公开(公告)号：US20100099077A1

公开(公告)日：2010-04-22

申请号：US12445304

申请日：2007-10-15

申请人： Anand Natrajan ,  Qingping Jiang ,  David Sharpe

发明人： Anand Natrajan ,  Qingping Jiang ,  David Sharpe

IPC分类号： C12Q1/70 ,  C07D219/00 ,  C07D401/02 ,  G01N21/76 ,  G01N33/00 ,  G01N33/543 ,  G01N33/53

CPC分类号： C07D219/04 ,  Y10T436/13 ,  Y10T436/143333 ,  Y10T436/21

摘要： Chemiluminescent acridinium esters are provided which are fast light emitting and hydrolytically stable. The chemiluminescent acridinium esters are useful labels in assays for detecting or quantifying analytes.

摘要翻译： 提供化学发光的吖啶酯，其具有快速发光和水解稳定性。 化学发光吖啶酯是用于检测或定量分析物的测定中的有用标签。

公开(公告)号：US07611909B1

公开(公告)日：2009-11-03

申请号：US11266902

申请日：2005-11-04

申请人： Anand Natrajan ,  Qingping Jiang ,  David Sharpe ,  Say-Jong Law

发明人： Anand Natrajan ,  Qingping Jiang ,  David Sharpe ,  Say-Jong Law

IPC分类号： G01N33/533 ,  G01N21/76 ,  G01N33/53

CPC分类号： G01N33/582 ,  C07D219/04 ,  Y10S436/80 ,  Y10S436/815 ,  Y10S436/817 ,  Y10S530/812 ,  Y10T436/13

摘要： A method for the detection or quantitation of unlabeled target analyte in a biological sample, the method comprising labeling a target analyte for a biological sample suspected of containing unlabeled target analyte with an acridinium compound to form a labeled target analyte and providing the labeled target analyte to the biological sample, or providing the labeled target analyte to the biological sample, wherein the acridinium compound comprises an acridinium nucleus having an electron-donating substituent directly attached to the acridinium nucleus, with the electron-donating substituent attached at the C2 position. Chemiluminescent acridinium compounds useful in the method have emission maxima close to or in the near infrared (NIR) region (>590 nm). These chemiluminescent acridinium compounds when used in conjunction with short wavelength-emitting acridinium esters (with emission maxima below 450 nm) can be highly useful labels for the simultaneous detection of multiple target analytes in a single assay.

摘要翻译： 一种用于检测或定量生物样品中未标记的靶分析物的方法，所述方法包括用怀疑含有未标记的靶分析物的生物样品用吖啶鎓化合物标记目标分析物以形成标记的目标分析物，并将标记的目标分析物 生物样品或将标记的靶分析物提供给生物样品，其中吖啶鎓化合物包含具有直接连接到吖啶核的给电子取代基的吖啶核，其中给电子取代基连接在C2位置。 可用于该方法的化学发光吖啶鎓化合物具有接近或在近红外（NIR）区域（> 590nm）中的发射最大值。 当与短波长发射的吖啶酯（发射最大值低于450nm）结合使用时，这些化学发光吖啶鎓化合物可以是在单次测定中同时检测多种靶分析物的非常有用的标记。

公开(公告)号：US20060202179A1

公开(公告)日：2006-09-14

申请号：US11422095

申请日：2006-06-05

申请人： Qingping Jiang ,  Anand Natrajan ,  David Sharpe ,  Wen-Jee Wong ,  Say-Jong Law

发明人： Qingping Jiang ,  Anand Natrajan ,  David Sharpe ,  Wen-Jee Wong ,  Say-Jong Law

IPC分类号： C09K3/00

CPC分类号： C07D491/10 ,  C07D219/04 ,  C07F9/64 ,  C12Q1/42 ,  C12Q2334/00 ,  G01N33/533 ,  G01N33/582

摘要： A chemiluminescent substrate of a hydrolytic enzyme having the following general Formula I is disclosed, as follows: Lumi-M-P   Formula I where “Lumi” is a chemiluminescent moiety capable of producing light (a) by itself, (b) with MP attached and (c) with M attached. Examples of Lumi include chemiluminescent acridinium compounds, benzacridinium compounds, quinolinium compounds, isoquinolinium compounds, phenanthridinium compounds, and lucigenin compounds, spiroacridan compounds, luminol compounds and isoluminol compounds. M is a multivalent heteroatom having at least one lone pair of electrons selected from oxygen, nitrogen and sulfur, directly attached to the light emitting moiety of Lumi at one end and to P at the other end. P is a group that can be readily removed by hydrolytic enzymes. An enzymatic reaction utilizing the above compound is the following: where HE is a hydrolytic enzyme. Lumi-M is a chemiluminescent product having physical and/or chemical properties different from those of Lumi-M-P.

摘要翻译： 公开了具有以下通式I的水解酶的化学发光底物，如下所示：<？in-line-formula description =“In-line Formulas”end =“lead”？> Lumi-MP Formula I < line-formula description =“In-line Formulas”end =“tail”？>其中“Lumi”是能够自身产生光的化学发光部分（a），（b）MP附着和（c）附着M的化学发光部分。 Lumi的实例包括化学发光吖啶鎓化合物，苯并吖啶鎓化合物，喹啉鎓化合物，异喹啉鎓化合物，菲啶鎓化合物和光合精化合物，螺吡啶化合物，鲁米诺化合物和异鲁米诺化合物。 M是具有至少一个选自氧，氮和硫的孤对电子的多价杂原子，其一端直接连接到Lumi的发光部分，另一端直接附着于P。 P是可以通过水解酶容易地除去的基团。 使用上述化合物的酶反应如下：其中HE是水解酶。 Lumi-M是具有与Lumi-M-P不同的物理和/或化学性质的化学发光产物。

公开(公告)号：US07083986B2

公开(公告)日：2006-08-01

申请号：US10006421

申请日：2001-12-06

申请人： Anand Natrajan ,  Qingping Jiang ,  David Sharpe ,  Say-Jong Law

发明人： Anand Natrajan ,  Qingping Jiang ,  David Sharpe ,  Say-Jong Law

IPC分类号： G01N33/533 ,  G01N33/78 ,  G01N33/554 ,  G01N33/569 ,  C12Q1/68

CPC分类号： G01N33/582 ,  C07D219/04 ,  Y10S436/80 ,  Y10S436/815 ,  Y10S436/817 ,  Y10S530/812 ,  Y10T436/13

摘要： A method for the detection or quantitation of an analyte in a biological sample is disclosed. The method comprises the steps of selecting a biological sample suspected of containing a target analyte and binding the target analyte in the sample to a binding partner conjugated to an acridinium compound, wherein the acridinium compound comprises an acridinium nucleus having an electron-donating substituent directly attached to the acridinium nucleus at the C2 position. Chemiluminescent acridinium compounds useful in the method have emission maxima close to or in the near infrared (NIR) region (>590 nm). These chemiluminescent acridinium compounds when used in conjunction with short wavelength-emitting acridinium esters (with emission maxima below 450 nm) can be highly useful labels for the simultaneous detection of multiple target analytes in a single assay.

摘要翻译： 公开了用于检测或定量生物样品中的分析物的方法。 该方法包括以下步骤：选择怀疑含有目标分析物并将样品中的目标分析物结合到与吖啶鎓化合物结合的结合对象的生物样品，其中所述吖啶鎓化合物包含具有直接连接的给电子取代基的吖啶核 到C> 2位上的吖啶核。 可用于该方法的化学发光吖啶鎓化合物具有接近或在近红外（NIR）区域（> 590nm）中的发射最大值。 当与短波长发射的吖啶酯（发射最大值低于450nm）结合使用时，这些化学发光吖啶鎓化合物可以是在单次测定中同时检测多种靶分析物的非常有用的标记。

公开(公告)号：US20120225497A1

公开(公告)日：2012-09-06

申请号：US13510158

申请日：2010-11-12

申请人： Anand Natrajan ,  David Sharpe ,  Qingping Jiang

发明人： Anand Natrajan ,  David Sharpe ,  Qingping Jiang

IPC分类号： G01N33/543 ,  C07D401/12

CPC分类号： G01N33/54393 ,  C07D219/04 ,  C07D219/14 ,  C07D401/12 ,  C09B15/00 ,  Y10T436/13

摘要： Hydrophilic, chemiluminescent acridinium compounds containing zwitterions are disclosed. These acridinium compounds, when used as chemiluminescent labels in immunochemistry assays and the like, exhibit decreased non-specific binding to solid phases and provide increased assay sensitivity.

摘要翻译： 公开了含有两性离子的亲水的，化学发光的吖啶鎓化合物。 当这些吖啶鎓化合物在免疫化学测定等中用作化学发光标记时，表现出与固相的非特异性结合降低并提供增加的测定灵敏度。

公开(公告)号：US07785904B2

公开(公告)日：2010-08-31

申请号：US11764924

申请日：2007-06-19

申请人： Anand Natrajan ,  Qingping Jiang ,  David Sharpe ,  James Costello

发明人： Anand Natrajan ,  Qingping Jiang ,  David Sharpe ,  James Costello

IPC分类号： G01N33/533 ,  G01N21/76 ,  G01N33/53 ,  C07D219/00

CPC分类号： G01N33/533 ,  B82Y15/00 ,  C07D219/04 ,  C07D219/06 ,  G01N33/542 ,  G01N33/582 ,  G01N33/588 ,  Y10S435/968 ,  Y10S436/80 ,  Y10S436/805

摘要： The present invention relates to hydrophilic, high quantum yield acridinium compounds. It has been discovered that the placement of electron-donating groups in the acridinium ring system increases the amount of light that is emitted by the corresponding acridinium compound when its chemiluminescence is triggered by alkaline peroxide. More specifically, it has been found that the placement of one or two hydrophilic, alkoxy groups at the C-2 and/or C-7 position of the acridinium ring system of acridinium compounds increases their quantum yield and enhances the aqueous solubility of these compounds. The present hydrophilic, high quantum yield, acridinium compounds are useful chemiluminescent labels for improving the sensitivity of immunoassays.

摘要翻译： 本发明涉及亲水性高量子产率吖啶鎓化合物。 已经发现，当其化学发光由碱性过氧化物触发时，电子给体基团在吖啶环体系中的放置增加了相应的吖啶鎓化合物发射的光的量。 更具体地，已经发现，在吖啶鎓化合物的吖啶环体系的C-2和/或C-7位置上放置一个或两个亲水性烷氧基增加其量子产率并增强这些化合物的水溶性 。 本发明的亲水性，高量子产率的吖啶化合物是有用的化学发光标记，用于提高免疫测定的灵敏度。

公开(公告)号：US07459284B2

公开(公告)日：2008-12-02

申请号：US11422095

申请日：2006-06-05

申请人： Qingping Jiang ,  Anand Natrajan ,  David Sharpe ,  Wen-Jee Wong ,  Say-Jong Law

发明人： Qingping Jiang ,  Anand Natrajan ,  David Sharpe ,  Wen-Jee Wong ,  Say-Jong Law

IPC分类号： C12Q1/34 ,  C07D219/02

CPC分类号： C07D491/10 ,  C07D219/04 ,  C07F9/64 ,  C12Q1/42 ,  C12Q2334/00 ,  G01N33/533 ,  G01N33/582

摘要： A chemiluminescent substrate of a hydrolytic enzyme having the following general Formula I is disclosed, as follows: Lumi-M-P  Formula I where “Lumi” is a chemiluminescent moiety capable of producing light (a) by itself, (b) with MP attached and (c) with M attached. Examples of Lumi include chemiluminescent acridinium compounds, benzacridinium compounds, quinolinium compounds, isoquinolinium compounds, phenanthridinium compounds, and lucigenin compounds, spiroacridan compounds, luminol compounds and isoluminol compounds. M is a multivalent heteroatom having at least one lone pair of electrons selected from oxygen, nitrogen and sulfur, directly attached to the light emitting moiety of Lumi at one end and to P at the other end. P is a group that can be readily removed by hydrolytic enzymes. An enzymatic reaction utilizing the above compound is the following: where HE is a hydrolytic enzyme. Lumi-M is a chemiluminescent product having physical and/or chemical properties different from those of Lumi-M-P.

摘要翻译： 公开了具有以下通式I的水解酶的化学发光底物，如下所示：<？in-line-formula description =“In-line Formulas”end =“lead”？> Lumi-MP Formula I < line-formula description =“In-line Formulas”end =“tail”？>其中“Lumi”是能够自身产生光的化学发光部分（a），（b）MP附着和（c）附着M的化学发光部分。 Lumi的实例包括化学发光吖啶鎓化合物，苯并吖啶鎓化合物，喹啉鎓化合物，异喹啉鎓化合物，菲啶鎓化合物和光合精化合物，螺吡啶化合物，鲁米诺化合物和异鲁米诺化合物。 M是具有至少一个选自氧，氮和硫的孤对电子的多价杂原子，其一端直接连接到Lumi的发光部分，另一端直接附着于P。 P是可以通过水解酶容易地除去的基团。 使用上述化合物的酶反应如下：其中HE是水解酶。 Lumi-M是具有与Lumi-M-P不同的物理和/或化学性质的化学发光产物。

公开(公告)号：US20080014660A1

公开(公告)日：2008-01-17

申请号：US11764924

申请日：2007-06-19

申请人： Anand Natrajan ,  Qingping Jiang ,  David Sharpe ,  James Costello

发明人： Anand Natrajan ,  Qingping Jiang ,  David Sharpe ,  James Costello

IPC分类号： G01N33/543

CPC分类号： G01N33/533 ,  B82Y15/00 ,  C07D219/04 ,  C07D219/06 ,  G01N33/542 ,  G01N33/582 ,  G01N33/588 ,  Y10S435/968 ,  Y10S436/80 ,  Y10S436/805

摘要： The present invention relates to hydrophilic, high quantum yield acridinium compounds. It has been discovered that the placement of electron-donating groups in the acridinium ring system increases the amount of light that is emitted by the corresponding acridinium compound when its chemiluminescence is triggered by alkaline peroxide. More specifically, it has been found that the placement of one or two hydrophilic, alkoxy groups at the C-2 and/or C-7 position of the acridinium ring system of acridinium compounds increases their quantum yield and enhances the aqueous solubility of these compounds. The present hydrophilic, high quantum yield, acridinium compounds are useful chemiluminescent labels for improving the sensitivity of immunoassays.

摘要翻译： 本发明涉及亲水性高量子产率吖啶鎓化合物。 已经发现，当其化学发光由碱性过氧化物触发时，电子给体基团在吖啶环体系中的放置增加了相应的吖啶鎓化合物发射的光的量。 更具体地，已经发现，在吖啶鎓化合物的吖啶环体系的C-2和/或C-7位置上放置一个或两个亲水性烷氧基增加其量子产率并增强这些化合物的水溶性 。 本发明的亲水性，高量子产率的吖啶化合物是有用的化学发光标记，用于提高免疫测定的灵敏度。

公开(公告)号：US20050032147A1

公开(公告)日：2005-02-10

申请号：US10928300

申请日：2004-08-27

申请人： Qingping Jiang ,  Anand Natrajan ,  David Sharpe ,  Wen-Jee Wong ,  Say-Jong Law

发明人： Qingping Jiang ,  Anand Natrajan ,  David Sharpe ,  Wen-Jee Wong ,  Say-Jong Law

IPC分类号： C07D219/04 ,  C07D491/10 ,  C07F9/64 ,  C12Q1/42 ,  C12Q1/34 ,  C07H17/02

CPC分类号： C07D491/10 ,  C07D219/04 ,  C07F9/64 ,  C12Q1/42 ,  C12Q2334/00 ,  G01N33/533 ,  G01N33/582

摘要： A chemiluminescent substrate of a hydrolytic enzyme having the following general Formula I is disclosed, as follows: Lumi-M-P  Formula I where “Lumi” is a chemiluminescent moiety capable of producing light (a) by itself, (b) with MP attached and (c) with M attached. Examples of Lumi include chemiluminescent acridinium compounds, benzacridinium compounds, quinolinium compounds, isoquinolinium compounds, phenanthridinium compounds, and lucigenin compounds, spiroacridan compounds, luminol compounds and isoluminol compounds. M is a multivalent heteroatom having at least one lone pair of electrons selected from oxygen, nitrogen and sulfur, directly attached to the light emitting moiety of Lumi at one end and to P at the other end. P is a group that can be readily removed by hydrolytic enzymes. An enzymatic reaction utilizing the above compound is the following: where HE is a hydrolytic enzyme. Lumi-M is a chemiluminescent product having physical and/or chemical properties different from those of Lumi-M-P.

摘要翻译： 具有以下通式I的水解酶的化学发光底物公开如下：Lumi-MP式I其中“Lumi”是能够自身产生光的化学发光部分（a），（b）MP附着和（ c）与M连接。 Lumi的实例包括化学发光吖啶鎓化合物，苯并吖啶鎓化合物，喹啉鎓化合物，异喹啉鎓化合物，菲啶鎓化合物和光合精化合物，螺吡啶化合物，鲁米诺化合物和异鲁米诺化合物。 M是具有至少一个选自氧，氮和硫的孤对电子的多价杂原子，其一端直接连接到Lumi的发光部分，另一端直接附着于P。 P是可以通过水解酶容易地除去的基团。 使用上述化合物的酶反应如下：其中HE是水解酶。 Lumi-M是具有与Lumi-M-P不同的物理和/或化学性质的化学发光产物。

公开(公告)号：US6165800A

公开(公告)日：2000-12-26

申请号：US86003

申请日：1998-05-27

申请人： Qingping Jiang ,  Jun Xi ,  Anand Natrajan ,  David Sharpe ,  Marcus Baumann ,  Rolf Hilfiker ,  Erika Schmidt ,  Paul Senn ,  Fritz Thommen ,  Adrian Waldner ,  Alex Alder ,  Say-Jong Law

发明人： Qingping Jiang ,  Jun Xi ,  Anand Natrajan ,  David Sharpe ,  Marcus Baumann ,  Rolf Hilfiker ,  Erika Schmidt ,  Paul Senn ,  Fritz Thommen ,  Adrian Waldner ,  Alex Alder ,  Say-Jong Law

IPC分类号： C09B11/04 ,  C09B15/00 ,  C09K11/07 ,  G01N33/533 ,  G01N33/542 ,  G01N33/58 ,  C07D227/00 ,  G01N33/553

CPC分类号： C09B15/00 ,  C09B11/04 ,  G01N33/533 ,  G01N33/542 ,  G01N33/582 ,  Y10S436/80 ,  Y10S436/816 ,  Y10S436/817

摘要： A new class of chemiluminescent acridinium or benzacridinium compounds is disclosed by virtue of forming an intramolecular energy transfer conjugate (ETC) between the acridinium or benzacridinium compound and a luminophore. A method of extending the emission wavelengths of acridinium or benzacridinium esters in order to further reduce or eliminate the emission spectral overlap between the parent polysubstituted aryl Acridinium Esters (DMAE) and Benzacridinium Esters (LEAE) is disclosed. The ETC's retain the unique desired properties of acridinium or benzacridinium compounds including complete light emission in very short period of time, monophasic emission spectrum, simplicity of triggering mechanism, ability of labeling the biological molecules of interest to form a tracer, and good stability. Additionally, the range of the emission spectrum of an acridinium or benzacridinium compound can now be shifted at will and at longer leap through the choice of a luminophore as the integral part of an ETC molecule. Disclosed are chemiluminescent labeled conjugates comprising an acridinium or benzacridinium moiety covalently attached to a luminophore via a spacer, said moiety further conjugated to a biological molecule of interest, wherein said spacer is of an appropriate length to allow the excited species generated from said moiety to transfer energy efficiently to said luminophore, resulting in the emission of light in the spectral region of said luminophore. Also disclosed are binding assays using said conjugates, test kits comprising said conjugates and methods of preparing the conjugates.

摘要翻译： 通过在吖啶鎓或苯并吖啶鎓化合物和发光体之间形成分子内能量转移缀合物（ETC），公开了一类新的化学发光吖啶鎓或苯并吖啶鎓化合物。 公开了延长吖啶鎓或苯并吖啶酯的发射波长以进一步减少或消除母体多取代芳基吖啶酯（DMAE）和苯并吖啶酯（LEAE）之间的发射光谱重叠的方法。 ETC保留吖啶鎓或苯并吖啶鎓化合物独特的所需性质，包括在很短的时间内完全发光，单相发射光谱，触发机制简单，标记生物分子的能力，形成示踪剂，以及良好的稳定性。 此外，吖啶鎓或苯并吖啶鎓化合物的发射光谱的范围现在可以随意移动，并且通过选择发光体作为ETC分子的组成部分而更长的跨越。 公开了化学发光标记的缀合物，其包含通过间隔基共价连接到发光体的吖啶鎓或苯并吖啶鎓部分，所述部分还与感兴趣的生物分子缀合，其中所述间隔物具有适当长度以允许从所述部分产生的激发物质转移 能量有效地发送到所述发光体，导致发光在所述发光体的光谱区域。 还公开了使用所述缀合物的结合测定法，包含所述缀合物的测试试剂盒和制备缀合物的方法。