Biochemical Method (e.g., Using An Enzyme Or Whole Viable Micro-organism, Etc.) Patents (Class 506/26)
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Patent number: 12281354Abstract: The present disclosure provides a method for monitoring residual disease in a subject. Generally, the method comprises determining a frequency of cancer mutations from a first sample obtained from a tumor biopsy from the subject; determining a frequency of the cancer mutations discovered in the first sample from a second sample comprising cell-free deoxyribonucleic acid (cfDNA) molecules that is obtained from the subject after the subject has undergone a course of treatment for cancer; and determining a presence or absence of cancer in the subject based on an analysis of the frequency of the cancer mutations from sequence data from the second sample, wherein adapters are ligated to at least 20% of the cfDNA molecules using more than a 10× molar excess of adapters relative to the cfDNA molecules in the population of cfDNA molecules.Type: GrantFiled: May 29, 2024Date of Patent: April 22, 2025Assignee: Guardant Health, Inc.Inventors: AmirAli Talasaz, Stefanie Ann Ward Mortimer
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Patent number: 12270074Abstract: Methods and compositions for analyzing a library comprising a plurality of amplicons comprising identifier sequences are provided, for example, a library of amplicons in a cell or tissue sample attached to a solid support. For example, amplicons are sequenced using a polymerase to incorporate a plurality of cognate nucleotides into the sequencing primer or an extension product thereof to generate a plurality of extension products.Type: GrantFiled: February 27, 2024Date of Patent: April 8, 2025Assignee: 10X GENOMICS, INC.Inventors: Patrick J. Marks, Michael Schnall-Levin
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Patent number: 12252734Abstract: Methods of uniquely labeling or barcoding molecules within a cell, a plurality of cells, and/or a tissue are provided. Kits for uniquely labeling or barcoding molecules within a cell, a plurality of cells, and/or a tissue are also provided. The molecules to be labeled may include, but are not limited to, RNAs, cDNAs, DNAs, proteins, peptides, and/or antigens.Type: GrantFiled: August 24, 2023Date of Patent: March 18, 2025Assignee: University of WashingtonInventors: Georg Seelig, Richard Muscat, Alexander B. Rosenberg
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Patent number: 12241059Abstract: The disclosure provides methods for creating long oligonucleotide reagents that include barcodes and other element for sequencing library preparation, where the oligonucleotides are created by multiple tiers of ligation of shorter oligos. The disclosed methods work to extend short oligos that are attached to particles, thereby allowing one to create particles that carry large number of long sample preparation oligonucleotides without being required to synthesize those full-length molecules with a polymerase.Type: GrantFiled: July 15, 2021Date of Patent: March 4, 2025Assignee: Illumina, Inc.Inventors: Robert Meltzer, Kristina Fontanez, Yi Xue
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Patent number: 12227741Abstract: The invention provides methods of performing multi-parameter analysis of single cells. Specifically, the present invention is based, in part, on leveraging a separation of reaction volume scales to conduct high-throughput single cell multi-parameter measurements and library preparation on the same single cell using double emulsion micro-droplets and sorting using flow cytometry.Type: GrantFiled: July 1, 2019Date of Patent: February 18, 2025Assignees: CZ Biohub SF, LLC, The Board of Trustees of the Leland Stanford Junior UniversityInventors: Polly Fordyce, Kara Brower, Sandy Klemm, William Greenleaf
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Patent number: 12215310Abstract: Described herein are probiotics, more particularly [to] the probiotic yeast Saccharomyces boulardii. Even more particularly described herein are enhanced probiotic potency S. boulardii. Also described here are mutant alleles useful to develop yeast strains with enhanced production of acetic acid. In addition, described here is the use of such yeast strains for the production of dietary supplements or pharmaceutical compositions to improve gastrointestinal comfort.Type: GrantFiled: September 14, 2018Date of Patent: February 4, 2025Assignees: VIB VZW, Katholieke Universiteit LeuvenInventors: Johan Thevelein, Benjamin Offei, Maria Remedios Foulquié Moreno, Paul Vandecruys
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Patent number: 12186747Abstract: Single use cartridges for testing biological samples are provided that include multiple processing channels. A single use cartridge includes an aliquot staging well, a first amplification well, a second amplification well, an actuation port, and a fluid channel control valve assembly. The fluid channel control valve assembly is reconfigurable between a first fluid channel configuration and a second fluid channel configuration.Type: GrantFiled: December 9, 2021Date of Patent: January 7, 2025Assignee: Amazon Technologies, Inc.Inventors: William Brian Greger, Aida Martin Galan, Manuela Alanis, Emanuel Elizalde, Luciano Braggio
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Patent number: 12139751Abstract: The present disclosure relates in some aspects to methods and compositions for analysis of a target nucleic acid, such as in situ detection of a region of interest in a polynucleotide in a tissue sample. In some embodiments, provided herein are templated ligation probes (e.g., RNA-templated ligation probes) and selector probes for generation of a circularized ligated probe comprising an insertion sequence of a selector probe, wherein the circularized ligated probe is amplified in a rolling circle amplification reaction to generate a product that is detected in the sample.Type: GrantFiled: July 29, 2022Date of Patent: November 12, 2024Assignee: 10X GENOMICS, INC.Inventors: Jorge Iván Hernández Neuta, Malte Kühnemund, Jessica Östlin, Xiaoyan Qian, Toon Verheyen
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Patent number: 12110560Abstract: The present disclosure provides a method for monitoring residual disease in a subject. Generally, the method comprises determining a frequency of cancer mutations from a first sample obtained from a tumor biopsy from the subject; determining a frequency of the cancer mutations discovered in the first sample from a second sample comprising cell-free deoxyribonucleic acid (cfDNA) molecules that is obtained from the subject after the subject has undergone a course of treatment for cancer; and determining a presence or absence of cancer in the subject based on an analysis of the frequency of the cancer mutations from sequence data from the second sample.Type: GrantFiled: March 4, 2024Date of Patent: October 8, 2024Assignee: Guardant Health, Inc.Inventor: AmirAli Talasaz
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Patent number: 12104200Abstract: The present disclosure provides methods and systems for processing nucleic acid molecules from one or more cells. A cell may be comprised in a cell bead. Processing may comprise uniquely identifying nucleic acid molecules. Nucleic acid molecules may be identified by barcoding. Barcoding may be combinatorial barcoding. Combinatorial barcoding may allow for generation of a large number of barcodes, thereby uniquely identifying nucleic acids from a large number of single cells. Combinatorial barcoding may be performed in successive operations. Successive operations may be performed in partitions.Type: GrantFiled: June 7, 2019Date of Patent: October 1, 2024Assignee: 10X GENOMICS, INCInventor: Michael Schnall-Levin
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Patent number: 12098396Abstract: Provided herein relates to DNA polymerase variants and kits including the same, where the DNA polymerase variant has an improved function and activity of performing template-independent nucleic acids synthesis using canonical nucleotides and non-canonical nucleotide analogues in a thermotolerant manner.Type: GrantFiled: September 29, 2022Date of Patent: September 24, 2024Inventor: Cheng-Yao Chen
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Patent number: 12091660Abstract: Compositions and methods are provided for detection of dynamic loci in a genome, where such loci may comprise structural variations as a result of DNA recombination; DNA duplication, insertions, deletions, transpositions, and epigenetic changes. The methods may utilize microfluidic platforms and functionalized polymer matrices to allow determination of mechanisms of cell-type-specific, programmed genomic heterogeneity. The method and compositions allow determination of mechanisms of cell-type-specific, programmed genomic heterogeneity.Type: GrantFiled: April 10, 2023Date of Patent: September 17, 2024Assignees: The Board of Trustees of the Leland Stanford Junior University, Board of Regents, The University of Texas SystemInventors: Massa Shoura, Andrew Z. Fire, Stephen Levene
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Patent number: 12087754Abstract: Provided is a method of fabricating a hybrid element, the method including forming a plurality of first elements on a first substrate, separating a plurality of second elements grown on a second substrate from the second substrate, a material of the second substrate being different from a material of the first substrate, and transferring the plurality of second elements, separated from the second substrate, onto the first substrate, wherein, in the transferring, the plurality of second elements are spaced apart from each other by a fluidic self-assembly method, and wherein each of the plurality of second elements includes a shuttle layer grown on the second substrate, an element layer grown on the shuttle layer, and an electrode layer on the element layer.Type: GrantFiled: February 8, 2022Date of Patent: September 10, 2024Assignee: SAMSUNG ELECTRONICS CO., LTD.Inventors: Kyungwook Hwang, Junsik Hwang, Dongho Kim, Hyunjoon Kim, Joonyong Park, Seogwoo Hong
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Patent number: 12077814Abstract: A method for low frequency somatic cell mutation identification and quantification, relating specifically to a method for transposon copy number and genome location identification. Specific sites of different transposon families are used, transposon insertion sequences are specifically enriched via library construction, high-throughput sequencing and bioinformatics analysis are used, and genome locations, copy numbers and types of transposons within samples are accurately identified. The method economically and accurately identifies copy numbers and genome locations of transposons.Type: GrantFiled: July 23, 2018Date of Patent: September 3, 2024Assignee: PEKING UNIVERSITYInventors: Liping Wei, Boxun Zhao, Yue Huang, Qixi Wu, Yongxin Ye, Xianing Zheng
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Patent number: 12071654Abstract: Provided herein are methods of normalizing nucleic acid libraries. The method uses nucleic acid probes with nucleic acid sequences that are complementary to one or more of these adaptor sequences are added to the nucleic acids libraries. The probes can hybridize to the adaptor sequences in the single stranded nucleic acid molecules derived from the libraries to form hybridization complexes. The probes are conjugated to a first binding member, which can interact with a second binding member that is conjugated to solid supports. The solid supports can then be collected and the single stranded nucleic acid molecules can be recovered in a volume of elution buffer to reach a desired concentration. As compared to standard methods, the methods are more efficient and cost-effective.Type: GrantFiled: April 1, 2020Date of Patent: August 27, 2024Assignee: SEQUENOM, INCInventors: Tricia Zwiefelhofer, Jason Nathanson
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Patent number: 12071656Abstract: Compositions, kits and methods are described that comprise one or more constructs, each construct comprising a ligand attached or conjugated to a polymer construct, e.g., an oligonucleotide sequence, by a linker, each ligand binding specifically to a single target located in or on the surface of a cell. The polymer construct comprises a) an Amplification Handle; b) a Barcode that specifically identifies a single ligand; c) an optional Unique Molecular Identifier that is positioned adjacent to the Barcode on its 5? or 3? end; and d) an Anchor for hybridizing to a complementary sequence, e.g., for generation of a double-stranded oligonucleotide. These compositions are used in methods, including high throughput methods, for detecting one or more targets or epitopes in a biological sample. These compositions are also used in a high throughput method for characterizing a cell by simultaneous detection of one or more epitopes located in or on the cell and its transcriptome.Type: GrantFiled: April 30, 2021Date of Patent: August 27, 2024Assignee: New York Genome Center, Inc.Inventors: Marlon Stoeckius, Peter Smibert, Brian Houck-Loomis
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Patent number: 12065697Abstract: Disclosed herein is a specific B-family DNA polymerase variants that exhibit an improved incorporation of nucleotide analogues for synthesizing polynucleotides and sequencing the associated nucleic acid template. More particularly, the DNA sequencing-by-synthesis method can be efficiently performed by said B-family DNA polymerase variants with a normal nucleic acid template and reversible dye-terminator nucleotides to precisely determine the sequence of associated nucleic acid template.Type: GrantFiled: June 28, 2022Date of Patent: August 20, 2024Inventor: Cheng-Yao Chen
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Patent number: 12054773Abstract: The present disclosure provides methods and systems for producing full-length sequencing information of transcriptomes from single cells or from the bulk. Random ligation and circularization of barcoded or non-barcoded complementary deoxyribonucleic molecules can be used to provide a circular template for amplification and subsequent sequencing.Type: GrantFiled: August 26, 2020Date of Patent: August 6, 2024Assignee: 10X GENOMICS, INC.Inventors: Vijay Kumar Sreenivasa Gopalan, Paul Ryvkin, Zachary Bent, Jessica Michele Terry, David Jaffe, Patrick Marks, Tarjei Sigurd Mikkelsen
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Patent number: 12057195Abstract: A method for prioritizing sequencing of nucleic acid molecules from two or more sources, comprising: (i) ligating one or more ends of each of a plurality of nucleic acid molecules to an adapter, wherein the adaptor is unique to each source and comprises a unique identifier nucleic acid sequence; (ii) pooling the nucleic acid molecules from each of the two or more sources; (iii) sequencing a plurality of nucleotides of an identifier nucleic acid sequence of an adapter; (iv) determining in real-time from which of the two or more sources the nucleic acid molecule being sequenced came; (v) determining, from a prioritization rule set and based on the determined source, a sequencing priority for the nucleic acid molecule; and (vi) allowing the sequencing process to proceed, or modifying the sequencing process, based on the determined sequencing priority.Type: GrantFiled: April 16, 2018Date of Patent: August 6, 2024Assignee: KONINKLIJKE PHILIPS N.V.Inventor: Brian David Gross
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Patent number: 12024566Abstract: An anti-SIRP? antibody that can be used as a tumor agent and an anti-tumor agent comprising the antibody as an active ingredient. An antibody that binds specifically to human SIRP? to inhibit binding of human SIRP? to CD47.Type: GrantFiled: July 9, 2019Date of Patent: July 2, 2024Assignees: NATIONAL UNIVERSITY CORPORATION KOBE UNIVERSITY, DAIICHI SANKYO COMPANY, LIMITEDInventors: Takashi Matozaki, Mayumi Sue, Kensuke Nakamura, Chigusa Yoshimura
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Patent number: 12018302Abstract: Glycerol-free enzyme formulations are described. In some embodiments, a glycerol-free enzyme formulation is stabilized by high salt concentration. The glycerol free enzyme formulation may comprise a reverse transcriptase enzyme.Type: GrantFiled: February 23, 2022Date of Patent: June 25, 2024Assignee: Thermo Fisher Scientific Baltics, UABInventors: Juozas Siurkus, Darius Kavaliauskas, Daumantas Matulis, Lina Baranauskiene
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Patent number: 12019015Abstract: The present invention discloses devices for independently-controllable, multi-chamber cuvettes for rapid, concurrent spectral analyses, embodied applications of same, and methods therein. Devices include: a multi-chamber cuvette having contiguous analysis chambers forming a single continuous inner cavity configured to contain a liquid in an inner-cavity volume, wherein each chamber is configured to serve as a measurement zone for the liquid in the inner cavity when the volume is filled with the liquid by regulation of hydrostatic pressure in the inner cavity in order to prevent fluid flow from a given chamber to another chamber, and wherein each volume in each zone is designated a zone volume; thermal-contact windows positioned in a chamber to enable independent temperature control of a zone volume in a zone; and cuvette optical windows, positioned in each chamber to provide independent optical access to each zone, adapted to enable analysis of each zone volume in each zone.Type: GrantFiled: September 23, 2023Date of Patent: June 25, 2024Inventor: Daniel N. J. Halbert
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Patent number: 12006547Abstract: A process for analysing chromosome regions and interactions relating to ALS and Huntington's disease.Type: GrantFiled: October 1, 2018Date of Patent: June 11, 2024Assignee: Oxford BioDynamics PLCInventors: Alexandre Akoulitchev, Aroul Selvam Ramadass, Ewan Hunter, Matthew Salter
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Patent number: 11999994Abstract: Described herein are compositions and methods for the production and quantification of barcoded or unique molecular identifier (UMI)-labeled substrates. In one aspect, the substrate is a bead comprising a template oligonucleotide that is elongated by successive extension reactions to provide a bead with an oligonucleotide comprising a plurality of barcodes and conserved anchor regions. Methods are also described for quantifying the amount of template oligonucleotide loaded onto the substrate and the products of the extension reaction after each round and after the final extension.Type: GrantFiled: January 13, 2022Date of Patent: June 4, 2024Assignee: INTEGRATED DNA TECHNOLOGIES, INC.Inventors: Joseph Dobosy, Scott D. Rose, Jeffrey A. Manthey, Shawn D. Allen, Steven A. Henck, Mark Behlke
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Patent number: 11986823Abstract: A microfluidic device includes an array unit and a nanostructure connected to the array unit, wherein the array unit comprises array cells with substances for a polymerase chain reaction. The array cells include nucleotides with stop properties according to the Sanger sequencing method and primers for an asymmetric polymerase chain reaction. The nanostructure is configured to determine lengths of nucleotide strands formed by the polymerase chain reaction.Type: GrantFiled: May 2, 2019Date of Patent: May 21, 2024Assignee: Robert Bosch GmbHInventor: Franz Laermer
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Patent number: 11981966Abstract: The present technology relates to methods for determining whether a patient diagnosed with breast cancer, colorectal cancer, melanoma or lung cancer will benefit from or is predicted to be responsive to treatment with an individual therapeutic agent or a specific combination of therapeutic agents. These methods are based on screening a patient's solid tumors and detecting alterations in target nucleic acid sequences corresponding to a specific set of cancer-related genes. Kits for use in practicing the methods are also provided.Type: GrantFiled: May 8, 2020Date of Patent: May 14, 2024Assignee: Quest Diagnostics Investments LLCInventors: Heather Sanders, Kevin Qu, James Prentice, Frederic Waldman
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Patent number: 11970736Abstract: The present disclosure relates to a next generation DNA sequencing method and use for accurate and massively parallel quantification of one or more nucleic acid targets, for example in large volumes of unpurified sample material. More particularly, the disclosed embodiments is related to a method and a kit comprising probes for detecting and quantifying genetic targets in complex samples. The disclosed embodiments includes two target-specific nucleic acid probes per genetic target, a barcode loop oligo and a bridge oligo or bridge oligo complex.Type: GrantFiled: August 31, 2022Date of Patent: April 30, 2024Assignee: Genomill Health OyInventors: Juha-Pekka Pursiheimo, Tatu Hirvonen, Anttoni Korkiakoski, Manu Tamminen
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Patent number: 11952626Abstract: Provided herein are systems and methods for processing biomolecules (e.g., nucleic acid molecules, proteins) from a sample. A method for processing biomolecules may comprise hybridizing a probe molecule to a target region of a nucleic acid molecule (e.g., a ribonucleic acid (RNA) molecule) and barcoding the probe-nucleic acid molecule complex or derivatives thereof. Such a method can comprise performing a nucleic acid reaction, e.g., extension, denaturation, and amplification. A method for processing a sample may comprise hybridizing probes to (i) target regions of a nucleic acid molecule (e.g., RNA molecule) and (ii) a reporter oligonucleotide of a feature binding group, and barcoding the probe-associated molecules. One or more processes of the methods described herein may be performed within a partition, such as a droplet or well.Type: GrantFiled: August 22, 2023Date of Patent: April 9, 2024Assignee: 10X GENOMICS, INC.Inventors: Katherine Pfeiffer, Andrew Scott Kohlway, Andrew John Hill, Paul Eugene Lund
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Patent number: 11946101Abstract: The invention provides improved methods, compositions, and kits for detecting ploidy of chromosome regions, e.g. for detecting cancer or a chromosomal abnormality in a gestating fetus. The methods can utilize a set of more than 200 SNPs that are found within haploblocks and can include analyzing a series of target chromosomal regions related to cancer or a chromosomal abnormality in a gestating fetus. Finally the method may use knowledge about chromosome crossover locations or a best fit algorithm for the analysis. The compositions may comprise more than 200 primers located within haplotype blocks known to show CNV.Type: GrantFiled: June 21, 2022Date of Patent: April 2, 2024Assignee: Natera, Inc.Inventors: Huseyin Eser Kirkizlar, Raheleh Salari, Styrmir Sigurjonsson, Bernhard Zimmermann, Allison Ryan, Naresh Vankayalapati
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Patent number: 11920123Abstract: A cell analyzing device includes a control circuit. The control circuit acquires data of an observation image. The control circuit specifies a colony of a cultured cell in the observation image. The control circuit calculates a ratio at which the cultured cell occupies a predetermined range included in the observation image as an occupancy rate. The control circuit calculates a size of the colony. The control circuit determines a state of the cultured cell based on the occupancy rate and the size of the colony.Type: GrantFiled: July 15, 2020Date of Patent: March 5, 2024Assignee: Evident CorporationInventors: Yasunobu Iga, Taiji Mine, Yoshinobu Akahori
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Patent number: 11905553Abstract: Provided herein are compositions and methods for accurate and scalable Primary Template-Directed Amplification (PTA) nucleic acid amplification and sequencing methods, and their applications for research, diagnostics, and treatment.Type: GrantFiled: January 28, 2019Date of Patent: February 20, 2024Assignee: ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.Inventors: Charles Gawad, John Easton, Veronica Gonzalez-Pena
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Patent number: 11898205Abstract: This disclosure relates to methods for increasing capture efficiency of a spatial array using rolling circle amplification of a padlock probe that hybridizes to a capture probe. Also provided are methods for using such spatial arrays to detect a biological analyte in a biological sample.Type: GrantFiled: February 2, 2021Date of Patent: February 13, 2024Assignee: 10x Genomics, Inc.Inventor: Felice Alessio Bava
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Patent number: 11900595Abstract: Disclosed herein, inter alia, are methods and systems of image analysis useful for identifying and/or quantifying features in patterns.Type: GrantFiled: May 5, 2021Date of Patent: February 13, 2024Assignee: Singular Genomics Systems, Inc.Inventors: Fedor Trintchouk, Eli N. Glezer
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Patent number: 11859249Abstract: There is disclosed a method of generating a massively parallel sequencing library comprising the steps of: a) providing a primary WGA DNA library (pWGAlib), including fragments comprising a WGA library universal sequence adapter; b) performing a single PCR cycle on the pWGAlib using a first primer (1PR) comprising from 5? to 3? a first sequencing adapter (1PR5SA) and a first primer 3? section (1PR3S) hybridizing to the reverse complementary of the WGA library universal sequence adapter; c) performing a single PCR cycle on the on the product of step b) using a second primer (2PR) comprising from 5? to 3? a second sequencing adapter (2PR5SA) different from the 1PR5SA, and a second primer 3? section (2PR3S) hybridizing to the WGA library universal sequence adapter reverse complementary; d) amplifying by PCR the product of step c) using a third primer comprising the 1PR5SA and a fourth primer comprising 2PR5SA.Type: GrantFiled: July 20, 2018Date of Patent: January 2, 2024Assignee: Menarini Silicon Biosystems S.p.A.Inventors: Valentina Del Monaco, Nicolò Manaresi, Genny Buson, Paola Tononi
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Patent number: 11845084Abstract: Provided are methods and related devices for preparing a cell and tissue culture, including a hanging drop culture. Microwells are specially loaded with cell mixtures using a removable reservoir and forcing cells into the underlying microwells. The removable reservoir is removed and the cells partitioned into the individual microwells and covered by an immiscible layer of fluid. The microwells and immiscible layer is inverted and the cells in the microwells cultured. The microwells may have shape-controlling elements to control the three-dimensional shape of the culture.Type: GrantFiled: May 4, 2021Date of Patent: December 19, 2023Assignees: The Board of Trustees of the University of Illinois, Mayo Foundation for Medical Education and ResearchInventors: Anurup Ganguli, Rashid Bashir, Panagiotis Z. Anastasiadis, George Vasmatzis
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Patent number: 11845984Abstract: A method for sequencing a biological molecule, such as a nucleic acid molecule, and a method for detecting and/or correcting sequencing error(s) in the sequencing results are provided. Kits and systems based on the above methods are also provided.Type: GrantFiled: July 13, 2020Date of Patent: December 19, 2023Assignee: CYGNUS BIOSCIENCES (BEIJING) CO., LTD.Inventors: Yanyi Huang, Zitian Chen, Wenxiong Zhou, Haifeng Duan, Li Kang, Shuo Qiao
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Patent number: 11795496Abstract: A method of determining responsiveness to therapy for rheumatoid arthritis.Type: GrantFiled: June 24, 2016Date of Patent: October 24, 2023Assignee: Oxford Biodynamics PLCInventors: Aroul Ramadass, Ewan Hunter, Alexandre Akoulitchev
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Patent number: 11783917Abstract: The technology disclosed processes input data through a neural network and produces an alternative representation of the input data. The input data includes per-cycle image data for each of one or more sequencing cycles of a sequencing run. The per-cycle image data depicts intensity emissions of one or more analytes and their surrounding background captured at a respective sequencing cycle. The technology disclosed processes the alternative representation through an output layer and producing an output and base calls one or more of the analytes at one or more of the sequencing cycles based on the output.Type: GrantFiled: March 20, 2020Date of Patent: October 10, 2023Inventors: Kishore Jaganathan, John Randall Gobbel, Amirali Kia
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Patent number: 11759761Abstract: Methods of generating a nucleic acid signature for identifying particles associated in a partition are provided. In one aspect, the method comprises: partitioning a sample into a plurality of partitions comprising a particle comprising a solid support surface, the solid support surface having a plurality of oligonucleotide primers conjugated thereon, wherein the oligonucleotide primers comprise a barcode sequence, and wherein the partitions have 0, 1, or more than 1 particles per partition; providing in a partition a substrate comprising a barcode sequence or repeating clonal barcode sequences; and in the partition, associating a first particle conjugated to oligonucleotide primers comprising a first barcode sequence and a second particle conjugated to oligonucleotide primers comprising a second barcode sequence to a barcode sequence from the substrate, thereby generating a nucleic acid signature for the particles in the partition.Type: GrantFiled: July 20, 2021Date of Patent: September 19, 2023Assignee: Bio-Rad Laboratories, Inc.Inventors: Ronald Lebofsky, Nicholas Heredia
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Patent number: 11739373Abstract: Provided herein, in some embodiments, are systems, methods, compositions, and kits for detecting and quantifying analytes using a primary analyte binding molecule conjugated to a nucleic acid template.Type: GrantFiled: February 5, 2019Date of Patent: August 29, 2023Assignee: G1 Sciences, LLCInventor: Sudha Haran
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Patent number: 11702649Abstract: The present invention relates to the analysis of complex single cell sequencing libraries. Disclosed are methods for enrichment of library members based on the presence of cell-of origin barcodes to identify and concentrate DNA that is relevant to interesting cells or components that would be expensive or difficult to study otherwise. Also, disclosed are methods of capturing cDNA library molecules by use of CRISPR systems, hybridization or PCR. The present invention allows for identifying the properties of rare cells in single cell RNA-seq data and accurately profile them through clustering approaches. Further information on transcript abundances from subpopulations of single cells can be analyzed at a lower sequencing effort. The methods also allow for linking TCR alpha and beta chains at the single cell level.Type: GrantFiled: October 23, 2018Date of Patent: July 18, 2023Assignees: The Broad Institute, Inc., Massachusetts Institute of TechnologyInventors: Paul Blainey, Navpreet Ranu, Todd Gierahn, J. Christopher Love
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Patent number: 11687791Abstract: According to some embodiments of the present disclosure, a device is disclosed. In embodiments, the device stores a computer program comprised of a set of encoded executable instructions; a genomic differentiation object and genomic regulation instructions (GRI) that were used to encode the set of encoded executable instructions. The device further includes a processing system comprising a VDAX and a set of processing cores. The VDAX is configured to: receive encoded instructions to be executed from the set of encoded executable instructions and decode the encoded instructions into decoded executable instruction based on a modified genomic differentiation object and sequences extracted from metadata associated with the encoded instructions. In these embodiments, the modified genomic differentiation object is modified from the genomic differentiation object using the GRI.Type: GrantFiled: February 10, 2022Date of Patent: June 27, 2023Assignee: Quantum Digital Solutions CorporationInventors: William C. Johnson, Karen Ispiryan, Gurgen Khachatryan
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Patent number: 11655499Abstract: Provided herein are methods and systems for establishing the presence of a sequence element in nucleic acid molecules. The sequence element may comprise a fused gene, a reporter gene, or another useful sequence for cell and tissue engineering, such as those used for labeling cells, identifying successfully transfected or transduced cells, etc. A method provided herein may additionally allow for barcoding of nucleic acid molecules and analysis of libraries of barcoded nucleic acid molecules.Type: GrantFiled: February 25, 2020Date of Patent: May 23, 2023Assignee: 10X GENOMICS, INC.Inventor: Katherine Pfeiffer
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Patent number: 11643682Abstract: Provided herein are compositions and methods for accurate and scalable Primary Template-Directed Amplification (PTA) nucleic acid amplification and sequencing methods, and their applications for research, diagnostics, and treatment.Type: GrantFiled: August 31, 2022Date of Patent: May 9, 2023Assignee: ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.Inventors: Charles Gawad, John Easton, Veronica Gonzalez-Pena
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Patent number: 11634766Abstract: Provided herein include methods and compositions for analyzing nucleic acid in individual cells. In some embodiments, the methods herein include generating, within individual cells, fragmented cellular genomic DNA and cDNA copies of cellular RNA molecules, barcoding the fragmented genomic DNA and the cDNA within each cell such that the genomic DNA and the cDNA from the same cell receive the same unique barcode sequence, isolating the barcoded genomic DNA and cDNA, and characterizing one or more features of the individual cells based, at least in part, on sequencing of the isolated barcoded genomic DNA and the cDNA.Type: GrantFiled: February 4, 2020Date of Patent: April 25, 2023Assignees: The Broad Institute, Inc., Massachusetts Institute of Technology, President and Fellows of Harvard CollegeInventors: Jason Daniel Buenrostro, Sai Ma, Aviv Regev
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Patent number: 11635427Abstract: The invention generally relates to performing sandwich assays in droplets. In certain embodiments, the invention provides methods for detecting a target analyte that involve forming a compartmentalized portion of fluid including a portion of a sample suspected of containing a target analyte and a sample identifier, a first binding agent having a target identifier, and a second binding agent specific to the target analyte under conditions that produce a complex of the first and second binding agents with the target analyte, separating the complexes, and detecting the complexes, thereby detecting the target analyte.Type: GrantFiled: July 24, 2020Date of Patent: April 25, 2023Assignee: Bio-Rad Laboratories, Inc.Inventors: Michael L. Samuels, Darren Roy Link
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Patent number: 11623219Abstract: Air-matrix digital microfluidics (DMF) apparatuses and methods of using them to prevent or limit evaporation and surface fouling of the DMF apparatus. In particular, described herein are air-matrix DMF apparatuses and methods of using them including thermally controllable regions with a wax material that may be used to selectively encapsulate a reaction droplet in the air gap of the apparatus; additional aqueous droplets may be combined with the encapsulated droplet even after separating from the wax, despite residual wax coating, by merging with an aqueous droplet having a coating of a secondary material (e.g., an oil or other hydrophobic material) that may remove the wax from the droplet and/or allow combining of the droplets.Type: GrantFiled: April 4, 2018Date of Patent: April 11, 2023Assignee: mirOculus Inc.Inventors: Mais J. Jebrail, Alexandra Judy Cho, Foteini Christodoulou
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Patent number: 11624064Abstract: Provided herein are methods of enriching mutated cell free nucleic acids for detection and diagnosis of cancer. Also provided are methods using a CRISPR-Cas system to target and deplete unwanted more abundant cell free nucleic acid sequences thereby enriching for less abundant sequences.Type: GrantFiled: June 13, 2017Date of Patent: April 11, 2023Assignee: GRAIL, LLCInventors: Gordon Cann, Alex Aravanis, Arash Jamshidi, Rick Klausner, Richard Rava
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Patent number: 11618808Abstract: Some embodiments described herein relate to a substrate with a surface comprising a silane or a silane derivative covalently attached to optionally substituted cycloalkene or optionally substituted heterocycloalkene for direct conjugation with a functionalized molecule of interest, such as a polymer, a hydrogel, an amino acid, a nucleoside, a nucleotide, a peptide, a polynucleotide, or a protein. In some embodiments, the silane or silane derivative contains optionally substituted norbornene or norbornene derivatives. Method for preparing a functionalized surface and the use in DNA sequencing and other diagnostic applications are also disclosed.Type: GrantFiled: March 5, 2021Date of Patent: April 4, 2023Assignee: Illumina, Inc.Inventors: Lorenzo Berti, Andrew A. Brown, Wayne N. George
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Patent number: 11608494Abstract: This invention relates to, in part, compositions of beta-lactamases and methods of using these enzymes in, for example, gastrointestinal tract (GI tract) disorders such as C. difficile infection (CDI).Type: GrantFiled: December 8, 2021Date of Patent: March 21, 2023Assignee: Theriva Biologics, Inc.Inventors: Michael Kaleko, Sheila Connelly