Method Specially Adapted For Identifying A Library Member Patents (Class 506/2)
  • Patent number: 10883939
    Abstract: An imaging apparatus comprises: (i) an illumination waveguide configured to propagate light by total internal reflection, wherein an evanescent field illuminates an object in close relation to the illumination waveguide; (ii) an array of light-sensitive areas arranged on a common substrate with the illumination waveguide for detecting light from the object; and (iii) a controller configured to control forming of an interference pattern in the illumination waveguide, wherein the interference pattern comprises at least one element of constructive interference for selectively illuminating a portion of the object, the at least one element having a dimension with a size in a range of 100 nm-10 ?m; wherein the controller is configured to sequentially change the interference pattern in relation to the object such that different portions are illuminated and light from different portions is sequentially detected.
    Type: Grant
    Filed: June 15, 2019
    Date of Patent: January 5, 2021
    Assignee: IMEC VZW
    Inventors: Pol Van Dorpe, Niels Verellen
  • Patent number: 10870880
    Abstract: The present disclosure provides a system and method for the detection of rare mutations and copy number variations in cell free polynucleotides. Generally, the systems and methods comprise sample preparation, or the extraction and isolation of cell free polynucleotide sequences from a bodily fluid; subsequent sequencing of cell free polynucleotides by techniques known in the art; and application of bioinformatics tools to detect rare mutations and copy number variations as compared to a reference. The systems and methods also may contain a database or collection of different rare mutations or copy number variation profiles of different diseases, to be used as additional references in aiding detection of rare mutations, copy number variation profiling or general genetic profiling of a disease.
    Type: Grant
    Filed: May 8, 2020
    Date of Patent: December 22, 2020
    Assignee: GUARDANT HEALTH, INC.
    Inventors: AmirAli Talasaz, Stefanie Ann Ward Mortimer
  • Patent number: 10853244
    Abstract: A method of writing data to a DNA strand comprises cutting an address block of a selected address-data block unit of the DNA strand to form first and second DNA strings, and inserting a replacement address-data block that includes a replacement data segment between the first DNA string and the second DNA string to provide a rewritten DNA strand having valid address followed by valid data and an invalid address followed by invalid data.
    Type: Grant
    Filed: May 25, 2017
    Date of Patent: December 1, 2020
    Assignee: SANDISK TECHNOLOGIES LLC
    Inventors: Christopher Petti, Srikanth Ranganathan
  • Patent number: 10851417
    Abstract: The invention relates to a high throughput method for determining telomere length of mammalian chromosomal DNA; primers for use in said method; a kit comprising said primers; use of said method to diagnose or prognose or to determine the risk of developing a telomere shortening disease such as cancer, ageing, neurological disorders including Alzheimer's disease, Parkinson's disease and other dementias, brain infarction, heart disease, chronic HIV infection, chronic hepatitis, skin diseases, chronic inflammatory bowel disease including ulcerative colitis, anaemia, atherosclerosis, Barrett's oesophagus and cancers including pre-cancerous conditions, infertility, telomere syndromes including dyskeratosis congenita, aplastic anaemia, idiopathic pulmonary fibrosis, familial myelodysplastic syndrome-acute myeloid leukaemia, Hoyeraal-Hreiderasson syndrome, Revesz syndrome, Coats plus syndrome, bone marrow failure, and cryptogenic liver cirrhosis.
    Type: Grant
    Filed: October 14, 2015
    Date of Patent: December 1, 2020
    Assignee: UNIVERSITY COLLEGE CARDIFF CONSULTANTS LIMITED
    Inventors: Duncan Baird, Kevin Norris
  • Patent number: 10844428
    Abstract: The disclosed embodiments concern methods, apparatus, systems and computer program products for determining sequences of interest using unique molecular index (UMI) sequences that are uniquely associable with individual polynucleotide fragments, including sequences with low allele frequencies and long sequence length. In some implementations, the UMIs include both physical UMIs and virtual UMIs. In some implementations, the unique molecular index sequences include non-random sequences. System, apparatus, and computer program products are also provided for determining a sequence of interest implementing the methods disclosed.
    Type: Grant
    Filed: April 15, 2016
    Date of Patent: November 24, 2020
    Assignee: Illumina, Inc.
    Inventors: Sante Gnerre, Byoungsok Jung, Emrah Kostem, Alex Aravanis, Alex So, Xuyu Cai, Zhihong Zhang, Frank J. Steemers
  • Patent number: 10837063
    Abstract: The present disclosure provides a system and method for the detection of rare mutations and copy number variations in cell free polynucleotides. Generally, the systems and methods comprise sample preparation, or the extraction and isolation of cell free polynucleotide sequences from a bodily fluid; subsequent sequencing of cell free polynucleotides by techniques known in the art; and application of bioinformatics tools to detect rare mutations and copy number variations as compared to a reference. The systems and methods also may contain a database or collection of different rare mutations or copy number variation profiles of different diseases, to be used as additional references in aiding detection of rare mutations, copy number variation profiling or general genetic profiling of a disease.
    Type: Grant
    Filed: November 30, 2017
    Date of Patent: November 17, 2020
    Assignee: GUARDANT HEALTH, INC.
    Inventor: AmirAli Talasaz
  • Patent number: 10837055
    Abstract: Disclosed are methods for determining at least one sequence of interest of a fetus of a pregnant mother. In various embodiments, the method can determine one or more sequences of interest in a test sample that comprises a mixture of maternal cellular DNA and mother-and-fetus cfDNA. In some embodiments, methods are provided for determining whether the fetus has a genetic disease. In some embodiments, methods are provided for determining whether the fetus is homozygous in a disease causing allele when the mother is heterozygous of the same allele. In some embodiments, methods are provided for determining whether the fetus has a copy number variation (CNV) or a non-CNV genetic sequence anomaly.
    Type: Grant
    Filed: August 9, 2018
    Date of Patent: November 17, 2020
    Assignee: Illumina, Inc.
    Inventors: Anupama Srinivasan, Darya I. Chudova, Richard P. Rava
  • Patent number: 10816504
    Abstract: In one embodiment, a device is described. The device includes a material defining a reaction region. The device also includes a plurality of chemically-sensitive field effect transistors have a common floating gate in communication with the reaction region. The device also includes a circuit to obtain respective output signals from the chemically-sensitive field effect transistors indicating an analyte within the reaction region.
    Type: Grant
    Filed: October 24, 2019
    Date of Patent: October 27, 2020
    Assignee: Life Technologies Corporation
    Inventors: Jonathan M. Rothberg, Keith G. Fife, James Bustillo, Jordan Owens
  • Patent number: 10787703
    Abstract: Genomic DNA contains embedded ribonucleotides (rNMPs) that are incorporated during DNA replication and repair, or formed during DNA damage. The modifications have been linked to genome instability and disease, but no method currently exists to profile their locations genome-wide. rNMP incorporation has been extensively studied in recent years; however, locating sites of rNMP incorporation in genomic DNA has not yet been possible. Disclosed herein is a unique method for mapping rNMPs in genomic DNA that exploits the unique ligation mechanism of Arabidopsis thaliana tRNA ligase (AtRNL), normally involved in tRNA maturation. As disclosed herein AtRNL captures 2?,3?-cyclic phosphate or 2?-phosphate termini of DNA derived from alkaline cleavage of a DNA oligonucleotide (oligo) at an embedded rNMP, ligating the 2?-phosphate end to the 5?-phosphate terminus of the same DNA molecule and producing a ssDNA circle containing an embedded rNMP.
    Type: Grant
    Filed: January 9, 2017
    Date of Patent: September 29, 2020
    Assignee: Georgia Tech Research Corporation
    Inventors: Francesca Storici, Jay Hesselberth, Kyung Duk Koh
  • Patent number: 10781483
    Abstract: Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs 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 analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.
    Type: Grant
    Filed: November 21, 2016
    Date of Patent: September 22, 2020
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Lubomir Sebo, Gene Shen, Stephen Yue, Honey Osuna, Yuri Lapin, Louis Brogley, Andrei Fedorov
  • Patent number: 10781481
    Abstract: Methods, polynucleotides, kits, and reaction mixtures are disclosed for the enriching of short polynucleotide molecules that have a length within a desired target length range. A Type IIS or Type III restriction enzyme is used to cleave polynucleotides at cleavage sites located at a distance from the restriction enzyme recognition sites. For example, a mixture of polynucleotides can be formed by inserting DNA molecules between a recognition site for the restriction enzyme and a region of non-naturally-occurring nucleotides that block cleavage by the restriction enzymes. If a polynucleotide contains a DNA molecule with a length within a target range, then the cleavage site will be within the blocking region, and cleavage will not occur. Polynucleotides containing DNA molecules with lengths outside the target range can be cleaved. By selectively enriching, through PCR or other means, polynucleotides that are intact, a concentrated population of polynucleotides of a target length can be formed.
    Type: Grant
    Filed: April 27, 2017
    Date of Patent: September 22, 2020
    Assignee: Bio-Rad Laboratories, Inc.
    Inventor: Rongdian Fu
  • Patent number: 10770183
    Abstract: The present invention provides method of classifying a subject into a necrotizing meningoencephalitis (NME) disease risk group. The method may include assessing the presence of one or more marker (e.g., SNPs or risk loci) in a sample from the subject. For example, detection of the presence of one or more markers that are associated with an increased risk of NME can indicate that the subject should be classified into a risk group.
    Type: Grant
    Filed: October 22, 2018
    Date of Patent: September 8, 2020
    Assignees: The Translational Genomics Research Institute, University of Georgia Research Foundation, Inc.
    Inventors: Matthew Huentelman, Scott Schatzberg, Renee Barber
  • Patent number: 10752946
    Abstract: High-fidelity, high-throughput nucleic acid sequencing enables healthcare practitioners and patients to gain insight into genetic variants and potential health risks. However, previous methods of nucleic acid sequencing often introduce sequencing errors (for example, mutations that arise during the preparation of a nucleic acid library, during amplification, or sequencing). Provided herein are methods and compositions for sequencing nucleic acids. Further provided are methods of identifying an error in a nucleic acid sequence.
    Type: Grant
    Filed: January 17, 2018
    Date of Patent: August 25, 2020
    Assignee: MYRIAD WOMEN'S HEALTH, INC.
    Inventors: Clement S. Chu, Noah C. Welker, Henry H. Lai
  • Patent number: 10753899
    Abstract: A whole blood measurement method associated to hematocrit (HCT) and a whole blood measurement circuit thereof is applied in the detection of HCT of a whole blood sample to be tested. Herein, a time to digital converting circuit (TDC) is used for counting charging time or discharging time of a fixed capacitor and a to-be-tested sample, and a capacitance difference that is related to HCT is generated according to the charging time or the discharging time, so as to provide a reference for a whole blood feature test.
    Type: Grant
    Filed: November 1, 2018
    Date of Patent: August 25, 2020
    Assignee: HOLTEK SEMICONDUCTOR INC.
    Inventors: Kuo-Hsiang Chen, Kuo-Yang Li, Hung-Yu Liu
  • Patent number: 10731150
    Abstract: Multimeric barcoding reagents for labelling a target nucleic acid comprise: first and second barcode molecules linked together, wherein each of the barcode molecules comprises a nucleic acid sequence comprising a barcode region; and first and second barcoded oligonucleotides. The multimeric barcoding reagents enable spatial sequencing. A single multimeric barcoding reagent can be used to label sub-sequences of an intact nucleic acid molecule or co-localised fragments of a nucleic acid molecule. The labelled sub-sequences can be sequenced and the sequencing data processed to determine the sequence of sub-sequences from a single intact nucleic acid molecule or from co-localised fragments of a nucleic acid molecule. Corresponding libraries, kits, methods and uses are provided.
    Type: Grant
    Filed: January 11, 2019
    Date of Patent: August 4, 2020
    Assignee: CS Genetics Limited
    Inventor: Lucas Brandon Edelman
  • Patent number: 10718020
    Abstract: Methods and kits for selectively enriching non-random polynucleotide sequences are provided. Methods and kits for generating libraries of sequences are provided. Methods of using selectively enriched non-random polynucleotide sequences for detection of fetal aneuploidy are provided.
    Type: Grant
    Filed: September 28, 2016
    Date of Patent: July 21, 2020
    Assignee: Verinata Health, Inc.
    Inventors: Yue-Jen Chuu, Richard P. Rava
  • Patent number: 10718013
    Abstract: Method and sample vessels are provided for amplification and sequencing of nucleic acids in a sample.
    Type: Grant
    Filed: June 2, 2016
    Date of Patent: July 21, 2020
    Assignee: BioFire Defense, LLC. et al.
    Inventors: Mark Aaron Poritz, Kirk Max Ririe, Christopher Paul Pasko, Ann Michelle Demogines, Robert John Crisp, Margarita Rogatcheva, Robert Cornelius Trauscht, Matthew Kam Jones, Tyler Lane Healy
  • Patent number: 10699802
    Abstract: Embodiments of a method and/or system (e.g., for microsatellite instability detection associated with at least one cancer condition; etc.) can include: determining a microsatellite-related background model; determining one or more loci associated with microsatellite instability based on the microsatellite-related background model; and/or determining a microsatellite instability characterization (e.g., a binary status determination between microsatellite instability such as MSI-H, and microsatellite stability such as MSS; etc.) for the user. Additionally or alternatively, embodiments of the method and/or system can include facilitating treatment provision for one or more users based on the microsatellite instability characterization.
    Type: Grant
    Filed: October 9, 2018
    Date of Patent: June 30, 2020
    Assignee: Strata Oncology, Inc.
    Inventors: Bryan Johnson, Dan Rhodes, Scott Tomlins
  • Patent number: 10696965
    Abstract: Provided herein are methods, systems, and compositions for seamless nucleic acid assembly. Methods, systems, and compositions as provided herein provide for efficient assembly of nucleic acids without primer removal. Methods, systems, and compositions for seamless nucleic acid assembly comprise use of an endonuclease or exonuclease, optionally in conjunction with additional enzymes to assemble nucleic acids or polynucleotides.
    Type: Grant
    Filed: June 12, 2018
    Date of Patent: June 30, 2020
    Assignee: TWIST BIOSCIENCE CORPORATION
    Inventors: Rebecca Nugent, Siyuan Chen, Elian Lee, Nathan Raynard
  • Patent number: 10683538
    Abstract: The present invention provides a method of determining integrity and/or quantity of cell free DNA (cfDNA) in a bio logical sample comprising amplifying target sequences with at least a first primer/probe set and at least a second primer probe/set, amplifying the target sequences of differing lengths, and monitoring for detection of the labels of the oligonucleotide probes, and determining the integrity and/or quantity of the cfDNA based on the level of detection of the label of the oligonucleotide probe from the first primer/probe set compared to the level detection of the label of the oligonucleotide probe from the second primer/probe set. The present invention also provides methods for generating a library with the cfDNA for sequencing and analysis.
    Type: Grant
    Filed: April 18, 2016
    Date of Patent: June 16, 2020
    Assignee: The Translational Genomics Research Institute
    Inventors: Muhammed Murtaza, Tania Contente-Cuomo
  • Patent number: 10683491
    Abstract: The present invention relates to subtilase variants suitable for use in, e.g., cleaning or detergent compositions, such as laundry detergent compositions and dish wash compositions, including automatic dish wash compositions. The present invention also relates to isolated DNA sequences encoding the variants, expression vectors, host cells, and methods for producing and using the variants of the invention.
    Type: Grant
    Filed: December 3, 2015
    Date of Patent: June 16, 2020
    Assignee: NOVOZYMES A/S
    Inventors: Miguel Duarte Guilherme Pereira Toscano, Leonardo De Maria
  • Patent number: 10676734
    Abstract: Provided are methods, compositions, reagents, kits that are useful for detecting a specific nucleic acid region in genome with high efficiency and high sensitivity.
    Type: Grant
    Filed: July 11, 2017
    Date of Patent: June 9, 2020
    Assignee: LIFE TECHNOLOGIES CORPORATION
    Inventor: Pei-Zhong Tang
  • Patent number: 10655175
    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, the output signals indicating chemical reactions occurring proximate to the sensors of the sensor array.
    Type: Grant
    Filed: October 8, 2018
    Date of Patent: May 19, 2020
    Assignee: Life Technologies Corporation
    Inventors: Todd Rearick, Mark Milgrew, Jonathan Schultz, Chris Papalias, Kim Johnson
  • Patent number: 10626443
    Abstract: Provided herein are methods for enriching a biological sample for a target nucleic acid, and analyzing the nucleic acid. In some cases, a biological sample is enriched for target nucleic acids associated with a cancer or tumor. In some cases, a biological sample is enriched for target nucleic acids, and the target nucleic acids vary in length. In some cases, one or more probes are used to enrich the biological sample for the target nucleic acid. In some cases, one or more probes hybridize to one or more ends of a target nucleic acid.
    Type: Grant
    Filed: August 10, 2017
    Date of Patent: April 21, 2020
    Assignee: GRAIL, Inc.
    Inventors: Eugeni Namsaraev, Maneesh Jain
  • Patent number: 10626455
    Abstract: Improved single molecule sequencing methods, compositions, and devices, are provided. In a first aspect, the present invention provides a multi-pass method of sequencing a target sequence using nanopore sequencing, the method comprising: i) providing a non-naturally occurring concatemer nucleic acid molecule comprising a plurality of copies of the target sequence; ii) nanopore sequencing at least three copies of the target sequence in the concatemer, thereby obtaining a multi-pass sequence dataset, wherein the multi-pass sequence dataset comprises target sequence datasets for the at least three copies of the target sequence; and iii) using the multi-pass sequence dataset to determine the target sequence.
    Type: Grant
    Filed: November 10, 2015
    Date of Patent: April 21, 2020
    Assignees: BGI Shenzhen, BGI Shenzhen Co., Ltd.
    Inventors: Handong Li, Y. Tom Tang, Jing Yu, Hui Jiang, Wenwei Zhang, Guangyi Fan, He Zhang, Kailong Ma, Chunyu Geng
  • Patent number: 10597653
    Abstract: The invention provides methods for generating a nucleic acid library. Target-specific primer-probes are hybridized to a target nucleic acid fragment to create a hybridization product. Each of the target-specific primer-probes comprises a target-specific sequence and a first adaptor sequence. The target nucleic acid fragment comprises a target genomic region of interest, wherein said target genomic region of interest comprises an exon of a gene and the target-specific primer-probes are tiled across the exon of the gene. The target nucleic acid fragment further comprises a second adaptor sequence different from said first adaptor sequence. Following hybridization, the target-specific primer-probes are extended to create double-stranded extension products and further amplified, thereby generating the nucleic acid library.
    Type: Grant
    Filed: April 17, 2017
    Date of Patent: March 24, 2020
    Assignee: Illumina, Inc.
    Inventors: Andrea Sabot, Roberto Rigatti, Min-Jui Richard Shen
  • Patent number: 10590464
    Abstract: Presented herein are methods and compositions for enhancing utilization of surface primers during the surface amplification process. The methods are useful for surface amplification at improved densities. The methods and compositions provided herein enable creation of clusters which are brighter, but at the same densities as currently achieved using standard cluster amplification.
    Type: Grant
    Filed: May 27, 2016
    Date of Patent: March 17, 2020
    Assignee: Illumina Cambridge Limited
    Inventors: Jonathan Mark Boutell, Gary Mark Skinner
  • Patent number: 10576471
    Abstract: Disclosed herein are devices, systems and methods for conducting a reaction using electrowetting in a vertical or substantially vertical position. Some embodiments disclosed herein provide fluidic cartridges for use in a substantially vertical position comprising: (a) a front substrate; (b) a back substrate; (c) a droplet operations gap formed between the front substrate and the back substrate; and (d) a plurality of electrodes on the front substrate or the back substrate, wherein the plurality of electrodes are configured to transport a droplet along a substantially vertical plane defined by the front substrate and the back substrate.
    Type: Grant
    Filed: March 18, 2016
    Date of Patent: March 3, 2020
    Assignee: ILLUMINA, INC.
    Inventors: James Osmus, Richard L. Lemoine, Jian Gong, Sz-Chin Steven Lin
  • Patent number: 10571426
    Abstract: A pixel circuit acts as a sensing element in a sensing device. The pixel circuit includes a sensing electrode, a first gate electrically connected to the sensing electrode, a second gate in electrical communication with the first gate, and a readout device that is electrically connected to the second gate. An input voltage applied to the sensing electrode is amplified between the first gate and the second gate, the amplification being measured as an output signal from the readout device to perform a sensing operation. For example, the output signal may be relatable to pH, analyte measurements, or other properties of sample liquids analyzed by the sensing device. A sensing device may include multiple pixels disposed on a substrate, each pixel including said pixel circuit. Driver circuits controlled by control electronics are configured to generate signals that selectively address the pixels and to read out voltages at the sensing electrodes.
    Type: Grant
    Filed: August 13, 2018
    Date of Patent: February 25, 2020
    Assignee: Sharp Life Science (EU) Limited
    Inventors: Benjamin James Hadwen, Campbell Donald Brown, Christopher James Brown, Gregory Gay, Sally Anderson
  • Patent number: 10557169
    Abstract: Modified nucleic acid adapters are provided that collectively provide a mixture of nucleotides at the 3? end of 5? adapters and at the 5? end of 3? adapters such that at least one adapter in each set has any given nucleotide at position 1, i.e., the nucleotide position available for ligation to a small RNA, and has any given nucleotide at position 2 adjacent to position 1 for use in overcoming bias during nucleic acid manipulation, such as small RNA characterization and/or profiling by, e.g., deep sequencing, along with methods for use of the modified adapters in small RNA characterization. The modified adapters have at least two mixed nucleotides at the adapter terminus to be ligated to a nucleic acid such as a small RNA.
    Type: Grant
    Filed: November 3, 2016
    Date of Patent: February 11, 2020
    Assignee: Mount Sinai School of Medicine
    Inventors: Ravi Sachidanandam, Anitha Jayaprakash, Brian Brown
  • Patent number: 10533221
    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. In some cases, this disclosure provides methods for the generation of polynucleotide barcode libraries, and for the attachment of such polynucleotides to target polynucleotides.
    Type: Grant
    Filed: October 19, 2018
    Date of Patent: January 14, 2020
    Assignee: 10X GENOMICS, INC.
    Inventors: Benjamin Hindson, Mirna Jarosz, Paul Hardenbol, Michael Schnall-Levin, Kevin Ness, Serge Saxonov
  • Patent number: 10525148
    Abstract: Embodiments of the invention provide methods of creating clinical models for different forms of metastatic cancer. The methods may include obtaining samples from subjects with metastatic cancer, determining an allelic status of one or more markers in the samples (e.g., creating a molecular profile of the subject's cancer), and using model organisms with subject-derived xenografts for treatment selection.
    Type: Grant
    Filed: March 25, 2015
    Date of Patent: January 7, 2020
    Assignee: The Translational Genomics Research Institute
    Inventor: Bodour Salhia
  • Patent number: 10529443
    Abstract: The disclosure provides methods to assemble genomes of eukaryotic or prokaryotic organisms. The disclosure further provides methods for haplotype phasing and meta-genomics assemblies.
    Type: Grant
    Filed: November 27, 2018
    Date of Patent: January 7, 2020
    Assignee: The Regents of the University of California
    Inventors: Richard E. Green, Jr., Liana F. Lareau
  • Patent number: 10526601
    Abstract: In certain embodiments, the present invention provides a way of “digitally” marking different the alleles of different chromosomes by using a transposase to insert differently barcoded transposons into genomic DNA before further analysis. According to this method, each allele becomes marked with a unique pattern of transposon barcodes. Because each unique pattern of transposon barcodes identifies a particular allele, the method facilitates determinations of ploidy and copy number variation, improves the ability to discriminate among homozygotes, heterozygotes, and patterns arising from sequencing errors, and allows loci separated by uninformative stretches of DNA to be identified as linked loci, thereby facilitating haplotype determinations. Also provided is a novel artificial transposon end that includes a barcode sequence in two or more positions that are not essential for transposition.
    Type: Grant
    Filed: May 21, 2015
    Date of Patent: January 7, 2020
    Assignee: Digenomix Corporation
    Inventors: Lei Xi, Xiaohui Wang, Marc Unger, David Ruff
  • Patent number: 10508300
    Abstract: This disclosure provides, inter alia, a probe system probe system for analyzing a nucleic acid sample. In some embodiments, the probe system may comprise: a set of identifier oligonucleotides of sequence B, a set of splint oligonucleotides of formula X?-A?-B?-Z?, wherein sequence A? is complementary to a genomic fragment and sequence B? is complementary to at least one member of the set of identifier oligonucleotides, and one or more probe sequences comprising X and Z. Each splint oligonucleotide is capable of hybridizing to the probe sequences, a member of the set of identifier oligonucleotides and a genomic fragment, thereby producing a ligatable complex of formula X-A-B-Z. The probe system can be used to identify a chromosome aneuploidy in cell free DNA, for example.
    Type: Grant
    Filed: September 16, 2016
    Date of Patent: December 17, 2019
    Assignee: Vanadis Diagnostics
    Inventors: Carl Oscar Fredrik Dahl, Olof John Ericsson, Filip Karlsson, Fredrik Roos
  • Patent number: 10457937
    Abstract: Provided herein are devices and methods for the micro-isolation of biological cellular material. A micro-isolation device described can comprise a photomask that protects regions of interest against DNA-destroying illumination. The micro-isolation device can further comprise photosensitive material defining access wells following illumination and subsequent developing of the photosensitive material. The micro-isolation device can further comprise a chambered microfluidic device comprising channels providing access to wells defined in photosensitive material. The micro-isolation device can comprise a chambered microfluidic device without access wells defined in photosensitive material where valves control the flow of gases or liquids through the channels of the microfluidic device.
    Type: Grant
    Filed: January 31, 2018
    Date of Patent: October 29, 2019
    Assignees: CALIFORNIA INSTITUTE OF TECHNOLOGY, UNIVERSITY OF SOUTHERN CALIFORNIA, CURATE BIOSCIENCES LLC
    Inventors: Emil P. Kartalov, Cheng-Chung Lee, Paul Predki
  • Patent number: 10457990
    Abstract: Embodiments of the present invention provide methods, systems, and apparatus for deducing the fetal DNA fraction in maternal plasma without using paternal or fetal genotypes. Maternal genotype information may be obtained from a maternal-only DNA sample or may be assumed from shallow-depth sequencing of a biological sample having both maternal and fetal DNA molecules. Because sequencing may be at shallow depths, a locus may have only few reads and may fail to exhibit a non-maternal allele even if a non-maternal allele is present. However, normalized parameters that characterize non-maternal alleles sequenced can be used to provide an accurate estimate of the fetal DNA fraction, even if the amount of non-maternal alleles is in error. Methods described herein may not need high-depth sequencing or enrichment of specific regions. As a result, these methods can be integrated into widely used non-invasive prenatal testing and other diagnostics.
    Type: Grant
    Filed: September 22, 2016
    Date of Patent: October 29, 2019
    Assignee: The Chinese University of Hong Kong
    Inventors: Yuk-Ming Dennis Lo, Peiyong Jiang, Kwan Chee Chan, Rossa Wai Kwun Chiu
  • Patent number: 10457948
    Abstract: The present invention resides in a method for the manufacture of a disulphide-requiring biopharmaceutical having an element of at least tertiary structure using wild type E. coli.
    Type: Grant
    Filed: November 6, 2015
    Date of Patent: October 29, 2019
    Assignee: University of Kent
    Inventor: Colin Robinson
  • Patent number: 10441588
    Abstract: The present disclosure relates to chemical compounds, methods for their discovery, and their therapeutic and research use. In particular, the present disclosure provides compounds as therapeutic agents against bacterial infections (e.g., biofilms). The present disclosure also provides topical formulations for use in methods for treating bacterial infections.
    Type: Grant
    Filed: September 21, 2017
    Date of Patent: October 15, 2019
    Assignees: Curators of the University of Missouri, Nanova, Inc.
    Inventors: Hongmin Sun, David W. Anderson, Feng Qi
  • Patent number: 10435685
    Abstract: 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: Grant
    Filed: January 14, 2016
    Date of Patent: October 8, 2019
    Assignee: Pacific Biosciences of California, Inc.
    Inventors: Yu-Chih Tsai, Igor Drasko Vilfan, Khai Luong
  • Patent number: 10421997
    Abstract: The present invention relates to a method of identifying a nucleotide at a defined position and determining the sequence of a target polynucleotide using an electro-switchable biosensor, as well as devices comprising an electro-switchable biosensor and uses thereof.
    Type: Grant
    Filed: February 3, 2015
    Date of Patent: September 24, 2019
    Assignee: Roche Diagnostics Oeprations, Inc.
    Inventors: Dieter Heindl, Andreas Langer, Ulrich Rant, Ralf Strasser, Michael Schraeml
  • Patent number: 10408675
    Abstract: An enclosed benchtop analytical device, as well as systems, processes, and techniques related thereto are disclosed. A benchtop analytical device can include an enclosure enclosing a probe and a sample. A compliance component can determine satisfaction of one or more compliance rules, such as a compliance rule relating to an enclosure being in an operable configuration based on a lid of the enclosure being closed. If the compliance rule(s) is determined to be satisfied, the compliance component may enable the release of optical energy for interrogation of the sample via the probe. In some embodiments, the enclosure can enclose a sample plate that can be used to conveniently and accurately retain a sample in a suitable position within the enclosure.
    Type: Grant
    Filed: February 15, 2018
    Date of Patent: September 10, 2019
    Assignee: MarqMetrix, Inc.
    Inventors: Brian James Marquardt, John Scott Van Vuren
  • Patent number: 10407739
    Abstract: Disclosed are methods of identifying a methicillin-resistant Staphylococcus aureus (MRSA) in a sample wherein the methods involve detecting a S. aureus-specific nucleic acid sequence, mecA and mecC, in the sample. Kits for determining the presence of MRSA in a sample are also provided.
    Type: Grant
    Filed: September 19, 2014
    Date of Patent: September 10, 2019
    Assignee: QUEST DIAGNOSTICS INVESTMENTS INCORPORATED
    Inventors: Lakshmi Nair, Heather Vincent, Huong Mai, Michael Aye, Michelle Tabb, Maurice Exner
  • Patent number: 10395759
    Abstract: Methods and systems for determining copy number variants are disclosed. An example method can comprise applying a sample grouping technique to select reference coverage data, normalizing sample coverage data comprising a plurality of genomic regions, and fitting a mixture model to the normalized sample coverage data based on the selected reference coverage data. An example method can comprise identifying one or more copy number variants (CNVs) according to a Hidden Markov Model (HMM) based on the normalized sample coverage data and the fitted mixture model. An example method can comprise outputting the one or more copy number variants.
    Type: Grant
    Filed: May 18, 2015
    Date of Patent: August 27, 2019
    Assignee: REGENERON PHARMACEUTICALS, INC.
    Inventors: Jeffrey Reid, Lukas Habegger, Jonathan Packer, Evan Maxwell
  • Patent number: 10392425
    Abstract: The present invention provides multivalent CD20-binding molecules, and compositions thereof, such as enriched compositions comprising large proportions of multivalent CD20-binding molecule relative to monovalent CD20-binding molecule. Certain multivalent CD20-binding molecules of the present invention comprise 1) two or more CD20 binding regions and 2) one or more Shiga toxin effector polypeptide regions derived from an A Subunit of a member of the Shiga toxin family. Certain multivalent CD20-binding molecules of the present invention, and compositions thereof, have uses for selective killing specific cell types and as therapeutics for the treatment of a variety of diseases, including cancers, tumors, and immune disorders.
    Type: Grant
    Filed: February 4, 2016
    Date of Patent: August 27, 2019
    Assignee: Molecular Templates, Inc.
    Inventors: Eric Poma, Erin Willert, Jason Kim, Jack Higgins, Jensing Liu, Rodney Flores-Lefranc
  • Patent number: 10370717
    Abstract: The present invention provides for methods of measuring levels of micro RNAs for the diagnosis, treatment and/or monitoring the progression of post-traumatic stress disorder (PTSD) or traumatic brain injury (TBI) in a subject having or suspected of having PTSD and/or TBI. The methods, in general comprise measuring levels of at least one of miR-142-5p, miR-19b, miR-1928, miR-223-3p, miR-322*, miR-324, miR-421-3p, miR-463* and miR-674* is a sample from a subject suffering from or suspected of having PTSD and/or TBI.
    Type: Grant
    Filed: April 21, 2015
    Date of Patent: August 6, 2019
    Assignee: The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
    Inventors: Radha K. Maheshwari, Nagaraja S. Balakathiresan, Manish Bhomia, Raghavendar Chandran
  • Patent number: 10337072
    Abstract: Described herein are methods of measuring, in a genomic sample from an individual, the relative frequency of a target sequence (that is, its copy number) with respect to a control sequence of known copy number at a different genomic locus in the same genome, wherein the target and control sequences differ by at least one single nucleotide variation (SNV). These methods involve both the target sequence and the control sequence in a single reaction/container, using a pair of primers that prime amplification of both the target sequence and the control sequence, or a single downstream primer and two upstream primers (that differs only at the position of the SNV between the target and control sequences), and measuring the abundance of each of the target sequence and the control sequence using SNV-specific labeled probes or primers, or a melting curve analysis that distinguishes between the amplified control and target sequences. The methods are exemplified with various different amplifications process.
    Type: Grant
    Filed: January 8, 2016
    Date of Patent: July 2, 2019
    Assignee: The Board of Trustees of the University of Illinois
    Inventors: Matthew E. Hudson, Brian W. Diers, Tong Geon Lee
  • Patent number: 10329605
    Abstract: A method for detecting a low-occurrence mutation in isolated DNA adds a blocking probe to reagents during amplification of the isolated DNA. The blocking probe is an oligonucleotide complementary to wild-type DNA corresponding to the sample. The blocking probe spans a site of a suspected mutation within a region of interest in the isolated DNA. After amplification, fragments of the amplified DNA is sequenced using next generating sequencing and an output is generated to display the sequenced fragments. In some embodiments, the blocking probe is locked nucleic acid (LNA).
    Type: Grant
    Filed: April 20, 2016
    Date of Patent: June 25, 2019
    Assignee: NEOGENOMICS LABORATORIES, INC.
    Inventor: Maher Albitar
  • Patent number: 10323282
    Abstract: The invention is directed to methods and compositions for collecting a non-placental biological samples of cells and quantifying and comparing levels of expression of microRNAs to characterize a preeclampsia-related condition. The samples may be collected before or after an intervention or may be collected over a period of time. One of the samples may be a control sample. Patients may then be treated according to their response.
    Type: Grant
    Filed: May 21, 2013
    Date of Patent: June 18, 2019
    Assignee: Edward E. Winger, M.D., Professional Corporation
    Inventors: Edward E. Winger, Jane L. Reed
  • Patent number: 10323279
    Abstract: This disclosure provides methods and compositions for sample processing, particularly for sequencing applications. Included within this disclosure are bead compositions, such as diverse libraries of beads attached to large numbers of oligonucleotides containing barcodes. Often, the beads provides herein are degradable. For example, they may contain disulfide bonds that are susceptible to reducing agents. The methods provided herein include methods of making libraries of barcoded beads as well as methods of combining the beads with a sample, such as by using a microfluidic device.
    Type: Grant
    Filed: August 1, 2018
    Date of Patent: June 18, 2019
    Assignee: 10X GENOMICS, INC.
    Inventors: Christopher Hindson, Michael Schnall-Levin, Andrew Price, Paul Hardenbol, Yuan Li