Using Gel-filled Capillary Patents (Class 204/455)
  • Patent number: 6375819
    Abstract: 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 carrousel 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: Grant
    Filed: August 13, 1999
    Date of Patent: April 23, 2002
    Assignee: Spectrumedix Corporation
    Inventors: Qingbo Li, Changsheng Liu, Thomas E. Kane, John R. Kernan, Bernard Sonnenschein, Michael V. Sharer
  • Patent number: 6372106
    Abstract: Methods for reducing peak broadening associated with the establishment of a run field in a capillary electrophoresis process, and apparatus useful for carrying out such methods, are described. Such methods include defining a maximum ramp rate to be used during an initial electric field ramp, defining a minimum period over which the run field is established, and/or maintaining a temperature of a separation medium to within certain ranges during the initial electric field ramp. In addition, methods for determining a ramp rate effective for reducing peak broadening are disclosed.
    Type: Grant
    Filed: July 26, 1999
    Date of Patent: April 16, 2002
    Assignee: Applera Corporation
    Inventors: Ben F. Johnson, Eric S. Nordman
  • Publication number: 20020033338
    Abstract: A method of preparing an electrophoretic support comprising washing of at least a portion of the surface of a silicon-containing support member supporting an electrophoretic matrix with a weak alkali solution and supporting of said matrix by said support member; an electrophoretic gel comprising a polyacrylamide polymer obtained by polymerizing acrylamide or a derivative thereof in the presence of two or more polar organic solvents; a method of electrophoresis employing a gel prepared by said preparation method; and a method of electrophoresis employing said electrophoretic gel.
    Type: Application
    Filed: May 11, 2001
    Publication date: March 21, 2002
    Inventor: Yoshihide Hayashizaki
  • Publication number: 20020033337
    Abstract: Devices, systems and methods for use in separating sample materials into different fractions that employ bulk fluid flow for loading of samples followed by electrophoretic separation of the sample material. Devices employ configurations that optionally allow bulk sample loading with some or no displacement of a separation matrix within a separation conduit. Methods of using these devices, and systems that incorporate these devices are also envisioned.
    Type: Application
    Filed: July 31, 2001
    Publication date: March 21, 2002
    Inventors: Walter Ausserer, Luc J. Bousse, Robert S. Dubrow, Steven A. Sundberg, Andrea W. Chow, Benjamin N. Wang
  • Publication number: 20020029968
    Abstract: Compositions and methods are provided for performing capillary electrophoresis using a composition comprising in combination in an aqueous buffered medium a coating polymer and a sieving polymer, where the sieving polymer is more hydrophilic than the coating polymer and is present in greater amount. Of particular interest are uncrosslinked acrylamide polymer mixtures for coating plastic channels and providing sieving for performing DNA separations in microfluidic devices. Polyacrylamide or N,N-dimethyl acrylamide is used with a N,N-dialkyl acrylamide copolymer, either separately or together for sieving and coating, serving as the medium in capillary electrophoresis DNA separations.
    Type: Application
    Filed: May 1, 2001
    Publication date: March 14, 2002
    Applicant: Aclara BioSciences, Inc.
    Inventors: Hongdong Roy Tan, Alexander Sassi, Ingrid Cruzado
  • Publication number: 20020029969
    Abstract: A microelectrophoresis chip comprises a substrate in which there are formed one or more channels, one channel for each sample to be evaluated. The channels extend for the length of the chip, a distance of generally around 1 cm, and are about 1 to 10 &mgr;m wide and 1 to 10 &mgr;m in depth. The channels are filed with a homogeneous separation matrix which acts as an obstacle to the electrophoretic migration of the charged molecules. Microelectrodes disposed in the channels are used to induce an electric filed within the homogeneous separation medium. When a voltage is applied across two or more of the microelectrodes, the charged molecules are induced to move and separate according to the electric field density, the type of solvent film, and the charge, shape and size of the charged molecule.
    Type: Application
    Filed: July 16, 2001
    Publication date: March 14, 2002
    Inventors: Thomas D. Yager, Paul Waterhouse, Alexandre M. Izmailov, Bruno C. Maruzzo, John K. Stevens, Marina T. Larson
  • Publication number: 20020027076
    Abstract: The present invention relates generally to the electrophoretic separation of biomolecules, including but not limited to proteins, peptides, DNA and RNA. The methods of this invention are particularly useful when applied to two-dimensional gel electrophoresis.
    Type: Application
    Filed: May 7, 2001
    Publication date: March 7, 2002
    Inventors: George Harding, Elias Klein, Jon Klein
  • Patent number: 6352633
    Abstract: An automated capillary zone 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 carrousel arrangement to eliminate cross-contamination resulting from reuse of the same buffer tray on consecutive executions from electrophoresis. The system also has a container connected to the detection end of the capillaries. The container is provided with valving which facilitate cleaning the capillaries, loading buffer into the capillaries, introducing samples to be electrophoresced into the capillaries, and performing capillary zone electrophoresis on the thus introduced samples.
    Type: Grant
    Filed: August 31, 1999
    Date of Patent: March 5, 2002
    Assignee: Spectrumedix Corporation
    Inventors: Changsheng Liu, Thomas E Kane, Qingbo Li
  • Patent number: 6344145
    Abstract: Apparatus and method for improving the resolution of non-pressure driven capillary chromatographic systems, and particularly for capillary electrochromatography (CEC) systems. By reducing the cross-sectional area of a packed capillary column by means of a second open capillary contiguous with the outlet end of a packed capillary column, where the packed capillary column has a cross sectional area of between about 2 and 5 times that of the open capillary column, the phenomenon of band broadening in the transition region between the open capillary and the packed capillary column, where the individual components of the mixture are analyzed, can be eliminated, thereby providing for a significant improvement in resolution and more accurate detection and analysis.
    Type: Grant
    Filed: April 10, 2000
    Date of Patent: February 5, 2002
    Assignee: Sandia Corporation
    Inventors: Michael G. Garguilo, Phillip H. Paul, David J. Rakestraw
  • Patent number: 6337212
    Abstract: Reactor systems that include a reaction receptacle that includes a plurality of reservoirs disposed in the surface of a substrate. The reactor system also typically includes a temperature control element having at least a first heat exchanger thermally coupled to it. The heat exchanger is, in turn, disposed within the at least one of the reservoirs whereby the heat exchanger transfers heat to or from a fluid disposed within the reservoir, which heat is conducted to or from the temperature control element.
    Type: Grant
    Filed: November 2, 2000
    Date of Patent: January 8, 2002
    Assignee: Caliper Technologies Corp.
    Inventors: Robert Nagle, Robert S. Dubrow
  • Publication number: 20010025791
    Abstract: The present invention provides methods for separating a compound, including a membrane polypeptide. The method includes the use of a bicontinuous lipidic phase. The invention also provides devices that include a bicontinuous lipidic cubic phase, and a kit for use in separating a compound, including a mixture that includes a lipid and an aqueous phase and instructions for using the mixture.
    Type: Application
    Filed: December 15, 2000
    Publication date: October 4, 2001
    Inventors: Ehud M. Landau, Javier V. Navarro
  • Publication number: 20010023825
    Abstract: A method is disclosed for moving, isolating and/or identifying particles in a sample by placing said sample in a spatially varying electrical field wherein the spatially varying electrical field is following a mathematical nonmonotonous function, selected from the group consisting of linear, hyperbolic, parabolic, parabolic functions or y˜xp/q and combinations thereof wherein p q means an integer. Also various devices are disclosed for performing the method.
    Type: Application
    Filed: November 29, 2000
    Publication date: September 27, 2001
    Inventors: Leonid Frumin, Sergey E. Peltek, Gleb V. Zilberstein, Shmuel Bukshpan, Uriel Halavee
  • Publication number: 20010023827
    Abstract: This invention relates to an electrophoresis separation medium having a gel matrix of at least one random, linear copolymer comprising a primary comonomer and at least one secondary comonomer, wherein the comonomers are randomly distributed along the copolymer chain. The primary comonomer is an acrylamide or an acrylamide derivative that provides the primary physical, chemical, and sieving properties of the gel matrix. The at least one secondary comonomer imparts an inherent physical, chemical, or sieving property to the copolymer chain. The primary and secondary comonomers are present in a ratio sufficient to induce desired properties that optimize electrophoresis performance. The invention also relates to a method of separating a mixture of biological molecules using this gel matrix, a method of preparing the novel electrophoresis separation medium, and a capillary tube filled with the electrophoresis separation medium.
    Type: Application
    Filed: April 30, 2001
    Publication date: September 27, 2001
    Inventors: Changsheng Liu, Li Qingbo
  • Publication number: 20010020588
    Abstract: 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: Application
    Filed: January 23, 2001
    Publication date: September 13, 2001
    Applicant: Whitehead Institute for Biomedical Research
    Inventors: Aram S. Adourian, Daniel J. Ehrlich, Lance B. Koutny, Paul T. Matsudaira, Dieter R. Schmalzing
  • Publication number: 20010017263
    Abstract: An injection syringe 14 for injecting a gel into a capillary 111, a charging syringe 15 for charging the injection syringe 14 with the gel 10 are attached to a block 17. A check valve 16 is inserted between the both syringes, and the check valve 16 works so as to prevent the gel 10 from flowing back to the charging syringe 15. As the result, the gel charging can be automated, and accordingly the processing ability of the electrophoretic instrument can be improved.
    Type: Application
    Filed: February 26, 2001
    Publication date: August 30, 2001
    Inventors: Tomohiro Shoji, Yoshiyuki Okishima, Masaya Kojima, Muneo Maeshima
  • Patent number: 6270640
    Abstract: Chiral separations can be enhanced through the use of polymerized dipeptide-surfactant or oligopeptide-surfactant chiral micelles. Because polymerized micelles eliminate much of the complex dynamic behavior associated with conventional micelles, polymerized chiral micelles have stronger chiral recognition properties than do otherwise-identical, “conventional” or non-polymerized chiral micelles. Recovery of chiral ligands from polymerized chiral micelles is often easier, as the chiral ligands may typically be recovered by simple extraction with an appropriate organic solvent. By contrast, recovering the solute from a conventional, non-polymerized micellar medium by extraction with an organic solvent frequently results in the formation of troublesome emulsion systems. Polymerized chiral micelle systems are therefore beneficial in both preparative-scale and process-scale separations.
    Type: Grant
    Filed: April 22, 1999
    Date of Patent: August 7, 2001
    Assignee: Board of Supervisors of Louisiana State University and Agricultural and Mechanical College
    Inventors: Isiah M. Warner, Eugene J. Billiot, Shahab A. Shamsi, Stefan J. Thibodeaux
  • Publication number: 20010008212
    Abstract: A polymer material useful as the porous dielectric medium for microfluidic devices generally and electrokinetic pumps in particular. The polymer material is produced from an inverse (water-in-oil) emulsion that creates a 3-dimensional network characterized by small pores and high internal volume, characteristics that are particularly desirable for the dielectric medium for electrokinetic pumps. Further, the material can be cast-to-shape inside a microchannel. The use of bifunctional monomers provides for charge density within the polymer structure sufficient to support electroosmotic flow. The 3-dimensional polymeric material can also be covalently bound to the channel walls thereby making it suitable for high-pressure applications.
    Type: Application
    Filed: February 28, 2001
    Publication date: July 19, 2001
    Inventors: Timothy J. Shepodd, Leroy Whinnery, William R. Even
  • Patent number: 6261430
    Abstract: A microelectrophoresis chip comprises a substrate in which there are formed one or more channels, one channel for each sample to be evaluated. The channels extend for the length of the chip, a distance of generally around 1 cm, and are about 1 to 10 &mgr;m wide and 1 to 10 &mgr;m in depth. The channels are filled with a homogeneous separation matrix which acts as an obstacle to the electrophoretic migration of the charged molecules. Microelectrodes disposed in the channels are used to induce an electric filed within the homogeneous separation medium. When a voltage is applied across two or more of the microelectrodes, the charged molecules are induced to move and separate according to the electric field density, the type of solvent film, and the charge, shape and size of the charged molecule.
    Type: Grant
    Filed: February 17, 2000
    Date of Patent: July 17, 2001
    Assignee: Visible Genetics Inc.
    Inventors: Thomas D. Yager, Paul Waterhouse, Alexandre M. Izmailov, Bruno C. Maruzzo, John K. Stevens, Marina T. Larson
  • Publication number: 20010007305
    Abstract: An apparatus and method is provided for obtaining a preparative-scale, free-fluid electrophoretic separator with high resolution as well as an analytical capability commensurate with capillary zone electrophoresis. The electrophoretic focusing apparatus and method of the present invention combines features of electrophoresis and isoelectric focusing to accomplish large scale purifications and fractionations that have not previously been possible, and features a separation chamber bounded by precision-pore insulated screens, a plurality of purge chambers, a plurality of electrode chambers, and a plurality of pump means. The separation device of the invention is capable of high speed of separation and short residency of sample through the use of high voltage gradients which are produced by relatively low voltages applied across the narrow chamber dimensions.
    Type: Application
    Filed: February 21, 2001
    Publication date: July 12, 2001
    Inventors: Percy H. Rhodes, Robert S. Snyder
  • Patent number: 6224775
    Abstract: A method for separating a mixture of at least two chemical compounds which first involves loading and sintering a frit material in a capillary to form a first retaining frit. After removing substantially all unsintered frit material from the capillary, a packing material made up of a substrate coated with a linear carbohydrate polymer is loaded into the capillary adjacent to the first retaining frit to form a stationary phase. More frit material is loaded in the capillary and is sintered to form a second retaining frit adjacent to the packing material on the side opposite from the first retaining frit. Substantially all unsintered frit material is again removed from the capillary. The chemical mixture is then introduced into the capillary at one of the retaining frits, and migration of the mixture across the packing material is induced by applying a voltage across the capillary. Differences in electroosmotic flow velocity between the compounds cause them to separate during migration.
    Type: Grant
    Filed: September 3, 1998
    Date of Patent: May 1, 2001
    Assignee: Villanova University
    Inventors: Joe P. Foley, Sally J. Grieb
  • Patent number: 6207031
    Abstract: 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: Grant
    Filed: September 14, 1998
    Date of Patent: March 27, 2001
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Aram S. Adourian, Daniel J. Ehrlich, Lance B. Koutny, Paul T. Matsudaira, Dieter R. Schmalzing
  • Patent number: 6153073
    Abstract: 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: Grant
    Filed: August 11, 1999
    Date of Patent: November 28, 2000
    Assignee: Caliper Technologies Corp.
    Inventors: Robert S. Dubrow, Colin B. Kennedy, Luc J. Bousse
  • Patent number: 6132580
    Abstract: 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: Grant
    Filed: September 28, 1995
    Date of Patent: October 17, 2000
    Assignee: The Regents of the University of California
    Inventors: Richard A. Mathies, Adam T. Woolley
  • Patent number: 6117293
    Abstract: The invention relates to a method for producing hydrophilic monomers which are particularly useful for electrophoresis and to electrophoresis compositions and coating compositions. The method uses the steps of reacting a (meth)acryloyl with an aminoalcohol in the presence of a base in a polar solvent, optionally filtering an aqueous solution of the reaction product, deionizing an aqueous solution of the reaction product, and removing the solvent.
    Type: Grant
    Filed: July 31, 1998
    Date of Patent: September 12, 2000
    Assignee: BioWhittaker Molecular Applications, Inc.
    Inventors: Tianhong Zhang, Noriko Kusukawa
  • Patent number: 6117326
    Abstract: The present invention provides for the convenient preparation, purification, use and re-use of capillary electrochromatography columns that employ polymer gel materials as the separation media. The problems associated with employing crosslinked polymer gels is overcome through the use of physically entangled polymer gels, which comprise, as polymerized units: 1) 5% to 80% by weight of an ionizable monomer; 2) 0.1% to 50% by weight of a monomer containing a retentive ligand; and 3) 10% to 80% by weight of a nonionic monomer.
    Type: Grant
    Filed: March 31, 1999
    Date of Patent: September 12, 2000
    Assignee: Rohm and Haas Company
    Inventors: Mark Richard Schure, Willie Lau
  • Patent number: 6074542
    Abstract: The present invention describes a method and apparatus utilizing a capillary coating of linear and crosslinked polymers and copolymers of acrylamidomonomers or methacrylamides bearing two hydroxyethyl residues. The method and apparatus employ this coating to maintain coating integrity and suppress electroosmotic flow under basic conditions in capillary electrophoresis.
    Type: Grant
    Filed: June 3, 1999
    Date of Patent: June 13, 2000
    Inventors: Vladislav Dolnik, Marcella Chiari
  • Patent number: 6068767
    Abstract: Apparatus and method for improving the resolution of non-pressure driven capillary chromatographic systems, and particularly for capillary electrochromatography (CEC) systems. By reducing the cross-sectional area of a packed capillary column by means of a second open capillary contiguous with the outlet end of a packed capillary column, where the packed capillary column has a cross sectional area of between about 2 and 5 times that of the open capillary column, the phenomenon of band broadening in the transition region between the open capillary and the packed capillary column, where the individual components of the mixture are analyzed, can be eliminated, thereby providing for a significant improvement in resolution and more accurate detection and analysis.
    Type: Grant
    Filed: October 29, 1998
    Date of Patent: May 30, 2000
    Assignee: Sandia Corporation
    Inventors: Michael G. Garguilo, Phillip H. Paul, David J. Rakestraw
  • Patent number: 6027627
    Abstract: 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: Grant
    Filed: June 29, 1998
    Date of Patent: February 22, 2000
    Assignee: Spectrumedix Corporation
    Inventors: Qingbo Li, Thomas E. Kane, Changsheng Liu, Bernard Sonnenschein, Michael V. Sharer, John R. Kernan
  • Patent number: 6001230
    Abstract: 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: Grant
    Filed: April 29, 1993
    Date of Patent: December 14, 1999
    Assignee: Beckman Coulter, Inc.
    Inventor: Victor Paul Burolla
  • Patent number: 6001232
    Abstract: A viscosity-adjustable medium for use in separation methods is described. In particular, a block copolymer composition is described which exists as a low viscosity solution at a temperature outside of the temperature range of electrophoresis and which self-assembles into a gel-like polymer network at electrophoresis operating temperatures. A system is described for conducting molecular separation in a capillary column using the viscosity-adjustable medium. In addition, a method is also described for separating charged molecules.
    Type: Grant
    Filed: September 4, 1996
    Date of Patent: December 14, 1999
    Assignee: The Research Foundation of State University of New York
    Inventors: Benjamin Chu, Chunhung Wu
  • Patent number: 5993626
    Abstract: A capillary electrophoresis method for resolving transferrin glycoforms in a sample is described. The capillary comprises a lumen, an inlet and an outlet. The lumenal surface of the capillary is charge-neutral and the capillary contains a buffer containing a polymeric matrix. The transferrin sample is contacted with the inlet of the capillary. A voltage is applied to the capillary such that the inlet is a cathode and the outlet is an anode and such that the voltage is effective for resolving transferrin glycoforms. A method for diagnosing chronic alcoholism or carbohydrate-deficient glycoprotein syndrome using CE to resolve abnormal populations of transferrin glycoforms is also described.
    Type: Grant
    Filed: January 24, 1997
    Date of Patent: November 30, 1999
    Inventors: James P. Landers, Rajani Prasad, Robert P. Oda, Robert L. Stout
  • Patent number: 5993634
    Abstract: 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: Grant
    Filed: May 9, 1996
    Date of Patent: November 30, 1999
    Assignee: CuraGen Corporation
    Inventors: John W. Simpson, Jonathan M. Rothberg, Gregory T. Went
  • Patent number: 5976336
    Abstract: 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: Grant
    Filed: April 25, 1997
    Date of Patent: November 2, 1999
    Assignee: Caliper Technologies Corp.
    Inventors: Robert S. Dubrow, Colin B. Kennedy, Luc J. Bousse
  • Patent number: 5968331
    Abstract: 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: Grant
    Filed: November 7, 1995
    Date of Patent: October 19, 1999
    Assignee: Hitachi, Ltd.
    Inventors: Hideki Kambara, Satoshi Takahashi, Takashi Anazawa, Takashi Yamada
  • Patent number: 5964996
    Abstract: Macrocyclic antibiotics having ring structures with at least 10 members act as separation agents in crystallization, precipitation, filtration, electrophoresis and chromatography. The macrocyclic antibiotics include ansamacrolides, macrolides, macrocyclic peptides, polyenes and derivatives thereof. The process has been found to be especially advantageous for separation of optical isomers by electrophoresis and chromatography.
    Type: Grant
    Filed: November 6, 1998
    Date of Patent: October 12, 1999
    Assignee: Curators of the University of Missouri
    Inventor: Daniel Armstrong
  • Patent number: 5964999
    Abstract: Methods for profiling oligosaccharides released from glycoproteins and methods for the electrophoretic separation of high mannose, complex and hybrid oligosaccharides are disclosed. The methods include first providing an analytical sample which includes at least one released oligosaccharide and introducing the sample into an electrophoretic channel containing a separation medium having a pH less than 8 and greater than 2.5. Then applying a sufficiently high electric field causes the released oligosaccharides to migrate and separate within the electrophoretic channel in accordance with their molecular size or charge to mass ratio. Detecting the separated oligosaccharides provides glycoprotein conjugate profiling information. Preferred embodiments include using a separation medium which includes lithium acetate buffer having a pH of about 4.75 and a gel of about 0.4% polyethylene oxide.
    Type: Grant
    Filed: December 18, 1996
    Date of Patent: October 12, 1999
    Assignee: Beckman Instruments, Inc.
    Inventors: Andras Guttman, Nelson H. Cooke
  • Patent number: 5963456
    Abstract: 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: Grant
    Filed: November 27, 1996
    Date of Patent: October 5, 1999
    Assignee: Beckman Instruments, Inc.
    Inventors: Gerald L. Klein, Steven P. Katzmann
  • Patent number: 5948227
    Abstract: 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: Grant
    Filed: December 17, 1997
    Date of Patent: September 7, 1999
    Assignee: Caliper Technologies Corp.
    Inventor: Robert S. Dubrow
  • Patent number: 5938905
    Abstract: A high-pressure electrophoresis apparatus is formed by a high-pressure tubing (101) in which at least one column-shaped cell is arranged, said cell comprising two cell portions being arranged in the operating condition one above the other which form a cathode buffer solution reservoir (12) and an anode buffer solution reservoir (123) separated by a supporting member (122) which supports a carrier column loadable with a separating gel. Following implementation of high-pressure electrophoresis the carrier gel is extruded from the carrier column and subjected to further electrophoresis at normal pressure implemented on a slab gel.
    Type: Grant
    Filed: February 28, 1997
    Date of Patent: August 17, 1999
    Assignee: Max-Planck-Gesellschaft zur Forderung der Wissenschaften e.V.
    Inventors: Robert Clegg, Leonardo Erijman
  • Patent number: 5916426
    Abstract: The invention provides uncharged water-soluble silica-adsorbing polymers for suppressing electroendoosmotic flow and to reduce analyte-wall interactions in capillary electrophoresis. In one aspect of the invention, one or more of such polymers are employed as components of a separation medium for the separation of biomolecules, such as polynucleotides, polysaccharides, proteins, and the like, by capillary electrophoresis. Generally, such polymers are characterized by (i) water solubility over the temperature range between about 20.degree. C. to about 50.degree. C., (ii) concentration in a separation medium in the range between about 0.001% to about 10% (weight/volume), (iii) molecular weight in the range of about 5.times.10.sup.3 to about 1.times.10.sup.6 daltons, and (iv) absence of charged groups in an aqueous medium having pH in the range of about 6 to about 9.
    Type: Grant
    Filed: August 19, 1997
    Date of Patent: June 29, 1999
    Assignee: The Perkin-Elmer Corporation
    Inventors: Ramakrishna S. Madabhushi, Steven M. Menchen, J. William Efcavitch, Paul D. Grossman
  • Patent number: 5916428
    Abstract: 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: Grant
    Filed: July 7, 1998
    Date of Patent: June 29, 1999
    Assignee: Spectrumedix Corporation
    Inventors: Thomas E. Kane, Qingbo China Li, John R. Kernan
  • Patent number: 5891313
    Abstract: 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: Grant
    Filed: November 8, 1995
    Date of Patent: April 6, 1999
    Assignee: The Perkin-Elmer Corp.
    Inventors: Ben F. Johnson, Steven M. Menchen, Will Bloch
  • Patent number: 5863401
    Abstract: Homogeneous competitive immunoassay methods for simultaneously detecting analytes using capillary electrophoresis and fluorescent detection systems are described. The methods are useful for detecting and/or quantitating the concentration of a plurality of drugs of abuse in a single urine sample using a single assay method.
    Type: Grant
    Filed: July 3, 1997
    Date of Patent: January 26, 1999
    Assignee: Beckman Instruments, Inc.
    Inventor: Fu-Tai A. Chen
  • Patent number: 5840388
    Abstract: A coated microcapillary column for high performance electrophoresis is disclosed. A preferred microcapillary includes a fused silica capillary column, the inner surface of the column having an interconnected polymeric coating of a polyvinyl alcohol (PVA) based polymer covalently attached to the column wall by Si--O--Si bonds. The resulting coated microcapillary column has good hydrolytic and pH stability and minimizes electroosmotic flow and interactions between sample components and the capillary wall. Also disclosed are a method of forming a polymeric coating layer for any surface by polymerizing the appropriate organic compounds in an organic solvent and a method of forming a column with a hydrophilic polymeric coating by directly converting an attached hydrophobic polymeric coating material to a hydrophilic polymeric coating material.
    Type: Grant
    Filed: May 22, 1997
    Date of Patent: November 24, 1998
    Assignee: Northeastern University
    Inventors: Barry L. Karger, Wolfgang Goetzinger
  • Patent number: 5759369
    Abstract: An electrophoresis separation medium is disclosed comprising a matrix of a copolymer composed of a linear hydrophilic polymer segment having a selected substantially uniform segment length and hydrophobic polymer segments carried on each end. Also disclosed is an electrophoresis method employing the separation medium which permits high resolution separation of polynucleotides, especially in DNA sequencing operations.
    Type: Grant
    Filed: March 24, 1995
    Date of Patent: June 2, 1998
    Assignee: The Perkin-Elmer Corporation
    Inventors: Steven Michael Menchen, Mitchell A. Winnik, Ben F. Johnson
  • Patent number: 5741639
    Abstract: A device for combined bioaffinity assay and electrophoretic separation is provided, which comprises a capillary system having two stages, a first stage in which bioaffinity interactions of analyte molecules and molecular recognition elements are performed, and a second stage, in which electrophoretic separation of the analyte molecules and subsequent detection of the separated species is accomplished. Within the first capillary stage the molecular recognition elements are attached and immobilized to the inside capillary wall, for example, by adsorption or by covalent binding to the capillary material. The method for combined bioaffinity assay and electrophoretic separation comprises flowing an analyte through a capillary system having two stages. In a first capillary stage the analyte molecules are captured by respective molecular recognition elements present in that stage.
    Type: Grant
    Filed: February 28, 1995
    Date of Patent: April 21, 1998
    Assignee: Ciba-Geigy Corp.
    Inventors: Kees Ensing, Peter Oroszlan, Aran Paulus, Carlo S. Effenhauser
  • Patent number: 5728282
    Abstract: A capillary electrophoresis separation matrix for single-stranded nucleic acids, along with methods for using and preparing the matrix, are disclosed. The separation matrix provides denaturing conditions and contains hydroxyethyl cellulose (HEC) in combination with urea, and preferably also includes formamide. The separation matrix may be used for DNA sizing and sequencing applications and provides a single-base resolution to approximately 500 base pairs. The separation matrix is inexpensive, easy to prepare, requires no polymerization steps, and is of low enough viscosity to be pumped easily into and out of capillary tubes for electrophoresis. The low viscosity allows for high throughput of samples and reuse of the capillary tubes for numerous separations.
    Type: Grant
    Filed: April 12, 1996
    Date of Patent: March 17, 1998
    Assignee: Molecular Dynamics
    Inventors: John S. Bashkin, David L. Barker, Richard F. Johnston
  • Patent number: 5695626
    Abstract: The invention provides a side-entry optical excitation geometry for use in a multiplexed capillary electrophoresis system. A charge-injection device is optically coupled to capillaries in the array such that the interior of a capillary is imaged onto only one pixel. In Sanger-type 4-label DNA sequencing reactions, nucleotide identification ("base calling") is improved by using two long-pass filters to split fluorescence emission into two emission channels. A binary poly(ethyleneoxide) matrix is used in the electrophoretic separations.
    Type: Grant
    Filed: June 18, 1996
    Date of Patent: December 9, 1997
    Assignee: Iowa State University Research Foundation
    Inventors: Edward S. Yeung, Huan-Tsang Chang, Eliza N. Fung
  • Patent number: 5665216
    Abstract: A capillary column for high performance electrophoretic separation and detection of SDS proteins and system for using the same is disclosed. A preferred column includes a capillary, a static or dynamic layer of coating material on the inner surface of the capillary wall, and a hydrophilic polymer network which is UV-transparent in the tube, filling it. The capillary column is particularly useful in any electrophoresis system requiring UV-transparent materials.
    Type: Grant
    Filed: October 7, 1991
    Date of Patent: September 9, 1997
    Assignee: Northeastern University
    Inventors: Barry L. Karger, Katalin Ganzler, Aharon S. Cohen
  • Patent number: RE37606
    Abstract: The filing of an internally coated capillary with a gel in its polymerized state without damaging the gel. The coating prevents bonding of the gel to the inside of the capillary. The gel comprises up to 6% acrylamide and 0-5% crosslinker. The gel can be advantageously and conveniently used in automated electrophoresis systems for automatic replacement of spent gel.
    Type: Grant
    Filed: August 5, 1999
    Date of Patent: March 26, 2002
    Assignee: Beckman Coulter, Inc.
    Inventor: Andras Guttman