Patents Assigned to Pacific Biosciences of California, Inc.
  • Patent number: 10234393
    Abstract: Arrays of integrated analytical devices and their methods for production are provided. The arrays are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The devices allow the highly sensitive discrimination of optical signals using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices include an integrated diffractive beam shaping element that provides for the spatial separation of light emitted from the optical reactions.
    Type: Grant
    Filed: February 20, 2018
    Date of Patent: March 19, 2019
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Annette Grot, Ravi Saxena, Paul Lundquist
  • Patent number: 10190158
    Abstract: A circuit comprising a substrate with sectors on the substrate is provided, each sector comprising clock and data lines, a controller in electrical communication with the clock and data lines, a counter bias line, an amplifier input line and nano-electronic measurement devices on the substrate. A source of each device is coupled to the counter bias line and a drain of each device is coupled to the amplifier input line to obtain an electrical signal on the drain, the identity of which is determined by electrical interaction between the device and a charge label. Each device drain is gated by a corresponding switch between an on state, in which the drain is connected to the amplifier input line, and an off state, in which the drain is isolated from the amplifier input line. The controller controls switch states responsive to clock signal line pulses and data input line data.
    Type: Grant
    Filed: August 3, 2016
    Date of Patent: January 29, 2019
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Stephen Turner, Jonas Korlach, Steven Warren
  • Patent number: 10184148
    Abstract: Compositions, kits, methods and systems for single molecule nucleotide sequencing comprising producing polymerase reactions having lithium that control the median pulse width for incorporated nucleotides are disclosed. The levels of lithium are used to control pulse width while allowing other sequencing parameters to remain within a desirable range.
    Type: Grant
    Filed: April 5, 2017
    Date of Patent: January 22, 2019
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Andrei Fedorov, John Lyle, Keith Bjornson, Jeremiah Hanes
  • Patent number: 10167455
    Abstract: Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions, and/or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing. Such properties can include enhanced metal ion coordination, reduced exonuclease activity, reduced reaction rates at one or more steps of the polymerase kinetic cycle, decreased branching fraction, altered cofactor selectivity, increased yield, increased thermostability, increased accuracy, increased speed, increased readlength, and the like. Also provided are nucleic acids which encode the polymerases with the aforementioned phenotypes, as well as methods of using such polymerases to make a DNA or to sequence a DNA template.
    Type: Grant
    Filed: May 16, 2017
    Date of Patent: January 1, 2019
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Satwik Kamtekar, Lei Jia, Robin Emig, Erik Miller, Walter H. Lee
  • Patent number: 10161002
    Abstract: Nucleic acid compositions, methods of making and using such compositions that comprise modular functional groups that can be configured to provide desired functionality to different nucleotide types through a swappable and preferably non-covalent linkage component. Such compositions are useful in a variety of applications including nucleic acid analyses.
    Type: Grant
    Filed: December 13, 2017
    Date of Patent: December 25, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Jonas Korlach, Jeffrey Wegener
  • Patent number: 10150872
    Abstract: Multimeric protected fluorescent reagents and their methods of synthesis are provided. The reagents are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The reagents contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements. The reagents also contain coupling elements connect monomeric compounds into multimeric forms, thereby increasing brightness.
    Type: Grant
    Filed: February 4, 2016
    Date of Patent: December 11, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Frank Zheng, Jeremiah Hanes, Gene Shen, Louis Brogley, Stephen Yue, Yuri Lapin, John Lyle, Honey Osuna, Andrei Fedorov, Lubomir Sebo
  • Patent number: 10144963
    Abstract: Optical analytical devices and their methods of use are provided. The devices are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The devices include integrated illumination elements and optical waveguides for illumination of the optical reactions. The devices further provide for the efficient coupling of optical excitation energy from the waveguides to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices of the invention are well suited for miniaturization and high throughput.
    Type: Grant
    Filed: April 17, 2017
    Date of Patent: December 4, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Paul Lundquist, Stephen Turner
  • Patent number: 10138515
    Abstract: An analytical device including an optically opaque cladding, a sequencing layer including a substrate disposed below the cladding, and a waveguide assembly for receiving optical illumination and introducing illumination into the device. The illumination may be received from a top, a side edge, and a bottom of the device. The waveguide assembly may include a nanoscale aperture disposed in the substrate and extending through the cladding. The aperture defines a reaction cell for receiving a set of reactants. In various aspects, the device includes a sensor element and the illumination pathway is through the sensor element. Waveguides and illumination devices, such as plasmonic illumination devices, are also disclosed. Methods for forming and operating the devices are also disclosed.
    Type: Grant
    Filed: September 3, 2015
    Date of Patent: November 27, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Adrian Fehr, Nathaniel Joseph McCaffrey, Stephen Turner
  • Patent number: 10125391
    Abstract: Real time electronic sequencing methods, devices, and systems are described. Arrays of nanoFET devices are used to provide sequence information about a template nucleic acid in a polymerase-template complex bound to the nanoFET. A sequencing reaction mixture comprising nucleotide analogs having conductivity labels is introduced to the array of nanoscale electronic elements comprising nanoFETs under conditions of polymerase mediated nucleic acid synthesis. The polymerase enzyme template complex is attached to the gate of the nanoFET in an orientation whereby the nucleotide exit region of the polymerase enzyme is directed toward the gate of the nanoFET. Methods for producing nanoFET arrays are provided.
    Type: Grant
    Filed: August 3, 2016
    Date of Patent: November 13, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Stephen Turner, Jonas Korlach, Satwik Kamtekar, Jeremiah Hanes
  • Patent number: 10113197
    Abstract: Methods, Compositions, and Systems are provided for obtaining polymerase-template complex mixtures with improved levels of active polymerase. In some aspects active polymerase-template complex is separated by affinity for nucleoside phosphate moieties attached to a resin. In some aspects, a polymerase-template complex is exposed to reaction conditions in which a complementary strand to the template is produced. The extended reaction mixture is purified by reaction with a resin comprising nucleoside phosphate moieties. This purified mixture can be loaded onto substrates and can be used for further analyzes including single molecule sequencing.
    Type: Grant
    Filed: December 12, 2014
    Date of Patent: October 30, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Lei Sun, Insil Park
  • Patent number: 10081836
    Abstract: Methods, compositions, and systems are provided that allow for reliable sequencing of the initial sequence region of a sequence of interest. The methods of the invention allow for more reliable barcoding of subpopulations of nucleic acids to be sequenced.
    Type: Grant
    Filed: July 15, 2016
    Date of Patent: September 25, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Tyson A. Clark, Jonas Korlach, Cheryl Heiner, Kevin Travers, Erik Miller
  • Publication number: 20180258481
    Abstract: The present invention provides novel compositions, methods and apparatus for DNA sequencing that can be performed, e.g., in a two-electrode chamber. The present invention also provides a method for sequencing a nucleic acid comprising immobilizing a plurality of complexes comprising a target nucleic acid, a primer nucleic acid, and a polymerase onto a surface, contacting the surface with a plurality of charged particles comprising a nucleotide phosphate by applying an electric field, reversing the electric field to transport unbound charged particles away from the surface, and detecting the incorporation of a nucleotide phosphate into a single molecule of the primer nucleic acid.
    Type: Application
    Filed: May 10, 2018
    Publication date: September 13, 2018
    Applicant: PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
    Inventor: John G.K. Williams
  • Patent number: 10066258
    Abstract: FRET-labeled compounds are provided for use in analytical reactions. In certain embodiments, FRET-labeled nucleotide analogs are used in place of naturally occurring nucleoside triphosphates or other analogs in analytical reactions comprising nucleic acids, for example, template-directed nucleic acid synthesis, DNA sequencing, RNA sequencing, single-base identification, hybridization, binding assays, and other analytical reactions.
    Type: Grant
    Filed: December 14, 2016
    Date of Patent: September 4, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Xiangxu Kong, Gene Shen
  • Patent number: 10030264
    Abstract: Methods for performing analytical reactions and compositions for use in such methods, where the methods have reduced signal levels deriving from non-specific adsorption of detected reagents to other components of the analytical method, e.g., other reagents, solid phase components, vessels, etc.
    Type: Grant
    Filed: January 6, 2015
    Date of Patent: July 24, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Andrei Fedorov, Stephen Yue, Lei Sun, Gene Shen, John Lyle
  • Patent number: 10023911
    Abstract: Computer implemented methods, and systems performing such methods for processing signal data from analytical operations and systems, and particularly in processing signal data from sequence-by-incorporation processes to identify nucleotide sequences of template nucleic acids and larger nucleic acid molecules, e.g., genomes or fragments thereof.
    Type: Grant
    Filed: October 13, 2015
    Date of Patent: July 17, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Austin B. Tomaney, Kenneth Mark Maxham, David Holden, Kevin Hester, Devon Murphy, Patrick Marks
  • Patent number: 10023605
    Abstract: Compositions, methods, and systems are provided for nucleotide analogs comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Nucleotide analogs of the invention have a protein shield between the dye moieties and nucleotide moieties of the analog. The nucleotide analogs have two avidin proteins connected by a central dye component, and each avidin protein is further connected to a nucleotide component. The protein can prevent the direct interaction of the dye moiety with the enzyme carrying out nucleotide synthesis preventing photodamage to the enzyme. The nucleotide analogs of the invention can have multiple dyes and multiple nucleotide moieties.
    Type: Grant
    Filed: June 1, 2015
    Date of Patent: July 17, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Keith Bjornson, Jeremiah Hanes, Erik Miller, Satwik Kamtekar, Lubomir Sebo, Louis Brogley
  • Patent number: 10000798
    Abstract: The present invention provides novel compositions, methods and apparatus for DNA sequencing that can be performed, e.g., in a two-electrode chamber. The present invention also provides a method for sequencing a nucleic acid comprising immobilizing a plurality of complexes comprising a target nucleic acid, a primer nucleic acid, and a polymerase onto a surface, contacting the surface with a plurality of charged particles comprising a nucleotide phosphate by applying an electric field, reversing the electric field to transport unbound charged particles away from the surface, and detecting the incorporation of a nucleotide phosphate into a single molecule of the primer nucleic acid.
    Type: Grant
    Filed: October 7, 2014
    Date of Patent: June 19, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventor: John G. K. Williams
  • Patent number: 10000805
    Abstract: Compositions, methods and systems are provided for isolating DNA having a modified or unnatural base. Circular DNA fragments, each comprising a double stranded DNA central region and single stranded regions on the ends of the double stranded regions, are obtained. Some of the fragments have one or more modified or unnatural base. The DNA fragments are treated with a primer and a polymerase such that the polymerase extends the primer to copy at least one of the strand of the double stranded region. This results in rendering the other strand single stranded. A binding protein or antibody that is specific to the modified or unnatural base is then used to isolate strands containing the modified or unnatural bases. Methods for loading such complexes onto substrates and for single molecule sequencing of such complexes are also provided.
    Type: Grant
    Filed: September 20, 2016
    Date of Patent: June 19, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Thang Pham, Arunashree Bhamidipati, Kevin Travers, Eric Olivares, Tyson A. Clark, Jonas Korlach
  • Patent number: RE47067
    Abstract: The invention relates to devices and methods for nanopore sequencing. The invention includes arrays of nanopores having incorporated electronic circuits, for example, in CMOS. The invention includes devices having sample and reference pores connecting sample, measurement and reference chambers, wherein potential measurements in each chamber is used to provide an accurate determination of current through a sample nanopore, improving nanopore sequencing.
    Type: Grant
    Filed: July 28, 2015
    Date of Patent: October 2, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Stephen Turner, Nathaniel McCaffrey, Jeffrey Wegener, Adrian Fehr
  • Patent number: RE47177
    Abstract: Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions, and/or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing. Such properties include increased resistance to photodamage, and can also include enhanced metal ion coordination, reduced exonuclease activity, reduced reaction rates at one or more steps of the polymerase kinetic cycle, decreased branching fraction, altered cofactor selectivity, increased yield, increased thermostability, increased accuracy, increased speed, increased readlength, and the like. Also provided are nucleic acids which encode the polymerases with the aforementioned phenotypes, as well as methods of using such polymerases to make a DNA or to sequence a DNA template.
    Type: Grant
    Filed: January 24, 2018
    Date of Patent: December 25, 2018
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Satwik Kamtekar, Arek Bibillo, Keith Bjornson, Fred Christians, Colleen Cutcliffe, Jeremiah Hanes, Lei Jia, Walter Lee, Erik Miller, Pranav Patel