Showing papers on "Biochip published in 2004"

Self-contained, fully integrated biochip for sample preparation, polymerase chain reaction amplification, and DNA microarray detection.

Abstract: A fully integrated biochip device that consists of microfluidic mixers, valves, pumps, channels, chambers, heaters, and DNA microarray sensors was developed to perform DNA analysis of complex biological sample solutions. Sample preparation (including magnetic bead-based cell capture, cell preconcentration and purification, and cell lysis), polymerase chain reaction, DNA hybridization, and electrochemical detection were performed in this fully automated and miniature device. Cavitation microstreaming was implemented to enhance target cell capture from whole blood samples using immunomagnetic beads and accelerate DNA hybridization reaction. Thermally actuated paraffin-based microvalves were developed to regulate flows. Electrochemical pumps and thermopneumatic pumps were integrated on the chip to provide pumping of liquid solutions. The device is completely self-contained: no external pressure sources, fluid storage, mechanical pumps, or valves are necessary for fluid manipulation, thus eliminating possibl...

Disposable smart lab on a chip for point-of-care clinical diagnostics

Abstract: This paper presents the development of a disposable plastic biochip incorporating smart passive microfluidics with embedded on-chip power sources and integrated biosensor array for applications in clinical diagnostics and point-of-care testing. The fully integrated disposable biochip is capable of precise volume control with smart microfluidic manipulation without costly on-chip microfluidic components. The biochip has a unique power source using on-chip pressurized air reservoirs, for microfluidic manipulation, avoiding the need for complex microfluidic pumps. In addition, the disposable plastic biochip has successfully been tested for the measurements of partial oxygen concentration, glucose, and lactate level in human blood using an integrated biosensor array. This paper presents details of the smart passive microfluidic system, the on-chip power source, and the biosensor array together with a detailed discussion of the plastic micromachining techniques used for chip fabrication. A handheld analyzer capable of multiparameter detection of clinically relevant parameters has also been developed to detect the signals from the cartridge type disposable biochip. The handheld analyzer developed in this work is currently the smallest analyzer capable of multiparameter detection for point-of-care testing.

Architectural-level synthesis of digital microfluidics-based biochips

Abstract: Microfluidics-based biochips offer a promising platform for massively parallel DNA analysis, automated drug discovery, and real-time biomolecular recognition. Current techniques for full-custom design of droplet-based "digital" biochips do not scale well for concurrent assays and for next-generation system-on-chip (SOC) designs that are expected to include fluidic components. We propose a system design methodology that attempts to apply classical architectural-level synthesis techniques to the design of digital microfluidics-based biochips. We first develop an optimal scheduling strategy based on integer linear programming. Since the scheduling problem is NP-complete, we also develop two heuristic techniques that scale well for large problem instances. A clinical diagnostic procedure, namely multiplexed in-vitro diagnostics on human physiological fluids, is used to evaluate the proposed method.

Smart disposable plastic lab-on-a-chip for point-of-care testing

Abstract: Disclosed herein is a fully-integrated, disposable biochip for point-of-care testing of clinically relevant parameters. Specifically, in accordance with an embodiment of the present invention, the biochip is designed for POCT (point-of-care-testing) of an array of metabolic parameters including partial pressure of oxygen, Glucose, and Lactate concentration from venous blood samples. The biochip is fabricated on a low-cost plastic substrate using mass manufacturing compatible fabrication processes. Furthermore, the biochip contains a fully-integrated metallic micro-needle for blood sampling. The biochip also uses smart passive microfluidics in conjunction with low-power functional on-chip pressure generators for microfluidic sequencing. The design, configuration, assembly and operation of the biochip are ideally suited for a disposable biochip specifically targeted towards POCT applications.

DNA biochip arraying, detection and amplification strategies

Abstract: Research on DNA biochips is advancing rapidly and has yielded several commercial platforms. This review presents, critically comments upon and compares DNA-biochip-arraying methods and techniques. It also discusses methods for detecting and amplifying hybridization events. The review focuses on miniaturization of these systems for diagnostic applications of biochip technology.

Module placement for fault-tolerant microfluidics-based biochips

Abstract: Microfluidics-based biochips are soon expected to revolutionize clinical diagnosis, DNA sequencing, and other laboratory procedures involving molecular biology. Most microfluidic biochips today are based on the principle of continuous fluid flow and they rely on permanently etched microchannels, micropumps, and microvalves. We focus here on the automated design of “digital” droplet-based microfluidic biochips. In contrast to conventional continuous-flow systems, digital microfluidics offers dynamic reconfigurability; groups of cells in a microfluidics array can be reconfigured to change their functionality during the concurrent execution of a set of bioassays. We present a simulated annealing-based technique for module placement in such biochips. The placement procedure not only addresses chip area, but also considers fault tolerance, which allows a microfluidic module to be relocated elsewhere in the system when a single cell is detected to be faulty. Simulation results are presented for case studies involving the polymerase chain reaction and multiplexed in vitro clinical diagnostics.

Electrokinetically controlled DNA hybridization microfluidic chip enabling rapid target analysis.

Abstract: Biosensors and more specifically biochips exploit the interactions between a target analyte and an immobilized biological recognition element to produce a measurable signal. Systems based on surface nucleic acid hybridization, such as microarrays, are particularly attractive due to the high degree of selectivity in the binding interactions. One of the drawbacks of this reaction is the relatively long time required for complete hybridization to occur, which is often the result of diffusion-limited reaction kinetics. In this work, an electrokinetically controlled DNA hybridization microfluidic chip will be introduced. The electrokinetic delivery technique provides the ability to dispense controlled samples of nanoliter volumes directly to the hybridization array (thereby increasing the reaction rate) and rapidly remove nonspecific adsorption, enabling the hybridization, washing, and scanning procedures to be conducted simultaneously. The result is that all processes from sample dispensing to hybridization detection can be completed in as little as 5 min. The chip also demonstrates an efficient hybridization scheme in which the probe saturation level is reached very rapidly as the targets are transported over the immobilized probe site enabling quantitative analysis of the sample concentration. Detection levels as low as 50 pM have been recorded using an epifluorescence microscope.

Biochip devices for ion transport measurement, methods of manufacture, and methods of use

Abstract: The present invention provides biochips for ion transport measurement, ion transport measuring devices that comprise biochips, and methods of using ion transport measuring devices and biochips that allow for the direct analysis of ion transport functions or properties. The present invention provides biochips, devices, apparatuses, and methods that allow for automated detection of ion transport functions or properties. The present invention also provides methods of making biochips and devices for ion transport measurement that reduce the cost and increase the efficiency of manufacture, as well as improve the performance of the biochips and devices. These biochips and devices are particularly appropriate for automating the detection of ion transport functions or properties, particularly for screening purposes.

Ultrasensitive Detection of DNA Hybridization Using Carbon Nanotube Field-Effect Transistors

Abstract: We have sensitively detected DNA hybridization using carbon nanotube field-effect transistors (CNTFETs) in real time. Amino modified peptide nucleic acid (PNA) oligonucleotides at 5' end were covalently immobilized onto the Au surface of the back gate. For 11-mer PNA oligonucletide probe, full-complementary DNA with concentration as low as 6.8 fM solution could be effectively detected. Our CNTFET-based biochip is a promising candidate for the development of an integrated, high-throughput, multiplexed DNA biosensor for medical, forensic and environmental diagnostics.

Real-time virus trapping and fluorescent imaging in microfluidic devices

Abstract: We have used dielectrophoretic filters within microfluidic biochips to capture from a flow and image virus particles in real-time. The verification of capture was performed by fluorescently labeling the particles using dual or triple labeling. These nonmechanical filters can be very valuable in the sample preparation, purification, and concentration of viral particles from a mixed sample. The described imaging methodology can be used for real-time imaging of nanometer scale virus particles for analysis of capture, detection, and characterization of these particles within micro and nanoscale sensors.

Applications of biochips: from diagnostics to personalized medicine.

Abstract: This review examines the role of advances in biochip and microarray technologies in the development of personalized medicine. Biochips (eg, GeneChip, CYP450, electrochemical biochips, protein biochips, microfluidic biochips and nanotechnology-based biochips) are assuming an important role in molecular diagnostics, and their application in point-of-care diagnosis is expected to facilitate the development of personalized medicine. Gene expression profiling by microarrays should advance the progress of personalized cancer treatment based on the molecular classification of subtypes. Refinements in biochip miniaturization with the advent of nanotechnology will further contribute to molecular diagnostics and the development of personalized medicine.

Micro patterning of cell and protein non-adhesive plasma polymerized coatings for biochip applications.

Abstract: Micro scale patterning of bioactive surfaces is desirable for numerous biochip applications. Polyethyleneoxide-like (PEO-like) coating with non-fouling functionality has been deposited using low frequency AC plasma polymerization. The non-fouling properties of the coating were tested with human cells (HeLa) and fluorescence labeled proteins (isothiocyanate-labeled bovine serum albumin, i.e. FITC-BSA). The PEO-like coatings were fabricated by plasma polymerization of 12-crown-4 (ppCrown) with plasma polymerized hexene (ppHexene) as adhesion layer. The coatings were micro patterned using conventional cleanroom photolithography and lift-off. Single cell arrays showed sharp contrast in cell adhesion between the untreated glass surface and the ppCrown layer. Similarly, proteins adsorbed selectively to untreated glass but not to ppCrown. The simplicity of the lift-off technique and the sturdiness and versatility of the plasma-polymerized coatings, make this technology highly suitable for bio-MEMS and biochip applications, where patterned high contrast non-fouling surfaces are needed.

A packaging technique for polymer microfluidic platforms.

Abstract: A new technique, resin-gas injection, has been developed for bonding and surface modification of polymer microfluidic devices. This method can easily bond biochips with complex flow patterns. A cascade micromixer and a multichannel DNA sequencing chip were demonstrated experimentally. By adding surface modification agents, the interfacial free energy of the substrate with water can be controlled. Local modification of the channel surface can also be achieved through sequential resin-gas injection in conjunction with a masking technique. For application, this technique is used to form a layer of dry monolithic stationary hydrogel on the walls of a microchannel, serving as a sieving material for electrophoresis separation of DNA fragments. The reagent loading and the electrophoresis separation efficiency of this technique were compared experimentally with the conventional linear polymer solution method used in the microchannel-based DNA sequencing process. It is found that our method has the advantages of more user-friendly operation, easier and faster sample loading, but slightly less separation efficiency.

Design of a luminescent biochip with nanodiamonds and bacterial luciferase

Abstract: An “aluminum oxide film-adhesive layer-nanodiamond-luciferase” supramolecular structure is prepared on a flat plate. It is demonstrated that, in this structure, the enzyme retains the catalytic activity. The structure prepared can be treated as a luminescent biochip prototype for use in bioluminescent analysis.

On-chip sample preparation for whole blood analysis

Abstract: A novel filter-less separation technique for separating suspended particles from a solution is disclosed. More specifically, an on-chip bioparticle separator is disclosed, which relies on the differential force exerted by application of a series of high magnitude, short duration pressure pulses on bioparticles in suspension within microchannels, resulting in separation of suspended bioparticles. The filter-less separation technique is inherently suited to μTAS (Micro Total Analysis System) since it exploits uniquely microscale phenomena to achieve separation. The on-chip bioparticle separator can be easily integrated with a disposable biochip, can be fabricated using low-cost, rapid manufacturing techniques, and can provide high performance for separation of bioparticles without the use of specialized or expensive equipment. Embodiments of the present invention address a significant challenge in the development of disposable microfluidic biochips, specifically, providing a reliable solution for separating bioparticles in a microfluidic system that may be immediately applied for a variety of microfluidic biochip applications.

Fully integrated protein lab-on-a-chip with smart microfluidics for spot array generation

Abstract: Techniques for the fabrication of fully-integrated lab-on-a-chips (or biochips) specifically oriented towards point-of-care detection of biomolecules using immunoassay based detection techniques are disclosed. A primary task for the development of such biochips is the development of techniques to precisely deposit and localize the capture antibody on pre-determined locations over the biochip. The use of selective surface modification, specifically control over the surface energy, to achieve localized adsorption of the capture antibody is disclosed. Another approach, also disclosed, describes the use of smart passive microfluidics to confine the flow of the capture antibody along certain paths of the biochip and thereby control the locations over which the capture antibody is adsorbed. Furthermore, the use of an integrated microlens array as means of enhancing the detection sensitivity of the biochip is also disclosed.

Biochip and biochip kit, and method of producing the same and method of using the same

Abstract: There are provided a biochip and a biochip kit, in which a target contained in an analyte is reacted with a probe with high efficiency in a short time, B/F separation efficiency is high, and high-sensitive quantitative determination and detection can be realized, and a production process thereof, and a method for reacting a target contained in an analyte with a probe, and, for example, separation and fractionation method and a detection and identification method for a target contained in an analyte, using the biochip kit. The biochip according to the present invention comprises a well(s) provided with a filter comprising straight pores, with a uniform pore diameter, provided at uniform pore spacings. A dispersion with probe-supported particles dispersed therein is contained in the well, and an analyte is placed in the well(s) to react the analyte with the probe-supported particles. A solution such as an analyte solution can be introduced into or discharged from the well through the filter.

Design of a confocal microfluidic particle sorter using fluorescent photon burst detection

Abstract: An instrumental system is described for detecting and sorting single fluorescent particles such as microspheres, bacteria, viruses, or even smaller macromolecules in a flowing liquid. The system consists of microfluidic chips (biochips), computer controlled high voltage power supplies, and a fluorescence microscope with confocal optics. The confocal observation volume and detection electro-optics allow measurements of single flowing fluorescent particles. The output of the avalanche photodiode (single photon detector) is coupled to a real-time photon-burst detection device, which output can address the control of high voltage power supplies for sorting purposes. Liquid propulsion systems like electro-osmotic flow and plain electric fields to direct the particles through the observation volume have been tested and evaluated. The detection and real-time sorting of fluorescent microspheres are demonstrated. Applications of these biochips for screening of bacteriophages-type biolibraries are briefly discussed.

Dendrimer-based DNA extraction methods and biochips

Abstract: The present invention provides a dendrimer-based biochip, wherein a flow channel through which a solution containing biopolymer molecules is flowed is formed in the substrate of the biochip, a plurality of dendrimer molecules one end of each of which is bound to the walls of the flow channel are formed thereon, and probe biopolymer or antibody molecules are bound to the tips of the dendrimer molecules so that, if the probe biopolymer molecules are bound, then target biopolymer molecules can be captured by means of a complementary combination and, if the antibody molecules are bound, then protein can be extracted by means of antigen-antibody reaction, whereby biopolymers can be retrieved in a highly efficient manner.

Biochip, biochip kit, and method for manufacturing and using the same

Abstract: PROBLEM TO BE SOLVED: To provide a biochip permitting a target substance in a specimen to react with a probe for a short time with high efficiency, having high B/F separation efficiency and enabling quantitative detection of high sensitivity, a biochip kit and its manufacturing method, a reaction method of the target substance in the specimen with the probe using the biochip, a separation/fractionation method of the target substance in the specimen and a detection/identification method of the target substance. SOLUTION: This biochip is equipped with a well provided with a filter having straight pores having a uniform pore size formed thereto at a uniform pore interval. A dispersion, in which probe carrier particles are dispersed, is housed in the well and the specimen is charged in the well to be reacted with probe carrier particles. A solution such as a specimen solution or the like is introduced into the well through the filter or discharged from the well. COPYRIGHT: (C)2005,JPO&NCIPI

Single nucleotide polymorphism analysis by chip-based hybridization and direct current electrical detection of gold-labeled DNA.

Abstract: Single nucleotide polymorphism (SNP) analysis at the point of care requires a low cost detection technology that is capable of miniaturization, multiplexing, and high sensitivity. Direct current electrical detection (DCED) of DNA following nanoparticle labeling and silver enhancement is a promising candidate technology for point-of-care diagnostics. In this work we present, for the first time, SNP analysis in PCR products from patient samples using DCED, taking this platform technology a step closer to practical application. We developed a silane functionalized polymer for coating of biochip surfaces. This polymeric coating is stable under harsh conditions and has exceptionally high binding capacity. Allele-specific oligonucleotide probes were immobilized on chips coated with this polymer. Biotinylated PCR products of the human cholesteryl ester transfer protein gene from different patients were hybridized to the chips, labeled with gold nanoparticles, and autometallographically enhanced. The chips were scanned for DC electrical resistance by applying movable electrodes to the surface. Eighteen of nineteen patient samples were assigned the correct genotype. Our results demonstrate that SNP analysis of patient samples is feasible with DCED.