With Injector Patents (Class 204/604)
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Patent number: 6482364Abstract: The present invention provides for techniques for transporting materials using electrokinetic forces through the channels of a microfluidic system. The subject materials are transported in regions of high ionic concentration, next to spacer material regions of high ionic concentration, which are separated by spacer material regions of low ionic concentration. Such arrangements allow the materials to remain localized for the transport transit time to avoid mixing of the materials. Using these techniques, an electropipettor which is compatible with the microfluidic system is created so that materials can be easily introduced into the microfluidic system. The present invention also compensates for electrophoretic bias as materials are transported through the channels of the microfluidic system by splitting a channel into portions with positive and negative surface charges and a third electrode between the two portions, or by diffusion of the electrophoresing materials after transport along a channel.Type: GrantFiled: May 3, 2001Date of Patent: November 19, 2002Assignee: Caliper Technologies Corp.Inventors: J. Wallace Parce, Michael R. Knapp
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Publication number: 20020166592Abstract: A microfluidic system has an electroosmotic flow (EOF) pumping means for propelling fluids through a series of microchannels and selection valves. Pump channels are configured in groups which may be fabricated singly or in multiple groups onto a substrate. A bubble-free electric connection joint provides for the application of voltages across pump channels while simultaneously blocking the passage of fluids through the joint. Bubble-free electrodes are also provided to prevent electrolysis and bubble formation in or close to the microfluidic channels. The selection valves provide for routing functions within the microfluidic system and can also be configured to route fluids outside the system. A rate monitoring system is provided for determining and compensating for system flow rates. In one application the microfluidic system may be configured to operate as a small volume pipettor or other fluid transport or analysis device.Type: ApplicationFiled: February 11, 2002Publication date: November 14, 2002Inventors: Shaorong Liu, Juan Lu
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Patent number: 6464852Abstract: A multichannel electrophoretic cassette structure is disclosed comprising distinct regions for loading and detection with different spacing between channels. A method and an apparatus are further disclosed enabling multicolor fluorescent detection from a non-coplanar bundle of multiple channels. A method for fabricating monolithic multichannel cassettes for electrophoresis and fluorescent detection is also described.Type: GrantFiled: December 3, 1999Date of Patent: October 15, 2002Assignee: State University of New York at Stony BrookInventors: Vera Gorfinkel, Mikhail Gouzman, Luryi Serge
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Publication number: 20020144907Abstract: An end of a capillary storing a sample in its interior is inserted into a sample reservoir in a microchip and positioned near an inlet of a channel connecting to the sample reservoir. Electrodes are placed in the other end of the capillary and a waste reservoir. A predetermined voltage is applied between the electrodes so that a potential is applied between the other end of capillary and waste reservoir. As a result, the sample in the capillary is introduced electrophoretically into a separating medium in the channel. When the sample has been introduced into the channel after the lapse of a specified time, the voltage application between the electrodes is stopped and the capillary is pulled out of the sample reservoir. The sample can be introduced into the channel without placing it in the sample reservoir in a filling amount.Type: ApplicationFiled: April 8, 2002Publication date: October 10, 2002Applicant: SHIMADZU CORPORATIONInventor: Rintaro Yamamoto
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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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Publication number: 20020139672Abstract: The present invention easies a connection between electrodes of a capillary array device and a connection plate for supplying a high voltage to the electrodes.Type: ApplicationFiled: March 19, 2002Publication date: October 3, 2002Inventors: Syouzou Kasai, Yoshiyuki Okishima, Tomonari Morioka, Yasushi Shimizu, Hiroyuki Tanaka, Takayasu Furukawa, Noriyuki Shimoda, Seiichi Ugai
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Patent number: 6454924Abstract: Embodiments of the invention are directed to microfluidic devices. In one embodiment, a microanalysis chip comprises a body having at least one transfer-separation channel with a channel bottom that has a bottom opening. The transfer-separation channel terminates in a discharge aperture.Type: GrantFiled: February 23, 2001Date of Patent: September 24, 2002Assignee: Zyomyx, Inc.Inventors: Paul Jedrzejewski, Steffen Nock, Peter Wagner, Pierre Indermuhle, Frank G. Zaugg
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Publication number: 20020130044Abstract: An apparatus for manipulating fluid samples is described. The apparatus comprises a micro-chip device having at least a first and second covered channel with openings at either end of said first and second covered channel. The first and second covered channels intersect to form a common intersection. In use at least three of the openings to said first and second covered channels are connected to a multi-port valve to control the pressure in the device.Type: ApplicationFiled: March 19, 2001Publication date: September 19, 2002Inventors: Joel S. Rossier, Frederic Reymond, Hye Jin Lee, Xiaoxia Bai, Hubert H. Girault
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Patent number: 6451188Abstract: 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: March 30, 2000Date of Patent: September 17, 2002Assignee: Caliper Technologies Corp.Inventors: Steven A. Sundberg, J. Wallace Parce, Calvin Y. H. Chow
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Patent number: 6447661Abstract: Methods, apparatus and systems are provided for introducing large numbers of different materials into a microfluidic analytical device rapidly, efficiently and reproducibly. In particular, improved integrated pipettor chip configurations, e.g. sippers or electropipettors, are described which are capable of sampling extremely small amounts of material for which analysis is desired, transporting material into a microfluidic analytical channel network, and performing the desired analysis on the material.Type: GrantFiled: October 12, 1999Date of Patent: September 10, 2002Assignee: Caliper Technologies Corp.Inventors: Andrea W. Chow, Robert S. Dubrow, J. Wallace Parce, Steven A. Sundberg, Jeffrey A. Wolk, Ring-Ling Chien, Steven James Gallagher, Michael R. Knapp, Anne R. Kopf-Sill, Tammy Burd Mehta
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Publication number: 20020121444Abstract: The invention relates to an apparatus for performing gel protein extractions and methods of using the apparatus.Type: ApplicationFiled: January 15, 2002Publication date: September 5, 2002Inventors: Cheng Lee, Don DeVoe
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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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Publication number: 20020112959Abstract: Methods, devices, and systems for unbiased transport of materials on a microfluidic device are disclosed, including methods of maintaining the starting composition of an analyte during transport, and methods of simultaneously analyzing both cationic and anionic components of an analyte. Analyte is loaded into a four-way junction of channels by controlled differential pressure applied to the channels. After analyte loading, an electrical potential is established, forcing charged species into at least one of two separation channels.Type: ApplicationFiled: October 4, 2001Publication date: August 22, 2002Inventors: Qifeng Xue, Ian Gibbons, Randy M. McCormick
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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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Publication number: 20020104759Abstract: A microanalysis system, comprising a microchip, a common well in the microchip, and multiple wells in the microchip, each of the multiple wells being connected for fluid flow to the common well by a channel. The common well is a waste well, and the multiple wells are sample introduction wells. The common well is at the center of the microchip. The channels radiate outward from the common well, and are equally circumferentially spaced. A buffer introduction channel is provided that intersects each of the channels.Type: ApplicationFiled: December 7, 2001Publication date: August 8, 2002Applicant: The Board of Governors of the University of Alberta and Micralyne Inc.Inventor: Christopher J. Backhouse
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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: 6423198Abstract: 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: September 8, 2000Date of Patent: July 23, 2002Assignee: Zeptosens AGInventors: Andreas Manz, D. Jed Harrison, Carlo S. Effenhauser
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Patent number: 6423536Abstract: A method and device for preparing nanoscale reactions. An automated system utilizes an array of reaction chambers. The ends of the chambers are temporarily sealed with deformable membranes and reactions effected by incubation or temperature cycling. Reaction mixtures may be assembled by using the reaction containers to meter reaction components. After the reaction is finished, the reaction containers may be dispensed onto a substrate and the reaction products analyzed. An automated transfer device may be used for automated transport of the reaction container array or other transportable elements.Type: GrantFiled: May 23, 2000Date of Patent: July 23, 2002Assignee: Molecular Dynamics, Inc.Inventors: Stevan B. Jovanovich, David J. Roach, Andrew G. Hadd, Bo E. R. Hellman
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Publication number: 20020092770Abstract: The invention is directed to a high throughput capillary electrophoresis (CE) system, which comprises multiple mobile CE detector modules that are transportable by a programmable fluid-handling arm assembly to fixed samples in microtiter plate wells for analysis. The CE system of the invention is capable of simultaneously automating sample preparation and multiple CE analysis of the sample in a continuous timely process. The CE detector modules of the invention may be equipped with any suitable detection method, such as an ultraviolet (UV) absorbance or a laser-induced fluorescence (LIF) detector.Type: ApplicationFiled: December 3, 2001Publication date: July 18, 2002Inventors: Herbert J. Hedberg, Brian Kangas
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Publication number: 20020084185Abstract: 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: ApplicationFiled: March 30, 2000Publication date: July 4, 2002Inventors: Steven A Sundberg, J Wallace Parce, Calvin Y H Chow
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Publication number: 20020079224Abstract: The present invention relates to a sample analysis system with chip-based electrophoresis device, particularly, the chip electrophoresis is connected to the dynamic flow-based auto-sampling device to introduce the sample into the chip-based electrophoresis device. By utilizing the derivatization biochemistry method to have a surface modification on the sample loading channel, it prevents the sample from being adhered to the wall of the sample loading channel, and hence increases the sample loading rate, reduces cross-contamination of samples and performs specific bio-reaction by using the immobilization of matter including antigen, antibody, protein, or enzyme. This invention makes use of the continuous split flow and electric voltage control to work with the detecting unit, signal collecting unit, and signal processing unit so that the sample undergoes a timely, fast, continuous analysis without having interference from the sample of other time.Type: ApplicationFiled: June 15, 2001Publication date: June 27, 2002Inventors: Shu-Hiu Chen, Gwo-Bin Lee, Chung-Shi Yang, Yi-Hung Lin, Wan-Chou Sung, Guan-Ruey Huang
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Publication number: 20020079223Abstract: A method of separating components having a given negative or positive charge and contained in a sample is disclosed. The method involves, in one embodiment, loading a microchannel with a sample, placed between a trailing-edge electrolyte having a selected concentration of a titratable species, and a leading-edge electrolyte.Type: ApplicationFiled: August 20, 2001Publication date: June 27, 2002Inventors: Stephen J. Williams, Hong Dong Tan, Hung Pin Kao, Wyatt N. Vreeland
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Patent number: 6406604Abstract: An electrophoresis apparatus is generally disclosed for sequentially analyzing a single sample or multiple samples having one or more analytes in high or low concentrations. The apparatus comprises a relatively large-bore transport capillary which intersects with a plurality of small-bore separation capillaries. Analyte concentrators, having antibody-specific (or related affinity) chemistries, are stationed at the respective inter-sections of the transport capillary and separation capillaries to bind one or more analytes of interest. The apparatus allows the performance of two or more dimensions for the optimal separation of analytes.Type: GrantFiled: November 8, 1999Date of Patent: June 18, 2002Inventor: Norberto A. Guzman
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Patent number: 6402919Abstract: The invention relates to a capillary electrophoresis apparatus, comprising background solution containing reservoirs, which are interconnected by way of a separating capillary (1), current electrodes (E) connected to a voltage source, and a detector (4) essentially in the proximity of the outlet end of the separating capillary (1), as well as one or more solution reservoirs (R1-R3) on the injection side of the apparatus and one or more solution reservoirs (R4-R6) on the detector side of the apparatus, the ends of the separating capillary (1) being placed in expansions (5, 7), intended for feeding various solutions from the reservoirs (R1-R6) and extending from the bottom ends of capillary tubes (2, 3), said expansions extending as waste ducts (W1, W2) to waste containers, said waste containers being located at a distance from the ends of the separating capillary (1), and the current electrodes (E) being located in the waste ducts (W1, W2), preferably in the proximity of the discharge ends thereof.Type: GrantFiled: May 25, 2000Date of Patent: June 11, 2002Assignee: Valtion Teknillinen TutkimuskeskusInventor: Rauno Virtanen
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Patent number: 6391562Abstract: There is used at least one probe array obtained by arraying particles having various probes, respectively, fixed thereon (probe particles) in a definite order in a holder. A plurality of capillaries or grooves packed with various kinds, respectively, of probe particles are arrayed in parallel, and one of particles contained in each capillary or groove is injected into another capillary or groove to produce a probe array in which the various kinds of probe particles are arrayed in a constant and definite order. Various fluorophore-labeled DNA's are measured at the same time by attaching various probes to particles, respectively, of different sizes. A probe array composed of various fixed DNA probes can easily be produced, and there can be provided a probe array for detecting various DNA's which is composed of various fixed arbitrary DNA probes.Type: GrantFiled: March 16, 2001Date of Patent: May 21, 2002Assignee: Hitachi, Ltd.Inventors: Hideki Kambara, Kazunori Okano
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Patent number: 6387236Abstract: A multi-channel capillary electrophoresis apparatus is disclosed. The apparatus includes a capillary array assembly comprising a plurality of capillaries, each capillary having a capillary outlet, and an outlet support for supporting the capillary outlets. The apparatus further includes a cuvette defining a receiving slot, a gap region, and a detection zone, where the receiving slot is adapted to removably receive the outlet support, and wherein when the outlet support is inserted into the receiving slot, the capillary outlets are positioned in the gap region in proximity to the detection zone, and a flow channel is formed by the outlet support and the receiving slot such that the flow channel is in fluid communication with the gap region. In addition, the apparatus includes a front plumbing block in fluid communication with the flow channel for supplying a fluid flow through the gap region sufficient to transport material downstream from the capillary outlets to the detection zone.Type: GrantFiled: March 13, 2001Date of Patent: May 14, 2002Assignee: PE Corporation (NY)Inventors: Eric S. Nordman, John Shigeura, Albert L. Carrillo, David M. Demorest, Philip J. Wunderle
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Publication number: 20020053399Abstract: Methods are provided for the fabrication of polymeric microchannel structures having enclosed microchannels of capillary dimension. The microchannel structures are constructed of a base plate and a cover, sealed together. Microchannel structures having walls of a plastic material are formed in a generally planar surface of at least the base plate. The cover has at least one generally planar surface, and the microchannel structures are enclosed by bonding the planar surfaces of the cover and the base plate together. In some embodiments the surfaces of the cover and base plate are both of plastic material, and are directly thermally bonded. In some embodiments a bonding material is applied to one of the surface prior to bringing the surfaces together. Suitable bonding materials are disclosed.Type: ApplicationFiled: December 7, 2001Publication date: May 9, 2002Applicant: Aclara Biosciences, IncInventors: David S. Soane, Herbert H. Hooper, M. Goretty Alonso-Amigo
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Publication number: 20020046949Abstract: A table is used to position eight specimen reservoirs of an electrophoretic chip into which a specimen is firstly dispensed to a specimen dispensing position. A specimen dispensing mechanism is used to move a head to thereby suck a test-specimen contained in eight different wells of specimen plates into eight nozzles respectively and then move the head to the specimen dispensing position, thus dispensing the test-specimen sucked into the nozzles into the specimen reservoirs simultaneously. The table is used to sequentially position the specimen reservoirs to the specimen dispensing position and then the specimen dispensing mechanism is used to sequentially dispensing the specimen into the specimen reservoirs.Type: ApplicationFiled: October 22, 2001Publication date: April 25, 2002Applicant: Shimadzu CorporationInventors: Shin Nakamura, Toru Kaji, Rintaro Yamamoto
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Patent number: 6375819Abstract: An automated electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The system includes a stacked, dual carrousel arrangement to eliminate cross-contamination resulting from reuse of the same buffer tray on consecutive executions from electrophoresis. The system also has a gel delivery module containing a gel syringe/a stepper motor or a high pressure chamber with a pump to quickly and uniformly deliver gel through the capillary tubes. The system further includes a multi-wavelength beam generator to generate a laser beam which produces a beam with a wide range of wavelengths.Type: GrantFiled: August 13, 1999Date of Patent: April 23, 2002Assignee: Spectrumedix CorporationInventors: Qingbo Li, Changsheng Liu, Thomas E. Kane, John R. Kernan, Bernard Sonnenschein, Michael V. Sharer
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Patent number: 6375817Abstract: The present invention is directed to apparatus and methods for rapid, automated, microscale sample analysis using pressure differentials. The invention includes an apparatus having intersecting channels for introduction of a sample and separation of that sample into its components. The sample introduction and separation channels preferably are etched in a microfabricated device, such as a microchip, to form a junction. Pressure gradients are applied to the channels to form a sample plug in the separation channel. The separation channel may have disposed within it a medium for separation of the components suspected to be contained in the sample. For example, with the proper medium, a voltage gradient may be applied along the separation channel to separate the components of the sample electrophoretically. The apparatus also may include means for detecting the components of the sample subsequent to separation.Type: GrantFiled: April 16, 1999Date of Patent: April 23, 2002Assignee: PerSeptive Biosystems, Inc.Inventors: Todd A. Taylor, William W. Carson, Lance Koutny
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Patent number: 6372484Abstract: An apparatus is described for performing polymerase chain reaction (PCR) and capillary electrophoresis (CE) within a single, integrated and disposable device. Fluid enters the device via a sample charging port. From the sample charging port, the fluid travels through an inflow channel to the polymerase chain reaction chamber. This chamber is formed at a thin tab extension of a top portion of the device, and is generally defined by a cavity within the thin tab extension. After PCR is performed, the fluid leaves the polymerase chain reaction chamber through an outflow channel into a first sample well. A vent channel is connected to the first sample well for venting the first sample well to ambient atmosphere. The first sample well and a second sample well are in fluid communication by a sample channel. An electrophoresis separation channel is orthogonal to and intersects the sample channel, and has a first and second electrophoresis buffer well at each end.Type: GrantFiled: January 21, 2000Date of Patent: April 16, 2002Assignee: E.I. duPont de Nemours and CompanyInventors: Miriam Lisa Ronchi, David J. Regester, Robert Kenneth Kobos, Raymond E. Jackson, Jr.
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Publication number: 20020040850Abstract: An automated capillary zone electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The system includes a stacked, dual carrousel arrangement to eliminate cross-contamination resulting from reuse of the same buffer tray on consecutive executions from electrophoresis. The system also has a container connected to the detection end of the capillaries. The container is provided with valving which facilitate cleaning the capillaries, loading buffer into the capillaries, introducing samples to be electrophoresced into the capillaries, and performing capillary zone electrophoresis on the thus introduced samples.Type: ApplicationFiled: December 11, 2001Publication date: April 11, 2002Applicant: SpectruMedix CorporationInventors: Changsheng Liu, Thomas E. Kane, Qingbo Li
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Patent number: 6365024Abstract: An automated electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The system includes a stacked, dual carrousel arrangement to eliminate cross-contamination resulting from reuse of the same buffer tray on consecutive executions from electrophoresis. The system also has a gel delivery module containing a gel syringe/a stepper motor or a high pressure chamber with a pump to quickly and uniformly deliver gel through the capillary tubes. The system further includes a multi-wavelength beam generator to generate a laser beam which produces a beam with a wide range of wavelengths.Type: GrantFiled: August 11, 1999Date of Patent: April 2, 2002Assignee: Spectrumedix CorporationInventors: Qingbo Li, Thomas E. Kane, Changsheng Liu, Bernard Sonnenschein, Michael V. Sharer, John R. Kernan
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Publication number: 20020036140Abstract: In a method for controlling sample introduction in microcolumn separation techniques, more particularly in capillary electrophoresis (CE), where a sample is injected as a sample plug into a sampling device which comprises at least a channel for the electrolyte buffer and a supply and drain channel for the sample. The supply and drain channels discharge into the electolyte channel at respective supply and drain ports. The distance between the supply port and the drain port geometrically defines a sample volume. The injection of the sample plug into the electrolyte channel is accomplished electrokinetically by applying an electric field across the supply and drain channels for a time at least long enough that the sample component having the lowest electrophoretic mobility is contained within the geometrically defined volume. The supply and drain channels each are inclined to the electrolyte channel. Means are provided for electrokinetically injecting the sample into the sample volume.Type: ApplicationFiled: November 28, 2001Publication date: March 28, 2002Inventors: Andreas Manz, D. Jed Harrison, Carlo S. Effenhauser
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Publication number: 20020033337Abstract: Devices, systems and methods for use in separating sample materials into different fractions that employ bulk fluid flow for loading of samples followed by electrophoretic separation of the sample material. Devices employ configurations that optionally allow bulk sample loading with some or no displacement of a separation matrix within a separation conduit. Methods of using these devices, and systems that incorporate these devices are also envisioned.Type: ApplicationFiled: July 31, 2001Publication date: March 21, 2002Inventors: Walter Ausserer, Luc J. Bousse, Robert S. Dubrow, Steven A. Sundberg, Andrea W. Chow, Benjamin N. Wang
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Patent number: 6352633Abstract: An automated capillary zone electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The system includes a stacked, dual carrousel arrangement to eliminate cross-contamination resulting from reuse of the same buffer tray on consecutive executions from electrophoresis. The system also has a container connected to the detection end of the capillaries. The container is provided with valving which facilitate cleaning the capillaries, loading buffer into the capillaries, introducing samples to be electrophoresced into the capillaries, and performing capillary zone electrophoresis on the thus introduced samples.Type: GrantFiled: August 31, 1999Date of Patent: March 5, 2002Assignee: Spectrumedix CorporationInventors: Changsheng Liu, Thomas E Kane, Qingbo Li
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Publication number: 20020017464Abstract: The present invention provides for techniques for transporting materials using electrokinetic forces through the channels of a microfluidic system. The subject materials are transported in regions of high ionic concentration, next to spacer material regions of high ionic concentration, which are separated by spacer material regions of low ionic concentration. Such arrangements allow the materials to remain localized for the transport transit time to avoid mixing of the materials. Using these techniques, an electropipettor which is compatible with the microfluidic system is created so that materials can be easily introduced into the microfluidic system. The present invention also compensates for electrophoretic bias as materials are transported through the channels of the microfluidic system by splitting a channel into portions with positive and negative surface charges and a third electrode between the two portions, or by diffusion of the electrophoresing materials after transport along a channel.Type: ApplicationFiled: May 3, 2001Publication date: February 14, 2002Inventors: J. Wallace Parce, Michael R. Knapp
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Patent number: 6342142Abstract: A microchip apparatus and method provide fluidic manipulations for a variety of applications, including sample injection for microchip liquid chromatography. The microchip is fabricated using standard photolitographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis is performed in channels formed in the substrate. Injections are made by electro-osmotically pumping sample through the injection channel that crosses the separation channel, followed by a switching of the potentials to force a plug into the separation channel.Type: GrantFiled: April 27, 1999Date of Patent: January 29, 2002Assignee: UT-Battelle, LLCInventor: J. Michael Ramsey
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Publication number: 20020008030Abstract: A microchip apparatus and method provide fluidic manipulations for a variety of applications, including sample injection for microchip liquid chromatography. The microchip is fabricated using standard photolithographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis is performed in channels formed in the substrate. Injections are made by electro-osmotically pumping sample through the injection channel that crosses the separation channel, followed by a switching of the potentials to force a plug into the separation channel.Type: ApplicationFiled: July 20, 2001Publication date: January 24, 2002Inventor: J. Michael Ramsey
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Publication number: 20020009392Abstract: Methods for reducing fluid carryover by microfluidic devices including capillary element and/or fluid motion. Capillary elements coated with hydrophobic or hydrophilic coatings to resist fluid carryover are also provided. Microfluidic device handling systems are additionally included.Type: ApplicationFiled: March 26, 2001Publication date: January 24, 2002Inventors: Jeffrey A. Wolk, J. Wallace Parce, Robert Nagle, Colin B. Kennedy, Syed Husain, Advit Bhatt, Garrett Unno
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Publication number: 20020008029Abstract: A method and device for injecting a liquid sample into an electrolyte channel in a microfluidics device is disclosed. The device has a channel network that includes an electrolyte channel having upstream and downstream channel portions and first, second, and third side channels that intersect the electrolyte channel between the two channel portions at first, second, and third ports, respectively. In the method, a sample is moved electrokinetically into the electrolyte channel, to form a defined sample volume therein. By simultaneously controlling the voltage applied to the three side channels, and at least one of the upstream and downstream channel end portions, the sample volume element can be shaped to have a desired leading- and trailing-edge shape and/or distribution of sample components within the volume elements.Type: ApplicationFiled: February 10, 2001Publication date: January 24, 2002Inventors: Stephen J. Williams, Hong Dong Tan, Hung Pin Kao, Wyatt N. Vreeland
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Publication number: 20010049148Abstract: Ultra-high throughput systems and methods are used for sampling large numbers of different materials from surfaces of substantially planar library storage components. The systems and methods typically employ: microfluidic devices having integrated capillary elements for carrying out the analysis of the sampled materials; library storage components, e.g., planar solid substrates, capable of retaining thousands, tens of thousands and hundreds of thousands of different materials in small areas; sensing systems for allowing rapid and accurate sampling of the materials by the microfluidic devices, and associated instrumentation for control and analysis of the overall operation of these systems.Type: ApplicationFiled: December 28, 2000Publication date: December 6, 2001Inventors: Jeffrey A. Wolk, Sherri Ann Biondi, J. Wallace Parce, Morten J. Jensen, Anne R. Kopf-Sill
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Publication number: 20010045358Abstract: Analytical systems and methods that use a modular interface structure for providing an interface between a sample substrate and an analytical unit, where the analytical unit typically has a particular interface arrangement for implementing various analytical and control functions. Using a number of variants for each module of the modular interface structure advantageously provides cost effective and efficient ways to perform numerous tests using a particular substrate or class of substrates with a particular analytical and control systems interface arrangement. Improved optical illumination and detection system for simultaneously analyzing reactions or conditions in multiple parallel microchannels are also provided.Type: ApplicationFiled: July 31, 2001Publication date: November 29, 2001Inventors: Anne R. Kopf-Sill, Andrea W. Chow, Peter C. Jann, Morten J. Jensen, Michael Spaid, Colin B. Kennedy, Michael Kennedy
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Patent number: 6322683Abstract: Microfluidic devices are fabricated by fabricating structures that are used to align elements that are to be attached to the devices or tools that are to be used in further fabrication steps on those devices. Elements to be attached include additional substrate layers, external sampling elements, e.g. capillaries, and the like. Preferred alignment structures include wells over which reservoirs are positioned, notches for use with alignment keys to align substrate layers or for receiving additional structural elements, and targets or guide holes for receiving tooling in further fabrication steps.Type: GrantFiled: April 14, 1999Date of Patent: November 27, 2001Assignee: Caliper Technologies Corp.Inventors: Jeffrey A. Wolk, Richard J. McReynolds, J. Wallace Parce
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Publication number: 20010040096Abstract: A sample plate assembly for an electrophoresis apparatus including a tray at a sample supply portion of a capillary array, an adapter for the tray, a sample plate mounted on the adapter, a septer mounted on the sample plate and a septer holder mounted on the septer. Thereby, many number of samples can be automatically supplied to capillaries in a multi capillary array.Type: ApplicationFiled: April 27, 2001Publication date: November 15, 2001Inventors: Shuhei Yamamoto, Hiromi Yamashita, Masatoshi Kitagawa
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Publication number: 20010040095Abstract: A capillary array includes a light detection portion, a sample supply portion, a buffer solution supply portion and a voltage application portion which are necessary functions for electrophoresis, thereby, when assembling the capillary array into an electrophoresis apparatus, the same can be immediately used. Accordingly, a capillary array is provided which can be easily incorporated into an electrophoresis apparatus.Type: ApplicationFiled: May 1, 2001Publication date: November 15, 2001Inventors: Yasushi Shimizu, Toshiaki Kita, Kiyoshi Tsukada, Akihiro Suzuki, Tomonari Morioka, Masaya Kojima, Ryoji Inaba, Daizo Tokinaga, Shuhei Yamamoto, Yoshiyuki Okishima, Masao Fukunaga, Takayasu Furukawa, Tomohiro Shoji
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Publication number: 20010035351Abstract: The present invention provides a microfluidic analytical device and accompanying methods for injecting a sample and separating the components therein comprising an injection channel and an intersecting separation channel, the two channels formed to be in continuous fluid communication with one another. The separation channel preferably includes a separation material for resolving the components in a sample. The methods include using a first force, preferably a pressure differential, and a second force, preferably an electric field, to move samples through the microchannels. The device and methods are specially adapted to accommodate multiple sample injection and separation. Thus, the device and methods allow for increased sample throughput and are simple and inexpensive to carry out compared to related devices and methods.Type: ApplicationFiled: March 9, 2001Publication date: November 1, 2001Inventors: Peter C. Simpson, Ezra Van Gelder
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Publication number: 20010027918Abstract: Microfluidic methods, devices, and systems are provided for monitoring and controlling flow rates in response to one or more marker signals. The marker signals are used to provide an indication of flow rate in the various channels of the devices. Signals obtained from the markers are deconvoluted and used in a feedback loop to make flow rate adjustments.Type: ApplicationFiled: January 11, 2001Publication date: October 11, 2001Inventors: J. Wallace Parce, Claudia B. Jaffe
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Publication number: 20010027919Abstract: A multi-capillary type electrophoresis analysis apparatus has a sample tray for containing a plurality of samples, wherein part of the sample tray is made from a conductive material. Samples are introduced by applying a high voltage from a high voltage power supply between the sample tray and a coupler in a state in which one-ends of the capillaries are inserted in the samples contained in the sample tray. The apparatus eliminates the necessity of individually inserting electrodes in a plurality of samples contained in the sample tray, thereby making easy works for analysis.Type: ApplicationFiled: May 10, 2001Publication date: October 11, 2001Applicant: Hitachi, Ltd.Inventors: Imai Kazumichi, Osamu Uchida