With Detailed Detection System (e.g., Including A Light Source And A Camera, Etc.) Patents (Class 204/612)
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Patent number: 6143151Abstract: To sequence long strands of DNA, clone strands having lengths longer than 100 bases are, in one embodiment, marked on one end with biotin. These strands are divided into 4 aliquots and each aliquot: (1) is uniquely chemically treated to randomly terminate the strands at the non-biotinylated end at a selected type of base; and (2) is moved continuously by electrophoresis through a different one of four identical channels. In the one embodiment, the strands are randomly terminated at a selected base type and they are moved into avidin, which due to high affinity, combines with the biotin marked ends of shorter strands before the longer strands are fully resolved in the gel. The avidin is marked with fluorescein, the strands are scanned and the signals are decoded. In another embodiment, the strands are synthesized, with termination at a selected base type and marked either by the above method of by ethidium bromide.Type: GrantFiled: December 11, 1995Date of Patent: November 7, 2000Assignee: Li-Cor, Inc.Inventors: Lyle Richard Middendorf, John Brumbaugh
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Patent number: 6143153Abstract: To sequence long strands of DNA, clone strands having lengths longer than 100 bases are, in one embodiment, marked on one end with biotin. These strands are divided into 4 aliquots and each aliquot: (1) is uniquely chemically treated to randomly terminate the strands at the nonbiotinylated end at a selected type of base; and (2) is moved continuously by electrophoresis through a different one of four identical channels. In the one embodiment, the strands are randomly terminated at a selected base type and they are moved into avidin, which due to high affinity, combines with the biotin marked ends of shorter strands before the longer strands are fully resolved in the gel. The avidin is marked with fluorescein, the strands are scanned and the signals are decoded. In another embodiment, the strands are synthesized, with termination at a selected base type and marked either by the above method of by ethidium bromide.Type: GrantFiled: July 10, 1997Date of Patent: November 7, 2000Assignee: The Board of Regents of the University of NebraskaInventors: Lyle R. Middendorf, John Brumbaugh
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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: 6103084Abstract: An apparatus for electroporation stores a level of charge, specified by a user, on a capacitor, which is delivered to a cuvette through an optically isolated high voltage switch. The capacitor is charged through a charging system, including a current mode pulse width modulation control circuit, which monitors the current in the primary winding of a transformer and supplies a pulse width modulated signal, limiting the current on every pulse to a level set by the microcontroller, to the controlling transistor in order to generate the drive to the primary winding of the transformer. A controlled amount of energy is transferred through each pulse to the capacitor. The microcontroller monitors the voltage on the capacitor up to a threshold level to predict the number of pulses necessary to store the requested amount of charge on the capacitor. The microcontroller will then count the number of pulses until the number of pulses necessary to store the requested amount of charge on the capacitor has been reached.Type: GrantFiled: June 6, 1995Date of Patent: August 15, 2000Assignee: Eppendorf Netheler-Hinz GmbHInventor: David Alan Uhen
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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: 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: 6040586Abstract: A data collection method for scanning a scan window comprising one or more channels is described. In the method of the invention an integrated signal (S) is measured across a scan window including one or more channels using an integrating detector. Next, a velocity-normalized integrated signal (Sn) is determined based on the integrated signal (S) and a scan velocity.Type: GrantFiled: May 5, 1998Date of Patent: March 21, 2000Assignee: The Perkin-Elmer CorporationInventor: Tor Slettnes
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Patent number: 6027628Abstract: A gel cassette for electrophoresis includes opposed plastic plates holding a gel therebetween. An upper buffer tank can be adhered to one of the plates by double backed tape that is sandwiched between the tank and plate, thereby avoiding the use of a rubber sealing gasket between the tank and plate. As a result, the distance between the tank and the plate is kept constant. A buffer solution in the tank communicates with the gel. The cassette can then be placed in a lower buffer tank and an electric field applied to the buffer solutions to effect electrophoresis of DNA fragments that have been placed in the gel. In an alternate embodiment, a window is formed in one of the plastic plates to allow laser light to pass into the cassette and excite a fluorescent tag in the DNA. The fluorescence then passes back through the window for detection by a sensor, to automatically determine the DNA sequence of the sample in the gel in accordance with auto DNA sequencing principles.Type: GrantFiled: February 23, 1998Date of Patent: February 22, 2000Inventors: Hidetaka Yamamura, Richard T. L. Chan
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Patent number: 6017435Abstract: A method of imaging molecules of interest within a biological sample includes shining a UV light onto the sample and detecting the molecular UV absorption. Where the molecules of interest are themselves UV absorbers, the intrinsic absorption of those molecules may be used. If the molecules of interest are not good UV absorbers, UV-absorbing tag molecules may be used. The method may be used in molecular imaging devices of all types, and in DNA sequencers. A novel diamond-based detector is disclosed which is suitable for many applications.Type: GrantFiled: April 23, 1998Date of Patent: January 25, 2000Assignee: Imperial College of Science, Technology and MedicineInventors: John Francis Hassard, Stuart Hassard, Alison Mary Mainwood
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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: 6007691Abstract: The subject invention provides methods and kits for conveniently diagnosing various physiological conditions that produce altered levels of specific carbohydrates, known as diagnostic carbohydrates. Measurement of the levels of the diagnostic carbohydrates is performed by fluorophore assisted carbohydrate electrophoresis. Physiological conditions of particular interest that may be ascertained by the subject invention include carbohydrate metabolism diseases, autoimmune diseases, neoplasia, toxic chemical exposure and microbial infections. Fluorophore assisted carbohydrate electrophoresis diagnosis may be applied to various patient specimens, including blood, urine and skin.Type: GrantFiled: April 23, 1993Date of Patent: December 28, 1999Assignee: Glyko, Inc.Inventor: John C. Klock, Jr.
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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: 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: 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: 5949899Abstract: A system for measuring and analyzing an image of a gel electrophoresis, includes measuring apparatus and a processor. The measuring apparatus includes a frame mountable in a fixed location relative to the image, including a bar extending along a first axis, a carriage coupled to the bar and slidable along the first axis, an alignment device extending transversely from the carriage along a second axis for aligning selected components of the image, and a distance sensor operatively coupled to the carriage for sensing the distance travelling by the carriage and generating distance signals. The processor is operatively coupled to the measuring apparatus and processes the distance signals and generates maps based thereon. The subject system is well suited for constructing restriction enzyme maps for an image of bands created by subjecting DNA to gel electrophoresis.Type: GrantFiled: October 1, 1996Date of Patent: September 7, 1999Assignee: Nebular Vision Research & Development Inc.Inventor: David Ng
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Patent number: 5904822Abstract: This invention relates to a system and methods for the straightening an electrophoresis gel image in the vertical and horizontal directions, and for analyzing a straightened gel image. The system includes an input unit for receiving raw data from the electrophoresis gel, a straightening unit for providing a straightened gel image, an output unit for portraying the raw data from the electrophoresis gel and the straightened gel image, and a an analyzing unit for analyzing the data portrayed in the straightened gel image. The system features a dye boost feature for boosting the intensity of bands, filtering means for modifying the gel image, and a genotype editing feature for editing the results of an automatic gel analysis. The system allows for manual and automatic analysis of the straightened gel image according to a specified set of analysis parameters providing a range of analysis stringency levels.Type: GrantFiled: November 13, 1996Date of Patent: May 18, 1999Assignee: The University of Iowa Research FoundationInventor: Thomas L. Casavant
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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: 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: 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: 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: 5865974Abstract: A substantially closed cassette for conducting therein electrophoresis separation which includes a closed chamber, the chamber includes therein a body of gel, at least one ion source having a volume smaller than the volume of the gel for providing ions for driving the electrophoresis separation and electrodes for connecting the cassette to an external electrical power source, thereby enabling to drive the electrophoresis separation.Type: GrantFiled: April 26, 1996Date of Patent: February 2, 1999Assignee: Ethrog Biotechnology Ltd.Inventors: Shmuel Cabilly, Uri Yogev
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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: 5863403Abstract: To sequence DNA automatically, fluorescently marked DNA are electrophoresed in a plurality of channels through a gel electrophoresis slab; wherein the DNA samples are resolved in accordance with the size of DNA fragments in the gel electrophoresis slab into fluorescently marked DNA bands. The separated samples are scanned photoelectrically with a laser and a sensor, wherein the laser scans with scanning light at a scanning light frequency within the absorbance spectrum of said fluorescently marked DNA samples and light is sensed at the emission frequency of the marked DNA. The light is modulated from said laser at a predetermined modulation frequency and fluorescent light emitted by said DNA bands at said modulation frequency is detected, whereby background noise from the medium through which the light is transmitted is discriminated against.Type: GrantFiled: August 26, 1996Date of Patent: January 26, 1999Assignee: The Board of Regents of the University of NebraskaInventors: Lyle Richard Middendorf, John Albert Brumbaugh, Gi Young Jang
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Patent number: 5846395Abstract: An electrophoresis apparatus for automatically performing medical assays includes an electrophoresis platform which cooperates with a gantry assembly. The electrophoresis platform and the gantry assembly are movable along paths that are perpendicular to each other. An applicator assembly includes pipettes which transfer fluid samples from a specimen tray to an electrophoresis plate mounted on the electrophoresis platform. The electrophoresis platform then moves to a position into the gantry assembly, where electrophoresis is conducted to separate the samples into different fractions. The electrophoresis platform then moves beneath a reagent pouring station where a reagent is applied to make the separated fractions fluoresce under ultraviolet light. The electrophoresis platform is then moved beneath the gantry assembly again, and an air knife in the gantry assembly spreads the reagent.Type: GrantFiled: April 25, 1997Date of Patent: December 8, 1998Assignee: Helena Laboratories CorporationInventors: Robert J. Sarrine, Henry A. Garsee, Charles D. Kelley, Michael T. Everitt, Earl W. Boone, Philip A. Guadagno, Eric H. Petersen, Tipton L. Golias
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Patent number: 5799773Abstract: A method and apparatus for correcting an image of an electrophoresis gel for lens and detector non-uniformities is provided. The removal of such non-uniformities, in conjunction with a uniform illumination source, allows quantitative measurements of an electrophoresis gel to be made, thus increasing the information which can be obtained from an electrophoretic analysis. Lens and detector non-uniformities are removed by first determining the magnitude of the non-uniformities using a calibration standard. The calibration standard has a uniform emittance, preferably in the same wavelength band as the labeled regions of the electrophoresis gel. By placing the calibration standard in close proximity to the entrance aperture of the lens, the calibration process is relatively insensitive to illumination source non-uniformities. Thus an image of the calibration standard taken with the same lens settings as the unknown provides detailed information on the lens and detector non-uniformities.Type: GrantFiled: March 10, 1997Date of Patent: September 1, 1998Assignee: Bio-Rad Laboratories, Inc.Inventors: David M. Heffelfinger, Craig Van Horn
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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: 5755943Abstract: To sequence DNA, DNA samples marked with flourscent infrared dye are applied at a plurality of locations for electrophoresing in a plurality of channels through a gel electrophoresis slab. The channels are scanned with a laser and a sensor, that include a microscope focused on the gel slab. The focal point and slab are adjusted with respect to each other so that the focal point of the microscope remains on the gel slab during a scan. The data from the scan is directly used to amplitude modulate density readings on a display, and the scan is displayed in a horizontal sweep of a cathode ray tube, whereby said cathode ray tube provides intensity displays of bands representing DNA. Different sizes of glass gel sandwiches may be mounted to the same console for different sequencing tasks.Type: GrantFiled: July 8, 1996Date of Patent: May 26, 1998Assignee: Li-Cor, Inc.Inventors: Lyle Richard Middendorf, Robert Clark Bruce, Robert David Eckles
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Patent number: 5710628Abstract: Improved detection methods and apparatus which may be used individually or in various combinations enhance the ability of the electrophoresis apparatus to detect fluorophore-labeled materials in short periods of time.Type: GrantFiled: December 12, 1994Date of Patent: January 20, 1998Assignee: Visible Genetics Inc.Inventors: Paul Waterhouse, John A. Renfrew, John K. Stevens
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Patent number: 5667656Abstract: 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: May 14, 1996Date of Patent: September 16, 1997Assignee: Hitachi, Ltd.Inventor: Hideki Kambara
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Patent number: 5628891Abstract: An electrophoresis gel carrier includes end mounts, each having a buffer well and retainer elements constructed to support an electrophoresis medium gel so that the gel is in communication with the buffer well. Each end mount includes a base plate which defines the buffer well as well as a lower retainer element. Each end mount also includes an upper retainer element which when aligned with the lower retainer defines an opening in fluid communication with the buffer well. The openings in each of the end mounts receive opposite ends of the electrophoresis medium gel so that the gel is in communication with the buffer well. An apparatus is provided which allows a number of electrophoresis gels, mounted in gel carriers, to be analyzed using a single detector.Type: GrantFiled: December 6, 1995Date of Patent: May 13, 1997Assignee: AAT Laboratories, Inc.Inventor: Richard K. Lee
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Patent number: 5616228Abstract: The electrophoresis apparatus has a capillary filled with gel for use in electrophoresis. A first buffer solution container is provided for storing a buffer solution and introducing a sample labelled with a fluorescent substance into an inlet of said capillary for electrophoresis. A second buffer solution container is provided for storing a buffer solution containing a luminous solution, into which said sample is continually introduced from an outlet of said capillary after electrophoresis. Electrophoresis means is provided for subjecting said sample to electrophoresis by applying a predetermined value of voltage to said gel through which said sample is being transferred while being electrophoresed. Light receiving means is disposed underneath the outlet of said capillary to read fluorescence emitted from said sample from bottom in a direction in which said sample is approaching closer.Type: GrantFiled: September 28, 1995Date of Patent: April 1, 1997Assignee: Hitachi Software Engineering Co., Ltd.Inventors: Hisanori Nasu, Kenji Yamamoto, Hitoshi Fujimiya
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Patent number: 5614073Abstract: Disclosed is a method for and an apparatus for detecing amines or amino acids, which apparatus generally includes a capillary electrophoresis separation tube with a post-capillary reactor positioned at the end of the tube to immediately receive separated samples from the tube. The post-capillary reactor includes a solution of Ru(bpy).sub.3.sup.2+ buffered with a base. The post capillary reactor further includes an electrode assembly for providing current to the solution to convert nonluminescing Ru(bpy).sub.3.sup.2+ to luminescing Ru(bpy).sub.3.sup.3+. The method generally includes separating the desired analyte from the sample, contacting the analyte with the solution to produce luminescence, and then photometrically measuring the amount of analyte present as a function of the luminescence.Type: GrantFiled: March 13, 1995Date of Patent: March 25, 1997Assignee: Board of Trustees of the University of ArkansasInventors: Donald R. Bobbitt, Warren A. Jackson
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Patent number: 5607568Abstract: An assembly suitable for identifying a code sequence of at least a portion of a biomolecule in a free-solution embodiment. The assembly comprises first means for migrating and separating a portion of a biomolecule in a free-solution; second means comprising a near-field probe for generating a super-resolution chemical analysis of a portion of a biomolecule; and, third means for correlating the super-resolution chemical analysis of the portion of the biomolecule with a broad spectral content of a referent biomolecule, for generating a code sequencing of the portion of the biomolecule.Type: GrantFiled: March 16, 1995Date of Patent: March 4, 1997Assignee: International Business Machines CorporationInventors: Frederic Zenharusern, Hemantha K. Wickramasinghe
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Patent number: 5583279Abstract: An electrophoresis apparatus for automatically performing medical assays includes an electrophoresis platform which cooperates with a gantry assembly. The electrophoresis platform and the gantry assembly are movable along paths that are perpendicular to each other. An applicator assembly includes pipettes which transfer fluid samples from a specimen tray to an electrophoresis plate mounted on the electrophoresis platform. The electrophoresis platform then moves to a position into the gantry assembly, where electrophoresis is conducted to separate the samples into different fractions. The electrophoresis platform then moves beneath a reagent pouring station where a reagent is applied to make the separated fractions fluoresce under ultraviolet light. The electrophoresis platform is then moved beneath the gantry assembly again, and an air knife in the gantry assembly spreads the reagent.Type: GrantFiled: June 7, 1995Date of Patent: December 10, 1996Assignee: Helena Laboratories CorporationInventors: Robert J. Sarrine, Henry A. Garsee, Charles D. Kelley, Michael T. Everitt, Earl W. Boone, Philip A. Guadagno, Eric H. Petersen, Tipton L. Golias
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Patent number: 5582702Abstract: A substantially closed cassette for conducting therein electrophoresis separation which includes a closed chamber, the chamber includes therein a body of gel, means for providing ions for driving the electrophoresis separation and electrodes for connecting the cassette to an external electrical power source, thereby enabling to drive the electrophoresis separation.Type: GrantFiled: April 26, 1995Date of Patent: December 10, 1996Assignee: Ethrog Biotechnology Ltd.Inventors: Shmuel Cabilly, Uri Yogev
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Patent number: 5571388Abstract: 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: March 1, 1994Date of Patent: November 5, 1996Assignee: Li-Cor, Inc.Inventors: Gabor Patonay, Narasimhachari Narayanan, Lucjan Strekowski, Lyle R. Middendorf, Malgorzata Lipowska
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Patent number: 5569366Abstract: Processes for the electrophoretic analysis of monosaccharides and/or polysaccharides are disclosed. The processes generally first include providing a composition having derivatized mono and/or polysaccharide components which are monosaccharide and/or polysaccharide labelled with a fluorescing charged compound. Then introducing the composition into an electrophoretic medium and applying an electric field across the electrophoretic medium causes the derivatized monosaccharide and/or polysaccharide components to differentially migrate within the electrophoretic medium. Then detecting the derivatized monosaccharide and/or polysaccharide components is accomplished by laser exciting the derivatized monosaccharide and/or polysaccharide components and monitoring fluorescent emission of the derivatized monosaccharide and/or polysaccharide components. The processes provide extremely low detection limits of the labelled components.Type: GrantFiled: January 27, 1995Date of Patent: October 29, 1996Assignee: Beckman Instruments, Inc.Inventors: Fu-Tai A. Chen, Ming-Sun Liu, Ramon A. Evangelista
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Patent number: 5556529Abstract: The improved DNA base sequencer has a flat plate type gel electrophoretic unit that has multiple tracks for electrophoresing DNA fragments and which is held in a vertical position, a light exciting laser light applying unit that applies laser light to the respective tracks in the electrophoretic unit from one lateral side thereof in such a way that it crosses the tracks at right angles, and a fluorescence detecting unit that detects the fluorescence as generated from the DNA fragments illuminated with the laser light and which converts the detected fluorescence to an electric signal. The sequencer is characterized in that the fluorescence detecting unit comprises a fluorescence condensing lens, a fluorescence filtering unit and a solid-state imaging device, (e.g., a CCD line sensor), the fluorescence filtering unit being composed of at least two filters that selectively transmit fluorescences having different wavelengths and that are staggered with each other along a common longitudinal axis.Type: GrantFiled: July 10, 1995Date of Patent: September 17, 1996Assignee: Hitachi Electronics Engineering Co., Ltd.Inventor: Ryozi Nemoto
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Patent number: 5552322Abstract: The improved DNA base sequencer comprises a flat plate type gel electrophoretic means that has a multiple of tracks for electrophoresing DNA fragments and which is held in a vertical position, a light exciting laser light applying means that applies laser light to the respective tracks in said electrophoretic means from one lateral side thereof in such a way that it crosses said tracks at right angles, and a fluorescence detecting means that detects the fluorescence as generated from the DNA fragments illuminated with the laser light and which converts the detected fluorescence to an electric signal, and it is characterized in that the fluorescence detecting means comprises an index-distributed lens array, a filter and a solid-state imaging device such as a CCD line sensor. This apparatus uses light-receiving optics that does not include a large and expensive optical device such as an image intensifier and which yet is capable of efficient fluorescence detection without "smiling" and other adverse effects.Type: GrantFiled: September 28, 1994Date of Patent: September 3, 1996Assignee: Hitachi Electronics Engineering Co., Ltd.Inventors: Ryozi Nemoto, Yoshinori Mishina
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Patent number: 5549805Abstract: To sequence DNA automatically, fluorescently marked DNA are electrophoresed in a plurality of channels through a gel electrophoresis slab; wherein the DNA samples are resolved in accordance with the size of DNA fragments in the gel electrophoresis slab into fluorescently marked DNA bands. The separated samples are scanned photoelectrically with a laser and a sensor, wherein the laser scans with scanning light at a scanning light frequency within the absorbance spectrum of said fluorescently marked DNA samples and light is sensed at the emission frequency of the marked DNA. The light is modulated from said laser at a predetermined modulation frequency and fluorescent light emitted by said DNA bands at said modulation frequency is detected, whereby background noise from the medium through which the light is transmitted is discriminated against.Type: GrantFiled: August 11, 1994Date of Patent: August 27, 1996Assignee: The Board of Regents of the University of NebraskaInventors: Lyle R. Middendorf, John A. Brumbaugh, Gi Y. Jang
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Patent number: 5543018Abstract: 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 through 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: February 13, 1995Date of Patent: August 6, 1996Assignee: Visible Genetics Inc.Inventors: John K. Stevens, Alexandre M. Ismailov
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Patent number: 5543026Abstract: This invention relates to an improved real-time scanning fluorescence electrophoresis apparatus for the electrophoretic analysis of fluorescently-labeled polynucleotide fragments. The apparatus is characterized by having an electrophoresis chamber containing an electrophoretic separation medium capable of accommodating multiple electrophoresis lanes arranged in a planar array, a fluorescence detector mounted on a translatable stage, a light source for exciting fluorescent molecules, and a computer for collecting data consisting of time, location, fluorescence wavelength and fluorescent intensity information. The improvements herein disclosed include, (i) using a spectral-array detector for detecting the emission light from the fluorescently-labeled polynucleotide fragments including the simultaneous detection of multiple fluorescent labels, and, (ii) a temperature control means to control the temperature of the electrophoretic separation medium during electrophoresis.Type: GrantFiled: February 7, 1994Date of Patent: August 6, 1996Assignee: The Perkin-Elmer CorporationInventors: Louis B. Hoff, Eric W. Lachenmeier, Yefim M. Raysberg, Eric S. Nordman
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Patent number: 5541067Abstract: The present invention pertains to a process which can be fully automated for accurately determining the alleles of STR genetic markers. More specifically, the present invention is related to performing PCR amplification on locations of DNA, labelling the PCR products, converting the labels into a signal, removing a reproducible PCR stutter pattern from the signal by means of a computational device, and then determining the genotype of the location of the DNA. An amplification can include multiple locations from the DNA of one or more individuals. The invention also pertains to genetics applications and systems which can effectively use this genotyping information.Type: GrantFiled: September 29, 1994Date of Patent: July 30, 1996Inventor: Mark W. Perlin
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Patent number: 5541420Abstract: The fraction collector according to the present invention comprises a separating means composed of electrophoresis tracks to separate samples by electrophoresis, and a transferring means to transfer the separated components eluted from said electrophoresis tracks, a transferring means which comprises the capillary sample transferring tubes which are placed with their ends close to the ends of said electrophoresis tracks at the specified gap, and which transfers the separated components eluted from each electrophoresis track, a transport means to supply the buffer solution to said gap and to carry said separated component to said sample transferring tube by sheathflow of said buffer solution, a fractionating means to fractionate the separated components having moved inside said sample transfer tube, a detecting means to detect the elution of said separated component by detecting the light emitted from said separated component, and a control means to control said fractionating means based on the signal gained bType: GrantFiled: December 21, 1994Date of Patent: July 30, 1996Assignee: Hitachi, Ltd.Inventor: Hideki Kambara
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Patent number: 5538613Abstract: An apparatus for detecting fluorescently-labeled molecules moving in an electrophoretic separation medium. The apparatus utilizes a scanning detection system in which multiple fluorophores are efficiently and simultaneously detected using dichroic mirrors to allow simultaneous detection of fluorescently-labeled molecules in ultrathin gels labeled with several fluorophores and to permit operation at speeds ten times faster than prior art gel separations. The apparatus also utilizes a detection system where lightweight collection optics are in motion while detection optics are fixed in a remote location, thereby allowing exceptionally high-speed scanning.Type: GrantFiled: October 19, 1995Date of Patent: July 23, 1996Assignee: GeneSys Technologies, Inc.Inventors: Robert L. Brumley, John A. Luckey
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Patent number: 5534125Abstract: To sequence DNA, DNA samples marked with flourscent infrared dye are applied at a plurality of locations for electrophoresing in a plurality of channels through a gel electrophoresis slab. The channels are scanned with a laser and a sensor, that include a microscope focused on the gel slab. The focal point and slab are adjusted with respect to each other so that the focal point of the microscope remains on the gel slab during a scan. The data from the scan is directly used to amplitude modulate density readings on a display, and the scan is displayed in a horizontal sweep of a cathode ray tube, whereby said cathode ray tube provides intensity displays of bands representing DNA. Different sizes of glass gel sandwiches may be mounted to the same console for different sequencing tasks.Type: GrantFiled: August 10, 1994Date of Patent: July 9, 1996Assignee: Li-Cor, Inc.Inventors: Lyle R. Middendorf, Robert C. Bruce, Robert D. Eckles
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Patent number: 5516409Abstract: 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: January 13, 1995Date of Patent: May 14, 1996Assignee: Hitachi, Ltd.Inventor: 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