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1. 发明授权

US09447447B2 Method and apparatus for testing cardiotoxicity and evaluating cardiomyocytes 有权
标题翻译：用于测试心脏毒性和评估心肌细胞的方法和装置
公开(公告)号：US09447447B2
公开(公告)日：2016-09-20
申请号：US13876992
申请日：2011-09-30
申请人： Kenji Yasuda , Tomoyuki Kaneko , Fumimasa Nomura
发明人： Kenji Yasuda , Tomoyuki Kaneko , Fumimasa Nomura
IPC分类号： C12M1/34 , C12Q1/02 , C12M1/42 , C12M1/36 , G01N33/50
CPC分类号： C12Q1/025 , C12M35/02 , C12M41/46 , C12M41/48 , G01N33/48728 , G01N33/5061 , G01N33/5088 , G01N2800/32
摘要： In the present invention, a cardiomyocyte cluster is disposed on a transparent substrate, and the quality of the cardiomyocytes is evaluated from the response of the cells to a forced pulsation stimulus applied to the cardiomyocytes. The cardiomyocyte cluster is disposed on the transparent substrate, and is exposed to the flow of a liquid containing an agent in a manner so that the agent acts on the cells, which configure a network. The extent of cardiac toxicity resulting from the agent is evaluated from measuring the fluctuations obtained from a comparison of adjacent cardiomyocytes of the network.
摘要翻译：在本发明中，将心肌细胞簇设置在透明基质上，根据细胞对施加于心肌细胞的强制脉动刺激的反应来评价心肌细胞的质量。将心肌细胞簇设置在透明基板上，并且以使得试剂作用于构成网络的细胞的方式暴露于含有试剂的液体的流动。通过测量从网络的相邻心肌细胞的比较获得的波动来评估由该试剂产生的心脏毒性的程度。

2. 发明申请

US20100178692A1 MODEL CELL CHIP, APPARATUS FOR EVALUATING DRUG EFFECT USING THE MODEL CELL CHIP AND METHOD OF EVALUATING DRUG EFFECT 有权
标题翻译：模型细胞芯片，使用模型细胞芯片评估药物效应的装置和评估药物效应的方法
公开(公告)号：US20100178692A1
公开(公告)日：2010-07-15
申请号：US12663468
申请日：2008-06-06
申请人： Kenji Yasuda , Atsushi Sugiyama , Kentaro Ando , Fumimasa Nomura , Hideyuki Terazono , Tomoyuki Kaneko , Mamoru Fukushima
发明人： Kenji Yasuda , Atsushi Sugiyama , Kentaro Ando , Fumimasa Nomura , Hideyuki Terazono , Tomoyuki Kaneko , Mamoru Fukushima
IPC分类号： C12M1/34
CPC分类号： G01N33/5061 , C12N2503/02 , G01N33/4836 , G01N33/54366
摘要： The present invention provides an apparatus for evaluating a drug effect enabling on-chip evaluation of the effect of a drug while the drug is acting on hERG-expressing cells. The present invention also provides a myocardial toxicity test apparatus and method therefor enabling in vitro myocardial toxicity testing that has previously been performed in vivo.A pulsating cell population and hERG-expressing cells (target model cells) are suitably isolated and arranged on a transparent substrate so that the two form gap junctions. The hERG-expressing cells are arranged on transparent electrodes provided on the transparent substrate. The hERG-expressing cells are exposed to a flow of a liquid containing a drug such that the drug acts thereon. The difference between the normal pulsation of hERG-expressing cells and the pulsation when a drug is acting thereon is captured via electric signals obtained from electrodes, and the properties of the change in potential are evaluated.
摘要翻译：本发明提供了一种药物效应评价装置，其能够在药物作用于表达hERG的细胞的同时对药物的作用进行片上评价。本发明还提供一种心肌毒性试验装置及其方法，其能够进行体外心肌毒性试验，其先前已在体内进行。脉动细胞群体和表达hERG的细胞（靶模型细胞）被适当地分离并排列在透明基底上，使得两个形成间隙连接。 hERG表达细胞设置在设置在透明基板上的透明电极上。将表达hERG的细胞暴露于含有药物的液体流中，使药物作用于其上。通过从电极获得的电信号捕获hERG表达细胞的正常脉动与药物作用于其上的脉动之间的差异，并评估电位变化的性质。

3. 发明申请

US20130230881A1 METHOD AND APPARATUS FOR TESTING CARDIOTOXICITY AND EVALUATING CARDIOMYOCYTES 有权
标题翻译：用于测试心脏病毒和评估心脏病的方法和装置
公开(公告)号：US20130230881A1
公开(公告)日：2013-09-05
申请号：US13876992
申请日：2011-09-30
申请人： Kenji Yasuda , Tomoyuki Kaneko , Fumimasa Nomura
发明人： Kenji Yasuda , Tomoyuki Kaneko , Fumimasa Nomura
IPC分类号： C12Q1/02
CPC分类号： C12Q1/025 , C12M35/02 , C12M41/46 , C12M41/48 , G01N33/48728 , G01N33/5061 , G01N33/5088 , G01N2800/32
摘要： In the present invention, a cardiomyocyte cluster is disposed on a transparent substrate, and the quality of the cardiomyocytes is evaluated from the response of the cells to a forced pulsation stimulus applied to the cardiomyocytes. The cardiomyocyte cluster is disposed on the transparent substrate, and is exposed to the flow of a liquid containing an agent in a manner so that the agent acts on the cells, which configure a network. The extent of cardiac toxicity resulting from the agent is evaluated from measuring the fluctuations obtained from a comparison of adjacent cardiomyocytes of the network.
摘要翻译：在本发明中，将心肌细胞簇设置在透明基质上，根据细胞对施加于心肌细胞的强制脉动刺激的反应来评价心肌细胞的质量。将心肌细胞簇设置在透明基板上，并且以使得试剂作用于构成网络的细胞的方式暴露于含有试剂的液体的流动。通过测量从网络的相邻心肌细胞的比较获得的波动来评估由该试剂产生的心脏毒性的程度。

4. 发明授权

US08202720B2 Model cell chip, apparatus for evaluating drug effect using the model cell chip and method of evaluating drug effect 有权
标题翻译：模型细胞芯片，使用模型细胞芯片评估药物效应的装置和药物效应评价方法
公开(公告)号：US08202720B2
公开(公告)日：2012-06-19
申请号：US12663468
申请日：2008-06-06
申请人： Kenji Yasuda , Atsushi Sugiyama , Kentaro Ando , Fumimasa Nomura , Hideyuki Terazono , Tomoyuki Kaneko , Mamoru Fukushima
发明人： Kenji Yasuda , Atsushi Sugiyama , Kentaro Ando , Fumimasa Nomura , Hideyuki Terazono , Tomoyuki Kaneko , Mamoru Fukushima
IPC分类号： C12M1/34 , C12M3/00 , C12N5/071 , A61K35/34
CPC分类号： G01N33/5061 , C12N2503/02 , G01N33/4836 , G01N33/54366
摘要： The present invention provides an apparatus for evaluating a drug effect enabling on-chip evaluation of the effect of a drug while the drug is acting on hERG-expressing cells. The present invention also provides a myocardial toxicity test apparatus and method therefor enabling in vitro myocardial toxicity testing that has previously been performed in vivo. A pulsating cell population and hERG-expressing cells (target model cells) are suitably isolated and arranged on a transparent substrate so that the two form gap junctions. The hERG-expressing cells are arranged on transparent electrodes provided on the transparent substrate. The hERG-expressing cells are exposed to a flow of a liquid containing a drug such that the drug acts thereon. The difference between the normal pulsation of hERG-expressing cells and the pulsation when a drug is acting thereon is captured via electric signals obtained from electrodes, and the properties of the change in potential are evaluated.
摘要翻译：本发明提供了一种药物效应评价装置，其能够在药物作用于表达hERG的细胞的同时对药物的作用进行片上评价。本发明还提供一种心肌毒性试验装置及其方法，其能够进行体外心肌毒性试验，其先前已在体内进行。脉动细胞群体和表达hERG的细胞（靶模型细胞）被适当地分离并排列在透明基底上，使得两个形成间隙连接。 hERG表达细胞设置在设置在透明基板上的透明电极上。将表达hERG的细胞暴露于含有药物的液体流中，使药物作用于其上。通过从电极获得的电信号捕获hERG表达细胞的正常脉动与药物作用于其上的脉动之间的差异，并评估电位变化的性质。

5. 发明授权

US08877457B2 Device for examining myocardial toxicity, chip for examining myocardial toxicity and method for examining myocardial toxicity 有权
标题翻译：用于检查心肌毒性的装置，用于检查心肌毒性的芯片和检查心肌毒性的方法
公开(公告)号：US08877457B2
公开(公告)日：2014-11-04
申请号：US13132781
申请日：2009-12-04
申请人： Kenji Yasuda , Atsushi Sugiyama , Tomoyuki Kaneko , Fumimasa Nomura
发明人： Kenji Yasuda , Atsushi Sugiyama , Tomoyuki Kaneko , Fumimasa Nomura
IPC分类号： C12Q1/02 , C12M1/34 , C12M3/00 , G01N33/50
CPC分类号： G01N33/5014 , C12N2503/02 , G01N33/48728 , G01N33/5061
摘要： Provided is a device and a method for examining myocardial toxicity, which can be realized in vitro in an equivalent manner as those conventionally carried out in vivo. A cell population as a pulsating pacemaker is arranged on a transparent substrate. Myocardial pulsating cells are arranged while being spaced apart appropriately. Fibroblast cells are arranged with/connected to the myocardial pulsating cells to form a cell network. Each of the myocardial pulsating cells and fibroblast cells forming the network is arranged on a transparent electrode provided on the transparent substrate. The cells forming the network are exposed to a flow of a solution containing a drug and QT delay due to the drug is evaluated.
摘要翻译：提供了一种用于检查心肌毒性的装置和方法，其可以以与在体内常规进行的那些相同的方式在体外实现。作为脉动起搏器的细胞群被布置在透明基底上。心肌搏动细胞被布置成适当间隔开。成纤维细胞与心肌脉动细胞排列/连接，形成细胞网络。形成网络的心肌脉动细胞和成纤维细胞分别设置在透明基板上的透明电极上。形成网络的细胞暴露于包含药物的溶液的流动并且由于药物的QT延迟被评估。

6. 发明申请

US20110262958A1 DEVICE FOR EXAMINING MYOCARDIAL TOXICITY, CHIP FOR EXAMINING MYOCARDIAL TOXICITY AND METHOD FOR EXAMINING MYOCARDIAL TOXICITY 有权
标题翻译：用于检查肌肉毒性的装置，用于检查心肌细胞毒性的芯片和检查心肌细胞毒性的方法
公开(公告)号：US20110262958A1
公开(公告)日：2011-10-27
申请号：US13132781
申请日：2009-12-04
申请人： Kenji Yasuda , Atsushi Sugiyama , Tomoyuki Kaneko , Fumimasa Nomura
发明人： Kenji Yasuda , Atsushi Sugiyama , Tomoyuki Kaneko , Fumimasa Nomura
IPC分类号： C12Q1/02 , C12M1/34
CPC分类号： G01N33/5014 , C12N2503/02 , G01N33/48728 , G01N33/5061
摘要： [Problem] To provide a device and a method for examining myocardial toxicity, which can be realized in vitro in an equivalent manner as those conventionally carried out in vivo.[Means for Solving the Problem] A cell population as a pulsating pacemaker is arranged on a transparent substrate, and then myocardial pulsating cells are arranged while being spaced apart appropriately. An appropriate number of fibroblast cells are arranged with/connected to the myocardial pulsating cells to form a cell network. Each of the myocardial pulsating cells and fibroblast cells forming the network is arranged on a transparent electrode provided on the transparent substrate. This cell network can be optically observed. The cells forming the network are exposed to a flow of a solution containing a drug. Na+ ion inhibition is evaluated by obtaining, as electric signals from the electrodes, difference between normal delay of propagation of pulse from one of the myocardial pulsating cells of the network to the last myocardial pulsating cell and delay of the same upon addition of a drug. Pulsation of one of the myocardial pulsating cells in the network is optically captured to detect change in the volume thereof to detect contraction rate upon action of a drug, thereby evaluating cardiac output. Pulsation of one of the myocardial pulsating cells in the network is electrically captured to determine influx/efflux amounts of Na+ ion, Ca2+ ion and K+ ion components, thereby evaluating QT delay due to the drug.
摘要翻译： [问题]提供一种用于检查心肌毒性的装置和方法，其可以以与在体内常规进行的那些相同的方式在体外实现。解决问题的手段将作为脉动起搏器的细胞群体布置在透明基底上，然后心轴脉动细胞被布置成适当间隔开。将合适数量的成纤维细胞与心肌脉冲细胞排列/连接以形成细胞网络。形成网络的心肌脉动细胞和成纤维细胞分别设置在透明基板上的透明电极上。可以光学观察该细胞网络。形成网络的细胞暴露于含有药物的溶液流中。通过从电极的电信号获得脉冲从网络的心肌搏动细胞到最后一个心肌搏动细胞的传播的正常延迟之间的差异以及在添加药物时的延迟来评估Na +离子抑制。在网络中的一个心肌搏动细胞的脉冲被光学捕获以检测其体积的变化以检测药物作用时的收缩率，从而评估心输出量。电网捕获心肌搏动细胞之一的脉冲，以确定Na +离子，Ca 2+离子和K +离子成分的流入/流出量，从而评估药物引起的QT延迟。

7. 发明申请

US20100173351A1 CARDIAC REENTRY MODEL CHIP AND APPARATUS AND METHOD FOR EVALUATING DRUG USING THE CARDIAC REENTRY MODEL CHIP 审中-公开
标题翻译：心脏复苏模型芯片和装置以及使用心脏重吸收模型评估药物的方法
公开(公告)号：US20100173351A1
公开(公告)日：2010-07-08
申请号：US12663441
申请日：2008-06-06
申请人： Kenji Yasuda , Atsushi Sugiyama , Kentaro Ando , Fumimasa Nomura , Hideyuki Terazono , Tomoyuki Kaneko , Mamoru Fukushima
发明人： Kenji Yasuda , Atsushi Sugiyama , Kentaro Ando , Fumimasa Nomura , Hideyuki Terazono , Tomoyuki Kaneko , Mamoru Fukushima
IPC分类号： C12Q1/02 , C12M1/00
CPC分类号： G01N33/5061 , G01N33/48728 , G01N33/5438
摘要： A chip has been developed that can accurately measure cell potential and cell morphology on a single cell basis. The chip also constitutes a cardiac model that comprises a closed loop whereupon cardiomyocytes and fibroblasts are suitably dispersed and arranged, and that can evaluate the effects of a drug thereon. An in vitro cardiac reentry model chip is fabricated by constructing a closed loop comprising cardiomyocytes and fibroblasts arrayed on transparent electrodes formed on a transparent substrate by using a constitution where single cells are enclosed in a specific spatial configuration. A pulse wave of a random cardiomyocyte or a specific cardiomyocyte is propagated on both sides of the loop, and the pulsation status of the cells in the loop is detected electrically. A drug is applied to this cardiac reentry model chip, and the benefit or toxicity of the drug to cardiomyocytes is evaluated by measuring the cell potentials of individual cells.
摘要翻译：已经开发了可以在单个细胞基础上精确测量细胞电位和细胞形态的芯片。该芯片还构成了心脏模型，其包括闭合环，由此心肌细胞和成纤维细胞适当地分散和排列，并且可以评价药物对其的影响。通过使用单细胞被封闭在特定的空间结构中的构造，构建包括心肌细胞和成纤维细胞的闭环，制成排列在透明电极上形成的透明电极上的闭环回路模型芯片。随机心肌细胞或特定心肌细胞的脉搏波在环的两侧传播，电路中检测到细胞的脉动状态。将药物应用于该心脏再入模型芯片，并通过测量个体细胞的细胞电位来评估药物对心肌细胞的益处或毒性。

8. 发明授权

US07868257B2 Via transmission lines for multilayer printed circuit boards 有权
标题翻译：通过多层印刷电路板的传输线
公开(公告)号：US07868257B2
公开(公告)日：2011-01-11
申请号：US10598134
申请日：2005-03-09
申请人： Taras Kushta , Kaoru Narita , Hirokazu Tohya , Takanori Saeki , Tomoyuki Kaneko
发明人： Taras Kushta , Kaoru Narita , Hirokazu Tohya , Takanori Saeki , Tomoyuki Kaneko
IPC分类号： H01R12/04 , H05K1/11
CPC分类号： H05K1/0222 , H05K1/0269 , H05K3/429 , H05K2201/09536 , H05K2201/09618 , H05K2201/09718 , H05K2201/09809
摘要： A via transmission line for a multilayer printed circuit board (PCB) in which a wave guiding channel is formed by a signal via or a number of signal vias, an assembly of ground vias surrounding the signal via or corresponding number of coupled signal vias, a set of ground plates from conductor layers of the multilayer PCB, and a clearance hole. In this via transmission line, the signal via, or the number of signal vias forms an inner conductive boundary, ground vias and ground plates from conductor layers of the multilayer PCB form an outer conductive boundary, and the clearance hole provides both isolation of the inner conductive boundary from the outer conductive boundary and high-performance broadband operation of the via transmission line by means of the predetermined clearance hole cross-sectional shape and dimensions where the cross-sectional shape of the clearance hole is defined by the arrangement of ground vias in the outer conductive boundary and dimensions of the clearance hole are determined according to a method to minimize frequency-dependent return losses caused by specific corrugations of the outer conductive boundary formed by ground plates in the wave guiding channel of the via transmission line.
摘要翻译：一种用于多层印刷电路板（PCB）的通孔传输线，其中通过信号通道或多个信号通路形成波导通道，围绕信号通孔或相应数量的耦合信号通孔的接地通孔的组件，多层PCB的导体层的接地板组以及间隙孔。在这个通过传输线路中，信号通孔或信号通道的数量形成内部导电边界，从多层PCB的导体层形成的接地孔和接地板形成外部导电边界，并且间隙孔提供内部通过外部导电边界的导电边界和通孔传输线的高性能宽带操作，借助于预定的间隙孔横截面形状和尺寸，其中间隙孔的横截面形状由接地通孔的布置根据通过在通孔传输线的波导通道中由接地板形成的外导电边界的特定波纹引起的频率相关的返回损耗的方法来确定间隙孔的外导电边界和尺寸。

9. 发明授权

US07463122B2 Compact via transmission line for printed circuit board and its designing method 有权
标题翻译：用于印刷电路板的紧凑型传输线及其设计方法
公开(公告)号：US07463122B2
公开(公告)日：2008-12-09
申请号：US10558888
申请日：2004-06-01
申请人： Taras Kushta , Kaoru Narita , Takanori Saeki , Tomoyuki Kaneko , Hirokazu Tohya
发明人： Taras Kushta , Kaoru Narita , Takanori Saeki , Tomoyuki Kaneko , Hirokazu Tohya
IPC分类号： H01P1/04
CPC分类号： H05K1/0222 , H01P3/06 , H05K1/024 , H05K1/0251 , H05K3/429 , H05K2201/0187 , H05K2201/09063 , H05K2201/09536 , H05K2201/09618 , H05K2201/09718 , H05K2201/09809
摘要： A compact via transmission line for a printed circuit board having preferred characteristic impedance and capable of miniaturizing the printed circuit board including a multilayer printed circuit board, and extending the frequency range of a via transmission line mounted on the printed circuit board, and a design method of the same. The transmission line has a central conductor forming an inner conductor layer boundary make up a signal via hole, a plurality of via holes arranged around the central conductor form an outer conductor layer boundary, and a plurality of conductor plates formed of a printed circuit board conductor layer, is further provided with a constitutive parameter adjustment clearance hole between the inner and outer conductor layer boundaries of the compact via transmission line, and electrically isolates to prevent cross-talk of a signal propagating through a signal via hole with other signals in a high-frequency signal band.
摘要翻译：一种用于具有优选特性阻抗并能够使包括多层印刷电路板的印刷电路板小型化并且扩展安装在印刷电路板上的通孔传输线的频率范围的印刷电路板的紧凑型通路传输线，以及设计方法一样的。传输线具有形成内导体层边界的中心导体，构成信号通孔，围绕中心导体布置的多个通孔形成外导体层边界，以及由印刷电路板导体形成的多个导体板通过传输线在压缩体的内部和外部导体层边界之间进一步设置本构参数调整间隙孔，并且电隔离以防止通过信号通孔传播的信号与其他信号在高电平中的串扰频率信号频带。

10. 发明申请

US20070209431A1 Inspection Method And Apparatus For Uneven Marks On Tire 有权
标题翻译：轮胎上不均匀标记的检查方法和装置
公开(公告)号：US20070209431A1
公开(公告)日：2007-09-13
申请号：US11596670
申请日：2005-05-18
申请人： Yoshitaka Fujisawa , Tomoyuki Kaneko
发明人： Yoshitaka Fujisawa , Tomoyuki Kaneko
IPC分类号： G01M17/02
CPC分类号： G06K9/2054 , G01B11/25 , G01M17/027
摘要： There are provided an inspection method of tire uneven marks capable of judging defect of three-dimensional form of the mark in a higher reliability without depending on a brightness distribution image of unevenness, and an inspection apparatus of tire uneven marks. The inspection method of tire uneven marks comprises a step of measuring heights of unevenness inclusive of marks to be inspected with respect to each area element in a predetermined tire surface region to acquire unevenness distribution data, a step of specifying a tire surface portion corresponding to a mark model in the tire surface region from data of three-dimensional form of a mark model previously prepared as a template of the each mark and the above acquired unevenness distribution data, and a step of determining a coincidence between the unevenness distribution data of the specified tire surface portion with respect to the each mark and data of three-dimensional form of the mark model to judge an acceptance of the three-dimensional form of the mark based on the coincidence.
摘要翻译：提供了一种轮胎不均匀标记的检查方法，其可以在不依赖于不均匀性的亮度分布图像的情况下以更高的可靠性判断标记的三维形状的缺陷，以及轮胎不均匀标记的检查装置。轮胎不均匀标记的检查方法包括以下步骤：在预定轮胎表面区域中测量相对于每个区域元件检查的标记的不平坦度的高度，以获取不均匀性分布数据;指定对应于根据预先准备为每个标记的模板的标记模型的三维形式的数据和上述获取的不均匀性分布数据，在轮胎表面区域中标记模型，以及确定指定的不均匀分布数据之间的一致性的步骤相对于每个标记的轮胎表面部分和标记模型的三维形式的数据，以基于重合来判断标记的三维形式的接受。

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