公开(公告)号：US20170307532A1

公开(公告)日：2017-10-26

申请号：US15518341

申请日：2014-10-16

Applicant: HITACHI HIGH-TECHNOLOGIES CORPORATION

Inventor： Michiru FUJIOKA ,  Tsuyoshi SONEHARA ,  Naoshi ITABASHI

IPC: G01N21/65 ,  G11B23/03 ,  G01N33/487 ,  G11B7/08 ,  G01Q60/22 ,  G11B7/1387 ,  G11B7/085 ,  G11B7/22

CPC classification number: G01N21/658 ,  G01N21/6458 ,  G01N21/65 ,  G01N33/48721 ,  G01Q60/22 ,  G11B7/08 ,  G11B7/08576 ,  G11B7/1387 ,  G11B7/22 ,  G11B23/0318

Abstract: The purpose of the present invention is to control, with a simple structure and high accuracy, irradiation of excitation light to a multi-nanopore substrate without interrupting a measurement. Irradiation of excitation light is performed concurrently to at least one nanopore and at least one reference object on a substrate mounted in an observation container 103. A position irradiated with the excitation light in a measurement sample is calculated on the basis of a signal generated from the reference object detected by a detector 109, and the measurement and a fixed position control is performed concurrently by performing measurement of the measurement object while a drive control part 115 controlling the position of the irradiation of the excitation light to the measurement sample on the basis of the calculation result, whereby an analysis of the measurement sample can be performed in a short time.

公开(公告)号：US20170045726A1

公开(公告)日：2017-02-16

申请号：US15305226

申请日：2015-03-12

Applicant: Hitachi High-Technologies Corporation

Inventor： Michiru FUJIOKA ,  Shuhei YAMAMOTO ,  Tsuyoshi SONEHARA ,  Hiromi KUSAKA ,  Akimasa OSAKA

IPC: G02B21/33 ,  G02B21/08 ,  G02B21/12 ,  G02B21/26

CPC classification number: G02B21/33 ,  G02B21/082 ,  G02B21/12 ,  G02B21/26 ,  G02B21/34

Abstract: In the microscope observation container according to the present invention, an observed sample is accommodated by an objective lens barrel provided with a housing extending along the radiation direction of excitation light and an objective lens fixed to an inside surface of the housing. The microscope observation container is provided with a structure for collecting a liquid immersion medium added by dispensation, the structure having a portion contacted by the objective lens barrel during observation. During observation the aforementioned portion is contacted by the objective lens barrel, and the liquid immersion medium is thereby sealed by the objective lens barrel and the structure. The aforementioned portion also has an elastic force, and is deformed so as to conform to the housing of the objective lens by the contact.

Abstract translation: 在根据本发明的显微镜观察容器中，通过设置有沿着激发光的辐射方向延伸的壳体的物镜筒和固定到壳体的内表面的物镜容纳观察到的样品。 显微镜观察容器设置有用于收集通过分配而添加的浸液介质的结构，该结构具有在观察期间与物镜镜筒接触的部分。 在观察期间，上述部分被物镜筒接触，并且液浸介质由此被物镜镜筒和结构密封。 上述部分还具有弹性力，并且通过接触而变形以与物镜的壳体一致。

公开(公告)号：US20200041483A1

公开(公告)日：2020-02-06

申请号：US16340995

申请日：2016-10-20

Applicant: HITACHI HIGH-TECHNOLOGIES CORPORATION

Inventor： Michiru FUJIOKA ,  Yusuke GOTO

IPC: G01N33/487 ,  G01N27/447 ,  C12Q1/6869

Abstract: The purpose of the present invention is to provide a method for treating biomolecules and a method for analyzing biomolecules with which it is possible to effectively suppress the clog of nanopores. The present invention is a method for treating biomolecules for analysis in which nanopores are used, wherein the method includes a step for preparing a sample solution that includes ammonium cations represented by a prescribed formula and biomolecules in which at least a portion of the higher-order structure has been fused.

公开(公告)号：US20180030506A1

公开(公告)日：2018-02-01

申请号：US15550144

申请日：2016-02-26

Applicant: Hitachi High-Technologies Corporation

Inventor： Michiru FUJIOKA

IPC: C12Q1/68

CPC classification number: C12Q1/6806 ,  C12Q1/6853 ,  C12Q1/6869 ,  G01N33/48721 ,  C12Q2525/161 ,  C12Q2525/301 ,  C12Q2527/107 ,  C12Q2531/113

Abstract: The present invention provides a method for constructing a single-stranded nucleic acid molecule for nucleic acid sequencing by means of a nanopore sequencer, said method including: a step in which at least one hairpin primer including a single-stranded region on the 3′ side and a pair of primers are used to synthesize a complementary strand of template DNA that includes the target sequence; and a step in which the synthesized complementary strand forms a hairpin structure inside a molecule and a template extension reaction is carried out. The obtained nucleic acid molecule includes both the target sequence and the complementary strand thereof in the sequence. Single strand construction enables analysis by nanopore sequencing, and the sequence of only the target nucleic acid, which does not include information of the complementary strand, is repeatedly analyzed, thus enabling analysis to be conducted with greater precision by addressing the problem of sequence errors.

公开(公告)号：US20190353636A1

公开(公告)日：2019-11-21

申请号：US16476860

申请日：2017-01-10

Applicant: HITACHI HIGH-TECHNOLOGIES CORPORATION

Inventor： Kazuma MATSUI ,  Yusuke GOTO ,  Rena AKAHORI ,  Takahide YOKOI ,  Michiru FUJIOKA

IPC: G01N33/487 ,  G01N27/447

Abstract: Provided are a first tank; a second tank; a thin film having a nanopore, which communicates the first tank to the second tank, and disposed between the first and second tanks; a first electrode provided in the first tank; and a second electrode provided in the second tank. A wall surface of the nanopore has an ion adsorption preventing structure to prevent desorption/adsorption of an ion contained in a solution filling the first tank and/or the second tank, and a voltage is applied between the first and second electrodes to measure an ion current flowing through the nanopore.

公开(公告)号：US20160109368A1

公开(公告)日：2016-04-21

申请号：US14890246

申请日：2014-05-09

Applicant: HITACHI HIGH-TECHNOLOGIES CORPORATION

Inventor： Michiru FUJIOKA ,  Motohiro YAMAZAKI ,  Toru YOKOYAMA

IPC: G01N21/64 ,  C12Q1/68

CPC classification number: G01N21/6486 ,  C12Q1/68 ,  G01N21/6408 ,  G01N2021/6415 ,  G01N2201/06113 ,  G01N2201/12 ,  G06F19/24

Abstract: Provided is a nucleic acid analyzer, which does not require manual processes by a highly trained operator such as a researcher and is easy to use, small-sized, capable of accepting multiple samples, and performs speedy analysis, and a nucleic acid analysis method using the analyzer. The analyzer and method perform detection in a plurality of exposure times, provide a program for determining a threshold for signal detection, and determine whether a faint signal peak is a false signal peak.

Abstract translation: 本发明提供一种核酸分析装置，其不需要由研究者等高度训练有素的操作者进行手动处理，易于使用，小型化，能够接受多个样品，并进行快速分析，并且使用核酸分析方法 分析仪。 分析器和方法在多个曝光时间中执行检测，提供用于确定信号检测阈值的程序，并且确定微弱信号峰值是否为假信号峰值。

公开(公告)号：US20190292589A1

公开(公告)日：2019-09-26

申请号：US16307636

申请日：2016-06-10

Applicant: Hitachi High-Technologies Corporation

Inventor： Michiru FUJIOKA ,  Yusuke GOTO ,  Takahide YOKOI

IPC: C12Q1/6869 ,  G01N27/447 ,  G01N33/487

Abstract: The purpose of the invention is to provide a method for analyzing biomolecules with which it is possible to easily suppress the occlusion of nanopores. The first embodiment of the invention is a method for analyzing biomolecules including a step for preparing a substrate having nanopores, a step for placing a sample solution including biomolecules and at least one compound selected from the group consisting of primary amines, secondary amines, guanidine compounds, and salts thereof on the substrate, and a step for detecting the changes in light or electrical signal generated when the biomolecules pass through the nanopores.

公开(公告)号：US20190137431A1

公开(公告)日：2019-05-09

申请号：US16304517

申请日：2017-04-11

Applicant: Hitachi High-Technologies Corporation

Inventor： Yoshimitsu YANAGAWA ,  Yusuke GOTO ,  Michiru FUJIOKA

IPC: G01N27/22 ,  C12Q1/6869

Abstract: An object of the present invention is to provide a biomolecule measuring device that can decrease the influence of crosstalk between chambers. A biomolecule measuring device according to the present invention supplies, to electrodes equipped on chambers, voltages modulated differently to each other.

公开(公告)号：US20180313813A1

公开(公告)日：2018-11-01

申请号：US15772196

申请日：2015-11-24

Applicant: Hitachi High-Technologies Corporation

Inventor： Michiru FUJIOKA ,  Nobuyuki ISOSHIMA ,  Wataru SATO

IPC: G01N33/487 ,  C12Q1/6816

CPC classification number: C12Q1/68 ,  G01N33/48721

Abstract: A biological sample analyzer using a nanopore, said analyzer comprising: a first chamber that storing a solvent; a baseboard provided with a nanopore through which a biological sample passes; a second chamber which is positioned adjacently to the first chamber via the baseboard and stores the solvent; a first electrode formed in the first chamber; a second electrode formed in the second chamber; a detector detecting the biological sample which has passed through the nanopore; and a stirrer stirring the solvent in the first chamber.

公开(公告)号：US20170023409A1

公开(公告)日：2017-01-26

申请号：US15120792

申请日：2015-01-16

Applicant: HITACHI HIGH-TECHNOLOGIES CORPORATION

Inventor： Tsuyoshi SONEHARA ,  Hiromi KUSAKA ,  Akira FUJII ,  Shuhei YAMAMOTO ,  Takeshi OOURA ,  Michiru FUJIOKA

IPC: G01J3/44 ,  G01N21/65 ,  G02B21/16 ,  G02B21/24 ,  G02B21/36 ,  G02B27/14 ,  G01J3/02 ,  G02B21/00

CPC classification number: G01J3/44 ,  G01J3/0208 ,  G01J3/021 ,  G01J3/0229 ,  G01J3/0248 ,  G01J3/10 ,  G01J3/4406 ,  G01N21/6458 ,  G01N21/65 ,  G02B7/28 ,  G02B7/32 ,  G02B21/0004 ,  G02B21/16 ,  G02B21/244 ,  G02B21/36 ,  G02B21/365 ,  G02B27/141

Abstract: With a microspectroscopy device provided with an objective lens with a high numerical aperture, a defocus arises from thermal drift, etc., necessitating auto-focusing. Conventional auto-focus based on through-focus image acquisition takes time, and thus, it cannot be applied to continuous measurement over a long time wherein high-speed sampling is carried out. The present invention addresses this problem by having a defocus-sensing beam that has either defocus or astigmatism fall incident on the objective lens. Since how the image of the spot of the beam for defocus sensing blurs differs depending on the orientation of the defocus, real-time detection of the amount and orientation of defocus becomes possible, and high-speed realtime auto-focus becomes possible.

Abstract translation: 利用具有高数值孔径的物镜的显微光谱装置，由于热漂移等引起散焦，需要自动聚焦。 基于通过聚焦图像获取的常规自动对焦需要时间，因此不能将其应用于长时间进行高速采样的连续测量。 本发明通过具有散焦或像散落在物镜上的散焦感测光束来解决这个问题。 由于用于散焦感测模糊的光束的斑点的图像根据散焦的取向而不同，所以可以实现对散焦的量和取向的实时检测，并且可以实现高速实时自动对焦。