Using Gel-filled Capillary Patents (Class 204/455)
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Patent number: 6878255Abstract: An apparatus for conducting a microfluidic process and analysis, including at least one elongated microfluidic channel, fluidic transport means for transport of fluids through the microfluidic channel, and at least one thick-film electrode in fluidic connection with the outlet end of the microfluidic channel. The present invention includes an integrated on-chip combination reaction, separation and thick-film electrochemical detection microsystem, for use in detection of a wide range of analytes, and methods for the use thereof.Type: GrantFiled: November 2, 2000Date of Patent: April 12, 2005Assignee: Arrowhead Center, Inc.Inventors: Joseph Wang, Baomin Tian, Eskil Sahlin
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Patent number: 6878254Abstract: A sieving medium for use in the separation of analytes in a sample containing at least one such analyte comprises a monomeric non-ionic surfactant of the of the general formula, B-A, wherein A is a hydrophilic moiety and B is a hydrophobic moiety, present in a solvent at a concentration forming a self-assembled micelle configuration under selected conditions and having an aggregation number providing an equivalent weight capable of effecting the size separation of the sample solution so as to resolve a target analyte(s) in a solution containing the same, the size separation taking place in a chromatography or electrophoresis separation system.Type: GrantFiled: February 27, 2002Date of Patent: April 12, 2005Assignee: Iowa State University Research Foundation, Inc.Inventors: Edward S. Yeung, Wei Wei
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Patent number: 6849722Abstract: 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: June 7, 2001Date of Patent: February 1, 2005Assignee: 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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Patent number: 6846399Abstract: 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: GrantFiled: February 28, 2001Date of Patent: January 25, 2005Assignee: Sandia National LaboratoriesInventors: Timothy J. Shepodd, Leroy Whinnery, Jr., William R. Even, Jr.
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Patent number: 6841055Abstract: 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: GrantFiled: May 11, 2001Date of Patent: January 11, 2005Assignee: RikenInventor: Yoshihide Hayashizaki
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Patent number: 6837977Abstract: The invention relates to a capillary electrophoresis-based method of screening complex materials for any unidentified affinity ligand that binds to a target of interest. The method subjects a plug of a mixture of the target and a complex material sample, and a separate plug of a known, tight-binding competitive ligand, to capillary electrophoresis under conditions optimized to allow mingling of the two plugs during the capillary electrophoresis run. Preferably, migration of the competitive ligand is tracked.Type: GrantFiled: June 23, 2000Date of Patent: January 4, 2005Assignee: Cetek CorporationInventors: Yuriy M. Dunayevskiy, Dallas E. Hughes
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Publication number: 20040266021Abstract: A method of injecting, isolating and separating mixed analytes from one or more samples. The method includes collecting successive fractions from each of a plurality of samples at discrete points in time. Fractions may be analyzed at the time of collecting, or later, using one or more detector systems. In one embodiment, a processor controls the elutions of fractions by modulating the migration field in a separation pathway. The processor also controls distribution of the fraction into a particular collection well of a plurality of collection wells.Type: ApplicationFiled: January 28, 2002Publication date: December 30, 2004Inventors: Andras Guttman, Liang Shi, Xun Wang
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Patent number: 6830670Abstract: A medium comprises an electrolyte wherein is dissolved at least an assembly of block copolymers characterized in that the block copolymers: are present in the electrolyte at a concentration level to provide the medium with the property of reversibly passing from a state of viscosity V1, obtained at a temperature T1, to a viscosity state V2 greater by at least 100% than V1, obtained at a temperature T2, and comprise in their structure at least: two non-contiguous polymeric segments having in the electrolyte a lower critical solubility temperature (LCST) and having an average number of atoms along their skeleton more than 50; and a polymeric segment soluble in the electrolyte at temperatures T1 and T2. The invention also concerns the use of the medium for separating analytes.Type: GrantFiled: October 1, 2001Date of Patent: December 14, 2004Assignees: Institut Curie, Centre National de la Recherche Scientifique (C.N.R.S.), Universite Pierre et Marie Curie-Paris VIInventors: Jean-Louis Viovy, Dominique Hourdet, Jan Sudor
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Patent number: 6787016Abstract: 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: GrantFiled: May 1, 2001Date of Patent: September 7, 2004Assignee: Aclara Biosciences, Inc.Inventors: Hongdong Roy Tan, Alexander Sassi, Ingrid Cruzado
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Patent number: 6783992Abstract: Methods for selectively separating at least one component from a multi-component componant fluidic sample are provided. In the subject methods, the fluidic sample is introduced into a micro-fluidic device that includes at least one micro-valve made up of a phase reversible material. The multi-component fluidic sample is then contacted with the microvalve in a microfluidic device under conditions sufficient for the at least one component to enter the microvalve, while the remaining constituents of the fluidic sample remain outside of the microvalve. Also provided are kits for use in practicing the subject methods, where the kits include at least a microfluidic device having a microvalve and instructional material (or means for obtaining the same) on how to use the device in the subject methods. The subject devices find use in a variety of applications, including sample desalting and concentration applications.Type: GrantFiled: January 3, 2001Date of Patent: August 31, 2004Assignee: Agilent Technologies, Inc.Inventors: Karla M. Robotti, Hongfeng Yin
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Patent number: 6780617Abstract: A device for processing a biological sample includes a processing unit having at least one opening to receive a sample vessel and a plurality of processing stations positioned along the opening. The processing stations each have a compression member adapted to compress the sample vessel within the opening and thereby move the sample within the sample vessel among the processing stations. An energy transfer element can be coupled to one or more of the processing stations for transferring thermal energy to the sample at a processing station. The device can be used for PCR processing of nucleic acid samples. A sample vessel of the present invention can be a tubule flow-chamber having a plurality of segments separated by pressure gates. The sample vessel minimizes sample handling by providing a closed tubule in which distinct processing steps can be carried out in each of the segments of the tubule.Type: GrantFiled: February 13, 2001Date of Patent: August 24, 2004Assignee: Chen & Chen, LLCInventor: Shuqi Chen
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Patent number: 6706162Abstract: The invention provides compositions, methods and kits for high speed, high resolution of analytes by capillary electrophoresis starting with uncoated capillaries. The compositions comprise a sieving component, comprising a non-crosslinked acrylamide polymer, and a surface interaction component, comprising at least one uncharged and non-crosslinked water-soluble silica-adsorbing polymer. Methods for employing the novel compositions in capillary electrophoresis are provided. Kits comprising the novel compositions for use in the novel methods are also provided.Type: GrantFiled: September 25, 2000Date of Patent: March 16, 2004Assignee: Applera CorporationInventors: Karl O. Voss, Aldrich N. K. Lau
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Patent number: 6680208Abstract: A method and device is disclosed for rapidly identifying a large number of proteins by placing a protein mixture in a sample chamber of an electrophoresis gel, and performing electrophoresis to separate the mixture by molecular weight, in a direction of separation, into a two-dimensional separation pattern in the gel. The separation pattern is transferred to a membrane, such as a sheet of nitrocellulose, and a plate with a set of separate, side-by-side slots is then applied to the membrane. A different antibody mixture is introduced into each of the slots by perfusing each antibody mixture under pressure through the slots. The antibody mixture that is perfused through each slot recognizes several different proteins of sufficiently different molecular weights that different protein bands can be resolved by the antibody mixture in each slot.Type: GrantFiled: November 19, 1999Date of Patent: January 20, 2004Assignee: Becton, Dickinson and CompanyInventors: Roberto Campos-González, Steven Darrell Hume
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Publication number: 20040003994Abstract: The capillary electrophoresis device using one pressure-resistant syringe (125) is capable of automatically suctioning in polymer solution and injecting polymer solution into a capillary array (100). An electric hook (131) is installed for pulling up the syringe plunger on a push-in action type syringe (125). A check valve (124) is inserted between a polymer bottle (123) and syringe to prevent solution from flowing back into the polymer bottle. As a result, one syringe portion of polymer solution can be suctioned and injected, a large volume of polymer solution can be continuously used and device processing capability is improved.Type: ApplicationFiled: September 20, 2002Publication date: January 8, 2004Inventors: Tomihiro Shoji, Masaya Kojima, Yoshiyuki Okishima, Ryijo Inaba
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Patent number: 6660148Abstract: 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: GrantFiled: February 26, 2001Date of Patent: December 9, 2003Assignee: Hitachi, Ltd.Inventors: Tomohiro Shoji, Yoshiyuki Okishima, Masaya Kojima, Muneo Maeshima
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Patent number: 6660147Abstract: The present invention provides, in one aspect, an apparatus for electrophoretic separation of analytes. In one aspect, the apparatus comprises a disc-shaped substrate defining (1) a central reservoir region, (2) a plurality of electrophoretic channels in fluid communication with, and emanating substantially radially from, the central reservoir region, the channels being coplanar with each other, and each channel having (i) a proximal end which is linked to the reservoir region, and (ii) a distal end, and preferably (3) for each channel, at least one chamber, and preferably three chambers, linked by a passageway in fluid communication with the distal end of that channel.Type: GrantFiled: July 14, 2000Date of Patent: December 9, 2003Assignee: Applera CorporationInventors: Timothy M. Woudenberg, Reid B. Kowallis
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Publication number: 20030196896Abstract: A method and apparatus are disclosed for screening separation media for performance in capillary electrophoresis. In one aspect the invention comprises concurrently loading a plurality of capillaries from one corresponding end of each with a respective plurality of separation media, adding a sample to each capillary, advancing the samples through the capillaries under an applied electric field, measuring a property of the samples or components thereof as they advance through the capillaries, and using the measured properties to identify one or more preferred sets of separation media. At least one of the steps of loading or advancing are carried out simultaneously over the plurality of capillaries.Type: ApplicationFiled: April 17, 2002Publication date: October 23, 2003Inventors: Thomas Harding McWaid, Oleg Kolosov, Gerrit Klaerner, Miroslav Petro, Son Hoai Nguyen, Sigrid Kuebler
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Patent number: 6613512Abstract: Electrokinetic devices having a computer for correcting for electrokinetic effects are provided. Methods of correcting for electrokinetic effects by establishing the velocity of reactants and products in a reaction in electrokinetic microfluidic devices are also provided. These microfluidic devices can have substrates with channels, depressions, and/or wells for moving, mixing and monitoring precise amounts of analyte fluids.Type: GrantFiled: December 5, 2000Date of Patent: September 2, 2003Assignee: Caliper Technologies Corp.Inventors: Anne R. Kopf-Sill, Andrea W. Chow, Claudia B. Jaffe, Steven A. Sunberg, John Wallace Parce
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Patent number: 6610186Abstract: The invention concerns a method for separating particles or molecules whereby these particles or molecules are introduced in a separating medium and a moving force is applied to them in said medium. The method is characterised in that the separating medium is a ferrofluid, i.e. a colloidal suspension of magnetic particles and a magnetic field is applied to this ferrofluid generating therein at least an alternation of a zone rich in magnetic particles and a zone poor in magnetic particles, part at least of the region of the ferrofluid in which this alternation is generated is passed through by the particles or molecules to be separated during their migration.Type: GrantFiled: August 30, 1999Date of Patent: August 26, 2003Assignee: Centre National de la Recherche Scientifique (CNRS)Inventors: Pascal Mayer, Jérôme Bibette, Jean-Louis Viovy
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Publication number: 20030156993Abstract: A microfluidic device for achieving protein separation based on charge and molecular weight or size is provided and includes: (1) a first substrate having a raised structure protruding from a first face of the first substrate such that the raised structure partially defines a microfluidic cavity; (2) a second substrate having a raised section protruding from a first face of the second section, wherein the raised section has a shape and dimensions complementary to the microfluidic cavity to permit the raised section to be received between the raised structure to enclose the microfluidic cavity. The raised section seals with the raised structure in a liquid tight manner while still permitting removal of the first and second substrates from one another.Type: ApplicationFiled: December 11, 2002Publication date: August 21, 2003Inventor: Sau Lan Tang Staats
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Publication number: 20030150728Abstract: The invention relates to a method and a device for detecting marked biopolymers, especially nucleic acid fragments in a gel matrix. A parallel separation takes place in a number of microcapillaries that are filled with a gel matrix.Type: ApplicationFiled: February 6, 2003Publication date: August 14, 2003Inventor: Rudolf Rigler
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Publication number: 20030146097Abstract: Various embodiments provide, for example, buffer compositions and/or sieving formulations useful in connection with electrophoresis instruments, such as capillary electrophoresis (CE) devices. In various embodiments, a buffer composition can include Bis-Tris, TAPS and/or TAPSO, and, optionally, a chelating agent, such as EDTA. Methods of separating samples containing bio-molecules, such as DNA or RNA, are also described.Type: ApplicationFiled: July 19, 2002Publication date: August 7, 2003Applicant: APPLERA CORPORATIONInventors: Kevin J. Hacker, Karl O. Voss
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Patent number: 6602391Abstract: An apparatus and method are described for capillary separation of macromolecules and precise post-separation blotting. Apparatus include disposable separating element (capillary), which contains a sieving or interaction matrix inside, an external layer of blotting material, positioned close to the boundary of said sieving or interaction matrix, and the membrane with changeable permeability for separated material; said membrane separates blotting layer from the sieving or interaction matrix. After separation of macromolecules in capillary with initially non-permeable walls, chemical or physical modification of the membrane is performed, which is followed by changing the vector of driving forces for transfer, so that separated molecules are moved through the walls of the capillary and blotted to the outer layer of separating element, which contains blotting material. Means of modification of the membrane include chemical or physical modification, leading to changes in permeability.Type: GrantFiled: March 5, 2001Date of Patent: August 5, 2003Inventor: Vladimir B. Serikov
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Publication number: 20030132113Abstract: The invention relates to a method by which a sample can be taken from a process and be analyzed by means of a capillary electrophoresis apparatus on-line, and to a capillary electrophoresis apparatus which comprises containers containing a background electrolyte solution, the containers communicating with each other by mediation of a separation capillary (1), current electrodes (E) connected to a source of voltage, and a detector (4) substantially in the vicinity of the exit end of the separation capillary (1), as well as one or more solution containers on the injection side of the apparatus, at least one of the containers being a sample collector in which the sample coming from the process is collected, and one or more solution containers on the detector side of the apparatus, the ends of the said separation capillary (1) being located in expansions (5, 6) continuing from the lower ends of capillary ducts (2, 3) intended for feeding in various solutions from the containers, the said expansions continuing asType: ApplicationFiled: December 9, 2002Publication date: July 17, 2003Inventors: Timo Sarme, Rauno Virtanen
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Publication number: 20030127328Abstract: A multi-capillary electrophoresis apparatus is provided for reducing errors during analysis caused by fluctuations in electrophoresis time among plural capillaries of the apparatus. The multi-capillary electrophoresis apparatus can contain a multi-capillary array that has a separation medium filled therein for isolating a sample. A detector component can be provided at a position remote from a sample injecting end of the array for acquiring information from the sample. A buffer container can be provided for holding a buffer solution into which the sample injecting end can be immersed. One or more temperature controlling component devices can be arranged for controlling a temperature of the buffer solution, of the detector component, or of both the buffer solution and the detector component.Type: ApplicationFiled: December 4, 2002Publication date: July 10, 2003Inventors: Eric S. Nordman, Miho Ozawa, Masaya Kojima, Ryoji Inaba, Yoshitaka Kodama, Motohiro Yamazaki
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Publication number: 20030121783Abstract: The present invention includes apparatus for simultaneous loading of multiple samples for molecular separation, including a separation area with walls wherein at least one of the walls has apertures having loading sites, a gel located within the separation area, and a plurality of wells within the gel. The apertures are connected to the plurality of wells by channels structurally configured to convey samples from the apertures to the wells.Type: ApplicationFiled: February 24, 2003Publication date: July 3, 2003Inventors: Shmuel Cabilly, Uri Yogev, Ilana Margalit
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Publication number: 20030106797Abstract: The present method provides methods and apparatus for separating proteins using a series of electrophoretic methods that utilize controlled fractionation and labeling techniques to resolve mixtures of proteins. The samples for each electrophoretic method other than the initial method, contain only a subset of proteins resolved in the preceding method. The methods can be used in a variety of different applications including, creating proteomic databases, comparative expression studies, diagnostics, structure activity relationships and metabolic engineering investigations.Type: ApplicationFiled: January 13, 2003Publication date: June 12, 2003Applicant: Target Discovery, Inc.Inventors: Luke V. Schneider, Michael P. Hall, Robert Petesch
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Patent number: 6576104Abstract: An apparatus and a method for reading a gel electrophoresis pattern can read the gel electrophoresis pattern of a sample, such as a nucleic acid and a protein, with high sensitivity and without requiring the use of an expensive device structure such as a laser light source of unique type.Type: GrantFiled: March 15, 1994Date of Patent: June 10, 2003Assignee: Hitachi Engineering Software Co., Ltd.Inventors: Hisanori Nasu, Yoshitaka Nakamura, Hitoshi Fujimiya, Kenji Yamamoto
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Publication number: 20030075447Abstract: The present invention provides for a column for use in capillary electrochromatography including a tube, wherein the tube includes an inner surface having a positively or negatively charged, chemically-bonded stationary coating thereon. The present invention further provides for a method of making a column for use in capillary electrochromatography, including a tube, wherein the tube includes an inner surface having a positively or negatively charged chemically-bonded stationary coating thereon, wherein the steps include filling the column with a sol-gel solution, maintaining the sol-gel solution within the column, and forcing the sol-gel solution out of the column with an inert gas. Further, the present invention provides for a method of analytical separation with a column including an inner layer having a positively charged chemically-bonded stationary coating thereon that reverses the direction of electroosmotic flow in the column compared with a column without the positive surface charge.Type: ApplicationFiled: January 24, 2002Publication date: April 24, 2003Inventors: Abdul Malik, James D. Hayes
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Patent number: 6542691Abstract: A glass capillary array for fluorescence analysis is provided which is capable of preventing reduction of the transmittance of a laser beam through the glass capillaries during electrophoretic DNA fluorescence analysis, and a method of manufacturing the glass capillary array. The glass capillary array for fluorescence analysis is comprised of a plurality of glass capillaries each having a rectangular cross section and having an internal hole formed therein, and arranged in a row along a direction of irradiation of a laser beam for fluorescence analysis. The glass capillary array has a fluorescence analysis section comprising a portion of each of the glass capillaries positioned in a region including an optical axis of the laser beam and a vicinity thereof, and the glass capillaries are joined together substantially into a single body using a transparent material in at least the fluorescence analysis section.Type: GrantFiled: October 25, 2001Date of Patent: April 1, 2003Assignee: Nippon Sheet Glass Co., Ltd.Inventors: Toshiaki Mizuno, Akihiko Hattori, Takehiko Kitamori
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Patent number: 6524790Abstract: Electrokinetic devices having a computer for correcting for electrokinetic effects are provided. Methods of correcting for electrokinetic effects by establishing the velocity of reactants and products in a reaction in electrokinetic microfluidic devices are also provided. These microfluidic devices can have substrates with channels, depressions, and/or wells for moving, mixing and monitoring precise amounts of analyte fluids.Type: GrantFiled: June 8, 1998Date of Patent: February 25, 2003Assignee: Caliper Technologies Corp.Inventors: Anne R. Kopf-Sill, Andrea W. Chow, Claudia B. Cohen, Steven A. Sundberg, John Wallace Parce
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Publication number: 20030000838Abstract: A sieving medium for use in the separation of analytes in a sample containing at least one such analyte comprises a monomeric non-ionic surfactant of the of the general formula, B-A, wherein A is a hydrophilic moiety and B is a hydrophobic moiety, present in a solvent at a concentration forming a self-assembled micelle configuration under selected conditions and having an aggregation number providing an equivalent weight capable of effecting the size separation of the sample solution so as to resolve a target analyte(s) in a solution containing the same, the size separation taking place in a chromatography or electrophoresis separation system.Type: ApplicationFiled: February 27, 2002Publication date: January 2, 2003Inventors: Edward S. Yeung, Wei Wei
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Publication number: 20020195342Abstract: One embodiment of the invention relates to a microfluidic apparatus for performing two dimensional biomolecular separations. According to one aspect of the invention, after a first dimension separation in a first microchannel, the sample material is electrokinetically and simultaneously transferred to an array of microchannels in the second dimension (e.g., by changing the electric potentials at the reservoirs connected to the microchannels). Preferably any separation accomplished in the first dimension is completely retained upon transfer to the second dimension. According to another aspect of the invention, the separation in the second dimension is performed using a temperature gradient (e.g., a spatial or temporal temperature gradient). According to one embodiment of the invention, the biomolecular material comprises DNA and the first dimension separation is a sized-based separation and the second dimension separation is a sequence-based separation.Type: ApplicationFiled: May 1, 2002Publication date: December 26, 2002Inventors: Cheng Sheng Lee, Donald Lad DeVoe
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Publication number: 20020189948Abstract: A low molecular weight non-entangled polyvinylpyrrolidone for use as a separation media for microchannel electrophoretic separation. The separation media may be used in a system in which multiple samples of small compounds are injected into a single microchannel at time spaced intervals followed by a continuous detection interval.Type: ApplicationFiled: June 15, 2001Publication date: December 19, 2002Inventors: Marek Minarik, Melanie M. Mahtani
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Publication number: 20020175079Abstract: The invention provides a device and method for the manipulation of materials (e.g., particles, cells, macromolecules, such as proteins, nucleic acids or other moieties) in a fluid sample. The device comprises a substrate having a plurality of microstructures and an insulator film on the structures. Application of a voltage to the structures induces separation of materials in the sample. The device and method are useful for a wide variety of applications such as dielectrophoresis (DEP) or the separation of a target material from other material in a fluid sample.Type: ApplicationFiled: April 8, 2002Publication date: November 28, 2002Applicant: CepheidInventors: Lee A. Christel, Gregory T.A. Kovacs, William A. McMillan, M. Allen Northrup, Kurt E. Petersen, Farzad Pourahmadi
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Publication number: 20020170825Abstract: The invention provides a microfluidic apparatus for performing 2-D biomolecular separations. The microfluidic 2-D device may include first and second planar substrates which include at least a first dimension microchannel extending in a first direction and an array of second dimension microchannels extending in a second direction, preferably, orthogonal to the first dimension. The ends of at least some of the microchannels are in fluid communication with a plurality of reservoirs. The substrates may further include a number of microchannels and reservoirs. The reservoirs are in electrical communication with a plurality of electrodes and voltage power sources. The device enables two dimensional separations of proteins and other biomolecules. According to another aspect of the invention, an isoelectric point based separation is enabled in a first dimension, and a size based separation in a second dimension.Type: ApplicationFiled: May 1, 2002Publication date: November 21, 2002Inventors: Cheng Sheng Lee, Don DeVoe
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Publication number: 20020166769Abstract: An apparatus and method are described for capillary separation of macromolecules and precise post-separation blotting. Apparatus include disposable separating element (capillary), which contains a sieving or interaction matrix inside, an external layer of blotting material, positioned close to the boundary of said sieving or interaction matrix, and the membrane with changeable permeability for separated material; said membrane separates blotting layer from the sieving or interaction matrix. After separation of macromolecules in capillary with initially non-permeable walls, chemical or physical modification of the membrane is performed, which is followed by changing the vector of driving forces for transfer, so that separated molecules are moved through the walls of the capillary and blotted to the outer layer of separating element, which contains blotting material. Means of modification of the membrane include chemical or physical modification, leading to changes in permeability.Type: ApplicationFiled: March 5, 2001Publication date: November 14, 2002Inventor: Vladimir B. Serikov
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Patent number: 6475361Abstract: The present invention relates to an electrophoresis apparatus having a filling/refilling system and methods of using the same. The electrophoresis apparatus comprises a first buffer chamber comprising a solid portion, at least one inlet channel in said solid portion, and at least one outlet channel in said solid portion, wherein said at least one inlet channel is in fluid communication with at least one inlet port, said at least one outlet channel is in fluid communication with at least one outlet port and said at least one inlet channel is in fluid communication with said at least one outlet channel. The electrophoresis apparatus also comprises a plurality of capillaries having first ends, second ends, and intermediate portions disposed between said first ends and said second ends, wherein said first ends extend into said first buffer chamber and are in fluid communication with said at least one inlet channel and said at least one outlet channel.Type: GrantFiled: August 19, 1999Date of Patent: November 5, 2002Assignee: Tetragen SAInventors: Irena N. Merenkova, Maxim Brevnov
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Patent number: 6475364Abstract: A method of characterizing a polypeptide, comprising providing a first capillary channel having a separation buffer disposed within, wherein the separation buffer comprises a non-crosslinked polymer solution, a buffering agent, a detergent, and a lipophilic dye. The separation buffer is provided such that, at the time of detection, the detergent concentration in the buffer is not above the critical micelle concentration. The polypeptide is introduced into one end of the capillary channel. An electric field is applied across a length of the capillary channel, which transports polypeptides of different sizes through the polymer solution at different rates. The polypeptide is then detected as it passes a point along the length of the capillary channel.Type: GrantFiled: February 2, 2000Date of Patent: November 5, 2002Assignee: Caliper Technologies Corp.Inventors: Robert S. Dubrow, Christopher Bloxsom, Calvin Y. H. Chow, J. Wallace Parce
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Publication number: 20020153251Abstract: Microfluidic devices are provided where barriers are introduced between different compartments of the device to prevent fluid flow between the two compartments. Different materials and methods are employed for the introduction and removal of the barriers, including reversible gel particle expansion, reversible gellation, in situ polymerization, magnetic beads, and the like. In this way mixing of agents may be temporally controlled during the operation of the device, where the barriers may be used in a passive manner or as an active agent involved in the operation being performed in the device.Type: ApplicationFiled: April 11, 2002Publication date: October 24, 2002Inventors: Alexander Sassi, Aran Paulus
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Publication number: 20020148729Abstract: The method entails using capillary electrophoresis or capillary isoelectric focusing to separate intact microbes. The capillary system can be a conventional capillary tube or a microfluidic device.Type: ApplicationFiled: February 26, 2002Publication date: October 17, 2002Inventor: Daniel Armstrong
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Patent number: 6464850Abstract: The invention relates to a method for producing hydrophilic monomers which are particularly useful for electrophoresis and to electrophoresis compositions and coating compositions. The electrophoresis gel compositions and electrophoresis polymer compositions are hydrolytically stable and have high resolution. 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 29, 1999Date of Patent: October 15, 2002Assignee: BioWhittaker Molecular Applications, Inc.Inventors: Tianhong Zhang, Noriko Kusukawa, Mark Garner
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Publication number: 20020146839Abstract: A method of injecting, isolating and separating mixed analytes from one or more samples. The method includes collecting successive fractions from each of a plurality of samples at discrete points in time. Fractions may be analyzed at the time of collecting, or later, using one or more detector systems. In one embodiment, a processor controls the elutions of fractions by modulating the migration field in a separation pathway. The processor also controls distribution of the fraction into a particular collection well of a plurality of collection wells.Type: ApplicationFiled: January 28, 2002Publication date: October 10, 2002Inventors: Andras Guttman, Liang Shi, Xun Wang
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Patent number: 6461492Abstract: A multi-capillary electrophoresis apparatus arranged with a fixed sample injection holder opposite a detection side holder within the same plane and an epi-optical detection system. A sample is injected sequentially and separated components are successively fed to the detection part for analysis by fluorescence. The epi-optical system adjusts the parallelism between the detection side holder and scanning axis of the detector. Thus, a capillary electrophoretic apparatus can detect fluorescence from a fluorochrome bonded to samples as a label without influence by Raman scattering or Rayleigh scattering.Type: GrantFiled: November 19, 1999Date of Patent: October 8, 2002Assignees: The Institute of Physical and Chemical Research, Shimadzu CorporationInventors: Yoshihide Hayashizaki, Hideshi Fujiwake, Shin Nakamura
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Patent number: 6444461Abstract: Integrated systems, apparatus, software, and methods for performing biochemical analysis, including DNA sequencing, genomic screening, purification of nucleic acids and other biological components and drug screening are provided. Microfluidic devices, systems and methods for using these devices and systems for performing a wide variety of fluid operations are provided. The devices and systems of are used in performing fluid operations which require a large number of iterative, successive or parallel fluid manipulations, in a microscale, or sealed and readily automated format.Type: GrantFiled: September 20, 2000Date of Patent: September 3, 2002Assignee: Caliper Technologies Corp.Inventors: Michael Knapp, John Wallace Parce, Luc J. Bousse, Anne R. Kopf-Sill
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Publication number: 20020117398Abstract: A sample is separated and separated components thereof are successively fed to a part to be detected. A laser beam of at least 600 nm from a laser beam source of an optical measuring part is applied to the part to be detected through a dichroic mirror and a lens, for making a fluorochrome bonded to the separated components absorb multiphotons, exciting the fluorochrome and making the same fluoresce. The optical measuring part captures the fluorescence so that photomultipliers detect fluorescence of not more than 510 nm in wavelength, fluorescence longer than 510 nm and not more than 560 nm in wavelength, fluorescence longer than 560 nm and not more than 580 nm in wavelength and fluorescence longer than 580 in wavelength respectively. Thus, a capillary electrophoretic apparatus can detect fluorescence from a fluorochrome bonded to samples as a label without influence by Raman scattering or Rayleigh scattering.Type: ApplicationFiled: April 22, 2002Publication date: August 29, 2002Inventors: Yoshihide Hayashizaki, Hideshi Fujiwake, Shin Nakamura
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Patent number: 6440284Abstract: 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, 1999Date of Patent: August 27, 2002Assignee: Caliper Technologies Corp.Inventor: Robert S. Dubrow
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Patent number: 6432290Abstract: The present invention provides an on-chip packed reactor bed design that allows for an effective exchange of packing materials such as beads at a miniaturized level. The present invention extends the function of microfluidic analysis systems to new applications including on-chip solid phase extraction (SPE) and on-chip capillary electrochromatography (CEC). The design can be further extended to include integrated packed bed immuno- or enzyme reactors.Type: GrantFiled: November 26, 1999Date of Patent: August 13, 2002Assignee: The Governors of the University of AlbertaInventors: D. Jed Harrison, Richard Oleschuk, Loranelle Shultz-Lockyear, Cameron Skinner, Paul Li
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Patent number: 6428670Abstract: A holder for a capillary cassette closes a chamber, and is fixed to a detection side holder fixing member. An acidic solution container, an alkaline solution container, a pure water container and a drain container are arranged on a reservoir stage having a dry chamber. A holder up/down mechanism and a stage moving mechanism successively bring an end of a capillary array into contact with an acidic solution, an alkaline solution, pure water and nitrogen gas, and the chamber is decompressed for successively introducing these into capillary columns and performing pretreatment. Thereafter a gel container is arranged in the chamber, which in turn is pressurized for charging the capillary columns with a gel.Type: GrantFiled: November 19, 1999Date of Patent: August 6, 2002Assignees: The Institute of Physical and Chemical Research, Shimadzu CorporationInventors: Yoshihide Hayashizaki, Rintaro Yamamoto
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Patent number: RE37941Abstract: The filling 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: December 31, 2002Assignee: Beckman Coulter, Inc.Inventor: Andras Guttman