By Electrophoresis Patents (Class 356/344)
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Patent number: 6301931Abstract: An improved apparatus and method for vacuum fusion bonding of large, patterned glass plates. One or both glass plates are patterned with etched features such as microstructure capillaries and a vacuum pumpout moat, with one plate having at least one hole therethrough for communication with a vacuum pumpout fixture. High accuracy alignment of the plates is accomplished by a temporary clamping fixture until the start of the fusion bonding heat cycle. A complete, void-free fusion bond of seamless, full-strength quality is obtained through the plates; because the glass is heated well into its softening point and because of a large, distributed force that is developed that presses the two plates together from the difference in pressure between the furnace ambient (high pressure) and the channeling and microstructures in the plates (low pressure) due to the vacuum drawn.Type: GrantFiled: November 24, 1999Date of Patent: October 16, 2001Assignee: The Regents of the University of CaliforniaInventors: Steve P. Swierkowski, James C. Davidson, Joseph W. Balch
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Patent number: 6296749Abstract: A system and method is disclosed for chromatography and electrophoresis using circular optical scanning. One or more rectangular microchannel plates or radial microchannel plates has a set of analysis channels for insertion of molecular samples. One or more scanning devices repeatedly pass over the analysis channels in one direction at a predetermined rotational velocity and with a predetermined rotational radius. The rotational radius may be dynamically varied so as to monitor the molecular sample at various positions along a analysis channel. Sample loading robots may also be used to input molecular samples into the analysis channels. Radial microchannel plates are built from a substrate whose analysis channels are disposed at a non-parallel angle with respect to each other. A first step in the method accesses either a rectangular or radial microchannel plate, having a set of analysis channels, and second step passes a scanning device repeatedly in one direction over the analysis channels.Type: GrantFiled: April 13, 1999Date of Patent: October 2, 2001Assignee: The Regents of the University of CaliforniaInventors: Joseph W. Balch, Laurence R. Brewer, James C. Davidson, Joseph R. Kimbrough
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Patent number: 6284119Abstract: A DNA base sequencer including a gel electrophoretic means having tracks for electrophoresing fluorophore-labelled DNA fragments, a laser diode as a light source for illuminating said tracks with exciting laser light and a CCD sensor for detecting the fluorescence emitted from the illuminated DNA fragments, the laser diode has a control unit including a Peltier device for controlling the temperature of the laser diode, a Peltier device temperature setting generating means having a processor and a memory, and a temperature control circuit that generates a drive current to the Peltier device for controlling its temperature. The CCD sensor receives part of the exciting light from the laser diode as stray light and detects its wavelength.Type: GrantFiled: August 30, 1999Date of Patent: September 4, 2001Assignee: Hitachi Electronics Engineering Co., Ltd.Inventors: Hiroaki Machida, Yusuke Miyazaki, Mitsuyoshi Koizumi
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Patent number: 6245507Abstract: The present invention provides a hyperspectral imaging apparatus and methods for employing such an apparatus for multi-dye/base detection of a nucleic acid molecule coupled to a solid surface.Type: GrantFiled: August 18, 1998Date of Patent: June 12, 2001Assignee: Orchid BioSciences, Inc.Inventor: Valery Bogdanov
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Patent number: 6233048Abstract: The present invention provides a microfluidic system for fast, accurate and low cost electrophoretic analysis of materials in the fields of chemistry, biochemistry, biotechnology, molecular biology and numerous other fields. Light from periodically spaced regions along a channel in the microfluidic system are received by a photodetector. The intensity of light received by the photodetector is modulated by the movement of species bands through the channel under electrophoretic forces. By Fourier analysis, the velocity of each species band is determined and the identification of the species is made by its electrophoretic mobility in the channel.Type: GrantFiled: December 8, 1998Date of Patent: May 15, 2001Assignee: Caliper Technologies Corp.Inventor: J Wallace Parce
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Patent number: 6224830Abstract: An improved absorbance or detection cell for a microfluid device, and in accordance with an aspect of the invention, the absorbance cell comprises a bottom plate having a channel bearing surface in which a channel having a fluid inlet and fluid outlet is defined, a top plate having a channel facing surface bound to the channel bearing surface of the bottom plate and first and second reflecting elements formed on opposed sides of the channel to form a waveguide through which the channel extends such that radiation propagating along the waveguide makes multiple passes across the channel, the waveguide having a radiation input end and a radiation output end.Type: GrantFiled: January 30, 1998Date of Patent: May 1, 2001Assignee: The Governors of the University of AlbertaInventors: D. Jed Harrison, Graham H. McKinnon, Nghia H. Chiem, Gregor Ocvirk, Hossein Salimi-Moosavi, Yutao Jiang
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Patent number: 6201628Abstract: A scanning apparatus is provided to obtain automated, rapid and sensitive scanning of substrate fluorescence, optical density or phosphorescence. The scanner uses a constant path length optical train, which enables the combination of a moving beam for high speed scanning with phase-sensitive detection for noise reduction, comprising a light source, a scanning mirror to receive light from the light source and sweep it across a steering mirror, a steering mirror to receive light from the scanning mirror and reflect it to the substrate, whereby it is swept across the substrate along a scan arc, and a photodetector to receive emitted or scattered light from the substrate, wherein the optical path length from the light source to the photodetector is substantially constant throughout the sweep across the substrate. The optical train can further include a waveguide or mirror to collect emitted or scattered light from the substrate and direct it to the photodetector.Type: GrantFiled: November 19, 1998Date of Patent: March 13, 2001Assignee: University of WashingtonInventors: David A. Basiji, Gerrit J. van den Engh
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Patent number: 6144455Abstract: A fluorometer has a partly transparent mirror through which excitation light is directed to the sample and via which emitted light from the sample is reflected. Thus a high sensitivity and, furthermore, as homogenous a measurement sensitivity distribution as possible within a vessel are achieved. Measuring can be carried out from either above or below. The device is applicable for use especially when the fluorometer has simultaneously a plurality of samples.Type: GrantFiled: March 20, 1998Date of Patent: November 7, 2000Assignee: Labsystems OyInventors: Jukka Tuunanen, Timo Karmeniemi
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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: 6131072Abstract: A system and method for identifying lanes in images generated from DNA sequencing and fragment analysis is described. One example method includes a computer implemented method of determining the locations of lanes of separated samples. Each lane corresponds to a sample being separated by flowing the sample through a media. The method includes the following elements. Place some samples on the media. Cause the samples to separate into the lanes. Create a digital image of the lanes. Fit some curves to the lane images. Each curve corresponds to a lane formed from a separated sample.Type: GrantFiled: February 3, 1998Date of Patent: October 10, 2000Assignee: PE Applied Biosystems, a division of Perkin-ElmerInventors: David P. Holden, Andrew L. Diamond
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Patent number: 6120667Abstract: After a sample stage moves and brings a sample titer plate toward and into contact with a capillary array end, a high voltage is applied across electrodes for a prescribed time for injecting samples. Thereafter an electrophoresis reservoir comes into contact with the capillary array end, for starting electrophoresis. When electrophoresed/separated DNA fragments pass through a detection part, an excitation/photoreceiving optical system is scanned so that photomultipliers detect fluorescence from four types of fluorescent materials labeling the samples. The excitation/photoreceiving optical system comprises an epi-optical system and a confocal optical system, and is scanned at a high speed.Type: GrantFiled: January 14, 1998Date of Patent: September 19, 2000Assignees: Japan Science and Technology Corporation, The Institute of Physical and Chemical Research, Shimadzu CorporationInventors: Yoshihide Hayashizaki, Shin Nakamura, Katsuya Kashiwagi
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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: 6068753Abstract: An apparatus for electrophoresing a sample and for thereafter either scanning in the visible mode or the fluorescent mode, under control of a central processor, to provide scanning densitometry of the electrophoresed sample, and with the fluorescent mode scanning being performed in situ. The apparatus includes a gantry which moves from left to right in the XY plane. The gantry draws, delivers and deposits the samples and reagents, and includes safety devices to prevent the gantry from movement and damage when there are obstructions in the path of the gantry. A fluorescent scanning unit is moved by X- and Y-direction motors to position a photomultiplier over an electrophoresed sample. In this way, the electrophoretic sample can remain fixed in place during sample delivery, ultraviolet exposure and measurement operations.Type: GrantFiled: May 1, 1997Date of Patent: May 30, 2000Assignee: Helena Laboratories CorporationInventors: Robert J. Sarrine, Charles D. Kelley, Henry A. Garsee, Tipton L. Golias
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Patent number: 6066245Abstract: A system and method for illuminating an optically active sample and collecting scattered light emitted by the sample. Preferably, the sample is a fluorescently labeled and fluoresces light. The system includes a fiber optic bundle, including at least one illuminating fiber for emitting an illuminating beam, and including at least one collecting fiber disposed adjacent the illuminating fiber. The system further includes an optical apparatus for focusing the illuminating beam, for directing the focused illuminating beam to the fluorescently labeled sample to cause the sample to emit fluoresced light, and for directing at least some of the fluoresced light emitted by the sample to the collecting fiber.Type: GrantFiled: December 27, 1996Date of Patent: May 23, 2000Assignee: Genetic Biosystems, Inc.Inventor: Peter Trost
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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: 6039925Abstract: The improved fluorescence detector comprises a tubular electrophoretic device through which a sample labelled with four kinds of fluorescent dye is caused to migrate, illumination optics for illuminating the tubular electrophoretic device with exciting light and detection optics for detecting the fluorescence emitted from the sample illuminated with the exciting light and it is characterized in that a plurality of tubular electrophoretic devices (1) are arranged in a row, a plurality of graded-index lenses (9) are arranged parallel to and in the same number as said plurality of tubular electrophoretic devices (1), each lens array being composed of four vertically stacked graded-index lenses, a plurality of bandpass filter arrays (11) are also arranged parallel to and in the same number as said plurality of electrophoretic devices (1), each filter array being composed of four filters arranged vertically in a row, and a light-receiving element of a planar type (13) is provided at the back of the rows of said baType: GrantFiled: July 28, 1998Date of Patent: March 21, 2000Assignee: Hitachi Electronics Engineering Co., Ltd.Inventor: Ryoji Nemoto
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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: 6017434Abstract: This invention is an integrated instrument for the 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, 1995Date of Patent: January 25, 2000Assignee: CuraGen CorporationInventors: John W. Simpson, Jonathan Marc Rothberg, Gregory T. Went
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Patent number: 6014213Abstract: A high dynamic range apparatus for separation and detection of polynucleotide fragments has a housing adapted to receive an electrophoresis gel holder containing an electrophoresis gel loaded with fluorophore-labeled samples; one or more laser diodes for providing radiation of a frequency suitable for excitation of the fluorophore which irradiates a an array of excitation/detection sites on the electrophoresis gel; an array of detectors aligned with the excitation/detection sites for collecting fluorescent emissions; and one or more components for increasing the dynamic range of the instrument by at least an order of magnitude.Type: GrantFiled: March 18, 1997Date of Patent: January 11, 2000Assignee: Visible Genetics Inc.Inventors: Paul Waterhouse, Alexandre M. Izmailov, Henryk Zaleski, John A. Renfrew, James W. Cassidy
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Patent number: 6008055Abstract: Systems and methods for inducing and detecting sample analyte(s) identifying fluorescence are disclosed. In particular, a system which includes at least two fiber optic means, within a "throw-away" modular component system component with at least four ports, in which sample analyte fluorescence is caused to occur, by the application of energy to sample analyte(s), is disclosed. The present invention system provides that sample analyte(s) fluorescence inducing energy be entered via an optic fiber means and that produced fluorescence be provided to a detector system via a second optic fiber means. A preferred source of sample analyte(s) fluorescence inducing energy includes lasers, and a preferred method by which to provide sample analyte(s) to the present invention system involves electrophoresis.Type: GrantFiled: June 30, 1998Date of Patent: December 28, 1999Assignee: Transgenomic, Inc.Inventors: Jianzhong Zhu, Arthur P. D'Silva
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Patent number: 6005663Abstract: Improved detection methods and apparatus which may be used individually or in combinations enhance the ability of the electrophoresis apparatus to detect fluorophore-labeled materials in short periods of time.Type: GrantFiled: August 18, 1997Date of Patent: December 21, 1999Assignee: Visible Genetics Inc.Inventors: Paul Waterhouse, John A. Renfrew, John K. Stevens
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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: 5963456Abstract: A method and apparatus for displaying capillary electrophoresis data wherein absorbance with respect to time is related to graphic values within a graphic range or scale of values and selected graphic values are displayed with respect to time. The selected graphic values may comprise a range hues, color saturation and/or brightness or may represent a monochromatic scale. The resulting representation may be horizontally aligned with the corresponding electrophoretogram absorbance values to provide both a quantitative value (electrophoretogram absorbance values) and qualitative (graphic stripe) display.Type: GrantFiled: November 27, 1996Date of Patent: October 5, 1999Assignee: Beckman Instruments, Inc.Inventors: Gerald L. Klein, Steven P. Katzmann
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Patent number: 5958694Abstract: The present invention is generally directed to microfluidic systems and methods of using such systems in the determination of the nucleotide sequence of target nucleic acid sequences (referred to herein as the "target"). In particular, the present invention provides methods and systems for determining the relative positions within a target nucleic acid sequence that are occupied by a given nucleotide, e.g., A, T, G or C, by separating mixtures of nested sets of fragments of the target nucleic acid, which sets each include fragments that terminate in a different given nucleotide.Type: GrantFiled: October 16, 1997Date of Patent: September 28, 1999Assignee: Caliper Technologies Corp.Inventor: Theo T. Nikiforov
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Patent number: 5951838Abstract: A method and apparatus for achieving uniform illumination in an electrophoresis apparatus is provided. Uniform illumination allows quantitative measurements of an electrophoresis gel to be made, thus increasing the information which can be obtained from an electrophoretic analysis. Uniform illumination is achieved by scanning the light source, preferably in a trans-illumination mode, across the sample gel in a direction perpendicular to the axis of the source. The light source is comprised of one or more light bulbs placed in a light tray. Variations in light intensity near the source end portions may be minimized using a variety of techniques including extended light bulbs, filters, reflectors, diffusers, or supplemental sources.Type: GrantFiled: March 10, 1997Date of Patent: September 14, 1999Assignee: Bio-Rad Laboratories, Inc.Inventors: David M. Heffelfinger, Craig Van Horn
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Patent number: 5953133Abstract: A scanning apparatus for scanning and reading a luminescent pattern of a sample in a flat-plate shape, having a placing member for placing the sample as an object for reading; a light condensing member for condensing light emitted from the luminescent pattern of the sample; a movement member for moving the light condensing member relative to the placing member; a light receiving member for dividing the light of the luminescent pattern of the sample condensed by the light condensing member into predetermined segments and receiving the light by scanning the light from the segments in a one-dimensional way; a photoelectrical conversion member for converting optical signals of the light received by the light receiving member into electrical signals; a control member for controlling a scan by the light receiving member in accordance with the electrical signals from the photoelectrical conversion member; and a data processing member for converting the electrical signals from the photoelectrical conversion member inType: GrantFiled: May 1, 1996Date of Patent: September 14, 1999Assignee: Hitachi Software Engineering Co., Ltd.Inventors: Hitoshi Fujimiya, Kenji Yamamoto, Toshiaki Ito, Hisanori Nasu
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Patent number: 5938908Abstract: A capillary electrophoresis system comprising a plurality of capillaries filled with a migration medium in which samples to which fluorephore labels are added migrate, a light source providing an excitation light exciting the fluorephore labels, a photo detector detecting a fluorescence radiated from the fluorephore labels, and light focusing means placed between the plurality of capillaries to which the excitation light is irradiated. The parts of the plurality of capillaries to which the excitation light is irradiated and the light focusing means are arranged in a plane shape. The excitation light is irradiated through the plurality of capillaries and the light focusing means, the capillaries and light focusing means alternatively placed in the parts where an excitation light is irradiated. The light focusing means consisting of cylindrical rod lenses.Type: GrantFiled: April 22, 1997Date of Patent: August 17, 1999Assignees: Hitachi, Ltd., Hitachi Software Engineering Co., Ltd.Inventors: Takashi Anazawa, Hideki Kambara, Satoshi Takahashi, Kazumichi Imai, Hisanori Nasu
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Patent number: 5936730Abstract: A bio-molecule analyzer including a plurality of test sites on a transparent substrate, each test site having probe molecules attached thereto. An array of addressable light sources are positioned in optical alignment with a corresponding test site. A solution containing sample molecules is positioned in contact with the plurality of test sites. A detector array having a plurality of photodetectors positioned in optical alignment with the array of addressable light sources, one photodetector corresponding to each light source, and a light filter positioned between the detector array and the plurality of test sites for absorbing the light from the light sources and transmitting the light from the test sites to the detector array.Type: GrantFiled: September 8, 1998Date of Patent: August 10, 1999Assignee: Motorola, Inc.Inventors: Barbara M. Foley, Wenbin Jiang, Davis H. Hartman, Huinan Yu, Sean Gallagher
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Patent number: 5917608Abstract: A surface plasmon sensor comprises a prism, a metal film, which is formed on one surface of the prism and is brought into contact with a sample, and a light source for producing a light beam. An optical system causes the light beam to pass through the prism and to impinge upon an interface between the prism and the metal film such that various different angles of incidence may be obtained with respect to the interface. A photodetector detects an intensity of the light beam, which has been totally reflected from the interface, with respect to each of the various different angles of incidence. An electrode stands facing the metal film with a liquid sample intervening therebetween, and a DC voltage is applied across the electrode and the metal film. A substance contained in the liquid sample is thus analyzed quickly and with a high sensitivity.Type: GrantFiled: April 29, 1998Date of Patent: June 29, 1999Assignee: Fuji Photo Film Co., Ltd.Inventors: Masayuki Naya, Taizo Akimoto
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Patent number: 5903348Abstract: A system for aligning the optical components of a chemical analysis system in which capillaries or optical fibers are supported by a micromechanied substrate. The system provides for alignment of elements of an electrophoresis system in an efficient high sampling rate capability.Type: GrantFiled: March 12, 1997Date of Patent: May 11, 1999Assignee: NZ Applied Technologies, Inc.Inventors: Paul Melman, Marvin Tabasky
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Patent number: 5900131Abstract: Changes in polarized light incident on a detection zone within a separation matrix are used to detect optically active molecules within the separation matrix. The separation and detection of optically active molecules within the detection zone is done by loading a sample containing optically active molecules onto a separation matrix; applying a motive force to cause the sample to migrate though the separation matrix and to separate into a plurality of subgroups of optically active molecules; directing an incident beam of polarized radiation to the detection zone; processing the collected exiting beam with an optical component which discriminates between radiation having the same polarization as the incident beam and radiation having a different polarization from the incident beam; and measuring the intensity of the processed exiting beam.Type: GrantFiled: August 28, 1996Date of Patent: May 4, 1999Assignee: Visible Genetics, Inc.Inventors: John K. Stevens, Alexandre M. Ismailov
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Patent number: 5900934Abstract: An apparatus to effect multiple simultaneous separations to measure absorbance, comprising a photodetector array comprising a plurality of photosensitive elements connected to provide a serial output. The elements are typically pixels of a photodiode array (PDA). The elements are illuminated by a light source positioned to illuminate at least a portion of the photodetector array. The light source may be a an AC or DC mercury lamp or other useable light source for chromatography. An array of separation channels is disposed between the light source and the photodetector array, each of the separation channels having a lumen, a sample introduction end and a detection region disposed opposite the sample introduction end. Typically and as disclosed herein the array is a multiple parallel capillary electrophoresis system.Type: GrantFiled: October 6, 1997Date of Patent: May 4, 1999Assignee: Waters Investments LimitedInventors: Anthony C. Gilby, William W. Carson
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Patent number: 5897760Abstract: A method and apparatus for correcting non-uniformities in the source and the lens assembly of an electrophoresis apparatus is provided. Assuming a detector with a uniform responsivity, correcting for source and lens non-uniformities allows quantitative measurements of an electrophoresis gel to be made, thus increasing the information which can be obtained from an electrophoretic analysis. The non-uniformities due to the illumination source are characterized by sampling a portion of the source with a linear detector array and creating a correction data file. In order to sample the source, a mirror or beamsplitter is appropriately positioned, for example along the central optical axis of the electrophoresis apparatus. Similarly, a correction data file representing the non-uniformities due to the lens assembly is created using a secondary linear source of known uniformity. After the correction data files are stored, an image of the sample is taken and a sample data file is created.Type: GrantFiled: March 10, 1997Date of Patent: April 27, 1999Assignee: Bio-Rad Laboratories, Inc.Inventors: David M. Heffelfinger, Craig Van Horn
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Patent number: 5898493Abstract: Capillary electrophoresis (CE) is interfaced with low temperature fluorescence line-narrowing (FLN) spectroscopy for on-line structural characterization of separated molecular analytes.Type: GrantFiled: June 6, 1997Date of Patent: April 27, 1999Assignee: Iowa State University Research Foundation, Inc.Inventors: Ryszard J. Jankowiak, Gerald J. Small, Peter A. Shields
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Patent number: 5892581Abstract: In order to suppress base line drift due to change in a light source and to start analysis with a short waiting time so as to improve quantitative accuracy of analysis, a detected signal in a measurement wavelength and a detected signal in a reference wavelength are measured at each of arbitrary light intensity points by varying light intensity of a light source, and the corresponding relationship between the wavelengths is stored. An incident light intensity of the measurement wavelength is estimated from a detected signal in the reference wavelength based on the stored data.Type: GrantFiled: September 24, 1997Date of Patent: April 6, 1999Assignee: Hitachi, Ltd.Inventors: Toshihiko Sakaide, Masahito Ito, Yoshio Fujii, Shigeru Matsui
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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: 5867266Abstract: Apparatus for optical analysis of a sample material includes a channel block incorporating microfabricated channels and an integral gel material. Illuminating optics direct light to the sample material and light reflected from, refracted by and/or emitted by the sample is collected by collection optics for detection. The gel material is formed within the channels and includes multiple closely spaced pillars to form a porous separator for sample material to be analyzed.Type: GrantFiled: April 17, 1996Date of Patent: February 2, 1999Assignee: Cornell Research Foundation, Inc.Inventor: Harold G. Craighead
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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: 5856866Abstract: An image producing apparatus includes at least one light emitting diode stimulating ray source, a filter for cutting a stimulating ray emitted from the at least one light emitting diode stimulating ray source and allowing only fluorescent light generated by stimulation of a fluorescent substance by the stimulating ray to pass therethrough, and a solid state image sensor for detecting the fluorescent light transmitted through the filter. According to the thus constituted image producing apparatus, it is possible to safely produce a fluorescent image at low cost.Type: GrantFiled: October 30, 1997Date of Patent: January 5, 1999Assignee: Fuji Photo Film Co., Ltd.Inventors: Hitoshi Shimizu, Yukinori Nishioka
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Patent number: 5852495Abstract: The present invention provides a microfluidic system for fast, accurate and low cost electrophoretic analysis of materials in the fields of chemistry, biochemistry, biotechnology, molecular biology and numerous other fields. Light from periodically spaced regions along a channel in the microfluidic system are received by a photodetector. The intensity of light received by the photodetector is modulated by the movement of species bands through the channel under electrophoretic forces. By Fourier analysis, the velocity of each species band is determined and the identification of the species is made by its electrophoretic mobility in the channel.Type: GrantFiled: September 30, 1997Date of Patent: December 22, 1998Assignee: Caliper Technologies CorporationInventor: J. Wallace Parce
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Patent number: 5846702Abstract: A new group of Os(II) and Os(III) compounds useful as redox mediators in electrochemical biosensors. These compounds have 1) low oxidation potential, 2) fast reaction kinetics between the electroactive center of an enzyme and the compound, 3) slow oxidation of osmium by oxygen, and 4) excellent solubility in aqueous medium. These mediators are particularly useful as a component of a reagent used in an electrochemical biosensor, wherein the biosensor is useful for measuring analytes from a biological fluid, such as blood.Type: GrantFiled: December 20, 1996Date of Patent: December 8, 1998Assignee: Boehringer Mannheim CorporationInventors: Zhi David Deng, Gerald F. Sigler, Nigel A. Surridge, Christopher D. Wilsey, Robert J. McEnroe, Walter W. Jernigan, Rebecca W. Muddiman
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Patent number: 5840877Abstract: Electrophoresis gels of enhanced selectivity are produced by adding a preformed polymer to a polymerization solution containing at least one monomer and at least one cross-linker. The polymer must be of such a chemical composition and molecular weight that its presence during free-radical polymerization results in a new topology of gel polymers, so that under the influence of an electric field, such as during electrophoresis, the passage of long DNA molecules through the gel is retarded proportionally more than the passage of the short ones. The polymer needs to be added at specific ratio to the monomer and the cross-linker, and the enhanced selectivity is achievable only within a certain range of ratios of polymer(s), monomer(s) and cross linker(s). That range is dependent on all three essential gel components, the polymer, the monomer and the cross-linker.Type: GrantFiled: September 5, 1996Date of Patent: November 24, 1998Assignee: Guest Elchrom ScientificInventor: Branko Kozulic
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Patent number: 5783397Abstract: A method in which natural sample components are simultaneously fractionated and screened for compounds that bind tightly to specific molecules of interest is disclosed. Such newly isolated ligands are good candidates for potential therapeutic or diagnostic compounds. The natural sample is first combined with a potential target molecule and then subjected to capillary electrophoresis (CE). Charged (or even neutral) compounds present in the natural sample that bind to the added target molecule can alter its normal migration time upon CE, by changing its charge-to-mass ratio, or will cause a variation in peak shape or area. Complex formation can be detected by simply monitoring the migration of the target molecule during electrophoresis. Any new ligands that bind to the target molecule will be good candidates for therapeutic or diagnostic compounds. Interfering, weak-binding ligands commonly present in crude extracts are not detected.Type: GrantFiled: June 12, 1996Date of Patent: July 21, 1998Assignee: Northeastern UniversityInventors: Dallas E. Hughes, Barry L. Karger
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Patent number: 5784152Abstract: A method and apparatus of analyzing samples contained in a microplate is provided. The instrument is capable of measuring fluorescence, luminescence, and/or absorption within multiple locations within a sample well. The instrument is tunable over the excitation and/or detection wavelengths. Neutral density filters are used to extend the sensitivity range of the absorption measuring aspect of the instrument. Due to the wavelength tuning capabilities of the instrument, the spectral dependence of the measured fluorescence, luminescence, and absorption of the materials in question can be analyzed. The combination of a data processor and a look-up table improve the ease of operation of the instrument. Several different formats are available for the output data including creation of a bit map of the sample.Type: GrantFiled: October 11, 1996Date of Patent: July 21, 1998Assignee: Bio-Rad LaboratoriesInventors: David M. Heffelfinger, Franklin R. Witney, Chris Cunanan
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Patent number: 5784154Abstract: The separations resulting from capillary electrophoresis performed in a microbore capillary tube are detected on-line by focusing a light beam in the form of a line or sheet of light on the capillary passage in which the separations take place so that the width of the sheet of light encompasses the length of the passage in which separations of interest are expected to take place. The separations form concentration gradients in the capillary passage encompassed by the light beam and cause refraction of portions of the light beam and variations in the intensity of the light beam due to such refraction. Alternately, the separated components may absorb light of certain frequencies so if the light beam includes light of the certain frequencies, variation in the intensity of the light beam is caused by such absorbance.Type: GrantFiled: November 13, 1996Date of Patent: July 21, 1998Assignee: Anthony R. TorresInventor: Janusz B. Pawliszyn
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Patent number: 5776767Abstract: A virtual DNA sequencer combines a plurality of individual DNA sequencers. Samples of DNA or other nucleic acid from subjects are prepared and allocated in real time to particular lanes or sets of lanes in electrophoresis plates of the individual sequencers, with records kept of the allocations. The data resulting from the electrophoresis runs is collected and collated according to the identities of the subjects. The individual sequencers are networked, and each individual sequencer is preferably equipped with a data buffer large enough to accommodate all or substantially all of a data run, thus protecting the virtual sequencer from loss of valuable data in the event that the network is disrupted for some portion of the time of the data run. In this way, a plurality of sequencers is virtually the same as a single sequencer with a very large number of tracks each of which can run for a much longer sequencing run than an individual sequencer.Type: GrantFiled: December 12, 1995Date of Patent: July 7, 1998Assignee: Visible Genetics Inc.Inventors: John K. Stevens, James M. Dunn, Gregory Dee, James W. Cassidy
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Patent number: 5774214Abstract: A multi-mode apparatus for capturing light patterns emitted or absorbed by a planar sample, such as an electropheresis gel, is made possible by a unique tray and sample holder system which positions a sample at a pre-determined focal plane of the solid state camera integral to the apparatus. Each sample is fixed in a sample holder specific to the mode of labeling of the sample. The tray is configured to retain each sample holder at a different elevation with respect to the side walls of the tray for proper placement of the sample at the focal plane. The tray side walls are adapted to position a sample holder at the proper elevation depending on the sampling mode and illumination technique selected. The sample holder includes a combination of transparent, translucent, or opaque plates designed to allow illumination and imaging of the sample for the particular labeling method employed.Type: GrantFiled: December 12, 1996Date of Patent: June 30, 1998Assignee: Photometrics, Ltd.Inventor: Keith Neil Prettyjohns
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Patent number: 5763277Abstract: The present invention system includes an axially oriented end of a fiber optic present in an axially oriented system component bore in which, during use, sample analyte fluorescence is caused to occur. The present invention system and method provides that sample analyte(s) fluorescence inducing energy be entered along a path which is other than essentially parallel to the axially oriented system component bore and that detected fluorescence be transmitted to a detector by the fiber optic. A preferred source of sample analyte(s) fluorescence inducing energy is a laser system, and a preferred method by which to provide sample analyte(s) to the present invention system axially oriented system component bore involves use of electrophoresis.Type: GrantFiled: June 10, 1996Date of Patent: June 9, 1998Assignee: Transgenomic IncorporatedInventors: Jiazhong Zhu, Arthur P. D'Silva
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Patent number: 5759374Abstract: An electrophoresis apparatus includes a plurality of first capillaries containing a separation medium, such as a gel, and an optical cell in which one end of each of the first capillaries is disposed. Samples labeled with fluorophores and introduced into the first capillaries, and an electric field is applied to the first capillaries to cause the samples to migrate through the first capillaries into the optical cell. A light source excites the fluorophores with light when the samples are in the optical cell, causing the fluorophores to emit fluorescence, and a photo-detecting system detects the fluorescence emitted by the fluorophores. The ends of the first capillaries in the optical cell may be arranged in a straight line. The light source may include a He--Ne laser emitting light having a wavelength of 594 nm, and the fluorophores may include either sulforhodamine or a derivative of sulforhodamine.Type: GrantFiled: June 25, 1996Date of Patent: June 2, 1998Assignee: Hitachi, Ltd.Inventors: Satoshi Takahashi, Hideki Kambara
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Patent number: RE36826Abstract: An electrophoresis pattern reading system of fluorescent type is comprised of a detachable migration unit comprising a gel functioning as a base for electrophoresis and a gel-supporting body for supporting the gel; an electrophoresis unit, to which the migration unit is mounted, for performing electrophoresis by applying migrating voltage to the gel to which a sample labeled with a fluorescent substance is added; and a reading unit including an instrumentation subunit for reading an electrophoresis pattern, to which the migration unit is mounted after electrophoresis and which receives fluorescence emitted from the fluorescent substance of the sample on the gel upon application of light to the gel.Type: GrantFiled: December 3, 1993Date of Patent: August 22, 2000Assignee: Hitachi Software Engineering Co., Ltd.Inventors: Hitoshi Fujimiya, Shigeo Nakajima, Hisanori Nasu, Keigi Koga