Patents by Inventor Masataka Shirai

Masataka Shirai has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Patent number: 11454577
    Abstract: Provided is, in a sample of a cell or a micro region at a position designated in a microscope image of a tissue section, an apparatus and a method for analyzing a biomolecule, which are capable of collecting and analyzing a biomolecule in a single cell or in a micro region without damaging surrounding cells.
    Type: Grant
    Filed: October 3, 2018
    Date of Patent: September 27, 2022
    Assignee: HITACHI, LTD.
    Inventor: Masataka Shirai
  • Patent number: 11446662
    Abstract: A system for capturing a biomolecule in a single cell includes: a two-dimensional array having single cell capture holes on one surface of a substrate, and biomolecule capture areas inside the substrate each comprising a biomolecule capture member for capturing a biomolecule extracted from individual cells respectively captured by the single cell capture holes; a flow channel for flowing a sample containing cells to be assayed, from a 1st direction parallel to the surface of the substrate; a structure on the surface of the substrate and opposed to the 1st direction on the downstream side of each of the single cell capture holes; a 1st application means applying a 1st flow, and a 1st control means; and a 2nd application means applying a 2nd flow orthogonal to the one surface of the substrate toward each biomolecule capture area from each corresponding single cell capture hole, and a 2nd control means.
    Type: Grant
    Filed: March 28, 2016
    Date of Patent: September 20, 2022
    Assignee: HITACHI, LTD.
    Inventors: Tomoyuki Sakai, Masataka Shirai
  • Patent number: 11299727
    Abstract: A device is provided for capturing a nucleic acid in a single cell, having: a two-dimensional array comprising a substrate, a plurality of single cell capturing holes provided on one surface of the substrate, and a nucleic acid capturing region comprising, on the inside of the substrate, a nucleic acid capturing body, which is configured to capture the nucleic acids extracted from the individual cells respectively captured by the single cell capturing hole; a flow channel which is provided adjacent to the nucleic acid capturing region of the substrate, and is configured to discharge a solution in the nucleic acid capturing region; and a cylindrical structure body which is arranged on the substrate at the time of introducing a cell suspension and encloses a plurality of the single cell capturing holes, wherein the cylindrical structure body is removed after the cells are captured by the single cell capturing holes.
    Type: Grant
    Filed: March 6, 2017
    Date of Patent: April 12, 2022
    Assignee: HITACHI, LTD.
    Inventors: Tomoyuki Sakai, Masataka Shirai
  • Patent number: 11214796
    Abstract: The present invention provides a method and/or means for collecting and analyzing an individual cell in a tissue, and at the same time, quantitatively monitoring the expression levels of various genes while keeping two-dimensional information in the tissue. Specifically, the present invention provides a method comprising preparing a cDNA library from mRNA while keeping two-dimensional cellular distribution information and obtaining the gene expression levels at any site or all sites at a level of single cell. More specifically, the present invention provides a method comprising preparing a cDNA library in a sheet-form from mRNA while keeping two-dimensional cellular distribution information and repeatedly using the cDNA library in the detection of the gene expression, thereby allowing measurement of the expression distribution for a number of genes at a high accuracy.
    Type: Grant
    Filed: June 13, 2017
    Date of Patent: January 4, 2022
    Assignee: HITACHI, LTD.
    Inventors: Masataka Shirai, Hideki Kambara, Kiyomi Taniguchi
  • Publication number: 20210388422
    Abstract: The present invention relates to a method, a device, and an apparatus for analyzing the expression of a gene in single cells. Specifically, the present invention relates to: a device for gene expression analysis, characterized by including a support, in which a nucleic acid probe having a test nucleic acid capture sequence and a known sequence, and further containing a cell recognition tag sequence which differs depending on the difference in position on the surface of the support or in the vicinity of the surface thereof, and a common primer sequence having a known sequence is two-dimensionally distributed and immobilized on the surface of the support or in the vicinity of the surface thereof; and a method and an apparatus using the device for gene expression analysis.
    Type: Application
    Filed: May 18, 2021
    Publication date: December 16, 2021
    Inventors: Masataka SHIRAI, Hideki KAMBARA, Kiyomi TANIGUCHI, Maiko TANABE
  • Patent number: 11053536
    Abstract: The present invention relates to a method, a device, and an apparatus for analyzing the expression of a gene in single cells. Specifically, the present invention relates to: a device for gene expression analysis, characterized by including a support, in which a nucleic acid probe having a test nucleic acid capture sequence and a known sequence, and further containing a cell recognition tag sequence which differs depending on the difference in position on the surface of the support or in the vicinity of the surface thereof, and a common primer sequence having a known sequence is two-dimensionally distributed and immobilized on the surface of the support or in the vicinity of the surface thereof; and a method and an apparatus using the device for gene expression analysis.
    Type: Grant
    Filed: July 30, 2012
    Date of Patent: July 6, 2021
    Assignee: Hitachi, Ltd.
    Inventors: Masataka Shirai, Hideki Kambara, Kiyomi Taniguchi, Maiko Tanabe
  • Patent number: 11041760
    Abstract: In multiplex CARS, a fingerprint region is a region where signals are densely concentrated. Information about the intensities and spatial distribution of these signals is important in cell analysis. However, there has been a problem in that the signal intensities are low. Accordingly, mechanisms 702 and 703 for adjusting the power branching ratio between light that enters a photonic crystal fiber 705 and pumping light; mechanisms 710 and 711 for adjusting the divergence/convergence state of the pumping light; and mechanisms 706 and 2101 for adjusting the divergence/convergence state of Stokes light are provided to enable adjustment for emphasizing a desired wavelength band.
    Type: Grant
    Filed: March 11, 2015
    Date of Patent: June 22, 2021
    Assignee: HITACHI HIGH-TECH CORPORATION
    Inventors: Manabu Shiozawa, Koichi Watanabe, Masataka Shirai
  • Publication number: 20210181076
    Abstract: Provided is, in a sample of a cell or a micro region at a position designated in a microscope image of a tissue section, an apparatus and a method for analyzing a biomolecule, which are capable of collecting and analyzing a biomolecule in a single cell or in a micro region without damaging surrounding cells.
    Type: Application
    Filed: October 3, 2018
    Publication date: June 17, 2021
    Applicant: HITACHI, LTD.
    Inventor: Masataka SHIRAI
  • Patent number: 10876106
    Abstract: In order to interpret an arbitrary sequence region in many genes in many cells, it is necessary to degrade a nucleic acid into fragments and introduce a sequence that is different from one cell to another into each of the fragments. However, in the conventional configuration for analyzing many cells, there has been a problem that mixing of the degraded fragments among areas occurs before a tag sequence unique for each of the areas is introduced. The present invention provides a system for capturing a nucleic acid extracted from a cell in each of plural areas on a substrate and synthesizing a complementary DNA (cDNA) of the nucleic acid for each of the areas, wherein the system also includes a means for immediately introducing a tag sequence unique for each of the areas to the reaction product.
    Type: Grant
    Filed: April 9, 2015
    Date of Patent: December 29, 2020
    Assignee: HITACHI, LTD.
    Inventors: Maiko Tanabe, Masataka Shirai, Tomoyuki Sakai
  • Publication number: 20200385712
    Abstract: A method for analyzing gene expression in a cell using a device, the method including: introducing a plurality of cells into microreactors so that a single cell corresponds to each microreactor, capturing mRNA from the single cell on the probe, synthesizing first cDNA by subjecting the captured mRNA to a reverse transcription reaction, to produce a first cDNA library derived from the single cell on the solid supports, washing the solid supports, a step of synthesizing second cDNA from the first cDNA library, performing fragmentation of double-stranded DNA containing the first and second cDNA and addition of a tag sequence, removing a component other than an immobilized double-stranded DNA fragment by washing the solid supports with a washing solution, performing amplification of the double-stranded DNA fragment, and performing, for the amplified sequence, analysis of gene expression in each single cell, using the cell identification sequence and the molecule identification sequence.
    Type: Application
    Filed: November 9, 2018
    Publication date: December 10, 2020
    Applicant: HITACHI, LTD.
    Inventors: Kiyomi TANIGUCHI, Masataka SHIRAI
  • Publication number: 20200354781
    Abstract: The purpose of the present invention is to provide a single cell analysis device in which the improvement of the nucleic acid capturing efficiency and the improvement of the cell capturing efficiency are both achieved and a highly accurate single cell analysis data is thereby obtained. The present invention relates to an improvement of a cell analysis device including a two-dimensional array chip having a plurality of cell capture parts capable of capturing a single cell in each of the capture parts, and nucleic acid capture parts corresponding to the respective cell capture parts, the nucleic acid capture parts being capable of capturing a nucleic acid extracted from the cell captured by the cell capture part.
    Type: Application
    Filed: July 28, 2020
    Publication date: November 12, 2020
    Inventors: Masataka SHIRAI, Tomoyuki SAKAI, Kenko UCHIDA
  • Patent number: 10752941
    Abstract: The purpose of the present invention is to provide a single cell analysis device in which the improvement of the nucleic acid capturing efficiency and the improvement of the cell capturing efficiency are both achieved and a highly accurate single cell analysis data is thereby obtained. The present invention relates to an improvement of a cell analysis device including a two-dimensional array chip having a plurality of cell capture parts capable of capturing a single cell in each of the capture parts, and nucleic acid capture parts corresponding to the respective cell capture parts, the nucleic acid capture parts being capable of capturing a nucleic acid extracted from the cell captured by the cell capture part.
    Type: Grant
    Filed: December 1, 2015
    Date of Patent: August 25, 2020
    Assignee: HITACHI HIGH-TECH CORPORATION
    Inventors: Masataka Shirai, Tomoyuki Sakai, Kenko Uchida
  • Patent number: 10646869
    Abstract: (1) Plural reaction chambers each including at least one cell capturing unit and at least one nucleic acid capturing unit connected via a flow channel, (2) a first liquid flow channel commonly connected to the plural reaction chambers on a first surface side, (3) plural second liquid flow channels connected to the plural reaction chambers in a one-on-one relationship on the first surface side, and (4) a third liquid flow channel commonly connected to the plural reaction chambers on a second surface side opposite to the first surface, are provided in a flow cell device for single cell analysis.
    Type: Grant
    Filed: February 3, 2015
    Date of Patent: May 12, 2020
    Assignee: Hitachi, Ltd.
    Inventors: Masataka Shirai, Tomoyuki Sakai
  • Publication number: 20190194645
    Abstract: A device is provided for capturing a nucleic acid in a single cell, having: a two-dimensional array comprising a substrate, a plurality of single cell capturing holes provided on one surface of the substrate, and a nucleic acid capturing region comprising, on the inside of the substrate, a nucleic acid capturing body, which is configured to capture the nucleic acids extracted from the individual cells respectively captured by the single cell capturing hole; a flow channel which is provided adjacent to the nucleic acid capturing region of the substrate, and is configured to discharge a solution in the nucleic acid capturing region; and a cylindrical structure body which is arranged on the substrate at the time of introducing a cell suspension and encloses a plurality of the single cell capturing holes, wherein the cylindrical structure body is removed after the cells are captured by the single cell capturing holes.
    Type: Application
    Filed: March 6, 2017
    Publication date: June 27, 2019
    Applicant: Hitachi ,Ltd.
    Inventors: Tomoyuki SAKAI, Masataka SHIRAI
  • Publication number: 20180304262
    Abstract: (1) Plural reaction chambers each including at least one cell capturing unit and at least one nucleic acid capturing unit connected via a flow channel, (2) a first liquid flow channel commonly connected to the plural reaction chambers on a first surface side, (3) plural second liquid flow channels connected to the plural reaction chambers in a one-on-one relationship on the first surface side, and (4) a third liquid flow channel commonly connected to the plural reaction chambers on a second surface side opposite to the first surface, are provided in a flow cell device for single cell analysis.
    Type: Application
    Filed: February 3, 2015
    Publication date: October 25, 2018
    Inventors: Masataka SHIRAI, Tomoyuki SAKAI
  • Publication number: 20180272349
    Abstract: A system for capturing a biomolecule in a single cell includes: a two-dimensional array having single cell capture holes on one surface of a substrate, and biomolecule capture areas inside the substrate each comprising a biomolecule capture member for capturing a biomolecule extracted from individual cells respectively captured by the single cell capture holes; a flow channel for flowing a sample containing cells to be assayed, from a 1st direction parallel to the surface of the substrate; a structure on the surface of the substrate and opposed to the 1st direction on the downstream side of each of the single cell capture holes; a 1st application means applying a 1st flow, and a 1st control means; and a 2nd application means applying a 2nd flow orthogonal to the one surface of the substrate toward each biomolecule capture area from each corresponding single cell capture hole, and a 2nd control means.
    Type: Application
    Filed: March 28, 2016
    Publication date: September 27, 2018
    Applicant: Hitachi, Ltd.
    Inventors: Tomoyuki SAKAI, Masataka SHIRAI
  • Publication number: 20180265918
    Abstract: The purpose of the present invention is to provide a single cell analysis device in which the improvement of the nucleic acid capturing efficiency and the improvement of the cell capturing efficiency are both achieved and a highly accurate single cell analysis data is thereby obtained. The present invention relates to an improvement of a cell analysis device including a two-dimensional array chip having a plurality of cell capture parts capable of capturing a single cell in each of the capture parts, and nucleic acid capture parts corresponding to the respective cell capture parts, the nucleic acid capture parts being capable of capturing a nucleic acid extracted from the cell captured by the cell capture part.
    Type: Application
    Filed: December 1, 2015
    Publication date: September 20, 2018
    Inventors: Masataka SHIRAI, Tomoyuki SAKAI, Kenko UCHIDA
  • Patent number: 10030240
    Abstract: In order to conduct gene expression analysis of a number of genes in a number of cells, it has been necessary to separate cells, extract genes therefrom, amplify nucleic acids, and perform sequence analysis. However, separation of cells imposes damages on the cells, and it requires the use of an expensive system. Gene expression analysis in each cell can be carried out with high accuracy by arranging a pair of structures comprising a cell trapping section and a nucleic acid trapping section in a vertical direction to extract individual genes in relevant cells, synthesizing cDNA in the nucleic acid trapping section, amplifying nucleic acids, and analyzing the sequences using a next-generation sequencer.
    Type: Grant
    Filed: March 12, 2013
    Date of Patent: July 24, 2018
    Assignee: Hitachi, Ltd.
    Inventors: Masataka Shirai, Hideki Kambara, Kiyomi Taniguchi, Maiko Tanabe
  • Publication number: 20180195105
    Abstract: The present invention optically obtains characteristic values of a plurality of biological samples from a specimen; compares the characteristic values with examination information associated with the same specimen obtained in advance; and calculates an indicator to determine, based on a result of the comparison, whether a process is continued to genetic analysis of the biological samples or a re-preparation of samples from the same specimen is performed. By this method, it is possible to achieve more reliable biomarker detection by ensuring validity through appropriate selection of test samples while reducing cost, effort, and time for analysis in single cell analysis or analysis of a group of a small number of cells.
    Type: Application
    Filed: June 24, 2015
    Publication date: July 12, 2018
    Inventors: Takahide YOKOI, Masataka SHIRAI
  • Publication number: 20180119135
    Abstract: In order to interpret an arbitrary sequence region in many genes in many cells, it is necessary to degrade a nucleic acid into fragments and introduce a sequence that is different from one cell to another into each of the fragments. However, in the conventional configuration for analyzing many cells, there has been a problem that mixing of the degraded fragments among areas occurs before a tag sequence unique for each of the areas is introduced. The present invention provides a system for capturing a nucleic acid extracted from a cell in each of plural areas on a substrate and synthesizing a complementary DNA (cDNA) of the nucleic acid for each of the areas, wherein the system also includes a means for immediately introducing a tag sequence unique for each of the areas to the reaction product.
    Type: Application
    Filed: April 9, 2015
    Publication date: May 3, 2018
    Inventors: Maiko TANABE, Masataka SHIRAI, Tomoyuki SAKAI