With Detailed Detection Patents (Class 204/452)
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Patent number: 6224733Abstract: An electrophoresis apparatus includes a plurality of capillaries through which samples labeled with a plurality of fluorophores migrate, a pair of electrodes which generate an electric field which causes the samples labeled with the fluorophores to migrate through the capillaries, a light source which emits laser light which irradiates the samples labeled with the fluorophores at irradiation positions respectively corresponding to the capillaries in a direction which is perpendicular to a direction in which the samples migrate and which is parallel to a plane formed by the capillaries, thereby exciting the fluorophores to emit fluorescence at the irradiation positions, a photodetector which detects the fluorescence emitted by the fluorophores, and a holder which holds the capillaries at intervals of 1 mm or less near the irradiation positions.Type: GrantFiled: September 21, 1999Date of Patent: May 1, 2001Assignee: Hitachi, Ltd.Inventors: Satoshi Takahashi, Hideki Kambara
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Patent number: 6221226Abstract: The present invention generally provides methods and systems for monitoring and controlling electroosmotic flow rates in microfluidic systems. Generally, such methods and systems monitor flow rates in electroosmotically driven microfluidic systems by flowing signaling elements within these channels and measuring the flow rate of these signals. The methods of monitoring flow rates are also applied to methods and systems for continuously monitoring and controlling these flow rates in electroosmotically driven microfluidic systems.Type: GrantFiled: October 7, 1999Date of Patent: April 24, 2001Assignee: Caliper Technologies Corp.Inventor: Anne R. Kopf-Sill
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Methods and apparatus for processing a sample of biomolecular analyte using a microfabricated device
Patent number: 6207031Abstract: A technique processes a sample of biomolecular analyte. The technique uses an apparatus having a support assembly that receives and supports a test module, a load assembly that loads the sample of biomolecular analyte onto the test module, an electrophoresis assembly that applies a current to the test module such that components within the sample separate by electrophoresis, and a controller that controls operations of the load assembly and the electrophoresis assembly. The load assembly and the electrophoresis assembly are coupled to the support assembly. The controller controls the operation of the load assembly in an automated manner. Preferably, the test module includes a dielectric plate member having an upper planar surface and a lower planar surface that is spaced apart from and coplanar with the upper planar surface. The dielectric plate member has at least one set of channels that includes an injection channel and a separation channel.Type: GrantFiled: September 14, 1998Date of Patent: March 27, 2001Assignee: Whitehead Institute for Biomedical ResearchInventors: Aram S. Adourian, Daniel J. Ehrlich, Lance B. Koutny, Paul T. Matsudaira, Dieter R. Schmalzing -
Patent number: 6162341Abstract: 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: September 11, 1998Date of Patent: December 19, 2000Assignee: The Perkin-Elmer CorporationInventors: Eric S. Nordman, John Shigeura, Albert L. Carrillo, David M. Demorest, Philip J. Wunderle
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Patent number: 6156177Abstract: A method for analyzing samples includes the steps of introducing samples labeled with fluorophores into a first end of each of a plurality of electrophoresis lanes including a separation medium, a second end of each of the electrophoresis lanes being disposed in an optical cell filled with a buffer solution, applying an electric field to the electrophoresis lanes to separate the samples labeled with the fluorophores and cause the separated samples labeled with the fluorophores to migrate through the electrophoresis lanes into the buffer solution in the optical cell, exciting, with light from a light source, the fluorophores labeling the separated samples in the buffer solution in the optical cell to emit fluorescence in the buffer solution in the optical cell, and detecting, with a photodetector, the fluorescence emitted by the fluorophores labeling the separated samples in the buffer solution in the optical cell.Type: GrantFiled: March 14, 2000Date of Patent: December 5, 2000Assignee: Hitachi, Ltd.Inventors: Satoshi Takahashi, Hideki Kambara
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Patent number: 6156576Abstract: Fast lysis of a single cell or cellular component thereof is performed by generating a shock wave in a medium in which the cell or cellular component thereof is positioned. The cell or cellular component thereof is either positioned by laser tweezers or cultured as an adhered cell or cellular component thereof to minimize manipulation trauma. The disclosed method completely lyses a single cell or cellular component thereof in a controllable manner in milliseconds or less followed immediately by the loading of the cellular contents into a capillary for analyte separation and detection. The cell or cellular component thereof is adjacent the inlet of an electrophoretic column through which a gravity siphon flow of the medium is maintained. The lysed contents of the cell or cellular component thereof enter the electrophoretic column in less than 33 msec, are separated and analyzed by laser induced fluorescence.Type: GrantFiled: March 6, 1998Date of Patent: December 5, 2000Assignee: The Regents of the University of CaliforniaInventors: Nancy L. Allbritton, Christopher E. Sims, Michael W. Berns, Gavin D. Meredith, Tatiana B. Krasieva, Bruce J. Tromberg
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Patent number: 6147347Abstract: A mass spectrometer includes a sample passage through which a sample solution flows towards a tip of the sample passage, a gas passage which produces a gas flow along the sample passage towards an orifice of the gas passage, a gas supplier which supplies a gas to the gas passage so that the gas flow has a velocity effective for spraying the sample solution near the tip of the sample passage, and an analyzer which analyzes a mass of gaseous ions formed from the sample solution sprayed by the gas flow. The gas flow has a characteristic value F/S between 350 meters/second (m/s) and 700 m/s, where F is a flow rate of the gas at standard conditions (20.degree. C., 1 atmosphere), and S is a difference between a cross section of the orifice and a cross section of the sample passage at the orifice. An exposed length of the sample passage between an external opening of the orifice and the tip of the sample passage may be between -0.25 mm and 1.2 mm.Type: GrantFiled: June 9, 1999Date of Patent: November 14, 2000Assignee: Hitachi, Ltd.Inventors: Atsumu Hirabayashi, Minoru Sakairi, Yasuaki Takada, Hideaki Koizumi, Kaoru Umemura
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Patent number: 6140048Abstract: System and method for distinguishing at least two types of molecule groups that are bound to analyte molecules and which have different fluorescent characteristics. The system performs differentiation using time-resolved fluorescence measurement and includes a light source that exposes a first sample volume to light that is suitable for exciting the at least two types of molecule groups to fluorescence. The system also includes a detector for detecting fluorescence radiation emitted from a second sample volume that at least partially overlaps the first sample volume, and a control unit that is designed to activate the light source for a time interval T.sub.1 and, after time interval T.sub.2 has passed, to activate the detector for a time interval T.sub.3. According to this system, the illumination and detection of emitted fluorescence radiation is performed at least 1,000 times per millisecond, the detector signals recorded with a recording unit during time interval T.sub.Type: GrantFiled: May 22, 1998Date of Patent: October 31, 2000Assignee: Roche Diagnostics GmbHInventors: Ralph Muller, Markus Sauer, Christoph Zander
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Patent number: 6132579Abstract: A liquid is separated into its constituent species by electrophoresis along a capillary channel. A plurality of the channels is provided in the thickness of an injection molded plastics disc. The disc is rotatably mounted such that samples are dispensed into successive channels. When all twelve channels have been used, the disc is replaced with a fresh one.Type: GrantFiled: January 26, 1999Date of Patent: October 17, 2000Assignee: Eastman Kodak CompanyInventors: Stephen J. Edwards, Stephanie J. McIntyre
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Patent number: 6132578Abstract: An electrophoresis separation and detection apparatus for separating and detecting fluorophore-labeled samples by electrophoresis, which comprises a migrating and separating means for electrophoresis separation of the samples labeled with two or more kinds of fluorophore labels, respectively; an irradiating means which casts two or more kinds of exciting lights having different wavelengths on a plurality of positions in all the electrophoresis lanes or on the extensions of all the electrophoresis lanes substantially at the same time; and a detecting means which detects the samples separated by the electrophoresis, at the positions on which the exciting lights are casted, wherein each fluorophore label is composed of a substance for excitation which is excited by the exciting light and a substance for emission which emits light owing to energy transfer from the substance for excitation; two or more kinds of substances are used as each of the substance for excitation and the substance for emission; and the deteType: GrantFiled: June 23, 1997Date of Patent: October 17, 2000Assignees: Hitachi, Ltd., Hitachi Electronics Engineering Co., Ltd.Inventors: Hideki Kambara, Keiichi Nagai, Hiroaki Machida
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Patent number: 6126804Abstract: A new approach and instrument for field identification of micro-organisms and DNA fragments using a small and disposable device containing integrated polymerase chain reaction (PCR) enzymatic reaction wells, attached capillary electrophoresis (CE) channels, detectors, and read-out all on/in a small hand-held package. The analysis instrument may be made inexpensively, for example, of plastic, and thus is disposable, which minimizes cross contamination and the potential for false positive identification between samples. In addition, it is designed for multiple users with individual applications. The integrated PCR/CE is manufactured by the PCR well and CE channels are "stamped" into plastic depressions where conductive coatings are made in the wells and ends of the CE microchannels to carry voltage and current to heat the PCR reaction mixtures and simultaneously draw DNA bands up the CE channels.Type: GrantFiled: September 23, 1997Date of Patent: October 3, 2000Assignee: The Regents of the University of CaliforniaInventor: Brian D. Andresen
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Patent number: 6120666Abstract: A microfabricated device and method for electrokinetic transport of a liquid phase biological or chemical material is described. In accordance with one aspect of the present invention there is provided a microchip that is adapted for the simultaneous spatial confinement of electrokinetically driven fluidic material streams on a substrate. The apparatus includes a focusing chamber formed in a surface of the substrate and in fluid communication with two sample fluid channels and three focusing fluid channels. The device further includes electromotive means operatively connected to the sources of the sample fluid and the source of focusing fluid for electrokinetically driving the respective streams of the sample and focusing fluids through the respective channels into the focusing chamber such that the focusing fluid streams spatially confine the first and second sample fluid streams within the focusing chamber.Type: GrantFiled: June 16, 1998Date of Patent: September 19, 2000Assignee: UT-Battelle, LLCInventors: Stephen C. Jacobson, J. Michael Ramsey
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Patent number: 6103537Abstract: The present invention concerns methods for masking inhomogeneity of a member of a specific binding pair (sbp) employed in a capillary electroseparation. The method comprises binding the sbp member to synthetic particles that become localized during capillary electroseparation. Also disclosed is one embodiment of the present invention, which is a method for conducting a capillary electroseparation specific binding assay. The method involves the electroseparation of a labeled first member of a specific binding pair that is bound in a complex from labeled first member that is not bound in the complex. The complex comprises the first member and a second member of a specific binding pair. A combination is provided comprising a sample suspected of containing an analyte, a labeled first member of a specific binding pair, and a second member of a specific binding pair under conditions for forming a complex between labeled first member and the second member.Type: GrantFiled: September 30, 1998Date of Patent: August 15, 2000Assignee: ACLARA Biosciences, Inc.Inventors: Edwin F. Ullman, Gregory B. Stauber
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Patent number: 6103083Abstract: The present invention relates to an electrophoresis apparatus having a plurality of capillaries arranged in a plane such that a curving contour is formed by the intersection points of each of the capillaries with the plane. The apparatus may be used to determine the sequence of nucleic acids. The present invention also relates to methods of using the electrophoresis apparatus and methods of making the electrophoresis apparatus.Type: GrantFiled: February 20, 1998Date of Patent: August 15, 2000Assignee: TetragenInventors: Irena N. Merenkova, Maxim Brevnov
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Patent number: 6086737Abstract: To sequence DNA automatically, DNA marked with far infrared, near infrared, or infrared fluorescent dyes are electrophoresed in a plurality of channels through a gel electrophoresis slab or capillary tubes wherein the DNA samples are resolved in accordance with the size of DNA fragments in the gel electrophoresis slab or capillary tubes into fluorescently marked DNA bands. The separated samples are scanned photoelectrically with a laser diode and a sensor, wherein the laser scans with scanning light at a wavelength within the absorbance spectrum of said fluorescently marked DNA samples and light is sensed at the emission wavelength of the marked DNA.Type: GrantFiled: July 11, 1995Date of Patent: July 11, 2000Assignee: Li-Cor, Inc.Inventors: Gabor Patonay, Narasimhachari Narayanan, John A. Brumbaugh, Lyle Richard Middendorf
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Patent number: 6068749Abstract: A subatmospheric, variable pressure sample delivery chamber, useful as an electrospray ionization device for introducing a sample into a mass spectrometer or as a sample delivery device for delivery of a sample to a collection device at subatmospheric pressures, is disclosed. The sample delivery chamber is configured to maintain an operating pressure between 1 and 750 Torr, preferably between 50 and 700 Torr. The chamber has an inlet port for introduction of a gas and an exit port capable of being coupled either to a sampling orifice for an analytical device, usually a mass spectrometer, or directly to a pump for removal of gas. A sample delivery device extends from outside the chamber into the interior of the chamber.Type: GrantFiled: January 17, 1997Date of Patent: May 30, 2000Assignee: Northeastern UniversityInventors: Barry L. Karger, Frantisek Foret, Daniel P. Kirby
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Patent number: 6056859Abstract: A method for staining immobilized nucleic acids includes the steps of affixing DNA probes to a solid substrate, moving target DNA material into proximity with the DNA probes, whereby the target DNA hybridized with specific ones of the DNA probes, and moving a fluorescent dye into proximity with the hybridized target DNA, whereby the fluorescent dye binds to the hybridized DNA to enable subsequent detection of fluorescence.Type: GrantFiled: February 12, 1997Date of Patent: May 2, 2000Assignee: Lockheed Martin Energy Research CorporationInventors: J. Michael Ramsey, Robert S. Foote, Stephen C. Jacobson
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Patent number: 6048444Abstract: A capillary electrophoresis apparatus of the invention has: a plurality of capillaries which are filled with a migration medium and have first ends into which samples are injected and second ends in which components included in the samples are eluted; a sheath flow cell in which the second ends are arranged in a straight line at first predetermined intervals and are terminated and a sheath flow is formed; a buffer solution vessel for housing a buffer solution flowing in the sheath flow cell; a drain vessel housing the buffer solution flowed from the sheath flow cell; an optical system emitting laser light to a part near the second ends; and a fluorescent detection system for detecting fluorescent light generated from fluorophore labelling the components included in the sample eluted near the second ends by the emission of laser light, wherein the buffer solution flows from the lower part to the upper part of the sheath flow cell, thereby forming a sheath flow in the sheath flow cell.Type: GrantFiled: November 26, 1997Date of Patent: April 11, 2000Assignee: Hitachi, Ltd.Inventors: Satoshi Takahashi, Hideki Kambara, Takashi Yamada
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Patent number: 6048498Abstract: Microfluidic apparatus which include a planar device and polymeric holder assembly are provided. The polymeric holder assembly includes a cavity disposed through the holder, providing optical access to the top and bottom of the planar device when the device is mounted in the polymeric holder. The planar device includes microscale channels disposed within the device.Type: GrantFiled: November 12, 1998Date of Patent: April 11, 2000Assignee: Caliper Technologies Corp.Inventor: Colin B. Kennedy
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Patent number: 6042710Abstract: The present invention provides methods of electrophoretically separating macromolecular species, as well as compositions and systems useful in carrying out such methods. Specifically, the methods of the present invention comprise providing a substrate that has at least a first capillary channel disposed therein. The surface of the channel has a first surface charge associated therewith, and is filled with a water soluble surface adsorbing polymer solution that bears a net charge that is the same as the charge on the capillary surface.Type: GrantFiled: May 11, 1999Date of Patent: March 28, 2000Assignee: Caliper Technologies Corp.Inventor: Robert S. Dubrow
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Patent number: 6042708Abstract: In order to irradiate a constant range of a separation passage of a microchip, light from a light source linearly extending along the separation passage is transmitted through a cylindrical lens and a bandpass filter and introduced into the separation passage. The light transmitted through the separation passage of the microchip is introduced into a photocell array through a cylindrical lens and detected. Measurement is repetitively performed and accumulated to determine migration patterns.Type: GrantFiled: October 14, 1997Date of Patent: March 28, 2000Assignee: Shimadzu CorporationInventors: Hiroaki Nakanishi, Akihiro Arai, Yosuke Iwata
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Patent number: 6027627Abstract: An automated electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The system includes a stacked, dual carousel arrangement to eliminate cross-contamination resulting from reuse of the same buffer tray on consecutive executions from electrophoresis. The system also has a gel delivery module containing a gel syringe/a stepper motor or a high pressure chamber with a pump to quickly and uniformly deliver gel through the capillary tubes. The system further includes a multi-wavelength beam generator to generate a laser beam which produces a beam with a wide range of wavelengths.Type: GrantFiled: June 29, 1998Date of Patent: February 22, 2000Assignee: Spectrumedix CorporationInventors: Qingbo Li, Thomas E. Kane, Changsheng Liu, Bernard Sonnenschein, Michael V. Sharer, John R. Kernan
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Patent number: 6027624Abstract: The automated capillary electrophoresis method and apparatus analyzes a sample in real time or near real time in order to identify the presence of a number of different ions as well as other sample parameters, such as the relative concentrations of each ion identified in the sample. By performing capillary electrophoresis in an automated fashion, the automated capillary electrophoresis method and apparatus may be configured to monitor a manufacturing process online with little, if any, input from the system operator. The automated capillary electrophoresis method and apparatus also provides a base line such that the analysis results can be compared and can be more meaningfully interrupted. The automated capillary electrophoresis method and apparatus initially performs capillary electrophoresis upon a sample containing at least one ion to obtain data over time which relates to a predetermined property of the sample, such as the degree of transparency of at least a portion of the sample.Type: GrantFiled: May 7, 1997Date of Patent: February 22, 2000Assignee: Troy State UniversityInventors: Moore Ugochukwu Asouzu, Shawn Anderson
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Patent number: 6001230Abstract: An integrated apparatus for capillary electrophoresis which is automated using conveyors which carry vials containing electrolytes and samples, a capillary contained in a modular, portable, and interchangeable cartridge, and actuators for bringing the capillary into flow communication with the fluids in the vials. Electropotential is applied to the ends of the capillary to cause electrophoretic separation. The cartridge may include an opening to allow detection of fluid in the capillary using a detector provided in the apparatus.Type: GrantFiled: April 29, 1993Date of Patent: December 14, 1999Assignee: Beckman Coulter, Inc.Inventor: Victor Paul Burolla
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Patent number: 5993634Abstract: This invention is an integrated instrument for high-capacity electrophoretic analysis of biopolymer samples. It comprises a specialized high-voltage, electrophoretic module in which the migration lanes are formed between a bottom plate and a plurality of etched grooves in a top plate, the module permitting concurrent separation of 80 or more separate samples. In thermal contact with the bottom plate is a thermal control module incorporating a plurality of Peltier heat transfer devices for the control of temperature and gradients in the electrophoretic medium. Fragments are detected by a transmission imaging spectrograph which simultaneously spatially focuses and spectrally resolves the detection region of all the migration lanes. The spectrograph comprises a transmission dispersion element and a CCD array to detect signals. Signal analysis comprises the steps of noise filtering, comparison in a configuration space with signal prototypes, and selection of the best prototype.Type: GrantFiled: May 9, 1996Date of Patent: November 30, 1999Assignee: CuraGen CorporationInventors: John W. Simpson, Jonathan M. Rothberg, Gregory T. Went
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Patent number: 5989402Abstract: The present invention is generally directed to improved methods, structures and systems for interfacing microfluidic devices with ancillary systems that are used in conjunction with such devices. These systems typically include control and monitoring systems for controlling the performance of the processes carried out within the device, e.g., controlling internal fluid transport and direction, monitoring and controlling environmental conditions and monitoring results of the processes performed, e.g., detection.Type: GrantFiled: August 29, 1997Date of Patent: November 23, 1999Assignee: Caliper Technologies Corp.Inventors: Calvin Y. H. Chow, John Wallace Parce, Richard J. McReynolds, Colin B. Kennedy, Luc J. Bousse
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Patent number: 5985120Abstract: The separation profile results of capillary zone electrophoresis can be analyzed very rapidly, e.g., in 45 seconds or less, if the results are analyzed using a successive subtracting procedure to establish the separation profile as a function of time and projecting this separation profile forward in time to quantitatively analyze the separate species in the profile. The projection step can be accomplished using an algorithm along with or without Fourier transform (FT) techniques and the quantitative analysis can be carried out using principle component regression analysis (PCA) or suitable calibration procedures.Type: GrantFiled: June 12, 1997Date of Patent: November 16, 1999Assignee: University of MassachusettsInventors: Ashok L. Cholli, Eugene F. Barry, Sukant K. Tripathy, Jayant Kumar
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Patent number: 5964998Abstract: An electrophoresis apparatus for detecting samples migrating in migration portions includes a plurality of gel separation portions separate from one another and having respective ends disposed along a straight line, a plurality of migration portions equal in number to the gel separation portions and disposed along a straight line following respective ones of the gel separation portions, a light source for generating light which passes through the migration portions, the light propagating along a straight line extending through all of the migration portions, a plurality of optical fibers having respective first ends and respective second ends, the first ends of the optical fibers being disposed facing respective points where the light from the light source passes through respective ones of the migration portions, the optical fibers being equal in number to or greater in number than the migration portions, and an optical detector optically coupled to the second ends of the optical fibers for receiving light froType: GrantFiled: September 16, 1997Date of Patent: October 12, 1999Assignee: Hitachi, Ltd.Inventor: Hideki Kambara
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Patent number: 5954932Abstract: A method for analyzing samples includes forming a plurality of sheath flows of a buffer solution, each of the sheath flows being formed at one end of a respective one of a plurality of capillaries each containing a separation medium, causing samples to migrate through the capillaries into the sheath flows, and detecting the samples in the sheath flows.Type: GrantFiled: June 2, 1998Date of Patent: September 21, 1999Assignee: Hitachi, Ltd.Inventors: Satoshi Takahashi, Hideki Kambara
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Patent number: 5954931Abstract: An electrophoresis apparatus includes a substrate (34) which supports a filling region (22) and a plurality of electrophoresis lanes (20). The filling region (22) communicates a sample to the plurality of electrophoresis lanes (20). A method of electrophoresis includes providing the above-described electrophoresis apparatus, applying a sample to the filling region (22), the plurality of electrophoresis lanes (20) receiving the sample from the filling region (22), and electrophoresing the sample in the plurality of electrophoresis lanes (20).Type: GrantFiled: January 24, 1997Date of Patent: September 21, 1999Assignee: Motorola, Inc.Inventors: George N. Maracas, William L. Reber, Cary D. Perttunen
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Patent number: 5932080Abstract: Identification and quantification of constituents of a sample is achieved by mobility-based electropherograms obtained from capillary electrophoresis, the mobilities being normalized by zero correction followed by division by the mobility of a selected marker. Zero correction is achieved either relative to a separate marker or by calculation based on the same marker. The resulting electropherograms are more recognizable since they more closely resemble the scanned separation patterns obtained with planar gels, and individual constituents of the sample are more easily and reliably identified since their positions in the electropherogram are substantially constant from one electropherogram to the next and hence reproducible to a high degree of accuracy.Type: GrantFiled: May 30, 1997Date of Patent: August 3, 1999Assignee: Bio-Rad Laboratories, Inc.Inventor: Robert K. Likuski
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Patent number: 5922184Abstract: Identification and quantification of paraproteins in a sample is achieved by Fourier analysis of mobility-based electropherograms obtained from capillary electrophoresis. The use of a computer algorithm to analyze capillary electrophoresis data, provides the clinician with methods of detecting levels of paraproteins in serum as low as 0.05 g/dL. Additionally, an individual paraprotein can be located on an electropherogram and used to monitor its increased or decreased production in an individual.Type: GrantFiled: July 21, 1997Date of Patent: July 13, 1999Assignee: Bio-Rad Laboratories, Inc.Inventors: Steven R. Binder, Caroline Scolari, Robert K. Likuski
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Patent number: 5916428Abstract: An automated electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The capillary cartridge has two embodiments. In one embodiment, the second ends of the capillary tubes are also arranged is such an array. In a second embodiment, the second ends communicate with an interior cavity of pressure cell from which solutions, gels and the like may be introduced. The pressure cell allows for applying high pressure to clean out the capillary tubes. An apparatus for performing automated capillary gel electrophoresis using such a cartridge is also disclosed.Type: GrantFiled: July 7, 1998Date of Patent: June 29, 1999Assignee: Spectrumedix CorporationInventors: Thomas E. Kane, Qingbo China Li, John R. Kernan
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Patent number: 5900132Abstract: A holder (10) is provided for securing a capillary (30) having a window section (28) including first and second edges (46) (48) to a mount (80). The holder (10) comprises a retaining surface (14) for securing the capillary (30) to the holder (10) and a mounting surface (18) for detachably securing the holder (10) to the mount (80). The retaining surface (14) is attached to the capillary (30) proximate to the opposed first and second edges (46), (48), with a portion of the window section (28) exposed. Since the capillary (30) is secured proximate the opposed first and second edges (46), (48), the fragile capillary window section (28) is protected during manufacturing or installation into an electrophoretic system (32). The retaining surface (14) preferably is sized and shaped to retain a plurality of capillaries (30) to allow for the substantially simultaneous testing of multiple capillaries (30).Type: GrantFiled: June 28, 1996Date of Patent: May 4, 1999Assignee: Beckman Coulter, Inc.Inventors: Charles A. Keenan, Stephen L. Pentoney, Jr., Brian D. Peterson, Jack D. McNeal
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Patent number: 5891314Abstract: A method and apparatus for correcting non-uniformities in the lens assembly of an electrophoresis apparatus is provided. Assuming a detector with a uniform responsivity as well as a uniform illumination source, correcting for lens non-uniformities allows accurate quantitative measurements of an electrophoresis gel to be made, thus increasing the information which can be obtained from an electrophoretic analysis. Applying the system, the non-uniformities due to the lens assembly are first characterized for a range of aperture and magnification settings. A look-up table is then created which contains the non-uniformities and/or correction data files for the lens assembly according to the aperture and magnification settings. In order to correct a sample image, the aperture and magnification settings used to obtain the sample image are provided to the system processor. These settings may be automatically obtained by the processor or manually input by the user.Type: GrantFiled: March 10, 1997Date of Patent: April 6, 1999Assignee: Bio-Rad Laboratories, Inc.Inventors: David M. Heffelfinger, Craig Van Horn
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Patent number: 5888363Abstract: An apparatus and method for interfacing a capillary with a detector is disclosed. In particular, a capillary that is used in a capillary electrophoresis technique is interfaced with an off-column detector that is destructive of the sample or that will otherwise create adverse affects on the operations of the capillary electrophoresis. By way of example only, a nitrogen chemiluminescent detector using pyro-chemiluminescent techniques is discussed. An interface between the separation and detection systems is essential to prevent interference between the two systems. The interface apparatus and method are achieved by creating a closed connection between the two systems within which the pressure and sample flow rate can be controlled. Pressure control is achieved through the introduction and venting of gas into and from the integrated system. Interference between interfaced systems is then prevented by equalizing the pressure in the interface apparatus with the head pressure on the inlet end of the capillary.Type: GrantFiled: September 3, 1996Date of Patent: March 30, 1999Assignee: Antek Instruments, Inc.Inventors: Mohammad Amin Abubaker, Eugene M. Fujinari, John R. Petersen, Michael G. Bissell
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Patent number: 5888366Abstract: A capillary made of plastics material that is suited for use in capillary electrophoresis. The capillary has its inner surface chemically modified for the generation of properties different from those of the original plastic capillary material. In the process of producing such capillaries, a premanufactured capillary is treated with a chemical reagent which generates functional groups directly on the capillary surface or generates attachment sites, on the capillary surface to which functional groups are later bonded.Type: GrantFiled: August 19, 1997Date of Patent: March 30, 1999Assignee: Hewlett-Packard CompanyInventors: Heinz Engelhardt, Thomas Schmitt, Konstantin Shoiket
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Patent number: 5879528Abstract: A means and method for indirect detection of constituent components of a mixture separated in a chemical separation process. Fluorescing ions are distributed across the area in which separation of the mixture will occur to provide a generally uniform background fluorescence intensity. For example, the mixture is comprised of one or more charged analytes which displace fluorescing ions where its constituent components separate to. Fluorescing ions of the same charge as the charged analyte components cause a displacement. The displacement results in the location of the separated components having a reduced fluorescence intensity to the remainder of the background. Detection of the lower fluorescence intensity areas can be visually, by photographic means and methods, or by automated laser scanning.Type: GrantFiled: August 14, 1991Date of Patent: March 9, 1999Assignee: Iowa State University Research FoundationInventors: Edward S. Yeung, Lance B. Koutny, Barry L. Hogan, King C. Chan, Yinfa Ma
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Patent number: 5876675Abstract: Microfluidic devices and systems, and particularly, microfluidic devices that are easier to handle by the operator, without damaging, contaminating or otherwise fouling, as a result of manual contact with the device. These microfluidic devices and systems include manual handling structures, to allow handling of the small scale devices with minimal potential for fouling as a result of manual contact with the device.Type: GrantFiled: August 5, 1997Date of Patent: March 2, 1999Assignee: Caliper Technologies Corp.Inventor: Colin B. Kennedy
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Patent number: 5871628Abstract: An advanced imaging spectrograph system provides for slab-gel DNA sequencing and genotyping with high throughput sequencing. The system is based on the integration of improved electrophoresis structures with an imaging spectrophotometer that records the entire emission spectra along an imaging line across a sequencing gel (or capillary array). The system includes spectral shape matching to improve dye identification allowing the use of dyes having nearly any emission spectra and allowing greater than four dye multiplexing.Type: GrantFiled: August 22, 1996Date of Patent: February 16, 1999Assignees: The University of Texas System, Science Applications International CorporationInventors: Ali Dabiri, Harold R. Garner
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Patent number: 5869273Abstract: The subject invention provides methods and kits for detecting increased bone resorption in patients. These methods and kits use chondroitin sulfate, a glycosaminoglycan, as a marker for bone resorption. Levels of chondroitin sulfate are detected in samples of urine or serum taken from patients. Measurements of chondroitin sulfate levels are made by methods such as fluorophore-assisted carbohydrate electrophoresis (FACE). Knowledge of increased bone resorption rates is useful in diagnosis of bone disorders such as osteoporosis.Type: GrantFiled: September 13, 1996Date of Patent: February 9, 1999Assignee: Glyko, Inc.Inventor: John C. Klock
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Patent number: 5863401Abstract: Homogeneous competitive immunoassay methods for simultaneously detecting analytes using capillary electrophoresis and fluorescent detection systems are described. The methods are useful for detecting and/or quantitating the concentration of a plurality of drugs of abuse in a single urine sample using a single assay method.Type: GrantFiled: July 3, 1997Date of Patent: January 26, 1999Assignee: Beckman Instruments, Inc.Inventor: Fu-Tai A. Chen
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Patent number: 5861124Abstract: An apparatus for detecting denaturation of a nucleic acid, including: denaturation condition controlling means for controlling condition of denaturation under which a double-stranded nucleic acid is separated into a first single-stranded nucleic acid and a second single-stranded nucleic acid; excitation light irradiation means for irradiating the double-stranded nucleic acid before denaturation, and the first single-stranded nucleic acid and second single-stranded nucleic acid after the denaturation; fluorescence detection means for detecting fluorescence emission based on the excitation light irradiation; and processing means for receiving, storing and processing a signal supplied from the fluorescence detection means.Type: GrantFiled: August 29, 1994Date of Patent: January 19, 1999Assignee: Hamamatsu Photonics KKInventors: Shigeru Hosoi, Tadashi Fukami, Akihiko Tsuji, Makiko Hiyoshi
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Patent number: 5858187Abstract: A microchip device includes a focusing channel, in which an electric field strength established in the focusing channel is controlled relative to an electric field strength established in a material transport channel segment to spatially focus the material traversing the material transport channel segment.Type: GrantFiled: September 26, 1996Date of Patent: January 12, 1999Assignee: Lockheed Martin Energy Systems, Inc.Inventors: John Michael Ramsey, Stephen C. Jacobson
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Patent number: 5858644Abstract: A method for detecting an analyte in a sample uses both the specificity of an enzymatic reaction and the separation power of capillary electrophoresis.Type: GrantFiled: May 30, 1995Date of Patent: January 12, 1999Assignee: Beckman Instruments, Inc.Inventor: Fu-Tai Albert Chen
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Patent number: 5856082Abstract: The present invention provides analytical devices for the characterization of the primary structure of proteins and peptides, comprising a microenzyme reactor, a separation device, an interface between the microenzyme reactor and the separation device, a mass spectrometer, and an interface between the separation device and the mass spectrometer. Also provided are methods for characterizing a protein or peptide utilizing such devices.Type: GrantFiled: August 31, 1994Date of Patent: January 5, 1999Assignee: University of British ColumbiaInventors: Rudolf H. Aebersold, Lawrence N. Amankwa
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Patent number: 5853668Abstract: A first reactant is immobilized i.e. in a porous matrix (50), adjacent a sample electrode (46) within a reaction chamber. Energizing of the electrode (46) electrophoretically attracts a mobile second reactant and/or electrolytically induces appropriate reaction conditions to enhance reaction of the first and second reactants. Polarity reversals between the sample electrode (46) and remote electrodes (38), (42), (44) cause unreacted second reactant and/or by-products to migrate away from the immobilized first reactant. The techniques are useful for sequential chemical reactions such as sequencing or construction of proteins, polysaccharides and nucleic acids where cyclical additions and removals of reactants are required. The techniques are amenable to automated micro and nano scale construction and operation and allow direct electrophoretic (38) interfacing with chromatographic, HPCE and mass spectrophotometric equipment.Type: GrantFiled: May 25, 1995Date of Patent: December 29, 1998Assignee: Ludwig Institute for Cancer ResearchInventors: Geoffrey Stephen Begg, Richard John Simpson, Antony Wilks Burgess
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Patent number: 5833827Abstract: The capillary array electrophoresis system of the present invention comprises a plurality of capillaries whose inside is filled with migration medium and at least parts of which are aligned in a plane, a means for making lasers substantially simultaneously irradiate transparent parts of the plurality of capillaries along the direction of alignment of the plurality of capillaries so as to excite fluorephore labels of migrated and separated samples, a fluorescence detection means for detecting fluorescence radiating from the fluorephore labels, from a direction crossing the direction of the alignment, the transparent parts of the plurality of capillaries are surrounded by a transparent gas, the cross section of the capillary of the transparent part is a circle and the ratio of the outside diameter to the inside diameter of the capillary ranges from 1 to 7.Type: GrantFiled: September 23, 1996Date of Patent: November 10, 1998Assignee: Hitachi, Ltd.Inventors: Takashi Anazawa, Satoshi Takahashi, Hideki Kambara
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Patent number: 5833826Abstract: An electrophoresis system including means for reducing the distortion of a sample zone eluting from a capillary electrophoresis separation capillary is disclosed. The system includes one or more separation capillaries, each separation capillary having an inlet end and an outlet end; a first electrode in electrical communication with the inlet ends of the separation capillaries; a second electrode in electrical communication with the outlet ends of the separation capillaries; and one or more focusing electrodes in electrical communication with the outlet ends of the separation capillaries. In operation, the voltage of each of the electrodes is adjusted such that (i) the sample zone is transported from the inlet end to the outlet end of the separation capillaries and (ii) the distortion of the sample zone eluting from the separation capillaries is reduced.Type: GrantFiled: December 13, 1996Date of Patent: November 10, 1998Assignee: The Perkin-Elmer CorporationInventor: Eric S. Nordman
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Patent number: 5810985Abstract: Disclosed are methods of electrochemical analysis of an analyte in a sample. The methods include providing a sample comprising an analyte, and introducing the sample into a capillary tube containing electrophoretic running buffer and a reactant. According to the methods of the invention, one or both of the analyte and the reactant is electrically charged. Chemical contact between analyte and reactant induced by their relative electrophoretic mobility results in the breaking or formation of a covalent bond of one of the analyte or the reactant to produce a detectable product. The methods also include the steps of imposing along the length of the capillary tube an electric current for a time sufficient to bring into chemical contact within the tube analyte and reactant so as to allow formation of product, and detecting the product.Type: GrantFiled: February 9, 1995Date of Patent: September 22, 1998Assignee: Purdue Research FoundationInventors: Jianmin Bao, Bryan Joseph Harmon, Dale Hansen Patterson, Fred E. Regnier