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1. 发明授权

US5547848A Immunoassay element containing a pulverized water-insoluble polysaccharide and process for immunoassay 失效
标题翻译：含有粉碎水不溶性多糖的免疫测定元件和免疫测定方法
公开(公告)号：US5547848A
公开(公告)日：1996-08-20
申请号：US393240
申请日：1995-02-23
申请人： Hiroshi Shinoki , Toshikage Hiraoka , Masashi Ogawa
发明人： Hiroshi Shinoki , Toshikage Hiraoka , Masashi Ogawa
IPC分类号： G01N33/542 , G01N33/543 , G01N33/558 , G01N33/535 , G01N33/548
CPC分类号： G01N33/54386 , G01N33/558
摘要： An immunoassay element for quantitatively analyzing a ligand by determining the change in enzymatic activity. When the ligand is a low molecular weight antigen, competitive reactions between the ligand, enzyme-labelled antibody and conjugate of the antigen and high molecular weight compound are utilized. When the ligand is a macromolecular antigen, a reaction between the ligand and an enzyme-labelled antibody is utilized directly. The immunoassay element comprises a substrate layer containing a non-diffusible substrate which forms a diffusible material in the presence of the enzyme, and a reagent layer for detecting the thus formed diffusible material. The non-diffusible substrate is composed of a pulverized insoluble polysaccharide. The reagent layer may further contain a fragmenting enzyme for further fragmenting the non-diffusible material. Also provided are processes for quantitatively analyzing both of low molecular weight and macromolecular antigens contained in any samples by the use of the immunoassay elements of the invention.
摘要翻译：用于通过确定酶活性的变化定量分析配体的免疫测定元件。当配体是低分子量抗原时，配体，酶标记抗体与抗原结合物和高分子量化合物之间的竞争性反应被利用。当配体是大分子抗原时，直接使用配体和酶标记的抗体之间的反应。免疫测定元件包括含有在酶存在下形成可扩散材料的不扩散基底的基底层和用于检测由此形成的可扩散材料的试剂层。非扩散性基材由粉碎的不溶性多糖组成。试剂层可以进一步包含用于进一步碎裂非扩散材料的碎裂酶。还提供了通过使用本发明的免疫测定元件定量分析任何样品中所含的低分子量和大分子抗原的方法。

2. 发明授权

US06589754B1 Immunoassay element and process for immunoassay 失效
标题翻译：免疫测定元件和免疫测定方法
公开(公告)号：US06589754B1
公开(公告)日：2003-07-08
申请号：US08946685
申请日：1997-10-08
申请人： Toshikage Hiraoka , Tetsuji Tanimoto , Yoshihiko Makino , Tadashi Ninomiya , Hiroshi Shinoki , Yoshihiro Ashihara , Naofumi Hora , Masashi Ogawa
发明人： Toshikage Hiraoka , Tetsuji Tanimoto , Yoshihiko Makino , Tadashi Ninomiya , Hiroshi Shinoki , Yoshihiro Ashihara , Naofumi Hora , Masashi Ogawa
IPC分类号： G01N3353
CPC分类号： G01N33/54386
摘要： An immunoassay element for quantitatively analyzing a macromolecular antigen by determining the change in enzymatic activity caused by a reaction between the macromolecular polymer antigen and an enzyme-labelled antibody. The immunoassay element comprises a substrate layer containing a non-diffusible substrate which forms a diffusible material in the presence of the enzyme, and a reagent layer containing a fragmenting enzyme for further fragmenting the diffusible material into a lower molecular weight product. Also provided is a process for quantitatively analyzing a macromolecular antigen in a sample by the use of the immunoassay element.
摘要翻译：一种用于通过测定由高分子聚合物抗原和酶标记的抗体之间的反应引起的酶活性的变化来定量分析大分子抗原的免疫测定元件。免疫测定元件包括含有在酶存在下形成可扩散材料的不扩散基底的基底层和含有用于进一步将可扩散材料分解成较低分子量产物的碎裂酶的试剂层。还提供了通过使用免疫测定元件定量分析样品中的大分子抗原的方法。

3. 发明授权

US5447846A Homogeneous Immunoassay process using covalent conjugate of enzyme and plural monoclonal antibodies for different epitopes on analyte 失效
标题翻译：均质免疫测定方法使用酶和多种单克隆抗体的共价缀合物对分析物上的不同表位进行
公开(公告)号：US5447846A
公开(公告)日：1995-09-05
申请号：US91661
申请日：1993-07-14
申请人： Hiroshi Shinoki , Masashi Ogawa
发明人： Hiroshi Shinoki , Masashi Ogawa
IPC分类号： G01N33/542 , G01N33/543 , G01N33/58 , G01N33/68 , G01N33/53
CPC分类号： G01N33/581 , G01N33/542 , G01N33/54386 , G01N33/6857 , Y10S435/964 , Y10S435/969 , Y10S435/97 , Y10S435/972 , Y10S530/866
摘要： An enzyme-labelled antibody adapted for use in a homogeneous immunoassay is provided. The enzyme-labelled antibody is a conjugate of an enzyme with two or more different monoclonal antibodies, each of the monoclonal antibodies being capable of specifically recognizing and binding to a different epitope of the same antigen. By using the enzyme-labelled antibody in the homogeneous enzyme immunoassay process, an analyte can be quantitatively analyzed at a higher sensitivity through a simple operation. Also provided is a dry immunoassay element comprising an immunological reaction layer containing the enzyme-labelled antibody. By the provision of such an immunoassay element, a further simplified quick analysis of an analyte is realized to give an accurate result.
摘要翻译：提供适用于均相免疫测定法的酶标记抗体。酶标记的抗体是酶与两种或更多种不同单克隆抗体的缀合物，每种单克隆抗体能够特异性识别并结合相同抗原的不同表位。通过在均相酶免疫测定法中使用酶标记的抗体，可以通过简单的操作以更高的灵敏度对分析物进行定量分析。还提供了包含含有酶标记抗体的免疫反应层的干免疫测定元件。通过提供这样的免疫测定元件，实现了分析物的进一步简化的快速分析以给出准确的结果。

4. 发明授权

US5882935A Analysis element and method for analyzing glycated hemoglobin content ratio 失效
标题翻译：分析元素及分析糖化血红蛋白含量的方法
公开(公告)号：US5882935A
公开(公告)日：1999-03-16
申请号：US544133
申请日：1995-10-17
申请人： Kikuo Hirai , Hiroshi Shinoki , Masashi Ogawa , Yoshihiko Makino
发明人： Kikuo Hirai , Hiroshi Shinoki , Masashi Ogawa , Yoshihiko Makino
IPC分类号： G01N33/53 , G01N33/52 , G01N33/542 , G01N33/72 , H01L21/302 , H01L21/304 , H01L21/306 , H01L21/76
CPC分类号： G01N33/723 , G01N33/721
摘要： An analysis element for analyzing both amounts of glycated hemoglobin and total hemoglobin in an aqueous liquid sample to determine glycated hemoglobin content ratio in the sample. The element comprises a substrate layer for receiving a reaction mixture after the completion of an immunological reaction between the glycated hemoglobin in the sample and an enzyme-labelled antibody against the glycated hemoglobin, and a reagent layer. The substrate layer contains a non-diffusible substrate which forms a diffusible material in the presence of the enzyme of the enzyme-labelled antibody, the activity of the enzyme being effected relative to the steric hindrance due to the immunological reaction. The reagent layer contains a reagent composition for reacting with the diffusible material to form a dye detectable colorimetrically in a wavelength range which is not effected by an absorption spectrum of the hemoglobin. The total hemoglobin retained in the substrate layer and the dye formed in the reagent layer are colorimetrically analyzed separately, and the glycated hemoglobin content ratio is calculated from respective values. An analysis method using this analysis element is also provided.
摘要翻译：分析元素，用于分析含水液体样品中糖化血红蛋白和总血红蛋白的量，以测定样品中糖化血红蛋白含量的比例。该元件包括用于在样品中的糖化血红蛋白和糖化血红蛋白的酶标记抗体完成后的反应混合物和试剂层的基底层。底物层含有在酶标记抗体的酶存在下形成可扩散材料的非扩散性底物，该酶的活性相对于由于免疫反应引起的空间位阻影响。试剂层含有用于与可扩散材料反应的试剂组合物，以形成可在不受血红蛋白的吸收光谱影响的波长范围内比色测定的染料。分别保留在基材层中的总血红蛋白和形成在试剂层中的染料，并根据各值计算糖化血红蛋白含量比。还提供了使用该分析元素的分析方法。

5. 发明授权

US06287785B1 Homogenous enzyme immunoassay process 失效
标题翻译：均质酶免疫测定法
公开(公告)号：US06287785B1
公开(公告)日：2001-09-11
申请号：US09488371
申请日：2000-01-20
申请人： Hiroshi Shinoki , Osamu Seshimoto
发明人： Hiroshi Shinoki , Osamu Seshimoto
IPC分类号： G01N33533
CPC分类号： G01N33/535 , G01N33/542 , G01N33/54306 , Y10S435/963 , Y10S435/964 , Y10S435/969 , Y10S435/972 , Y10S436/823 , Y10S530/866
摘要： An improved homogeneous enzyme immunoassay process for quantitatively analyzing an antigen by determining the change in the enzymatic activity caused by a reaction between the antigen and an enzyme-labeled antibody. The antigen is reacted with an enzyme-labeled antibody, followed by the reaction with a second antibody capable of recognizing and binding to a different epitope and then with a third antibody capable of recognizing and binding to the second antibody. The enzymatic activity of the labeling enzyme is determined by a water-insoluble substrate. Using the water-insoluble substrate, steric hindrance is enhanced. A highly-sensitive analysis can be carried out by a simple operation even when the antigen has a molecular weight falling within an intermediate range, for example, a range of M.W. 10,000 to 70,000.
摘要翻译：一种改进的均匀酶免疫测定方法，用于通过测定由抗原和酶标记的抗体之间的反应引起的酶活性的变化来定量分析抗原。使抗原与酶标记的抗体反应，然后与能够识别和结合不同表位的第二抗体反应，然后与能够识别和结合第二抗体的第三抗体反应。标记酶的酶活性由水不溶性底物决定。使用水不溶性底物，空间位阻增强。即使当抗原具有分子量落在中间范围内时，也可以通过简单的操作进行高灵敏度分析，例如，10,000至70000MW的范围。

6. 发明申请

US20050019790A1 Fixation of nucleotide derivatives to solid carrier 审中-公开
标题翻译：核苷酸衍生物固定于固体载体
公开(公告)号：US20050019790A1
公开(公告)日：2005-01-27
申请号：US10777585
申请日：2004-02-12
申请人： Yoshihide Iwaki , Yoshihiko Makino , Hiroshi Shinoki , Satoru Kuhara , Kosuke Tashiro , Shigeru Muta
发明人： Yoshihide Iwaki , Yoshihiko Makino , Hiroshi Shinoki , Satoru Kuhara , Kosuke Tashiro , Shigeru Muta
IPC分类号： G01N33/53 , B01J19/00 , C12M1/00 , C12N15/09 , C40B40/06 , C40B60/14 , G01N33/566 , G01N37/00 , C12Q1/68 , B05D3/00 , C12M1/34
CPC分类号： B01J19/0046 , B01J2219/00351 , B01J2219/00527 , B01J2219/00529 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/00608 , B01J2219/00612 , B01J2219/00626 , B01J2219/00637 , B01J2219/00659 , B01J2219/00689 , B01J2219/00722 , C40B40/06 , C40B60/14
摘要： A micro-array for analysis of DNA is prepared by the steps of spotting onto a solid carrier in its predetermined area in which plural reactive groups are fixed an aqueous solution which contains a thickening agent and probe molecules (e.g., DNA fragments) having a group reactive with the reactive group of the solid carrier to produce covalent bonding; spotting onto the solid carrier in a different area having the same reactive groups an aqueous solution (same or different); incubating the aqueous solution-spotted solid carrier to produce the covalent bondings; and washing the solid carrier with an aqueous medium to remove the thickening agent from the solid carrier. An electrostatic bonding can be utilized in place of the covalent bonding.
摘要翻译：用于分析DNA的微阵列通过以下步骤制备：将固定载体固定在其中固定有多个反应性基团的预定区域的固体载体上，所述固定载体含有增稠剂的水溶液和具有基团的探针分子（例如，DNA片段）与固体载体的反应性基团反应产生共价键; 在具有相同反应性基团的不同区域的固体载体上发现水溶液（相同或不同）; 孵育水溶液点固体载体以产生共价键; 并用水介质洗涤固体载体以从固体载体中除去增稠剂。可以使用静电键来代替共价键。

7. 发明授权

US4966607A Method of producing dyed polysaccharide:amino or imino starch derivative with reactive dye 失效
标题翻译：生产染色多糖的方法：具有活性染料的氨基或亚氨基淀粉衍生物
公开(公告)号：US4966607A
公开(公告)日：1990-10-30
申请号：US339014
申请日：1989-04-14
申请人： Hiroshi Shinoki , Mitsunori Ono
发明人： Hiroshi Shinoki , Mitsunori Ono
IPC分类号： C08B31/00 , C08B31/12 , C09B62/78 , C09B69/10 , D06P3/00 , D06P3/58
CPC分类号： C09B69/10 , C08B31/00 , C08B31/12 , D06P3/58
摘要： A method of producing a dyed polysaccharide which comprises linking a dye, capable of linking to amino group or imino group, to a starch derivative having a glucose derivative unit shown in a general formula [I] as a partial structure of the starch derivative. ##STR1## In the formula [I], R represents an arylene group or an alkylene group, R.sub.1, represents hydrogen atom or an alkyl group, and X and Y represent linking portions to other portions of the starch molecule, respectively.According to the method of the invention, dyed polysaccharides can readily be obtained by using a commercial reactive dye at room temperature under neutral conditions.
摘要翻译：染色多糖的制造方法，其特征在于，将通式[I]所示的具有葡萄糖衍生物单元的淀粉衍生物与淀粉衍生物的部分结构连接，将能够与氨基或亚氨基连接的染料连接。 [I]在式[I]中，R表示亚芳基或亚烷基，R 1表示氢原子或烷基，X和Y分别表示与淀粉分子的其它部分的连接部分。根据本发明的方法，在室温下在中性条件下使用市售的活性染料可以容易地得到染色的多糖。

8. 发明授权

US06733975B2 DNA chip and its preparation 有权
标题翻译： DNA芯片及其制备
公开(公告)号：US06733975B2
公开(公告)日：2004-05-11
申请号：US10042703
申请日：2002-03-21
申请人： Tadahisa Sato , Koki Nakamura , Hiroshi Shinoki
发明人： Tadahisa Sato , Koki Nakamura , Hiroshi Shinoki
IPC分类号： C12Q168
CPC分类号： C40B40/06 , B01J19/0046 , B01J2219/00387 , B01J2219/00608 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00628 , B01J2219/00637 , B01J2219/00722 , C40B60/14
摘要： An analytical element (typically DNA chip) composed of a solid carrier and a group of nucleotide derivatives or their analogues fixed to the solid carrier can be produced by bringing nucleotide derivatives or the analogues having an alkyne group at one terminal into contact with a zero-valent metal film (e.g., silver metal film or copper metal film) placed on the solid carrier.
摘要翻译：可以通过使核苷酸衍生物或在一个末端具有炔基的类似物与零载体接触来制备由固体载体和固定在固体载体上的一组核苷酸衍生物或其类似物组成的分析元件（通常为DNA芯片）（例如银金属膜或铜金属膜）放置在固体载体上。

9. 发明授权

US06642375B2 Fluorescent substances 失效
标题翻译：荧光物质
公开(公告)号：US06642375B2
公开(公告)日：2003-11-04
申请号：US09731279
申请日：2000-12-06
申请人： Hiroko Inomata , Hiroshi Shinoki , Masayoshi Kojima , Yukio Sudo , Junji Nishigaki , Osamu Seshimoto
发明人： Hiroko Inomata , Hiroshi Shinoki , Masayoshi Kojima , Yukio Sudo , Junji Nishigaki , Osamu Seshimoto
IPC分类号： C07H1904
CPC分类号： G01N33/582
摘要： The present invention provides a fluorescent substance which is represented by a formula: A-B-C wherein A is a residue of natural or synthetic nucleotide, oligonucleotide, polynucleotide, or derivative thereof, and binds to B at a base moiety in said residue, or A is a residue of avidin or streptavidin; B is a divalent linking group or a single bond; and C is a monovalent group derived from a general formula (I) and binds to B at a reactive group present in R1 or R2: wherein R1 and R2 each independently represent an alkyl group that may be substituted with a reactive group capable of covalently bonding to A-B-; R3, R4, R5, and R6 each independently represent an alkyl group, and R3 and R4, and/or R5 and R6 may bind to each other to form a saturated carbon-ring together with a carbon atom(s) to which they bind; V1, V2, V3, V4, V5, V6, V7, V8, V9 and V10 each independently represent a hydrogen atom or a monovalent substituent, and two adjacent groups thereof may bind to form a ring; L1, L2, and L3 represent a substituted or unsubstituted methine group; each of m, n, s, and t represents 0 or 1, provided that m+n=1 and s+t=1; p represents 1, 2, or 3; M represents a counter ion; and q represents a number required to neutralize the charge of a molecule. The fluorescent substance of the present invention is useful as a labeling substance for nucleic acids, or as a reagent for analyzing biological components such as nucleic acids, proteins or sugars.
摘要翻译：本发明提供一种荧光物质，其由下式表示：AB-C，其中A是天然或合成的核苷酸，寡核苷酸，多核苷酸或其衍生物的残基，并与所述残基中的碱基部分的B结合，或A是抗生物素蛋白或链霉亲和素的残基; B是二价连接基团或单键; 和C是衍生自通式（I）的一价基团，并且在R 1或R 2中存在的反应性基团上与B结合：其中R 1和R 2各自独立地表示烷基，可以被能够与AB-共价结合的反应性基团取代; R 3，R 4，R 5和R 6各自独立地表示烷基，R 3和R 4和/或R 5和R 6独立地表示烷基，可以彼此结合形成饱和碳环与它们所结合的碳原子一起; V 1，V 2，V 3，V 4，V 5，V 6，V 7，V 8，V 9和V 10 独立地表示氢原子或一价取代基，其两个相邻基团可以结合形成环; L 1，L 2和L 3表示取代或未取代的次甲基; m，n，s和t中的每一个表示0或1，条件是m + n = 1且s + t = 1; p表示1,2或3; M表示抗衡离子; q表示中和分子电荷所需的数。本发明的荧光物质可用作核酸的标记物质，或用作分析核酸，蛋白质或糖类等生物成分的试剂。

10. 发明授权

US06531323B1 Agglutination assay method and element in a dry system 有权
标题翻译：凝集测定方法和干燥系统中的元素
公开(公告)号：US06531323B1
公开(公告)日：2003-03-11
申请号：US09493574
申请日：2000-01-28
申请人： Hiroshi Shinoki , Yoshikazu Amano
发明人： Hiroshi Shinoki , Yoshikazu Amano
IPC分类号： G01N33546
CPC分类号： G01N33/54313 , G01N33/54393 , Y10S435/969 , Y10S436/805
摘要： An agglutination assay method for quantitatively determination of an analyte in a liquid sample using particles bearing an anti-analyte. A non-fluid substance which retains the particles while suppressing the diffusion of the particles therein is used as a medium which is to be a place where the agglutination of the particles takes place. Upon analysis, a solation agent is added to the non-fluid substance medium to increase the fluidity of the non-fluid substance, thereby the particles bearing the anti-analyte can diffuse in the medium to cause the agglutination with the analyte. Preferably, the solation agent is added to the non-fluid medium together with the sample. The non-fluid substance medium containing the particle-labeled anti-analyte can be stored with a higher stability in the dry state. A dry analysis element for enabling such analysis method is also provided.
摘要翻译：用于使用带有抗分析物的颗粒定量测定液体样品中的分析物的凝集测定方法。使用保持颗粒同时抑制颗粒扩散的非流体物质作为发生颗粒凝集的地方的介质。分析后，向非流体物质介质中加入溶剂，以增加非流体物质的流动性，从而带有抗分析物的颗粒可以在介质中扩散以引起与分析物的凝集。优选地，将溶剂与样品一起添加到非流体介质中。含有颗粒标记的抗分析物的非流体物质介质可以在干燥状态下以更高的稳定性储存。还提供了用于实现这种分析方法的干燥分析元件。

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