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1. 发明授权

US08389959B2 Fluorescence analyzing device and fluorescence analyzing method 有权
标题翻译：荧光分析装置及荧光分析方法
公开(公告)号：US08389959B2
公开(公告)日：2013-03-05
申请号：US13147147
申请日：2009-11-30
申请人： Satoshi Takahashi , Tsuyoshi Sonehara , Tomoyuki Sakai , Takanobu Haga , Hirokazu Kato , Nobutaka Kumazaki , Takuya Matsui
发明人： Satoshi Takahashi , Tsuyoshi Sonehara , Tomoyuki Sakai , Takanobu Haga , Hirokazu Kato , Nobutaka Kumazaki , Takuya Matsui
IPC分类号： G01N21/64
CPC分类号： G01N21/648 , G01J3/10 , G01J3/14 , G01J3/36 , G01J3/4406 , G01N21/6452
摘要： The present invention has an object to provide a method for efficiently detecting an image with a smaller number of pixels.The invention relates to fluorescence analysis which uses a substrate having a plurality of regions for being capable of immobilizing biologically-related molecules in positions of lattice points of a lattice structure, and which causes the fluorescence from a certain lattice point to be wavelength-dispersed in a direction other than the direction toward the adjacent closest lattice point. According to an embodiment, for example, the number of pixels of a two-dimensional sensor required for fluorescence analysis of the regions with the biologically-related molecules immobilized can be set to several hundred times to fifty times smaller than that in the conventional case without degrading the measurement accuracy. This can achieve the improvement of throughput, reduction in price, and/or improvement of the operability of an analyzing device.
摘要翻译：本发明的目的是提供一种用于有效检测具有较少像素数的图像的方法。本发明涉及使用具有多个区域的基板的荧光分析，其能够将生物相关分子固定在格子结构的格点的位置，并且使得来自特定格子点的荧光波长分散在除了朝向相邻最近格子点的方向之外的方向。根据一个实施例，例如，具有生物相关分子固定的区域的荧光分析所需的二维传感器的像素数量可以设定为比常规情况下少几百次到五十次，而没有降低测量精度。这可以实现分析装置的吞吐量的提高，价格的降低和/或改善可操作性。

2. 发明申请

US20110284768A1 FLUORESCENCE ANALYZING DEVICE AND FLUORESCENCE ANALYZING METHOD 有权
标题翻译：荧光分析装置和荧光分析方法
公开(公告)号：US20110284768A1
公开(公告)日：2011-11-24
申请号：US13147147
申请日：2009-11-30
申请人： Satoshi Takahashi , Tsuyoshi Sonehara , Tomoyuki Sakai , Takanobu Haga , Hirokazu Kato , Nobutaka Kumazaki , Takuya Matsui
发明人： Satoshi Takahashi , Tsuyoshi Sonehara , Tomoyuki Sakai , Takanobu Haga , Hirokazu Kato , Nobutaka Kumazaki , Takuya Matsui
IPC分类号： G01N21/64
CPC分类号： G01N21/648 , G01J3/10 , G01J3/14 , G01J3/36 , G01J3/4406 , G01N21/6452
摘要： The present invention has an object to provide a method for efficiently detecting an image with a smaller number of pixels.The invention relates to fluorescence analysis which uses a substrate having a plurality of regions for being capable of immobilizing biologically-related molecules in positions of lattice points of a lattice structure, and which causes the fluorescence from a certain lattice point to be wavelength-dispersed in a direction other than the direction toward the adjacent closest lattice point. According to an embodiment, for example, the number of pixels of a two-dimensional sensor required for fluorescence analysis of the regions with the biologically-related molecules immobilized can be set to several hundred times to fifty times smaller than that in the conventional case without degrading the measurement accuracy. This can achieve the improvement of throughput, reduction in price, and/or improvement of the operability of an analyzing device.
摘要翻译：本发明的目的是提供一种用于有效检测具有较少像素数的图像的方法。本发明涉及使用具有多个区域的基板的荧光分析，其能够将生物相关分子固定在格子结构的格点的位置，并且使得来自特定格子点的荧光波长分散在除了朝向相邻最近格子点的方向之外的方向。根据一个实施例，例如，具有生物相关分子固定的区域的荧光分析所需的二维传感器的像素数量可以设定为比常规情况下少几百次到五十次，而没有降低测量精度。这可以实现分析装置的吞吐量的提高，价格的降低和/或改善可操作性。

3. 发明申请

US20090168061A1 FLUORESCENCE DETECTION APPARATUS 失效
标题翻译：荧光检测装置
公开(公告)号：US20090168061A1
公开(公告)日：2009-07-02
申请号：US12339285
申请日：2008-12-19
申请人： Takanobu Haga , Satoshi Takahashi , Nobutaka Kumazaki , Hirokazu Kato , Tsuyoshi Sonehara
发明人： Takanobu Haga , Satoshi Takahashi , Nobutaka Kumazaki , Hirokazu Kato , Tsuyoshi Sonehara
IPC分类号： G01N21/64
CPC分类号： G01N21/648 , G01N21/6428
摘要： A fluorescent detection apparatus relates to an analysis technique for qualitatively detecting or quantifying biomolecules by producing an evanescent field on a surface of a substrate, exciting fluorescently labelled biomolecules on the substrate surface in the evanescent field, and detecting the resultant fluorescent light emitted from the biomolecules. The fluorescent detection apparatus has a configuration in which a well is provided in a surface opposing to a sample substrate of a prism, the well is filled with a matching liquid, and the matching liquid is filled between the sample substrate and the prism, thereby improving operability and providing a stable evanescent field.
摘要翻译：荧光检测装置涉及用于通过在基底表面上产生ev逝场来激发生物分子进行定性检测或定量的分析技术，在ev逝场中激发荧光标记的生物分子，并检测从生物分子发射的荧光。荧光检测装置具有在与棱镜的样品基板相对的表面上设置有阱的构造，在该阱中填充有匹配液体，并且将匹配液体填充在样品基板与棱镜之间，由此提高可操作性，并提供稳定的消逝场。

4. 发明授权

US07751041B2 Fluorescence detection apparatus 失效
标题翻译：荧光检测装置
公开(公告)号：US07751041B2
公开(公告)日：2010-07-06
申请号：US12339285
申请日：2008-12-19
申请人： Takanobu Haga , Satoshi Takahashi , Nobutaka Kumazaki , Hirokazu Kato , Tsuyoshi Sonehara
发明人： Takanobu Haga , Satoshi Takahashi , Nobutaka Kumazaki , Hirokazu Kato , Tsuyoshi Sonehara
IPC分类号： G01J3/30
CPC分类号： G01N21/648 , G01N21/6428
摘要： A fluorescent detection apparatus relates to an analysis technique for qualitatively detecting or quantifying biomolecules by producing an evanescent field on a surface of a substrate, exciting fluorescently labelled biomolecules on the substrate surface in the evanescent field, and detecting the resultant fluorescent light emitted from the biomolecules. The fluorescent detection apparatus has a configuration in which a well is provided in a surface opposing to a sample substrate of a prism, the well is filled with a matching liquid, and the matching liquid is filled between the sample substrate and the prism, thereby improving operability and providing a stable evanescent field.
摘要翻译：荧光检测装置涉及用于通过在基底表面上产生ev逝场来激发生物分子进行定性检测或定量的分析技术，在ev逝场中激发荧光标记的生物分子，并检测从生物分子发射的荧光。荧光检测装置具有在与棱镜的样品基板相对的表面上设置有阱的构造，在该阱中填充有匹配液体，并且将匹配液体填充在样品基板与棱镜之间，由此提高可操作性，并提供稳定的消逝场。

5. 发明申请

US20110105358A1 SINGLE MOLECULE REAL TIME SEQUENCER, NUCLEIC ACID ANALYZER AND SINGLE MOLECULE REAL TIME SEQUENCING METHOD 审中-公开
标题翻译：单分子实时序列分析仪，核酸分析仪和单分子实时测序方法
公开(公告)号：US20110105358A1
公开(公告)日：2011-05-05
申请号：US13001294
申请日：2009-06-08
申请人： Hirokazu Kato , Satoshi Takahashi , Nobutaka Kumazaki , Takanobu Haga
发明人： Hirokazu Kato , Satoshi Takahashi , Nobutaka Kumazaki , Takanobu Haga
IPC分类号： C40B30/04 , C40B40/06
CPC分类号： C12Q1/6874 , B01J2219/00529 , B01J2219/00596 , B01J2219/00608 , B01J2219/00711 , B01J2219/00722 , B01L3/502707 , B82Y30/00 , G01N21/648 , C12Q2523/313 , C12Q2523/319 , C12Q2561/113 , C12Q2565/628 , C12Q2525/186 , C12Q2563/107 , C12Q2565/631
摘要： An object of the present invention relates to selectively control an extension reaction within a desired area in a substrate. In the present invention, an oligo probe arranged with a caged compound at the terminal thereof is immobilized to a reaction field area in the substrate. After pouring a reaction solution into a flow cell including the reaction field area, the reaction field area alone is irradiated with light to associate the photodegradation-active protecting group at the terminal of the oligo probe that has been immobilized in the reaction field area and thus to selectively control initiation of a polymerase extension reaction. In the flow cell, a plural number of the reaction field areas are arranged at constant interval on the substrate. The flow cell immobilized to a moving stage is moved by a distance equal to the interval between the adjacent reaction field areas and then light irradiation is carried out to measure the extension reaction continuously. By repeating these operations, the base extension reaction is stably measured in the flow cell without using complicated channels or without replacing the reaction solution.
摘要翻译：本发明的目的在于选择性地控制基材中所需区域内的延伸反应。在本发明中，在其末端配置有笼状化合物的寡探针固定在基板的反应场区域。在将反应溶液倒入包括反应场区域的流动池中后，单独的反应场区域用光照射以将固定在反应场区域中的寡探针末端的光降解活性保护基团与之结合以选择性地控制聚合酶延伸反应的起始。在流动池中，多个反应场区以恒定间隔排列在基板上。固定在移动台上的流动池移动等于相邻反应场区间的距离，然后进行光照射以连续测量延伸反应。通过重复这些操作，在流通池中稳定地测量碱扩展反应，而不使用复杂的通道或不更换反应溶液。

6. 发明授权

US08324596B2 Total internal reflection fluorescence (TIRF) observation device 有权
标题翻译：全内反射荧光（TIRF）观察装置
公开(公告)号：US08324596B2
公开(公告)日：2012-12-04
申请号：US13055854
申请日：2009-05-20
申请人： Nobutaka Kumazaki , Satoshi Takahashi , Hirokazu Kato , Takanobu Haga
发明人： Nobutaka Kumazaki , Satoshi Takahashi , Hirokazu Kato , Takanobu Haga
IPC分类号： G01N21/64
CPC分类号： G01N21/648 , G02B21/16
摘要： A device and method for fluorescence observation have good operability, high sensitivity, and high acid reliability. The device is used for fluorescence observation using evanescent light. The angle of incidence of the excitation light is adjusted so that the excitation light is totally reflected from the surface of a substrate irrespective of the angle of the substrate surface. The method includes a step of shining the excitation light on the observation substrate while continuously varying the angle of the excitation light with respect to the observation substrate. In addition, the method includes a step of sensing the shone excitation light via optical sensors, and a step of setting the angle of total reflection according to the result of the sensing by the optical sensors. In the present device and method, the direction in which the shone excitation light travels varies with the angle of incidence.
摘要翻译：用于荧光观察的装置和方法具有良好的可操作性，高灵敏度和高酸可靠性。该器件用于使用ev逝光的荧光观察。调整激发光的入射角，使得激发光从衬底表面全反射，而与衬底表面的角度无关。该方法包括在激发光相对于观察基板的角度连续变化的同时在观察基板上照射激发光的步骤。此外，该方法包括通过光学传感器感测照射激发光的步骤，以及根据光学传感器的感测结果设定全反射角度的步骤。在本装置和方法中，照射激发光的行进方向随入射角而变化。

7. 发明申请

US20090242804A1 METHOD FOR FLUORESCENCE ANALYSIS AND FLUORESCENCE ANALYZER 有权
标题翻译：荧光分析和荧光分析仪的方法
公开(公告)号：US20090242804A1
公开(公告)日：2009-10-01
申请号：US12400321
申请日：2009-03-09
申请人： Takayuki OBARA , Satoshi Takahashi , Akira Maekawa , Takuya Matsui , Nobutaka Kumazaki
发明人： Takayuki OBARA , Satoshi Takahashi , Akira Maekawa , Takuya Matsui , Nobutaka Kumazaki
IPC分类号： G01N21/64
CPC分类号： G01N21/648 , G01N21/15 , G01N21/274 , G01N21/6452
摘要： The present invention aims at reducing background noise derived from a substance that is present in the vicinity of a target substance such as a DNA and protein and attached to the surface of a substrate without an effect on a fluorescent dye labeling the target substance. The substrate that has a probe and is capable of interacting with the target substance is irradiated with noise removing light such that an evanescent field is generated on the surface of the substrate. A target substance and a foreign particle, which are non-specifically stuck to the surface of the substrate, are decomposed by the evanescent field generated by the irradiation with the noise removing light. The evanescent field present near the surface of the substrate has almost no effect on the probe. It is possible to reduce the background noise derived from the substance that is present in the vicinity of the target substance and attached to the surface of the substrate and suppress effects on the probe and the target substance interacting with the probe.
摘要翻译：本发明旨在减少由存在于目标物质（例如DNA和蛋白质）附近的物质衍生的背景噪声，并附着于基材表面，而不影响标记目标物质的荧光染料。具有探针并且能够与目标物质相互作用的基板被消除噪声的光照射，使得在基板的表面上产生ev逝场。非特异性地粘附在基板表面上的目标物质和外来粒子被消除噪声的光照射产生的ev逝场分解。在衬底表面附近存在的消逝场对探针几乎没有影响。可以减少由存在于目标物质附近并附着于基板表面的物质导致的背景噪声，并抑制与探针相互作用的探针和目标物质的影响。

8. 发明申请

US20110121204A1 TOTAL REFLECTION FLUORESCENCE OBSERVATION DEVICE 有权
标题翻译：总反射荧光观察装置
公开(公告)号：US20110121204A1
公开(公告)日：2011-05-26
申请号：US13055854
申请日：2009-05-20
申请人： Nobutaka Kumazaki , Satoshi Takahashi , Hirokazu Kato , Takanovu Haga
发明人： Nobutaka Kumazaki , Satoshi Takahashi , Hirokazu Kato , Takanovu Haga
IPC分类号： G01J1/58
CPC分类号： G01N21/648 , G02B21/16
摘要： A technique and device for fluorescence observation with good operability, high sensitivity, acid high reliability. The device is used for fluorescence observation using evanescent light. The angle of incidence of the excitation light is adjusted so that the excitation light is always totally reflected from the surface of a substrate irrespective of the angle of the surface of the substrate. The method includes a step of shining the excitation light on the observation substrate while continuously varying the angle of the excitation light with respect to the observation substrate, a step of sensing the shone excitation light by means of optical sensors, and a step of setting the angle of total reflection according to the result of the sensing by the optical sensors. The direction in which the shone excitation light travels varies with the angle of incidence. That is, the excitation light travels as the transmitted light, the reflected light, or the surface propagating light. These lights are sensed by the corresponding optical sensors, and how the angle of incidence of the excitation light is with respect to the critical angle is determined. The angle of incidence of the excitation light is varied depending on the result of the determination, thereby realizing an optimum total reflection angle.
摘要翻译：用于荧光观察的技术和装置，操作性好，灵敏度高，酸度高可靠性。该器件用于使用ev逝光的荧光观察。调节激发光的入射角，使得激发光始终从基板的表面全反射，而与基板的表面的角度无关。该方法包括在观察基板上照射激发光的步骤，同时连续地改变激发光相对于观察基板的角度，通过光学传感器感测照射激发光的步骤，以及将根据光学传感器的感测结果，全反射角度。照射激发光的行进方向随入射角而变化。也就是说，激发光作为透射光，反射光或表面传播光行进。这些光被相应的光学传感器感测，并且确定激发光的入射角相对于临界角如何。激发光的入射角取决于确定的结果而变化，从而实现最佳的全反射角。

9. 发明授权

US08294122B2 Method for fluorescence analysis and fluorescence analyzer 有权
标题翻译：荧光分析方法和荧光分析仪
公开(公告)号：US08294122B2
公开(公告)日：2012-10-23
申请号：US12400321
申请日：2009-03-09
申请人： Takayuki Obara , Satoshi Takahashi , Akira Maekawa , Takuya Matsui , Nobutaka Kumazaki
发明人： Takayuki Obara , Satoshi Takahashi , Akira Maekawa , Takuya Matsui , Nobutaka Kumazaki
IPC分类号： G01N21/64
CPC分类号： G01N21/648 , G01N21/15 , G01N21/274 , G01N21/6452
摘要： The present invention aims at reducing background noise derived from a substance that is present in the vicinity of a target substance such as a DNA and protein and attached to the surface of a substrate without an effect on a fluorescent dye labeling the target substance. The substrate that has a probe and is capable of interacting with the target substance is irradiated with noise removing light such that an evanescent field is generated on the surface of the substrate. A target substance and a foreign particle, which are non-specifically stuck to the surface of the substrate, are decomposed by the evanescent field generated by the irradiation with the noise removing light. The evanescent field present near the surface of the substrate has almost no effect on the probe. It is possible to reduce the background noise derived from the substance that is present in the vicinity of the target substance and attached to the surface of the substrate and suppress effects on the probe and the target substance interacting with the probe.
摘要翻译：本发明旨在减少由存在于目标物质（例如DNA和蛋白质）附近的物质衍生的背景噪声，并附着于基材表面，而不影响标记目标物质的荧光染料。具有探针并且能够与目标物质相互作用的基板被消除噪声的光照射，使得在基板的表面上产生ev逝场。非特异性地粘附在基板表面上的目标物质和外来粒子被消除噪声的光照射产生的ev逝场分解。在衬底表面附近存在的消逝场对探针几乎没有影响。可以减少由存在于目标物质附近并附着于基板表面的物质导致的背景噪声，并抑制与探针相互作用的探针和目标物质的影响。

10. 发明申请

US20140110259A1 METHOD AND DEVICE FOR OPTICAL ANALYSIS OF BIOPOLYMER 审中-公开
标题翻译：用于光学分析生物聚合物的方法和装置
公开(公告)号：US20140110259A1
公开(公告)日：2014-04-24
申请号：US14123345
申请日：2012-05-29
申请人： Satoshi Takahashi , Nobutaka Kumazaki
发明人： Satoshi Takahashi , Nobutaka Kumazaki
IPC分类号： G01N27/447
CPC分类号： G01N27/44704 , B82Y15/00 , G01N21/658 , G01N27/44791 , G01N33/48721
摘要： A biopolymer optical analysis apparatus is provided with a biopolymer characteristic analysis chip including a solid substrate, nanopores provided in the substrate, and electrically conductive thin films on the substrate, at least portions of the thin films facing the nanopores, a light source and an irradiation optical system for producing Raman scattered lights from biopolymers entering the nanopores, and a detection device including a Raman scattered light collecting system, a separating component that splits collected light into transmitted light and reflected light, an image-forming optical system through which the split lights form images, and a two-dimensional detector for detecting the lights forming the images. External light from the light source and the irradiation optical system is applied to the characteristic analysis chip, and the detection device detects Raman scattered lights from biopolymers in the analysis chip. Characteristics of monomer units constituting the biopolymers are analyzed from the results of detection.
摘要翻译：生物聚合物光学分析装置具有生物聚合物特性分析芯片，其包括固体基材，设置在基材中的纳米孔，以及基材上的导电薄膜，至少部分薄膜面对纳米孔，光源和照射用于从进入纳米孔的生物聚合物制造拉曼散射光的光学系统，以及包括拉曼散射光收集系统，将收集的光分离成透射光和反射光的分离组件的检测装置，分光灯形成图像，以及用于检测形成图像的光的二维检测器。来自光源和照射光学系统的外部光被应用于特征分析芯片，并且检测装置从分析芯片中的生物聚合物检测拉曼散射光。从检测结果分析构成生物聚合物的单体单元的特征。

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