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1. 发明申请

US20080227124A1 Solid phases optimized for chemiluminescent detection 审中-公开
公开(公告)号：US20080227124A1
公开(公告)日：2008-09-18
申请号：US12076235
申请日：2008-03-14
申请人： Brooks Edwards , Timothy G. Geiser , Steven M. Menchen , Alison L. Sparks , John C. Voyta
发明人： Brooks Edwards , Timothy G. Geiser , Steven M. Menchen , Alison L. Sparks , John C. Voyta
IPC分类号： G01N33/53 , G01N21/76 , B05D3/02 , C12Q1/00
CPC分类号： C12Q1/6823 , B01J2219/00659 , B01J2219/00702 , B01J2219/00722 , B01J2219/00725 , C40B40/06 , C40B40/10 , C40B50/14 , G01N33/54393 , Y10S436/805 , Y10S436/823
摘要： Solid supports for chemiluminescent assays are provided. The solid support includes a plurality of probes covalently or physically attached to the support surface and a chemiluminescent enhancing moiety incorporated onto the surface or into the bulk of the support. The solid support can be a multi-layered support including an upper probe binding layer (e.g., an azlactone polymer layer or porous functional polyamide layer) adjacent to a cationic microgel layer. The azlactone-functional polymer can be a copolymer of dimethylacrylamide and vinylazlactone crosslinked with ethylenediamine. The cationic microgel layer can be a cross-linked quaternary onium salt containing polymer. A method and a kit for conducting chemiluminescent assays using the solid supports is also provided. The kit comprises a dioxetane substrate, a biopolymer probe-enzyme complex, and a solid support. The solid support can be an azlactone functional polymer layer adjacent to a cationic microgel layer; a porous polyamide functional layer adjacent to a cationic microgel layer; or a quaternized azlactone functional polymer layer.

2. 发明授权

US07368296B2 Solid phases optimized for chemiluminescent detection 有权
标题翻译：为化学发光检测优化的固相
公开(公告)号：US07368296B2
公开(公告)日：2008-05-06
申请号：US10046730
申请日：2002-01-17
申请人： Brooks Edwards , Timothy G. Geiser , Steven M. Menchen , Alison L. Sparks , John C. Voyta
发明人： Brooks Edwards , Timothy G. Geiser , Steven M. Menchen , Alison L. Sparks , John C. Voyta
IPC分类号： G01N33/545 , G01N33/533 , C07C211/62
CPC分类号： C12Q1/6823 , B01J2219/00659 , B01J2219/00702 , B01J2219/00722 , B01J2219/00725 , C40B40/06 , C40B40/10 , C40B50/14 , G01N33/54393 , Y10S436/805 , Y10S436/823
摘要： Solid supports for chemiluminescent assays are provided. The solid support includes a plurality of probes covalently or physically attached to the support surface and a chemiluminescent enhancing moiety incorporated onto the surface or into the bulk of the support. The solid support can be a multi-layered support including an upper probe binding layer (e.g., an azlactone polymer layer or porous functional polyamide layer) adjacent to a cationic microgel layer. The azlactone-functional polymer can be a copolymer of dimethylacrylamide and vinylazlactone crosslinked with ethylenediamine. The cationic microgel layer can be a cross-linked quaternary onium salt containing polymer. A method and a kit for conducting chemiluminescent assays using the solid supports is also provided. The kit comprises a dioxetane substrate, a biopolymer probe-enzyme complex, and a solid support. The solid support can be an azlactone functional polymer layer adjacent to a cationic microgel layer; a porous polyamide functional layer adjacent to a cationic microgel layer; or a quaternized azlactone functional polymer layer.
摘要翻译：提供了化学发光测定的固体支持物。固体支持物包括共价或物理连接到支持物表面上的多个探针和结合到表面或载体的大部分中的化学发光增强部分。固体支持物可以是包含邻近阳离子微凝胶层的上探针结合层（例如，吖内酯聚合物层或多孔功能性聚酰胺层）的多层载体。吖内酯官能聚合物可以是与乙二胺交联的二甲基丙烯酰胺和乙烯基内酯的共聚物。阳离子微凝胶层可以是交联的含季铵盐的聚合物。还提供了使用固体支持物进行化学发光测定的方法和试剂盒。试剂盒包括二氧杂环丁烷底物，生物聚合物探针 - 酶复合物和固体支持物。固体支持物可以是与阳离子微凝胶层相邻的吖内酯官能聚合物层; 与阳离子微凝胶层相邻的多孔聚酰胺官能层; 或季铵化的吖内酯官能聚合物层。

3. 发明授权

US5783381A Chemiluminescent 1,2-dioxetanes 失效
公开(公告)号：US5783381A
公开(公告)日：1998-07-21
申请号：US545174
申请日：1995-10-19
申请人： Irena Bronstein , Brooks Edwards , Alison Sparks , John C. Voyta
发明人： Irena Bronstein , Brooks Edwards , Alison Sparks , John C. Voyta
IPC分类号： G01N31/00 , C07D305/06 , C07D321/00 , C07F7/18 , C09K11/07 , C12Q1/34 , G01N21/78 , G01N33/52 , C12Q1/00
CPC分类号： C12Q1/34 , C07D321/00 , C07F7/1856 , G01N33/52 , Y10S435/975
摘要： Dioxetanes that can be triggered by bases are provided which can be used to detect bases in organic solvents, aqueous preparations and detect gaseous bases in the atmosphere. The dioxetanes can be used to detect the release of bases from various labels, as a means to detect the presence of a base released by physical or natural processes, to calibrate light measuring apparatus and to determine the amount of reducing or oxidizing agent present in the base.

4. 发明授权

US5342966A Purification of stablewater-soluble dioxetanes 失效
标题翻译：稳定的水溶性二氧杂环丁烷的纯化
公开(公告)号：US5342966A
公开(公告)日：1994-08-30
申请号：US517322
申请日：1990-05-01
申请人： Brooks Edwards , John C. Voyta
发明人： Brooks Edwards , John C. Voyta
IPC分类号： C07D321/00 , C07F9/655 , C09K11/06 , C09K11/07 , C12Q1/42 , G01N21/76 , G01N33/532 , C07F9/12
CPC分类号： C07D321/00 , C07F9/65512
摘要： Methods are disclosed for purifying chemiluminescent water-soluble 1,2-dioxetane derivatives suitable for use as reporter molecules in a variety of biological analytical systems, including enzyme-linked immunoassays, nucleic acid probe techniques, and structural determinations. The methods are based upon high pressure, medium pressure or low pressure liquid chromatography using as the stationary phase alkaline pH-stable compositions with the chromatographic characteristics of reversed-phase adsorbents, at alkaline pH values, and in the absence of acid-forming compounds or compounds with an unshared pair of electrons. Desalting of substantially pure water soluble 1,2-dioxetane derivatives may be accomplished by the same chromatographic systems or by molecular sieve chromatography systems, but in the absence of salt buffers. Under some circumstances, purification and desalting may be combined in a single chromatographic step. Substantially pure chemiluminescent water-soluble 1,2-dioxetane derivatives prepared by the methods of the invention are also disclosed.
摘要翻译：公开了用于纯化适合用作各种生物分析系统中的报告分子的化学发光水溶性1,2-二氧杂环丁烷衍生物的方法，包括酶联免疫测定，核酸探针技术和结构测定。该方法基于使用具有反相吸附剂的色谱特性，碱性pH值和不存在酸形成化合物的稳定相碱性pH稳定组合物的高压，中压或低压液相色谱法具有非共享电子对的化合物。基本上纯的水溶性1,2-二氧环乙烷衍生物的脱盐可以通过相同的色谱系统或分子筛色谱系统来完成，但是在不存在盐缓冲液的情况下。在某些情况下，纯化和脱盐可以在单个色谱步骤中组合。还公开了通过本发明的方法制备的基本纯化学发光的水溶性1,2-二氧杂环丁烷衍生物。

5. 发明授权

US4931569A Purification of stable water-soluble dioxetanes 失效
标题翻译：稳定的水溶性二氧杂环丁烷的纯化
公开(公告)号：US4931569A
公开(公告)日：1990-06-05
申请号：US244006
申请日：1988-09-14
申请人： Brooks Edwards , John C. Voyta
发明人： Brooks Edwards , John C. Voyta
IPC分类号： C07D321/00 , C07F9/655 , C09K11/06 , C09K11/07 , C12Q1/42 , G01N21/76 , G01N33/532
CPC分类号： C07D321/00 , C07F9/65512
摘要： Methods are disclosed for purifying chemiluminescent water-soluble 1,2-dioxetane derivatives suitable for use as reporter molecules in a variety of biological analytical systems, including enzyme-linked immunoassays, nucleic acid probe techniques, and structural determinations. The methods are based upon high pressure, medium pressure or low pressure liquid chromatography using as the stationary phase alkaline pH-stable compositions with the chromatographic characteristics of reversed-phase adsorbents, at alkaline pH values, and in the absence of acid-forming compounds or compounds with an unshared pair of electrons. Desalting of substantially pure water soluble 1,2-dioxetane derivatives may be accomplished by the same chromatographic systems or by molecular sieve chromatography systems, but in the absence of salt buffers. Under some circumstances, purification and desalting may be combined in a single chromatographic step. Substantially pure chemiluminescent water-soluble 1,2-dioxetane derivatives prepared by the methods of the invention are also disclosed.
摘要翻译：公开了用于纯化适合用作各种生物分析系统中的报告分子的化学发光水溶性1,2-二氧杂环丁烷衍生物的方法，包括酶联免疫测定，核酸探针技术和结构测定。该方法基于使用具有反相吸附剂的色谱特性，碱性pH值和不存在酸形成化合物的稳定相碱性pH稳定组合物的高压，中压或低压液相色谱法具有非共享电子对的化合物。基本上纯的水溶性1,2-二氧环乙烷衍生物的脱盐可以通过相同的色谱系统或分子筛色谱系统来完成，但是在不存在盐缓冲液的情况下。在某些情况下，纯化和脱盐可以在单个色谱步骤中组合。还公开了通过本发明的方法制备的基本纯化学发光的水溶性1,2-二氧杂环丁烷衍生物。

6. 发明授权

US5994073A Enhancement of chemiluminescent assays 失效
标题翻译：增强化学发光测定
公开(公告)号：US5994073A
公开(公告)日：1999-11-30
申请号：US850009
申请日：1997-05-01
申请人： Irena Y. Bronstein , Brooks Edwards , John C. Voyta
发明人： Irena Y. Bronstein , Brooks Edwards , John C. Voyta
IPC分类号： C07D321/00 , C12Q1/68
CPC分类号： C09K11/07 , C07F9/12 , C07F9/6551
摘要： Chemiluminescent bioassays for the presence or concentration of an analyte in a sample use 1,2-dioxetanes as substrates for the enzyme of an enzyme complex that bind to the analyte. The chemiluminescence obtained from the decomposition of the dioxetane triggered by the enzyme through the formation of the corresponding 1,2-dioxetane oxyanion of the enzyme complex is enhanced by the addition of TBQ as an enhancement agent. Other polymeric quaternary onium salts can be used as enhancement agents in conjunction with enhancement additives which improve the ability of the enhancement agent to form hydrophobic regions in the aqueous sample, in which regions the 1,2-dioxetane oxyanion and its chemiluminescent decomposition products can be sequestered. A kit for performing such assays is also provided.
摘要翻译：用于样品中分析物的存在或浓度的化学发光生物测定使用1,2-二氧杂环丁烷作为与分析物结合的酶复合物的酶的底物。通过添加TBQ作为增强剂，增强了通过酶复合物形成相应的1,2-二氧杂环丁烷氧阴离子而由酶引发的二氧杂环丁烷的分解获得的化学发光。其他聚合季铵盐可用作增强剂与增强添加剂一起使用，增强添加剂改善增强剂在水样品中形成疏水区的能力，其中1,2-二氧环乙烷氧阴离子及其化学发光分解产物可以是隔离还提供了用于进行这种测定的试剂盒。

7. 发明授权

US5843681A Dioxetane compounds for the chemiluminescent detection of proteases, methods of use and kits therefore 失效
标题翻译：因此，用于化学发光检测蛋白酶的二氧杂环丁烷化合物，使用方法和试剂盒
公开(公告)号：US5843681A
公开(公告)日：1998-12-01
申请号：US728990
申请日：1996-10-11
申请人： Irena Bronstein , Brooks Edwards , Christopher Martin , Alison Sparks , John C. Voyta
发明人： Irena Bronstein , Brooks Edwards , Christopher Martin , Alison Sparks , John C. Voyta
IPC分类号： G01N33/573 , C07D321/00 , C07K5/072 , C07K5/08 , C07K5/09 , C07K5/10 , C12Q1/37 , G01N33/58
CPC分类号： C07K5/06095 , C07D321/00 , C07K5/0802 , C07K5/0817 , C07K5/1002 , C12Q1/37 , G01N33/582 , Y10S530/807
摘要： 1, 2-dioxetane compounds bearing a proteolytic enzyme specific amino acid or peptide are provided, which amino acid or peptide can be removed by action of the corresponding protease. When the amino acid or peptide is removed, the 1,2-dioxetane decomposes with chemiluminescence, the generation of light providing a rapid, ultra-sensitive and convenient means for detecting the presence of the protease in the sample being inspected. The amount of light generated, or degree of chemiluminescence, can be correlated with the amount of protease present. Immunoassays, as well as DNA hybridization and DNA probe assays are provided.
摘要翻译：提供了带有蛋白水解酶特异性氨基酸或肽的1,2-二氧杂环丁烷化合物，该氨基酸或肽可以通过相应的蛋白酶的作用除去。当去除氨基酸或肽时，1,2-二氧杂环丁烷以化学发光分解，产生光，提供快速，超灵敏和方便的手段，用于检测待检样品中蛋白酶的存在。产生的光量或化学发光度可以与存在的蛋白酶的量相关。提供免疫测定，以及DNA杂交和DNA探针测定。

8. 发明授权

US5591591A Dioxetane compounds for the chemiluminescent detection of proteases, methods of use and kits therefore 失效
标题翻译：用于化学发光检测蛋白酶的二氧杂环丁烷化合物，使用方法及其试剂盒
公开(公告)号：US5591591A
公开(公告)日：1997-01-07
申请号：US385788
申请日：1995-02-09
申请人： Irena Bronstein , Brooks Edwards , Christopher Martin , Alison Sparks , John C. Voyta
发明人： Irena Bronstein , Brooks Edwards , Christopher Martin , Alison Sparks , John C. Voyta
IPC分类号： G01N33/573 , C07D321/00 , C07K5/072 , C07K5/08 , C07K5/09 , C07K5/10 , C12Q1/37 , G01N33/58 , C07K5/06
CPC分类号： C07K5/06095 , C07D321/00 , C07K5/0802 , C07K5/0817 , C07K5/1002 , C12Q1/37 , G01N33/582 , Y10S530/807
摘要： 1,2-dioxetane compounds bearing a proteolytic enzyme specific amino acid or peptide are provided, which amino acid or peptide can be removed by action of the corresponding protease. When the amino acid or peptide is removed, the 1,2-dioxetane decomposes with chemiluminescence, the generation of light providing a rapid, ultra-sensitive and convenient means for detecting the presence of the protease in the sample being inspected. The amount of light generated, or degree of chemiluminescence, can be correlated with the amount of protease present. Immunoassays, as well as DNA hybridization and DNA probe assays are provided.
摘要翻译：提供了带有蛋白水解酶特异性氨基酸或肽的1,2-二氧环乙烷化合物，该氨基酸或肽可以通过相应的蛋白酶的作用除去。当去除氨基酸或肽时，1,2-二氧杂环丁烷以化学发光分解，产生光，提供快速，超灵敏和方便的手段，用于检测待检样品中蛋白酶的存在。产生的光量或化学发光度可以与存在的蛋白酶的量相关。提供免疫测定，以及DNA杂交和DNA探针测定。

9. 发明授权

US08865478B2 Reagents, kits and methods for detecting biological molecules by energy transfer from an activated chemiluminescent substrate to an energy acceptor dye 有权
标题翻译：通过从活化化学发光底物到能量受体染料的能量转移来检测生物分子的试剂，试剂盒和方法
公开(公告)号：US08865478B2
公开(公告)日：2014-10-21
申请号：US12126094
申请日：2008-05-23
申请人： Rouh-Rong Juo , John C. Voyta , Brooks Edwards
发明人： Rouh-Rong Juo , John C. Voyta , Brooks Edwards
IPC分类号： G01N33/533 , C12M1/34 , G01N33/543 , G01N33/58 , G01N33/542
CPC分类号： G01N33/543 , G01N33/533 , G01N33/542 , G01N33/54313 , G01N33/573 , G01N33/581 , G01N2333/916
摘要： Reagents, kits and methods for detecting biological molecules by energy transfer from an activated chemiluminescent substrate to an energy acceptor dye such as a J-aggregated dye are described.
摘要翻译：描述了通过从活化化学发光底物到能量受体染料如J-聚集染料的能量转移来检测生物分子的试剂，试剂盒和方法。

10. 发明申请

US20090047688A1 REAGENTS, KITS AND METHODS FOR DETECTING BIOLOGICAL MOLECULES BY ENERGY TRANSFER FROM AN ACTIVATED CHEMILUMINESCENT SUBSTRATE TO AN ENERGY ACCEPTOR DYE 有权
标题翻译：通过能量转移从激活的CHEMILUMINESCENT底物到能量受体染料检测生物分子的试剂，试剂盒和方法
公开(公告)号：US20090047688A1
公开(公告)日：2009-02-19
申请号：US12126094
申请日：2008-05-23
申请人： Rouh-Rong Juo , John C. Voyta , Brooks Edwards
发明人： Rouh-Rong Juo , John C. Voyta , Brooks Edwards
IPC分类号： G01N33/53 , G01N21/76 , C12Q1/42
CPC分类号： G01N33/543 , G01N33/533 , G01N33/542 , G01N33/54313 , G01N33/573 , G01N33/581 , G01N2333/916
摘要： Reagents, kits and methods for detecting biological molecules by energy transfer from an activated chemiluminescent substrate to an energy acceptor dye such as a J-aggregated dye are described.
摘要翻译：描述了通过从活性化学发光底物到能量受体染料如J-聚集染料的能量转移来检测生物分子的试剂，试剂盒和方法。

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