Method Specially Adapted For Identifying A Library Member Patents (Class 506/2)
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Patent number: 11168356Abstract: 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: GrantFiled: November 1, 2018Date of Patent: November 9, 2021Assignees: The Chinese University of Hong Kong, GRAIL, Inc.Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang
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Patent number: 11167041Abstract: 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: GrantFiled: November 18, 2020Date of Patent: November 9, 2021Assignee: 4D MOLECULAR THERAPEUTICS INC.Inventors: David H. Kirn, Melissa Kotterman, David Schaffer
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Patent number: 11154865Abstract: 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: GrantFiled: September 6, 2017Date of Patent: October 26, 2021Assignee: Lariat Biosciences, Inc.Inventors: Jonathan W. Larson, Alexandra Damiano
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Patent number: 11149307Abstract: 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: GrantFiled: February 4, 2021Date of Patent: October 19, 2021Assignee: GUARDANT HEALTH, INC.Inventors: AmirAli Talasaz, Helmy Eltoukhy, Stefanie Ann Ward Mortimer
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Patent number: 11150179Abstract: 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: GrantFiled: January 5, 2018Date of Patent: October 19, 2021Assignee: Illumina, Inc.Inventors: Robert Langlois, Paul Belitz
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Patent number: 11142798Abstract: 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: GrantFiled: November 17, 2016Date of Patent: October 12, 2021Assignee: GENOMICARE BIOTECHNOLOGY (SHANGHAI) CO. LTDInventors: Qiang Xu, Guan Wang, Chun Dai
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Patent number: 11117113Abstract: 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: GrantFiled: December 16, 2016Date of Patent: September 14, 2021Assignee: FLUIDIGM CORPORATIONInventor: Peilin Chen
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Patent number: 11104960Abstract: 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: GrantFiled: September 13, 2019Date of Patent: August 31, 2021Assignees: Exact Sciences Development Company, LLC, Mayo Foundation for Medical Education and ResearchInventors: David A. Ahlquist, William R. Taylor, John B. Kisiel, Douglas W. Mahoney, Tracy C. Yab, Graham P. Lidgard, Hatim T. Allawi
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Patent number: 11098355Abstract: 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: GrantFiled: May 25, 2017Date of Patent: August 24, 2021Assignee: Oxford Nanopore Technologies Ltd.Inventors: Andrew John Heron, Daniel Ryan Garalde, James White
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Patent number: 11098358Abstract: 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: GrantFiled: April 30, 2020Date of Patent: August 24, 2021Assignee: BECTON, DICKINSON AND COMPANYInventors: Clark Mason, Liping Yu
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Patent number: 11091804Abstract: 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: GrantFiled: January 24, 2020Date of Patent: August 17, 2021Assignee: Natera, Inc.Inventors: Bernhard Zimmermann, Matthew Hill, Philippe Lacroute, Michael Dodd, Alexander Wong
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Patent number: 11078533Abstract: Methods and compositions for digital profiling of nucleic acid sequences present in a sample are provided.Type: GrantFiled: May 12, 2020Date of Patent: August 3, 2021Assignee: President and Fellows of Harvard CollegeInventors: Xiaoliang Sunney Xie, Katsuyuki Shiroguchi, Peter A. Sims, Tony Z. Jia
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Patent number: 11066701Abstract: 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: GrantFiled: May 18, 2018Date of Patent: July 20, 2021Inventor: Kalim U. Mir
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Patent number: 11047006Abstract: 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: GrantFiled: June 22, 2020Date of Patent: June 29, 2021Assignee: UNIVERSITY OF WASHINGTON THROUGH ITS CENTER FOR COMMERCIALIZATIONInventors: Jesse Salk, Lawrence A. Loeb, Michael Schmitt
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Patent number: 11041812Abstract: 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: GrantFiled: January 12, 2018Date of Patent: June 22, 2021Assignee: SFC CO., LTD.Inventors: Moon-Chan Hwang, Jong-Tae Je
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Patent number: 11028438Abstract: 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: GrantFiled: May 5, 2020Date of Patent: June 8, 2021Assignee: Life Technologies CorporationInventors: Todd Rearick, Mark Milgrew, Jonathan Schultz, Chris Papalias, Kim Johnson
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Patent number: 11029308Abstract: 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: GrantFiled: October 27, 2017Date of Patent: June 8, 2021Assignee: DUKE UNIVERSITYInventor: Hiro Matsunami
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Patent number: 11028429Abstract: 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: GrantFiled: May 31, 2018Date of Patent: June 8, 2021Assignee: The General Hospital CorporationInventors: J. Keith Joung, Shengdar Tsai
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Patent number: 11021749Abstract: 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: GrantFiled: August 20, 2020Date of Patent: June 1, 2021Assignee: 10X GENOMICS, INC.Inventors: Benjamin Hindson, Kevin Ness, Serge Saxonov, Paul Hardenbol
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Patent number: 11008609Abstract: 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: GrantFiled: August 31, 2018Date of Patent: May 18, 2021Assignee: Life Technologies CorporationInventors: Geoffrey Lowman, Timothy Looney, Lifeng Lin, Elizabeth Linch, Lauren Miller
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Patent number: 11007523Abstract: 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: GrantFiled: August 31, 2018Date of Patent: May 18, 2021Assignee: MGI TECH CO., LTD.Inventors: Chen Li, Cheng Frank Zhong, Yu Liu, Yiwen Ouyang
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Patent number: 11001874Abstract: 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: GrantFiled: August 12, 2020Date of Patent: May 11, 2021Assignee: King Abdulaziz UniversityInventors: Aisha Elaimi, Ashraf Dallol, Adeel Chaudhary, Adel Abuzinadah, Muhammad Hussain Al-Qahtani
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Patent number: 11001837Abstract: The present invention provides a low-frequency mutation enrichment sequencing method for free target DNA in plasma, comprising plasma DNA extraction and library construction, general library TT COLD PCR amplification enrichment, probe enrichment capture, PCR and sequencing of captured products, and positive and negatice double-strand error-correction low-frequency information analysis.Type: GrantFiled: February 18, 2016Date of Patent: May 11, 2021Assignee: Geneplus—BeijingInventors: Xiaoxing Lv, Xin Yi, Meiru Zhao, Yanfang Guan, Tao Liu, Ling Yang
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Patent number: 10998105Abstract: Provided here are systems and methods for predicting risk of a substance use disorder and for providing decision support to healthcare professionals to implement a treatment regimen recommendation and mitigate any potential risk of a substance use disorder.Type: GrantFiled: August 27, 2020Date of Patent: May 4, 2021Assignee: Prescient Medicine Holdings, Inc.Inventor: Keri Donaldson
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Patent number: 10995304Abstract: The present invention relates to novel protease variants exhibiting improved stability and or improved wash performance in liquid detergent. The variants of the invention are 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: GrantFiled: December 14, 2015Date of Patent: May 4, 2021Assignee: NOVOZYMES A/SInventors: Miguel Duarte Guilherme Pereira Toscano, Esben Peter Friis, Rolf Thomas Lenhard, Signe Eskildsen Larsen, Astrid Munch, Bena-Marie Lue, Mikael Bauer
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Patent number: 10982265Abstract: 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: GrantFiled: April 20, 2020Date of Patent: April 20, 2021Assignee: GUARDANT HEALTH, INC.Inventors: AmirAli Talasaz, Stefanie Ann Ward Mortimer
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Patent number: 10983968Abstract: A method for the economic assessment of residual oil zones (“ROZ”), support for the engineering of the design of CO2 enhanced oil recovery (“EOR”) systems associated with production of petroleum from ROZ, support of EOR operations, and subsequent management and monitoring of CO2 sequestered in ROZ is disclosed. This efficient identification and assessment of ROZs significantly increases the geographic footprint and target locations into which CO2 can be injected and ultimately utilized and permanently sequestered in a commercial fashion generating value to partially offset the parasitic costs associated with the capture of anthropogenic CO2. Microbial self limitation (MSL) conditions of an ROZ are exploited for the assessment and management purposes of the ROZ.Type: GrantFiled: October 28, 2019Date of Patent: April 20, 2021Assignee: ARCADIS Corporate Services, Inc.Inventor: David B. Vance
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Patent number: 10984890Abstract: Systems, methods, and devices for generating synthetic genomic datasets and validating bioinformatic pipelines for genomic analysis are disclosed. In preferred embodiments, synthetic maternal and paternal datasets with known variants are used with matched normal synthetic datasets to validate various bioinformatic pipelines. Bioinformatic pipelines are evaluated using the synthetic datasets to assess design changes and improvements. Accuracy, PPV, specificity, sensitivity, reproducibility, and limit of detection of the pipelines in calling variants in synthetic datasets is reported.Type: GrantFiled: June 30, 2017Date of Patent: April 20, 2021Assignee: NantOmics, LLCInventors: Charles Joseph Vaske, Rahul Parulkar, John Zachary Sanborn, Stephen Benz, Mark Johnson
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Patent number: 10978175Abstract: The invention relates to a method for identifying one or more polymorphisms in nucleic acid samples, comprising: (a) performing a reproducible complexity reduction on a plurality of nucleic acid samples to provide a plurality of libraries of the nucleic acid samples comprising amplified fragments, wherein the reproducible complexity reduction comprises amplifying fragments of the nucleic acid samples using one or more primers to obtain the amplified fragments, and wherein the amplified fragments in each library comprise a unique identifier sequence to indicate origin of each library obtained by the reproducible complexity reduction; (b) combining the plurality of libraries to obtain a combined library and sequencing at least a portion of the combined library to obtain sequences; (c) aligning the sequences to obtain an alignment; and (d) identifying one or more polymorphisms in the plurality of nucleic acid samples.Type: GrantFiled: July 19, 2019Date of Patent: April 13, 2021Assignee: KEYGENE N.V.Inventors: Michael Josephus Theresia Van Eijk, Henricus Johannes Adam Van Der Poel
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Patent number: 10968536Abstract: Methods, compositions and kits are provided herein for insertional modification of nucleic acids by, for example transposase-mediated covalent insertion of insertion sequence into a sample nucleic acid molecule. Using sequence of the insertion to direct amplification of adjacent nucleic acid sequence, and using bar codes to map amplified sequence to partitions, one can map sample nucleic acid sequence to single molecules of the nucleic acid sample that are derived directly from the sample nucleic acid molecule.Type: GrantFiled: February 25, 2016Date of Patent: April 6, 2021Assignees: JUMPCODE GENOMICS, INC., THE SCRIPPS RESEARCH INSTITUTEInventors: Keith Brown, Daniel R. Salomon, Steven Head, Azeem Siddique, Phillip Ordoukhanian
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Patent number: 10971765Abstract: A system that includes an energy device having an active region configured to generate or consume electrical energy provided by an electrical current is discussed. A current limiter is disposed between the energy device and a current collector layer. The current limiter controls the current flow between the energy device and the current collector layer. A plurality of electrochemical transistors (ECTs) are arranged in an array such that each ECT in the array provides localized current control for the energy device. Each ECT includes a gate electrode, a drain electrode, a source electrode, and a channel disposed between the drain and the source electrodes. An electrolyte electrically couples the gate electrode to the channel such that an electrical signal at the gate electrode controls electrical conductivity of the channel. The current collector layer is a shared drain or source electrode for the ECTs.Type: GrantFiled: October 5, 2018Date of Patent: April 6, 2021Assignee: Palo Alto Research Center IncorporatedInventors: Sean E. Doris, Warren B. Jackson, Adrien Pierre
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Patent number: 10961570Abstract: A high-throughput and rapid nucleic acids detection method based on capillary microarrays comprises the steps that firstly, microarray containing a number of hydrophilic and vertical micro-channels is fabricated by capillary assembling, casting and machining, and the outer surface of the capillary array is coated with super-hydrophobic Ultra-Ever Dry paint; secondly, different primer sets are individually loaded into the micro-channels and air-dried to adhere them on the inner surface, and then the microarray is anchored into a reaction tube; thirdly, the reaction mixture is introduced into every microchannel at once through capillary force by a special designed sample-loading adaptor, and then the amplification reaction is performed in the temperature control device; and finally, the fluorescence can either be measured continually during the reaction for real-time detection or be recorded once in the end for endpoint detection. Moreover, the products can also be recovered for other use later.Type: GrantFiled: April 2, 2016Date of Patent: March 30, 2021Assignee: SHANGHAI JIAO TONG UNIVERSITYInventors: Shengce Tao, Litao Yang, Ning Shao, Jiaying Hu, Jianwei Chen, Dabing Zhang
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Patent number: 10961568Abstract: The invention generally relates to sequencing library preparation methods. In certain embodiments, two or more template nucleic acids are joined together by a linking molecule, such as a PEG derivative. Identical copies of a nucleic acid fragment or both strands of a duplex fragment may be linked together. The linked nucleic acids are amplified, creating linked amplicons. Emulsion PCR with linked primers creates linked template nucleic acids for seeding sequencing clusters and errors can be readily identified by their presence on only one of the linked fragments.Type: GrantFiled: March 28, 2017Date of Patent: March 30, 2021Assignee: Boreal Genomics, Inc.Inventors: Joel Pel, Andrea Marziali
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Patent number: 10961576Abstract: The disclosure provides detection apparatus having one or more nanopores, methods for making apparatus having one or more nanopore and methods for using apparatus having one or more nanopores. Uses include, but are not limited to detection and sequencing of nucleic acids.Type: GrantFiled: December 9, 2019Date of Patent: March 30, 2021Assignee: Illumina, Inc.Inventors: Boyan Boyanov, Jeffrey G Mandell, Kevin L Gunderson, Jingwei Bai, Liangliang Qiang, Bradley Baas
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Patent number: 10954509Abstract: Described herein is a method for isolating microbial DNA from a sample that comprises host DNA and microbial DNA. In some embodiments, the method may comprise: obtaining a tagged DNA sample, wherein the tagged DNA sample contains host DNA and microbial DNA, both comprising an appended universal adaptor; b) hybridizing the extracted DNA, in solution, with affinity-tagged RNA probes generated by in vitro transcribing, in the presence of an affinity-tagged ribonucleotide, a library of fragmented host DNA that has been ligated to an RNA promoter adaptor; c) binding the product of step b) with a capture agent that is tethered to a substrate, in the presence of RNA oligonucleotides that are complementary to or have the same sequence as one or more strands of the universal adaptor, thereby capturing the host DNA on the substrate; and d) collecting the unbound DNA, wherein the unbound DNA comprises the microbial DNA.Type: GrantFiled: May 1, 2017Date of Patent: March 23, 2021Assignee: The Board of Trustees of the Leland Stanford Junior UniversityInventors: Carlos D. Bustamante, Meredith L. Carpenter
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Patent number: 10927405Abstract: Described herein are methods, compositions and kits for identifying modifications that could lead to false positive detections in nucleic acid sequencing. In some embodiments, the methods, compositions and kits provided herein are useful for reducing potential of false positive detection of variants caused by errors during sample preparation or sequencing.Type: GrantFiled: January 11, 2019Date of Patent: February 23, 2021Assignee: NUGEN TECHNOLOGIES, INC.Inventors: Douglas A. Amorese, Stephanie C. Huelga, Bin Li
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Patent number: 10927394Abstract: The invention relates to new methods for synthesising polynucleotide molecules according to a predefined nucleotide sequence. The invention also relates to methods for the assembly of synthetic polynucleotides following synthesis, as well as systems and kits for performing the synthesis and/or assembly methods.Type: GrantFiled: January 19, 2018Date of Patent: February 23, 2021Assignee: Oxford Nanopore Technologies LimitedInventors: John Milton, Sobia Nayyar, Jan Riedl, Ryosuke Ogaki
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Patent number: 10920271Abstract: The present invention relates to a method of using nanopores to obtain sequence information of sample DNAs in ss test DNAs. The method comprises using speed bumps to stall the ss test DNAs in the nanopores at random positions of the ss test DNAs to obtain sequence information of each and every nucleotides of the sample DNAs, and to construct the whole sequences of the sample DNAs. The present invention also relates to identification and/or isolation of test DNAs having desired sequence(s) using nanopore detectors facilitated by speed bump.Type: GrantFiled: April 17, 2019Date of Patent: February 16, 2021Inventors: Randall W. Davis, Roger J. A. Chen
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Patent number: 10920268Abstract: The present disclosure provides improved methods for isolating asymmetrically-primed and/or asymmetrically-tagged nucleic acid complexes that find use in downstream analytical analyses, including sequence analysis. Compositions comprising such complexes and kits and systems for generating such complexes are also provided.Type: GrantFiled: July 16, 2018Date of Patent: February 16, 2021Assignee: Pacific Biosciences of California, Inc.Inventors: Lei Sun, Sassan Sheikholeslami, Natasha Popovich, David Christopher Scherer
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Patent number: 10920272Abstract: The invention relates to a high-throughput method for characterizing the genome-wide activity of editing nucleases in vitro.Type: GrantFiled: November 26, 2019Date of Patent: February 16, 2021Assignee: St. Jude Children's Research Hospital, Inc.Inventors: Shengdar Q. Tsai, Cicera R. Lazzarotto
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Patent number: 10900974Abstract: A method for identifying interactions of DNA, RNA, and/or protein molecules in a cell includes distributing a cell lysate or fraction thereof into a plurality of lysate suspensions, adding a unique nucleotide tag to each lysate suspension to tag each DNA, RNA, and/or protein, pooling the tagged suspensions, and repeating the tagging, pooling, and sorting (distributing) as desired to decrease the probability that non-interacting molecules will receive all of the same nucleotide tags.Type: GrantFiled: March 22, 2017Date of Patent: January 26, 2021Assignee: California Institute of TechnologyInventors: Sofia A. Quinodoz, Mitchell Guttman
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Patent number: 10883939Abstract: 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: GrantFiled: June 15, 2019Date of Patent: January 5, 2021Assignee: IMEC VZWInventors: Pol Van Dorpe, Niels Verellen
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Patent number: 10870880Abstract: 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: GrantFiled: May 8, 2020Date of Patent: December 22, 2020Assignee: GUARDANT HEALTH, INC.Inventors: AmirAli Talasaz, Stefanie Ann Ward Mortimer
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Patent number: 10853244Abstract: 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: GrantFiled: May 25, 2017Date of Patent: December 1, 2020Assignee: SANDISK TECHNOLOGIES LLCInventors: Christopher Petti, Srikanth Ranganathan
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Patent number: 10851417Abstract: 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: GrantFiled: October 14, 2015Date of Patent: December 1, 2020Assignee: UNIVERSITY COLLEGE CARDIFF CONSULTANTS LIMITEDInventors: Duncan Baird, Kevin Norris
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Patent number: 10844428Abstract: 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: GrantFiled: April 15, 2016Date of Patent: November 24, 2020Assignee: Illumina, Inc.Inventors: Sante Gnerre, Byoungsok Jung, Emrah Kostem, Alex Aravanis, Alex So, Xuyu Cai, Zhihong Zhang, Frank J. Steemers
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Patent number: 10837055Abstract: 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: GrantFiled: August 9, 2018Date of Patent: November 17, 2020Assignee: Illumina, Inc.Inventors: Anupama Srinivasan, Darya I. Chudova, Richard P. Rava
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Patent number: 10837063Abstract: 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: GrantFiled: November 30, 2017Date of Patent: November 17, 2020Assignee: GUARDANT HEALTH, INC.Inventor: AmirAli Talasaz
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Patent number: 10816504Abstract: 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: GrantFiled: October 24, 2019Date of Patent: October 27, 2020Assignee: Life Technologies CorporationInventors: Jonathan M. Rothberg, Keith G. Fife, James Bustillo, Jordan Owens
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Patent number: 10787703Abstract: 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: GrantFiled: January 9, 2017Date of Patent: September 29, 2020Assignee: Georgia Tech Research CorporationInventors: Francesca Storici, Jay Hesselberth, Kyung Duk Koh