Patents by Inventor Michael W. Hunkapiller
Michael W. Hunkapiller has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 6432642Abstract: Binary probe and clamp compositions conduct methods for target hybridization detection. Where the probe is a substrate for exonuclease cleavage, the composition provides quantitation and detection of PCR products, by real-time and end-point measurements. Where the probe is an amplification primer, the composition provides an improved method for labelling and detection of PCR products. Probes and clamps may be labelled with fluorescent dyes, quenchers, hybridization-stabilizing moieties, chemiluminescent dyes, and affinity ligands. Clamps may be nucleic acid analogs, such as 2-aminoethylglycine PNA.Type: GrantFiled: January 15, 1999Date of Patent: August 13, 2002Assignee: PE Corporation (NY)Inventors: Kenneth J. Livak, Michael Egholm, Michael W. Hunkapiller
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Patent number: 6258539Abstract: The present invention relate to methods and compositions for simultaneously analyzing multiple different polynucleotides of a polynucleotide composition comprising multiple diverse polynucleotide sequences. The subject methods and compositions may also be applied to analyze or identify single polynucleotides; however, the subject methods and compositions are particularly useful for analyzing large diverse populations of polynucleotides, e.g., cDNA libraries. Most embodiments of the invention involve hybridizing terminus probes (of known base sequence) to adapter-modified restriction fragment generated from polynucleotide for analysis, and subsequently joining the terminus probes and internal fragment probes to each other. The terminus probe hybridizes to bases of restriction endonuclease recognition site present at the terminus of a restriction fragment generated from the polynucleotide for analysis.Type: GrantFiled: April 30, 1999Date of Patent: July 10, 2001Assignee: The Perkin-Elmer CorporationInventors: Michael W. Hunkapiller, John H. Richards
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Patent number: 6232067Abstract: The present invention relate to methods and compositions for simultaneously analyzing multiple different polynucleotides of a polynucleotide composition comprising multiple diverse polynucleotide sequences. The subject methods and compositions may also be applied to analyze or identify single polynucleotides; however, the subject methods and compositions are particularly useful for analyzing large diverse populations of polynucleotides, e.g., cDNA libraries. Most embodiments of the invention involve hybridizing terminus probes (of known base sequence) and internal fragment probes (of known base sequence) at adjacent positions on an adapter-modified restriction fragment generated from polynucleotide for analysis, and subsequently joining the terminus probes and internal fragment probes to each other. The terminus probe hybridizes to bases of restriction endonuclease recognition site present at the terminus of a restriction fragment generated from the polynucleotide for analysis.Type: GrantFiled: August 17, 1998Date of Patent: May 15, 2001Assignee: The Perkin-Elmer CorporationInventors: Michael W. Hunkapiller, John H. Richards
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Patent number: 6200748Abstract: This invention provides a duplex comprising an oligonucleotide primer and a template, wherein the primer is coupled chemically to a chromophore or fluorophore so as to allow chain extension by a polymerase. In one embodiment, the primer is extended by a polymerase to generate the complement of the template. In a further embodiment, the extended primer is separated from the template for use in a number of methods, including sequencing reactions. Methods of generating these compositions of matter are further provided.Type: GrantFiled: June 7, 1995Date of Patent: March 13, 2001Assignee: California Institute of TechnologyInventors: Lloyd M. Smith, Leroy E. Hood, Michael W. Hunkapiller, Tim J. Hunkapiller, Charles R. Connell
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Patent number: 6054266Abstract: Nucleic acid sequences are detected by a multi-step process, involving labeling sample nucleic acid sequences, duplexing the labeled sample with a probe having a coupling element, immobilizing all of the duplexed probe and target sequence and unduplexed probe, separating specifically immobilized nucleic acid from free and non-specifically immobilized nucleic acid, releasing specifically immobilized nucleic acid, and detecting the presence of the sequence of interest by means of the label. The labeled sequence may be characterized by sizing, e.g. electrophoresis. The method provides for a sensitive and rapid means for accurate detection of sequences of interest in a wide variety of situations.Type: GrantFiled: November 23, 1988Date of Patent: April 25, 2000Assignee: Applied Biosystems, Inc.Inventors: Mel N. Kronick, Douglas H. Keith, Lincoln J. McBride, Norman M. Whiteley, Michael W. Hunkapiller
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Patent number: 5962223Abstract: The invention provides a method for diagnosis of genetic abnormalities or other genetic conditions which can be readily automated. The method is used to determine the presence or absence of a target sequence in a sample of denatured nucleic acid and entails hybridizing the sample with a probe complementary to a diagnostic portion of the target sequence (the diagnostic probe), and with a probe complementary to a nucleotide sequence contiguous with the diagnostic portion (the contiguous probe), under conditions wherein the diagnostic probe remains bound substantially only to the sample nucleic acid containing the target sequence. The diagnostic probe and contiguous probe are then covalently attached to yield a target probe which is complementary to the target sequence, and the probes which are not attached are removed.Type: GrantFiled: December 19, 1995Date of Patent: October 5, 1999Assignee: The Perkin-Elmer CorporationInventors: Norman M. Whiteley, Michael W. Hunkapiller, Alexander N. Glazer
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Patent number: 5942609Abstract: The present invention concerns methods of assembly of a polynucleotide on a solid-support by performing steps of annealing, ligation, and extension. The steps may be repeated in a cyclical manner to assemble immobilized double- or single-stranded polynucleotides with functional gene properties. The immobilized polynucleotides may be amplified by the polymerase chain reaction, and detected and quantitated by an exonuclease assay with a self-quenching, fluorescent probe. The polynucleotide may be cleaved from the solid-support by chemical or enzymatic cleavage.Type: GrantFiled: November 12, 1998Date of Patent: August 24, 1999Assignee: The Porkin-Elmer CorporationInventors: Michael W. Hunkapiller, Andrew C. Hiatt
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Patent number: 5821058Abstract: A process for the electrophoretic analysis of DNA fragments produced in DNA sequencing operations wherein chromophores or fluorophores are used to tag the DNA fragments produced by the sequencing chemistry and permit the detection and characterization of the fragments as they are resolved by electrophoresis through a gel. Preferably four different fragment sets are tagged with the fluorophores fluorescein, Texas Red, tetramethyl rhodamine, and 7-nitrobenzofurazan. A system for the electrophoretic analysis of DNA fragments produced in DNA sequencing operations comprising: a source of chromophore or fluorescent tagged DNA fragments; a zone for contacting an electrophoresis gel; means for introducing said tagged DNA fragments to said zone; and photometric means for monitoring said tagged DNA fragments as they move through said gel.Type: GrantFiled: December 21, 1994Date of Patent: October 13, 1998Assignee: California Institute of TechnologyInventors: Lloyd M. Smith, Leroy E. Hood, Michael W. Hunkapiller, Tim J. Hunkapiller, Charles R. Connell
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Patent number: 5747249Abstract: A process for the electrophoretic analysis of DNA fragments produced in DNA sequencing operations wherein chromophores or fluorophores are used to tag the DNA fragments produced by the sequencing chemistry and permit the detection and characterization of the fragments as they are resolved by electrophoresis through a gel. Preferably four different fragment sets are tagged with the fluorophores fluorescein, Texas Red, tetramethyl rhodamine, and 7-nitro-benzofurazan. A system for the electrophoretic analysis of DNA fragments produced in DNA sequencing operations comprising: a source of chromophore or fluorescent tagged DNA fragments; a zone for contacting an electrophoresis gel; means for introducing said tagged DNA fragments to said zone; and photometric means for monitoring said tagged DNA fragments as they move through said gel.Type: GrantFiled: December 21, 1994Date of Patent: May 5, 1998Assignee: California Institute of TechnologyInventors: Lloyd M. Smith, Leroy E. Hood, Michael W. Hunkapiller, Tim J. Hunkapiller, Charles R. Connell
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Patent number: 5521065Abstract: A method of testing for the presence or absence of a target sequence in a mixture of single-stranded nucleic acid fragments is disclosed. The method involves reacting a mixture of single-stranded nucleic acid fragments with a first probe which is complementary to a first region of the target sequence, and with a second probe which is complementary to a second region of the target sequence, where the first and second target regions are contiguous with one another, under hybridization conditions in which the two probes become stably hybridized to their associated target regions. Following hybridization, any of the first and second probes hybridized to contiguous first and second target regions are ligated, and the sample is tested for the presence of expected probe ligation product. The presence of ligated product indicates that the target sequence is present in the sample.Type: GrantFiled: June 8, 1994Date of Patent: May 28, 1996Assignee: Applied Biosystems, Inc.Inventors: Norman M. Whiteley, Michael W. Hunkapiller, Alexander N. Glazer
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Patent number: 5273715Abstract: An automated system for providing a preselected sequence of chemicals to a reaction. This apparatus includes a track on which a set of cartridges are placed in a preselected order corresponding to an order in which they are to be used in a reaction process. These cartridges are moved past a point at which these chemicals are extracted for use in the process. The chemicals are preferably in liquid form and are contained in containing having a top seal through which a needle can penetrate to extract chemicals for use in the process. These containers preferably contain the aliquot portion needed for the process, thereby providing a mechanism for providing accurate amounts of each chemical to the process.Type: GrantFiled: November 6, 1992Date of Patent: December 28, 1993Assignee: Applied Biosystems, Inc.Inventors: John Bridgham, Timothy G. Geiser, Michael W. Hunkapiller, Stephen B. H. Kent, Mark P. Marplott, Paul O. Ramstad
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Patent number: 5242794Abstract: The invention provides a method for diagnosis of genetic abnormalities or other genetic conditions which can be readily automated. The method is used to determine the presence or absence of a target sequence in a sample of denatured nucleic acid and entails hybridizing the sample with a probe complementary to a diagnostic portion of the target sequence (the diagnostic probe), and with a probe complementary to a nucleotide sequence contiguous with the diagnostic portion (the contiguous probe), under conditions wherein the diagnostic probe remains bound substantially only to the sample nucleic acid containing the target sequence. The diagnostic probe and contiguous probe are then covalently attached to yield a target probe which is complementary to the target sequence, and the probes which are not attached are removed.Type: GrantFiled: June 5, 1989Date of Patent: September 7, 1993Assignee: Applied Biosystems, Inc.Inventors: Norman M. Whiteley, Michael W. Hunkapiller, Alexander N. Glazer
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Patent number: 5186898Abstract: An apparatus is provided for automatically constructing a polypeptide of high purity, up to 50 amino acids in length, using only single couplings. The apparatus includes an activation system for receiving protected amino acids, one kind at a time, having a common vessel (an activator vessel) in which to activate each of the amino acids. Also included is a reaction vessel for containing a resin used in solid-phase peptide synthesis for attaching a peptide chain thereto. A transfer system is also provided, which operates under control of a computer, to transfer the activated species from the activation system to the reaction vessel and to transfer amino acids, reagents, gases, and solvents from one part of the apparatus to another. The activator system also includes a temperature controlled concentrator vessel in which an activator solvent is replaced by a coupling solvent to enhance the coupling of the activated species to the peptide chain in the reaction vessel.Type: GrantFiled: March 24, 1989Date of Patent: February 16, 1993Assignee: Applied Biosystems, Inc.Inventors: John Bridgham, Timothy G. Geiser, Michael W. Hunkapiller, Stephen B. H. Kent, Mark P. Marriott, Paul O. Ramstad, Eric S. Nordman
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Patent number: 5171534Abstract: A system for the electrophoretic analysis of DNA fragments produced in DNA sequencing operations comprising: a source of chromophore or fluorescent tagged DNA fragments; a zone for contacting an electrophoresis gel; means for introducing said tagged DNA fragments to said zone; and photometric means for monitoring said tagged DNA fragments as they move through said gel.Type: GrantFiled: October 15, 1990Date of Patent: December 15, 1992Assignee: California Institute of TechnologyInventors: Lloyd M. Smith, Leroy E. Hood, Michael W. Hunkapiller, Tim J. Hunkapiller
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Patent number: 4883750Abstract: The invention provides a method for diagnosis of genetic abnormalities or other genetic conditions which can be readily automated. The method is used to determine the presence or absence of a target sequence in a sample of denatured nucleic acid and entails hybridizing the sample with a probe complementary to a diagnostic portion of the target sequence (the diagnostic probe), and with a probe complementary to a nucleotide sequence contiguous with the diagnostic portion (the contiguous probe), under conditions wherein the diagnostic probe remains bound substantially only to the sample nucleic acid containing the target sequence. The diagnostic probe and contiguous probe are then covalently attached to yield a target probe which is complementary to the target sequence, and the probes which are not attached are removed.Type: GrantFiled: December 13, 1984Date of Patent: November 28, 1989Assignee: Applied Biosystems, Inc.Inventors: Norman M. Whiteley, Michael W. Hunkapiller, Alexander N. Glazer
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Patent number: 4852017Abstract: An apparatus and process are used to cyclicly degrade a peptide to be sequenced, arriving at a set of amino acid residues for each cycle. The amount of each amino acid residue is quantitatively measured in each set, then a background level is fit to each cycle to obtain a background fit. A measure of dispersion is then calculated for the background fit, and the measured amounts of amino acid residues in each cycle are normalized relative to the background fit. The largest normalized background-corrected residue amount in each cycle then provides a sequence assignment that can be used for further correction steps if desired.Type: GrantFiled: June 19, 1987Date of Patent: July 25, 1989Assignee: Applied Biosystems, Inc.Inventor: Michael W. Hunkapiller
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Patent number: 4837726Abstract: A process and apparatus for quantitating chromatographic information uses a discrete, linear, translation invariant filter function a.sub.N.sup..alpha., where N is a measure of the filter function width and .alpha. is a parameter whose value determines signal to noise characteristics of the filter function. First a chromatographic analysis of a sample is performed to obtain a first chromatogram. Then the first chromatogram is filtered with the filter function, with N set to approximate the width of peaks obtained in the first chromatogram, and .alpha. is set to filter out high frequency noise from the first chromatogram to obtain a second chromatogram having a first filtered baseline. The second chromatogram is then filtered with .alpha. set to resolution enhance peaks in the second chromatogram to obtain a third chromatogram having a baseline which is substantially the same as the first filtered baseline.Type: GrantFiled: June 19, 1987Date of Patent: June 6, 1989Assignee: Applied Biosystems, Inc.Inventor: Michael W. Hunkapiller
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Patent number: 4816513Abstract: An apparatus is provided for automatically constructing a polypeptide of high purity, up to 50 amino acids in length, using only single couplings. The apparatus includes an activation system for receiving protected amino acids, one kind at a time, having a common vessel (an activator vessel) in which to activate each of the amino acids. Also included is a reaction vessel for containing a resin used in solid-phase peptide synthesis for attaching a peptide chain thereto. A transfer system is also provided, which operates under control of a computer, to transfer the activated species from the activation system to the reaction vessel and to transfer amino acids, reagents, gases, and solvents from one part of the apparatus to another. The activator system also includes a temperature controlled concentrator vessel in which an activator solvent is replaced by a coupling solvent to enhance the coupling of the activated species to the peptide chain in the reaction vessel.Type: GrantFiled: May 22, 1987Date of Patent: March 28, 1989Assignee: Applied Biosystems, Inc.Inventors: John Bridgham, Timothy G. Geiser, Michael W. Hunkapiller, Stephen B. H. Kent, Mark P. Marriott, Paul O. Ramstad, Eric S. Nordman
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Patent number: 4811218Abstract: A real-time, automated, nucleic acid sequencing apparatus that offers high speed, definitive sequencing on many samples at the same time. The apparatus permits more than one clone to be sequenced at a time, thus vastly decreasing the time required to sequence longer fragments and reducing sequencing costs accordingly. The apparatus detects electromagnetic radiation from a plurality of lanes in an electrophoresis system wherein the plurality of lanes are arranged in a planar array. The apparatus includes an optical system for detecting the radiation at a plurality of wavelengths and is made up of a collection element, a filter for selectively transmitting the plurality of wavelengths received from the collection element, and a detection system for measuring intensity of the radiation received from the filter means.Type: GrantFiled: June 2, 1986Date of Patent: March 7, 1989Assignee: Applied Biosystems, Inc.Inventors: Michael W. Hunkapiller, Charles R. Connell, William J. Mordan, John D. Lytle, John A. Bridgham
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Patent number: 4704256Abstract: An improved apparatus and method for the sequential performance of chemical processes on a sample of chemical material wherein the sample is embedded in a solid matrix of fluid permeable material located within a reaction chamber and is sequentially subjected to a plurality of fluids passed through the chamber in a pressurized stream, causing chemical interaction between the sample and the fluids.Type: GrantFiled: November 10, 1982Date of Patent: November 3, 1987Assignee: California Institute of TechnologyInventors: Leroy E. Hood, Michael W. Hunkapiller, William J. Dreyer, Rodney M. Hewick, Anton W. Stark