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1. 发明授权

US06183978B2 Luciferase assay, compositions and kits for use in connection therewith 有权
标题翻译：荧光素酶测定，用于与其结合使用的组合物和试剂盒
公开(公告)号：US06183978B2
公开(公告)日：2001-02-06
申请号：US09148782
申请日：1998-09-04
申请人： Irena Bronstein , Corinne E. M. Olesen , John C. Voyta , Yu-Xin Yan
发明人： Irena Bronstein , Corinne E. M. Olesen , John C. Voyta , Yu-Xin Yan
IPC分类号： C12Q166
CPC分类号： C12Q1/66
摘要： An assay for the presence of luciferase in a biological sample offers heightened sensitivity, signal intensity and persistence. The assay is sensitive down to 50 fg luciferase. The biological sample is combined with essential ingredients luciferin, ADP, myokinase and Mg++. The myokinase converts ADP to ATP, necessary for the luciferase reaction, and AMP, which retards the reaction kinetics. The resulting assay exhibits a persistent glow emission which makes it adaptable to automation.
摘要翻译：荧光素酶在生物样品中的存在检测提供了更高的灵敏度，信号强度和持续性。该测定法灵敏度低至50μg萤光素酶。生物样品与必需成分荧光素，ADP，肌激酶和Mg ++组合。肌动蛋白酶将ADP转化为ATP，这是荧光素酶反应所必需的，而AMP则延缓了反应动力学。所得测定显示持续的辉光发射，使其适应于自动化。

2. 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。

3. 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。

4. 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.

5. 发明授权

US6132956A Chemiluminescent 1,2-dioxetanes 失效
标题翻译：化学发光的1,2-二氧杂环丁烷
公开(公告)号：US6132956A
公开(公告)日：2000-10-17
申请号：US964552
申请日：1997-11-05
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.
摘要翻译：提供可由碱触发的二氧杂环丁烷，可用于检测有机溶剂，含水制剂中的碱，并检测大气中的气态碱。二氧杂环丁烷可用于检测各种标记物中碱的释放，作为检测通过物理或天然过程释放的碱的存在的手段，校准光测量装置并确定存在于基础。

6. 发明授权

US5871938A 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：US5871938A
公开(公告)日：1999-02-16
申请号：US935066
申请日：1997-09-22
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。

7. 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。

8. 发明申请

US20120309103A1 METHOD FOR MEASURING LUMINESCENCE AT A LUMINESCENCE DETECTION WORKSTATION 有权
标题翻译：用于在发光检测工作站测量发光的方法
公开(公告)号：US20120309103A1
公开(公告)日：2012-12-06
申请号：US13584628
申请日：2012-08-13
申请人： Michael Gambini , John C. Voyta , John Atwood , Susan A. Atwood-Stone , Bruce E. DeSimas, II , Edward Lakatos , Jeff Levi , Israel Metal , George Sabak , Yongdong Wang
发明人： Michael Gambini , John C. Voyta , John Atwood , Susan A. Atwood-Stone , Bruce E. DeSimas, II , Edward Lakatos , Jeff Levi , Israel Metal , George Sabak , Yongdong Wang
IPC分类号： G01N21/76
CPC分类号： G01N21/763 , G01N21/15 , G01N21/274 , G01N21/276 , G01N21/31 , G01N21/6452 , G01N21/6456 , G01N21/6486 , G01N21/76 , G01N33/581 , G01N2021/6471 , G01N2333/90241 , Y10T436/115831
摘要： A luminescence detecting apparatus and method for analyzing luminescent samples is disclosed. Luminescent samples are placed in a plurality of sample wells in a tray, and the tray is placed in a visible-light impervious chamber containing a charge coupled device camera. The samples may be injected in the wells, and the samples may be injected with buffers and reagents, by an injector. In the chamber, light from the luminescent samples pass through a collimator, a Fresnel field lens, a filter, and a camera lens, whereupon a focused image is created by the optics on the charge-coupled device (CCD) camera. The use of a Fresnel field lens, in combination with a collimator and filter, reduces crosstalk between samples below the level attainable by the prior art. Preferred embodiments of the luminescence detecting apparatus and method disclosed include central processing control of all operations, multiple wavelength filter wheel, and robot handling of samples and reagents. Preferred embodiments of processing software integrated with the invention include elements for mechanical alignment, outlier shaving, edge detection and masking, manipulation of multiple integration times to expand the dynamic range, crosstalk correction, dark subtraction interpolation and drift correction, multi-component analysis applications specifically tailored for luminescence, and uniformity correction.
摘要翻译：公开了一种用于分析发光样品的发光检测装置和方法。将发光样品放置在托盘中的多个样品孔中，并且将托盘放置在包含电荷耦合器件照相机的可见光不透水室中。样品可以注入孔中，样品可以通过注射器注入缓冲液和试剂。在室中，来自发光样品的光通过准直仪，菲涅尔场透镜，滤光器和照相机镜头，由此电荷耦合器件（CCD）照相机上的光学器件产生聚焦图像。使用菲涅耳场透镜与准直器和滤光器结合使得样品之间的串扰降低到现有技术可获得的水平以下。发光检测装置和方法的优选实施例包括所有操作，多波长滤光轮和样品和试剂的机器人处理的中央处理控制。与本发明集成的处理软件的优选实施例包括用于机械对准，异常刮削，边缘检测和掩蔽的元件，多次积分时间的操纵以扩大动态范围，串扰校正，暗减法内插和漂移校正，特别是多组分分析应用适合发光和均匀性校正。

9. 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。

10. 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。

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