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1. 发明授权

US06399305B1 Protection of partial complementary nucleic acid fragment using a electroconductive chip and intercalator 有权
标题翻译：使用导电芯片和嵌入剂保护部分互补核酸片段
公开(公告)号：US06399305B1
公开(公告)日：2002-06-04
申请号：US09588950
申请日：2000-06-07
申请人： Yoshihiko Makino , Yoshihiko Abe , Makoto Takagi , Shigeori Takenaka , Kenichi Yamashita , Masashi Ogawa
发明人： Yoshihiko Makino , Yoshihiko Abe , Makoto Takagi , Shigeori Takenaka , Kenichi Yamashita , Masashi Ogawa
IPC分类号： C12Q168
CPC分类号： C12Q1/6825 , Y10T436/143333 , C12Q2563/173 , C12Q2563/113
摘要： A method of analyzing a nucleic acid fragment sample to judge whether the nucleic acid fragment sample is uncomplementary, partly complementary or complementary to a DNA fragment in its specific base sequence is conducted by the steps of: bringing an aqueous solution of the nucleic acid fragment sample into contact with a DNA chip having an electroconductive substrate and the DNA fragment fixed onto the substrate in the presence of an electrochemical thread intercalator; measuring an electric current flowing from or to the electroconductive substrate along the DNA fragment under application of a potential to the substrate; and comparing the electric current measured above with a referential electric current which is prepared employing a DNA chip equivalent to the above DNA chip, the intercalator, and an aqueous solution of a nucleic acid fragment which is complementary to the DNA fragment of the DNA chip.
摘要翻译：分析核酸片段样品以判断核酸片段样品是否与其特异性碱基序列中的DNA片段不互补，部分互补或互补的方法通过以下步骤进行：使核酸片段样品的水溶液与具有导电性基体的DNA芯片接触，并且在电化学线性嵌入剂的存在下固定在基材上的DNA片段;测量在施加电位下沿着DNA片段向基片流向或流到导电基底的电流 ; 并使用与上述DNA芯片相当的DNA芯片，嵌入剂和与DNA芯片的DNA片段互补的核酸片段的水溶液制备的参考电流来比较上述电流。

2. 发明授权

US06294670B1 Probe for detecting a highly ordered structural site of a single stranded nucleic acid of a gene, and a method and a device for detecting the same 失效
标题翻译：用于检测基因的单链核酸的高度有序结构位点的探针，以及用于检测基因的单链核酸的方法和装置
公开(公告)号：US06294670B1
公开(公告)日：2001-09-25
申请号：US09313992
申请日：1999-05-19
申请人： Shigeori Takenaka
发明人： Shigeori Takenaka
IPC分类号： C07F100
CPC分类号： C07F17/02
摘要： The invention provides a probe for detecting a highly ordered structural site of a nucleic acid of a gene by specifically binding with the structural site to generate an electrochemical response. The inventive probe comprises a cyclic ligand containing ferrocenyl group and a DNA threading intercalating moiety, such as 1, 4, 5, 8-tetrasubstituted naphthalene, 9, 10-disubstituted anthracene, and 1, 5-disubstituted anthraquinone. Current of the cyclic ligand is not observed due to interaction such as stacking or so called charge transfer between ferrocenyl group and the DNA threading intercalating moiety in conventional electrolyte. The binding of the ligand with a highly ordered structural site of a single stranded nucleic acid, where nucleic base inserts between the cavity of cyclic ligand, inhibits the intramolecular interaction of the ligand to convert the ligand into its electrically active form, and as a result, current is observed.
摘要翻译：本发明提供了用于通过与结构位点特异性结合来检测基因核酸的高度有序结构位点以产生电化学响应的探针。本发明的探针包括含有二茂铁基的环状配体和DNA穿线插层部分，例如1,4,5,8-四取代萘，9,10-二取代蒽和1,5-二取代蒽醌。由于在二茂铁基和常规电解质中的DNA穿线插入部分之间的相互作用如堆叠或所谓的电荷转移，没有观察到环状配体的电流。配体与单链核酸的高度有序结构位点的结合，其中核碱基插入环状配体的空腔之间，抑制配体的分子内相互作用以将配体转化为其电活性形式，结果，观察电流。

3. 发明授权

US06261780B1 Quantitative analysis of biochemical compound utilizing electrochemical reaction 失效
标题翻译：利用电化学反应定量分析生化化合物
公开(公告)号：US06261780B1
公开(公告)日：2001-07-17
申请号：US09477973
申请日：2000-01-05
申请人： Masashi Ogawa , Shigeori Takenaka , Makoto Takagi
发明人： Masashi Ogawa , Shigeori Takenaka , Makoto Takagi
IPC分类号： C12Q168
CPC分类号： C12Q1/60 , C12Q1/001 , C12Q1/26 , C12Q1/54 , C12Q1/6825 , C12Q2563/173 , C12Q2545/114 , C12Q2527/137
摘要： A method for quantitatively analyzing a biochemical compound such as glucose or cholesterol is performed by bringing the biochemical compound into contact with double stranded DNA fragments which are fixed onto a surface of an electrode at their one terminals and in which electrochemically active threading intercalators are intercalated, in an aqueous medium under application of electric potential to the electrode in the presence of an oxidase capable of oxidizing the biochemical compound and becoming a reduced oxidase, and detecting an electric current flowing between the electrode and another electrode placed in the aqueous medium.
摘要翻译：通过使生物化学化合物与固定在电极表面上的双链DNA片段接触并进行电化学活性穿插嵌入剂的插入，进行定量分析生物化学化合物如葡萄糖或胆固醇的方法，在能够氧化生物化学化合物并变成还原氧化酶的氧化酶存在下向电极施加电位的水性介质中，并且检测在电极和置于水性介质中的另一电极之间流动的电流。

4. 发明申请

US20110100812A1 ELECTRODE MODULE 失效
标题翻译：电极模块
公开(公告)号：US20110100812A1
公开(公告)日：2011-05-05
申请号：US12988285
申请日：2009-04-02
申请人： Shigeori Takenaka , Yoshiaki Hano , Minoru Yamada , Kimio Morimoto , Hiroshi Endo , Hiroshi Yasutake , Shinobu Sato , Keiichi Otsuka
发明人： Shigeori Takenaka , Yoshiaki Hano , Minoru Yamada , Kimio Morimoto , Hiroshi Endo , Hiroshi Yasutake , Shinobu Sato , Keiichi Otsuka
IPC分类号： G01N27/30
CPC分类号： G01N27/403
摘要： An electrode module includes a working electrode, a counter electrode, a reference electrode and a well (container) for retaining an electrolytic solution and is used in electrochemical measuring instruments. This electrode module is produced by integrating the well with at least one of the working electrode, the counter electrode and the reference electrode. This integrated electrode includes a chip-like electrode having a thin membrane of an electrode material formed on the surface of a chip-like base metal. This chip-like electrode is disposed on and integrated with the bottom of the well in a detachable manner. There is provided the compact, low price electrode module of high repetition use efficiency with no need of maintenance and having easy handling.
摘要翻译：电极模块包括用于保持电解液的工作电极，对电极，参比电极和阱（容器），并用于电化学测量仪器中。该电极模块通过将阱与工作电极，对电极和参考电极中的至少一个集成来制造。该集成电极包括具有形成在芯片状母材表面上的电极材料的薄膜的芯片状电极。这种芯片状电极以可拆卸的方式设置在阱的底部并与其一体化。提供了高重复使用效率的紧凑，价格低廉的电极模块，无需维护和易于处理。

5. 发明授权

US06916614B1 Gene detecting chip, detector, and detecting method 失效
标题翻译：基因检测芯片，检测器和检测方法
公开(公告)号：US06916614B1
公开(公告)日：2005-07-12
申请号：US09868576
申请日：2000-10-20
申请人： Shigeori Takenaka , Kazuhiko Uchida , Takatoshi Miyahara
发明人： Shigeori Takenaka , Kazuhiko Uchida , Takatoshi Miyahara
IPC分类号： B01L3/00 , G01N27/07 , G01N27/403 , G01N35/10 , C12Q1/68
CPC分类号： G01N27/3275 , B01J2219/00653
摘要： A detecting chip (2) comprising a body (5) and a frame (4) both detachable from each other. A large number of projecting pin electrodes (10) are arranged in a matrix inside the body (5). Oligonucleotide consisting of different gene sequences is fixed to the pin electrode (10). A common electrode is so disposed in a recess (8) in a frame (4) as to be out of contact with the pin electrodes (10). A DNA sample is placed in the recess (8). By applying a voltage between the common electrode and the pin electrodes (10), a current is detected to detect a hybridized two-strand DNA, thus analyzing a gene DNA.
摘要翻译：一种检测芯片（2），包括彼此分离的主体（5）和框架（4）。大量突出的针脚电极（10）以矩阵形式布置在主体（5）内。由不同基因序列组成的寡核苷酸固定在针电极（10）上。公共电极被设置在框架（4）的凹部（8）中，以与引脚电极（10）脱离接触。将DNA样品置于凹部（8）中。通过在公共电极和针状电极（10）之间施加电压，检测电流以检测杂交的双链DNA，从而分析基因DNA。

6. 发明授权

US06864055B2 Method for detecting nucleic acids 有权
标题翻译：检测核酸的方法
公开(公告)号：US06864055B2
公开(公告)日：2005-03-08
申请号：US09887625
申请日：2001-06-22
申请人： Yoshihiko Makino , Yoshihiko Abe , Masashi Ogawa , Makoto Takagi , Shigeori Takenaka , Kenichi Yamashita
发明人： Yoshihiko Makino , Yoshihiko Abe , Masashi Ogawa , Makoto Takagi , Shigeori Takenaka , Kenichi Yamashita
IPC分类号： G01N33/53 , C07B61/00 , C07K14/00 , C12M1/00 , C12N15/09 , C12Q1/68 , G01N27/416 , G01N33/566 , B01D57/02 , C12P19/34 , G01N30/02
CPC分类号： C12Q1/6825 , C07K14/003 , C12Q1/6837 , C40B40/00 , C12Q2565/501 , C12Q2565/102 , C12Q2565/607
摘要： A method of detecting nucleic acid fragments in plural samples is performed by the steps of: attaching an electroconductive label to nucleic acid fragments in one sample and attaching a different electroconductive label to nucleic acid fragments in another sample; preparing a mixture of these samples; spotting the mixture on an electroconductive microarray having plural electrodes onto which probe molecules complementary to the nucleic acid fragments are fixed, so that hybridization between the nucleic acid fragments and the probe molecules on the electroconductive microarray can proceed to form hybrid structures; applying to the electrode an electric potential corresponding to the oxidation-reduction potential of the former label and detecting on the electrode an electric current; applying to the electrode an electric potential corresponding to the oxidation-reduction potential of the latter label and detecting on the electrode an electric current; and comparing the electric current detected in the former detecting procedure and that detected in the latter detecting procedure.
摘要翻译：通过以下步骤进行检测多个样品中的核酸片段的方法：将导电标记物附着在一个样品中的核酸片段上，并将不同的导电标记连接到另一个样品中的核酸片段; 准备这些样品的混合物; 在具有多个电极的导电微阵列上将该混合物点样，在该导电微阵列上固定有与核酸片段互补的探针分子，使得导电微阵列上的核酸片段和探针分子之间的杂交可以进行以形成杂化结构; 向所述电极施加与所述前标签的氧化还原电位相对应的电位，并在所述电极上检测电流; 向所述电极施加与后一标签的氧化还原电位相对应的电位，并在所述电极上检测电流; 并比较前一检测程序检测的电流和后一检测程序中检测的电流。

7. 发明授权

US06713255B1 DNA chip, PNA chip, and their preparation methods 有权
标题翻译： DNA芯片，PNA芯片及其制备方法
公开(公告)号：US06713255B1
公开(公告)日：2004-03-30
申请号：US09589221
申请日：2000-06-07
申请人： Yoshihiko Makino , Yoshihiko Abe , Makoto Takagi , Shigeori Takenaka , Kenichi Yamashita , Masashi Ogawa
发明人： Yoshihiko Makino , Yoshihiko Abe , Makoto Takagi , Shigeori Takenaka , Kenichi Yamashita , Masashi Ogawa
IPC分类号： C12Q168
CPC分类号： C07K14/003 , B01J19/0046 , B01J2219/00529 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/00608 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00626 , B01J2219/00637 , B01J2219/00641 , B01J2219/00659 , B01J2219/00722 , B01J2219/00729 , C07B2200/11 , C07H21/00 , C12Q1/6837 , C40B40/06 , C12Q2565/607
摘要： A DNA chip (or PNA chip) composed of a solid carrier and plural DNA fragments (or PNA fragments) fixed onto is the solid carrier at each one end, wherein a plurality of short chain spacer molecules having a hydrophilic moiety at each one end are fixed at each another end onto a surface of the solid carrier having no DNA fragments (or no PNA fragments) on its surface is effective for high sensitive quantitative analysis of a nucleic acid fragment complementary to the DNA fragment (or PNA fragment).
摘要翻译：由固体载体和固定在其上的多个DNA片段（或PNA片段）组成的DNA芯片（或PNA芯片）是每一端的固体载体，其中在每一端具有亲水部分的多个短链间隔基分子是固定在其表面上没有DNA片段（或没有PNA片段）的固体载体的表面上对于与DNA片段（或PNA片段）互补的核酸片段的高敏感性定量分析是有效的。

8. 发明授权

US06528648B2 Detecting reagent for double-stranded nucleic acid and double-stranded nucleic acid detecting method 失效
标题翻译：双链核酸检测试剂和双链核酸检测方法
公开(公告)号：US06528648B2
公开(公告)日：2003-03-04
申请号：US10012211
申请日：2001-12-05
申请人： Kazuko Matsumoto , Takahiko Nojima , Hideo Tashiro , Yasumitsu Kondoh , Shigeori Takenaka
发明人： Kazuko Matsumoto , Takahiko Nojima , Hideo Tashiro , Yasumitsu Kondoh , Shigeori Takenaka
IPC分类号： C07D29100
CPC分类号： C09B57/10 , C09B57/08 , C12Q1/6816 , C12Q2563/173
摘要： The present invention provides a novel detecting reagent for double-stranded nucleic acid, and a method of using it to detect double-stranded nucleic acid formed by hybridization with a probe, with absolutely no labeling of the target nucleic acid. The detecting reagent for double-stranded nucleic acid of the invention is characterized by comprising, in the same molecule, a naphthalenediimide group which is intercalatable into double-stranded nucleic acid and a &bgr;-diketone group capable of forming a lanthanoid metal complex.
摘要翻译：本发明提供了一种用于双链核酸的新型检测试剂及其用于检测与探针杂交形成的双链核酸的方法，绝对没有靶核酸的标记。双重检测试剂其特征在于在相同分子中包含可插入双链核酸的萘二酰亚胺基团和能够形成镧系元素金属络合物的β-二酮基团。

9. 发明授权

US08623183B2 Electrode module 失效
标题翻译：电极模块
公开(公告)号：US08623183B2
公开(公告)日：2014-01-07
申请号：US12988285
申请日：2009-04-02
申请人： Shigeori Takenaka , Yoshiaki Hano , Minoru Yamada , Kimio Morimoto , Hiroshi Endo , Hiroshi Yasutake , Shinobu Sato , Keiichi Otsuka
发明人： Shigeori Takenaka , Yoshiaki Hano , Minoru Yamada , Kimio Morimoto , Hiroshi Endo , Hiroshi Yasutake , Shinobu Sato , Keiichi Otsuka
IPC分类号： G01N27/403 , G01N27/28
CPC分类号： G01N27/403
摘要： An electrode module includes a working electrode, a counter electrode, a reference electrode and a well (container) for retaining an electrolytic solution and is used in electrochemical measuring instruments. This electrode module is produced by integrating the well with at least one of the working electrode, the counter electrode and the reference electrode. This integrated electrode includes a chip-like electrode having a thin membrane of an electrode material formed on the surface of a chip-like base metal. This chip-like electrode is disposed on and integrated with the bottom of the well in a detachable manner. There is provided the compact, low price electrode module of high repetition use efficiency with no need of maintenance and having easy handling.
摘要翻译：电极模块包括用于保持电解液的工作电极，对电极，参比电极和阱（容器），并用于电化学测量仪器中。该电极模块通过将阱与工作电极，对电极和参考电极中的至少一个集成来制造。该集成电极包括具有形成在芯片状母材表面上的电极材料的薄膜的芯片状电极。这种芯片状电极以可拆卸的方式设置在阱的底部并与其一体化。提供了高重复使用效率的紧凑，价格低廉的电极模块，无需维护和易于处理。

10. 发明授权

US06951936B2 Probe for detecting a highly ordered structural site of a single stranded nucleic acid of a gene, and a method and a device for detecting the same 失效
标题翻译：用于检测基因的单链核酸的高度有序结构位点的探针，以及用于检测基因的单链核酸的方法和装置
公开(公告)号：US06951936B2
公开(公告)日：2005-10-04
申请号：US09902633
申请日：2001-07-12
申请人： Shigeori Takenaka
发明人： Shigeori Takenaka
IPC分类号： C12N15/09 , C07F17/02 , C12Q1/68 , C07F1/00
CPC分类号： C07F17/02
摘要： The invention provides a probe for detecting a highly ordered structural site of a nucleic acid of a gene by specifically binding with the structural site to generate an electrochemical response. The inventive probe comprises a cyclic ligand containing ferrocenyl group and a DNA threading intercalating moiety, such as 1,4,5,8-tetrasubstituted naphthalene, 9,10-disubstituted anthracene, and 1,5-disubstituted anthraquinone. Current of the cyclic ligand is not observed due to interaction such as stacking or so called charge transfer between ferrocenyl group and the DNA threading intercalating moiety in conventional electrolyte. The binding of the ligand with a highly ordered structural site of a single stranded nucleic acid, where nucleic base inserts between the cavity of cyclic ligand, inhibits the intramolecular interaction of the ligand to convert the ligand into its electrically active form, and as a result, current is observed.
摘要翻译：本发明提供了用于通过与结构位点特异性结合来检测基因核酸的高度有序结构位点以产生电化学响应的探针。本发明的探针包括含有二茂铁基的环状配体和DNA穿线插层部分，例如1,4,5,8-四取代萘，9,10-二取代蒽和1,5-二取代蒽醌。由于在二茂铁基和常规电解质中的DNA穿线插入部分之间的相互作用如堆叠或所谓的电荷转移，没有观察到环状配体的电流。配体与单链核酸的高度有序结构位点的结合，其中核碱基插入环状配体的空腔之间，抑制配体的分子内相互作用以将配体转化为其电活性形式，结果，观察电流。

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