公开(公告)号：US07999941B2

公开(公告)日：2011-08-16

申请号：US12282611

申请日：2007-03-14

申请人： Tomohiko Matsushita ,  Hideyuki Yamashita ,  Takeo Nishikawa ,  Megumi Moriyama ,  Ryosuke Hasui ,  Shigeru Aoyama

发明人： Tomohiko Matsushita ,  Hideyuki Yamashita ,  Takeo Nishikawa ,  Megumi Moriyama ,  Ryosuke Hasui ,  Shigeru Aoyama

IPC分类号： G01N21/55

CPC分类号： G01N21/553 ,  G01J3/02 ,  G01J3/0256 ,  G01J3/0294

摘要： A metal layer 13 made of Au or the like is formed on the upper surface of a transparent substrate 12. Dielectric layers 14a, 14b and 14c with different thicknesses are formed on the upper surface of the metal layer 13 (any one of the dielectric layers can have a thickness of 0) to form respective determination areas 15a, 15b and 15c. Further, different types of antibodies 22a, 22b and 22c are fixed on the upper surfaces of the respective dielectric layers 14a, 14b and 14c. Then, light is directed to the determination areas 15a, 15b and 15c, then signals of light reflected by the determination areas 15a, 15b and 15c are received, the light is dispersed, and analyses are performed on signals resulted from the light dispersion to detect the conditions of the surfaces of the respective determination areas, at the same time.

摘要翻译： 在透明基板12的上表面上形成有由Au等制成的金属层13.在金属层13的上表面上形成具有不同厚度的电介质层14a，14b和14c（介电层中的任何一个 可以具有0的厚度）以形成相应的确定区域15a，15b和15c。 此外，不同类型的抗体22a，22b和22c固定在各个电介质层14a，14b和14c的上表面上。 然后，将光导向确定区域15a，15b和15c，然后接收由确定区域15a，15b和15c反射的光的信号，散射光，并且对由光散射产生的信号进行分析以检测 同时确定各个确定区域的表面条件。

公开(公告)号：US20100067015A1

公开(公告)日：2010-03-18

申请号：US12282611

申请日：2007-03-14

申请人： Tomohiko Matsushita ,  Hideyuki Yamashita ,  Takeo Nishikawa ,  Megumi Moriyama ,  Ryosuke Hasui ,  Shigeru Aoyama

发明人： Tomohiko Matsushita ,  Hideyuki Yamashita ,  Takeo Nishikawa ,  Megumi Moriyama ,  Ryosuke Hasui ,  Shigeru Aoyama

IPC分类号： G01N21/55 ,  G01N21/27 ,  B29C59/02 ,  B44C1/22

CPC分类号： G01N21/553 ,  G01J3/02 ,  G01J3/0256 ,  G01J3/0294

摘要： A metal layer 13 made of Au or the like is formed on the upper surface of a transparent substrate 12. Dielectric layers 14a, 14b and 14c with different thicknesses are formed on the upper surface of the metal layer 13 (any one of the dielectric layers can have a thickness of 0) to form respective determination areas 15a, 15b and 15c. Further, different types of antibodies 22a, 22b and 22c are fixed on the upper surfaces of the respective dielectric layers 14a, 14b and 14c. Then, light is directed to the determination areas 15a, 15b and 15c, then signals of light reflected by the determination areas 15a, 15b and 15c are received, the light is dispersed, and analyses are performed on signals resulted from the light dispersion to detect the conditions of the surfaces of the respective determination areas, at the same time.

摘要翻译： 在透明基板12的上表面上形成有由Au等制成的金属层13.在金属层13的上表面上形成具有不同厚度的电介质层14a，14b和14c（介电层中的任何一个 可以具有0的厚度）以形成相应的确定区域15a，15b和15c。 此外，不同类型的抗体22a，22b和22c固定在各个电介质层14a，14b和14c的上表面上。 然后，将光导向确定区域15a，15b和15c，然后接收由确定区域15a，15b和15c反射的光的信号，散射光，并且对由光散射产生的信号进行分析以检测 同时确定各个确定区域的表面条件。

公开(公告)号：US07839508B2

公开(公告)日：2010-11-23

申请号：US12042910

申请日：2008-03-05

申请人： Takeo Nishikawa ,  Tomohiko Matsushita ,  Hideyuki Yamashita ,  Ryosuke Hasui ,  Satoshi Fujita ,  Yutaro Okuno ,  Shigeru Aoyama

发明人： Takeo Nishikawa ,  Tomohiko Matsushita ,  Hideyuki Yamashita ,  Ryosuke Hasui ,  Satoshi Fujita ,  Yutaro Okuno ,  Shigeru Aoyama

IPC分类号： G01N21/00

CPC分类号： G01N21/554 ,  B82Y15/00 ,  G01N21/253 ,  G01N2021/0346 ,  G01N2021/0378 ,  G01N2021/0382 ,  G01N2021/054

摘要： A sensor chip has a metal layer formed on a surface of a substrate, where a plurality of microscopic concave part is formed in a measurement region of the surface of the metal layer. When light of linear polarization is irradiated onto the measurement region, local resonance electric field generates at opposing metal layer surfaces in the concave part. The reflected light thereof is received to measure reflectance. The light of linear polarization is irradiated so that the polarizing surface becomes orthogonal to the longitudinal direction of the concave part.

摘要翻译： 传感器芯片具有形成在基板的表面上的金属层，在金属层的表面的测量区域中形成有多个微观凹部。 当线偏振光照射在测量区域上时，在凹部的相对的金属层表面产生局部共振电场。 接收其反射光以测量反射率。 照射线偏振光，使得偏振面与凹部的长度方向正交。

公开(公告)号：US20080218761A1

公开(公告)日：2008-09-11

申请号：US12042910

申请日：2008-03-05

申请人： Takeo Nishikawa ,  Tomohiko Matsushita ,  Hideyuki Yamashita ,  Ryosuke Hasui ,  Satoshi Fujita ,  Yutaro Okuno ,  Shigeru Aoyama

发明人： Takeo Nishikawa ,  Tomohiko Matsushita ,  Hideyuki Yamashita ,  Ryosuke Hasui ,  Satoshi Fujita ,  Yutaro Okuno ,  Shigeru Aoyama

IPC分类号： G01N21/55

CPC分类号： G01N21/554 ,  B82Y15/00 ,  G01N21/253 ,  G01N2021/0346 ,  G01N2021/0378 ,  G01N2021/0382 ,  G01N2021/054

摘要： A sensor chip has a metal layer formed on a surface of a substrate, where a plurality of microscopic concave part is formed in a measurement region of the surface of the metal layer. When light of linear polarization is irradiated onto the measurement region, local resonance electric field generates at opposing metal layer surfaces in the concave part. The reflected light thereof is received to measure reflectance. The light of linear polarization is irradiated so that the polarizing surface becomes orthogonal to the longitudinal direction of the concave part.

摘要翻译： 传感器芯片具有形成在基板的表面上的金属层，在金属层的表面的测量区域中形成有多个微观凹部。 当线偏振光照射在测量区域上时，在凹部的相对的金属层表面产生局部共振电场。 接收其反射光以测量反射率。 照射线偏振光，使得偏振面与凹部的长度方向正交。

公开(公告)号：US20070224639A1

公开(公告)日：2007-09-27

申请号：US11477153

申请日：2006-06-28

申请人： Tomohiko Matsushita ,  Takeo Nishikawa ,  Hideyuki Yamashita ,  Masaaki Ikeda ,  Shigeru Aoyama ,  Tetsuichi Wazawa ,  Hiroshi Sezaki

发明人： Tomohiko Matsushita ,  Takeo Nishikawa ,  Hideyuki Yamashita ,  Masaaki Ikeda ,  Shigeru Aoyama ,  Tetsuichi Wazawa ,  Hiroshi Sezaki

IPC分类号： G01N33/53 ,  C12M3/00

CPC分类号： G01N33/54353

摘要： A substrate for immobilizing biomolecules comprises a chip substrate, a hydrophilic monolayer, and a lipid bilayer, and a biochip comprising the substrate for immobilizing biomolecules on which biomolecules are immobilized. The substrate for immobilizing biomolecules includes a transparent chip substrate, a metal layer provided on the chip substrate, a monolayer provided on the metal layer, and a lipid bilayer provided on the monolayer. The metal layer is composed of fine particles of Au, the monolayer is composed of self-assembled molecules represented by X—(CH2)n—OH (where X is a thiol group), and the lipid bilayer is composed of self-assembled phospholipids. The monolayer and the lipid bilayer are relatively flexibly bound together via hydrogen bonds. In the biochip, a receptor is immobilized on the lipid bilayer via a biorecognition molecule.

摘要翻译： 用于固定生物分子的底物包括芯片底物，亲水性单层和脂质双层，以及包含用于固定其上固定生物分子的生物分子的底物的生物芯片。 用于固定生物分子的基板包括透明芯片衬底，设置在芯片衬底上的金属层，设置在金属层上的单层和设置在单层上的脂质双层。 金属层由Au的细颗粒构成，单层由由X（CH 2）n -OH表示的自组装分子组成（其中X为 硫醇基），脂质双层由自组装磷脂组成。 单层和脂质双层通过氢键相对灵活地结合在一起。 在生物芯片中，通过生物识别分子将受体固定在脂质双层上。

公开(公告)号：US20080037022A1

公开(公告)日：2008-02-14

申请号：US10589044

申请日：2005-02-10

申请人： Takeo Nishikawa ,  Shigeru Aoyama ,  Tomohiko Matsushita ,  Shigemi Norioka ,  Tetsuichi Wazawa

发明人： Takeo Nishikawa ,  Shigeru Aoyama ,  Tomohiko Matsushita ,  Shigemi Norioka ,  Tetsuichi Wazawa

IPC分类号： G01N21/55 ,  B05D5/12 ,  G02B5/28

CPC分类号： G01N21/554 ,  Y10T428/31678

摘要： In a surface plasmon resonance sensor including a chip with a substrate 102 and a metal layer 103, a prism 104, an optical system 105 serving as a light source, and a light detector 106, the metal layer 103 is configured by a flat part 109 formed into a thin film, and convex parts formed from metal particles 110 and the like arranged spaced apart from each other. When light enters the metal layer 103 of such configuration, resonance angle arising from the flat part 109 and the convex parts are respectively obtained. The change in index of refraction of a medium contacted by the metal layer is detected from such resonance angle.

摘要翻译： 在包括具有基板102和金属层103的芯片的表面等离子体共振传感器，棱镜104，用作光源的光学系统105和光检测器106中，金属层103由平坦部分109 形成为薄膜，并且由彼此间隔开设置的金属颗粒110等形成的凸部。 当光进入这种结构的金属层103时，分别获得从平坦部分109和凸起部分产生的共振角度。 从这种共振角度检测与金属层接触的介质的折射率的变化。

公开(公告)号：US20070211254A1

公开(公告)日：2007-09-13

申请号：US10582188

申请日：2004-12-08

申请人： Tomohiko Matsushita ,  Takeo Nishikawa ,  Yuko Tsuda ,  Shigemi Norioka ,  Tetsuichi Wazawa ,  Shigeru Aoyama

发明人： Tomohiko Matsushita ,  Takeo Nishikawa ,  Yuko Tsuda ,  Shigemi Norioka ,  Tetsuichi Wazawa ,  Shigeru Aoyama

IPC分类号： G01N21/55

CPC分类号： G01N21/7703 ,  G01N21/553

摘要： At both ends of a waveguide 43 having a plurality of cores 51, light emitting elements 47 and light receiving elements 49 are disposed so as to face end faces of the cores 51. A switch 44 is overlapped over the waveguide 43. In the switch 44, switching windows 52 each can be switched between a state where light propagating through the core 51 is passed and a state where the light is reflected are arranged in the vertical and horizontal directions, and the switching windows 52 are arranged along the top faces of the cores 51. A test board 45 having a plurality of channels 60 in each of which a metallic thin film 61 is formed is disposed over the switch 44, and receptors 62 are fixed on the metallic thin film 61 in the channels 60. A specimen containing a specific ligand is passed in each of the channels 60.

摘要翻译： 在具有多个芯51的波导43的两端，发光元件47和光接收元件49设置成面对芯51的端面。 开关44重叠在波导43上。 在开关44中，切换窗52各自可以在通过芯51传播的光通过的状态和反射光的状态沿垂直和水平方向布置，并且切换窗口52沿着 芯51的顶面。 具有多个通道60的测试板45中的每一个形成有金属薄膜61设置在开关44上方，并且通道60中的金属薄膜61上固定有受体62。 含有特定配体的样品通过每个通道60。

公开(公告)号：US06856359B2

公开(公告)日：2005-02-15

申请号：US10422644

申请日：2003-04-24

申请人： Tomohiko Matsushita ,  Takeo Nishikawa ,  Shigeru Aoyama

发明人： Tomohiko Matsushita ,  Takeo Nishikawa ,  Shigeru Aoyama

IPC分类号： B01L3/00 ,  G02F1/13

CPC分类号： B01L3/502715 ,  B01L2300/0636 ,  B01L2300/0654 ,  B01L2300/0877 ,  G02B6/0046

摘要： A biochip includes a liquid crystal panel having liquid crystal cells each corresponding to each sample on a substrate. The liquid crystal panel includes an upper polarization filter, an upper transparent electrode, an upper orientation film, a liquid crystal, a lower orientation film, a lower transparent electrode and a lower polarization filter in this order. By application of voltage to a desired liquid crystal cell, external light is selectively radiated onto the sample. Thus, it is possible to achieve downsizing, cost reduction and high-speed operation of a biochip reader.

摘要翻译： 生物芯片包括具有各自对应于基板上的每个样品的液晶单元的液晶面板。 液晶面板依次包括上偏振滤光器，上透明电极，上取向膜，液晶，下取向膜，下透明电极和下偏振滤光器。 通过将电压施加到期望的液晶单元，外部光被选择性地辐射到样品上。 因此，可以实现生物芯片读取器的小型化，降低成本和高速运行。

公开(公告)号：US07906344B2

公开(公告)日：2011-03-15

申请号：US10594698

申请日：2005-03-30

申请人： Tomohiko Matsushita ,  Shigeru Aoyama ,  Takeo Nishikawa ,  Shingo Nagaoka ,  Tetsuichi Wazawa

发明人： Tomohiko Matsushita ,  Shigeru Aoyama ,  Takeo Nishikawa ,  Shingo Nagaoka ,  Tetsuichi Wazawa

IPC分类号： G01N33/553

CPC分类号： G01N21/648 ,  Y10S435/808 ,  Y10S436/805

摘要： The metal fine particles 33 are sparsely fixed on the surface of the transparent substrate 32, and the acceptor 35 for attaching the specific ligand is immobilized on the transparent substrate 32 or the metal fine particles 33. The prism 36 is closely attached to the lower surface of the transparent substrate 32, and the excitation light enters the transparent substrate 32 through the prism 36. The incident light is totally reflected at the surface of the transparent substrate 32, and the evanescent light generated at the surface and the metal fine particles 33 locally plasmon resonate. As the evanescent light and the metal fine particles locally plasmon resonate, a strong electric field is enclosed in the vicinity of the metal fine particles. When the surface arranged with the metal fine particles 33 and the acceptor 35 is contacted to the analysis sample solution containing ligand modified with light emitting molecules, only the light emitting molecule modifying a specific ligand attached to the acceptor emits light.

摘要翻译： 金属微粒33被稀疏地固定在透明基板32的表面上，用于附着特定配体的受主35被固定在透明基板32或金属微粒33上。棱镜36紧密地附着在下表面 并且激发光通过棱镜36进入透明基板32.入射光在透明基板32的表面全反射，并且在表面产生的ev逝光和金属微粒33局部地反射 等离子体共振。 当瞬间光和金属微粒局部等离子体共振时，强电场被包围在金属微粒附近。 当配置有金属微粒33和受体35的表面与含有用发光分子改性的配体的分析样品溶液接触时，只有修饰与受体相连的特定配体的发光分子发光。

公开(公告)号：US20050046758A1

公开(公告)日：2005-03-03

申请号：US10902495

申请日：2004-07-29

申请人： Tomohiko Matsushita ,  Shigeru Aoyama ,  Takeo Nishikawa ,  Yuko Tsuda ,  Shigemi Norioka ,  Tetsuichi Wazawa

发明人： Tomohiko Matsushita ,  Shigeru Aoyama ,  Takeo Nishikawa ,  Yuko Tsuda ,  Shigemi Norioka ,  Tetsuichi Wazawa

IPC分类号： G01N33/53 ,  B81C1/00 ,  B81C99/00 ,  G01N33/48 ,  G01N33/50 ,  G01N35/00 ,  G01N37/00 ,  G02F1/017 ,  G02F1/13 ,  H01S5/34

CPC分类号： B82Y20/00 ,  B01J2219/00382 ,  B01J2219/00385 ,  B01J2219/00436 ,  B01J2219/00527 ,  B01J2219/00576 ,  B01J2219/00596 ,  B01J2219/00605 ,  B01J2219/00612 ,  B01J2219/00617 ,  B01J2219/00619 ,  B01J2219/00621 ,  B81B2201/0214 ,  B81B2201/06 ,  B81C1/00206 ,  B81C99/009 ,  B82Y5/00 ,  B82Y10/00 ,  G02F2001/01791 ,  G02F2202/32 ,  H01S5/3412

摘要： A method of mass-producing minute structures such as biochips, protein chips, quantum dots, and quantum chips involves arranging an antigen two-dimensionally on a board and arranging probes two-dimensionally facing the same direction so that the binding sites of the probes may bind to the antigen. An inorganic substance such as Ni is deposited on the board from the upper side of the probes by sputtering or evaporation to form a thin film layer and on the top surface of the flatly formed thin film layer, a supporting layer is formed by separating out the same inorganic substance using electrotyping. Then, by peeling the thin film layer and the supporting layer off of the board together, the mother stamper having cavities for the patterns of biomolecules is obtained.

摘要翻译： 大规模生产生物芯片，蛋白质芯片，量子点和量子芯片的微小结构的方法包括将二维布置在板上，并将探针二维排列成相同的方向，使得探针的结合位点 结合抗原。 无机物质如Ni通过溅射或蒸发从探针的上侧沉积在板上以形成薄膜层，并且在平坦形成的薄膜层的顶表面上，通过分离出 使用电化学的相同无机物质。 然后，通过将薄膜层和支撑层从板上剥离在一起，获得具有用于生物分子图案的空腔的母模。