With Injector Patents (Class 204/604)
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Methods and apparatus for processing a sample of biomolecular analyte using a microfabricated device
Publication number: 20010020588Abstract: A technique processes a sample of biomolecular analyte. The technique uses an apparatus having a support assembly that receives and supports a test module, a load assembly that loads the sample of biomolecular analyte onto the test module, an electrophoresis assembly that applies a current to the test module such that components within the sample separate by electrophoresis, and a controller that controls operations of the load assembly and the electrophoresis assembly. The load assembly and the electrophoresis assembly are coupled to the support assembly. The controller controls the operation of the load assembly in an automated manner. Preferably, the test module includes a dielectric plate member having an upper planar surface and a lower planar surface that is spaced apart from and coplanar with the upper planar surface. The dielectric plate member has at least one set of channels that includes an injection channel and a separation channel.Type: ApplicationFiled: January 23, 2001Publication date: September 13, 2001Applicant: Whitehead Institute for Biomedical ResearchInventors: Aram S. Adourian, Daniel J. Ehrlich, Lance B. Koutny, Paul T. Matsudaira, Dieter R. Schmalzing -
Patent number: 6287520Abstract: The present invention provides for techniques for transporting materials using electrokinetic forces through the channels of a microfluidic system. The subject materials are transported in regions of high ionic concentration, next to spacer material regions of high ionic concentration, which are separated by spacer material regions of low ionic concentration. Such arrangements allow the materials to remain localized for the transport transit time to avoid mixing of the materials. Using these techniques, an electropipettor which is compatible with the microfluidic system is created so that materials can be easily introduced into the microfluidic system. The present invention also compensates for electrophoretic bias as materials are transported through the channels of the microfluidic system by splitting a channel into portions with positive and negative surface charges and a third electrode between the two portions, or by diffusion of the electrophoresing materials after transport along a channel.Type: GrantFiled: January 21, 2000Date of Patent: September 11, 2001Assignee: Caliper Technologies Corp.Inventors: J. Wallace Parce, Michael R. Knapp
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Publication number: 20010019019Abstract: A multi-channel capillary electrophoresis apparatus is disclosed. The apparatus includes a capillary array assembly comprising a plurality of capillaries, each capillary having a capillary outlet, and an outlet support for supporting the capillary outlets. The apparatus further includes a cuvette defining a receiving slot, a gap region, and a detection zone, where the receiving slot is adapted to removably receive the outlet support, and wherein when the outlet support is inserted into the receiving slot, the capillary outlets are positioned in the gap region in proximity to the detection zone, and a flow channel is formed by the outlet support and the receiving slot such that the flow channel is in fluid communication with the gap region. In addition, the apparatus includes a front plumbing block in fluid communication with the flow channel for supplying a fluid flow through the gap region sufficient to transport material downstream from the capillary outlets to the detection zone.Type: ApplicationFiled: March 13, 2001Publication date: September 6, 2001Applicant: The Perkin-Elmer CorporationInventors: Eric S. Nordman, John Shigeura, Albert L. Carrillo, David M. Demorest, Philip J. Wunderle
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Patent number: 6284525Abstract: The present invention generally relates to miniaturized devices for carrying out and controlling chemical reactions and analyses. In particular, the present invention provides devices which have miniature temperature controlled reaction chambers for carrying out a variety of synthetic and diagnostic applications, such as PCR amplification, nucleic acid hybridization, chemical labeling, nucleic acid fragmentation and the like.Type: GrantFiled: August 29, 2000Date of Patent: September 4, 2001Assignee: Affymetrix, Inc.Inventors: Richard A. Mathies, Adam T. Woolley
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Patent number: 6284113Abstract: The present invention concerns devices, apparatus and methods for transferring liquids. One aspect of the present invention is a device comprising a plate having a plurality of transfer elements. Each of the transfer elements comprises an aperture in the plate where the aperture is capable of being electrically activated. The plate has one of more attaching elements for attaching the plate to a multiwell plate to form a sealed system except for the apertures of the transfer elements. Usually, the device is adapted for sealing attachment to a multiwell plate. In a method in accordance with the present invention a quantity of liquid is disposed to a second side of a plate having a plurality of apertures in the plate. The apertures are capable of being electrically activated. The liquid is present in a closed well except for the apertures in the plate. To simultaneously expel liquid from the apertures, the apertures are electrically activated.Type: GrantFiled: September 15, 1998Date of Patent: September 4, 2001Assignee: Aclara BioSciences, Inc.Inventors: Torleif Ove Bjornson, Timothy F. Smith
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Patent number: 6280589Abstract: In a method for controlling sample introduction in microcolumn separation techniques, more particularly in capillary electrophoresis (CE), where a sample is injected as a sample plug into a sampling device which comprises at least a channel for the electrolyte buffer and a supply and drain channel for the sample. The supply and drain channels discharge into the electolyte channel at respective supply and drain ports. The distance between the supply port and the drain port geometrically defines a sample volume. The injection of the sample plug into the electrolyte channel is accomplished electrokinetically by applying an electric field across the supply and drain channels for a time at least long enough that the sample component having the lowest electrophoretic mobility is contained within the geometrically defined volume. The supply and drain channels each are inclined to the electrolyte channel. Means are provided for electrokinetically injecting the sample into the sample volume.Type: GrantFiled: April 12, 1994Date of Patent: August 28, 2001Assignee: Zeptosens AGInventors: Andreas Manz, D. Jed Harrison, Carlo S. Effenhauser
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Patent number: 6274089Abstract: Microfluidic devices for performing integrated reaction and separation operations. The devices include a planar substrate having a first surface with an integrated channel network disposed therein. The reaction region in the integrated microscale channel network has a mixture of at least first and second reactants located therein, wherein the mixture interacts to produce one or more products. The reaction region is configured to maintain contact between the first and second reactants contained within it. The device also includes a separation region in the integrated channel network, where the separation region is configured to separate the first reactant from the product, when the first reactant and product are flowing through the separation region. The conductivity of a fluid in the reaction region is higher than the conductivity of a fluid in the separation region.Type: GrantFiled: June 8, 1998Date of Patent: August 14, 2001Assignee: Caliper Technologies Corp.Inventors: Andrea W. Chow, Anne R. Kopf-Sill, J. Wallace Parce, Steven A. Sundberg
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Patent number: 6267858Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.Type: GrantFiled: June 24, 1997Date of Patent: July 31, 2001Assignee: Caliper Technologies Corp.Inventors: J. Wallace Parce, Anne R. Kopf-Sill, Luc J. Bousse
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Patent number: 6267859Abstract: The DNA sample preparation apparatus of the present invention comprises a base plate having a plurality of first grooves for fixing two or more kinds of DNA samples or primers to the inner surfaces of the grooves, respectively, a second groove communicating with the plurality of the first grooves, wherein a reaction solution is introduced into the first grooves to be reacted with the two or more kinds of said DNA samples or primers independently at the same time.Type: GrantFiled: November 8, 1999Date of Patent: July 31, 2001Assignee: Hitachi, LTDInventor: Hideki Kambara
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Methods and apparatus for processing a sample of biomolecular analyte using a microfabricated device
Patent number: 6207031Abstract: A technique processes a sample of biomolecular analyte. The technique uses an apparatus having a support assembly that receives and supports a test module, a load assembly that loads the sample of biomolecular analyte onto the test module, an electrophoresis assembly that applies a current to the test module such that components within the sample separate by electrophoresis, and a controller that controls operations of the load assembly and the electrophoresis assembly. The load assembly and the electrophoresis assembly are coupled to the support assembly. The controller controls the operation of the load assembly in an automated manner. Preferably, the test module includes a dielectric plate member having an upper planar surface and a lower planar surface that is spaced apart from and coplanar with the upper planar surface. The dielectric plate member has at least one set of channels that includes an injection channel and a separation channel.Type: GrantFiled: September 14, 1998Date of Patent: March 27, 2001Assignee: Whitehead Institute for Biomedical ResearchInventors: Aram S. Adourian, Daniel J. Ehrlich, Lance B. Koutny, Paul T. Matsudaira, Dieter R. Schmalzing -
Patent number: 6190521Abstract: The invention relates to a method and device for introducing a sample into the separation capillary of a capillary zone electrophoresis apparatus, which capillary zone electrophoresis apparatus comprises two reservoirs which contain a background electrolyte solution, the reservoirs being interconnected by a capillary tube which contains background electrolyte solution; electrodes placed in the reservoirs, the electrodes being connected to a high-voltage source; and a detector at the outlet end of the capillary.Type: GrantFiled: September 4, 1998Date of Patent: February 20, 2001Assignee: Valtion Teknillinen TutkimuskeskusInventor: Rauno Virtanen
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Patent number: 6162341Abstract: A multi-channel capillary electrophoresis apparatus is disclosed. The apparatus includes a capillary array assembly comprising a plurality of capillaries, each capillary having a capillary outlet, and an outlet support for supporting the capillary outlets. The apparatus further includes a cuvette defining a receiving slot, a gap region, and a detection zone, where the receiving slot is adapted to removably receive the outlet support, and wherein when the outlet support is inserted into the receiving slot, the capillary outlets are positioned in the gap region in proximity to the detection zone, and a flow channel is formed by the outlet support and the receiving slot such that the flow channel is in fluid communication with the gap region. In addition, the apparatus includes a front plumbing block in fluid communication with the flow channel for supplying a fluid flow through the gap region sufficient to transport material downstream from the capillary outlets to the detection zone.Type: GrantFiled: September 11, 1998Date of Patent: December 19, 2000Assignee: The Perkin-Elmer CorporationInventors: Eric S. Nordman, John Shigeura, Albert L. Carrillo, David M. Demorest, Philip J. Wunderle
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Patent number: 6156576Abstract: Fast lysis of a single cell or cellular component thereof is performed by generating a shock wave in a medium in which the cell or cellular component thereof is positioned. The cell or cellular component thereof is either positioned by laser tweezers or cultured as an adhered cell or cellular component thereof to minimize manipulation trauma. The disclosed method completely lyses a single cell or cellular component thereof in a controllable manner in milliseconds or less followed immediately by the loading of the cellular contents into a capillary for analyte separation and detection. The cell or cellular component thereof is adjacent the inlet of an electrophoretic column through which a gravity siphon flow of the medium is maintained. The lysed contents of the cell or cellular component thereof enter the electrophoretic column in less than 33 msec, are separated and analyzed by laser induced fluorescence.Type: GrantFiled: March 6, 1998Date of Patent: December 5, 2000Assignee: The Regents of the University of CaliforniaInventors: Nancy L. Allbritton, Christopher E. Sims, Michael W. Berns, Gavin D. Meredith, Tatiana B. Krasieva, Bruce J. Tromberg
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Patent number: 6153073Abstract: The present invention generally provides microfluidic devices which incorporate improved channel and reservoir geometries, as well as methods of using these devices in the analysis, preparation, or other manipulation of fluid borne materials, to achieve higher throughputs of such materials through these devices, with lower cost, material and/or space requirements.Type: GrantFiled: August 11, 1999Date of Patent: November 28, 2000Assignee: Caliper Technologies Corp.Inventors: Robert S. Dubrow, Colin B. Kennedy, Luc J. Bousse
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Patent number: 6149787Abstract: Methods, apparatus and systems are provided for introducing large numbers of different materials into a microfluidic analytical device rapidly, efficiently and reproducibly. In particular, improved integrated pipettor chip configurations, e.g. sippers or electropipettors, are described which are capable of sampling extremely small amounts of material for which analysis is desired, transporting material into a microfluidic analytical channel network, and performing the desired analysis on the material.Type: GrantFiled: October 14, 1998Date of Patent: November 21, 2000Assignee: Caliper Technologies Corp.Inventors: Andrea W. Chow, Robert S. Dubrow, J. Wallace Parce, Steven A. Sundberg, Jeffrey A. Wolk
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Patent number: 6148508Abstract: A method for fabricating a capillary element for electrokinetic transport of materials. The method comprises providing a first capillary element which has a first capillary channel disposed through its length. The capillary channel comprises first and second ends and an outer surface. A continuous layer of an electrically conductive material is applied along a length of the outer surface such that the continuous layer of electrically conductive material extends along the outer surface to a point proximal to, but not up to at least one of the first and second ends. The capillary element is then segmented into at least first and second separate capillary element portions at an intermediate point of the capillary element and the continuous layer.Type: GrantFiled: March 12, 1999Date of Patent: November 21, 2000Assignee: Caliper Technologies Corp.Inventor: Jeffrey A. Wolk
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Patent number: 6143152Abstract: A capillary array electrophoresis (CAE) micro-plate with an array of separation channels connected to an array of sample reservoirs on the plate. The sample reservoirs are organized into one or more sample injectors. One or more waste reservoirs are provided to collect wastes from reservoirs in each of the sample injectors. Additionally, a cathode reservoir is also multiplexed with one or more separation channels. To complete the electrical path, an anode reservoir which is common to some or all separation channels is also provided on the micro-plate. Moreover, the channel layout keeps the distance from the anode to each of the cathodes approximately constant.Type: GrantFiled: November 7, 1997Date of Patent: November 7, 2000Assignee: The Regents of The University of CaliforniaInventors: Peter C. Simpson, Richard A. Mathies, Adam T. Woolley
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Patent number: 6132580Abstract: The present invention generally relates to miniaturized devices for carrying out and controlling chemical reactions and analyses. In particular, the present invention provides devices which have miniature temperature controlled reaction chambers for carrying out a variety of synthetic and diagnostic applications, such as PCR amplification, nucleic acid hybridization, chemical labeling, nucleic acid fragmentation and the like.Type: GrantFiled: September 28, 1995Date of Patent: October 17, 2000Assignee: The Regents of the University of CaliforniaInventors: Richard A. Mathies, Adam T. Woolley
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Patent number: 6132582Abstract: A sample handling system in a multi-channel capillary electrophoresis apparatus is disclosed. The sample handling system includes a work surface for supporting a plurality of samples located at a plurality of work surface coordinates and a sample loading assembly comprising a plurality of loading wells. At least one of the loading wells includes a capillary fixedly positioned therein. The system further includes a programmable sample transfer device for automatically transferring a sample from a work surface coordinate to a loading well. The invention further includes methods for using the sample handling system.Type: GrantFiled: September 14, 1998Date of Patent: October 17, 2000Assignee: The Perkin-Elmer CorporationInventors: Howard Gregg King, John Shigeura, Eric S. Nordman, Sean Matthew Desmond
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Patent number: 6132579Abstract: A liquid is separated into its constituent species by electrophoresis along a capillary channel. A plurality of the channels is provided in the thickness of an injection molded plastics disc. The disc is rotatably mounted such that samples are dispensed into successive channels. When all twelve channels have been used, the disc is replaced with a fresh one.Type: GrantFiled: January 26, 1999Date of Patent: October 17, 2000Assignee: Eastman Kodak CompanyInventors: Stephen J. Edwards, Stephanie J. McIntyre
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Patent number: 6110339Abstract: Separation matrices useful in the formation of solid-state mm- to cm-scale devices for the rapid, high-resolution separation of single-stranded DNA ladder bands generated by the Sanger dideoxy- or Maxam/Gilbert chemical DNA sequencing procedures are formed from a solid support (1) having a plurality of posts (4) disposed on a first major surface thereof to form an obstacle course of posts (4) and pores (5). The posts are arranged in a regular X, Y array and are separated one from another by a distance of 100 nm or less, preferably 10 to 30 nm, and are optionally separated into lanes 2. The separation matrix can be manufactured by first forming a mold, preferably a reusable mold using lithography techniques. The mold is the reverse of the desired pattern of posts and pores of the obstacle course, and is used for casting the obstacle course. The cast obstacle course is then fused to a solid support and separated from the mold.Type: GrantFiled: December 16, 1997Date of Patent: August 29, 2000Assignee: Visible Genetics Inc.Inventors: Thomas D. Yager, Paul Waterhouse, Alexandre M. Izmailov, Bruno Maruzzo, John K. Stevens, Marina T. Larson
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Patent number: 6103199Abstract: The present invention concerns an apparatus for conducting a microfluidic process. The apparatus comprises integral first and second plates. The first plate comprises an array of sample receiving elements for receiving a plurality of samples from an array of sample containers and dispensing the samples. The second plate comprises a planar array of microfluidic networks of cavity structures and channels for conducting a microfluidic process. Also disclosed is a method for processing an array of samples. At least a portion of each sample in an array of sample wells is simultaneously transferred to a corresponding array of microfluidic networks of cavity structures and channels by means of a corresponding array of sample receiving elements that is in integral fluid communication with the array of microfluidic networks. The samples are then processed.Type: GrantFiled: September 15, 1998Date of Patent: August 15, 2000Assignee: ACLARA Biosciences, Inc.Inventors: Torleif Ove Bjornson, Randy M. McCormick, David S. Soane
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Patent number: 6093300Abstract: A base plate is made of an insulating material, and comprised of a flat surface and a connector part connected therewith. A plurality of wells are vertically and transversely arranged on the surface of the base plate at regular intervals respectively, and the respective wells are provided with individual electrode patterns reaching the connector part from bottoms thereof through the surface of the base plate. The connector part is connected to an external high-voltage application part.Type: GrantFiled: March 9, 1998Date of Patent: July 25, 2000Assignees: Japan Science and Technology Corporation, The Institute of Physical and Chemical Research, Shimadzu CorporationInventors: Yoshihide Hayashizaki, Shin Nakamura
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Patent number: 6090251Abstract: Fluid introduction is facilitated through the use of a port which extends entirely through a microfluidic substrate. Capillary forces can be used to retain the fluid within the port, and a series of samples or other fluids may be introduced through a single port by sequentially blowing the fluid out through the substrate and replacing the removed fluid with an alternate fluid, or by displacing the fluid in part with additional fluid. In another aspect, microfluidic substrates have channels which varying in cross-sectional dimension so that capillary action spreads a fluid only within a limited portion of the channel network. In yet another aspect, the introduction ports may include a multiplicity of very small channels leading from the port to a fluid channel, so as to filter out particles or other contaminants which might otherwise block the channel at the junction between the channel and the introduction port.Type: GrantFiled: June 6, 1997Date of Patent: July 18, 2000Assignee: Caliper Technologies, Inc.Inventors: Steven A. Sundberg, J. Wallace Parce, Calvin Y. H. Chow
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Patent number: 6086736Abstract: A capillary electrophoresis system (10) comprising: a separation capillary (20) with a first distal tip (30) and a second distal tip (140); a source vessel (50) containing a solution (40); a microreservoir-electrode (59) comprising a wire loop; a power source (60) connected to the microreservoir-electrode by wire (57); a control system (200); a detector (90); and a final destination vessel (160) containing electrolyte (150) and a ground electrode (155).Type: GrantFiled: March 30, 1998Date of Patent: July 11, 2000Assignee: Texas Tech UniversityInventors: Purnendu K. Dasgupta, Kazimierz Surowiec
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Patent number: 6086825Abstract: Fluid introduction is facilitated through the use of a port which extends entirely through a microfluidic substrate. Capillary forces can be used to retain the fluid within the port, and a series of samples or other fluids may be introduced through a single port by sequentially blowing the fluid out through the substrate and replacing the removed fluid with an alternate fluid, or by displacing the fluid in part with additional fluid. In another aspect, microfluidic substrates have channels which varying in cross-sectional dimension so that capillary action spreads a fluid only within a limited portion of the channel network. In yet another aspect, the introduction ports may include a multiplicity of very small channels leading from the port to a fluid channel, so as to filter out particles or other contaminants which might otherwise block the channel at the junction between the channel and the introduction port.Type: GrantFiled: March 23, 1999Date of Patent: July 11, 2000Assignee: Caliper Technologies CorporationInventors: Steven A. Sundberg, J. Wallace Parce, Calvin Y. H. Chow
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Patent number: 6068751Abstract: A microfluidic delivery system (20) and microfluidic system (100) control flows of a liquid or a gas through elongated capillaries (62, 126) that are enclosed along at least one surface by a layer (42, 114) of a malleable material. An electrically-powered actuator included in the systems (20, 100) extends toward or retracts a blade from the layer (42, 114) of a malleable material to either occlude or open capillaries. Reservoirs (46, 124) included in a pouch (22, 108) together with the capillaries (62, 126) supply fluids whose flow is controlled by movement of the blades. The microfluidic system (100) permits dispensing at will, under microprocessor control at predetermined flow rates, liquids, samples, chemicals, reagents and body fluids, and mixing them together and/or reacting for diagnostic medical or analytical tests, DNA sequencing etc.Type: GrantFiled: December 17, 1996Date of Patent: May 30, 2000Inventor: Armand P. Neukermans
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Patent number: 6068752Abstract: The present invention generally provides microfluidic devices which incorporate improved channel and reservoir geometries, as well as methods of using these devices in the analysis, preparation, or other manipulation of fluid borne materials, to achieve higher throughputs of such materials through these devices, with lower cost, material and/or space requirements.Type: GrantFiled: August 11, 1999Date of Patent: May 30, 2000Assignee: Caliper Technologies Corp.Inventors: Robert S. Dubrow, Colin B. Kennedy, Luc J. Bousse
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Patent number: 6063251Abstract: An automated electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. Electrical crosstalk between neighboring capillaries is attenuated using a protective tubing formed from an electrically insulative material. This crosstalk attenuation is provided in the form of sheathing, either around individual capillaries, or around bundles of spaced apart capillaries. Crosstalk attenuation may be enhanced by passing a nonconductive gas or liquid through lumens formed in the protective tubing, in which lumens the capillary tubes are present.Type: GrantFiled: May 30, 1997Date of Patent: May 16, 2000Assignee: Spectrumedix CorporationInventors: Thomas E. Kane, John R. Kernan, Changsheng Liu, Qingbo Li
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Patent number: 6056859Abstract: A method for staining immobilized nucleic acids includes the steps of affixing DNA probes to a solid substrate, moving target DNA material into proximity with the DNA probes, whereby the target DNA hybridized with specific ones of the DNA probes, and moving a fluorescent dye into proximity with the hybridized target DNA, whereby the fluorescent dye binds to the hybridized DNA to enable subsequent detection of fluorescence.Type: GrantFiled: February 12, 1997Date of Patent: May 2, 2000Assignee: Lockheed Martin Energy Research CorporationInventors: J. Michael Ramsey, Robert S. Foote, Stephen C. Jacobson
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Patent number: 6042709Abstract: The present invention provides for techniques for transporting materials using electrokinetic forces through the channels of a microfluidic system. The subject materials are transported in regions of high ionic concentration, next to spacer material regions of high ionic concentration, which are separated by spacer material regions of low ionic concentration. Such arrangements allow the materials to remain localized for the transport transit time to avoid mixing of the materials. Using these techniques, an electropipettor which is compatible with the microfluidic system is created so that materials can be easily introduced into the microfluidic system. The present invention also compensates for electrophoretic bias as materials are transported through the channels of the microfluidic system by splitting a channel into portions with positive and negative surface charges and a third electrode between the two portions, or by diffusion of the electrophoresing materials after transport along a channel.Type: GrantFiled: November 24, 1998Date of Patent: March 28, 2000Assignee: Caliper Technologies Corp.Inventors: J. Wallace Parce, Michael R. Knapp
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Patent number: 6033628Abstract: In a method of forming a microchannel and/or microcavity structure by bonding together two elements (1, 2) having opposed plane surfaces of the same or different material, one or both surfaces having open channels and/or cavities, bonding is effected by applying to one or both element surfaces (1, 2) a thin layer (3) of a solution of a material capable of fusing with and having a lower melting point than that of the material or materials of the two element surfaces (1, 2) in a solvent which substantially does not dissolve the element surface material or materials. The solvent is then removed, and the two elements (1, 2) are brought together and heated to a temperature where the dissolved material is caused to melt but not the element surface material or materials.Type: GrantFiled: April 27, 1998Date of Patent: March 7, 2000Assignee: Agilent Technologies, Inc.Inventors: Patrick Kaltenbach, Sally A. Swedberg, Klaus E. Witt, Fritz Bek, Laurie S. Mittelstadt
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Patent number: 6027627Abstract: An automated electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The system includes a stacked, dual carousel arrangement to eliminate cross-contamination resulting from reuse of the same buffer tray on consecutive executions from electrophoresis. The system also has a gel delivery module containing a gel syringe/a stepper motor or a high pressure chamber with a pump to quickly and uniformly deliver gel through the capillary tubes. The system further includes a multi-wavelength beam generator to generate a laser beam which produces a beam with a wide range of wavelengths.Type: GrantFiled: June 29, 1998Date of Patent: February 22, 2000Assignee: Spectrumedix CorporationInventors: Qingbo Li, Thomas E. Kane, Changsheng Liu, Bernard Sonnenschein, Michael V. Sharer, John R. Kernan
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Patent number: 6017765Abstract: A fluorescence detection capillary array electrophoresis analyzer comprising a capillary array holder holding a plurality of capillary array units and a transferring unit for transferring in turn the capillary array units held by the capillary array holder to a sample injection station, a fluorescence detection station or a gel refresh station, which reduces the time required for pre-electrophoresis and replacement of a used gel by fresh gel, and conducts efficient and automatic analysis. Furthermore, the analyzer automatically discharges residual samples remaining in the capillaries, and hence automatically analyzes a large number of samples by electrophoresis.Type: GrantFiled: February 20, 1998Date of Patent: January 25, 2000Assignee: Hitachi, Ltd.Inventors: Takashi Yamada, Hideki Kambara
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Patent number: 6010607Abstract: A microchip laboratory system and method provide fluid manipulations for a variety of applications, including sample injection for microchip chemical separations. The microchip is fabricated using standard photolithographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis and electrochromatography are performed in channels formed in the substrate. Analytes are loaded into a four-way intersection of channels by electrokinetically pumping the analyte through the intersection, followed by switching of the potentials to force an analyte plug into the separation channel.Type: GrantFiled: September 16, 1998Date of Patent: January 4, 2000Assignee: Lockheed Martin Energy Research CorporationInventor: J. Michael Ramsey
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Patent number: 6010608Abstract: A microchip laboratory system and method proved fluid manipulations for a variety of applications, including sample injection for microchip chemical separations. The microchip is fabricated using standard photolithographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis and electrochromatography are performed in channels formed in the substrate. Analytes are loaded into a four-way intersection of channels by electrokinetically pumping the analyte through the intersection, followed by switching of the potentials to force an analyte plug into the separation channel.Type: GrantFiled: September 16, 1998Date of Patent: January 4, 2000Assignee: Lockheed Martin Energy Research CorporationInventor: J. Michael Ramsey
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Patent number: 6001230Abstract: An integrated apparatus for capillary electrophoresis which is automated using conveyors which carry vials containing electrolytes and samples, a capillary contained in a modular, portable, and interchangeable cartridge, and actuators for bringing the capillary into flow communication with the fluids in the vials. Electropotential is applied to the ends of the capillary to cause electrophoretic separation. The cartridge may include an opening to allow detection of fluid in the capillary using a detector provided in the apparatus.Type: GrantFiled: April 29, 1993Date of Patent: December 14, 1999Assignee: Beckman Coulter, Inc.Inventor: Victor Paul Burolla
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Patent number: 5976336Abstract: The present invention generally provides microfluidic devices which incorporate improved channel and reservoir geometries, as well as methods of using these devices in the analysis, preparation, or other manipulation of fluid borne materials, to achieve higher throughputs of such materials through these devices, with lower cost, material and/or space requirements.Type: GrantFiled: April 25, 1997Date of Patent: November 2, 1999Assignee: Caliper Technologies Corp.Inventors: Robert S. Dubrow, Colin B. Kennedy, Luc J. Bousse
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Patent number: 5972187Abstract: The present invention provides for techniques for transporting materials using electrokinetic forces through the channels of a microfluidic system. The subject materials are transported in regions of high ionic concentration, next to spacer material regions of high ionic concentration, which are separated by spacer material regions of low ionic concentration. Such arrangements allow the materials to remain localized for the transport transit time to avoid mixing of the materials. Using these techniques, an electropipettor which is compatible with the microfluidic system is created so that materials can be easily introduced into the microfluidic system. The present invention also compensates for electrophoretic bias as materials are transported through the channels of the microfluidic system by splitting a channel into portions with positive and negative surface charges and a third electrode between the two portions, or by diffusion of the electrophoresing materials after transport along a channel.Type: GrantFiled: March 20, 1998Date of Patent: October 26, 1999Assignee: Caliper Technologies CorporationInventors: J. Wallace Parce, Michael R. Knapp
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Patent number: 5968331Abstract: A sample holding device for electrophoresis apparatus according to the present invention wherein a plurality of sample holding capillaries are laid out in an array and are immobilized to the supporting jig. This sample holding device is configured to ensure the lower ends of the capillaries can contact the sample injection portion of the electrophoresis separation part of the electrophoresis apparatus, and provides easy sample injection and prevents the gel capillaries of the electrophoresis separation part from being damaged when sample holding capillaries are filled with gels, thereby allowing repeated use of the gel capillaries of the electrophoresis separation part.Type: GrantFiled: November 7, 1995Date of Patent: October 19, 1999Assignee: Hitachi, Ltd.Inventors: Hideki Kambara, Satoshi Takahashi, Takashi Anazawa, Takashi Yamada
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Patent number: 5963456Abstract: A method and apparatus for displaying capillary electrophoresis data wherein absorbance with respect to time is related to graphic values within a graphic range or scale of values and selected graphic values are displayed with respect to time. The selected graphic values may comprise a range hues, color saturation and/or brightness or may represent a monochromatic scale. The resulting representation may be horizontally aligned with the corresponding electrophoretogram absorbance values to provide both a quantitative value (electrophoretogram absorbance values) and qualitative (graphic stripe) display.Type: GrantFiled: November 27, 1996Date of Patent: October 5, 1999Assignee: Beckman Instruments, Inc.Inventors: Gerald L. Klein, Steven P. Katzmann
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Patent number: 5954931Abstract: An electrophoresis apparatus includes a substrate (34) which supports a filling region (22) and a plurality of electrophoresis lanes (20). The filling region (22) communicates a sample to the plurality of electrophoresis lanes (20). A method of electrophoresis includes providing the above-described electrophoresis apparatus, applying a sample to the filling region (22), the plurality of electrophoresis lanes (20) receiving the sample from the filling region (22), and electrophoresing the sample in the plurality of electrophoresis lanes (20).Type: GrantFiled: January 24, 1997Date of Patent: September 21, 1999Assignee: Motorola, Inc.Inventors: George N. Maracas, William L. Reber, Cary D. Perttunen
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Patent number: 5948231Abstract: Compositions, methods, and apparatus for performing ultrafast binding assays by capillary electrophoresis or other electroseparation techniques are disclosed. In one embodiment, a first binding partner carries a detectable label and a second binding partner is modified to be highly charged. When used in combination with a sample containing an analyte with which both binding partners can interact and bind thereto, a three-membered complex is formed. The electrophoretic mobility difference between the unbound and complex-bound forms of labeled first binding partner is such that electroseparation and subsequent detection of an analyte can be accomplished. The compositions, methods, and apparatus disclosed herein also permit quantitative determination of the concentration of an analyte in a sample.Type: GrantFiled: May 8, 1997Date of Patent: September 7, 1999Assignee: PerSeptive Biosystems, Inc.Inventors: Martin Fuchs, Wassim A. Nashabeh, Dieter R. Schmalzing
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Patent number: 5942093Abstract: Method and apparatus for controlling precisely the composition and delivery of liquid at sub-.mu.L/min flow rate. One embodiment of such a delivery system is an electro-osmotically driven gradient flow delivery system that generates dynamic gradient flows with sub-.mu.L/min flow rates by merging a plurality of electro-osmotic flows. These flows are delivered by a plurality of delivery arms attached to a mixing connector, where they mix and then flow into a receiving means, preferably a column. Each inlet of the plurality of delivery arms is placed in a corresponding solution reservoir. A plurality of independent programmable high-voltage power supplies is used to apply a voltage program to each of the plurality of solution reservoirs to regulate the electro-osmotic flow in each delivery arm. The electro-osmotic flow rates in the delivery arms are changed with time according to each voltage program to deliver the required gradient profile to the column.Type: GrantFiled: June 18, 1997Date of Patent: August 24, 1999Assignee: Sandia CorporationInventors: David J. Rakestraw, Deon S. Anex, Chao Yan, Rajeev Dadoo, Richard N. Zare
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Patent number: 5935522Abstract: An apparatus particularly suited for subjecting biological samples to any necessary sample preparation tasks, subjecting the sample to rapid thermal cycling, and then subjecting the sample to subsequent on-line analysis using one or more of a number of analytical techniques. The apparatus includes a chromatography device including an injection means, a chromatography pump, and a chromatography column. In addition, the apparatus also contains a capillary electrophoresis device consisting of a capillary electrophoresis column with an inlet and outlet end, a means of injection, and means of applying a high voltage to cause the differential migration of species of interest through the capillary column.Type: GrantFiled: June 30, 1997Date of Patent: August 10, 1999Assignee: University of Utah Research FoundationInventors: Harold P. Swerdlow, Carl T. Wittwer
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Patent number: 5916428Abstract: An automated electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The capillary cartridge has two embodiments. In one embodiment, the second ends of the capillary tubes are also arranged is such an array. In a second embodiment, the second ends communicate with an interior cavity of pressure cell from which solutions, gels and the like may be introduced. The pressure cell allows for applying high pressure to clean out the capillary tubes. An apparatus for performing automated capillary gel electrophoresis using such a cartridge is also disclosed.Type: GrantFiled: July 7, 1998Date of Patent: June 29, 1999Assignee: Spectrumedix CorporationInventors: Thomas E. Kane, Qingbo China Li, John R. Kernan
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Patent number: 5900130Abstract: A method and device are provided for transporting a liquid sample into a third microchannel from an intersection of at least a first, a second, and a fourth microchannel, by stages. In a first stage, liquid sample is moved in and from the fourth microchannel through the intersection and into the second microchannel and concurrently carrier liquid is moved in and from the first and third microchannels through the intersection and into the second microchannel. Thereafter in a second stage, at least part of the contents of the intersection is moved into the third channel and concurrently a part of the contents of the second and fourth microchannels is moved through the intersection and into the third microchannel. Thereafter in a third stage, carrier liquid is moved from the first microchannel simultaneously through the intersection and into the second, third, and fourth microchannels.Type: GrantFiled: June 18, 1997Date of Patent: May 4, 1999Assignee: Alcara BioSciences, Inc.Inventors: Dominic Benvegnu, Randy M. McCormick
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Patent number: 5891313Abstract: A capillary electrophoresis system and method of electrokinetically loading a capillary electrophoresis sample into a separation medium in a capillary tube in which an entangled polymer matrix is formed having the sample embedded therein. The matrix has a mesh size effective to retard movement of macromolecules such as DNA sequencing templates through the matrix when an electric field is applied across the matrix. The entangled polymer matrix is formed by a linear polymer having a molecular weight of at least 20K Daltons. Furthermore, the invention includes stable denaturants useful for the electrophoresis of nucleic acids.Type: GrantFiled: November 8, 1995Date of Patent: April 6, 1999Assignee: The Perkin-Elmer Corp.Inventors: Ben F. Johnson, Steven M. Menchen, Will Bloch
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Patent number: 5885430Abstract: An automated electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The capillary cartridge has two embodiments. In one embodiment, the second ends of the capillary tubes are also arranged is such an array. In a second embodiment, the second ends communicate with an interior cavity of pressure cell from which solutions, gels and the like may be introduced. The pressure cell allows for applying high pressure to clean out the capillary tubes. An apparatus for performing automated capillary gel electrophoresis using such a cartridge is also disclosed.Type: GrantFiled: October 4, 1996Date of Patent: March 23, 1999Assignee: Spectrumedix CorporationInventors: John R. Kernan, Thomas E. Kane
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Patent number: 5858187Abstract: A microchip device includes a focusing channel, in which an electric field strength established in the focusing channel is controlled relative to an electric field strength established in a material transport channel segment to spatially focus the material traversing the material transport channel segment.Type: GrantFiled: September 26, 1996Date of Patent: January 12, 1999Assignee: Lockheed Martin Energy Systems, Inc.Inventors: John Michael Ramsey, Stephen C. Jacobson