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1. 发明申请

WO0004366A9 DETECTOR AND SCREENING DEVICE FOR ION CHANNELS 审中-公开
标题翻译：用于离子通道的检测器和筛选装置
公开(公告)号：WO0004366A9
公开(公告)日：2000-06-02
申请号：PCT/US9916170
申请日：1999-07-16
申请人： AURORA BIOSCIENCES CORP
发明人： TSIEN ROGER Y , COASSIN PETER J , PHAM ANDREW A , HAROOTUNIAN ALEC TATE , VUONG MINH
IPC分类号： G01N21/64 , G01N1/00 , G01N21/03 , G01N21/25 , G01N35/02 , G01N37/00 , G02B6/04 , G01N1/10 , G01N21/29 , G01N21/47
CPC分类号： G01N21/6452 , G01N2021/6419 , G01N2021/6421 , G01N2021/6478 , G01N2021/6484 , G01N2201/0639
摘要： The invention provides for a detector assembly, fiber assembly (204) and screening system for optical measurements. The invention includes a method of simultaneously measuring at least two optical properties of emitted light from at least one sample in a plurality of addressable wells (206) of a multiwell plate. The method including: aligning the wells of the plate to a plurality of ball lenses (205), directing electromagnetic radiation from an appropriate light source (201) coaxially through the symmetry axis of each ball lens, and detecting emitted light focused by the ball lenses from the sample.
摘要翻译：本发明提供了用于光学测量的检测器组件，光纤组件（204）和筛选系统。本发明包括同时测量来自多孔板的多个可寻址孔（206）中的至少一个样品的发射光的至少两种光学性质的方法。该方法包括：将板的孔与多个球透镜（205）对准，将来自适当光源（201）的电磁辐射同轴地穿过每个球透镜的对称轴线，并检测由球透镜聚焦的发射光从样品。

2. 发明申请

WO0127635A8 MULTIWELL SCANNER AND SCANNING METHOD 审中-公开
标题翻译：多屏扫描仪和扫描方法
公开(公告)号：WO0127635A8
公开(公告)日：2003-10-23
申请号：PCT/US0028447
申请日：2000-10-12
申请人： AURORA BIOSCIENCES CORP
发明人： VUONG T MINH
IPC分类号： G01N21/64 , A61K45/00 , A61P43/00 , B01J19/00 , C12M1/34 , C12Q1/37 , C12Q1/42 , C12Q1/48 , C40B60/14 , G01N21/25 , G01N21/76 , G01N33/15 , G01N33/483 , G01N33/50 , G01N33/566 , G01N35/02 , G01N37/00
CPC分类号： G01N21/253 , B01J19/0046 , B01J2219/00315 , B01J2219/00317 , B01J2219/00707 , B01J2219/0072 , B01L2300/0893 , C40B60/14 , G01N21/76 , G01N35/028
摘要： A multiwell plate scanner comprises a detector for measuring an attribute of a sample which is scanned continuously over wells of a multiwell plate. A signal obtained during the scan may be sampled and digitized based on detector position over the multiwell plate. The scanner is also disclosed for scanning microarrays, bio-chips and areas of samples not having physical separations. The scanner may be used in a high throughput screening system comprising a storage and retrieval module, a sample distribution module, a reagent distribution module, and a detector which incorporates the scanner. The screening system may further comprise a transport module and a data processing and integration module for transporting samples between the components of the system and for controlling system operation. In a further aspect, the present invention comprises methods and apparatus to compensate for variations, inconsistencies and other differences in the dimensions, configuration and/or materials of the platform in which an assay is performed. Another aspect of the invention is a system and method for performing an assay to detect the effect of a reagent on a target. The present invention is also directed to compositions and therapeutics identified by the disclosed methods. A further aspect of the present invention is a method of testing a therapeutic for therapeutic activity and toxicology by identifying a compound using a method of the present invention and monitoring the toxicology and efficacy of the therapeutic in an in vivo model.
摘要翻译：多孔板扫描器包括用于测量在多孔板的孔上连续扫描的样品的属性的检测器。在扫描期间获得的信号可以基于多孔板上的检测器位置被采样和数字化。还公开了用于扫描微阵列，生物芯片和不具有物理分离的样品区域的扫描仪。扫描仪可以用于包括存储和检索模块，样品分配模块，试剂分配模块和结合扫描仪的检测器的高通量筛选系统中。筛选系统还可以包括传送模块和数据处理和集成模块，用于在系统的组件之间传送样本并用于控制系统操作。在另一方面，本发明包括用于补偿其中进行测定的平台的尺寸，构型和/或材料的变化，不一致性和其它差异的方法和装置。本发明的另一方面是用于进行测定以检测试剂对靶标的影响的系统和方法。本发明还涉及通过所公开的方法鉴定的组合物和治疗剂。本发明的另一方面是通过使用本发明的方法鉴定化合物并在体内模型中监测治疗剂的毒理学和功效来测试治疗活性和毒理学治疗剂的方法。

3. 发明申请

WO0208748A9 ION CHANNEL ASSAY METHODS 审中-公开
标题翻译：离子通道测定方法
公开(公告)号：WO0208748A9
公开(公告)日：2003-06-12
申请号：PCT/US0121652
申请日：2001-07-09
申请人： AURORA BIOSCIENCES CORP , MAHER MICHAEL P , GONZALEZ JESUS E III
发明人： MAHER MICHAEL P , GONZALEZ JESUS E III
IPC分类号： G01N21/64 , C12Q1/02 , G01N21/78 , G01N27/416 , G01N33/15 , G01N33/50 , G01N33/68 , G01N37/00 , G01N33/483
CPC分类号： G01N33/502 , G01N33/5008 , G01N33/5044 , G01N33/5076 , G01N33/5088 , G01N33/6872
摘要： A method of characterizing the biological activity of a candidate compound may include exposing cells to the candidate compound, and then exposing the cells to a repetitive application of electric fields so as to set the transmembrane potential to a level corresponding to a pre-selected voltage dependent state of a target ion channel.
摘要翻译：表征候选化合物的生物活性的方法可以包括将细胞暴露于候选化合物，然后将细胞暴露于电场的重复施用，以将跨膜电位设定为与预选电压相关的水平目标离子通道的状态。

4. 发明申请

WO0127635A9 MULTIWELL SCANNER AND SCANNING METHOD 审中-公开
标题翻译：多屏扫描仪和扫描方法
公开(公告)号：WO0127635A9
公开(公告)日：2002-08-08
申请号：PCT/US0028447
申请日：2000-10-12
申请人： AURORA BIOSCIENCES CORP
发明人： VUONG T MINH
IPC分类号： G01N21/64 , A61K45/00 , A61P43/00 , B01J19/00 , C12M1/34 , C12Q1/37 , C12Q1/42 , C12Q1/48 , C40B60/14 , G01N21/25 , G01N21/76 , G01N33/15 , G01N33/483 , G01N33/50 , G01N33/566 , G01N35/02 , G01N37/00
CPC分类号： G01N21/253 , B01J19/0046 , B01J2219/00315 , B01J2219/00317 , B01J2219/00707 , B01J2219/0072 , B01L2300/0893 , C40B60/14 , G01N21/76 , G01N35/028
摘要： A multiwell plate scanner comprises a detector for measuring an attribute of a sample which is scanned continuously over wells of a multiwell plate. A signal obtained during the scan may be sampled and digitized based on detector position over the multiwell plate. The scanner is also disclosed for scanning microarrays, bio-chips and areas of samples not having physical separations. The scanner may be used in a high throughput screening system comprising a storage and retrieval module, a sample distribution module, a reagent distribution module, and a detector which incorporates the scanner. The screening system may further comprise a transport module and a data processing and integration module for transporting samples between the components of the system and for controlling system operation. In a further aspect, the present invention comprises methods and apparatus to compensate for variations, inconsistencies and other differences in the dimensions, configuration and/or materials of the platform in which an assay is performed. Another aspect of the invention is a system and method for performing an assay to detect the effect of a reagent on a target. The present invention is also directed to compositions and therapeutics identified by the disclosed methods. A further aspect of the present invention is a method of testing a therapeutic for therapeutic activity and toxicology by identifying a compound using a method of the present invention and monitoring the toxicology and efficacy of the therapeutic in an in vivo model.
摘要翻译：多孔板扫描器包括用于测量在多孔板的孔上连续扫描的样品的属性的检测器。在扫描期间获得的信号可以基于多孔板上的检测器位置被采样和数字化。还公开了用于扫描微阵列，生物芯片和不具有物理分离的样品区域的扫描仪。扫描仪可以用于包括存储和检索模块，样品分配模块，试剂分配模块和结合扫描仪的检测器的高通量筛选系统中。筛选系统还可以包括传送模块和数据处理和集成模块，用于在系统的组件之间传送样本并用于控制系统操作。在另一方面，本发明包括用于补偿其中进行测定的平台的尺寸，构型和/或材料的变化，不一致性和其它差异的方法和装置。本发明的另一方面是用于进行测定以检测试剂对靶标的影响的系统和方法。本发明还涉及通过所公开的方法鉴定的组合物和治疗剂。本发明的另一方面是通过使用本发明的方法鉴定化合物并在体内模型中监测治疗剂的毒理学和功效来测试治疗活性和毒理学治疗剂的方法。

5. 发明申请

WO0157242A3 METHODS OF PROTEIN DESTABILIZATION AND USES THEREOF 审中-公开
标题翻译：蛋白质去除方法及其用途
公开(公告)号：WO0157242A3
公开(公告)日：2002-06-13
申请号：PCT/US0103791
申请日：2001-02-02
申请人： AURORA BIOSCIENCES CORP , STACK JEFFREY H , WHITNEY MICHAEL , CUBITT ANDREW B , POLLOK BRIAN A
发明人： STACK JEFFREY H , WHITNEY MICHAEL , CUBITT ANDREW B , POLLOK BRIAN A
IPC分类号： A01K67/027 , A01K67/033 , A61K45/00 , A61P43/00 , C07K14/47 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12Q1/02 , C12Q1/48 , C12Q1/68 , C12Q1/37 , C12N15/00 , C12Q1/34 , G01N33/50 , G01N33/532 , G01N33/542
CPC分类号： C12Q1/485
摘要： This invention is directed towards methods of destabilizing proteins in living cells, and their use for the development of novel assays. In one embodiment, the invention comprises the use of non-cleavable multimerized ubiquitin fusion proteins to destabilize a target protein, such as a reporter moiety. In one aspect of this method the constructs also comprises a linker that operatively couples the reporter moiety to the multimerized ubiquitin fusion protein. In this embodiment, enzymatic modification of the linker results in a modulation of the coupling of the reporter protein to the multimerized ubiquitin domains resulting in a change in the stability of the reporter moiety. The level of the reporter moiety in the cell can then be used as a measure of the enzymatic activity in the cell. In another embodiment the invention provides for a generalized way of coordinately regulating the cellular concentration of a plurality of target proteins. In one aspect of this method, the target proteins are operatively coupled to a ubiquitin fusion protein via linker containing a protease cleavage site. Cleavage of the linker by a protease results in uncoupling of the target protein from the multimerized ubiquitin construct, and results in an increase in the stability and concentration of the target protein.
摘要翻译：本发明涉及使活细胞中的蛋白质失稳的方法及其用于开发新的测定方法。在一个实施方案中，本发明包括使用不可切割的多聚化泛素融合蛋白来不稳定靶蛋白，例如报道部分。在该方法的一个方面，构建体还包含使报道部分与多聚化泛素融合蛋白可操作地连接的连接体。在该实施方案中，接头的酶修饰导致报告蛋白与多聚泛素结构域的偶联的调节，导致报道部分稳定性的变化。然后可以将细胞中的报告物部分的水平用作细胞中酶活性的量度。在另一个实施方案中，本发明提供了协调调节多种靶蛋白的细胞浓度的一般化方式。在该方法的一个方面，靶蛋白通过含有蛋白酶切割位点的接头与泛素融合蛋白可操作地偶联。通过蛋白酶切割接头导致靶蛋白与多聚化泛素构建体解偶联，并导致靶蛋白的稳定性和浓度增加。

6. 发明申请

WO0208748A3 ION CHANNEL ASSAY METHODS 审中-公开
标题翻译：离子通道测定方法
公开(公告)号：WO0208748A3
公开(公告)日：2002-05-02
申请号：PCT/US0121652
申请日：2001-07-09
申请人： AURORA BIOSCIENCES CORP , MAHER MICHAEL P , GONZALEZ JESUS E III
发明人： MAHER MICHAEL P , GONZALEZ JESUS E III
IPC分类号： G01N21/64 , C12Q1/02 , G01N21/78 , G01N27/416 , G01N33/15 , G01N33/50 , G01N33/68 , G01N37/00 , G01N33/483
CPC分类号： G01N33/502 , G01N33/5008 , G01N33/5044 , G01N33/5076 , G01N33/5088 , G01N33/6872
摘要： A method of characterizing the biological activity of a candidate compound may include exposing cells to the candidate compound, and then exposing the cells to a repetitive application of electric fields so as to set the transmembrane potential to a level corresponding to a pre-selected voltage dependent state of a target ion channel.
摘要翻译：表征候选化合物的生物活性的方法可以包括将细胞暴露于候选化合物，然后将细胞暴露于电场的重复施用，以便将跨膜电位设定为与预选电压相关的水平目标离子通道的状态。

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