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。

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。

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。

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。

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。

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。

公开(公告)号：US20120097864A1

公开(公告)日：2012-04-26

申请号：US13380251

申请日：2010-06-04

申请人： Satoshi Takahashi ,  Tsuyoshi Sonehara ,  Takanobu Haga

发明人： Satoshi Takahashi ,  Tsuyoshi Sonehara ,  Takanobu Haga

IPC分类号： G01N21/64

CPC分类号： G01N21/6452 ,  G01N21/6428 ,  G01N2021/6417 ,  G01N2021/6419 ,  G01N2021/6421 ,  G01N2021/6441

摘要： Provided are a method and an apparatus for easily identifying and detecting fluorescent material types captured in respective reaction regions of a substrate, particularly, a method and an apparatus for identifying and measuring the fluorescence intensities of a plurality of fluorescent materials using a small pixel count. The fluorescence intensities of four or more types of fluorescent materials are divided by a dividing section at ratios different at least for each fluorescence maximum wavelength range, and are detected by at least one detector including pixels for detecting the light fluxes divided at the different ratios. The type of the fluorescent material is determined on the basis of the ratio of the detected fluorescence intensity of the same detection portion, and the fluorescence intensity is measured.

摘要翻译： 提供一种用于容易地识别和检测在基板的各个反应区域中捕获的荧光材料类型的方法和装置，特别是用于使用小像素数来识别和测量多种荧光材料的荧光强度的方法和装置。 四种或更多类型的荧光材料的荧光强度由至少对于每个荧光最大波长范围不同的比率除以分割部分，并且由至少一个检测器检测，包括用于检测以不同比率分割的光通量的像素。 基于检测出的相同检测部分的荧光强度的比例来测定荧光体的种类，测定荧光强度。

公开(公告)号：US08680484B2

公开(公告)日：2014-03-25

申请号：US13380251

申请日：2010-06-04

申请人： Satoshi Takahashi ,  Tsuyoshi Sonehara ,  Takanobu Haga

发明人： Satoshi Takahashi ,  Tsuyoshi Sonehara ,  Takanobu Haga

IPC分类号： G01N21/64

CPC分类号： G01N21/6452 ,  G01N21/6428 ,  G01N2021/6417 ,  G01N2021/6419 ,  G01N2021/6421 ,  G01N2021/6441

摘要： Provided are a method and an apparatus for easily identifying and detecting fluorescent material types captured in respective reaction regions of a substrate, particularly, a method and an apparatus for identifying and measuring the fluorescence intensities of a plurality of fluorescent materials using a small pixel count. The fluorescence intensities of four or more types of fluorescent materials are divided by a dividing section at ratios different at least for each fluorescence maximum wavelength range, and are detected by at least one detector including pixels for detecting the light fluxes divided at the different ratios. The type of the fluorescent material is determined on the basis of the ratio of the detected fluorescence intensity of the same detection portion, and the fluorescence intensity is measured.

摘要翻译： 提供一种用于容易地识别和检测在基板的各个反应区域中捕获的荧光材料类型的方法和装置，特别是用于使用小像素数来识别和测量多种荧光材料的荧光强度的方法和装置。 四种或更多类型的荧光材料的荧光强度由至少对于每个荧光最大波长范围不同的比率除以分割部分，并且由至少一个检测器检测，包括用于检测以不同比率分割的光通量的像素。 基于检测出的相同检测部分的荧光强度的比例来测定荧光体的种类，测定荧光强度。

公开(公告)号：US08680483B2

公开(公告)日：2014-03-25

申请号：US13141127

申请日：2009-12-22

申请人： Takanobu Haga ,  Tsuyoshi Sonehara ,  Kenko Uchida ,  Tomoyuki Sakai ,  Satoshi Takahashi

发明人： Takanobu Haga ,  Tsuyoshi Sonehara ,  Kenko Uchida ,  Tomoyuki Sakai ,  Satoshi Takahashi

IPC分类号： G01J1/58

CPC分类号： G01N21/6452 ,  G01N2021/6421 ,  G01N2021/6441 ,  G01N2021/6478

摘要： A fluorescence detector in which a sample substrate is provided with a structure unit comprising a prism or a diffraction grating. After excitation light falling on the sample substrate is totally reflected at a biomolecule-immobilized face that is located in the opposite side of the structure unit, the structure unit allows the emission of the reflected light therefrom. To ensure multiple visual field measurement, a sample substrate-driving unit is provided to scan the sample substrate.

摘要翻译： 一种荧光检测器，其中样品基板设置有包括棱镜或衍射光栅的结构单元。 落在样品基板上的激发光在位于结构单元的相对侧的生物分子固定面全面反射，结构单元允许从其发射反射光。 为了确保多个视野测量，提供了样品基板驱动单元以扫描样品基板。

公开(公告)号：US20110272596A1

公开(公告)日：2011-11-10

申请号：US13141127

申请日：2009-12-22

申请人： Takanobu Haga ,  Tsuyoshi Sonehara ,  Kenko Uchida ,  Tomoyuki Sakai ,  Satoshi Takahashi

发明人： Takanobu Haga ,  Tsuyoshi Sonehara ,  Kenko Uchida ,  Tomoyuki Sakai ,  Satoshi Takahashi

IPC分类号： G01N21/64

CPC分类号： G01N21/6452 ,  G01N2021/6421 ,  G01N2021/6441 ,  G01N2021/6478

摘要： A fluorescence detector in which a sample substrate is provided with a structure unit comprising a prism or a diffraction grating. After excitation light falling on the sample substrate is totally reflected at a biomolecule-immobilized face that is located in the opposite side of the structure unit, the structure unit allows the emission of the reflected light therefrom. To ensure multiple visual field measurement, a sample substrate-driving unit is provided to scan the sample substrate.

摘要翻译： 一种荧光检测器，其中样品基板设置有包括棱镜或衍射光栅的结构单元。 落在样品基板上的激发光在位于结构单元的相对侧的生物分子固定面全面反射，结构单元允许从其发射反射光。 为了确保多个视野测量，提供了样品基板驱动单元以扫描样品基板。