Integrated Apparatus Specially Adapted For Both Screening A Library And Identifying A Library Member Patents (Class 506/35)
  • Patent number: 11732300
    Abstract: Disclosed herein are methods of amplifying an analyte in a biological sample using a bridging oligonucleotide that hybridizes to a captured analyte. The methods disclosed herein include steps of (a) contacting a biological sample with a substrate having capture probes comprising a capture domain and a spatial barcode; (b) hybridizing the analyte to the capture domain; and (c) contacting the analyte to a bridging oligonucleotide comprising (i) a capture-probe-binding sequence, and (ii) an analyte-binding sequence; (d) extending the bridging oligonucleotide; and (e) determining (i) all or a part of the sequence of the analyte, or a complement thereof, and (ii) the spatial barcode, or a complement thereof, and using the determined sequence of (i) and (ii) to determine the location of the analyte in the biological sample.
    Type: Grant
    Filed: February 4, 2021
    Date of Patent: August 22, 2023
    Assignee: 10x Genomics, Inc.
    Inventor: Felice Alessio Bava
  • Patent number: 10913975
    Abstract: Presented are methods and compositions for spatial detection and analysis of nucleic acids in a tissue sample. The methods can enable the characterization of transcriptomes and/or genomic variations in tissues while preserving spatial information about the tissue.
    Type: Grant
    Filed: July 21, 2016
    Date of Patent: February 9, 2021
    Assignee: Illumina, Inc.
    Inventors: Alex So, Li Liu, Min-Jui Richard Shen, Neeraj Salathia, Kathryn M. Stephens, Anne Jager, Timothy Wilson, Justin Fullerton, Sean M. Ramirez, Shannon Kaplan, Rigo Pantoja, Bala Murali Venkatesan, Steven Modiano
  • Patent number: 10724078
    Abstract: A method is presented that enables the spatial mapping of nucleic acids of tissue samples with high resolution and without sacrificing the degree of multiplexing that is available from next-generation sequencing. The method is based on the application of patterns of barcoded oligonucleotides probes onto predefined locations in a region of interest in a tissue sample. Every nucleic acid analyzed can be allocated to a certain position inside the sample based on the barcode. Various printing technologies can be used and different ways of patterning can be employed, like a regular array with a certain pitch or alternatively an object-based patterning with defined regions of interest without shape constraints.
    Type: Grant
    Filed: April 13, 2016
    Date of Patent: July 28, 2020
    Assignee: KONINKLIJKE PHILIPS N.V.
    Inventors: Marc Van Driel, Reinhold Wimberger-Friedl, Anke Pierik
  • Patent number: 9879313
    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.
    Type: Grant
    Filed: June 25, 2014
    Date of Patent: January 30, 2018
    Assignee: Prognosys Biosciences, Inc.
    Inventors: Mark S. Chee, David A. Routenberg
  • Patent number: 9366631
    Abstract: The present disclosure provides fully integrated microfluidic systems to perform nucleic acid analysis. These processes include sample collection, nucleic acid extraction and purification, amplification, sequencing, and separation and detection. The present disclosure also provides optical detection systems and methods for separation and detection of biological molecules. In particular, the various aspects of the invention enable the simultaneous separation and detection of a plurality of biological molecules, typically fluorescent dye-labeled nucleic acids, within one or a plurality of microfluidic chambers or channels. The nucleic acids can be labeled with at least 6 dyes, each having a unique peak emission wavelength. The present systems and methods are particularly useful for DNA fragment sizing applications such as human identification by genetic fingerprinting and DNA sequencing applications such as clinical diagnostics.
    Type: Grant
    Filed: July 27, 2011
    Date of Patent: June 14, 2016
    Assignee: NetBio, Inc.
    Inventors: Eugene Tan, Heung Chuan Lam, Valery Leonidovich Bogdanov, Gregory John Kellogg, John A. Wright, Ulrich Hans Thomann, Richard F. Selden
  • Publication number: 20150094377
    Abstract: The invention generally relates to a molecular classification of disease predisposition and particularly to molecular markers for cancer predisposition and methods of use thereof.
    Type: Application
    Filed: December 5, 2014
    Publication date: April 2, 2015
    Inventors: Kirsten Timms, Brian Allen, Anne-Renee Hartman
  • Publication number: 20150080268
    Abstract: Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for a disease, such as treatments that were not initially identified as a treatment for the disease or not expected to be a treatment for a particular disease.
    Type: Application
    Filed: November 24, 2014
    Publication date: March 19, 2015
    Inventors: Daniel D. Von Hoff, David M. Loesch, Arlet Alarcon, Robert J. Penny, Alan Wright, Matthew J. McGinniss, Ryan P. Bender, Traci Pawlowski
  • Publication number: 20150080269
    Abstract: Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for a disease, such as treatments that were not initially identified as a treatment for the disease or not expected to be a treatment for a particular disease.
    Type: Application
    Filed: November 24, 2014
    Publication date: March 19, 2015
    Inventors: Daniel D. Von Hoff, David M. Loesch, Arlet Alarcon, Robert J. Penny, Alan Wright, Matthew J. McGinniss, Ryan P. Bender, Traci Pawlowski
  • Publication number: 20150065357
    Abstract: The present invention generally relates to methods of rapidly and efficiently searching biologically-related data space. More specifically, the invention includes methods of identifying bio-molecules with desired properties, or which are most suitable for acquiring such properties, from complex bio-molecule libraries or sets of such libraries. The invention also provides methods of modeling sequence-activity relationships. As many of the methods are computer-implemented, the invention additionally provides digital systems and software for performing these methods.
    Type: Application
    Filed: November 7, 2014
    Publication date: March 5, 2015
    Inventor: Richard John Fox
  • Publication number: 20140357502
    Abstract: In a first location of a mass spectrometer, a plurality of ionized molecules of an ion source are selected that have mass-to-charge ratios within a mass-to-charge ratio window width. The plurality of selected ionized molecules are transmitted from a first to a second location. Reagent ions are transmitted to the second location to reduce a charge state of one or more of the plurality of selected ionized molecules. A mass analyzer is used to analyze the plurality of reduced ionized molecules and produce a mass spectrum. A compound is identified from a peak of the spectrum that has a mass-to-charge ratio less than or equal to the highest mass-to-charge ratio in the window width if the noise is multiply charged and greater than the highest mass-to-charge ratio in the window width if the noise is singly charged.
    Type: Application
    Filed: November 28, 2012
    Publication date: December 4, 2014
    Inventors: John Lawrence Campbell, Yves Le Blanc, Alexandre V. Loboda, Igor Chernushevich
  • Patent number: 8815536
    Abstract: Apparatus, systems, and methods for detecting, screening and sampling of cells are disclosed.
    Type: Grant
    Filed: February 4, 2005
    Date of Patent: August 26, 2014
    Assignee: The Johns Hopkins University
    Inventor: Rolf U. Halden
  • Patent number: 8748111
    Abstract: The invention provides a bio-sensing nanodevice comprising: a stabilized G-protein coupled receptor on a support, a real time receptor-ligand binding detection method, a test composition delivery system and a test composition recognition program. The G-protein coupled receptor can be stabilized using surfactant peptide. The nanodevice provides a greater surface area for better precision and sensitivity to odorant detection. The invention further provides a microfluidic chip containing a stabilized G-protein coupled receptor immobilized on a support, and arranged in at least two dimensional microarray system. The invention also provides a method of delivering odorant comprising the step of manipulating the bubbles in complex microfluidic networks wherein the bubbles travel in a microfluidic channel carrying a variety of gas samples to a precise location on a chip. The invention further provides method of fabricating hOR17-4 olfactory receptor.
    Type: Grant
    Filed: January 28, 2011
    Date of Patent: June 10, 2014
    Assignee: Massachusetts Institute of Technology
    Inventors: Andreas Mershin, Brian Cook, Liselotte Kaiser, Johanna F. Bikker, Yoshikatsu Miura, Daisuke Niwa, Dai Ohnishi, Atsushi Tazuke, Shuguang Zhang
  • Publication number: 20140031263
    Abstract: A sensor system is formed from a micro machined resonant structure with multiple resonant elements, a tracking resonator control electronics, and signal processing algorithms. The moving elements of the resonator are coated with chemically active materials that change mass when exposed to the target chemical resulting in a change in frequency or period of oscillation. The changes in frequency or period are processed by multi-sensor chemical detection algorithms to identify chemical types and concentrations. In essence, the resonator and drive electronics form a closed loop oscillator operating at the resonator's natural frequency. The resonators are formed from silicon using photolithographic processes. The resonator design includes in-plane resonant motion combined with dynamic balance to operate with a high Q even in the presence of atmospheric pressure.
    Type: Application
    Filed: May 21, 2012
    Publication date: January 30, 2014
    Inventors: Brian L. Norling, John C.G. Dunfield
  • Publication number: 20130338046
    Abstract: Methods and apparatus relating to very large scale FET arrays for analyte measurements. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis.
    Type: Application
    Filed: June 4, 2013
    Publication date: December 19, 2013
    Inventors: Jonathan M. ROTHBERG, Wolfgang HINZ, Kim L. JOHNSON
  • Patent number: 8580344
    Abstract: This disclosure provides methods, devices and systems for using a stamp to enhance selectivity between surface layers of a substrate, and to facilitate functionalizing selected layers. An array of flat stamps may be used to concurrently stamp multiple regions of a substrate to transfer one or more substances to the topmost layer or layers of the substrate. If desired, the affected regions of the substrate may be isolated from each other through the use of a reactor plate that, when clamped to the substrate's surface, forms reaction wells in the area of stamping. The stamp area can, if desired, be configured for stamping the substrate after the reactor plate has been fitted, with the individual stamps sized and arranged in a manner that permits stamping within each reaction well.
    Type: Grant
    Filed: March 16, 2009
    Date of Patent: November 12, 2013
    Assignee: Intermolecular, Inc.
    Inventors: Nikhil D. Kalyankar, Zachary Fresco, Chi-I Lang
  • Publication number: 20130184186
    Abstract: Systems and methods for the detection of biomarkers. In at least one embodiment of a microarray system of the present disclosure, the microarray system comprises a microarray product comprising at least 100 diagnostic markers/cm2, a microarray identifier, and a stabilizing agent, a control microarray product comprising a first specific binding pair member that binds to a first detectable label, and a processor for providing information regarding the identification and concentration of markers on the microarray based on the identity of the array provided by the microarray identifier.
    Type: Application
    Filed: November 27, 2012
    Publication date: July 18, 2013
    Applicant: Companion Diagnostics Inc.
    Inventor: Companion Diagnostics Inc.
  • Patent number: 8357490
    Abstract: An integrated instrument for oligonucleotide synthesis and PCR, and a system and method thereof are disclosed. The integrated instrument is basically composed of two independent modules. The first module is a unit for chemical de novo synthesis of oligonucleotides such as oligonucleotide primers and/or oligonucleotide hybridization probes. The second module is a unit for performing an analytical polymerase chain reaction amplification in real time, i.e. a qPCR. The two modules are operatively linked to each other in such a way that a user can load a nucleic sample to be analyzed into the integrated instrument and perform a PCR reaction by programming the instrument without a previous external synthesis of oligonucleotide amplification primers.
    Type: Grant
    Filed: July 22, 2010
    Date of Patent: January 22, 2013
    Assignee: Roche Diagnostics Operations, Inc.
    Inventors: Thomas Froehlich, Martin Gutekunst, Dieter Heindl, Angelika Roesler, Rudolf Seibl
  • Patent number: 8273567
    Abstract: There is provided a portable measuring system having a biophotonic sensor. The portable measuring system also includes a tunable light source, an output intensity detector and an output wavelength detector, which are mounted therein. The portable measuring system can precisely measure a variation in the reflectivity spectrum and/or the transmittance spectrum of the biophotonic sensor before and after an antigen-antibody reaction by varying the wavelength of the tunable light source. Thus, the concentration of the antigen is precisely measured.
    Type: Grant
    Filed: May 16, 2008
    Date of Patent: September 25, 2012
    Assignee: Electronics and Telecommunications Research Institute
    Inventors: Hyun Sung Ko, Chul Huh, Kyung Hyun Kim, Jong Cheol Hong, Wan Joong Kim, Gun Yong Sung, Seon Hee Park
  • Publication number: 20110245111
    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.
    Type: Application
    Filed: April 5, 2011
    Publication date: October 6, 2011
    Applicant: Prognosys Biosciences, Inc.
    Inventor: Mark S. Chee
  • Publication number: 20110207619
    Abstract: An arrangement is provided in at least one embodiment, having a magazine for supplying a plurality of microfluidic devices. The microfluidic devices each contain at least one element/device for binding at least one biological molecule, wherein the at least one element/device for binding the at least one biological molecule can be moved relative to the microfluidic device. A sample presumably containing biological molecules to be examined is introduced into the microfluidic device. The biological molecule to be examined is bound by the at least one element/device for binding the biological molecule. In at least one embodiment, the at least one element/device for binding the at least one biological molecule, or the substrate-molecule complex, can then be moved in the microfluidic device, e.g. in accordance with a predetermined reaction sequence, for example by means of a magnetic field. The microfluidic device is transported through the arrangement.
    Type: Application
    Filed: November 29, 2007
    Publication date: August 25, 2011
    Inventors: Thomas Ehben, Mitja Schonecke, Christian Zilch
  • Publication number: 20110201529
    Abstract: The present invention provides a system for analyzing and screening disease related genes from microarray database. After normalizing the collected microarray datasets and related experiment data by using pre-processing unit, the relative important feature vector can be systematically extracted by the feature selection unit. The maximal likelihood discriminate rule of classification unit calculates probability statistics of the classification and diagonal quadratic discriminant analysis module is used to decide classification and set up disease prediction module. Also, the generalized rule induction information statistics calculation module of rule extraction unit is used to obtain organized information statistics and information theoretic rule induction algorithm module is employed to generate best relationship rule and associate rule module can be set up.
    Type: Application
    Filed: February 12, 2010
    Publication date: August 18, 2011
    Inventors: Liang-Tsung Huang, Chang-Sheng Wang
  • Patent number: 7947626
    Abstract: This invention comprises a method for generating functional neural networks using neural progenitor cells on microelectrode arrays (MEAs). The method involves dissociating neural progenitor cells from an embryo, propagating the neural progenitor cells, passaging the neural progenitor cells and seeding the neural progenitor cells on MEAs to produce a functional neural network. The neural progenitor cells may be continuously passaged to propagate an endless supply of neural progenitor cells. The resultant passaged progenitor cell derived neural network MEA may be used to detect and/or quantify various biological or chemical toxins.
    Type: Grant
    Filed: August 29, 2007
    Date of Patent: May 24, 2011
    Assignee: The United States of America as represented by the Secretary of the Navy
    Inventors: Wu Ma, Jinny Lin Liu, Thomas O'Shaughnessy
  • Patent number: 7932213
    Abstract: The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. A composition is provided that comprises an array of chemical compounds attached to a solid support, wherein the density of the array of compounds is at least 1000 spots per cm2. The inventive arrays are generated by: providing a solid support functionalized with a selected chemical moiety capable of interacting with a chemical compound to form an attachment and delivering compounds to the solid support having a density of at least 1000 spots per cm2. The present invention also provides methods for utilizing these arrays to identify small molecule partners for biological macromolecules of interest.
    Type: Grant
    Filed: February 20, 2003
    Date of Patent: April 26, 2011
    Assignee: President and Fellows of Harvard College
    Inventors: Seung Bum Park, David Barnes-Seeman, Angela N. Koehler, Stuart L. Schreiber
  • Patent number: 7902121
    Abstract: T cells are profiled with respect to their expression of antigen receptor. The cells are arrayed on a planar or three-dimensional substrate through binding to immobilized or partially diffused MHC-antigen complexes. The cells may further be characterized with respect to their ability to respond to external stimulus in the microenvironment. External stimuli include cell-cell interactions, response to factors, and the like.
    Type: Grant
    Filed: May 27, 2004
    Date of Patent: March 8, 2011
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Daniel Shin-Yu Chen, Yoav Soen, Daniel Lewis Kraft, Patrick O. Brown, Mark Davis
  • Publication number: 20110034340
    Abstract: The present invention discloses systems and methods for minimizing or eliminating steps in immunosorbent assays for single and multiple analytes by eliminating both the need to attach target molecules to the test well and the need to remove unbound antibodies through rinsing. The immunosorbent assay (ISA) is utilized for a single analyte or target and includes the step of mixing the immunologic molecules with the sample and detection. The present invention further discloses an immunosorbent assay for multiple analytes (ISAMA) for testing a plurality of analytes or targets in a single well using a modified ISA test wherein different tags are attached to different antibody pairs. Alternate embodiments use multiple types of scavenger antigens with corresponding elimination of the need for scavenger antibodies. The present invention discloses various types of test wells for the rapid and simultaneous testing of fluids for a plurality of components and a methodology for a continuous immunosorbent assay.
    Type: Application
    Filed: August 2, 2010
    Publication date: February 10, 2011
    Inventors: Derrick Charbonnet, Norman Scott Evans
  • Publication number: 20100248981
    Abstract: A device, method and system for ensuring proper orientation and installation of trays for processing biological sensors in an automated and flexible system are provided. The system comprises an instrument handling robot that transfers a plurality of arrays mounted on pegs on a strip to liquid reaction stations. In particular, the method comprises a first orientation marking on a tray and a second orientation marking on a deck, indicating the proper station in which the tray is placed for a specific process.
    Type: Application
    Filed: March 29, 2010
    Publication date: September 30, 2010
    Applicant: Affymetrix, INC.
    Inventor: Mohsen Shirazi
  • Patent number: 7745377
    Abstract: The invention provides peptide synthons having protected functional groups for attachment of desired moieties (e.g. functional molecules or probes). Also provided are peptide conjugates prepared from such synthons, and synthon and conjugate preparation methods including procedures for identifying the optimum probe attachment site. Biosensors are provided having environmentally sensitive dyes that can locate specific biomolecules within living cells and detect chemical and physiological changes in those biomolecules as the living cell is moving, metabolizing and reacting to its environment. Methods are included for detecting GTP activation of a Rho GTPase protein using polypeptide biosensors. When the biosensor binds GTP-activated Rho GTPase protein, the environmentally sensitive dye emits a signal of a different lifetime, intensity or wavelength than when not bound.
    Type: Grant
    Filed: May 5, 2005
    Date of Patent: June 29, 2010
    Assignee: The Scripps Research Institute
    Inventors: Klaus M. Hahn, Alexei Toutchkine, Rajeev Muthyala, Vadim Kraynov, Steven J. Bark, Dennis R. Burton, Chester Chamberlain
  • Publication number: 20100152066
    Abstract: Temperature control devices and methods are described. The described temperature control devices and methods comprise optical emission and detection assemblies and can be used in PCR and qPCR applications.
    Type: Application
    Filed: December 15, 2009
    Publication date: June 17, 2010
    Inventors: Imran R. MALIK, Axel Scherer
  • Publication number: 20090170716
    Abstract: Methods for sequencing nucleic acids are presented. Sequencing is accomplished through the detection of a redox active species that is indicative of nucleotide incorporation. In embodiments of the invention, an electrochemical signal indicative of nucleotide incorporation is amplified through cycling before it is detected. Arrays are provided that are capable of massively parallel nucleic acid sequence determination.
    Type: Application
    Filed: December 31, 2007
    Publication date: July 2, 2009
    Inventors: Xing Su, David Liu
  • Publication number: 20090149351
    Abstract: The invention relates to a device for containing, reacting and measuring, and a method of containing, reacting and measuring, and provides a device for containing, reacting and measuring, and a method of containing, reacting and measuring which is also able to effectively and quickly perform the reaction processing, measuring and identification.
    Type: Application
    Filed: December 2, 2008
    Publication date: June 11, 2009
    Applicant: PSS BIO INSTRUMENTS, INC.
    Inventor: Hideji TAJIMA
  • Publication number: 20090137410
    Abstract: A method for computer-based processing of biological data, comprising the steps of: selecting a gene as lead gene to be patented; searching homologues for the selected lead gene; creating a patent pool on the basis of the selected lead gene; generating and outputting a pool report for the planned patent application.
    Type: Application
    Filed: May 8, 2007
    Publication date: May 28, 2009
    Inventors: Oliver Schmitz, Alfons Weig, Mathieu Klein, Uwe Pressler, Alexander Levin, Florian Schauwecker, Udo Kampf, Anke Eisenmann
  • Publication number: 20090062150
    Abstract: Structural models for a rhomboid protease alone and bound to inhibitors and peptide substrates and compositions and methods for preparing rhomboid protease binding compounds and methods for using such rhomboid protease binding compounds for modulation of these proteases catalytic activity are disclosed herein.
    Type: Application
    Filed: November 9, 2007
    Publication date: March 5, 2009
    Inventor: Yigong Shi
  • Publication number: 20090036319
    Abstract: Aspects of the invention include methods of systems of pairwise filtering candidate probe nucleic acid sequences. Aspects of the invention further include methods and systems of selecting candidate probe nucleic acid sequences from plurality thereof, which methods and systems employ a pairwise elimination ranked record of a plurality of candidate probe nucleic acids for a genomic region of interest.
    Type: Application
    Filed: July 30, 2007
    Publication date: February 5, 2009
    Inventors: Nicholas M. Sampas, Brian Schane Giles, Peter G. Webb
  • Publication number: 20080312106
    Abstract: The invention relates to a substrate material for analyzing fluids which has first areas with a high porosity and second areas with a lower porosity.
    Type: Application
    Filed: November 28, 2006
    Publication date: December 18, 2008
    Applicant: KONINKLIJKE PHILIPS ELECTRONICS, N.V.
    Inventors: Ralph Kurt, Dirk Jan Broer, Roel Penterman, Emiel Peeters
  • Publication number: 20080075662
    Abstract: The invention concerns a method for analyzing nucleic acids using a small-size probe array comprising deoxylnostines (dl) instead of deoxyguanogines (dG). The invention also concerns such probe arrays and their use in methods for detecting and/or quantifying target oilgonucleotides present in DNA (deoxyribonucleic acid) or RNA (ribonucleic acid) molecules in a sample, in particular mRNA editing rate of the serotonin 5-HT2c receptor (5-HT2c-R). The invention further concerns a biochip or a reactor in liquid medium comprising such probe arrays as well as their uses, in particular for detecting and/or identifying genetic polymorphisms or for determining an mRNA editing rate, whether it is that of a 5-HT2c-R mRNA or any other RNA capable of being edited.
    Type: Application
    Filed: July 24, 2003
    Publication date: March 27, 2008
    Inventors: Jean-Jacques Madjar, Herve Berthomme