公开(公告)号：US20210132034A1

公开(公告)日：2021-05-06

申请号：US17123181

申请日：2020-12-16

Applicant: Hitachi, Ltd.

Inventor： Takahide Yokoi ,  Takashi Anazawa

IPC: G01N33/487 ,  C12Q1/6869 ,  G01N27/40

Abstract: Conventionally, only a pair of electrodes is provided and nanopores arranged in parallel are connected by an electrolyte solution, and therefore a change in anion current to be measured is a sum of changes in ion currents generated in the respective nanopores. The invention includes: a first solution chamber including a plurality of first electrodes; a second solution chamber including a second electrode which is a counter electrode of the first electrodes; a membrane provided between the first solution chamber and the second solution chamber, the membrane having a plurality of small holes; a measuring unit for applying a voltage between the first electrodes and the second electrode and measuring a current flowing between the first electrodes and the second electrode via the small holes; and an insulating structure forming unit for forming, in the first solution chamber, an insulating structure for insulating the first electrodes in a state in which a conductive liquid is filled between the small holes and the first electrodes and achieves parallel measurement of ion currents by using nanopores.

公开(公告)号：US20140243214A1

公开(公告)日：2014-08-28

申请号：US14241041

申请日：2013-02-26

Applicant: Hitachi, Ltd.

Inventor： Takanobu Haga ,  Itaru Yanagi ,  Naoshi Itabashi ,  Yoshimitsu Yanagawa ,  Takeshi Ohura ,  Takashi Anazawa

IPC: G01N33/487 ,  G01N27/414

CPC classification number: G01N33/48721 ,  G01N27/4145 ,  Y10T436/143333

Abstract: In an FET configuration having a channel with a small thickness, transistor characteristics vary for different FETs in the same array, and therefore when the same gate voltage is applied, the sensitivities of DNA detection may be insufficient. To this end, the change in the channel current when DNA passes through the nanopore is detected while applying an optimum gate voltage for each nanopore FET to attain a predetermined channel current value to a plurality of nanopore FETs disposed on the same substrate, and four types of bases constituting DNA are distinguished.

Abstract translation: 在具有小厚度的沟道的FET配置中，晶体管特性对于同一阵列中的不同FET而变化，因此当施加相同的栅极电压时，DNA检测的灵敏度可能不足。 为此，检测DNA通过纳米孔时的通道电流的变化，同时对每个纳米孔FET施加最佳的栅极电压，以对设置在同一基板上的多个纳米孔FET获得预定的通道电流值， 区分构成DNA的碱基。

公开(公告)号：US10955342B2

公开(公告)日：2021-03-23

申请号：US15741693

申请日：2015-08-21

Applicant: HITACHI, LTD.

Inventor： Takashi Anazawa ,  Yoshinobu Kohara ,  Chihiro Uematsu ,  Yusuke Goto

IPC: G01N21/64 ,  B01L7/00 ,  B01L3/00

Abstract: A light detection device comprises: a flow path section in which a plurality of lines of flow of a plurality of droplets 4 dispersed in oil and moving along a linear line of flow is retained on an array plane; a laser beam irradiation section which introduces a laser beam 3 in a direction in which the plurality of lines of flow are arrayed in the flow path section to irradiate the plurality of lines of flow; and a light detection section which detects emitted light generated from the plurality of lines of flow by the irradiation of the laser beam, from a vertical direction with respect to the array plane. A refractive index of the oil no and a refractive index of the droplets nd have a difference such that −0.02≤nd−no≤0.05.

公开(公告)号：US10274459B2

公开(公告)日：2019-04-30

申请号：US14378878

申请日：2013-07-31

Applicant: Hitachi, Ltd.

Inventor： Makiko Yoshida ,  Takahide Yokoi ,  Takashi Anazawa

IPC: G01N27/447 ,  C12Q1/6816 ,  C12Q1/6825 ,  G01N30/88

Abstract: An aspect of the present invention includes performing electrophoresis of a nucleic acid sample to be analyzed labeled for each base type, generating waveform data of detected intensity by detecting a label signal for the each base type, selecting another peak position for each peak position of the waveform data for each base type, calculating relative signal intensity of signal intensity in each position relative to the signal intensity in the other selected position, and analyzing existence of each base type in a base sequence coordinate position of the nucleic acid sample by comparing the relative signal intensity of the nucleic acid sample to be analyzed and the relative signal intensity of a known nucleic acid sample in each peak position. Accordingly, acquiring information about a gene mutation in trace amounts existing in a target gene region highly sensitively with high precision is realized.

公开(公告)号：US10030266B2

公开(公告)日：2018-07-24

申请号：US14895923

申请日：2013-06-27

Applicant: HITACHI, LTD.

Inventor： Itaru Yanagi ,  Riichiro Takemura ,  Yoshimitsu Yanagawa ,  Takahide Yokoi ,  Takashi Anazawa

IPC: C12Q1/6874 ,  H01L29/49 ,  H01L29/66 ,  G01N27/414 ,  H01L21/02 ,  H01L21/283 ,  H01L21/306 ,  H01L21/8234

Abstract: In the field of the next generation DNA sequencer, a method for integrating very high sensitive FET sensors having side gates and nanopores as devices used for identifying four kinds of base and for mapping the base sequence of DNA without using reagents, and a semiconductor device having selection transistors and amplifier transistors respectively corresponding to the FET sensors having side gates and nanopores respectively so as to be able to read the variation of a detection current based on the differences among the charges of the four kinds of base without deteriorating the detection sensitivity of the FET sensor, are presented.

公开(公告)号：US12031913B2

公开(公告)日：2024-07-09

申请号：US15036181

申请日：2013-12-25

Applicant: Hitachi, Ltd.

Inventor： Takashi Anazawa ,  Takahide Yokoi ,  Yuichi Uchiho

IPC: G01N21/64 ,  B01L3/00 ,  G01N21/03 ,  G01N21/05 ,  G01N27/447

CPC classification number: G01N21/6454 ,  B01L3/5027 ,  G01N21/6402 ,  G01N21/6452 ,  G01N27/447 ,  G01N27/44721 ,  G01N27/44726 ,  G01N27/44791 ,  B01L2300/0858 ,  B01L2300/0864 ,  G01N2021/0346 ,  G01N21/05 ,  G01N2201/06113

Abstract: Efficient simultaneous laser-irradiation-fluorescence detection is performed for a plurality of channels of a microchip and simple and highly sensitive parallel analysis of a plurality of samples is enabled. In a microchip 1 made of an optically transparent solid material m1 with a refractive index n1, a plurality of channels 2 filled with a material m2 with a refractive index n2 and a plurality of channels 3 filled with a material m3 with a refractive index n3 are alternately arranged in parallel on the same plane. Here, m1, m2 and m3 are selected such that a relation of n2

公开(公告)号：US10908143B2

公开(公告)日：2021-02-02

申请号：US15037420

申请日：2013-11-27

Applicant: Hitachi, Ltd.

Inventor： Takahide Yokoi ,  Takashi Anazawa

IPC: G01N33/487 ,  G01N27/40 ,  C12Q1/6869

Abstract: Conventionally, only a pair of electrodes is provided and nanopores arranged in parallel are connected by an electrolyte solution, and therefore a change in an ion current to be measured is a sum of changes in ion currents generated in the respective nanopores. The invention includes: a first solution chamber including a plurality of first electrodes; a second solution chamber including a second electrode which is a counter electrode of the first electrodes; a membrane provided between the first solution chamber and the second solution chamber, the membrane having a plurality of small holes; a measuring unit for applying a voltage between the first electrodes and the second electrode and measuring a current flowing between the first electrodes and the second electrode via the small holes; and an insulating structure forming unit for forming, in the first solution chamber, an insulating structure for insulating the first electrodes in a state in which a conductive liquid is filled between the small holes and the first electrodes and achieves parallel measurement of ion currents by using nanopores.

公开(公告)号：US20140336949A1

公开(公告)日：2014-11-13

申请号：US14122680

申请日：2012-10-19

Applicant: Hitachi, Ltd.

Inventor： Takahide Yokoi ,  Takashi Anazawa

IPC: C12Q1/68 ,  G06F19/22

CPC classification number: C12Q1/6869 ,  G01N27/44726 ,  G01N27/44782 ,  G16B30/00 ,  C12Q2565/125

Abstract: The conventional DNA sequencers for analyzing nucleotide sequences have no function of detecting minute polymorphisms. Any cross talk in the wavelengths of fluorescent substances for labeled DNA fragments hinders detection of weak-strength signals at the same coordinates, making it difficult to detect genetic mutations with small existence ratios, for example, in somatic mutations. Disclosed is a gene analyzer composed of a plurality of flow channels, each of which is used to electrophorese nucleic acid samples labeled for each of nucleotide types; a chromatogram data creating part for detecting a labeled signal for each of the nucleotide types for each of the nucleic acid samples in each of the plurality of flow channels and creating chromatogram data on signal strengths detected; a peak detection part for the peal values in the chromatogram data for each of the nucleotide types; and a data integrating part for integrating a plurality of chromatogram data.

Abstract translation: 用于分析核苷酸序列的常规DNA测序仪不具有检测微小多态性的功能。 用于标记DNA片段的荧光物质的波长中的任何串扰阻碍了在相同坐标处检测到弱强度信号，使得难以检测例如体细胞突变中存在比例小的遗传突变。 公开了一种由多个流路组成的基因分析仪，每个流路用于电泳每个核苷酸类型标记的核酸样品; 色谱图数据创建部分，用于检测每个多个流动通道中每个核酸样品的每个核苷酸类型的标记信号，并产生关于所检测的信号强度的色谱数据; 每个核苷酸类型的色谱数据中的峰值的峰值检测部分; 以及用于整合多个色谱图数据的数据整合部分。