公开(公告)号：US07006929B2

公开(公告)日：2006-02-28

申请号：US10479938

申请日：2002-06-05

申请人： Hiroaki Oka ,  Nobuhiko Ozaki ,  Hirokazu Sugihara ,  Satoshi Konishi

发明人： Hiroaki Oka ,  Nobuhiko Ozaki ,  Hirokazu Sugihara ,  Satoshi Konishi

IPC分类号： G06F19/00

CPC分类号： G01N33/48728

摘要： A sensor capable of simply and quickly measuring the electrical activities of a number of cells simultaneously and a device comprising the sensor and capable of detecting the signal transmission between subject cells are provided. The sensor comprises a plurality of electrodes provided on a substrate. The electrodes individually measure a signal generated by a biological sample held by each of the electrodes. Each of the electrodes comprises a depression for holding the biological sample, a throughhole which is in communication with the depression and penetrates to a rear side of the substrate, an electrode portion, and a drawing line from the electrode portion. The electrodes are arranged so that the samples held by the depressions electrically communicate with one another.

摘要翻译： 提供了能够简单且快速地同时测量多个单元的电活动的传感器，以及包括该传感器并且能够检测主体单元之间的信号传输的设备。 传感器包括设置在基板上的多个电极。 电极单独地测量由每个电极保持的生物样品产生的信号。 每个电极包括用于保持生物样品的凹陷，与凹陷连通并穿透到基底的后侧的通孔，电极部分和来自电极部分的引出线。 电极被布置成使得由凹陷保持的样品彼此电连通。

公开(公告)号：US07594984B2

公开(公告)日：2009-09-29

申请号：US11652605

申请日：2007-01-12

申请人： Hiroaki Oka ,  Nobuhiko Ozaki ,  Hirokazu Sugihara

发明人： Hiroaki Oka ,  Nobuhiko Ozaki ,  Hirokazu Sugihara

IPC分类号： G01N33/50 ,  G01N27/00 ,  G01N33/543 ,  C12Q1/00 ,  G01N17/04

CPC分类号： G01N33/48728 ,  G01N33/54373 ,  G01N33/5438

摘要： The present invention provides an apparatus for measuring activity signals of a biological sample comprising: a measurement chamber (A) storing a target liquid containing a biological sample; a porous insulating substrate (5) provided with a measurement electrode (1) on at least one side; and a conveying device (8) which conveys the target liquid stored in the measurement chamber (A) and passes the target liquid through the porous insulating substrate (5) from the measurement electrode (1) side, wherein the conveying device (8) is operated to trap the biological sample contained in the target liquid onto the measurement electrode (1), so that the activity signals of the biological sample are measured through the measurement electrode (1). According to the apparatus, activity signals emitted from the biological sample can be detected easily, rapidly and accurately.

摘要翻译： 本发明提供了一种用于测量生物样品的活动信号的装置，包括：存储含有生物样品的目标液体的测量室（A） 在至少一侧设置有测量电极（1）的多孔绝缘基板（5） 以及输送装置（8），其输送存储在测量室（A）中的目标液体，并将目标液体通过多孔绝缘基板（5）从测量电极（1）侧移动，其中输送装置（8）为 操作以将包含在目标液体中的生物样品捕获到测量电极（1）上，从而通过测量电极（1）测量生物样品的活性信号。 根据该装置，可以容易，快速且准确地检测从生物样品发射的活动信号。

公开(公告)号：US07462324B2

公开(公告)日：2008-12-09

申请号：US10495621

申请日：2002-11-19

申请人： Nobuhiko Ozaki ,  Hiroaki Oka ,  Hirokazu Sugihara

发明人： Nobuhiko Ozaki ,  Hiroaki Oka ,  Hirokazu Sugihara

IPC分类号： G01N27/00 ,  G01N15/06 ,  G01N33/53 ,  G01N25/18

CPC分类号： G01N33/48707 ,  B01L3/5027

摘要： A measurement device 10 includes a measurement cell 11. The measurement cell 11 includes a substrates 17 and a substrate 16 formed on the substrate 17. The substrates 16 and 17 are bonded to each other. Thus, a flow pass 9 is formed in the measurement cell 11. As shown in FIG. 3, on the substrate 17 of the measurement cell 11, provided are a concave well 19, a protruding microelectrode 1 connected to a terminal 4a and formed on a side wall surface of the well 19, communicating tubes 15a and 15b connected to both of side surfaces of the well 19 (i.e., the flow pass 9) to face to each other, resistance baths 6a and 6b connected to the communicating tubes 15a and 15b, thin film resistors 3a and 3b arranged in the resistance baths 6a and 6b, and a reference electrode 2 connected to a terminal 4b.

摘要翻译： 测量装置10包括测量单元11.测量单元11包括基板17和形成在基板17上的基板16.基板16和17彼此接合。 因此，在测量单元11中形成流路9。 如图3所示，在测量单元11的基板17上设置凹槽19，连接到端子4a并形成在井19的侧壁表面上的突出微电极1，连接到两侧的连通管15a和15b 孔19的表面（即，流路9）彼此相对，连接到连通管15a和15b的电阻槽6a和6b，布置在电阻槽6a和6b中的薄膜电阻器3a和3b，以及 参考电极2连接到端子4b。

公开(公告)号：US07326384B2

公开(公告)日：2008-02-05

申请号：US10208547

申请日：2002-07-29

申请人： Hiroaki Oka ,  Nobuhiko Ozaki ,  Hirokazu Sugihara

发明人： Hiroaki Oka ,  Nobuhiko Ozaki ,  Hirokazu Sugihara

IPC分类号： B32B5/02

CPC分类号： G01N33/48728

摘要： A device for detecting a physicochemical change in a biological sample comprising at least one measuring electrode provided by causing a conductive material to enter into a porous film, and a conductor connected to the measuring electrode.

摘要翻译： 一种用于检测生物样品中物理化学变化的装置，包括通过使导电材料进入多孔膜而提供的至少一个测量电极和连接到测量电极的导体。

公开(公告)号：US20070134651A1

公开(公告)日：2007-06-14

申请号：US11652605

申请日：2007-01-12

申请人： Hiroaki Oka ,  Nobuhiko Ozaki ,  Hirokazu Sugihara

发明人： Hiroaki Oka ,  Nobuhiko Ozaki ,  Hirokazu Sugihara

IPC分类号： C12Q1/00 ,  G06F19/00

CPC分类号： G01N33/48728 ,  G01N33/54373 ,  G01N33/5438

摘要： The present invention provides an apparatus for measuring activity signals of a biological sample comprising: a measurement chamber (A) storing a target liquid containing a biological sample; a porous insulating substrate (5) provided with a measurement electrode (1) on at least one side; and a conveying device (8) which conveys the target liquid stored in the measurement chamber (A) and passes the target liquid through the porous insulating substrate (5) from the measurement electrode (1) side, wherein the conveying device (8) is operated to trap the biological sample contained in the target liquid onto the measurement electrode (1), so that the activity signals of the biological sample are measured through the measurement electrode (1). According to the apparatus, activity signals emitted from the biological sample can be detected easily, rapidly and accurately.

公开(公告)号：US07172860B2

公开(公告)日：2007-02-06

申请号：US10678138

申请日：2003-10-06

申请人： Hiroaki Oka ,  Nobuhiko Ozaki ,  Hirokazu Sugihara

发明人： Hiroaki Oka ,  Nobuhiko Ozaki ,  Hirokazu Sugihara

IPC分类号： C12Q1/00

CPC分类号： G01N33/48728 ,  G01N33/54373 ,  G01N33/5438

摘要： The present invention provides an apparatus for measuring activity signals of a biological sample comprising: a measurement chamber (A) storing a target liquid containing a biological sample; a porous insulating substrate (5) provided with a measurement electrode (1) on at least one side; and a conveying device (8) which conveys the target liquid stored in the measurement chamber (A) and passes the target liquid through the porous insulating substrate (5) from the measurement electrode (1) side, wherein the conveying device (8) is operated to trap the biological sample contained in the target liquid onto the measurement electrode (1), so that the activity signals of the biological sample are measured through the measurement electrode (1). According to the apparatus, activity signals emitted from the biological sample can be detected easily, rapidly and accurately.

摘要翻译： 本发明提供了一种用于测量生物样品的活动信号的装置，包括：存储含有生物样品的目标液体的测量室（A） 在至少一侧设置有测量电极（1）的多孔绝缘基板（5） 以及输送装置（8），其输送存储在测量室（A）中的目标液体，并将目标液体通过多孔绝缘基板（5）从测量电极（1）侧移动，其中输送装置（8）为 操作以将包含在目标液体中的生物样品捕获到测量电极（1）上，从而通过测量电极（1）测量生物样品的活性信号。 根据该装置，可以容易，快速且准确地检测从生物样品发射的活动信号。

公开(公告)号：US06999905B2

公开(公告)日：2006-02-14

申请号：US10296007

申请日：2002-04-26

申请人： Ryuta Ogawa ,  Hiroaki Oka ,  Nobuhiko Ozaki ,  Hirokazu Sugihara

发明人： Ryuta Ogawa ,  Hiroaki Oka ,  Nobuhiko Ozaki ,  Hirokazu Sugihara

IPC分类号： G06F15/00

CPC分类号： G01D1/14

摘要： A method for extracting a signal of interest from a signal generated from at least one subject, comprises the steps of (A) obtaining a time-series signal generated from the subject as a data group consisting of a plurality of pieces of data, (B) obtaining a plurality of extracted data groups from the data group, wherein each extracted data group comprises a predetermined number of pieces of data selected from the data group, (C) calculating standard deviations of the plurality of extracted data groups to obtain a standard deviation group, and (D) referencing each standard deviation included in the standard deviation group and selecting the signal of interest.

摘要翻译： 一种用于从至少一个对象产生的信号中提取感兴趣的信号的方法，包括以下步骤：（A）获得从被摄体产生的时间序列信号作为由多条数据组成的数据组（B ）从所述数据组中获取多个提取的数据组，其中每个提取的数据组包括从所述数据组中选择的预定数量的数据，（C）计算所述多个提取的数据组的标准偏差以获得标准偏差 组和（D）参考包括在标准偏差组中的每个标准偏差并选择感兴趣的信号。

公开(公告)号：US20050004442A1

公开(公告)日：2005-01-06

申请号：US10495621

申请日：2002-11-19

申请人： Nobuhiko Ozaki ,  Hiroaki Oka ,  Hirokazu Sugihara

发明人： Nobuhiko Ozaki ,  Hiroaki Oka ,  Hirokazu Sugihara

IPC分类号： B01L3/00 ,  G01N33/487 ,  A61B5/05

CPC分类号： G01N33/48707 ,  B01L3/5027

摘要： A measurement device 10 includes a measurement cell 11. The measurement cell 11 includes a substrates 17 and a substrate 16 formed on the substrate 17. The substrates 16 and 17 are bonded to each other. Thus, a flow pass 9 is formed in the measurement cell 11. As shown in FIG. 3, on the substrate 17 of the measurement cell 11, provided are a concave well 19, a protruding microelectrode 1 connected to a terminal 4a and formed on a side wall surface of the well 19, communicating tubes 15a and 15b connected to both of side surfaces of the well 19 (i.e., the flow pass 9) to face to each other, resistance baths 6a and 6b connected to the communicating tubes 15a and 15b, thin film resistors 3a and 3b arranged in the resistance baths 6a and 6b, and a reference electrode 2 connected to a terminal 4b.

摘要翻译： 测量装置10包括测量单元11.测量单元11包括基板17和形成在基板17上的基板16.基板16和17彼此接合。 因此，在测量单元11中形成流路9。 如图3所示，在测量单元11的基板17上设置凹槽19，连接到端子4a并形成在井19的侧壁表面上的突出微电极1，连接到两侧的连通管15a和15b 孔19的表面（即，流路9）彼此相对，连接到连通管15a和15b的电阻槽6a和6b，布置在电阻槽6a和6b中的薄膜电阻器3a和3b，以及 参考电极2连接到端子4b。

公开(公告)号：US06890762B1

公开(公告)日：2005-05-10

申请号：US08913811

申请日：1997-01-24

申请人： Hirokazu Sugihara ,  Yasushi Kobayashi ,  Hiroaki Oka ,  Ryuta Ogawa ,  Makoto Taketani

发明人： Hirokazu Sugihara ,  Yasushi Kobayashi ,  Hiroaki Oka ,  Ryuta Ogawa ,  Makoto Taketani

IPC分类号： C12Q1/02 ,  G01N33/50 ,  G01N33/567 ,  C12Q1/04 ,  G01N33/48 ,  G01N33/53 ,  C12N27/00

CPC分类号： G01N33/5005 ,  C12Q1/02 ,  Y10S436/806 ,  Y10S436/807

摘要： A method of measuring the physical and chemical properties of tissue or cells and a device for the same is provided, with which the physical and chemical environment of the tissue or cells can be changed arbitrarily corresponding to experimental necessities. The device comprises a system 40 for keeping the physical and chemical environment surrounding the biological tissue or cells constant, a system 50 for arbitrarily changing the physical and chemical environment, observation systems 10 and 20 for observing the physical and chemical properties of the tissue or cells, and a system 30 for comparing the change of the physical and chemical properties of the tissue or cells before and after changing the physical and chemical environment. The observation system 10 is a potential measurement device for measuring the electrophysiological properties of the tissue or cells. This device comprises an integrated cell placement device 1 provided with a plurality of microelectrodes 11 on a substrate, a cell placement portion 6 for placing the tissue or cells on the microelectrodes 11, and a wiring pattern 12 for applying an electrical signal to the microelectrodes 11 and extracting an electrical signal from the microelectrodes 11.

摘要翻译： 提供了一种测量组织或细胞的物理和化学性质的方法及其装置，通过该方法可以根据实验需要任意改变组织或细胞的物理和化学环境。 该装置包括用于保持生物组织或细胞周围的物理和化学环境恒定的系统40，用于任意改变物理和化学环境的系统50，用于观察组织或细胞的物理化学性质的观察系统10和20 以及用于比较在改变物理和化学环境之前和之后组织或细胞的物理和化学性质的变化的系统30。 观察系统10是用于测量组织或细胞的电生理特性的电位测量装置。 该装置包括在基板上设置有多个微电极11的集成电池放置装置1，用于将组织或电池放置在微电极11上的电池放置部分6以及用于向微电极11施加电信号的布线图案12 以及从微电极11提取电信号。

公开(公告)号：US6132683A

公开(公告)日：2000-10-17

申请号：US220981

申请日：1998-12-23

申请人： Hirokazu Sugihara ,  Hiroaki Oka ,  Ken Shimono ,  Ryuta Ogawa ,  Makoto Taketani

发明人： Hirokazu Sugihara ,  Hiroaki Oka ,  Ken Shimono ,  Ryuta Ogawa ,  Makoto Taketani

IPC分类号： C12M1/34 ,  G01N33/487 ,  G01N27/26

CPC分类号： C12M41/46 ,  G01N33/4836

摘要： This invention relates to a low impedance cell potential measuring electrode assembly typically having a number of microelectrodes on an insulating substrate and having a wall enclosing the region including the microelectrodes. The device is capable of measuring electrophysiological activities of a monitored sample using the microelectrodes while cultivating those cells or tissues in the in the region of the microelectrodes. The invention utilizes independent reference electrodes to lower the impedance of the overall system and to therefore lower the noise often inherent in the measured data. Optimally the microelectrodes are enclosed by a physical wall used for controlling the atmosphere around the monitored sample.