公开(公告)号：US20130029872A1

公开(公告)日：2013-01-31

申请号：US13639350

申请日：2011-04-04

申请人： Yu Ishige ,  Masao Kamahori ,  Yusuke Goto

发明人： Yu Ishige ,  Masao Kamahori ,  Yusuke Goto

IPC分类号： C40B40/10 ,  C40B30/04

CPC分类号： G01N33/569 ,  G01N27/3275 ,  G01N33/5438

摘要： Provided are a device, whereby cells, a bacterium or a virus can be quantified in a single unit, an assay system and an assay method. A subject to be assayed such as cells, a bacterium or a virus, which are present on a sensor, can be quantified by using a sensor equipped with multiple electrodes, said electrodes being similar in size to the subject to be assayed, detecting, concerning each electrode, the presence or absence of the subject in the vicinity of the electrode, and adding up the electrodes in which the subject is detected.

摘要翻译： 提供了一种装置，其中细胞，细菌或病毒可以在单个单位中量化，测定系统和测定方法。 可以通过使用配备有多个电极的传感器来量化存在于传感器上的诸如细胞，细菌或病毒的受试者，所述电极的尺寸与要测定的受试者相似，检测有关 每个电极，在电极附近存在或不存在受试者，并且将检测到被检体的电极相加。

公开(公告)号：US08323468B2

公开(公告)日：2012-12-04

申请号：US12081736

申请日：2008-04-21

申请人： Masao Kamahori ,  Yu Ishige ,  Kotaro Yamashita ,  Yasuhisa Shibata ,  Masafumi Miyake

发明人： Masao Kamahori ,  Yu Ishige ,  Kotaro Yamashita ,  Yasuhisa Shibata ,  Masafumi Miyake

IPC分类号： G01N27/333

CPC分类号： G01N27/414

摘要： A crown ether derivative that acts as cation capturing ligand and alkanethiol having a longer carbon chain than a linker are immobilized, coexisting together, on the surface of a gold electrode, by using as the linker an insulating molecule (e.g., alkanethiol) that forms self-assembled monolayers. Electromotive force produced in association with cation coordination is measured by a potentiometer through a change in interfacial potential on the surface of the gold electrode. Further, an insulated gate field effect transistor formed on the same substrate as the gold electrode is used as the potentiometer. Furthermore, a straight-chain polymer physically adsorbed on the gold electrode is used in order to reduce the influence of the adsorption of impurities on the surface of the electrode during biological sample measurement.

摘要翻译： 作为阳离子捕获配体的冠醚衍生物和具有比接头长的碳链的链烷硫醇通过使用形成自身的绝缘分子（例如，链烷硫醇）固定在金电极的表面上并存在一起，在金电极的表面上共存 组合单层。 通过电极计通过金电极表面的界面电位的变化来测量与阳离子配位相关产生的电动势。 此外，与金电极形成在同一衬底上的绝缘栅场效应晶体管被用作电位计。 此外，使用物理吸附在金电极上的直链聚合物，以便在生物样品测量期间减少杂质在电极表面上的吸附的影响。

公开(公告)号：US08128796B2

公开(公告)日：2012-03-06

申请号：US12155919

申请日：2008-06-11

申请人： Yu Ishige ,  Masao Kamahori

发明人： Yu Ishige ,  Masao Kamahori

IPC分类号： G01N33/487

CPC分类号： G01N33/492

摘要： It is an object of this invention to measure small amounts of a plurality of sample solutions at the same time. The small amounts of sample solutions are respectively placed on measuring electrodes, a medium is placed across the plurality of sample solutions, a liquid joint of a reference electrode is brought into contact with the medium, and a potential difference between each of the measuring electrodes and the reference electrode via the medium is measured.

摘要翻译： 本发明的一个目的是同时测量少量的多个样品溶液。 将少量样品溶液分别放置在测量电极上，将介质放置在多个样品溶液上，使参考电极的液体接头与介质接触，并且测量电极和 通过介质测量参考电极。

公开(公告)号：US08246810B2

公开(公告)日：2012-08-21

申请号：US13064682

申请日：2011-04-08

申请人： Yu Ishige ,  Masao Kamahori

发明人： Yu Ishige ,  Masao Kamahori

IPC分类号： G01N33/50

CPC分类号： C12Q1/6825 ,  C12Q1/6869 ,  C12Q2565/607 ,  C12Q2565/301 ,  C12Q2563/113

摘要： Disclosed is a DNA analysis method and a DNA analyzer whose signal intensity is not lowered even when a material at a higher density is measured. There is supplied dATP, dTTP, dGTP, or dCTP from a dATP solution vessel, a dTTP solution vessel, a dGTP solution vessel, or a dCTP solution vessel, and this causes an extension reaction of a double-stranded DNA immobilized to a bead, to yield pyrophosphoric acid. The pyrophosphoric acid is converted into a redox compound by the actions of a reagent and an enzyme contained in a reaction buffer in a reaction buffer vessel. The redox compound causes a variation in surface potential of a measuring electrode bearing an electrochemically active material immobilized thereto through an insulating molecule, and this variation causes a variation in drain current of a field-effect transistor electrically connected to the measuring electrode. Thus, the extension reaction is detected.

摘要翻译： 公开了即使在测量较高密度的材料时信号强度也不降低的DNA分析方法和DNA分析仪。 从dATP溶液容器，dTTP溶液容器，dGTP溶液容器或dCTP溶液容器中提供dATP，dTTP，dGTP或dCTP，这导致固定在珠粒上的双链DNA的延伸反应， 得到焦磷酸。 通过反应缓冲容器中的反应缓冲液中所含的试剂和酶的作用将焦磷酸转化为氧化还原化合物。 氧化还原化合物导致通过绝缘分子固定有电化学活性材料的测量电极的表面电位变化，并且这种变化导致与测量电极电连接的场效应晶体管的漏极电流的变化。 因此，检测到延伸反应。

公开(公告)号：US08202409B2

公开(公告)日：2012-06-19

申请号：US11942862

申请日：2007-11-20

申请人： Yu Ishige ,  Masao Kamahori

发明人： Yu Ishige ,  Masao Kamahori

IPC分类号： G01N27/414

CPC分类号： G01N27/4035

摘要： A potentiometric sensor with suppressed leak current on the surface of an electrode and improved for a dynamic range and a response speed, in which a redox compound is immobilized through insulative molecules on the surface of a gold electrode, and a current between a source and drain of an insulated gate field-effect transistor along with reaction between an oxidized substance or a reduced substance produced by the reaction of a measured substance in a sample solution injector for supplying the sample solution containing the measured substance and an enzyme and a redox compound on the surface of the gold electrode, is monitored on real time to measure the change of the surface potential.

摘要翻译： 一种具有在电极表面上具有抑制的漏电流的电位传感器，并且改善了动态范围和响应速度，其中通过金电极表面上的绝缘分子固定氧化还原化合物，以及源极和漏极之间的电流 绝缘栅场效应晶体管与通过样品溶液注射器中的测量物质的反应产生的氧化物质或还原物质之间的反应，用于将含有测量物质的样品溶液与酶和氧化还原化合物反应 金电极的表面，被实时监测以测量表面电位的变化。

公开(公告)号：US20110276278A1

公开(公告)日：2011-11-10

申请号：US13126766

申请日：2009-10-29

申请人： Yu Ishige ,  Masao Kamahori ,  Kuniaki Nagamine

发明人： Yu Ishige ,  Masao Kamahori ,  Kuniaki Nagamine

IPC分类号： G01N27/00 ,  G06F19/00

CPC分类号： G01N27/3272 ,  G01N27/3277 ,  G01N33/49 ,  G01N33/66

摘要： Provided is a potentiometric sensor chip in which the positional relationship among a reference electrode, a measurement electrode, and a sample inlet which enables measurement from the start of a reaction is defined, and further provided is a method for detecting the start time of the reaction. A very small amount of sample is measured with high accuracy. The very small quantity of sample is measured by a rate assay. When a reference electrode (103) is disposed between a sample inlet (102) and a measurement electrode (104), a sample solution arrives at the reference electrode (103) earlier than at the measurement electrode (104), whereby the surface potential of the measurement electrode (104) can be measured simultaneously when the sample solution arrives at the measurement electrode (104) and dissolves a reagent and thereby a reaction starts. The arrival of the sample solution at the measurement electrode (104) can be sensed by detecting the discontinuous change of the voltage observed by a voltmeter (106) at this time.

摘要翻译： 提供了一种电位传感器芯片，其中定义了参考电极，测量电极和能够从反应开始进行测量的样品入口之间的位置关系，并且还提供了用于检测反应开始时间的方法 。 以高精度测量非常少量的样品。 通过速率测定法测量非常少量的样品。 当参考电极（103）设置在样品入口（102）和测量电极（104）之间时，样品溶液比测量电极（104）早到达参考电极（103），由此， 当样品溶液到达测量电极（104）并溶解试剂，从而开始反应时，可以同时测量测量电极（104）。 可以通过检测此时由电压表（106）观察到的电压的不连续变化来检测样品溶液到达测量电极（104）的到来。

公开(公告)号：US08394247B2

公开(公告)日：2013-03-12

申请号：US12222900

申请日：2008-08-19

申请人： Masao Kamahori ,  Yu Ishige ,  Kotaro Yamashita ,  Yasuhisa Shibata ,  Masafumi Miyake ,  Kuniaki Nagamine

发明人： Masao Kamahori ,  Yu Ishige ,  Kotaro Yamashita ,  Yasuhisa Shibata ,  Masafumi Miyake ,  Kuniaki Nagamine

IPC分类号： G01N27/333

CPC分类号： G01N27/414 ,  G01N27/3335

摘要： The present invention aims to simplify the structure and a fabrication method of an ion-selective electrode in an ion concentration measuring device that measures an anion, particularly a chloride ion, in a biological component. To this end, in a potential difference measuring unit, a quaternary ammonium salt derivative serving as a ligand for an anion is immobilized to the surface of a gold electrode by using as a linker an insulative molecule forming a self-assembled monolayer. The potential difference measuring unit measures an electromotive force generated with anion binding, as an interface potential change on the surface of the gold electrode. In order to reduce the influence of adsorption of impurities on the electrode surface, a high-molecular weight polymer is physically adsorbed on the gold electrode and thus used when a biological component is measured.

公开(公告)号：US07960113B2

公开(公告)日：2011-06-14

申请号：US12068206

申请日：2008-02-04

申请人： Yu Ishige ,  Masao Kamahori

发明人： Yu Ishige ,  Masao Kamahori

IPC分类号： C12Q1/68 ,  C12M1/40 ,  G01N33/531

CPC分类号： C12Q1/6825 ,  C12Q1/6869 ,  C12Q2565/607 ,  C12Q2565/301 ,  C12Q2563/113

摘要： Disclosed is a DNA analysis method and a DNA analyzer whose signal intensity is not lowered even when a material at a higher density is measured. There is supplied dATP, dTTP, dGTP, or dCTP from a dATP solution vessel, a dTTP solution vessel, a dGTP solution vessel, or a dCTP solution vessel, and this causes an extension reaction of a double-stranded DNA immobilized to a bead, to yield pyrophosphoric acid. The pyrophosphoric acid is converted into a redox compound by the actions of a reagent and an enzyme contained in a reaction buffer in a reaction buffer vessel. The redox compound causes a variation in surface potential of a measuring electrode bearing an electrochemically active material immobilized thereto through an insulating molecule, and this variation causes a variation in drain current of a field-effect transistor electrically connected to the measuring electrode. Thus, the extension reaction is detected.

摘要翻译： 公开了即使在测量较高密度的材料时信号强度也不降低的DNA分析方法和DNA分析仪。 从dATP溶液容器，dTTP溶液容器，dGTP溶液容器或dCTP溶液容器中提供dATP，dTTP，dGTP或dCTP，这导致固定在珠粒上的双链DNA的延伸反应， 得到焦磷酸。 通过反应缓冲容器中的反应缓冲液中所含的试剂和酶的作用将焦磷酸转化为氧化还原化合物。 氧化还原化合物导致通过绝缘分子固定有电化学活性材料的测量电极的表面电位变化，并且这种变化导致与测量电极电连接的场效应晶体管的漏极电流的变化。 因此，检测到延伸反应。

公开(公告)号：US07838226B2

公开(公告)日：2010-11-23

申请号：US11491128

申请日：2006-07-24

申请人： Masao Kamahori ,  Yu Ishige

发明人： Masao Kamahori ,  Yu Ishige

IPC分类号： C12Q1/68 ,  C12P19/34 ,  C12M1/00 ,  G01N15/06

CPC分类号： B82Y15/00 ,  B82Y30/00 ,  C12Q1/6834 ,  C12Q2565/607

摘要： With an insulated gate field effect transistor in which deoxyribonucleic acid (DNA) probes are immobilized on a gold electrode, extension reaction on the gold electrode is performed with DNA polymerase to directly measure an increased amount of a phosphate group caused by the extension reaction, that is, negative charge, by means of a current change between a source and a drain of the insulated gate field effect transistor. Thus, presence/absence of hybridization of target DNAs with the DNA probes, and presence/absence of the extension reaction are detected. Optimum immobilization density of the DNA probes on the gold electrode is set at 4×1012 molecules/cm2. To reduce surface potential fluctuation caused by external variation (influences of foreign substances), which is a problem when using the gold electrode in a solution, a high-frequency voltage equal to or above 1 kHz is applied between the gold electrode and a reference electrode by a power source.

摘要翻译： 使用绝缘栅场效应晶体管，其中脱氧核糖核酸（DNA）探针固定在金电极上，金电极上的延伸反应用DNA聚合酶进行，以直接测量由延伸反应引起的磷酸基团的增加量， 是通过绝缘栅场效应晶体管的源极和漏极之间的电流变化来产生负电荷。 因此，检测靶DNA与DNA探针杂交的存在/不存在以及延伸反应的存在/不存在。 金电极上DNA探针的最佳固定密度设定为4×10 12分子/ cm 2。 为了降低在溶液中使用金电极时的外部变化（异物的影响）引起的表面电位波动，在金电极和参比电极之间施加等于或大于1kHz的高频电压 由电源。

公开(公告)号：US20080314746A1

公开(公告)日：2008-12-25

申请号：US12155919

申请日：2008-06-11

申请人： Yu Ishige ,  Masao Kamahori

发明人： Yu Ishige ,  Masao Kamahori

IPC分类号： G01N33/487

CPC分类号： G01N33/492

摘要： It is an object of this invention to measure small amounts of a plurality of sample solutions at the same time. The small amounts of sample solutions are respectively placed on measuring electrodes, a medium is placed across the plurality of sample solutions, a liquid joint of a reference electrode is brought into contact with the medium, and a potential difference between each of the measuring electrodes and the reference electrode via the medium is measured.

摘要翻译： 本发明的一个目的是同时测量少量的多个样品溶液。 将少量样品溶液分别放置在测量电极上，将介质放置在多个样品溶液上，使参考电极的液体接头与介质接触，并且测量电极和 通过介质测量参考电极。