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1. 再颁专利

USRE38323E1 Cell potential measurement apparatus having a plurality of microelectrodes 有权
标题翻译：具有多个微电极的电池电位测量装置
公开(公告)号：USRE38323E1
公开(公告)日：2003-11-18
申请号：US09169188
申请日：1998-10-08
申请人： Hirokazu Sugihara , Akihito Kamei , Yasushi Kobayashi , Makoto Taketani , Tadayasu Mitsumata
发明人： Hirokazu Sugihara , Akihito Kamei , Yasushi Kobayashi , Makoto Taketani , Tadayasu Mitsumata
IPC分类号： C12M134
CPC分类号： G01N33/4836 , C12M41/46
摘要： A cell potential measurement apparatus, which uses a planar electrode enabling a multi-point simultaneous measurement of potential change arising from cell activities, is provided which can conduct measurements accurately and efficiently as well as can improve convenience of arranging measurement results. According to the configuration of the cell potential measurement apparatus of this invention, it includes an integrated cell holding instrument, which includes a planar electrode provided with a plurality of microelectrodes arranged in a matrix form on the surface of a substrate, a cell holding part for placing cells thereon, drawer patterns from the microelectrodes, and electric contact points for outside connections; an optical observation means for optical observations of cells; a stimulation signal supply means to be connected to the cell holding instrument for providing electric stimulation to the cells; and a signal processing means to be connected to the cell holding instrument for processing an output signal arising from electric physiological activities of the cells. It is preferable that a cell culturing means is also provided for maintaining a culture atmosphere of the cells placed on the integrated cell holding instrument.

2. 发明授权

US06297025B1 Measurement of complete electrical waveforms of tissue or cells 失效
标题翻译：测量组织或细胞的完整电波形
公开(公告)号：US06297025B1
公开(公告)日：2001-10-02
申请号：US08662629
申请日：1996-06-13
申请人： Hirokazu Sugihara , Akihito Kamei , Yasushi Kobayashi , Makoto Taketani , Tadayasu Mitsumata
发明人： Hirokazu Sugihara , Akihito Kamei , Yasushi Kobayashi , Makoto Taketani , Tadayasu Mitsumata
IPC分类号： C12Q102
CPC分类号： G01N33/4836 , C12M21/08 , C12M41/00 , C12M41/46
摘要： A method of observing a physical and chemical property of a tissue or cell by using an apparatus which comprises at least a cell culturing means, an environment conditioning means, an observing means and a comparing means, comprising the steps of (A) culturing the tissue or cell by the cell culturing means, (B) maintaining a first physical and chemical environment around the tissue or cell by the cell culturing means, (C) observing a first physical and chemical property of the tissue or cell in the first physical and chemical environment by the observing means, (D) changing the first physical and chemical environment to a second physical and chemical environment by the environment conditioning means, (E) observing a second physical and chemical property of the tissue or cell in the second physical and chemical environment by the observing means, and (F) comparing the first physical and chemical property of the tissue or cell with the second physical and chemical property of the tissue or cell by the comparing means.
摘要翻译：通过使用至少包含细胞培养装置，环境调节装置，观察装置和比较装置的装置观察组织或细胞的物理和化学性质的方法，包括以下步骤：（A）培养组织或细胞，（B）通过细胞培养装置保持组织或细胞周围的第一物理和化学环境;（C）观察第一物理和化学物质中组织或细胞的第一物理和化学性质环境，（D）通过环境调节装置将第一物理化学环境改变为第二物理化学环境;（E）观察第二物理和化学中组织或细胞的第二物理和化学性质环境，以及（F）将组织或细胞的第一物理和化学性质与组织的第二物理和化学性质进行比较或细胞。

3. 再颁专利

USRE40209E1 Cell potential measurement apparatus having a plurality of microelectrodes 有权
标题翻译：具有多个微电极的电池电位测量装置
公开(公告)号：USRE40209E1
公开(公告)日：2008-04-01
申请号：US09688077
申请日：2000-10-13
申请人： Hirokazu Sugihara , Akihito Kamei , Yasushi Kobayashi , Makoto Taketani , Tadayasu Mitsumata
发明人： Hirokazu Sugihara , Akihito Kamei , Yasushi Kobayashi , Makoto Taketani , Tadayasu Mitsumata
IPC分类号： C12M1/34
CPC分类号： C12M41/46 , G01N33/48728
摘要： A cell potential measurement apparatus, which uses a planar electrode enabling a multi-point simultaneous measurement of potential change arising from cell activities, is provided which can conduct measurements accurately and efficiently as well as can improve convenience of arranging measurement results. According to the configuration of the cell potential measurement apparatus of this invention, it includes an integrated cell holding instrument, which includes a planar electrode provided with a plurality of microelectrodes arranged in a matrix form on the surface of a substrate, a cell holding part for placing cells thereon, drawer patterns from the microelectrodes, and electric contact points for outside connections; an optical observation means for optical observations of cells; a stimulation signal supply means to be connected to the cell holding instrument for providing electric stimulation to the cells; and a signal processing means to be connected to the cell holding instrument for processing an output signal arising from electric physiological activities of the cells. It is preferable that a cell culturing means is also provided for maintaining a culture atmosphere of the cells placed on the integrated cell holding instrument.
摘要翻译：提供一种电池电位测量装置，其使用能够进行多点同时测量由电池活动引起的电位变化的平面电极，其可以精确且有效地进行测量，并且可以提高排列测量结果的便利性。根据本发明的电池电位测量装置的结构，它包括一个集成的电池保持仪器，它包括一个平面电极，该平面电极设置有以矩阵形式布置在基片表面上的多个微电极，在其上放置电池，来自微电极的抽屉图案和用于外部连接的电接触点; 用于细胞光学观察的光学观察装置; 刺激信号提供装置，连接到用于向细胞提供电刺激的细胞保持仪器; 以及信号处理装置，其连接到用于处理由电池的电生理活动引起的输出信号的电池保持装置。还优选还设置有用于维持放置在集成电池保持器具上的电池的培养气氛的细胞培养装置。

4. 发明授权

US5563067A Cell potential measurement apparatus having a plurality of microelectrodes 失效
标题翻译：具有多个微电极的电池电位测量装置
公开(公告)号：US5563067A
公开(公告)日：1996-10-08
申请号：US464116
申请日：1995-06-05
申请人： Hirokazu Sugihara , Akihito Kamei , Yasushi Kobayashi , Makoto Taketani , Tadayasu Mitsumata
发明人： Hirokazu Sugihara , Akihito Kamei , Yasushi Kobayashi , Makoto Taketani , Tadayasu Mitsumata
IPC分类号： C12M1/34 , G01N27/403 , G01N33/487
CPC分类号： G01N33/4836 , C12M41/46
摘要： A cell potential measurement apparatus, which uses a planar electrode enabling a multi-point simultaneous measurement of potential change arising from cell activities, is provided which can conduct measurements accurately and efficiently as well as can improve convenience of arranging measurement results. According to the configuration of the cell potential measurement apparatus of this invention, it includes an integrated cell holding instrument, which includes a planar electrode provided with a plurality of microelectrodes arranged in a matrix form on the surface of a substrate, a cell holding part for placing cells thereon, drawer patterns from the microelectrodes, and electric contact points for outside connections; an optical observation means for optical observations of cells; a stimulation signal supply means to be connected to the cell holding instrument for providing electric stimulation to the cells; and a signal processing means to be connected to the cell holding instrument for processing an output signal arising from electric physiological activities of the cells. It is preferable that a cell culturing means is also provided for maintaining a culture atmosphere of the cells placed on the integrated cell holding instrument.
摘要翻译：提供一种电池电位测量装置，其使用能够进行多点同时测量由电池活动引起的电位变化的平面电极，其可以精确且有效地进行测量，并且可以提高排列测量结果的便利性。根据本发明的电池电位测量装置的结构，它包括一个集成的电池保持仪器，它包括一个平面电极，该平面电极设置有以矩阵形式布置在基片表面上的多个微电极，在其上放置电池，来自微电极的抽屉图案和用于外部连接的电接触点; 用于细胞光学观察的光学观察装置; 刺激信号提供装置，连接到用于向细胞提供电刺激的细胞保持仪器; 以及信号处理装置，其连接到用于处理由电池的电生理活动引起的输出信号的电池保持装置。还优选还设置有用于维持放置在集成电池保持器具上的电池的培养气氛的细胞培养装置。

5. 发明授权

US5810725A Planar electrode 失效
标题翻译：平面电极
公开(公告)号：US5810725A
公开(公告)日：1998-09-22
申请号：US481149
申请日：1995-06-07
申请人： Hirokazu Sugihara , Makoto Taketani , Tadayasu Mitsumata
发明人： Hirokazu Sugihara , Makoto Taketani , Tadayasu Mitsumata
IPC分类号： A61N1/04 , A61N1/05 , G01N33/483 , G01N33/487 , A61B5/04
CPC分类号： G01N33/48728 , A61N1/0456 , A61N1/0476 , A61N1/0496 , A61N1/0551 , A61N1/0464 , A61N1/0488 , A61N1/0553
摘要： A planar electrode which enables multi-point simultaneous stimulation and recording of nerve cells over a long time is provided, which also has excellent response property. An ITO film is evaporated on the whole surface of an insulating substrate of the hard glass, and the ITO film is etched so that the central portion of each electrode is located on each intersection of 8.times.8 lattices, the center-to-center distances of nearest electrodes of each electrode are equal, and a lead wire is stretched radially. Then, for an insulating layer, negative photo-sensitive polyimide is spin-coated, and an insulating layer pattern is exposure-formed so that a 50 .mu.ms square hole is produced at the center of each electrode. Furthermore, to the exposed portion of each electrode (that is, the inside of the 50 .mu.ms square), Ni is evaporated in a film thickness of 500 nm, which is followed by evaporating gold (50 nm) and platinum black (about 1 .mu.m ). The contact with the external circuit of the section near the end opposite to the electrode of the lead wire was coated with gold and nickel.
摘要翻译：提供了能够长时间多点同时刺激和记录神经细胞的平面电极，其也具有优异的响应特性。在硬质玻璃的绝缘基板的整个表面上蒸发ITO膜，蚀刻ITO膜，使得每个电极的中心部分位于8×8晶格的每个交点上，中心距离最近每个电极的电极相等，引线径向拉伸。然后，对于绝缘层，旋转涂覆负光敏聚酰亚胺，并且将曝光形成绝缘层图案，使得在每个电极的中心处产生50微米的方孔。此外，对于每个电极的曝光部分（即，50μs均方的内部），以500nm的膜厚度蒸发Ni，然后蒸发金（50nm）和铂黑（约1 亩）。与导线的电极相对的端部附近的部分的外部电路的接触涂覆有金和镍。

6. 发明授权

US6151519A Planar electrode 有权
标题翻译：平面电极
公开(公告)号：US6151519A
公开(公告)日：2000-11-21
申请号：US160252
申请日：1998-09-22
申请人： Hirokazu Sugihara , Makoto Taketani , Tadayasu Mitsumata
发明人： Hirokazu Sugihara , Makoto Taketani , Tadayasu Mitsumata
IPC分类号： A61N1/04 , A61N1/05 , G01N33/483 , G01N33/487 , A61B5/04
CPC分类号： G01N33/48728 , A61N1/0456 , A61N1/0476 , A61N1/0496 , A61N1/0551 , A61N1/0464 , A61N1/0488 , A61N1/0553
摘要： A planar electrode which enables multi-point simultaneous stimulation and recording of nerve cells over a long time is provided, which also has excellent response property. An ITO film is evaporated on the whole surface of an insulating substrate of the hard glass, and the ITO film is etched so that the central portion of each electrode is located on each intersection of 8.times.8 lattices, the center-to-center distances of nearest electrodes of each electrode are equal, and a lead wire is stretched radially. Then, for an insulating layer, negative photo-sensitive polyimide is spin-coated, and an insulating layer pattern is exposure-formed so that a 50 .mu.ms square hole is produced at the center of each electrode. Furthermore, to the exposed portion of each electrode (that is, the inside of the 50 .mu.ms square), Ni is evaporated in a film thickness of 500 nm, which is followed by evaporating gold (50 nm) and platinum black (about 1 .mu.m). The contact with the external circuit of the section near the end opposite to the electrode of the lead wire was coated with gold and nickel.
摘要翻译：提供了能够长时间多点同时刺激和记录神经细胞的平面电极，其也具有优异的响应特性。在硬质玻璃的绝缘基板的整个表面上蒸发ITO膜，蚀刻ITO膜，使得每个电极的中心部分位于8×8晶格的每个交点处，最近的中心距离每个电极的电极相等，引线径向拉伸。然后，对于绝缘层，旋转涂覆负光敏聚酰亚胺，并且将曝光形成绝缘层图案，使得在每个电极的中心处产生50微米的方孔。此外，对于每个电极的曝光部分（即，50μs均方的内部），以500nm的膜厚度蒸发Ni，然后蒸发金（50nm）和铂黑（约1 亩）。与导线的电极相对的端部附近的部分的外部电路的接触涂覆有金和镍。

7. 发明授权

US06288527B1 Two-dimensional sensor using laps for measuring cell activity 失效
标题翻译：二维传感器使用圈测量细胞活性
公开(公告)号：US06288527B1
公开(公告)日：2001-09-11
申请号：US08661314
申请日：1996-06-13
申请人： Hirokazu Sugihara , Makoto Taketani , Akihito Kamei , Hiroshi Iwasaki
发明人： Hirokazu Sugihara , Makoto Taketani , Akihito Kamei , Hiroshi Iwasaki
IPC分类号： G01N2700
CPC分类号： G01N33/48728 , G01N27/305 , Y10S436/806
摘要： A two-dimensional sensor is described including a substrate having a Si layer, a SiO2 layer and a Si3N4 layer. On the surface of the Si back side, a thin film is formed by vapor deposition for making an effect electrode. On the surface of the Si3N4 front side, a fence is attached for containing a sample cell, culture medium and a reference electrode. This sensor is placed in an incubator and a bias voltage is applied between the effect and reference electrodes. When a high frequency modulated laser beam irradiates a spot on the back side of the sensor substrate, a signal of AC photocurrent is obtained from the effect electrode. This signal corresponds to a potential alteration due to the cell activity substantially at the spot. The signal is processed in a computer. Therefore, the beam spot size and location, corresponding to the size and the location of the measurement electrode, can be adjusted easily by focusing or moving the laser beam.
摘要翻译：描述了包括具有Si层，SiO 2层和Si 3 N 4层的衬底的二维传感器。在Si背面的表面上，通过气相沉积形成用于制作效应电极的薄膜。在Si3N4正面的表面上，附着有用于容纳样品池，培养基和参比电极的栅栏。将该传感器放置在培养箱中，并且在效果和参考电极之间施加偏置电压。当高频调制激光束照射传感器基板的背面的点时，从效应电极获得AC光电流的信号。该信号对应于由于细胞活性基本上在斑点的潜在的改变。信号在计算机中处理。因此，可以通过聚焦或移动激光束来容易地调整对应于测量电极的尺寸和位置的束斑尺寸和位置。

8. 发明授权

US06281670B1 Two-dimensional sensor having photoconductive layer for measuring cell activity 失效
标题翻译：具有用于测量细胞活性的光电导层的二维传感器
公开(公告)号：US06281670B1
公开(公告)日：2001-08-28
申请号：US08661316
申请日：1996-06-13
申请人： Hirokazu Sugihara , Makoto Taketani , Akihito Kamei , Hiroshi Iwasaki
发明人： Hirokazu Sugihara , Makoto Taketani , Akihito Kamei , Hiroshi Iwasaki
IPC分类号： G01N2700
CPC分类号： G01N33/48728 , G01N27/305 , Y10S436/806
摘要： A two-dimensional sensor includes a photoconductive layer whose conductivity increases at a light-irradiated spot, an insulating layer formed on the front surface of the photoconductive layer, an effect electrode formed on the back surface of the photoconductive layer, and a fence as a cell holder attached to the surface of the insulating layer for containing a cell, culture medium and a reference electrode. The sensor is placed in an incubator and a bias voltage is applied between the effect and reference electrodes. When a laser beam irradiates a spot of the back surface of the sensor, a signal is obtained from the effect electrode. This signal corresponds to a potential alteration due to the cell activity substantially at the laser-irradiated spot. The signal is processed in a computer. The beam spot size and location, corresponding to the size and the location of the measurement electrode, can be changed or adjusted easily by focusing or moving the laser beam.
摘要翻译：二维传感器包括在光照射点处的导电率增加的光电导层，形成在光电导层的前表面上的绝缘层，形成在光电导层的背面上的效应电极和作为附着在用于容纳细胞，培养基和参比电极的绝缘层的表面上的细胞保持器。将传感器放置在培养箱中，并在效应和参比电极之间施加偏压。当激光束照射传感器的背面的点时，从效应电极获得信号。该信号对应于由于细胞活性基本上在激光照射点处的电位改变。信号在计算机中处理。可以通过聚焦或移动激光束来容易地改变或调整对应于测量电极的尺寸和位置的束斑尺寸和位置。

9. 发明授权

US06890762B1 Method for measuring physiocochemical properties of tissues of cells, method for examining chemicals, and apparatus therefor 失效
标题翻译：用于测量细胞组织的生理化学性质的方法，用于检查化学品的方法及其装置
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。

10. 发明授权

US5233025A Amphetamine protein complex as immunogen for obtaining antibodies specific to methamphetamine 失效
标题翻译：安非他明蛋白复合物作为获得甲基苯丙胺特异性抗体的免疫原
公开(公告)号：US5233025A
公开(公告)日：1993-08-03
申请号：US651809
申请日：1991-02-07
申请人： Jinsei Miyazaki , Makoto Taketani , Tadayasu Mitsumata
发明人： Jinsei Miyazaki , Makoto Taketani , Tadayasu Mitsumata
IPC分类号： A61K47/48 , C07K16/44 , G01N33/531
CPC分类号： G01N33/531 , A61K47/4833 , C07K16/44
摘要： A N-(4-aminobutyl)amphetamine-protein complex has been synthesized to be used as an immunogen to prepare an antibody having a higher affinity to methamphetamine that to the hapten N-(4-aminobutyl)amphetamine. The antibody prepared by the use of the complex has 1,000 times the affinity to methamphetamine as that of an antibody prepeared by the use of N-(4-aminobutyl)methamphetamine-protein complex as an immunogen.
摘要翻译：已经合成了N-（4-氨基丁基）苯丙胺 - 蛋白质复合物作为免疫原，以制备对半抗原N-（4-氨基丁基）苯丙胺具有较高的对甲基苯丙胺的亲和力的抗体。通过使用该复合物制备的抗体与通过使用N-（4-氨基丁基）甲基苯丙胺 - 蛋白复合物作为免疫原而展示的抗体的甲基苯丙胺的亲和力为1,000倍。

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