With Injection Patents (Class 204/453)
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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: 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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Publication number: 20010008213Abstract: 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: ApplicationFiled: February 9, 2001Publication date: July 19, 2001Applicant: Ciba-Geigh CorporationInventors: Andreas Manz, D. Jed Harrison, Carlo S. Effenhauser
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Patent number: 6261431Abstract: A fully integrated monolithic small volume PCR-CE device in glass, or the like materials, is fabricated using thin film metal heaters and thermocouples to thermally cycle sub-microliter PCR volumes. Successful amplification of a PCR fragment is demonstrated on a PCR-CE chip. The process utilizes a linear polyacrylamide surface coating coupled with addition of BSA to the amplification buffer was necessary to obtain amplification efficiencies comparable to a positive control. The micro-reactor reduced significantly the time required for amplification and the reaction volume was in the sub-microlitre regime. Likewise addressed are the known problems connected with reliable microfabrication of metal coatings and the insulating layers required to shield these layers from the PCR reaction mix, and the longstanding unresolved issue of exposed metal regions in the PCR-CE chip resulting in electrolysis of water and bubble formation whenever a voltage is applied.Type: GrantFiled: December 28, 1998Date of Patent: July 17, 2001Assignee: Affymetrix, Inc.Inventors: Richard A. Mathies, Peter C. Simpson, Stephen J. Williams
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Publication number: 20010004964Abstract: 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 electrolyte 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: ApplicationFiled: February 9, 2001Publication date: June 28, 2001Applicant: Ciba-Geigy CorporationInventors: Andreas Manz, D. Jed Harrison, Carlo S. Effenhauser
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Patent number: 6235175Abstract: 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: October 2, 1998Date of Patent: May 22, 2001Assignee: Caliper Technologies Corp.Inventors: Robert S. Dubrow, Colin B. Kennedy, Luc J. Bousse
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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: 6156178Abstract: The apparatus and method of the present invention disclose a system in which multiple injections may be made into a capillary array. The injections are spaced in time with each injection followed by an interval of electrophoresis. Once all samples are loaded into the capillaries, continuous electrophoresis and detection is used to separate and detect target compounds within the sample. The interval between injections is matched to the target compound migration rate to be sufficient to allow the target compounds to be detectably separated when the compounds reach the detector.Type: GrantFiled: July 13, 1999Date of Patent: December 5, 2000Assignee: Molecular Dynamics, Inc.Inventors: Elaine S. Mansfield, Christine Peponnet, John S. Bashkin, Curtis R. Kautzer
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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: 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: 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: 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: 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: 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: 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: 6042710Abstract: The present invention provides methods of electrophoretically separating macromolecular species, as well as compositions and systems useful in carrying out such methods. Specifically, the methods of the present invention comprise providing a substrate that has at least a first capillary channel disposed therein. The surface of the channel has a first surface charge associated therewith, and is filled with a water soluble surface adsorbing polymer solution that bears a net charge that is the same as the charge on the capillary surface.Type: GrantFiled: May 11, 1999Date of Patent: March 28, 2000Assignee: Caliper Technologies Corp.Inventor: Robert S. Dubrow
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Patent number: 6033546Abstract: 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 15, 1998Date of Patent: March 7, 2000Assignee: Lockheed Martin Energy Research CorporationInventor: J. Michael Ramsey
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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: 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: 5993634Abstract: This invention is an integrated instrument for high-capacity electrophoretic analysis of biopolymer samples. It comprises a specialized high-voltage, electrophoretic module in which the migration lanes are formed between a bottom plate and a plurality of etched grooves in a top plate, the module permitting concurrent separation of 80 or more separate samples. In thermal contact with the bottom plate is a thermal control module incorporating a plurality of Peltier heat transfer devices for the control of temperature and gradients in the electrophoretic medium. Fragments are detected by a transmission imaging spectrograph which simultaneously spatially focuses and spectrally resolves the detection region of all the migration lanes. The spectrograph comprises a transmission dispersion element and a CCD array to detect signals. Signal analysis comprises the steps of noise filtering, comparison in a configuration space with signal prototypes, and selection of the best prototype.Type: GrantFiled: May 9, 1996Date of Patent: November 30, 1999Assignee: CuraGen CorporationInventors: John W. Simpson, Jonathan M. Rothberg, Gregory T. Went
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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: 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: 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: 5880071Abstract: The present invention provides for techniques for transporting materials using electrokinetic forces through the channels of a microfluidic system. The subject materials 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: December 6, 1996Date of Patent: March 9, 1999Assignee: Caliper Technologies CorporationInventors: J. Wallace Parce, Michael R. Knapp
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Patent number: 5843294Abstract: To inject sample into a capillary tube of an electrophoresis apparatus, a vacuum tank is connected to one end of the tube while the other end is in sample to impart a pressure difference across the tube. The pressure in the pressure chamber is sensed, integrated and used to determine and control the amount of sample drawn and to correct peak data.Type: GrantFiled: October 4, 1990Date of Patent: December 1, 1998Assignee: Isco, Inc.Inventor: Robert William Allington
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Patent number: 5814199Abstract: Direct measurement of soluble ionogenic atmospheric gases is implemented using a suppressed conductometric capillary electrophoresis separation system. A small circular wire loop is incorporated adjacent sampling end of a fused silica capillary, in the same plane as the capillary. Dipping the loop into a solution and then withdrawing forms a liquid film that is in fluid communication with the capillary and acts as a microreservoir. Elevating the film relative to the destination side injects part or all of the film contents into the capillary. This mechanism may be used to perform gas sampling in automated fashion with slightly modified commercial CE instrumentation. The film-bearing loop is lowered into a sample chamber and air is sampled for a preset time period at a preselected flow rate. Lifting the capillary introduces an aliquot from the film for analysis. The capillary is then dipped into a running electrolyte source vial and electrophoresis is commenced.Type: GrantFiled: September 20, 1996Date of Patent: September 29, 1998Assignee: Texas Tech UniversityInventor: Purnendu K. Dasgupta
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Patent number: 5800692Abstract: A preseparation processor for use in capillary electrophoresis is described. The preseparation processor contains sample processing material, preferably in the form of a membrane, for use in concentrating or chemically processing a sample, or catalyzing a chemical reaction. It is particularly suited to the concentration of dilute samples or the purification of contaminated samples. The preseparation processor facilitates reliable and reproducible separation of analytes by eliminating inconsistencies caused by a reversal of the electroosmotic flow otherwise induced by the sample processing material.Type: GrantFiled: April 17, 1995Date of Patent: September 1, 1998Assignee: Mayo Foundation for Medical Education and ResearchInventors: Stephen Naylor, Andrew J. Tomlinson, Linda M. Benson, Walter David Braddock, Robert P. Oda
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Patent number: 5779868Abstract: The present invention provides for techniques for transporting materials using electrokinetic forces through the channels of a microfluidic system. The materials are transported in slug regions of high ionic concentration, next to buffer material regions of high ionic concentration, which are separated by buffer 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: June 28, 1996Date of Patent: July 14, 1998Assignee: Caliper Technologies CorporationInventors: J. Wallace Parce, Michael R. Knapp
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Patent number: 5770029Abstract: Integrated electrophoretic microdevices comprising at least an enrichment channel and a main electrophoretic flowpath are provided. In the subject integrated devices, the enrichment channel and the main electrophoretic flowpath are positioned so that waste fluid flows away from said main electrophoretic flowpath through a discharge outlet. The subject devices find use in a variety of electrophoretic applications, including clinical assays.Type: GrantFiled: July 30, 1996Date of Patent: June 23, 1998Assignee: Soane BiosciencesInventors: Robert J. Nelson, Herbert H. Hooper, James Landers
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Patent number: 5766435Abstract: The present invention provides new methods for the concentration of ionic solutes, particularly ampholytes, such as, for example, peptides, proteins and nucleic acids. The methods are based on the fact that the electrophoretic migration velocities of solutes decrease upon a decrease in the absolute value of the zeta-potential of a solute or the pore size of the electrophoresis medium, and upon an increase in the cross-section of the electrophoresis chamber, the viscosity of the electrophoresis medium, or the electrical conductivity of the electrophoresis medium. When applied to capillary electrophoresis, the methods described herein permit concentration of a solution of solutes in the same capillary tube as is used for the electrophoretic analysis. Alternatively, however, the sample can be withdrawn from the capillary tube following concentration of the solution of solutes and processed by techniques other than high-performance capillary electrophoresis (HPCE).Type: GrantFiled: March 22, 1996Date of Patent: June 16, 1998Assignee: Bio-Rad Laboratories, Inc.Inventors: Jia-li Liao, Stellan Hjerten, Christopher Siebert
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Patent number: 5741412Abstract: A multiple capillary analyzer allows detection of light from multiple capillaries with a reduced number of interfaces through which light must pass in detecting light emitted from a sample being analyzed, using a modified sheath flow cuvette. A linear or rectangular array of capillaries is introduced into a rectangular flow chamber. Sheath fluid draws individual sample streams through the cuvette. The capillaries are closely and evenly spaced and held by a transparent retainer in a fixed position in relation to an optical detection system. Collimated sample excitation radiation is applied simultaneously across the ends of the capillaries in the retainer. Light emitted from the excited sample is detected by the optical detection system. The retainer is provided by a transparent chamber having inward slanting end walls. The capillaries are wedged into the chamber.Type: GrantFiled: October 23, 1996Date of Patent: April 21, 1998Assignee: University of AlbertaInventors: Norman J. Dovichi, Jian Zhong Zhang