Abstract: The present disclosure provides biochips and methods for making biochips. A biochip can comprise a nanopore in a membrane (e.g., lipid bilayer) adjacent or in proximity to an electrode. Methods are described for forming the membrane and insert-ing the nanopore into the membrane. The biochips and methods can be used for nucleic acid (e.g., DNA) sequencing. The present disclosure also describes methods for detecting, sorting, and binning molecules (e.g., proteins) using biochips.
Abstract: Apparatus and methods for analyzing single molecule and performing nucleic acid sequencing. An apparatus can include an assay chip that includes multiple pixels with sample wells configured to receive a sample, which, when excited, emits emission energy; at least one element for directing the emission energy in a particular direction; and a light path along which the emission energy travels from the sample well toward a sensor. The apparatus also includes an instrument that interfaces with the assay chip. The instrument includes an excitation light source for exciting the sample in each sample well; a plurality of sensors corresponding the sample wells. Each sensor may detect emission energy from a sample in a respective sample well. The instrument includes at least one optical element that directs the emission energy from each sample well towards a respective sensor of the plurality of sensors.
Type:
Grant
Filed:
November 19, 2019
Date of Patent:
March 29, 2022
Assignee:
Quantum-Si Incorporated
Inventors:
Jonathan M. Rothberg, Ali Kabiri, Jason W. Sickler, Brett J. Gyarfas, Jeremy Lackey, Gerard Schmid, Benjamin Cipriany, Jack Jewell, Lawrence C. West, Michael Ferrigno, Paul E. Glenn, Adam Ezra Cohen, Anthony Bellofiore
Abstract: The present disclosure provides methods and assay systems for use in spatially encoded biological assays, including assays to determine a spatial pattern of abundance, expression, and/or activity of one or more biological targets across multiple sites in a sample. In particular, the biological targets comprise proteins, and the methods and assay systems do not depend on imaging techniques for the spatial information of the targets. The present disclosure provides methods and assay systems capable of high levels of multiplexing where reagents are provided to a biological sample in order to address tag the sites to which reagents are delivered; instrumentation capable of controlled delivery of reagents; and a decoding scheme providing a readout that is digital in nature.
Abstract: The present disclosure relates to chemical compositions, kits, and apparatuses and methods for using these compositions, kits and apparatuses in various assays.
Type:
Grant
Filed:
September 4, 2019
Date of Patent:
March 22, 2022
Assignee:
NanoString Technologies, Inc.
Inventors:
Dwayne L. Dunaway, Elizabeth A. Manrao, Joseph M. Beechem, Rustem Khafizov, Sanghamithra Korukonda, Yi Deng, Dae Kim, Mark Gregory, Margaret Hoang
Abstract: Sub-millimeter scale three-dimensional (3D) structures are disclosed with customizable chemical properties and/or functionality. The 3D structures are referred to as drop-carrier particles. The drop-carrier particles allow the selective association of one solution (i.e., a dispersed phased) with an interior portion of each of the drop-carrier particles, while a second non-miscible solution (i.e., a continuous phase) associates with an exterior portion of each of the drop-carrier particles due to the specific chemical and/or physical properties of the interior and exterior regions of the drop-carrier particles. The combined drop-carrier particle with the dispersed phase contained therein is referred to as a particle-drop. The selective association results in compartmentalization of the dispersed phase solution into sub-microliter-sized volumes contained in the drop-carrier particles. The compartmentalized volumes can be used for single-molecule assays as well as single-cell, and other single-entity assays.
Type:
Grant
Filed:
July 28, 2021
Date of Patent:
March 22, 2022
Assignee:
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Inventors:
Dino Di Carlo, Chueh-Yu Wu, Ghulam Destgeer, Mengxing Ouyang
Abstract: A method of preparing a nucleic acid sample with target enrichment uses a reaction vessel, within which is added a chelating agent to a sample with heating to about 99° C. to provide a crude lysate. A PNA probe is provided at a concentration sufficient for binding and capture of discernible levels of target nucleic acid. The PNA probe may be attached to beads which are initially embedded in a wax body and are released during the heating so that the y are free to move and come into contact with the PNA probe and target DNA. After binding has occurred, the beads are magnetically attracted back into a pocket along with the wax, which is allowed to solidify before they are removed from the reaction vessel.
Type:
Grant
Filed:
November 20, 2018
Date of Patent:
March 15, 2022
Assignee:
Altratech Limited
Inventors:
Brian O'Farrell, Timothy Cummins, Cian Desmond O'Sullivan, Jorge Alvarez-Vicente
Abstract: A sensor apparatus for testing a biological sample, a system making use thereof and a method for testing a biological sample with the sensor apparatus and system.
Type:
Grant
Filed:
September 26, 2018
Date of Patent:
March 8, 2022
Assignee:
BOEHRINGER INGELHEIM VETMEDICA GMBH
Inventors:
Christoph Weber, Matthias Griessner, Nele Jenne
Abstract: The claimed invention relates to a method of processing a polynucleotide, by obtaining a sense polynucleotide strand comprising a homopolymeric region that is longer that the reading section of a nanopore; synthesizing an antisense polynucleotide strand under conditions in which a nucleotide analog is incorporated at random in a reverse complement of the homopolymer region, such that the length of the homopolymer region in the antisense polynucleotide strand is shorter than the reading section of the nanopore; and moving the antisense polynucleotide strand through the nanopore such that a proportion of the antisense polynucleotide strand interacts with the nanopore.
Type:
Grant
Filed:
February 5, 2020
Date of Patent:
March 1, 2022
Assignee:
Oxford Nanopore Technologies PLC
Inventors:
Clive Gavin Brown, James Anthony Clarke, Graham Hall, Gavin Harper, Andrew John Heron, James White
Abstract: The present invention relates to a method and kit for amplifying and detecting a quantity of nucleic acid. The invention is particularly relevant to isothermal amplification techniques carried out on a flow based assay device. The amplified nucleic acid may be detected on the device using an optical read-out.
Abstract: The present disclosure provides nucleic acid molecules, compositions, and kits comprising the same, and methods for producing templated assembly products.
Abstract: Methods, kits, and systems for fixation of RNA permitting its detection in intact tissue, such as, large volume of mammalian tissue are disclosed. The methods, kits, and systems utilize carbodiimide-based chemistry to stably retain RNAs in tissue clarified using CLARITY. Also provided herein are methods, kits, and systems for detection of RNAs in clarified tissue.
Type:
Grant
Filed:
February 9, 2017
Date of Patent:
February 22, 2022
Assignee:
The Board of Trustees of the Leland Stanford Junior University
Inventors:
Karl A. Deisseroth, Emily L. Sylwestrak, Priya Rajasethupathy, Matthew Wright
Abstract: The present disclosure provides molecular sensors. The molecular sensors may be flexible or linear and are oligonucleotide-based and have fluorescent groups. The molecular sensors may be used in methods to measure molecular crowding, identify of binding modes of various substrates, pharmaceutical drug screens, and in high-throughput methods.
Type:
Grant
Filed:
September 26, 2019
Date of Patent:
February 8, 2022
Assignee:
New York University
Inventors:
Chandrashekhar Uttamrao Murade, George Shubeita
Abstract: The present disclosure provides, in some aspects, methods and compositions for producing nucleic acid nanostructures having little to no kinetic barriers to self-assembly.
Type:
Grant
Filed:
April 11, 2017
Date of Patent:
February 1, 2022
Assignee:
President and Fellows of Harvard College
Inventors:
Nikhil Gopalkrishnan, Thomas E. Schaus, Peng Yin
Abstract: The invention relates to methods for conducting binding assays in an assay device that includes one or more storage and use zone. The storage zones of the assay device are configured to house one or more reagents used in an assay conducted in the use zone of the device.
Type:
Grant
Filed:
March 11, 2020
Date of Patent:
January 25, 2022
Assignee:
Meso Scale Technologies, LLC.
Inventors:
Sudeep Kumar, George Sigal, Michael Tsionsky
Abstract: An assay for detecting gene fragments, including: amplifying gene fragments comprising single-nucleotide polymorphisms (SNPs) to form an initial amplification product; isolating single strand oligonucleotides of interest from the initial amplification product; forming a solution comprising the oligonucleotides of interest and reporter molecules, each reporter molecule having a first oligonucleotide domain configured to hybridize with a complementary oligonucleotide of interest, and a second oligonucleotide domain configured to hybridize with a complementary capture probe; hybridizing, in the solution, the oligonucleotides of interest with the reporter molecules that have complementary first domains; applying the solution to the surface of a microarray including an array of capture probes fixed to a microarray slide; capturing the oligonucleotides of interest on the microarray by hybridizing the second oligonucleotide domains of the reporter molecules with complementary capture probes of the microarray; and de
Type:
Grant
Filed:
March 30, 2018
Date of Patent:
January 25, 2022
Inventors:
Marcella Chiari, Francesco Damin, Silvia Galbiati, Maurizio Ferrari
Abstract: The disclosure relates to a method for specific detection of a target analyte using probe DNA specific to the target analyte and non-functionalized, carbohydrate-capped metal nanoparticles such as non-functionalized, dextrin-capped gold nanoparticles. A sample mixture including a target DNA analyte and a probe DNA specific thereto is incubated to from a probe DNA-target DNA complex. The non-functionalized, carbohydrate-capped metal nanoparticles and an ionic species such as sodium chloride or other salt are added to the probe DNA-target DNA complex, and the mixture is incubated. Addition of the ionic species creates a detectable distinction, such as color of the resultant mixture, between stabilized metal nanoparticles when the probe DNA-target DNA complex is present and destabilized metal nanoparticles when the probe DNA-target DNA complex is absent. The method can be used for colorimetric detection of plant pathogens and associated diseases in agricultural production systems.
Type:
Grant
Filed:
March 16, 2018
Date of Patent:
January 18, 2022
Assignee:
BOARD OF TRUSTEES OF MICHIGAN STATE UNIVERSITY
Inventors:
Robert Day, Amy Baetsen-Young, Evangelyn C. Alocilja
Abstract: cfDNA reference material, for example, for use in verifying the accuracy and effectiveness of a diagnostic test, is generated from chromatin which may be sourced from whole cells. The chromatin may be treated with formaldehyde to form crosslinks between DNA and histones, for example, while the chromatin is contained within nuclear and/or plasma membranes. The fixed chromatin may be sheared by acoustic energy, which may also be used to lyse cell membranes within which the fixed chromatin may be contained. The sheared chromatin may be treated with an enzyme, such as micrococcal nuclease, to digest chromatin in linker regions of the DNA between nucleosomes and generate nucleosome material for use as cfDNA reference material.
Type:
Grant
Filed:
January 23, 2018
Date of Patent:
January 4, 2022
Assignee:
Covaris, Inc.
Inventors:
Hamid Khoja, James A. Laugharn, Jr., Hans-Ulrich Thomann
Abstract: The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.
Abstract: Disclosed are devices and methods for collection, labeling and matching biological samples containing nucleic acid in conjunction with collecting at least one ridge and valley signature such as a fingerprint or footprint of an individual. Such devices and methods are used in forensic, human identification, paternity, tissue typing, and screening technologies to rapidly process an individual's identity, determine the identity of an individual along with the genotype profile of the individual.
Type:
Grant
Filed:
June 27, 2019
Date of Patent:
December 28, 2021
Assignee:
LIFE TECHNOLOGIES CORPORATION
Inventors:
Michael Harrold, Lori Hennessy, Leonard Klevan
Abstract: Disclosed herein are improved methods and systems for sequencing nucleic acid that exploit the temperature-dependence of the emitted intensity of fluorescent dyes. The temperature of the sequencing reaction is adjusted during each sequencing cycle, and the emission, or lack of emission, of light meeting or exceeding a threshold by the fluorescent dyes at different temperatures, or within different temperature ranges, is used to detect the fluorescent labels of the incorporated dNTPs and thereby sequence the nucleic acid. The disclosed methods enable a determination of the dNTP incorporated at any given site with a reasonable number of chemistry steps without the complex optics necessary for prior-art systems.