Capillary Electrophoresis Type Patents (Class 204/601)
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Patent number: 6725882Abstract: Disclosed is a micro flowguide device comprising: a micro channel comprising at least one bubble trap to retard bubbles positioned in said bubble trap; an electrolytic bubble generating device to generate bubbles in said fluid by an electrolytic reaction; and a pressure source to supply a suited pressure to said fluid to pass through said micro channel; wherein said electrolytic bubble generating device causes bubbles to be generated at areas adjacent to said at least one bubble trap. Electrolytic bubbles are generated through a, localized electrolytic reaction enabled by the exposure of a set of DC-source-connected electrodes inside a conduit branch. Accumulated bubbles will be trapped and kept at several traps of the invented flowguide. When the backward pressure of trapped bubbles is rising to the level of forward pressure head, flow speed reduces to zero and channel branch is shut down.Type: GrantFiled: January 3, 2003Date of Patent: April 27, 2004Assignee: Industrial Technology Research InstituteInventors: Tim K. Shia, Jhy-Wen Wu, Nan-Kuang Yao, Yuan-Fong Kuo, Shaw-Hwa Pang
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Publication number: 20040071600Abstract: A plate assembly has a plate member (1, 21, 101) having a recessed portion (3, 23, 103), and a lid member (2, 22, 102) mounted on the plate member to cover the recessed portion. A gap is formed between the plate member and the lid member around the recessed portion so as to allow a liquid to permeate the gap due to capillarity while preventing the liquid from entering the recessed portion. If the liquid is an adhesive, the lid member (2, 22) is bonded to the plate member (1, 21), the plate member having a bonded surface (4, 26) which is formed so as to surround the recessed portion (3, 23), the plate member having an adhesive relief portion (25) which is formed around the bonded surface so as to be recessed from the bonded surface, the gap being formed between the bonded surface and the lid member so as to allow the adhesive to permeate the gap due to capillarity.Type: ApplicationFiled: July 21, 2003Publication date: April 15, 2004Inventor: Koichi Ono
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Patent number: 6716328Abstract: An architecture or layout for microchannel arrays using T or Cross (+) loading for electrophoresis or other injection and separation chemistry that are performed in microfluidic configurations. This architecture enables a very dense layout of arrays of functionally identical shaped channels and it also solves the problem of simultaneously enabling efficient parallel shapes and biasing of the input wells, waste wells, and bias wells at the input end of the separation columns. One T load architecture uses circular holes with common rows, but not columns, which allows the flow paths for each channel to be identical in shape, using multiple mirror image pieces. Another T load architecture enables the access hole array to be formed on a biaxial, collinear grid suitable for EDM micromachining (square holes), with common rows and columns.Type: GrantFiled: March 29, 2000Date of Patent: April 6, 2004Assignee: The Regents of the University of CaliforniaInventor: Stefan P. Swierkowski
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Publication number: 20040060822Abstract: A microfluidic device made from nanolaminate materials that are capable of electrophoretic selection of particles on the basis of their mobility. Nanolaminate materials are generally alternating layers of two materials (one conducting, one insulating) that are made by sputter coating a flat substrate with a large number of layers. Specific subsets of the conducting layers are coupled together to form a single, extended electrode, interleaved with other similar electrodes. Thereby, the subsets of conducting layers may be dynamically charged to create time-dependent potential fields that can trap or transport charge colloidal particles. The addition of time-dependence is applicable to all geometries of nanolaminate electrophoretic and electrochemical designs from sinusoidal to nearly step-like.Type: ApplicationFiled: September 30, 2002Publication date: April 1, 2004Applicant: The Regents of the University of CaliforniaInventors: Michael P. Surh, William D. Wilson, Troy W. Barbee, Stephen M. Lane
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Publication number: 20040058423Abstract: The invention provides apparatus and methods for subsecond lysis of selected cells in a cell chamber using a voltage pulse of 10 ms to 10 &mgr;s in duration followed by nearly simultaneous collection of the lysed cellular contents into a capillary electrophoresis tube or other suitable micro-collection device. Cell chambers and capillary electrophoresis tubes configured with electrodes for performing the electrical lysis are described. The influence of variables that govern the rate of cell lysis, such as inter-electrode distance, pulse duration, and pulse strength are also described. The methods are illustrated using fluorophores that are loaded into a cell then collected following electrical lysis, separated by electrophoresis, and then detected by laser-induced fluorescence detection in a capillary electrophoresis system.Type: ApplicationFiled: May 2, 2003Publication date: March 25, 2004Inventors: Nancy Albritton, Guann-Pyng Li, Mark Bachman, Christopher Sims, Futian Han
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Patent number: 6709559Abstract: Fluid introduction is facilitated through the use of a port which extends entirely through a microfluidic substrate. Capillary forces can be used to retain the fluid within the port, and a series of samples or other fluids may be introduced through a single port by sequentially blowing the fluid out through the substrate and replacing the removed fluid with an alternate fluid, or by displacing the fluid in part with additional fluid. In another aspect, microfluidic substrates have channels which varying in cross-sectional dimension so that capillary action spreads a fluid only within a limited portion of the channel network. In yet another aspect, the introduction ports may include a multiplicity of very small channels leading from the port to a fluid channel, so as to filter out particles or other contaminants which might otherwise block the channel at the junction between the channel and the introduction port.Type: GrantFiled: July 30, 2002Date of Patent: March 23, 2004Assignee: Caliper Technologies Corp.Inventors: Steven A. Sundberg, J. Wallace Parce, Calvin Y. H. Chow
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Patent number: 6706164Abstract: In a method for controlling sample introduction in microcolumn separation techniques, more particularly in capillary electrophoresis (CE), where a sample is injected as a sample plug into a sampling device which comprises at least a channel for the electrolyte buffer and a supply and drain channel for the sample. The supply and drain channels discharge into the electrolyte channel at respective supply and drain ports. The distance between the supply port and the drain port geometrically defines a sample volume. The injection of the sample plug into the electrolyte channel is accomplished electrokinetically by applying an electric field across the supply and drain channels for a time at least long enough that the sample component having the lowest electrophoretic mobility is contained within the geometrically defined volume. The supply and drain channels each are inclined to the electrolyte channel. Means are provided for electrokinetically injecting the sample into the sample volume.Type: GrantFiled: December 13, 2000Date of Patent: March 16, 2004Assignee: Zeptosens AGInventors: Andreas Manz, D. Jed Harrison, Carlo S. Effenhauser
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Patent number: 6706161Abstract: Methods and compositions for modifying the surface of a polymeric substrate are provided. In the subject methods, at least a portion of the surface of the polymeric substrate is contacted with a biofouling resistant surfactant composition. At least a portion of the surfactant molecules of the composition are end modified with a non-reactive, charged end group that is charge stable over a pH range of a bout 2 to 12. The subject methods and compositions find particular use with electrophoretic devices, such as capillary electrophoretic devices.Type: GrantFiled: June 10, 1998Date of Patent: March 16, 2004Assignee: Agilent Technologies, Inc.Inventors: Sally A. Swedberg, Karla M. Robotti, Karin Caldwell
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Publication number: 20040045828Abstract: The invention is directed to a capillary tube for electrophoresis that has a positively charged coating on the capillary inner surface that prevents positively charged analytes from adsorbing to the inner capillary surface. The capillary tube has an inner surface that is coated with a first polymer layer having a plurality of polymer groups comprising polyethylene imine, designated herein as (CH2CH2NH)x. The inner surface of the capillary typically has a second polymer layer covalently bonded to the first polymer layer. The invention includes a capillary tube where two or more than two polymer groups are covalently bonded to each other by a cross-linker. Also provided are an electrophoresis system the uses the coated capillary tubes, a method of performing electrophoresis that utilizes the coated capillary tubes, and a process for preparing the coated capillary tubes.Type: ApplicationFiled: September 9, 2002Publication date: March 11, 2004Inventors: Chitra K. Ratnayake, Isabel C. Flores
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Publication number: 20040040850Abstract: A modular multiple lane or capillary electrophoresis (chromatography) system that permits automated parallel separation and comprehensive collection of all fractions from samples in all lanes or columns, with the option of further on-line automated sample fraction analysis, is disclosed. Preferably, fractions are collected in a multi-well fraction collection unit, or plate. The multi-well collection plate is preferably made of a solvent permeable gel, most preferably a hydrophilic, polymeric gel such as agarose or cross-linked polyacrylamide.Type: ApplicationFiled: August 29, 2003Publication date: March 4, 2004Applicant: NORTHEASTERN UNIVERSITYInventors: Barry L. Karger, Lev Kotler, Frantisek Foret, Marek Minarik, Karel Kleparnik
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Patent number: 6699377Abstract: In a method for controlling sample introduction in microcolumn separation techniques, more particularly in capillary electrophoresis (CE), where a sample is injected as a sample plug into a sampling device which comprises at least a channel for the electrolyte buffer and a supply and drain channel for the sample. The supply and drain channels discharge into the electolyte channel at respective supply and drain ports. The distance between the supply port and the drain port geometrically defines a sample volume. The injection of the sample plug into the electrolyte channel is accomplished electrokinetically by applying an electric field across the supply and drain channels for a time at least long enough that the sample component having the lowest electrophoretic mobility is contained within the geometrically defined volume. The supply and drain channels each are inclined to the electrolyte channel. Means are provided for electrokinetically injecting the sample into the sample volume.Type: GrantFiled: December 22, 2000Date of Patent: March 2, 2004Assignee: Zeptosens AGInventors: Andreas Manz, D. Jed Harrison, Carlo S. Effenhauser
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Patent number: 6699378Abstract: In a method for controlling sample introduction in microcolumn separation techniques, more particularly in capillary electrophoresis (CE), where a sample is injected as a sample plug into a sampling device which comprises at least a channel for the electrolyte buffer and a supply and drain channel for the sample. The supply and drain channels discharge into the electrolyte channel at respective supply and drain ports. The distance between the supply port and the drain port geometrically defines a sample volume. The injection of the sample plug into the electrolyte channel is accomplished electrokinetically by applying an electric field across the supply and drain channels for a time at least long enough that the sample component having the lowest electrophoretic mobility is contained within the geometrically defined volume. The supply and drain channels each are inclined to the electrolyte channel. Means are provided for electrokinetically injecting the sample into the sample volume.Type: GrantFiled: December 22, 2000Date of Patent: March 2, 2004Assignee: Zeptosens AGInventors: Andreas Manz, D. Jed Harrison, Carlo S. Effenhauser
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Publication number: 20040035701Abstract: Nanofluidic entropic traps, comprising alternating thin and thick regions, sieve small molecules such as DNA or protein polymers and other molecules. The thick region is comparable or substantially larger than the molecule to be separated, while the thin region is substantially smaller than the size of the molecules to be separated. Due to the molecular size dependence of the entropic trapping effect, separation of molecules may be achieved. In addition, entropic traps are used to collect, trap and control many molecules in the nanofluidic channel. A fabrication method is disclosed to provide an efficient way to make nanofluidic constrictions in any fluidic devices.Type: ApplicationFiled: August 25, 2003Publication date: February 26, 2004Applicant: Cornell Research Foundation, Inc.Inventors: Jongyoon Han, Harold G. Craighead
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Patent number: 6695009Abstract: Methods of concentrating materials within microfluidic channel networks by moving materials into regions in which overall velocities of the material are reduced, resulting in stacking of the material within those reduced velocity regions. These methods, devices and systems employ static fluid interfaces to generate the differential velocities, as well as counter-current flow methods, to concentrate materials within microscale channels.Type: GrantFiled: October 30, 2001Date of Patent: February 24, 2004Assignee: Caliper Technologies Corp.Inventors: Ring-Ling Chien, Benjamin N. Wang
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Publication number: 20040026251Abstract: The invention relates to an electrophoresis device comprising a separation chamber that is provided with at least one sample inlet on the inlet side and outlets (9) for the electrophoretically treated sample species on the outlet side. The separation chamber is divided into two chamber parts (7, 8) by at least one separation element (2) which is selectively permeable for specific sample species and has a continuos inner space extending longitudinally, especially a hollow fiber, from the inlet to the outlet side. Electrodes (4) are disposed parallel to the separation element on both sides of the separation chamber.Type: ApplicationFiled: June 18, 2003Publication date: February 12, 2004Inventor: Gerhard Weber
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Publication number: 20040020773Abstract: An apparatus and method for determining and/or monitoring electrophysiological properties of ion channels of ion-channel containing structures uses AC driven location electrodes to drive objects for analysis to a measurement site. The measurement site may comprise an aperture between two solution-containing compartments, each compartment containing a respective measurement electrode. The aperture includes an adhesion region at its periphery and is dimensioned so that the object for analysis cannot pass through the aperture. Alternatively, the measurement site may comprise a measurement electrode surrounded by an adhesion region appropriately dimensioned to receive the object, to which the object may adhere, and a second measurement electrode remote therefrom.Type: ApplicationFiled: June 19, 2002Publication date: February 5, 2004Inventors: Lars Thomsen, Dirk Reuter, John Dodgson, Anders Wolff, Jamil El-Ali
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Publication number: 20040023410Abstract: Disclosed is a method and apparatus for matrix-assisted laser desorption ionization (MALDI), whereby the components of a sample separated by the column of a chromatographic separation device such as a liquid chromatograph or capillary electrophoresis are eluted and deposited on a sample support plate in a continuous track which both concentrates the sample components and preserves the fidelity of the separation. Analysis by MALDI is thus decoupled from the requirements of the separation and deposition and is performed by moving the continuous track relative to a focused laser beam in order to ionize the sample. The deposition capillary is in relative motion to the sample support plate with a speed of motion compatible with the liquid flow rate.Type: ApplicationFiled: August 5, 2002Publication date: February 5, 2004Inventor: Catherine Stacey
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Patent number: 6685809Abstract: A microfabricated device employing a bridging membrane and methods for electrokinetic transport of a liquid phase biological or chemical material using the same are described. The bridging membrane is deployed in or adjacent to a microchannel and permits either ionic current flow or the transport of gas species, while inhibiting the bulk flow of material. The use of bridging membranes in accordance with this invention is applicable to a variety of processes, including electrokinetically induced pressure flow in a region of a microchannel that is not influenced by an electric field, sample concentration enhancement and injection, as well as improving the analysis of materials where it is desired to eliminate electrophoretic bias. Other applications of the bridging membranes according to this invention include the separation of species from a sample material, valving of fluids in a microchannel network, mixing of different materials in a microchannel, and the pumping of fluids.Type: GrantFiled: February 4, 1999Date of Patent: February 3, 2004Assignee: UT-Battelle, LLCInventors: Stephen C. Jacobson, J. Michael Ramsey, Christopher T. Culbertson, William B. Whitten, Robert S. Foote
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Patent number: 6681788Abstract: Methods devices and systems that employ non-mechanical valve modules for controllably directing fluid and other material movement through integrated microscale channel networks. These non-mechanical valve modules apply forces that counter the driving forces existing through a given channel segment, via fluidly connected channel segments, so as to selectively arrest flow of material within the given channel segment.Type: GrantFiled: January 24, 2002Date of Patent: January 27, 2004Assignee: Caliper Technologies Corp.Inventors: J. Wallace Parce, Andrea W. Chow
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Patent number: 6677593Abstract: An electrospray ion source includes a chamber including a channel region therein, the channel including at least one inlet for directing a solution into the channel and at least a first and a second outlet for transmitting the solution or derivatives therefrom out from channel. Structure for separating ions in the solution is provided from separating the solution into at least a first and a second flow stream portion. The first flow stream portion is enriched in negative ions and the second flow stream portion is enriched in positive ions. The first flow stream portion is adapted to exit the chamber through the first outlet while the second flow stream portion is adapted to exit the chamber through the second outlet. A method of charge separation can include the step of simultaneously providing at least two gas phase ion stream portions having opposite polarity.Type: GrantFiled: August 28, 2002Date of Patent: January 13, 2004Assignee: UT-Battelle, LLCInventor: Gary J. Van Berkel
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Patent number: 6675821Abstract: With a method of controlling the flow in a flow system where a liquid flow contains a particle concentration, the liquid flow is surrounded by a carrier liquid. The liquid flow and carrier liquid are led into a central channel in which there is provided an observation area (4) where measurements of the liquid flow are effected. The result of the measurements are used to lead the liquid flow into one of several channels, in that control liquids are introduced into the liquid flow before this reaches the channels, the control liquids being derived from a capillary pump structure which pumps on the basis of an electro-kinetic effect, e.g. an electro-osmotic effect. In a preferred embodiment, the pump structure consists of two capillary structures, to each of which an electrical field can be applied. Depending on the strength of the field, the amount of control liquid will be able to be controlled so that the liquid flow with the particle concentration can be led to one of two channels.Type: GrantFiled: October 21, 2002Date of Patent: January 13, 2004Assignee: Scandinavian Micro Biodevices A/SInventor: Claus Barholm-Hansen
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Publication number: 20040003997Abstract: A capillary electrophoresis system includes a plurality of capillaries arranged in parallel on a vertical plane at an identical distance from each other, each of which has a sample injection end immersed in a cathode buffer 23 and pointed downward vertically to facilitate connection between the cathode buffer 23 and a sample solution. The sample elution end is connected via a pump block 11 and a connection tube 3 to an anode buffer 24. The height is made identical between the liquid levels for buffers 23 and 24 to prevent movement of the separation medium in the capillaries. The sample introduced from the sample injection end 20 moves upward vertically via electrophoresis to the sample elution end in the capillary and is passed through and detected at the fluorescence detection position 19. The effective separation length is thus decreased to 10 cm or less to attain high throughput.Type: ApplicationFiled: July 1, 2003Publication date: January 8, 2004Applicant: Hitachi, Ltd.Inventors: Takashi Anazawa, Takashi Irie, Masao Kamahori
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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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Publication number: 20040000483Abstract: The present invention is a capillary electrophoresis device, comprising a substrate; a first channel in the substrate, and having a buffer arm and a detection arm; a second channel in the substrate intersecting the first channel, and having a sample arm and a waste arm; a buffer reservoir in fluid communication with the buffer arm; a waste reservoir in fluid communication with the waste arm; a sample reservoir in fluid communication with the sample arm; and a detection reservoir in fluid communication with the detection arm. The detection arm and the buffer arm are of substantially equal length.Type: ApplicationFiled: February 10, 2003Publication date: January 1, 2004Inventors: Douglas J. Jackson, Thomas J. Roussel, Mark M. Crain, Richard P. Baldwin, Robert S. Keynton, John F. Naber, Kevin M. Walsh, John. G. Edelen
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Publication number: 20030230489Abstract: A low-dispersion methodology for designing microfabricated conduction channels for on-chip electrokinetic-based systems is presented. The technique relies on trigonometric relations that apply for ideal electrokinetic flows, allowing faceted channels to be designed on chips using common drafting software and a hand calculator. Flows are rotated and stretched along the abrupt interface between adjacent regions with differing permeability. Regions bounded by interfaces form flow “prisms” that can be combined with other designed prisms to obtain a wide range of turning angles and expansion ratios while minimizing dispersion. Designs are demonstrated using two-dimensional numerical solutions of the Laplace equation.Type: ApplicationFiled: June 6, 2003Publication date: December 18, 2003Inventors: Eric B. Cummings, Gregory J. Fiechtner
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Patent number: 6663757Abstract: The aim of the invention is to convectively move at least one liquid in a channel of a microsystem which comprises a predetermined channel direction. To this end, the liquid is, in a partial section of the channel, subjected to an electric field gradient and optionally to a thermal gradient. The gradients are generated in the partial section corresponding to a predetermined field direction, whereby the field direction differs from the channel direction.Type: GrantFiled: August 6, 2001Date of Patent: December 16, 2003Assignee: Evotec Technologies GmbHInventors: Günter Führ, Torsten Müller, Thomas Schnelle, Rolf Hagedorn
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Patent number: 6662830Abstract: Sample processing devices with electrophoresis channels and methods of loading the electrophoresis channels with electrophoresis sieving polymer while rotating the sample processing device are disclosed. In some instances, the electrophoresis channels may be arranged radially relative to the axis of rotation of the sample processing device. In other sample processing devices, the electrophoresis channels may be arranged in curved arcs that are concentric about the center of the sample processing device (which preferably corresponds to the axis of rotation).Type: GrantFiled: January 21, 2003Date of Patent: December 16, 2003Assignee: 3M Innovative Properties CompanyInventors: William Bedingham, Raj Rajagopal, Kannan Seshadri
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Publication number: 20030226754Abstract: A analyte species separation system including a fluid flow field disposed between confining surfaces, the flow field having a first flow component flowing in a first direction and a second flow component flowing in a second, transverse, direction, and an electric field configured to cause analyte species to move in the separation flow field at least in a direction opposite to the first flow component, a analyte injection channel in fluid communication with the flow field and an analyte separation target channel or otherwise a collector in fluid communication with the flow field, the system configure so that an analyte species in an analyte sample injected into the flow field traverses at least a portion of the flow field toward the collector target channel with said second flow component, enabling analyte species separation parallel to the first direction and movement in the second direction so that analyte species having mobilities outside a selected mobility range do not enter the target channel and/or an aType: ApplicationFiled: March 14, 2003Publication date: December 11, 2003Inventor: David A. Le Febre
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Publication number: 20030226756Abstract: An electrophoresis apparatus includes a multi-capillary array having a liquid or solid disposed between the capillaries of the array. The liquid or solid exhibits a refractive index higher than that of air and less than that of water and reduces the amount of laser beams scattered by the capillaries. Also provided are methods of adjusting refracted and reflected excitation light beams passing through capillaries of a multi-capillary array, to reduce loss of intensity of the laser beams and increase irradiation of respective samples disposed in the capillaries.Type: ApplicationFiled: September 30, 2002Publication date: December 11, 2003Inventors: Ryoji Inaba, Tomohiro Shoji, Shozo Kasai, Masaya Kojima, Yasushi Shimizu, Seiichi Ugai, Eric S. Nordman
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Patent number: 6660149Abstract: A modular multiple lane or capillary electrophoresis (chromatography) system that permits automated parallel separation and comprehensive collection of all fractions from samples in all lanes or columns, with the option of further on-line automated sample fraction analysis, is disclosed. Preferably, fractions are collected in a multi-well fraction collection unit, or plate (40). The multi-well collection plate (40) is preferably made of a solvent permeable gel, most preferably a hydrophilic, polymeric gel such as agarose or cross-linked polyacrylamide.Type: GrantFiled: April 24, 2000Date of Patent: December 9, 2003Assignee: Beckman Coulter, Inc.Inventors: Barry L. Karger, Lev Kotler, Frantisek Foret, Marek Minarik, Karel Kleparnik
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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: 20030217924Abstract: 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° C. to about 50° 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 5×103 to about 1×106 daltons, and (iv) absence of charged groups in an aqueous medium having pH in the range of about 6 to about 9.Type: ApplicationFiled: December 28, 2001Publication date: November 27, 2003Applicant: PE Corporation (NY)Inventors: Ramakrishna S. Madabhushi, Steven M. Menchen, J. William Efcavitch, Paul D. Grossman
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Publication number: 20030217923Abstract: 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: ApplicationFiled: May 24, 2002Publication date: November 27, 2003Inventors: D. Jed Harrison, Abebaw Belay Jemere
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Patent number: 6648015Abstract: The present invention provides multi-layer microfluidic systems, by providing additional substrate layers, e.g., third, fourth, fifth and more substrate layers, mated with the typically described first and second layers. Microfabricated elements, e.g., grooves, wells and the like, are manufactured into the surfaces between the various substrate layers. These microfabricated elements define the various microfluidic aspects or structures of the overall device, e.g., channels, chambers and the like. In preferred aspects, a separate microscale channel network is provided between each of the substrate layers.Type: GrantFiled: October 3, 2002Date of Patent: November 18, 2003Assignee: Caliper Technologies Corp.Inventor: Calvin Y. H. Chow
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Publication number: 20030205470Abstract: A microchip laboratory system and method provide fluid manipulations for a variety of applications, including sample injection for microchip chemical separations. The microchip is fabricated using standard photolithographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis and electrochromatography are performed in channels formed in the substrate. Analytes are loaded into a four-way intersection of channels by electrokinetically pumping the analyte through the intersection, followed by switching of the potentials to force an analyte plug into the separation channel.Type: ApplicationFiled: April 30, 2003Publication date: November 6, 2003Inventor: J. Michael Ramsey
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Patent number: 6637463Abstract: Methods and apparatus are presented for controlling fluid flow through flow paths with pressure gradient fluid control. Passive fluid flow barriers may be used to act as valves, thereby allowing the flow of fluids through flow paths to be regulated so as to allow fluids to be introduced via a single channel and subsequently split into multiple channels. Flow through the flow paths can be regulated to allow a series of sister wells or chambers to all fill prior to the fluid flowing beyond any one of the sister wells or chambers. Each flow path may have multiple segments, at least one of which is designed to balance the pressure drops of the flow paths to provide uniform flow of fluids through the flow paths. The configurations of the wells may also be modified by adding vents or flow dividers to enhance fluid flushing and gas removal capability.Type: GrantFiled: May 10, 2002Date of Patent: October 28, 2003Assignee: BioMicro Systems, Inc.Inventors: Ming Lei, Nils B. Adey, Michael R. McNeely
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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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Publication number: 20030196900Abstract: A hydrogel-driven micropump, comprising: two fluid chambers; a fluid channel, connecting the two fluid chambers; a first substrate plate and a second substrate plate, which are glass wafers produced by micromechanical working, each having accommodating spaces which are placed next to the two fluid chambers and connected by inward extending bridges, with electric terminals leading to the accommodating spaces; a middle substrate, sandwiched between the first and second substrate plates and made by a bulk micromachining process, having separated accommodating spaces close to ends thereof. A separating block is placed between the accommodating spaces. The middle substrate between the first and second substrate plates forms a micropump body. All of the substrates are separated by membranes. The accommodating spaces for electrophoretic fluid are located between the membranes and the first and second substrate plates, respectively, and insulating material.Type: ApplicationFiled: June 4, 2002Publication date: October 23, 2003Inventors: Sway Chuang, Morris Liang, Frank Fan, Wae-Honge Chen
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Patent number: 6632400Abstract: A microfluidic component having a microfluidic channel is bonded to an electronics component having a circuit for processing signals related to the microfluidic component. In an embodiment, the electronics component is a prefabricated integrated circuit chip that includes signal processing and/or process control functionality. The bonding of the microfluidic component to the electronics component provides a modular architecture in which different combinations of microfluidic components and electronics components can be used to create customized processing and analysis tools.Type: GrantFiled: June 22, 2000Date of Patent: October 14, 2003Assignee: Agilent Technologies, Inc.Inventors: Reid A. Brennen, Antonius A. A. M. van de Goor
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Patent number: 6627076Abstract: The present invention provides compact geometries for the layout of microchannel columns through the use of turns and straight channel segments. These compact geometries permit the use of long separation or reaction columns on a small microchannel substrate or, equivalently, permit columns of a fixed length to occupy a smaller substrate area. The new geometries are based in part on mathematical analyses that provide the minimum turn radius for which column performance in not degraded. In particular, we find that straight channel segments of sufficient length reduce the required minimum turn radius, enabling compact channel layout when turns and straight segments are combined. The compact geometries are obtained by using turns and straight segments in overlapped or nested arrangements to form pleated or coiled columns.Type: GrantFiled: October 19, 2001Date of Patent: September 30, 2003Assignee: Sandia National LaboratoriesInventor: Stewart Griffiths
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Patent number: 6627446Abstract: A substrate with a plurality of microchannels is movably deployed with other movable objects that will load sample into the microchannels, stimulate molecular migration, read the results of the migration, remove and replace the substrate, and prepare for a new run. The other objects include a gripper for engaging and moving the substrate, an electrode array of fine wires suitable for fitting into the microchannels for electromigration, and a scanning detector for reading migration results. A sequence of automatic operations is established so that one substrate after another may be moved into position, loaded with sample, stimulated for molecular migration, read with a beam, and then removed and replaced with a fresh substrate.Type: GrantFiled: July 2, 1998Date of Patent: September 30, 2003Assignee: Amersham Biosciences (SV) CorpInventors: David J. Roach, Robert T. Loder, Jr., Thomas M. Armstrong, Dennis W. Harris, Stevan B. Jovanovich, Richard F. Johnston
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Publication number: 20030178311Abstract: The troublesomeness during the setting of a plurality of capillaries is eliminated by composing pairs of electrodes, which are electrically connected to the common electrode, and capillaries.Type: ApplicationFiled: April 15, 2003Publication date: September 25, 2003Applicant: Hitachi, Ltd.Inventors: Muneo Maeshima, Kazumichi Imai, Masaya Kojima, Satoshi Takahashi, Hiromi Yamashita
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Publication number: 20030164295Abstract: An active matrix microfluidic platform employs thin film transistor active (“TFT”) matrix liquid crystal display technology to manipulate small samples of fluid for chemical, biochemical, or biological assays without moving parts, for example, using a two-dimensional matrix array of drive electrodes. The active matrix microfluidic platform may employ existing active matrix addressing schemes and/or commercial “off-the-shelf” animation software to program assay protocols. A feedback subsystem may determine an actual location of a fluid in the microfluidic structure, and provides location information to for display, for example, on an active matrix display, and/or to control movement of one or more fluid bodies in the microfluidic structure.Type: ApplicationFiled: November 26, 2002Publication date: September 4, 2003Applicant: Keck Graduate InstituteInventor: James D. Sterling
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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: 6613212Abstract: The invention concerns a multiple capillary electrophoresis system including many juxtaposed capillaries, at least one source for transmitting a beam designed to excite the molecules present in its path and inside the capillaries, and detection of the fluorescence of the molecules excited by said beam. The invention is arranged so as to detect the light emerging at the output of said capillaries and propagated along a direction wherein the capillaries extend and the detection resolution is sufficient for distinguishing the light emerging at the output of the capillaries from that coming from the walls thereof and/or their surrounding medium.Type: GrantFiled: February 7, 2000Date of Patent: September 2, 2003Assignee: Centre National de la Recherche ScientifiqueInventors: Rainer Siebert, Samuele Bottani, Hans Rebscher, Luc Valentin
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Patent number: 6613525Abstract: Integrated microfluidic devices comprising at least an enrichment channel (10) and a main electrophoretic flowpath (12) are provided. In the subject integrated devices, the enrichment channel and the main electrophoretic flowpath are positioned so that waste fluid flows away from said main electrophoretic flowpath through a discharge outlet (6). The subject devices find use in a variety of electrophoretic applications, including clinical assays, high throughput screening for genomics and pharmaceutical applications, point-or-care in vitro diagnostics, molecular genetic analysis and nucleic acid diagnostics, cell separations, and bioresearch generally.Type: GrantFiled: January 17, 2002Date of Patent: September 2, 2003Assignee: ACLARA Biosciences, Inc.Inventors: Robert J. Nelson, Herbert H. Hooper, Alan K. Hauser, Sharat Singh, Stephen J. Williams, Alexander P. Sassi
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Patent number: 6613211Abstract: Cell based assays are performed in a microfluidic device, where the cells are introduced into a reservoir and are contacted with one or more agents prior to or during their residence in the reservoir or in a capillary channel connected to the reservoir. The cells are moved by electrokinesis individually from the reservoir to a detector, where the status of the cells as a result of contacting said agents is determined. Conditions are provided for moving the cells electrophoretically or by electroosmotic force, where the cells may be viable or fixed, natural or genetically modified.Type: GrantFiled: August 17, 2000Date of Patent: September 2, 2003Assignee: Aclara BioSciences, Inc.Inventors: Randy M. McCormick, Gary J. Ciambrone, Ian Gibbons
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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: 20030155245Abstract: A capillary array comprising multiple capillaries and two holding substrates for arranging the aforementioned multiple capillaries in a substantially plane surface by sandwiching at least some of these capillaries mutually. One of the holding substrates has a detection window for transmitting the detected light emitted by a test sample by irradiation of light. Especially, this detection window comprises multiple light transmission areas provided to correspond to each capillary to transmit the detected light, and light cut-off areas provided between these light transmission areas to cut off the detected light. These light cut-off areas cut off light reflected from the surface of capillaries and hence improve the SN ratio, thereby ensuring high-precision detection.Type: ApplicationFiled: October 24, 2002Publication date: August 21, 2003Inventors: Tomonari Morioka, Yasushi Shimizu, Seiichi Ugai, Toshiaki Kita, Kiyoshi Tsukada
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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