Using Gel-filled Capillary Patents (Class 204/455)
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Publication number: 20020079220Abstract: A microchannel that can be used for separating two or more substances present in a sample has a first substrate and a second substrate with printed component printed on one or both of the substrates and is shaped to define a perimeter of the channel. The substrates are affixed to one another so that the component is sandwiched between the substrates and is in contact with both substrates. The microchannel is constructed using printing techniques to define the channel on one or both of the substrates.Type: ApplicationFiled: November 9, 2001Publication date: June 27, 2002Inventor: Janusz B. Pawliszyn
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Publication number: 20020056640Abstract: Devices and methods are disclosed for moving charged molecules through a medium by the application of a plurality of electrical fields of sufficient strength and applied for sufficient amounts of time so as to move the charged molecules through the medium. The devices although preferably small in size, preferably generate large numbers (100 or more) of electrical fields to a movement area which preferably contains a liquid buffered or gel medium. Mixtures of charged molecules are pulled through the gel by the force of the electrical fields. The fields are preferably activated simultaneously or sequentially one after another at various speeds to create complex force field distributions or moving field waves along the separation medium. Charged molecules capable of moving quickly through the gel will be moved along by the faster moving field waves and be separated from slower moving molecules.Type: ApplicationFiled: December 10, 2001Publication date: May 16, 2002Inventors: David S. Soane, Zoya M. Soane
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Publication number: 20020056639Abstract: Capillary electrophoresis is performed under conventional conditions in microchannels having a norbornene based polymer surface. The norbornene based polymers can be used as a solid substrate for forming the necessary features for a microfluidic device, where the entire device may be made of norbornene based polymer. Conveniently, a norbornene based polymer layer having a lower glass transition temperature may be used to adhere a cover or enclosing layer to the substrate to enclose the microchannels and provide a bottom for the reservoirs.Type: ApplicationFiled: July 20, 2001Publication date: May 16, 2002Inventors: Hilary Lackritz, Ingrid Cruzado, Hongdong Tan
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Patent number: 6383356Abstract: A drain joint of a pump block is opened, a piston (19a) is pushed while a piston (13a) is fixed, for charging a passage between a Luer-Lok joint (17) and an intersection part as well as a passage between the intersection part and the drain joint with a buffer. Thereafter the piston (13a) is pushed while the piston (19a) is fixed, to charge a passage (7a) with a polymer. Then, the drain joint is closed, the piston (13a) is pushed and the piston (19a) is pulled in response to the amount of pushing, for charging the passage between the intersection point and the Luer-Lok joint (17) with the polymer. Thereafter, the piston (13a) is pushed while the piston (19a) is fixed, to charge a capillary column with the polymer.Type: GrantFiled: November 24, 1999Date of Patent: May 7, 2002Assignee: Japan Science and Technology CorporationInventors: Yoshihide Hayashizaki, Shin Nakamura
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Patent number: 6379515Abstract: Process for the selective separation of electrically charged target molecules in an analytical mixture by means of capillary affinity gel electrophoresis, using a capillary tube which is at least partly filled with a polymer gel, whereby receptors for target molecules are covalently bound to the polymer, and an electric field of at least 50 volts/cm is applied, characterized in that (a) the capillary tube is charged with the analytical mixture, (b) in a first separation stage the target molecules in the analytical mixture are bound to the receptors and the remaining components are eluted, optionally while splitting open, and (c) in a second stage of the process the elution conditions are changed, optionally in stages, so that the affinity of the target molecules for the receptor is eliminated and the target molecules are eluted and detected, optionally whilst splitting open.Type: GrantFiled: November 19, 1998Date of Patent: April 30, 2002Assignee: Novartis AGInventors: Angelika Muscate-Magnussen, Aran Paulus, François Natt
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Publication number: 20020046949Abstract: A table is used to position eight specimen reservoirs of an electrophoretic chip into which a specimen is firstly dispensed to a specimen dispensing position. A specimen dispensing mechanism is used to move a head to thereby suck a test-specimen contained in eight different wells of specimen plates into eight nozzles respectively and then move the head to the specimen dispensing position, thus dispensing the test-specimen sucked into the nozzles into the specimen reservoirs simultaneously. The table is used to sequentially position the specimen reservoirs to the specimen dispensing position and then the specimen dispensing mechanism is used to sequentially dispensing the specimen into the specimen reservoirs.Type: ApplicationFiled: October 22, 2001Publication date: April 25, 2002Applicant: Shimadzu CorporationInventors: Shin Nakamura, Toru Kaji, Rintaro Yamamoto
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Patent number: 6375819Abstract: 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: GrantFiled: August 13, 1999Date of Patent: April 23, 2002Assignee: Spectrumedix CorporationInventors: Qingbo Li, Changsheng Liu, Thomas E. Kane, John R. Kernan, Bernard Sonnenschein, Michael V. Sharer
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Patent number: 6372106Abstract: 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: GrantFiled: July 26, 1999Date of Patent: April 16, 2002Assignee: Applera CorporationInventors: Ben F. Johnson, Eric S. Nordman
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Publication number: 20020033338Abstract: 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: ApplicationFiled: May 11, 2001Publication date: March 21, 2002Inventor: Yoshihide Hayashizaki
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Publication number: 20020033337Abstract: 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: ApplicationFiled: July 31, 2001Publication date: March 21, 2002Inventors: Walter Ausserer, Luc J. Bousse, Robert S. Dubrow, Steven A. Sundberg, Andrea W. Chow, Benjamin N. Wang
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Publication number: 20020029968Abstract: 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: ApplicationFiled: May 1, 2001Publication date: March 14, 2002Applicant: Aclara BioSciences, Inc.Inventors: Hongdong Roy Tan, Alexander Sassi, Ingrid Cruzado
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Publication number: 20020029969Abstract: 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: ApplicationFiled: July 16, 2001Publication date: March 14, 2002Inventors: Thomas D. Yager, Paul Waterhouse, Alexandre M. Izmailov, Bruno C. Maruzzo, John K. Stevens, Marina T. Larson
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Publication number: 20020027076Abstract: 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: ApplicationFiled: May 7, 2001Publication date: March 7, 2002Inventors: George Harding, Elias Klein, Jon Klein
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Patent number: 6352633Abstract: 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: GrantFiled: August 31, 1999Date of Patent: March 5, 2002Assignee: Spectrumedix CorporationInventors: Changsheng Liu, Thomas E Kane, Qingbo Li
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Patent number: 6344145Abstract: 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: GrantFiled: April 10, 2000Date of Patent: February 5, 2002Assignee: Sandia CorporationInventors: Michael G. Garguilo, Phillip H. Paul, David J. Rakestraw
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Patent number: 6337212Abstract: 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: GrantFiled: November 2, 2000Date of Patent: January 8, 2002Assignee: Caliper Technologies Corp.Inventors: Robert Nagle, Robert S. Dubrow
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Publication number: 20010025791Abstract: 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: ApplicationFiled: December 15, 2000Publication date: October 4, 2001Inventors: Ehud M. Landau, Javier V. Navarro
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Publication number: 20010023825Abstract: 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: ApplicationFiled: November 29, 2000Publication date: September 27, 2001Inventors: Leonid Frumin, Sergey E. Peltek, Gleb V. Zilberstein, Shmuel Bukshpan, Uriel Halavee
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Publication number: 20010023827Abstract: 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: ApplicationFiled: April 30, 2001Publication date: September 27, 2001Inventors: Changsheng Liu, Li Qingbo
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Methods and apparatus for processing a sample of biomolecular analyte using a microfabricated device
Publication number: 20010020588Abstract: A technique processes a sample of biomolecular analyte. The technique uses an apparatus having a support assembly that receives and supports a test module, a load assembly that loads the sample of biomolecular analyte onto the test module, an electrophoresis assembly that applies a current to the test module such that components within the sample separate by electrophoresis, and a controller that controls operations of the load assembly and the electrophoresis assembly. The load assembly and the electrophoresis assembly are coupled to the support assembly. The controller controls the operation of the load assembly in an automated manner. Preferably, the test module includes a dielectric plate member having an upper planar surface and a lower planar surface that is spaced apart from and coplanar with the upper planar surface. The dielectric plate member has at least one set of channels that includes an injection channel and a separation channel.Type: ApplicationFiled: January 23, 2001Publication date: September 13, 2001Applicant: Whitehead Institute for Biomedical ResearchInventors: Aram S. Adourian, Daniel J. Ehrlich, Lance B. Koutny, Paul T. Matsudaira, Dieter R. Schmalzing -
Publication number: 20010017263Abstract: 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: ApplicationFiled: February 26, 2001Publication date: August 30, 2001Inventors: Tomohiro Shoji, Yoshiyuki Okishima, Masaya Kojima, Muneo Maeshima
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Patent number: 6270640Abstract: 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: GrantFiled: April 22, 1999Date of Patent: August 7, 2001Assignee: Board of Supervisors of Louisiana State University and Agricultural and Mechanical CollegeInventors: Isiah M. Warner, Eugene J. Billiot, Shahab A. Shamsi, Stefan J. Thibodeaux
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Publication number: 20010008212Abstract: 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: ApplicationFiled: February 28, 2001Publication date: July 19, 2001Inventors: Timothy J. Shepodd, Leroy Whinnery, William R. Even
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Patent number: 6261430Abstract: 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: GrantFiled: February 17, 2000Date of Patent: July 17, 2001Assignee: Visible Genetics Inc.Inventors: Thomas D. Yager, Paul Waterhouse, Alexandre M. Izmailov, Bruno C. Maruzzo, John K. Stevens, Marina T. Larson
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Publication number: 20010007305Abstract: 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: ApplicationFiled: February 21, 2001Publication date: July 12, 2001Inventors: Percy H. Rhodes, Robert S. Snyder
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Patent number: 6224775Abstract: 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: GrantFiled: September 3, 1998Date of Patent: May 1, 2001Assignee: Villanova UniversityInventors: Joe P. Foley, Sally J. Grieb
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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: 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: 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: 6117326Abstract: 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: GrantFiled: March 31, 1999Date of Patent: September 12, 2000Assignee: Rohm and Haas CompanyInventors: Mark Richard Schure, Willie Lau
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Patent number: 6117293Abstract: 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: GrantFiled: July 31, 1998Date of Patent: September 12, 2000Assignee: BioWhittaker Molecular Applications, Inc.Inventors: Tianhong Zhang, Noriko Kusukawa
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Patent number: 6074542Abstract: 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: GrantFiled: June 3, 1999Date of Patent: June 13, 2000Inventors: Vladislav Dolnik, Marcella Chiari
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Patent number: 6068767Abstract: 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: GrantFiled: October 29, 1998Date of Patent: May 30, 2000Assignee: Sandia CorporationInventors: Michael G. Garguilo, Phillip H. Paul, David J. Rakestraw
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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: 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: 6001232Abstract: 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: GrantFiled: September 4, 1996Date of Patent: December 14, 1999Assignee: The Research Foundation of State University of New YorkInventors: Benjamin Chu, Chunhung Wu
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Patent number: 5993626Abstract: 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: GrantFiled: January 24, 1997Date of Patent: November 30, 1999Inventors: James P. Landers, Rajani Prasad, Robert P. Oda, Robert L. Stout
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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: 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: 5964996Abstract: 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: GrantFiled: November 6, 1998Date of Patent: October 12, 1999Assignee: Curators of the University of MissouriInventor: Daniel Armstrong
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Patent number: 5964999Abstract: 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: GrantFiled: December 18, 1996Date of Patent: October 12, 1999Assignee: Beckman Instruments, Inc.Inventors: Andras Guttman, Nelson H. Cooke
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Patent number: 5963456Abstract: A method and apparatus for displaying capillary electrophoresis data wherein absorbance with respect to time is related to graphic values within a graphic range or scale of values and selected graphic values are displayed with respect to time. The selected graphic values may comprise a range hues, color saturation and/or brightness or may represent a monochromatic scale. The resulting representation may be horizontally aligned with the corresponding electrophoretogram absorbance values to provide both a quantitative value (electrophoretogram absorbance values) and qualitative (graphic stripe) display.Type: GrantFiled: November 27, 1996Date of Patent: October 5, 1999Assignee: Beckman Instruments, Inc.Inventors: Gerald L. Klein, Steven P. Katzmann
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Patent number: 5948227Abstract: 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: December 17, 1997Date of Patent: September 7, 1999Assignee: Caliper Technologies Corp.Inventor: Robert S. Dubrow
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Patent number: 5938905Abstract: 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: GrantFiled: February 28, 1997Date of Patent: August 17, 1999Assignee: Max-Planck-Gesellschaft zur Forderung der Wissenschaften e.V.Inventors: Robert Clegg, Leonardo Erijman
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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: 5916426Abstract: 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: GrantFiled: August 19, 1997Date of Patent: June 29, 1999Assignee: The Perkin-Elmer CorporationInventors: Ramakrishna S. Madabhushi, Steven M. Menchen, J. William Efcavitch, Paul D. Grossman
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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: 5863401Abstract: 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: GrantFiled: July 3, 1997Date of Patent: January 26, 1999Assignee: Beckman Instruments, Inc.Inventor: Fu-Tai A. Chen
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Patent number: RE37606Abstract: 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: GrantFiled: August 5, 1999Date of Patent: March 26, 2002Assignee: Beckman Coulter, Inc.Inventor: Andras Guttman