Method Specially Adapted For Identifying A Library Member Patents (Class 506/2)
  • Patent number: 11365408
    Abstract: The disclosure provides DNA library preparation methods that do not require a purification between adapter ligation and PCR amplification. Adaptors are added to DNA fragments to form oligonucleotide extension products and the oligonucleotide extension products are amplified without stopping or interruption for a cleanup step. Excess materials, such as enzymes, adaptors, or co-factors, from the adaptor addition step do not interfere with the amplification step and the amplification step proceeds without regards to the presence of reagents from the ligation step. In preferred embodiments, the ligation and amplification step make use of a common priming sequence e.g., in the form of one of the adaptor oligos.
    Type: Grant
    Filed: February 6, 2019
    Date of Patent: June 21, 2022
    Assignee: NUGEN TECHNOLOGIES, INC.
    Inventors: Bin Li, Benjamin G. Schroeder, Manqing Hong, Maureen Peterson
  • Patent number: 11359248
    Abstract: Disclosed herein are methods for use in detection of single nucleotide variants (SNVs) or indels. The methods may comprise enriching cell-free DNA molecules for a panel of genomic regions and deep sequencing the enriched cfDNA to detect the SNVs or indels.
    Type: Grant
    Filed: October 21, 2021
    Date of Patent: June 14, 2022
    Assignee: GUARDANT HEALTH, INC.
    Inventors: Stefanie Ann Ward Mortimer, Amirali Talasaz, Darya Chudova, Helmy Eltoukhy
  • Patent number: 11359239
    Abstract: The present disclosure provides compositions, methods, systems, and devices for polynucleotide processing. Such polynucleotide processing may be useful for a variety of applications, including polynucleotide sequencing.
    Type: Grant
    Filed: May 7, 2021
    Date of Patent: June 14, 2022
    Assignee: 10X GENOMICS, INC.
    Inventors: Benjamin Hindson, Kevin Ness, Serge Saxonov, Paul Hardenbol
  • Patent number: 11345968
    Abstract: Disclosed herein are methods for use in detection of molecular residual disease. The methods may comprise deep sequencing a panel of genomic regions in cell-free DNA molecules and computer processing sequence reads to detect variants that are indicative of molecular residual disease.
    Type: Grant
    Filed: July 2, 2021
    Date of Patent: May 31, 2022
    Assignee: GUARDANT HEALTH, INC.
    Inventors: Stefanie Ann Ward Mortimer, AmirAli Talasaz, Darya Chudova, Helmy Eltoukhy
  • Patent number: 11332787
    Abstract: The present invention provides methods, compositions, and systems for distributing molecules and complexes into reaction sites. In particular, the methods, compositions, and systems of the present invention result in loading of polymerase enzyme complexes into a predetermined number of reaction sites, including nanoscale wells.
    Type: Grant
    Filed: June 28, 2019
    Date of Patent: May 17, 2022
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Jaime Juan Benitez-Marzan, Natasha Popovich, Lei Sun
  • Patent number: 11326160
    Abstract: This disclosure provides, among other things, a method for making a cDNA library. In some embodiments the method may comprise reverse transcribing mRNA to produce DNA:mRNA hybrids, treating the DNA:mRNA hybrids with RNAseH to produce mRNA fragments, and reverse transcribing the mRNA fragments.
    Type: Grant
    Filed: June 3, 2020
    Date of Patent: May 10, 2022
    Assignee: BIOO SCIENTIFIC CORPORATION
    Inventors: Kevin Allen, Adam Morris
  • Patent number: 11319596
    Abstract: The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.
    Type: Grant
    Filed: February 28, 2019
    Date of Patent: May 3, 2022
    Assignee: Natera, Inc.
    Inventors: Joshua Babiarz, Tudor Pompiliu Constantin, Lane A. Eubank, George Gemelos, Matthew Micah Hill, Huseyin Eser Kirkizlar, Matthew Rabinowitz, Onur Sakarya, Styrmir Sigurjonsson, Bernhard Zimmermann
  • Patent number: 11319591
    Abstract: Disclosed are methods for identifying the core regulatory circuitry or cell identity program of a cell or tissue, and related methods of diagnoses, screening, and treatment involving the core regulatory circuitry and/or cell identity programs identified using the methods.
    Type: Grant
    Filed: December 23, 2016
    Date of Patent: May 3, 2022
    Assignee: Whitehead Institute for Biomedical Research
    Inventors: Violaine Saint-Andre, Brian J. Abraham, Zi Peng Fan, Tong Ihn Lee, Richard A. Young
  • Patent number: 11306358
    Abstract: Provided is a method for determining a genetic condition of a fetus, the method including: an objective region selection step of selecting an objective region for determining the genetic condition, from regions on a human genome; a step of isolating a single cell from a maternal blood sample; a step of extracting genomic DNA from the single cell; a step of performing PCR amplification on the objective region using a primer set designed so as to perform the PCR amplification on the objective region using genomic DNA extracted from the single cell as a template; and a DNA sequencing step of decoding a DNA base sequence of a PCR amplification product of the objective region, in which the primer set designed so as to perform the PCR amplification on the objective region is designed through a method for designing a primer set used for the polymerase chain reaction, the method for designing a primer set including a first stage selection step based on a local alignment score and a second stage selection step based o
    Type: Grant
    Filed: September 22, 2017
    Date of Patent: April 19, 2022
    Assignee: FUJIFILM Corporation
    Inventors: Aya Ouchi, Takayuki Tsujimoto, Masaya Nagase, Yasuyuki Ishii
  • Patent number: 11306348
    Abstract: The present disclosure relates to methods, compositions, and kits for generating a library of tagged nucleic acid fragments without using PCR amplification, including methods and compositions for fragmenting and tagging nucleic acids (e.g., DNA) using transposome complexes immobilized on solid support.
    Type: Grant
    Filed: May 3, 2021
    Date of Patent: April 19, 2022
    Assignee: Illumina Cambridge Limited
    Inventors: Andrew Slatter, Esther Musgrave-Brown, Susan C. Verity, Niall Anthony Gormley
  • Patent number: 11306356
    Abstract: Methods and compositions are described herein for primer extension target enrichment of immune receptor (BCR or TCR) sequences.
    Type: Grant
    Filed: June 1, 2017
    Date of Patent: April 19, 2022
    Assignee: Roche Sequencing Solutions, Inc.
    Inventors: Jan Berka, Brian Godwin, Carolina Dallett, Sedide Ozturk, Joseph Platzer, Seoyoung Kim
  • Patent number: 11282610
    Abstract: The present disclosure provides methods for determining a probability that after any of a number of therapeutic interventions, an initial state of a subject, such as somatic cell mutational status of a subject with cancer, will develop a subsequent state. Such probabilities can be used to inform a health care provider as to particular courses of treatment to maximize probability of a desired outcome for the subject.
    Type: Grant
    Filed: September 3, 2020
    Date of Patent: March 22, 2022
    Assignee: GUARDANT HEALTH, INC.
    Inventors: Helmy Eltoukhy, AmirAli Talasaz
  • Patent number: 11268075
    Abstract: Provided are methods and compositions for activating oligonucleotide aptamer-deactivated DNA polymerases, comprising modifying the aptamer by uracil-DNA glycosylase enzymatic activity to reduce or eliminate binding of the oligonucleotide aptamer to the DNA polymerase, thereby activating DNA synthesis activity of the DNA polymerase in a reaction mixture. Mixtures for use in methods of the invention are also provided. In some aspects, the oligonucleotide aptamers are circular and comprise one or more deoxyuridine nucleotides providing for aptamer-specific recognition and modification of the circular aptamer by the uracil-DNA glycosylase enzymatic activity. Exemplary oligonucleotide aptamers, mixtures and methods employing uracil-DNA glycosylase enzymatic activity are provided.
    Type: Grant
    Filed: June 26, 2020
    Date of Patent: March 8, 2022
    Assignee: Cepheid
    Inventors: Igor V. Kutyavin, Sergey G. Lokhov
  • Patent number: 11268907
    Abstract: Methods of detecting compromise of at least one analyte reagent upon reaction with a test sample are disclosed. Also disclosed are reflectance spectroscopic diagnostic instruments that perform the method, and systems that contain same.
    Type: Grant
    Filed: December 12, 2017
    Date of Patent: March 8, 2022
    Assignee: Siemens Healthcare Diagnostics Inc.
    Inventors: Lloyd Schulman, Christopher Zimmerle, Julie Chaney
  • Patent number: 11268131
    Abstract: Reagents and methods for the analysis of nucleic acids (e.g. genomic DNA) of circulating microparticles (i.e. microparticles originating from blood) are provided. The methods comprise linking at least two fragments of a target nucleic acid of a circulating microparticle to produce a set of at least two linked fragments of the target nucleic acid. In the methods, fragments of a target nucleic acid may be linked by techniques such as barcoding, partitioning, ligation and/or separate sequencing. The sequencing of a set of linked fragments provides a set of informatically linked sequence reads corresponding to the sequences of fragments from a single microparticle.
    Type: Grant
    Filed: May 4, 2020
    Date of Patent: March 8, 2022
    Assignee: CS Genetics Limited
    Inventor: Lucas Brandon Edelman
  • Patent number: 11261492
    Abstract: The present invention relates to methods for detecting, enriching, and analyzing rare cells that are present in the blood, e.g. fetal cells. The invention further features methods of analyzing rare cell(s) to determine the presence of an abnormality, disease or condition in a subject, e.g. a fetus by analyzing a cellular sample from the subject.
    Type: Grant
    Filed: October 7, 2019
    Date of Patent: March 1, 2022
    Assignees: The General Hospital Corporation, Verinata Health, Inc., GPB Scientific, LLC
    Inventors: Ravi Kapur, Mehmet Toner, Zihua Wang, Martin Fuchs
  • Patent number: 11254976
    Abstract: A method including (a) providing an amplification reagent including an array of sites, and a solution having different target nucleic acids; and (b) reacting the amplification reagent to produce amplification sites each having a clonal population of amplicons from a target nucleic acid from the solution. The reacting can include simultaneously transporting the nucleic acids to the sites at an average transport rate, and amplifying the nucleic acids that transport to the sites at an average amplification rate, wherein the average amplification rate exceeds the average transport rate. The reacting can include producing a first amplicon from a nucleic acid that transports to each of the sites, and producing subsequent amplicons from the nucleic acid or from the first amplicon, wherein the average rate at which the subsequent amplicons are generated exceeds the average rate at which the first amplicon is generated.
    Type: Grant
    Filed: August 19, 2019
    Date of Patent: February 22, 2022
    Assignee: Illumina, Inc.
    Inventors: Min-Jui Richard Shen, Jonathan Mark Boutell, Kathryn M. Stephens, Mostafa Ronaghi, Kevin L. Gunderson, Bala Murali Venkatesan, M. Shane Bowen, Kandaswamy Vijayan
  • Patent number: 11254975
    Abstract: A method of amplifying a target nucleic acid (polynucleotide) contained in a particle including an enclosing lipid bilayer membrane according to the present invention includes the steps of: lysing the particle which is stored in a compartment constituted by a liquid in an amount of 100 ?l or less; and amplifying the target nucleic acid in the compartment.
    Type: Grant
    Filed: May 23, 2019
    Date of Patent: February 22, 2022
    Inventors: Toru Uchiyama, Masafumi Onodera
  • Patent number: 11248253
    Abstract: Methods are provided for correction of amplification bias and quantitation of adaptive immune cells in a sample using synthetic templates that include random oligonucleotide sequences.
    Type: Grant
    Filed: May 1, 2020
    Date of Patent: February 15, 2022
    Assignee: Adaptive Biotechnologies Corporation
    Inventors: Anna M. Sherwood, Ryan O. Emerson, Harlan S. Robins, Mark J. Rieder, Joe Parsons
  • Patent number: 11242542
    Abstract: This invention pertains to mutant Cas9 nucleic acids and proteins for use in CRISPR/Cas endonuclease systems, and their methods of use. In particular, the invention pertains to an isolated mutant Cas9 protein, wherein the isolated mutant Cas9 protein is active in a CRISPR/Cas endonuclease system, wherein the CRISPR/Cas endonuclease system displays reduced off-target editing activity and maintained on-target editing activity relative to a wild-type CRISPR/Cas endonuclease system. The invention also includes isolated nucleic acids encoding mutant Cas9 proteins, ribonucleoprotein complexes and CRISPR/Cas endonuclease systems having mutant Cas9 proteins that display reduced off-target editing activity and maintained on-target editing activity relative to a wild-type CRISPR/Cas endonuclease system.
    Type: Grant
    Filed: April 26, 2018
    Date of Patent: February 8, 2022
    Assignee: Integrated DNA Technologies, Inc.
    Inventors: Christopher Anthony Vakulskas, Nicole Mary Bode, Michael Allen Collingwood, Garrett Richard Rettig, Mark Aaron Behlke
  • Patent number: 11214798
    Abstract: Rapid nucleic acid libraries, methods of generation, kits, and compositions relating to library synthesis, including reagents, intermediaries and final products are disclosed herein. The disclosure enables rapid synthesis of libraries that allow independent verification of sequence information and rapid identification of sequence information with template of origin.
    Type: Grant
    Filed: September 6, 2019
    Date of Patent: January 4, 2022
    Assignee: iGenomX International Genomics Corporation
    Inventor: Keith Brown
  • Patent number: 11209368
    Abstract: A method and test kit are useful for detecting specific nucleic acid sequences. The process includes (1) matrix-dependent new synthesis of the target nucleic acid; (2) target-specific probe hybridization; and (3) detection of the hybridization event. In the first step, an oligonucleotide 1, which is marked by a marker 1 and is entirely or partially complementary to the target sequence, acts as a primer in the matrix-dependent new synthesis of the target nucleic acid and, in the second step, an oligonucleotide 2, which is marked by a marker 2 and, owing to its melting temperature being lower than that of the oligonucleotide 1, is not involved in the first step, partially or completely hybridizes with the DNA new synthesis product of oligonucleotide 1.
    Type: Grant
    Filed: July 23, 2018
    Date of Patent: December 28, 2021
    Assignee: IST Innuscreen GmbH
    Inventors: Elmara Graser, Timo Hillebrand
  • Patent number: 11208678
    Abstract: Disclosed are methods and kits for improving global gene expression analysis for a population of RNA molecules derived from a human urine sample. In an embodiment, the method comprises the step of selectively depleting miR-10a-5p fragments from the population of RNA molecules or selectively blocking miR-10a-5p fragments within the RNA population. The miR-10a-5p depleted or miR-10a-5p blocked population of RNA can be used in a variety of global gene expression analysis protocols, including next generation sequencing. In a further embodiment, the method comprises selectively depleting or blocking miR-10b-5p fragments within the RNA population. The miR-10a-5p and/or miR-10b-5p depleted or blocked populations of RNA can also be used in global gene expression analysis protocols, including next generation sequencing.
    Type: Grant
    Filed: July 23, 2018
    Date of Patent: December 28, 2021
    Assignee: Norgen Biotek Corp.
    Inventor: Yousef Haj-Ahmad
  • Patent number: 11193164
    Abstract: Provided herein are, inter alia, methods and compositions to detect, monitor and treat cancer, wherein the cancer includes amplified extrachromosomal oncogenes. The methods are useful for personalized treatment and exploit differential expression of amplified extrachromosomal oncogenes in cancer cells versus healthy cells.
    Type: Grant
    Filed: May 24, 2018
    Date of Patent: December 7, 2021
    Assignees: The Regents of the University of California, Ludwig Institute for Cancer Research Ltd
    Inventors: Paul Mischel, Prashant Mali, Vineet Bafna, Kristen Turner, Viraj Deshpande, Doruk Beyter
  • Patent number: 11192105
    Abstract: An analysis system may perform operations on an analyte that may be combined with multiple regents prior to being introduced into a flow cell. The instrument may include a volume into which the reagents to be combined with the analyte are aspirated one-by-one. The volume may be formed as a serpentine channel in a valve manifold associated with sippers for aspirating the reagents. The reagents may then be mixed by cycling a pump to move the reagents within the mixing volume or channel. For this, the reagents may be aspirated from a recipient into the volume or channel, ejected back into the recipient, and this process may be performed repeatedly to enhance mixing.
    Type: Grant
    Filed: March 23, 2020
    Date of Patent: December 7, 2021
    Assignee: Illumina, Inc.
    Inventors: Bradley Kent Drews, Michael Dai Wang, Umberto Ulmanella, Stephen Wayne Clark, Johanna Lynn Whitacre, Steven Scott Phelps, Michelle L. Alvarez, Michael Adalbert Niziolek, Debra Sue Bryan, Joshua Augustin Darland
  • Patent number: 11180800
    Abstract: The disclosure provides methods, compositions, systems, and kits for the concurrent detection and analysis of different structural and chemical forms of nucleic acids in a sample.
    Type: Grant
    Filed: May 13, 2020
    Date of Patent: November 23, 2021
    Assignee: Karius, Inc.
    Inventors: Timothy A. Blauwkamp, Rene Sit, Igor D. Vilfan
  • Patent number: 11180804
    Abstract: The present invention provides methods for analyzing polynucleotides such as genomic DNA. In some embodiments, the disclosure provides a method for preparing and amplifying a genomic DNA library in situ in a fixed biological sample. The method comprises treating a fixed biological sample with an insertional enzyme complex to produce tagged fragments of genomic DNA. The method further comprises circularizing the tagged fragments of genomic DNA. The method further comprises amplifying the tagged fragments of genomic DNA.
    Type: Grant
    Filed: July 24, 2018
    Date of Patent: November 23, 2021
    Assignees: Massachusetts Institute of Technology, President and Fellows of Harvard College
    Inventors: Fei Chen, Andrew C. Payne, Jason D. Buenrostro, Paul Reginato, Edward Stuart Boyden, Shahar Alon
  • Patent number: 11174503
    Abstract: Disclosed are systems and methods for simultaneous detection of DNA and RNA genetic alterations comprising gene splicing variants, mutations, indel, copy number changes, fusion and combination thereof, in a biofluid sample from the patient without physically separating RNA from DNA. The systems and methods are similarly applicable to the simultaneous detection of DNA and RNA genetic alterations in solid tissues comprising gene splicing variants, mutations, indel, copy number changes, fusion and combination thereof. The present method utilized a barcoding method for analysis. The streamlined methods improve the simplicity, quantification accuracy and detection sensitivity and specificity of non-invasive detections of biomarkers.
    Type: Grant
    Filed: September 21, 2017
    Date of Patent: November 16, 2021
    Assignee: Predicine, Inc.
    Inventors: Xiaohong Wang, Pan Du, Shidong Jia
  • Patent number: 11168356
    Abstract: Size-band analysis is used to determine whether a chromosomal region exhibits a copy number aberration or an epigenetic alteration. Multiple size ranges may be analyzed instead of focusing on specific sizes. By using multiple size ranges instead of specific sizes, methods may analyze more sequence reads and may be able to determine whether a chromosomal region exhibits a copy number aberration even when clinically-relevant DNA may be a low fraction of the biological sample. Using multiple ranges may allow for the use of all sequence reads from a genomic region, rather than a selected subset of reads in the genomic region. The accuracy of analysis may be increased with higher sensitivity at similar or higher specificity. Analysis may include fewer sequencing reads to achieve the same accuracy, resulting in a more efficient process.
    Type: Grant
    Filed: November 1, 2018
    Date of Patent: November 9, 2021
    Assignees: The Chinese University of Hong Kong, GRAIL, Inc.
    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang
  • Patent number: 11167041
    Abstract: Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of retinal cells as compared to the infectivity of the retinal cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and in clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more cells of the retina for the treatment of retinal disorders and diseases.
    Type: Grant
    Filed: November 18, 2020
    Date of Patent: November 9, 2021
    Assignee: 4D MOLECULAR THERAPEUTICS INC.
    Inventors: David H. Kirn, Melissa Kotterman, David Schaffer
  • Patent number: 11154865
    Abstract: In the invention described here, the conventional need for feedback control is eliminated by a passive, open-loop approach using a novel microfluidic droplet generator with a step enhancement. The invented droplet generator yields uniform droplet volumes over a wide range of operating pressures, delivering robust performance at a very low cost. The invention also describes a method of droplet generation whereby the step enhancement improves the performance of any squeeze-mode or dripping-mode droplet generator, including but not limited to bridge-mode and flow-focusing configurations. The performance of the invention is sufficiently stable that it can be operated manually yet still deliver best-in-class microfluidic performance. Thus, not only does the invention greatly simplify and reduce the cost of operation in the laboratory, it opens the possibility of performing precision biology out in the field and off of the electrical grid.
    Type: Grant
    Filed: September 6, 2017
    Date of Patent: October 26, 2021
    Assignee: Lariat Biosciences, Inc.
    Inventors: Jonathan W. Larson, Alexandra Damiano
  • Patent number: 11149307
    Abstract: Disclosed herein in are methods and systems for determining genetic variants (e.g., copy number variation) in a polynucleotide sample. A method for determining copy number variations includes tagging double-stranded polynucleotides with duplex tags, sequencing polynucleotides from the sample and estimating total number of polynucleotides mapping to selected genetic loci. The estimate of total number of polynucleotides can involve estimating the number of double-stranded polynucleotides in the original sample for which no sequence reads are generated. This number can be generated using the number of polynucleotides for which reads for both complementary strands are detected and reads for which only one of the two complementary strands is detected.
    Type: Grant
    Filed: February 4, 2021
    Date of Patent: October 19, 2021
    Assignee: GUARDANT HEALTH, INC.
    Inventors: AmirAli Talasaz, Helmy Eltoukhy, Stefanie Ann Ward Mortimer
  • Patent number: 11150179
    Abstract: Memory efficient methods determine corrected color values from image data acquired by a nucleic acid sequencer during a base calling cycle. Such methods may: (a) obtain an image of a substrate (e.g., a portion of a flow cell) including a plurality of sites where nucleic acid bases are read; (b) measure color values of the plurality of sites from the image of the substrate; (c) store the color values in a processor buffer of the sequencer's one or more processors; (d) retrieve partially phase-corrected color values of the plurality of sites, where the partially phase-corrected color values were stored in the sequencer's memory during an immediately preceding base calling cycle; (e) determine a prephasing correction; and (f) determine the corrected color values. In various implementations, these operations are all performed during a single base calling cycle. In certain embodiments, the methods additionally include using the corrected color values to make base calls for the plurality of sites.
    Type: Grant
    Filed: January 5, 2018
    Date of Patent: October 19, 2021
    Assignee: Illumina, Inc.
    Inventors: Robert Langlois, Paul Belitz
  • Patent number: 11142798
    Abstract: Disclosed are for monitoring tumor load in a patient by selecting a predetermined number of biomarker genes from DNA extracted from a tumor tissue sample from the patient to form a panel of biomarker genes (“customized genes”); isolating circulating cell-free DNA from a bodily fluid (body fluid) sample of the patient; enriching DNA sequences containing the biomarker genes in the cell-free DNA fragments; sequencing the enriched DNA; counting the number of mutated DNA and normal DNA sequencing reads in enriched DNA; and obtaining a tumor load of the patient. Optionally, the detection of mutations in genes related to therapeutic treatments (“medicine genes”) are carried out simultaneously with the testing of customized genes.
    Type: Grant
    Filed: November 17, 2016
    Date of Patent: October 12, 2021
    Assignee: GENOMICARE BIOTECHNOLOGY (SHANGHAI) CO. LTD
    Inventors: Qiang Xu, Guan Wang, Chun Dai
  • Patent number: 11117113
    Abstract: The present disclosure provides a “looping amplification” method to increase the specificity of nucleic acid amplification. This increased specificity facilitates multiplexing to a much higher degree than was previously possible.
    Type: Grant
    Filed: December 16, 2016
    Date of Patent: September 14, 2021
    Assignee: FLUIDIGM CORPORATION
    Inventor: Peilin Chen
  • Patent number: 11104960
    Abstract: Provided herein is technology for esophageal disorder screening and particularly, but not exclusively, to methods, compositions, and related uses for detecting the presence of esophageal disorders (e.g., Barrett's esophagus, Barrett's esophageal dysplasia, etc.). In addition, the technology provides methods, compositions and related uses for distinguishing between Barrett's esophagus and Barrett's esophageal dysplasia, and between Barrett's esophageal low-grade dysplasia, Barrett's esophageal high-grade dysplasia, and esophageal adenocarcinoma within samples obtained through endoscopic brushing or nonendoscopic whole esophageal brushing or swabbing using a tethered device (e.g. such as a capsule sponge, balloon, or other device).
    Type: Grant
    Filed: September 13, 2019
    Date of Patent: August 31, 2021
    Assignees: Exact Sciences Development Company, LLC, Mayo Foundation for Medical Education and Research
    Inventors: David A. Ahlquist, William R. Taylor, John B. Kisiel, Douglas W. Mahoney, Tracy C. Yab, Graham P. Lidgard, Hatim T. Allawi
  • Patent number: 11098358
    Abstract: Disclosed herein are methods for single-cell sequencing. In some examples, the methods include enriching a sample comprising a plurality of cells for cells of interest to produce an enriched cell sample; isolating one or more cells of interest in the enriched cell sample; and obtaining sequence information of one or more polynucleotides from each of the one or more isolated cells. Obtaining sequence information may include generating a molecularly indexed polynucleotide library from the one or more isolated cells. Enriching the sample may include focusing cells of interest in the sample using acoustic focusing.
    Type: Grant
    Filed: April 30, 2020
    Date of Patent: August 24, 2021
    Assignee: BECTON, DICKINSON AND COMPANY
    Inventors: Clark Mason, Liping Yu
  • Patent number: 11098355
    Abstract: The invention relates to a new method of characterising two or more target polynucleotides using a pore. The method involves sequentially attaching to a first polynucleotide one or more subsequent polynucleotides to form a concatenated polynucleotide.
    Type: Grant
    Filed: May 25, 2017
    Date of Patent: August 24, 2021
    Assignee: Oxford Nanopore Technologies Ltd.
    Inventors: Andrew John Heron, Daniel Ryan Garalde, James White
  • Patent number: 11091804
    Abstract: The invention provides methods for simultaneously amplifying multiple nucleic acid regions of interest in one reaction volume as well as methods for selecting a library of primers for use in such amplification methods. The invention also provides library of primers with desirable characteristics, such as minimal formation of amplified primer dimers or other non-target amplicons.
    Type: Grant
    Filed: January 24, 2020
    Date of Patent: August 17, 2021
    Assignee: Natera, Inc.
    Inventors: Bernhard Zimmermann, Matthew Hill, Philippe Lacroute, Michael Dodd, Alexander Wong
  • Patent number: 11078533
    Abstract: Methods and compositions for digital profiling of nucleic acid sequences present in a sample are provided.
    Type: Grant
    Filed: May 12, 2020
    Date of Patent: August 3, 2021
    Assignee: President and Fellows of Harvard College
    Inventors: Xiaoliang Sunney Xie, Katsuyuki Shiroguchi, Peter A. Sims, Tony Z. Jia
  • Patent number: 11066701
    Abstract: A method for template-directed sequencing-by-synthesis of an array of target polynucleotide can include: (a) providing an array of target polynucleotides in a fluidic vessel; (b) contacting the array of polynucleotides with a solution comprising (i) polymerization complex and (ii) reversibly terminating and differently labeled A,C,G, and T/U nucleotides; (c) incorporating one of the differently labeled nucleotides, using the polymerization complex, into a chain complementary to at least one of the array of polynucleotides; (d) binding imaging tags to the differently labeled nucleotides of step (c); (e) imaging and storing the identity and position of the imaging tags of step (d); (f) reversing termination (b)-(e); (g) repeating steps (b)-(e) and assembling a sequence for each of the array of target polynucleotides from the stored identity and position of the imaging tags, optionally as a homogeneous or one pot reaction. Additional methods of sequencing target polynucleotides are described herein.
    Type: Grant
    Filed: May 18, 2018
    Date of Patent: July 20, 2021
    Inventor: Kalim U. Mir
  • Patent number: 11047006
    Abstract: Next Generation DNA sequencing promises to revolutionize clinical medicine and basic research. However, while this technology has the capacity to generate hundreds of billions of nucleotides of DNA sequence in a single experiment, the error rate of approximately 1% results in hundreds of millions of sequencing mistakes. These scattered errors can be tolerated in some applications but become extremely problematic when “deep sequencing” genetically heterogeneous mixtures, such as tumors or mixed microbial populations. To overcome limitations in sequencing accuracy, a method Duplex Consensus Sequencing (DCS) is provided. This approach greatly reduces errors by independently tagging and sequencing each of the two strands of a DNA duplex. As the two strands are complementary, true mutations are found at the same position in both strands. In contrast, PCR or sequencing errors will result in errors in only one strand.
    Type: Grant
    Filed: June 22, 2020
    Date of Patent: June 29, 2021
    Assignee: UNIVERSITY OF WASHINGTON THROUGH ITS CENTER FOR COMMERCIALIZATION
    Inventors: Jesse Salk, Lawrence A. Loeb, Michael Schmitt
  • Patent number: 11041812
    Abstract: The present disclosure relates to a fluorogenic pH-sensitive dye and a film for detecting pH using the fluorogenic pH-sensitive dye on a polymer film. The fluorogenic pH-sensitive dye includes an aryl compound having a sulfonyl group (—SO2) and an agarose compound covalently bonded to the sulfonyl group (—SO2) of the aryl compound.
    Type: Grant
    Filed: January 12, 2018
    Date of Patent: June 22, 2021
    Assignee: SFC CO., LTD.
    Inventors: Moon-Chan Hwang, Jong-Tae Je
  • Patent number: 11028429
    Abstract: Sensitive, unbiased methods for genome-wide detection of potential off-target nuclease cleavage sites in DNA, e.g., in cell type-specific genomic DNA samples.
    Type: Grant
    Filed: May 31, 2018
    Date of Patent: June 8, 2021
    Assignee: The General Hospital Corporation
    Inventors: J. Keith Joung, Shengdar Tsai
  • Patent number: 11028438
    Abstract: In one implementation, a method is described. The method includes determining an operational characteristic of sensors of a sensor array. The method further includes selecting a group of sensors in the array based on the operational characteristic of sensors in the group. The method further includes enabling readout of the sensors in the selected group. The method further includes receiving output signals from the enabled sensors.
    Type: Grant
    Filed: May 5, 2020
    Date of Patent: June 8, 2021
    Assignee: Life Technologies Corporation
    Inventors: Todd Rearick, Mark Milgrew, Jonathan Schultz, Chris Papalias, Kim Johnson
  • Patent number: 11029308
    Abstract: The present invention relates to an odorant receptor based odorant sensor system and related methods. In particular, systems and methods are provided permitting detection and discrimination of an odorant molecule in a vapor/gaseous phase using a panel of odorant receptors expressed in heterologous cells.
    Type: Grant
    Filed: October 27, 2017
    Date of Patent: June 8, 2021
    Assignee: DUKE UNIVERSITY
    Inventor: Hiro Matsunami
  • Patent number: 11021749
    Abstract: The present disclosure provides compositions, methods, systems, and devices for polynucleotide processing. Such polynucleotide processing may be useful for a variety of applications, including polynucleotide sequencing.
    Type: Grant
    Filed: August 20, 2020
    Date of Patent: June 1, 2021
    Assignee: 10X GENOMICS, INC.
    Inventors: Benjamin Hindson, Kevin Ness, Serge Saxonov, Paul Hardenbol
  • Patent number: 11007523
    Abstract: A microfluidic device includes a substrate, a sensor, and one or more lamination films. The top surface of the substrate can include first recessed grooves forming first open channels and the bottom surface of the plastic substrate can include a first recessed cavity and second recessed groves forming second open channels. A first lamination film can be adhered with the top surface of the plastic substrate to form first closed channels. A second lamination film can be adhered to the bottom surface of the plastic substrate to form second closed channels. The sensor can be on the bottom surface of the substrate such that it overlies the first recessed cavity to form a flow cell with the sensor top surface inward facing. A first closed channel can be fluidically connected with a second closed channel and a first or second closed channel can be fluidically connected with the flow cell.
    Type: Grant
    Filed: August 31, 2018
    Date of Patent: May 18, 2021
    Assignee: MGI TECH CO., LTD.
    Inventors: Chen Li, Cheng Frank Zhong, Yu Liu, Yiwen Ouyang
  • Patent number: 11008609
    Abstract: The present disclosure provides methods, compositions, kits, and systems useful in the determination and evaluation of the immune repertoire using genomic DNA from a biological sample. In one aspect, target-specific primer panels provide for the effective amplification of sequences of T cell receptor and/or B cell receptor chains with improved sequencing accuracy and resolution over the repertoire. Nucleic acid sequences of variable regions associated with the immune cell receptor are determined to effectively portray clonal diversity of a biological sample and/or differences associated with the immune cell repertoire of a biological sample.
    Type: Grant
    Filed: August 31, 2018
    Date of Patent: May 18, 2021
    Assignee: Life Technologies Corporation
    Inventors: Geoffrey Lowman, Timothy Looney, Lifeng Lin, Elizabeth Linch, Lauren Miller
  • Patent number: 11001874
    Abstract: Methods of detecting aneuploidy in in vitro fertilized embryos are provided. A unique set of STR markers that can be rapidly and accurately quantified by multiplex PCR at the single cell level are used to analyze and select euploid embryos in an in vitro fertilization (IVF) setting. The markers include D13S284, D13S141, D18S54, D18S70, D21S266, D21S1951 and AMXY and are used to detect abnormalities in chromosomes 13, 18, 21 and the XY chromosomes.
    Type: Grant
    Filed: August 12, 2020
    Date of Patent: May 11, 2021
    Assignee: King Abdulaziz University
    Inventors: Aisha Elaimi, Ashraf Dallol, Adeel Chaudhary, Adel Abuzinadah, Muhammad Hussain Al-Qahtani