microchannel array structure embedded in a silicon substrate and a fabrication method thereof. The microchannel array structure of the present invention is formed deep inside the substrate and has high-density microscopic micro-channels. Besides, going through surface micromachining, physical and chemical properties of the silicon substrate are hardly influenced by the fabrication procedures. With microchannels buried in the substrate, the top of a microchannel array structure becomes flat, minimizing the effect of step height. That way, additional devices such as passive components, micro sensors, micro actuators and electronic devices can be easily integrated onto the microchannel array structure. The microchannel array structure of the present invention can be employed as a basic fluidic platform for miniaturizing and improving perfomances of electronic device coolers as well as such fluidic micro-electro-mechanical system (MEMS) devices as biochips, microfluidic components and chemical analyzers, lab-on-a-chips, polymerase chain reaction (PCR) amplifiers, micro reactors and drug delivery systems.

A Plastic Micro Injection Molding Technique Using Replaceable Mold-Disks for Disposable Microfluidic Systems and Biochips

Abstract: This paper presents an innovative plastic micro injection molding technique using replaceable disk-mold for applications to microfluidic systems and biochips. Precisely patterned and microfabricated wafer-type mold inserts can be easily loaded into the injection molding machine. Processing time for one chip was as fast as 10 seconds while hot embossing techniques require at least several minutes. Less than a few urn of precise patterns were also achieved. A promising new material has also been introduced and characterized using the developed injection molding technique as well as demonstrated for a disposable biochip.

Three dimensional format biochips

Abstract: A biochip is formed with a plurality of optically clear hydrogel cells attached to the top surface of a solid substrate in the form of an array. Each of the cells is formed of a hydrogel of polyethylene glycol, polypropylene glycol or a copolymer thereof having reactive isocyanate groups. Binding entities are immobilized in these cells, which entities are effective to selectively hybridize to or sequester a target biomolecule. Different binding entities are immobilized in different cells in an array to create a biochip that can be used to assay for a number of target biomolecules.

Method of manufacturing a microfluidic structure, in particular a biochip, and structure obtained by said method

Abstract: A method of manufacturing a microfluidic structure, in particular a biochip, said method consisting at least :- in manufacturing a three-dimensional micro-mould with means for defining a three-dimensional geometry including at least micro-wells and micro-grooves or micro-channels interconnecting said micro-wells ; and- in using only said three-dimensional micro-mould for molding a membrane made of a polymer material, said membrane incorporating at least said micro-wells and said micro-grooves or micro-channels, said membrane constituting a three-dimensional microfluidic structure

Application of an antibody biochip for p53 detection and cancer diagnosis.

Abstract: Detection of the p53 tumor suppressor gene is important in early cancer diagnostics because alterations in the gene have been associated with carcinogenic manifestations in several tissue types in humans. We have developed an antibody-based detection instrument, the biochip, to detect the presence of the anti-p53 antibody in human serum. The design of this highly integrated detector system is based on miniaturized phototransistors having multiple optical sensing elements, amplifiers, discriminators, and logic circuitry on an IC board. The system utilizes laser excitation and fluorescence signals to detect complex formation between the p53 monoclonal antibody and the p53 antigen. Recognition antibodies are immobilized on a nylon membrane platform and incubated in solutions containing antigens labeled with Cy5, a fluorescent cyanine dye. Subsequently, this membrane is placed on the detection platform of the biochip and fluorescence signal is induced using a 632.8-nm He-Ne laser. Using this immuno-biochip, we have been able to detect binding of the p53 monoclonal antibody to the human p53 cancer protein in biological matrices. The performance of the integrated phototransistors and amplifier circuits of the biochip, previously evaluated through measurement of the signal output response for various concentrations of fluorescein-labeled molecules, have illustrated the linearity of the microchip necessary for quantitative analysis. The design of this biochip permits sensitive, selective and direct measurements of a variety of antigen-antibody formations at very low concentrations. Furthermore, the acquisitions of the qualitative and quantitative results are accomplished rapidly, in about 15 min. These features demonstrate the potential of this antibody-based biochip for simple, rapid and early biomedical diagnostics of cancer.

Automated system and process for custom-designed biological array design and analysis

Abstract: There is disclosed an automated system and process for providing a fully automated process for the design, manufacture and analysis of data for biological array ('biochip') devices. Specifically, there is further disclosed a process and system for obtaining customer orders for custom-designed biochips comprising obtaining desired target sequences from the customer, wherein the target sequences consist essentially of oligonucleotide sequences, polypeptide sequences, or antigens to be bound; creating a sequence content motif for an array, wherein the sequence content motif consists essentially of oligonucleotide sequences, polypeptide sequences, or binding agents designed for complimentary binding; and applying the content motif to a surface suitable for later detection.

Slide-format proteomic biochips based on surface-enhanced nanocluster-resonance

Abstract: The most fundamental properties of metal nanoclusters, namely the high local-field enhancement and nanoscale resonance behavior of the cluster electron plasma when exited by electromagnetic radiation, have been used to set up a variety of sensors transducing biorecognitive interactions into optical signals. This paper focuses on applications of resonant-cluster technology, which enabled us to monitor biorecognitive binding of a variety of proteins on a chip, thus constructing high-throughput interaction-screening devices.

Use of an imaging photoelectric flat sensor for evaluating biochips and imaging method therefor

Abstract: The invention relates to the use of an imaging photoelectric flat sensor (14), e.g. a CC sensor, for contact imaging of the surface (11) of a biochip (13) by measuring radiation such as chemical luminescent, biological luminescent or fluorescent radiation emitted from the surface of the biochip. The invention also relates to an imaging method therefor. The biochip (13) is arranged at the smallest possible distance from a flat sensor (14). A local resolution, two-dimensional image of the radiation emitted from the surface of the functionalized area (12) can be detected by the flat sensor (14) without the need for an intermediate optical imaging system.

Multifunctional opto-electronic biochip detection system

Abstract: A multi-functional opto-electronic system is mainly applied to the real-time metrologies of biomedical or biochemical reactions as well as the in-situ manufacturing measurements of biochips. The configuration of this system is built up by integration of at least four different near-field optical metrological principles, which share a part of common optical path design and allow to turn on several functions such as ellipsometer, Laser Doppler vibrometer or interferometer (LDV/I), surface plasmon resonance (SPR) for amplitude and phase detection, phase shifting interference microscope, photon tunneling microscope, optical coherence tomography (OCT) and imaging microscope by switching few components in the system. With the creation of a novel opto-mechanical design and its associated signal processing methodologies, both the signal detection of the biomedical reactions and biomedical imaging concerned for the future trend in the modern biomedical sciences are achieved with high resolutions.

Biochip for the archiving and medical laboratory analysis of biological sample material

Abstract: A biochip for diagnostic use comprises a sample support consisting of a solid matrix, to whose surface the sample material to be analysed, originating from a biological organism, is bonded.