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1. 发明申请

US20050046758A1 Method of transcribing biomolecular patterns, method of manufacturing chip boards, and method of manufacturing biochips 失效
标题翻译：转录生物分子模式的方法，制造芯片板的方法以及制造生物芯片的方法
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。

2. 发明授权

US07579165B2 Methods for derivatizing protein or peptide with sulfonic acid groups 有权
标题翻译：用磺酸基团衍生蛋白质或肽的方法
公开(公告)号：US07579165B2
公开(公告)日：2009-08-25
申请号：US10962575
申请日：2004-10-13
申请人： Shigemi Norioka , Minoru Yamaguchi , Hiroki Kuyama , Takashi Obama , Eiji Ando , Takashi Nakazawa , Norikazu Ueyama , Taka-aki Okamura
发明人： Shigemi Norioka , Minoru Yamaguchi , Hiroki Kuyama , Takashi Obama , Eiji Ando , Takashi Nakazawa , Norikazu Ueyama , Taka-aki Okamura
IPC分类号： C07K1/13 , C07K1/14 , C07K14/00 , C12P21/06 , C12Q1/00 , C12Q1/34 , C12Q1/37 , G01N33/53 , G01N33/38 , G01N33/483
CPC分类号： C12N9/2462 , C07K1/1077 , C07K1/128 , C07K14/78
摘要： The present invention provides a method for effectively introducing sulfonic acid groups into the N-terminus of a protein or a peptide. The method comprises a modification step to react a N-terminus in a protein or peptide with a compound A which includes disulfide group and a cleavage step to cleave a disulfide bond of the disulfide group to convert into a sulfonic acid group. The present invention also provides a method of analyzing proteins or peptides easily and effectively on mass spectrometry and an intermediate that can be used to effectively derivatize proteins or peptides as sulfonic acid derivatives.
摘要翻译：本发明提供了将磺酸基团有效地引入蛋白质或肽的N-末端的方法。该方法包括使蛋白质或肽中的N末端与包含二硫键的化合物A和切割二硫键的二硫键以切割成磺酸基团的切割步骤进行反应的修饰步骤。本发明还提供了一种在质谱分析中容易且有效地分析蛋白质或肽的方法，以及可用于有效地将蛋白质或肽衍生为磺酸衍生物的中间体。

3. 发明申请

US20080037022A1 Surface Plasmon Resonance Sensor 审中-公开
标题翻译：表面等离子体共振传感器
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。

4. 发明授权

US07294707B2 Method for modifying protein or peptide C-terminal 有权
标题翻译：蛋白质或肽C端修饰方法
公开(公告)号：US07294707B2
公开(公告)日：2007-11-13
申请号：US10958298
申请日：2004-10-06
申请人： Takashi Nakazawa , Minoru Yamaguchi , Hiroki Kuyama , Eiji Ando , Norikazu Ueyama , Taka-aki Okamura , Shigemi Norioka
发明人： Takashi Nakazawa , Minoru Yamaguchi , Hiroki Kuyama , Eiji Ando , Norikazu Ueyama , Taka-aki Okamura , Shigemi Norioka
IPC分类号： C07K1/00
CPC分类号： C07K1/003
摘要： A simple and low-cost method of selectively modifying the C-terminal of a protein or peptide is provided. A method of modifying the C-terminal of a protein or peptide comprises forming an intramolecular oxazolone ring at the C-terminal of the protein or peptide that requires C-terminal modification, and then performing a ring-opening of the oxazolone ring to produce a protein or peptide with a modified C-terminal. Preferred forms include a method in which by reacting the oxazolone ring with a compound containing a nucleophilic group to effect an oxazolone ring-opening, a protein or peptide is produced in which the C-terminal is modified with the compound containing the nucleophilic group, as well as a method in which by reacting the oxazolone ring with an active esterifying agent to effect a ring-opening, the oxazolone is converted to an active ester, which by subsequent reaction with a compound containing a nucleophilic group, produces a protein or peptide in which the C-terminal has been modified with the compound containing the nucleophilic group.
摘要翻译：提供了选择性修饰蛋白质或肽的C-末端的简单且低成本的方法。修饰蛋白质或肽的C末端的方法包括在需要C末端修饰的蛋白质或肽的C-末端形成分子内的恶唑酮环，然后进行恶唑酮环的开环以产生具有修饰C末端的蛋白质或肽。优选的形式包括通过使恶唑酮环与含有亲核基团的化合物反应以进行恶唑酮开环的方法，制备其中C-末端用含有亲核基团的化合物修饰的蛋白质或肽作为以及通过使恶唑酮环与活性酯化剂反应以开环的方法，将恶唑酮转化成活性酯，其随后与含有亲核基团的化合物反应，产生蛋白质或肽其中C-末端已经与含有亲核基团的化合物一起被修饰。

5. 发明申请

US20050085622A1 Method for modifying protein or peptide C-terminal 有权
标题翻译：蛋白质或肽C端修饰方法
公开(公告)号：US20050085622A1
公开(公告)日：2005-04-21
申请号：US10958298
申请日：2004-10-06
申请人： Takashi Nakazawa , Minoru Yamaguchi , Hiroki Kuyama , Eiji Ando , Norikazu Ueyama , Taka-aki Okamura , Shigemi Norioka
发明人： Takashi Nakazawa , Minoru Yamaguchi , Hiroki Kuyama , Eiji Ando , Norikazu Ueyama , Taka-aki Okamura , Shigemi Norioka
IPC分类号： C07K1/113 , C07K1/00 , C07K1/08 , C07K14/00
CPC分类号： C07K1/003
摘要： A simple and low-cost method of selectively modifying the C-terminal of a protein or peptide is provided. A method of modifying the C-terminal of a protein or peptide comprises forming an intramolecular oxazolone ring at the C-terminal of the protein or peptide that requires C-terminal modification, and then performing a ring-opening of the oxazolone ring to produce a protein or peptide with a modified C-terminal. Preferred forms include a method in which by reacting the oxazolone ring with a compound containing a nucleophilic group to effect an oxazolone ring-opening, a protein or peptide is produced in which the C-terminal is modified with the compound containing the nucleophilic group, as well as a method in which by reacting the oxazolone ring with an active esterifying agent to effect a ring-opening, the oxazolone is converted to an active ester, which by subsequent reaction with a compound containing a nucleophilic group, produces a protein or peptide in which the C-terminal has been modified with the compound containing the nucleophilic group.
摘要翻译：提供了选择性修饰蛋白质或肽的C-末端的简单且低成本的方法。修饰蛋白质或肽的C末端的方法包括在需要C末端修饰的蛋白质或肽的C-末端形成分子内的恶唑酮环，然后进行恶唑酮环的开环以产生具有修饰C末端的蛋白质或肽。优选的形式包括通过使恶唑酮环与含有亲核基团的化合物反应以进行恶唑酮开环的方法，制备其中C-末端用含有亲核基团的化合物修饰的蛋白质或肽作为以及通过使恶唑酮环与活性酯化剂反应以开环的方法，将恶唑酮转化成活性酯，其随后与含有亲核基团的化合物反应，产生蛋白质或肽其中C-末端已经与含有亲核基团的化合物一起被修饰。

6. 发明申请

US20070211254A1 Optical Analyzing Unit and Optical Analyzing Device 失效
标题翻译：光学分析单元和光学分析设备
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。

7. 发明授权

US07501241B2 Method of transcribing biomolecular patterns, method of manufacturing chip boards, and method of manufacturing biochips 失效
标题翻译：转录生物分子模式的方法，制造芯片板的方法以及制造生物芯片的方法
公开(公告)号：US07501241B2
公开(公告)日：2009-03-10
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： C12Q1/68 , C12M1/34 , C08L89/00 , A61K8/73
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。

8. 发明授权

US07342663B2 Optical analyzing unit and optical analyzing device 失效
标题翻译：光学分析装置和光学分析装置
公开(公告)号：US07342663B2
公开(公告)日：2008-03-11
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。

9. 发明授权

US07041472B2 Method for selectively collecting N-terminal peptide fragment of protein 失效
标题翻译：选择性收集蛋白质N-末端肽片段的方法
公开(公告)号：US07041472B2
公开(公告)日：2006-05-09
申请号：US10739111
申请日：2003-12-19
申请人： Shigemi Norioka , Norikazu Ueyama , Taka-aki Okamura , Takashi Nakazawa , Minoru Yamaguchi , Eiji Ando
发明人： Shigemi Norioka , Norikazu Ueyama , Taka-aki Okamura , Takashi Nakazawa , Minoru Yamaguchi , Eiji Ando
IPC分类号： C12P21/06
CPC分类号： C12P21/06
摘要： The present invention provides a method for selectively collecting the N-terminal peptide fragments of a protein of interest whether or not the protein of interest is modified on the N-terminus. A method for selectively collecting the N-terminal peptide fragment of a protein, comprising: a protection step (1) of protecting side chain-amino groups of amino acid residues containing side chain-amino groups of a protein of interest to obtain a protected protein protected on the side chain-amino groups; a fragmentation step (2) of cleaving the protected protein into one N-terminal peptide fragment (a) containing the N-terminus of the peptide of interest and one or more of peptide fragments (b) other than the N-terminal peptide fragment (a); and a separation step (3) of separating the N-terminal peptide fragment (a) from the other peptide fragments (b) by selectively eluting the N-terminal peptide fragment (a) based on the difference in their reactivity or affinity to substrate, wherein the selective elution is achieved either by allowing the other peptide fragments (b) to bind to the substrate while allowing the N-terminal peptide fragment (a) to elute, or by allowing the N-terminal peptide fragment (a) to bind to the substrate while allowing the other peptide fragments (b) to elute and subsequently eluting the bound N-terminal peptide fragment (a).
摘要翻译：本发明提供了一种用于选择性收集目的蛋白质的N-末端肽片段的方法，无论目的蛋白质是否在N末端被修饰。一种用于选择性收集蛋白质的N-末端肽片段的方法，包括：保护步骤（1）保护含有目的蛋白质的侧链 - 氨基的氨基酸残基的侧链氨基以获得受保护的蛋白质保护侧链氨基; 将保护的蛋白质切割成包含目标肽的N末端的一个N-末端肽片段（a）和除了N-末端肽片段之外的一个或多个肽片段（b）的片段化步骤（2）一个）; 以及通过基于它们对底物的反应性或亲和力的差异来选择性地洗脱N末端肽片段（a），从而将N-末端肽片段（a）与其它肽片段（b）分离的分离步骤（3）其中所述选择性洗脱通过使其它肽片段（b）与底物结合同时允许N-末端肽片段（a）洗脱，或通过使N-末端肽片段（a）与同时允许其他肽片段（b）洗脱并随后洗脱结合的N-末端肽片段（a）。

10. 发明申请

US20050084927A1 Method for derivatizing protein or peptide to sulfonic acid derivative 有权
标题翻译：将蛋白质或肽衍生为磺酸衍生物的方法
公开(公告)号：US20050084927A1
公开(公告)日：2005-04-21
申请号：US10962575
申请日：2004-10-13
申请人： Shigemi Norioka , Minoru Yamaguchi , Hiroki Kuyama , Takashi Obama , Eiji Ando , Takashi Nakazawa , Norikazu Ueyama , Taka-aki Okamura
发明人： Shigemi Norioka , Minoru Yamaguchi , Hiroki Kuyama , Takashi Obama , Eiji Ando , Takashi Nakazawa , Norikazu Ueyama , Taka-aki Okamura
IPC分类号： C07K1/107 , C07K1/12 , C07K14/78 , C12N9/36 , C12P21/06 , C07K14/00
CPC分类号： C12N9/2462 , C07K1/1077 , C07K1/128 , C07K14/78
摘要： The present invention provides a method for effectively introducing sulfonic acid groups into the N-terminus of a protein or a peptide; a method capable of analyzing proteins or peptides easily and effectively on mass spectrometry; an intermediate that can be used to effectively derivatize proteins or peptides as sulfonic acid derivatives. A method for derivatizing a protein or peptide to a sulfonic acid derivative, comprising steps of: modification step to react a N-terminus in a protein or peptide with a compound A which includes disulfide group, to obtain a protein or peptide modified with the compound A at the N-terminus; and cleavage step to cleave a disulfide bond of the disulfide group to convert into a sulfonic acid group, thereby converting the modified protein or peptide into a sulfonic acid derivative. A method for analyzing the amino acid sequence of a protein or peptide, wherein the sulfonic acid derivative of a protein or a peptide obtained by the above method is subjected to mass spectrometry. A protein or peptide modified with a disulfide group-containing group at the N-terminus.
摘要翻译：本发明提供了有效地将磺酸基引入蛋白质或肽的N末端的方法; 能够在质谱上容易且有效地分析蛋白质或肽的方法; 可用于有效地将蛋白质或肽衍生为磺酸衍生物的中间体。一种将蛋白质或肽衍生为磺酸衍生物的方法，包括以下步骤：使蛋白质或肽中的N末端与包含二硫键的化合物A反应的修饰步骤，以获得用化合物修饰的蛋白质或肽 A在N端; 以及切割二硫键的二硫键转化为磺酸基的切割步骤，从而将修饰的蛋白质或肽转化为磺酸衍生物。分析蛋白质或肽的氨基酸序列的方法，其中通过上述方法获得的蛋白质或肽的磺酸衍生物进行质谱分析。在N末端用含二硫基的基团修饰的蛋白质或肽。

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