Patents Assigned to Pacific Biosciences of California, Inc.
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Patent number: 11718639Abstract: Compositions, methods, and systems are provided for fluorescent polymerase enzyme substrates comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Fluorescent polymerase enzyme substrates of the invention have a protein shield between the fluorescent dye moieties and nucleotide moieties of the polymerase enzyme substrate. The polymerase enzyme substrates have a nucleotide component and a dye component, each attached to a protein. The attachments can be covalent. The protein can, for example, prevent the direct interaction of the fluorescent dye moiety with the enzyme when carrying out nucleotide synthesis, preventing photodamage to the enzyme. The polymerase enzyme substrates of the invention can have multiple dyes and multiple nucleotide moieties.Type: GrantFiled: April 14, 2021Date of Patent: August 8, 2023Assignee: Pacific Biosciences of California, Inc.Inventors: Keith Bjornson, Jeremiah Hanes, Erik Miller, Satwik Kamtekar, Lubomir Sebo, Louis Brogley
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Publication number: 20230227900Abstract: A method for determining the presence of an allele, including (a) binding a polymerase to a double stranded nucleic acid that includes a primer hybridized to a template, the template including a first allele of a locus; (b) adding a nucleotide to the primer via catalytic activity of the polymerase, thereby producing an extended nucleic acid; (c) dissociating the polymerase from the extended nucleic acid; (d) detecting dissociation of the polymerase from the extended nucleic acid; and (e) comparing the dissociation of the polymerase from the extended nucleic acid to dissociation of the polymerase from a second double stranded nucleic acid, the second double stranded nucleic acid including a primer hybridized to the same position of the locus as the primer of the extended nucleic acid.Type: ApplicationFiled: September 27, 2022Publication date: July 20, 2023Applicant: Pacific Biosciences of California, Inc.Inventors: Denis MALYSHEV, Sean STROMBERG
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Patent number: 11705217Abstract: Methods and systems for single molecule sequencing using concatemers of copies of sense and antisense strands. Concatemers are provided, for example, by carrying out rolling circle amplification on a circular molecule having sense and antisense regions to produce repeated copies of the sense and antisense regions connected by linking regions. The circular molecules can be produced by ligating hairpin adapters to each end of a double-stranded nucleic acid having a sense and antisense strand. The ligations can be carried out, for example using blunt end ligation. In some cases, a single molecule consensus sequence for a single template molecule is obtained. A single read from each template molecule can be obtained by comparing the sequence information of the sense and antisense regions.Type: GrantFiled: January 19, 2018Date of Patent: July 18, 2023Assignee: Pacific Biosciences of California, Inc.Inventors: Kevin Travers, Geoff Otto, Stephen Turner, Cheryl Heiner, Congcong Ma
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Patent number: 11693182Abstract: Integrated target waveguide devices and optical analytical systems comprising such devices are provided. The target devices include an optical coupler that is optically coupled to an integrated waveguide and that is configured to receive optical input from an optical source through free space, particularly through a low numerical aperture interface. The devices and systems 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 provide for the efficient and reliable coupling of optical excitation energy from an optical source to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination. The devices and systems are well suited for miniaturization and high throughput.Type: GrantFiled: July 10, 2020Date of Patent: July 4, 2023Assignee: Pacific Biosciences of California, Inc.Inventors: Shang Wang, Mathieu Foquet, Paul Lundquist, Aaron Rulison, Mark McDonald, Ariel Herrmann
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Publication number: 20230192749Abstract: Protected fluorescent reagent compounds and their methods of synthesis are provided. The compounds 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 compounds 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.Type: ApplicationFiled: February 10, 2023Publication date: June 22, 2023Applicant: Pacific Biosciences of California, Inc.Inventors: Lubomir SEBO, Jeremiah HANES, Gene SHEN, Louis BROGLEY, Stephen YUE, Frank ZHENG, Yuri LAPIN, John LYLE, Honey OSUNA, Andrei FEDOROV
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Patent number: 11680950Abstract: A scanning apparatus that can include (a) a scan actuator including a linear actuator and a mount for a removeable vessel, wherein the mount has a mechanical fastener that is configured to engage a complementary mechanical fastener on the removeable vessel, and wherein the linear actuator is configured to translate the mount while the mechanical fastener engages the complementary mechanical fastener on the removeable vessel; (b) a reference surface; and (c) a preload configured to urge the vessel to contact the reference surface, wherein the linear actuator is configured to slide the vessel along the reference surface while the preload urges the vessel to contact the reference surface.Type: GrantFiled: February 20, 2020Date of Patent: June 20, 2023Assignee: Pacific Biosciences of California, Inc.Inventors: Matias Negatu, Alex Nemiroski, Drew Ival Frerichs, Dale Buermann, Michael John Erickstad, Rebecca McGinley, Harry Scott Rapoport, Arnold Oliphant, Eugene Pogrebinsky
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Publication number: 20230144475Abstract: 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: ApplicationFiled: July 11, 2022Publication date: May 11, 2023Applicant: Pacific Biosciences of California, Inc.Inventors: Paul LUNDQUIST, Stephen TURNER
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Patent number: 11642643Abstract: Methods, compositions, and systems for distributing nucleic acids into array regions are provided. The methods, compositions, and systems utilize nucleic acid condensing agents to increase efficiency of distribution of the nucleic acids into the array regions. Various methods for facilitating distribution of the nucleic acids to the array regions are provided.Type: GrantFiled: September 15, 2020Date of Patent: May 9, 2023Assignee: Pacific Biosciences of California, Inc.Inventors: Lei Sun, Jaime Juan Benitez-Marzan, Natasha Popovich, Sassan Sheikholeslami, Steven Lin, Aparna Vedula
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Patent number: 11644636Abstract: An objective lens is used for DNA sequencing. An example system includes a flow cell, the objective lens, and a camera. Light from the flow cell is imaged by the camera through the objective lens. The objective lens can provide a long working distance; a flat field curvature; a high numerical aperture; and/or a wide field of view.Type: GrantFiled: April 9, 2020Date of Patent: May 9, 2023Assignee: PACIFIC BIOSCIENCES OF CALIFORNIA, INC.Inventors: Donald V. Rosenberry, Dale Buermann
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Patent number: 11644406Abstract: An apparatus for evaluating focus, including (a) a stage configured to hold a specimen; and (b) an optical train including a radiation source, calibration optic, objective and detector, the optical train forming a first path wherein radiation from the radiation source is directed to the calibration optic and then a first portion of the radiation is directed to the detector, thereby forming a first image on the detector, wherein a second portion of the radiation follows a second path from the calibration optic then through the objective to the specimen, wherein the optical train forms a third path wherein radiation reflected from the specimen is transmitted through the objective, then to the detector, thereby forming a second image on the detector, and wherein the radiation that forms the first image is astigmatic.Type: GrantFiled: June 11, 2020Date of Patent: May 9, 2023Assignee: PACIFIC BIOSCIENCES OF CALIFORNIA, INC.Inventors: Yoshinao Taketomi, Dale Buermann, Maxim Abashin, Donald V. Rosenberry
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Patent number: 11640022Abstract: 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 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: GrantFiled: October 4, 2021Date of Patent: May 2, 2023Assignee: Pacific Biosciences of California, Inc.Inventors: Annette Grot, Shang Wang, Hans Callebaut, Paul Lundquist, Stephen Turner
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Patent number: 11629376Abstract: 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: GrantFiled: August 21, 2018Date of Patent: April 18, 2023Assignee: Pacific Biosciences of California, Inc.Inventors: Tyson A. Clark, Jonas Korlach, Cheryl Heiner, Kevin Travers, Erik Miller
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Publication number: 20230112975Abstract: Provided herein are systems, devices, and methods for improved optical waveguide transmission and alignment in an analytical system. Waveguides in optical analytical systems can exhibit variable and increasing back reflection of single-wavelength illumination over time, thus limiting their effectiveness and reliability. The systems are also subject to optical interference under conditions that have been used to overcome the back reflection. Novel systems and approaches using broadband illumination light with multiple longitudinal modes have been developed to improve optical transmission and analysis in these systems. Novel systems and approaches for the alignment of a target waveguide device and an optical source are also disclosed.Type: ApplicationFiled: August 15, 2022Publication date: April 13, 2023Applicant: Pacific Biosciences of California, Inc.Inventors: Alexey KURITSYN, Mark MCDONALD, Aaron RULISON, Russell BERMAN
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Patent number: 11624089Abstract: The invention provides a novel class of cyanine dyes that are functionalized with sulfonic acid groups and a linker moiety that facilitates their conjugation to other species and substituent groups which increase the water-solubility, and optimize the optical properties of the dyes. Also provided are conjugates of the dyes, methods of using the dyes and their conjugates and kits including the dyes and their conjugates.Type: GrantFiled: August 20, 2019Date of Patent: April 11, 2023Assignee: Pacific Biosciences of California, Inc.Inventors: Stephen Yue, Gene Shen, Wei-Chuan (David) Sun
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Patent number: 11608528Abstract: A method for determining sequences from sense and antisense strands of a nucleic acid, including (a) providing a nucleic acid cluster attached to a solid support, wherein the nucleic acid cluster includes a sense strand and an antisense strand of a concatemer, the concatemer including multiple copies of a sequence unit, the sequence unit including a target sequence and a primer binding site; (b) hybridizing a primer to a primer binding site in the antisense strand; (c) extending the primer along the antisense strand to determine the sequence from at least a portion of the target sequence in the antisense strand; (d) hybridizing a second primer to a primer binding site in the sense strand; and (e) extending the second primer along the sense strand to determine the sequence from at least a portion of the target sequence in the sense strand.Type: GrantFiled: July 21, 2022Date of Patent: March 21, 2023Assignee: Pacific Biosciences of California, Inc.Inventors: Kurt Patterson, Hari K. K. Subramanian, Brittany A. Rohrman, Fabian Block
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Patent number: 11584959Abstract: Methods are provided for reducing the complexity of a population of nucleic acids prior to performing an analysis of the nucleic acids, e.g., sequence analysis. The methods result in a subset of the initial population enriched for a target region, which is typically located within one or more target fragments. The methods are particularly useful for analyzing populations having a high degree of complexity, e.g., chromosomal-derived DNA, whole genomic DNA, or mRNA populations.Type: GrantFiled: March 24, 2020Date of Patent: February 21, 2023Assignee: Pacific Biosciences of California, Inc.Inventors: Thang Tat Pham, Yu-Chih Tsai, Jonas Korlach, Tyson A. Clark, Stephen Turner
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Patent number: 11578180Abstract: Disclosed herein are finished products, methods, compositions and kits for derivatizing plastic (e.g., “polymer”) surfaces in a manner that renders the surfaces appropriate for various downstream applications. For example, flow cells incorporating modified plastic surfaces provide greatly enhanced stability for retention of attached chemical species such as polypeptides and nucleic acids.Type: GrantFiled: July 17, 2018Date of Patent: February 14, 2023Assignee: PACIFIC BIOSCIENCES OF CALIFORNIA, INC.Inventor: Corey M. Dambacher
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Patent number: 11578093Abstract: Protected fluorescent reagent compounds and their methods of synthesis are provided. The compounds 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 compounds 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.Type: GrantFiled: August 28, 2020Date of Patent: February 14, 2023Assignee: Pacific Biosciences of California, Inc.Inventors: Lubomir Sebo, Jeremiah Hanes, Gene Shen, Louis Brogley, Stephen Yue, Frank Zheng, Yuri Lapin, John Lyle, Honey Osuna, Andrei Fedorov
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Patent number: 11578364Abstract: The present disclosure provides methods, compositions, and systems for distributing polymerase compositions into array regions. In particular, the described methods, compositions, and systems utilize density differentials and/or additives to increase efficiency in the distribution of polymerase compositions to a surface as compared to methods utilizing only diffusion control.Type: GrantFiled: June 23, 2020Date of Patent: February 14, 2023Assignee: Pacific Biosciences of California, Inc.Inventors: Sassan Sheikholeslami, Michael W. Hunkapiller, Natasha Popovich, Lei Sun, Erik Miller, Satwik Kamtekar
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Patent number: 11560591Abstract: This invention provides devices for use in various analytical applications including single-molecule analytical reactions. Methods for detecting analytes optically by propagating optical energy by waveguides within a substrate are provided. Analytical devices are provided which have both shallow and deep waveguides in which illumination light is transported through the deep waveguides and coupled into the shallow waveguides. The shallow waveguides provide evanescent field illumination to analytes, such as single-molecule analytes, within nanometer scale wells. Integrated devices including integrated detectors such as CMOS detectors are included.Type: GrantFiled: March 16, 2021Date of Patent: January 24, 2023Assignee: Pacific Biosciences of California, Inc.Inventors: Cheng Frank Zhong, Paul Lundquist, Mathieu Foquet, Jonas Korlach, Hovig Bayandorian