With Means For Applying An Electric Current Or Charge (e.g., Electrofusion, Electroporation, Etc.) Patents (Class 435/285.2)
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Patent number: 6492175Abstract: An electroporation and/or fusion treatment of microscopic objects occurs in a medium between at least two electrodes, with the electrodes being miniaturized electrodes in a microsystem with a channel structure which is set up for the flow-through of the medium with the objects.Type: GrantFiled: August 6, 2001Date of Patent: December 10, 2002Assignee: Evotec Bio Systems AGInventors: Torsten Müller, Thomas Schnelle, Günter Fuhr, Stephen Graham Shirley, Gabriele Gradl
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Patent number: 6489120Abstract: A method and system for detecting a target antigen using massively parallel immunoassay technology. In this system, high affinity antibodies of the antigen are covalently linked to small beads or particles. The beads are exposed to a solution containing DNA-oligomer-mimics of the antigen. The mimics which are reactive with the covalently attached antibody or antibodies will bind to the appropriate antibody molecule on the bead. The particles or beads are then washed to remove any unbound DNA-oligomer-mimics and are then immobilized or trapped. The bead-antibody complexes are then exposed to a test solution which may contain the targeted antigens. If the antigen is present it will replace the mimic since it has a greater affinity for the respective antibody. The particles are then removed from the solution leaving a residual solution. This residual solution is applied a DNA chip containing many samples of complimentary DNA.Type: GrantFiled: March 28, 2000Date of Patent: December 3, 2002Assignee: The United States of America as represented by the United States Department of EnergyInventor: Fred J. Stevens
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Patent number: 6489106Abstract: The present invention demonstrates that gene expression can be controlled in vitro using DNA (gene) sequences immobilized on a template with micron scale temperature heaters. Such expression is controllable by varying temperature of the template on a short time scale. The present invention further demonstrates that nucleic acid constructs controlled by the present method express protein either free or bound to the nucleic acid. Based on these findings, the present invention provides methods and apparatuses useful for the preparation of in vitro programmable protein networks and protein micro arrays.Type: GrantFiled: March 10, 2000Date of Patent: December 3, 2002Assignee: NEC Research Institute, Inc.Inventors: G. V. Shivashankar, Shumo Liu, Albert J. Libchaber
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Patent number: 6485961Abstract: An improved electrode for use in generating an electrical field in a saline solution is provided. In particular, a continuous crystalline metal nitride coated electrode is provided for use in a variety of saline solution applications, such as in an electrophoresis device for separating proteins or nucleic acids or an electroporation apparatus for the encapsulation of biologically-active substances in various cell populations. A method and apparatus are provided for the encapsulation of biologically-active substances in red blood cells, characterized by an optionally automated, continuous-flow, self-contained electroporation system which allows withdrawal of blood from a patient, separation of red blood cells, encapsulation of a biologically-active substances in the cells, and optional recombination of blood plasma and the modified red blood cells thereby producing blood with modified biological characteristics.Type: GrantFiled: July 18, 2000Date of Patent: November 26, 2002Assignee: MaxCyte, Inc.Inventor: Peter Meserol
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Publication number: 20020164776Abstract: A chamber for treating cells contained in a suspension in an electric field, the chamber having a vessel for holding the suspension and at least two electrodes with electrode surfaces that face each other. The suspension may be placed between the electrode surfaces and the electrodes are connectable to different poles of a source of voltage to generate an electric field between the electrode surfaces. The electrodes are laminate and continuous and are configured to generate a non-uniform field. Moreover, the electrodes have electrode surfaces made of electrically conductive material, wherein the electrode surface of at least one of the two electrodes is shaped such that a non-uniform field with several maxima distributed over the electrode surface may be generated between the two electrodes.Type: ApplicationFiled: March 26, 2002Publication date: November 7, 2002Inventors: Boris V. Beichmann, Olaf Faustmann, Kurt Lucas, Christian Taesler, Nico Gulzow, Wolfgang Lubker, Hans-Joachim Ricklefs, Nada Pavlovic
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Patent number: 6475722Abstract: The present invention discloses methodologies for the treatment of the surface(s) of DNA processing devices so as to greatly reduce DNA adsorption to the surface(s) exposed to the DNA-containing media. These aforementioned surface treatments include: (i) the deposition of thin-films of silicon-rich, silicon nitride and of hydroxyl-containing,low-temperature silicon oxide and (ii) the washing of surface with a basic, oxidative wash solution. The present invention also discloses the fabrication of DNA processing devices utilizing surface(s) treated by the methods described above. Such DNA processing devices include, for example, miniaturized electrophoresis and other DNA separation devices, miniaturized PCR reactors, and the like. The present invention further discloses methodologies for testing the degree of DNA adherence to a given surface. Additionally, the methodologies and devices of the present invention are also applicable to the processing of nucleic acids, in generally.Type: GrantFiled: November 16, 1998Date of Patent: November 5, 2002Assignee: CuraGen CorporationInventor: Steven A. Henck
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Publication number: 20020155611Abstract: The invention concerns a method for treating an aqueous flow colonized by cells with a pulsed electric field applied to a flow, characterized in that the applied field is substantially parallel to the direction of flow and to its application to the transfer of nucleic acids (RNA, DNA, oligonucleotides) into cells, to the transfer of proteins to cells, to the extraction of cytoplasmic macromolecules and molecules contained in the cells, to cell fusion and the production of hybrids and/or to insertion of membrane proteins. It also concerns an electropulsing chamber, a method for destroying cells and a membrane permeabilization method.Type: ApplicationFiled: October 15, 2001Publication date: October 24, 2002Inventors: Marie-Christine Vernhes, Pierre-Andre Rene Cabanes, Justin Teissie
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Patent number: 6468784Abstract: A method or an apparatus for selecting oocytes or eggs based on at least one objective criterion, such as membrane potential, comprises a step or means for selecting a plurality of oocytes or eggs having a certain size with a filter or the like, and a step or means for measuring a membrane potential of each of the oocytes or eggs thereby sorting out those with a membrane potential within a specified range. The selected oocytes or eggs are sold or transferred together with the measurement information or an injected sample of interest.Type: GrantFiled: December 20, 2001Date of Patent: October 22, 2002Assignee: Hitachi, Ltd.Inventors: Tomoko Takeshita, Jun Otomo, Shokichi Matsunami
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Publication number: 20020127723Abstract: The present invention is directed to an electrofusion microelectrode used in the alignment, manipulation, fusion, or electroporation of cells. This device is particularly useful for transplantation of cells and cellular components.Type: ApplicationFiled: February 28, 2002Publication date: September 12, 2002Inventor: Gianpiero D. Palermo
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Patent number: 6448065Abstract: The invention is based on the discovery that the sequence of monomers in a polymeric biomolecule can be determined in a self-contained, high pressure reaction and detection apparatus, without the need for fluid flow into or out from the apparatus. The pressure is used to control the activity of enzymes that digest the polymeric biomolecule to yield the individual monomers in the sequence in which they existed in the polymer. High pressures modulate enzyme kinetics by reversibly inhibiting those enzymatic processes which result in a higher average activation volume, when compared to the ground state, and reversibly accelerating those processes which have lower activation volumes than the ground state. Modulating the pressure allows the experimenter to precisely control the activity of the enzyme. Conditions can be found, for example, where the enzyme removes only one monomer (e.g., a nucleotide or amino acid) from the biomolecule before the pressure is again raised to a prohibitive level.Type: GrantFiled: March 19, 2001Date of Patent: September 10, 2002Assignee: BBI Bioseq. Inc.Inventors: James A. Laugharn, Jr., Robert A. Hess
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Patent number: 6440722Abstract: Integrated systems, apparatus, software, and methods for performing biochemical analysis, including DNA sequencing, genomic screening, purification of nucleic acids and other biological components and drug screening are provided. Microfluidic devices, systems and methods for using these devices and systems for performing a wide variety of fluid operations are provided. The devices and systems of are used in performing fluid operations which require a large number of iterative, successive or parallel fluid manipulations, in a microscale, or sealed and readily automated format.Type: GrantFiled: June 27, 2000Date of Patent: August 27, 2002Assignee: Caliper Technologies Corp.Inventors: Michael Knapp, John Wallace Parce, Luc J. Bousse, Anne R. Kopf-Sill
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Patent number: 6436699Abstract: This invention describes a capacity affinity sensor based on self-assembled monolayers on an electrode with immobilized recognition elements available to analyte in the surrounding solution. Additional insulation is provided by auxiliary self-assembled molecules. The sensor has exceptional sensitivity and wide operating range due to these parts of the invention. It is versatile because different kinds of recognition elements can be immobilized directly on the surface of the measuring electrode. The electrode then becomes selective to those molecules in the solution, the analytes, that show affinity to the recognition element on the surface. Compared to capacitive sensors described before those described here shows at least a 1000-fold better sensitivity because of the properties of the layer binding the recognition element.Type: GrantFiled: June 15, 2000Date of Patent: August 20, 2002Assignee: AB Sangtec MedicalInventors: Christine Berggren, Gillis Johansson
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Publication number: 20020108869Abstract: A device to facilitate electrophysiological measurements of a biological material comprises a plate having a plurality of wells that each have an end. At least some of the wells have a hole formed in the end, and the holes are configured to receive an individual cell such that a high resistance seal is formed between the cell and the end. A chamber is disposed adjacent the plate and is in fluid communication with each of the holes. A common electrode is disposed in the chamber, and a plurality of well electrodes are configured to be positioned within the wells. In this way, a voltage gradient may be created across cell membranes of cells that are positioned within the holes so that electrophysiological measurements of the cells may be taken.Type: ApplicationFiled: February 9, 2001Publication date: August 15, 2002Inventor: Alex Savtchenko
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Patent number: 6428959Abstract: Methods for determining the presence of double stranded nucleic acids in a sample are provided. In the subject methods, nucleic acids present in a fluid sample are translocated through a nanopore, e.g. by application of an electric field to the fluid sample. The current amplitude through the nanopore is monitored during the translocation process and changes in the amplitude are related to the passage of single- or double-stranded molecules through the nanopore. The subject methods find use in a variety of applications in which the detection of the presence of double-stranded nucleic acids in a sample is desired, e.g. in hybridization assays, such as Northern blot assays, Southern blot assays, array based hybridization assays, etc.Type: GrantFiled: September 6, 2000Date of Patent: August 6, 2002Assignee: The Regents of the University of CaliforniaInventor: David W. Deamer
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Patent number: 6420168Abstract: Histamine may be quantitatively measured by performing the following steps. First, an oocyte that expresses histamine receptors is held in a recess formed at the bottom of a vessel. Then, first and second electrodes are inserted into the oocyte. Subsequently, the membrane potential of the oocyte is measured by using the first electrode to stabilize this membrane potential at a predetermined level by driving a current through the second electrode using circuitry for clamping the membrane potential of the oocyte. A sample is then infused into a fine reacting tube having an antigen immobilized on its inner surface together with some buffer solution to promote a histamine releasing reaction. The solution containing histamines that is released in the fine reacting tube is transferred to the vessel to make contact with the oocyte in the vessel.Type: GrantFiled: October 30, 2001Date of Patent: July 16, 2002Assignee: Hitachi, Ltd.Inventors: Tomoko Takeshita, Jun Otomo
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Publication number: 20020074227Abstract: A microelement device has a plurality of microelements, which may be configured as microelectrodes, arranged on a substrate and adapted for making contact to cells present in a liquid environment. The cells are guided onto the microelectrodes, are isolated or are mechanically attracted to the microelectrodes. A negative-pressure force or a hydrodynamic force may be applied on the cells. Also described are a method for making contact to the cells, and a method for manufacturing the microelement device is disclosed.Type: ApplicationFiled: October 26, 2001Publication date: June 20, 2002Inventors: Wilfried Nisch, Alfred Stett, Ulrich Egert, Martin Stelzle
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Patent number: 6403338Abstract: Integrated systems, apparatus, software, and methods for performing biochemical analysis, including DNA sequencing, genomic screening, purification of nucleic acids and other biological components and drug screening are provided. Microfluidic devices, systems and methods for using these devices and systems for performing a wide variety of fluid operations are provided. The devices and systems of are used in performing fluid operations which require a large number of iterative, successive or parallel fluid manipulations, in a microscale, or sealed and readily automated format.Type: GrantFiled: June 27, 2000Date of Patent: June 11, 2002Assignee: Mountain ViewInventors: Michael Knapp, John Wallace Parce, Luc J. Bousse, Anne R. Kopf-Sill
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Patent number: 6403321Abstract: A structure including a substrate. A first electrode and a second electrode are arranged spaced apart from each other on the substrate. A polymer string is positioned on the substrate between the two electrodes, the polymer line has a width of less than about 50 nm.Type: GrantFiled: March 7, 2001Date of Patent: June 11, 2002Assignee: International Business Machines CorporationInventors: Ravi F. Saraf, Hemantha K. Wickramasinghe
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Publication number: 20020068338Abstract: An electroporation method and apparatus generating and applying an electric field according to a user-specified pulsing and temperature profile scheme. The apparatus includes a cuvette holder with a Peltier device forming part of the electrode structures that form part of the holder. Advantageously, one such pulse includes a low voltage pulse of a first duration, immediately followed by a high voltage of a second duration, immediately followed by a low voltage of a third duration. The low voltage electroporation field accumulates molecules at the surface of a cell, the appropriately high voltage field creates an opening in the cell, and the final low voltage field moves the molecule into the cell. The molecules may be DNA, portions of DNA, chemical agents, the receiving cells may be eggs, platelets, human cells, red blood cells, mammalian cells, plant protoplasts, plant pollen, liposomes, bacteria, fungi, yeast, sperm, or other suitable cells.Type: ApplicationFiled: September 20, 2001Publication date: June 6, 2002Applicant: GENETRONICS, INC.Inventors: Gurvinder Singh Nanda, Rejean Laverdiere, Gunter A. Hofmann
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Patent number: 6399361Abstract: This invention provides methods and apparatus for performing microanalytic and microsynthetic analyses and procedures. Specifically, the invention provides a microsystem platform for use with a micromanipulation device to manipulate the platform by rotation, thereby utilizing the centripetal force resulting from rotation of the platform to motivate fluid movement through microchannels embedded in the microplatform. The microsystem platforms of the invention are also provided having microfluidics components, resistive heating elements, temperature sensing elements, mixing structures, capillary and sacrificial valves, and methods for using these microsystems platforms for performing biological, enzymatic, immunological and chemical assays. An electronic spindle designed rotor capable of transferring electrical signals to and from the microsystem platforms of the invention is also provided.Type: GrantFiled: December 21, 2000Date of Patent: June 4, 2002Assignee: Tecan Trading AGInventors: Ian Brotherston, Michael B. Truelove
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Patent number: 6399362Abstract: A method of introducing biological material into cells includes providing one or more target cells and establishing a spray of substantially dispersed particles including biological material. The substantially dispersed particles have an electrical charge applied thereto such that one or,more of the substantially dispersed particles of the spray is introduced into one or more of the target cells. The spray of substantially dispersed particles may be established by dispensing a spray of microdroplets suspending particles. The electrical charge is concentrated on the suspended particles as the microdroplet evaporates. The suspended particles may include carrier particles with biological material or the suspended particles may be particles of biological material alone. The space charge effect of the concentrated electrical charge on the substantially dispersed particles of the spray enable one or more of the particles to be introduced into one or more of the target cells.Type: GrantFiled: May 23, 2000Date of Patent: June 4, 2002Assignee: Regents of the University of MinnesotaInventors: David Y. H. Pui, Da-Ren Chen
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Patent number: 6395493Abstract: Methods and apparatus are provided for the analysis and determination of the nature of repeat units in a genetic target. In one method of this invention, the nature of the repeat units in the genetic target is determined by the steps of providing a plurality of hybridization complex assays arrayed on a plurality of test sites, where the hybridization complex assay includes at least a nucleic acid target containing a simple repetitive DNA sequence, a capture probe having a first unique flanking sequence and n repeat units, where n=0,1,2 . . . , or fractions thereof, being complementary to the target sequence, and a reporter probe having a selected sequence complementary to the same target sequence strand wherein the selected sequence of the reporter includes a second unique flanking sequence and m repeat units, where m=0,1,2 . . . , or fractions thereof, but where the sum of repeat units in the capture probe plus reporter probe is greater than 0 (n+m>0).Type: GrantFiled: August 24, 2000Date of Patent: May 28, 2002Assignee: Nanogen, Inc.Inventors: Ronald G. Sosnowski, Eugene Tu
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Publication number: 20020061591Abstract: Among other things, the invention provides devices and methods for obtaining electric field-enhanced bioconjugation events. In particular, the invention provides for contactless electrodes for obtaining the electric field, such that transport and bioconjugation of charged molecules is obtained in the absence of current flow through the buffer, sample, and/or porous media.Type: ApplicationFiled: April 19, 2001Publication date: May 23, 2002Inventors: Vi-En Choong, George Maracas, Larry Akio Nagahara
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Publication number: 20020061589Abstract: An object of the invention is to provide a method for delivery of macromolecules into biological cells in the tissues of a patient and includes the steps of: (a) providing electrodes (16) in an electrode assembly (12), wherein the electrodes have fixed electrode surfaces (42) which are coated with at least one static layer of electrode releasable molecules (44) to be delivered; (b) providing a waveform generator (15) for generating electric fields; (c) establishing electrically conductive pathways between the electrodes (16) and the waveform generator (15); (d) locating the electrodes (16) such that the biological cells are situated therebetween, and (g) providing electric fields in the form of pulse waveforms from the waveform generator (15) to the electrodes (16), such that molecules in the at least one static layer of the electrode releasable molecules (44) on the electrodes (16) are delivered into the biological cells.Type: ApplicationFiled: August 3, 2001Publication date: May 23, 2002Inventors: Alan D. King, Richard E. Walters
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Patent number: 6391622Abstract: Integrated systems, apparatus, software, and methods for performing biochemical analysis, including DNA sequencing, genomic screening, purification of nucleic acids and other biological components and drug screening are provided. Microfluidic devices, systems and methods for using these devices and systems for performing a wide variety of fluid operations are provided. The devices and systems of are used in performing fluid operations which require a large number of iterative, successive or parallel fluid manipulations, in a microscale, or sealed and readily automated format.Type: GrantFiled: June 27, 2000Date of Patent: May 21, 2002Assignee: Caliper Technologies Corp.Inventors: Michael Knapp, John Wallace Parce, Luc J. Bousse, Anne R. Kopf-Sill
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Patent number: 6391624Abstract: An improved biological probe is disclosed that employs a plurality of groups of modified single-stranded DNA attached to a single electrode. Using a plurality of such groups increases the inherent sensitivity of the probe by providing additional hybridization location sites and also serves to improve performance by diminishing steric hindrance caused by the crowding and tangling of the long single-stranded oligionucleotide molecules. The modification of the oligionucleotides involves the attachment of electron donor and acceptor moieties that alters the electrochemical properties of the hybridized molecules. The selected groups of modified oligionucleotides are complementary to unique characteristic sequences of the target DNA or RNA. A sample that containing oligionucleotides of a target biological agent is brought into contact with the probe and complementary portions of the molecules will hybridize with the oligionucleotides attached to the probe.Type: GrantFiled: June 2, 2000Date of Patent: May 21, 2002Assignee: Lockheed Martin CorporationInventor: Clifford A. Megerle
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Patent number: 6379897Abstract: The present invention presents methods for gene expression monitoring that utilize microelectronic arrays to drive the transport and hybridization of nucleic acids. Procedures are described for generating mRNA expression samples for use in these methods from populations of cells, tissues, or other biological source materials, that may differ in their physiological and/or pathological state. Provided in the invention are methods for generating a reusable nucleic acid transcript library from mRNA in a sample of biological material. In order to improve gene expression monitoring on the microelectronic arrays, the transcripts are amplified to produce sample nucleic acid amplicons of a defined length. Because multiple sample amplicons may be selectively hybridized to controlled sites in the electronic array, the gene expression profiles of the polynucleotide populations from different sources can be directly compared in an array format using electronic hybridization methodologies.Type: GrantFiled: November 9, 2000Date of Patent: April 30, 2002Assignee: Nanogen, Inc.Inventors: Elaine M. Weidenhammer, Ling Wang, Xiao Xu, Michael J. Heller, Brenda F. Kahl
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Patent number: 6377057Abstract: Biologically active compounds are classified according to their effect on ion channels, changes in membrane potential and ionic currents, and the frequency content of action potentials that the compound(s) evoke in excitable cells. The spectral density changes of such evoked membrane potential or action potential are a characteristic for each channel type that is modulated by the test compound. A pattern of spectral changes in membrane potential is determined by contacting a responsive cell with a compound, and monitoring the membrane potential or ionic currents over time. These changes correlate with the effect of that compound, or class of compounds, on the ion channels of the responding cell. This pattern of spectral changes provides a unique signature for the compound, and provides a useful method for characterization of channel modulating agents.Type: GrantFiled: February 18, 1999Date of Patent: April 23, 2002Assignee: The Board of Trustees of the Leland Stanford Junior UniversityInventor: David Borkholder
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Patent number: 6375899Abstract: Methods, apparatus, and applications for use of a stacked, reconfigurable system for electrophoretic transport are provided. In one embodiment, a system having a first chamber including at least a bottom support and an intermediate support, and a second chamber, said second chamber including a bottom support and a top member, the first and second chambers being coupled through a via. Electrophoretic, and optional electro-osmotic and thermal, transport is effected. In another aspect of this invention, three or more chambers are coupled by an electrophoretic buss. The electrophoretic buss includes driving electrodes and is adapted to receive fluid containing materials for transport. The chambers are coupled to the electrophoretic buss and serve as a tap from the buss for delivery of charged materials. In one embodiment, certain functions are performed in different chambers.Type: GrantFiled: December 2, 1998Date of Patent: April 23, 2002Assignee: Nanogen, Inc.Inventors: Donald E. Ackley, Edward L. Sheldon, Michael K. Krihak
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Patent number: 6368851Abstract: A method is provided for measuring a state variable of a biological cell (3) located in a nutrient medium (2) and supported on and adhering to a support area (5). Within the support area (5) for the cell (3) and at a distance from the support area edge, an opening is made in the membrane of the cell (3). The edge of the cell membrane that surrounds the opening and adheres to the support area (5) seals off the liquid found inside the cell (3) from the nutrient medium (2). Through the opening the state variable (2) is measured. An apparatus for performing the method is also provided.Type: GrantFiled: May 27, 1999Date of Patent: April 9, 2002Assignee: Micronas GmbHInventors: Werner Baumann, Ralf Ehret, Mirko Lehmann, Günter Igel, Hans-Jürgen Gahle, Bernhard Wolf, Ulrich Sieben, Ingo Freund, Martin Brischwein
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Patent number: 6365400Abstract: A process is described for denaturing native double-stranded nucleic acid material into its individual strands in an electrochemical cell. The process disclosed is an electrical treatment of the nucleic acid with a voltage applied to the nucleic acid material by an electrode. The process may also employ a promoter compound such as methyl viologen to speed denaturation. The process may be used in the detection of nucleic acid by hybridizing with a labelled probe or in the amplification of DNA by a polymerase chain reaction or ligase chain reaction.Type: GrantFiled: June 20, 2000Date of Patent: April 2, 2002Assignee: Affymetrix, Inc.Inventor: Christopher J. Stanley
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Patent number: 6355485Abstract: A new and useful apparatus for producing cell electrofusion is provided. The apparatus comprises: a. a chamber with a substrate disposed therein, b. means for directing the cells to be fused toward one side of the substrate; and c. a device for inducing fusion of the portion of the cells.Type: GrantFiled: July 14, 2000Date of Patent: March 12, 2002Assignee: University of South FloridaInventors: Mark J. Jaroszeski, Richard A. Gilbert, Richard Heller
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Patent number: 6352853Abstract: This invention features high-density electrode arrays for use in electroporation. These arrays contain a plurality of electrode pairs where the electrodes in each electrode pair are flat and parallel to each other.Type: GrantFiled: November 16, 1999Date of Patent: March 5, 2002Assignee: Rosetta Inpharmatics, Inc.Inventors: Jeffrey S. King, Tod A. Flak
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Patent number: 6342364Abstract: The present invention provides a sensor that electrochemically determines cholesterol in low density lipoprotein by only one feed of a sample. The sensor has: an electrode system that is mounted on an electrically insulating base plate and includes at least a working electrode and a counter electrode; an enzyme layer formed on the base plate with the electrode system; and a reagent layer that is arranged before the enzyme layer in a sample solution supply path to the electrode system. The enzyme layer includes at least an oxidoreductase and an electron mediator. The reagent layer includes a reagent that depresses reactivity of cholesterol in lipoproteins other than the low density lipoprotein with the oxidoreductase, for example, a reagent that attaches to lipoproteins other than the low density lipoprotein to form a water-soluble complex.Type: GrantFiled: May 3, 2001Date of Patent: January 29, 2002Assignee: Matsushita Electric Industrial Co., Ltd.Inventors: Motokazu Watanabe, Keiko Yugawa, Shiro Nankai
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Publication number: 20020005354Abstract: The invention provides a microfabricated device for sorting cells based on a desired characteristic, for example, reporter-labeled cells can be sorted by the presence or level of reporter on the cells. The device includes a chip having a substrate into which is microfabricated at least one analysis unit. Each analysis unit includes a main channel, having a sample inlet channel, typically at one end, and a detection region along a portion of its length. Adjacent and downstream from the detection region, the main channel has a discrimination region or branch point leading to at least two branch channels. The analysis unit may further include additional inlet channels, detection points, branch points, and branch channels as desired. A stream containing cells is passed through the detection region, such that on average one cell occupies the detection region at a given time.Type: ApplicationFiled: August 13, 2001Publication date: January 17, 2002Applicant: California Institute of TechnologyInventors: Charles F. Spence, Anne Y. Fu, Stephen R. Quake, Frances H. Arnold
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Patent number: 6338960Abstract: Histamine may be quantitatively measured by performing the following steps. First, an oocyte that expresses histamine receptors is held in a recess formed at the bottom of a vessel. Then, first and second electrodes are inserted into the oocyte. Subsequently, the membrane potential of the oocyte is measured by using the first electrode to stabilize this membrane potential at a predetermined level by driving a current through the second electrode using circuitry for clamping the membrane potential of the oocyte. A sample is then infused into a fine reacting tube having an antigen immobilized on its inner surface together with some buffer solution to promote a histamine releasing reaction. The solution containing histamines that is released in the fine reacting tube is transferred to the vessel to make contact with the oocyte in the vessel.Type: GrantFiled: February 21, 2001Date of Patent: January 15, 2002Assignee: Hitachi, Ltd.Inventors: Tomoko Takeshita, Jun Otomo
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Patent number: 6337178Abstract: Histamine may be quantitatively measured by performing the following steps. First, an oocyte that expresses histamine receptors is held in a recess formed at the bottom of a vessel. Then, first and second electrodes are inserted into the oocyte. Subsequently, the membrane potential of the oocyte is measured by using the first electrode to stabilize this membrane potential at a predetermined level by driving a current through the second electrode using circuitry for clamping the membrane potential of the oocyte. A sample is then infused into a fine reacting tube having an antigen immobilized on its inner surface together with some buffer solution to promote a histamine releasing reaction. The solution containing histamines that is released in the fine reacting tube is transferred to the vessel to make contact with the oocyte in the vessel.Type: GrantFiled: April 30, 2001Date of Patent: January 8, 2002Assignee: Hitachi, Ltd.Inventors: Tomoko Takeshita, Jun Otomo
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Patent number: 6334980Abstract: Miniaturized, self-contained apparatus for conducting bio-chemical reactions and analyses is formed in a compact structure comprising a substrate which includes a plurality of reaction chambers and a plurality of analysis chambers which are in fluid communication with the reaction chambers. Independently controllable heaters and coolers are positioned in thermal contact with the reaction chambers to permit parallel processing of biological samples at different temperature cycles. The apparatus is especially useful for performing and analyzing the results of a polymerase chain reaction.Type: GrantFiled: September 25, 1998Date of Patent: January 1, 2002Assignee: Microfab Technologies Inc.Inventors: Donald J. Hayes, David B. Wallace, Christopher J. Frederickson
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Patent number: 6333189Abstract: Method of making an electrotransport device containing an analog of a parent polypeptide having one or more amino acid residues substituted relative to the parent polypeptide with an amino acid residue selected from the group consisting of proline, glycine and asparagine.Type: GrantFiled: November 20, 1997Date of Patent: December 25, 2001Assignee: ALZA CorporationInventors: Leslie A. Holladay, Kevin R. Oldenburg
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Patent number: 6329194Abstract: Histamine may be quantitatively measured by performing the following steps. First, an oocyte that expresses histamine receptors is held in a recess formed at the bottom of a vessel. Then, first and second electrodes are inserted into the oocyte. Subsequently, the membrane potential of the oocyte is measured by using the first electrode to stabilize this membrane potential at a predetermined level by driving a current through the second electrode using circuitry for clamping the membrane potential of the oocyte. A sample is then infused into a fine reacting tube having an antigen immobilized on its inner surface together with some buffer solution to promote a histamine releasing reaction. The solution containing histamines that is released in the fine reacting tube is transferred to the vessel to make contact with the oocyte in the vessel.Type: GrantFiled: February 21, 2001Date of Patent: December 11, 2001Assignee: Hitachi, Ltd.Inventors: Tomoko Takeshita, Jun Otomo
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Patent number: 6329154Abstract: Histamine may be quantitatively measured by performing the following steps. First, an oocyte that expresses histamine receptors is held in a recess formed at the bottom of a vessel. Then, first and second electrodes are inserted into the oocyte. Subsequently, the membrane potential of the oocyte is measured by using the first electrode to stabilize this membrane potential at a predetermined level by driving a current through the second electrode using circuitry for clamping the membrane potential of the oocyte. A sample is then infused into a fine reacting tube having an antigen immobilized on its inner surface together with some buffer solution to promote a histamine releasing reaction. The solution containing histamines that is released in the fine reacting tube is transferred to the vessel to make contact with the oocyte in the vessel.Type: GrantFiled: February 21, 2001Date of Patent: December 11, 2001Assignee: Hitachi, Ltd.Inventors: Tomoko Takeshita, Jun Otomo
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Patent number: 6323043Abstract: A method and apparatus for fabricating an array of biopolymers on a substrate using a biopolymer or biomonomer fluid, and using a dispensing head. The head has a reservoir chamber and at least one jet which can dispense droplets onto a substrate. The jet includes a capillary delivery chamber communicating with the reservoir chamber, which delivery chamber has an orifice. The jet further includes an ejector which, when activated, causes a droplet to be ejected from the orifice. The method includes loading the head by positioning the head with the orifice adjacent and facing a biomonomer or biopolymer fluid, and providing a load pressure to the reservoir chamber. The load pressure is sufficiently negative such that the fluid is drawn into the reservoir chamber through the orifice and delivery chamber, while simultaneously being insufficient to result in ambient atmosphere entering the delivery chamber through the orifice once the head has been loaded and no further fluid is facing and adjacent the orifice.Type: GrantFiled: April 30, 1999Date of Patent: November 27, 2001Assignee: Agilent Technologies, Inc.Inventors: Michael P. Caren, Carol T. Schembri, Peter G. Webb
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Patent number: 6319472Abstract: Methods, apparatus, and applications for use of a stacked, reconfigurable system for electrophoretic transport are provided. In one embodiment, a system having a first chamber including at least a bottom support and an intermediate support, and a second chamber, said second chamber including a bottom support and a top member, the first and second chambers being coupled through a via. Electrophoretic, and optional electro-osmotic and thermal, transport is effected. In another aspect of this invention, three or more chambers are coupled by an electrophoretic buss. The electrophoretic buss includes driving electrodes and is adapted to receive fluid containing materials for transport. The chambers are coupled to the electrophoretic buss and serve as a tap from the buss for delivery of charged materials. In one embodiment, certain functions are performed in different chambers.Type: GrantFiled: December 2, 1998Date of Patent: November 20, 2001Assignee: Nanogen, Inc.Inventors: Donald E. Ackley, Edward L. Sheldon, Michael K. Krihak
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Patent number: 6315940Abstract: A microelement device has a plurality of microelements, which may be configured as microelectrodes, arranged on a substrate and adapted for making contact to cells present in a liquid environment. The cells are guided onto the microelectrodes, are isolated or are mechanically attracted to the microelectrodes. A negative-pressure force or a hydrodynamic force may be applied on the cells. Also described are a method for making contact to the cells, and a method for manufacturing the microelement device is disclosed.Type: GrantFiled: May 13, 1999Date of Patent: November 13, 2001Assignee: NMI Naturwissenschaftliches und Medizinisches Institut an der Universitat Tubingen in ReutlingenInventors: Wilfried Nisch, Alfred Stett, Ulrich Egert, Martin Stelzle
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Publication number: 20010031499Abstract: A loading system for providing a cell suitable for delivery of an agent to a vertebrate, the system comprise a loading module for loading a cell with an agent; and a sensitization module in fluid communication with the loading module, the sensitization module for sensitizing a cell to an energy field, such that said cell is induced to release the agent upon exposure to said energy field. The system can be used to transform a cell, such as a red blood cell, into a delivery vehicle for delivering a therapeutic agent and/or an imaging agent to a vertebrate, and in particular, to a mammal, such as a human being.Type: ApplicationFiled: February 8, 2001Publication date: October 18, 2001Inventor: Anthony Patrick McHale
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Patent number: 6297025Abstract: A method of observing a physical and chemical property of a tissue or cell by using an apparatus which comprises at least a cell culturing means, an environment conditioning means, an observing means and a comparing means, comprising the steps of (A) culturing the tissue or cell by the cell culturing means, (B) maintaining a first physical and chemical environment around the tissue or cell by the cell culturing means, (C) observing a first physical and chemical property of the tissue or cell in the first physical and chemical environment by the observing means, (D) changing the first physical and chemical environment to a second physical and chemical environment by the environment conditioning means, (E) observing a second physical and chemical property of the tissue or cell in the second physical and chemical environment by the observing means, and (F) comparing the first physical and chemical property of the tissue or cell with the second physical and chemical property of the tissue or cell by the comparingType: GrantFiled: June 13, 1996Date of Patent: October 2, 2001Assignee: Matsushita Electric Industrial Co., LTDInventors: Hirokazu Sugihara, Akihito Kamei, Yasushi Kobayashi, Makoto Taketani, Tadayasu Mitsumata
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Patent number: 6287517Abstract: Methods of manufacture and devices for performing active biological operations utilize laminated structures. In the preferred embodiment, a first planar sample support includes at least one sample through hole, a planar electrode is disposed adjacent the first planar sample support, and includes an electrode through region, a second planar support includes a vent through hole, the planar electrode being in a laminated relationship between the first planar sample support and the second planar support, further characterized in that the sample through hole, electrode through hole and vent through hole are in overlapping arrangement. Preferably, some or all of the through holes, through regions and vent through holes are aligned. In one embodiment, the lateral dimension of the vent through hole is larger than the lateral dimension of the electrode through hole. In an alternative embodiment, the lateral dimension of the sample through hole is larger than the lateral dimension of the vent through hole.Type: GrantFiled: December 4, 1996Date of Patent: September 11, 2001Assignee: Nanogen, Inc.Inventors: Donald E. Ackley, Thomas R. Jackson, Edward L. Sheldon, III
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Patent number: 6287850Abstract: Agitation systems for reversibly directing fluid samples flow back and forth across a nucleic acid array, thereby promoting hybridization between targets in the fluid sample and probes on the nucleic acid array.Type: GrantFiled: April 29, 1999Date of Patent: September 11, 2001Assignee: Affymetrix, Inc.Inventors: Donald M. Besemer, Virginia W. Goss, James L. Winkler
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Patent number: 6287774Abstract: Methods, systems, kits for carrying out a wide variety of different assays that comprise providing a first reagent mixture which comprises a first reagent having a fluorescent label. A second reagent is introduced into the first reagent mixture to produce a second reagent mixture, where the second reagent reacts with the first reagent to produce a fluorescently labeled product having a substantially different charge than the first reagent. A polygon is introduced into at least one of the first and second reagent mixtures, and the fluorescent polarization in the second reagent mixture relative to the first reagent mixture is determined, this fluorescent polarization being indicative of the rate or extent of the reaction.Type: GrantFiled: May 21, 1999Date of Patent: September 11, 2001Assignee: Caliper Technologies Corp.Inventor: Theo T. Nikiforov
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Patent number: 6287768Abstract: Arrays of polymeric targets stably associated with the surface of a rigid solid support are provided. In the subject arrays, the polymeric targets are arranged at least according to size. The polymeric targets of the subject arrays are generally biopolymeric compounds, e.g. nucleic acids and proteins, where ribonucleic acids and proteins are the preferred polymeric targets. The subject arrays find use in a variety of different applications, and are particularly suited for use in high through gene expression analysis applications.Type: GrantFiled: March 3, 2000Date of Patent: September 11, 2001Assignee: Clontech Laboratories, Inc.Inventors: Alex Chenchik, Paul Siebert