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    • 1. 发明专利
    • Cell separation chip
    • 细胞分离芯片
    • JP2012239408A
    • 2012-12-10
    • JP2011111234
    • 2011-05-18
    • Hiroshima Univ国立大学法人広島大学
    • SAKAMOTO KENJIMIYAKE AKIRAYANASE YUKIHIDE MICHIHIRO
    • C12M3/00
    • C12M47/04
    • PROBLEM TO BE SOLVED: To provide a cell separation chip capable of diagnosis with high reliability by reducing the amount of samples.SOLUTION: The cell separation measuring chip 100 is formed by pasting a member 2 together with a substrate 1. As a vacant space having a volume in microliter order made between the substrate 1 and the member 2, measuring units 4A, 4B, a solution input unit 3 and a microflow channel 5 are installed. In the measuring units 4A, 4B, a thin metal membrane 6 to which cells to be measured are spotted is placed on the substrate 1. In the solution input unit 3, an input port for a solution, including cells to be measured and magnetically modified cells other than the same, is mounted on the member 2. The microflow channel 5 connects the solution input unit 3 to communicate with the measuring units 4A, 4B. Magnetic particles 7 generate a magnetic field gradient for disturbing the flow of the magnetically modified cells in the microflow channel 5.
    • 要解决的问题:通过减少样品量来提供能够以高可靠性诊断的细胞分离芯片。 解决方案:细胞分离测量芯片100通过将部件2与基板1粘贴而形成。作为在基板1和部件2之间制成体积为微升级的空位,测量单元4A,4B, 解决方案输入单元3和微流通道5被安装。 在测量单元4A,4B中,将要测量的单元的薄金属膜6放置在基板1上。在溶液输入单元3中,包括待测量单元和磁性修正的溶液输入端口 微通道5连接溶液输入单元3与测量单元4A,4B连通。 磁性粒子7产生磁场梯度,以扰乱微流道5中的磁修饰细胞的流动。版权所有:(C)2013,JPO&INPIT
    • 2. 发明专利
    • マルチウェル解析方法および刺激用マルチウェルチャンバチップ
    • 多层分析方法和刺激多孔室切片
    • JP2015031520A
    • 2015-02-16
    • JP2013159020
    • 2013-07-31
    • 国立大学法人広島大学Hiroshima Univ
    • HIDE MICHIHIROYANASE YUKIISHII KOKAWAGUCHI TOMOKO
    • G01N33/53G01N21/41G01N33/543G01N37/00
    • 【課題】同時に多種類の検体または刺激物の組み合わせによる刺激応答を効率的に解析することができ、かつ刺激物について、投入量の微量化および投入の簡便化を可能とする、マルチウェル解析方法および刺激用マルチウェルチャンバチップを提供する。【解決手段】マルチウェル解析方法は、まず、2つ以上の検体投入区画を有する検体用マルチウェルチップ1と、2つ以上の刺激物投入区画を有する刺激用マルチウェルチャンバチップ5について、各区画が対応するよう対向させる。次に、検体と刺激物との混合液柱11が隔離された状態として形成されるよう、それぞれのチップを所定の間隔を置いて近づける。その後、混合液柱11の液性を評価し、対応させた検体と刺激物との反応を解析する。この際、いずれか1つの混合液柱11における検体と刺激物との組み合わせは、他のいずれか1つの混合液柱11における検体と刺激物との組み合わせと異なっている。【選択図】図4
    • 要解决的问题:为了提供多孔分析方法和刺激多孔室芯片,其能够有效地分析由多种样品或兴奋剂的组合引起的刺激反应,同时微调输入量并简化输入程序 兴奋剂。解决方案:多孔分析方法首先反对具有两个或更多个样本输入部分的样本多孔芯片1和具有两个或更多个兴奋剂输入部分的刺激多孔室芯片5,使得相应部分彼此相对面对。 接下来,多孔分析方法将芯片彼此更靠近地间隔开预定空间,使得样品和刺激剂的混合物的柱11以分离的状态形成。 然后,多孔分析方法评估混合物柱11的流动性,并结合分析样品和兴奋剂之间的反应。 此时,任何一个混合物柱11中的样品和刺激剂的组合与其它任何混合物柱11中的样品和刺激剂的组合不同。
    • 3. 发明专利
    • Type-i allergy diagnosis device and type-i allergy diagnosis method
    • TYPE-I过敏诊断装置和I型过敏诊断方法
    • JP2014169880A
    • 2014-09-18
    • JP2013040589
    • 2013-03-01
    • Hiroshima Univ国立大学法人広島大学
    • HIDE MICHIHIROYANASE YUKIISHII KOKAWAGUCHI TOMOKOSAKAMOTO KENJI
    • G01N21/27
    • PROBLEM TO BE SOLVED: To provide a type-I allergy diagnosis device and a type-I allergy diagnosis method capable of accurately performing diagnosis using a minute specimen which can be kept in a freezer, and efficiently diagnosing a stimulant response caused by combining many kinds of specimens or antigens at the same time.SOLUTION: A type-I allergy diagnosis device 1 comprises a light source 2, a collimator lens 3, a polarizer 4, a prism 5, a metal thin film coat 6, a glass substrate 7, a multi-well chamber 8, an allergen administration multi-chamber 9, an objective lens 10, an imaging section 11 and a CPU 12. Image data 13 indicate a reflection light intensity image. The multi-well chamber 8 includes a number of sample administration divisions, a human IgE acceptor expression cell strain culture solution and a specimen are cultured after administration, and an antigen standard substance is administered in such a manner that a combination of a specimen and an antigen standard substance to be administered to any sample administration division becomes different from a combination of a specimen and an antigen standard substance to be administered to another sample administration division.
    • 要解决的问题:为了提供I型过敏诊断装置和能够使用能够保存在冷冻箱中的微小标本进行诊断的I型过敏诊断方法,能够有效地诊断由多种组合引起的兴奋剂反应 的样品或抗原。解决方案:I型过敏诊断装置1包括光源2,准直透镜3,偏振器4,棱镜5,金属薄膜涂层6,玻璃基板7, 多孔室8,变应原给药多室9,物镜10,摄像部11和CPU 12.图像数据13表示反射光强度图像。 多孔室8包括多个样品给药部,给药后培养人IgE受体表达细胞株培养液和标本,以这样的方式施用抗原标准物质, 要向任何样品施用部门施用的抗原标准物质与待施用的样品和抗原标准物质的组合不同于另一个样品施用部门。
    • 4. 发明专利
    • Cell segregation chip and method of manufacturing cell segregation chip
    • 细胞分裂芯片和制造细胞分裂芯片的方法
    • JP2014039499A
    • 2014-03-06
    • JP2012183611
    • 2012-08-22
    • Hiroshima Univ国立大学法人広島大学
    • YANASE YUKIHIDE MICHIHIROMIYAKE AKIRASUGIMOTO URARAARITOME KATSUHIROSAKAMOTO KENJI
    • C12M1/00C12M3/00G01N21/27G01N37/00
    • PROBLEM TO BE SOLVED: To provide a cell segregation chip and a method of manufacturing a cell segregation chip which is easily manufactured and capable of highly reliable diagnosis.SOLUTION: First, a pattern of fine flow passages is formed on a wafer (step S11). Then, PDMS (polydimethylsiloxane) containing magnetic particles is applied on the wafer where the flow passage pattern has been formed by using a spin coating method, that is, by using a spin coater (step S12). Then, PDMS containing the magnetic particles which have been applied on the wafer is solidified (step S13). Then, a PDMS layer is additionally formed on the solidified PDMS containing magnetic particles (step S14). Then, two layers of the solidified PDMS, that is, members are removed from the wafer (step S15). Then, a glass substrate is laminated on the member 2 such that fine flow passages are formed (step S16).
    • 要解决的问题:提供一种容易制造且能够高度可靠诊断的细胞分离芯片的制造方法。解决方案:首先,在晶片上形成细流路图案(步骤S11) 。 然后,通过使用旋转涂布法,即通过使用旋转涂布机(步骤S12)将含有磁性粒子的PDMS(聚二甲基硅氧烷)涂布在已经形成流路图案的晶片上。 然后,将已经施加在晶片上的磁性粒子的PDMS固化(步骤S13)。 然后,在含有磁性粒子的固化PDMS上另外形成PDMS层(步骤S14)。 然后,从晶片上除去两层固化的PDMS,即成员(步骤S15)。 然后,将玻璃基板层叠在构件2上,使得形成微细流动通道(步骤S16)。
    • 5. 发明专利
    • Analysis method of living cell and analysis system of living cell
    • 生活细胞分析方法和生活细胞分析系统
    • JP2012141296A
    • 2012-07-26
    • JP2011270166
    • 2011-12-09
    • Hiroshima Univ国立大学法人広島大学
    • HIDE MICHIHIROHIRAGUN TAKAAKIYANASE YUKI
    • G01N21/27C12M1/34C12Q1/04G01N33/48G01N33/543
    • PROBLEM TO BE SOLVED: To provide a living-cell analysis method and analysis system capable of, on a cell-by-cell basis, comprehensively and directly analyzing the state of a living cell.SOLUTION: An analysis method of a living cell includes: an exposure process to expose a living cell to an external stimulus; a permittivity measuring process to measure temporal change in permittivity of the living cell exposed to the external stimulus in the exposure process; and an extraction process to extract characteristics of the temporal change in the permittivity of the living cell measured in the permittivity measuring process. An analysis system of the living cell comprises: exposure means to expose the living cell to the external stimulus; permittivity measuring means to measure the temporal change in the permittivity of the living cell exposed to the external stimulus in the exposure process; and extraction means to extract the characteristics of the temporal change in the permittivity of the living cell measured in the permittivity measuring process.
    • 要解决的问题:提供能够在逐个基础的基础上全面且直接地分析活细胞的状态的活细胞分析方法和分析系统。 解决方案:活细胞的分析方法包括:暴露过程以将活细胞暴露于外部刺激; 介电常数测量过程,用于测量在暴露过程中暴露于外部刺激的活细胞的介电常数的时间变化; 以及提取在介电常数测量过程中测量的活细胞介电常数的时间变化特征的方法。 活细胞的分析系统包括:将活细胞暴露于外部刺激物的暴露手段; 介电常数测量装置,用于测量在暴露过程中暴露于外部刺激的活细胞的介电常数的时间变化; 提取装置,用于提取在介电常数测定过程中测定的活细胞的介电常数的时间变化特性。 版权所有(C)2012,JPO&INPIT
    • 6. 发明专利
    • Cell activity analyzer, method for analyzing cell activity, and method for identifying cell
    • 细胞活性分析仪,分析细胞活性的方法和识别细胞的方法
    • JP2011193752A
    • 2011-10-06
    • JP2010061710
    • 2010-03-17
    • Hiroshima Univ国立大学法人広島大学
    • HIDE MICHIHIROYANASE YUKI
    • C12M1/34C12M1/00C12M1/42C12Q1/02G01N21/27G01N33/53G01N33/543G01N33/553
    • C12M41/46C12M41/36
    • PROBLEM TO BE SOLVED: To analyze the activity of external stimuli to each living cell.SOLUTION: The cell activity analyzer 100 includes: a metal thin film 5 touching living cells C1 and C2; a prism 3 having a boundary surface F touching the metal thin film 5 substantially; a light source 1 emitting a parallel light beam with P polarization incident on the prism 3 with a predetermined angle of incidence to the boundary surface F so as to generate a surface plasmon resonance phenomenon; an objective lens 6 enlarging an image of intensity corresponding to the two-dimensional intensity distribution of the reflected light to a predetermined magnification; an imaging unit 7 for imaging the enlarged intensity image; an image acquisition unit 21 sampling data of the intensity image; a display unit 23 and an operation unit 24 for selecting at least a part of the images of the living cells C1 and C2 as a measured object from the data of the intensity image; and an image processing unit 22 extracting the brightness value of the measured object and calculates the information on the change in intensity of the reflected light of the measured object based on the change in the brightness value of the measured object before and after giving external stimuli to the living cells C1 and C2.
    • 要解决的问题:分析每个活细胞外部刺激的活性。解决方案:细胞活性分析仪100包括:接触活细胞C1和C2的金属薄膜5; 基本上具有接触金属薄膜5的边界面F的棱镜3; 以与入射到棱镜3上的P偏振光发射平行光束的光源1以预定的入射角入射到边界面F,以产生表面等离子体共振现象; 物镜6将与反射光的二维强度分布对应的强度的图像放大到规定的倍率; 用于对放大强度图像进行成像的成像单元7; 图像获取单元21对强度图像进行数据采样; 用于从强度图像的数据中选择活细胞C1和C2的至少一部分图像作为测量对象的显示单元23和操作单元24; 以及图像处理单元22,提取测量对象的亮度值,并且基于测量对象的亮度值在给予外部刺激之前和之后的变化来计算关于所测量对象的反射光的强度变化的信息 活细胞C1和C2。
    • 10. 发明专利
    • Method for immobilizing live cell and sensor for measuring activating function of live cell
    • 用于固定活细胞和传感器的方法,用于测量活细胞的活化功能
    • JP2007014327A
    • 2007-01-25
    • JP2006155125
    • 2006-06-02
    • Hiroshima UnivWakunaga Pharmaceut Co Ltd国立大学法人広島大学湧永製薬株式会社
    • HIDE MICHIHIROSUZUKI HIDEKIYANASE YUKI
    • C12N11/14C12M1/40G01N33/543
    • PROBLEM TO BE SOLVED: To provide a method for immobilizing a live cell especially suitable for evaluating activating functions of the live cell utilizing plasmon resonance and having an excellent sticking tendency in relation to the method for immobilizing the live cell in order to immobilize the live cell on the surface of a solid phase.
      SOLUTION: The method for immobilizing the live cell comprises immobilizing the live cell through a live cell immobilizing material composed of an organic compound having a thiol group and an amino group or an organic compound having a disulfide group and amino group on the surface of the solid phase. The live cell is preferably immobilized under physiological environments and the surface of the solid phase is preferably a metal surface having affinity for the thiol group or disulfide group. The organic compound is preferably an aminoalkanethiol or a disulfide type compound in which the two molecules thereof are bound. A sensor for measuring the activating functions of the live cell in which the live cell is immobilized on the tip of an optical fiber suitable for evaluating the activating functions of the live cell can be composed by utilizing the method for immobilizing the live cell.
      COPYRIGHT: (C)2007,JPO&INPIT
    • 要解决的问题:提供一种用于固定活细胞的方法,特别适用于利用等离子体共振来评价活细胞的活化功能,并且与固定活细胞的方法相比具有优异的粘附倾向,以便固定 在固相表面的活细胞。 解决方案:固定活细胞的方法包括:通过活性细胞固定化活性物质固定化活性物质,所述活细胞固定化材料由表面上具有硫醇基和氨基的有机化合物或具有二硫键和氨基的有机化合物组成 的固相。 活细胞优选在生理环境下固定,固相表面优选为对硫醇基或二硫基有亲和性的金属表面。 有机化合物优选为其两个分子结合的氨基烷硫醇或二硫化物型化合物。 用于测量活细胞的激活功能的传感器可以通过利用固定活细胞的方法来构成活细胞的活化功能,其中活细胞被固定在适合于评估活细胞的活化功能的光纤的末端上。 版权所有(C)2007,JPO&INPIT