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1. 发明申请

US20140323325A1 Molecular imaging and related methods 审中-公开
标题翻译：分子成像及相关方法
公开(公告)号：US20140323325A1
公开(公告)日：2014-10-30
申请号：US13999508
申请日：2014-03-04
申请人： Marc Beal , Ronald M. Cook , Peter Jay Coassin , Arturo Orjalo , Jekwan Ryu
发明人： Marc Beal , Ronald M. Cook , Peter Jay Coassin , Arturo Orjalo , Jekwan Ryu
IPC分类号： C12Q1/68 , G01N21/64
CPC分类号： C12Q1/6841 , C12Q1/6883 , C12Q1/6886 , C12Q2600/158 , G01N21/6428 , G01N21/6458 , G02B21/0004 , G02B21/0096 , G02B21/082 , G02B21/16 , G02B21/18 , C12Q2537/143 , C12Q2543/10 , C12Q2563/107 , C12Q2565/601
摘要： The present invention generally relates to imaging single molecules, or one or more collections of single molecules, and methods related to the imaging. In a method aspect, the present invention provides a method of imaging single molecules. The method comprises the steps of: a) exposing a test sample to a probe, wherein the probe comprises a first portion that specifically binds to a target molecule and a second portion that is detectable as the result of one or more chemical groups that interact with light at one or more wavelengths, wherein the probe binds to a target molecule to provide a complex; b) exposing the complex to one or more wavelengths of light that interact with the one or more chemical groups; c) detecting a result from the interacting of one or more wavelengths of light that interact with the one or more chemical groups to provide an image of one or more single molecules. The image possesses a resolution better than 450 nm over a view field area of at least 1×105 μm2, and wherein the image is obtained in a single detection step without variation of any detection settings.
摘要翻译：本发明一般涉及成像单分子，或单个分子的一个或多个集合，以及与成像有关的方法。在方法方面，本发明提供了单分子成像的方法。该方法包括以下步骤：a）将测试样品暴露于探针，其中所述探针包含特异性结合靶分子的第一部分和作为一个或多个化学基团相互作用的结果可检测的第二部分一个或多个波长的光，其中所述探针结合靶分子以提供复合物; b）将所述复合物暴露于与所述一个或多个化学基团相互作用的一个或多个波长的光; c）检测与一个或多个化学基团相互作用的一种或多种波长的光的相互作用的结果，以提供一个或多个单个分子的图像。该图像在至少1×105μm2的视野区域中的分辨率优于450nm，并且其中在单个检测步骤中获得图像而不改变任何检测设置。

2. 发明申请

US20110282041A1 STABILIZED NUCLEIC ACID DARK QUENCHER-FLUOROPHORE PROBES 有权
标题翻译：稳定的核酸深色探针 - 荧光探针
公开(公告)号：US20110282041A1
公开(公告)日：2011-11-17
申请号：US13193517
申请日：2011-07-28
申请人： Ronald M. Cook , Matt Lyttle
发明人： Ronald M. Cook , Matt Lyttle
IPC分类号： C07H19/10 , C07H21/00 , C07H19/06
CPC分类号： C12Q1/6876 , C07D219/04 , C07H19/06 , C07H19/073 , C09B31/02
摘要： The present invention provides a new class of solids supports for synthesis of modified oligomers of nucleic acids, and nucleic acid probes that have a format expediently synthesized on the new supports. Exemplary solid supports include at least one quencher bound through a linker to the solid support. Various exemplary embodiments include a moiety that stabilizes a duplex, triplex or higher order aggregation (e.g., hybridization) of nucleic acids of which the oligomer of the invention is a component. Other components of the solid support include moieties that stabilize aggregations of nucleic acids, e.g., intercalators, minor groove binding moieties, bases modified with a stabilizing moiety (e.g., alkynyl moieties, and fluoroalkyl moieties), and conformational stabilizing moieties, such as those described in commonly owned U.S. Patent Application Publication No. 2007/0059752.
摘要翻译：本发明提供了用于合成核酸修饰低聚物的新类固体支持物，以及具有在新载体上方便合成的形式的核酸探针。示例性的固体支持物包括通过连接体与固体支持物结合的至少一种猝灭剂。各种示例性实施方案包括稳定其本发明的低聚物是组分的核酸的双链体，三链体或更高级聚集（例如杂交）的部分。固体支持物的其它组分包括稳定核酸聚集的部分，例如嵌入剂，小槽结合部分，用稳定部分修饰的碱基（例如炔基部分和氟烷基部分）和构象稳定部分，例如描述的那些在共同拥有的美国专利申请公开No.2007 / 0059752中。

3. 发明授权

US5679539A Oxidized polyethylene or polypropylene particulate supports 失效
标题翻译：氧化聚乙烯或聚丙烯颗粒载体
公开(公告)号：US5679539A
公开(公告)日：1997-10-21
申请号：US377808
申请日：1995-01-24
申请人： Derek Hudson , Ronald M. Cook
发明人： Derek Hudson , Ronald M. Cook
IPC分类号： B01D15/32 , B01D15/36 , B01J20/32 , C07K1/04 , C07K17/08 , C12N11/08 , C12P21/06 , C07K17/06 , C12N11/06 , G01N33/549
CPC分类号： B01D15/325 , B01D15/361 , B01J20/0229 , B01J20/261 , B01J20/262 , B01J20/265 , B01J20/28004 , B01J20/28009 , B01J20/28026 , B01J20/287 , B01J20/289 , B01J20/3021 , B01J20/3092 , B01J20/3246 , B01J20/3248 , B01J20/3251 , B01J20/3272 , B01J20/328 , C07K1/042 , C07K17/08 , C12N11/08 , B01J2220/46 , B01J2220/54 , B01J2220/58 , Y10S530/815 , Y10S530/816
摘要： Polyolefin particles are chemically modified by oxidation to provide a large surface area and high loading. The particles result in low back pressure in column systems, and are economical to manufacture. The particles are useful as supports in a wide range of applications including general organic as well as biopolymer synthesis, library methods, purification processes and enzyme mediated processes. In a preferred embodiment, polyethylene or polypropylene particles are oxidized in a solution containing trifluoroacetic acid or trifluoromethane sulfonic acid, chromium trioxide and sulfuric acid to provide the particles with a chemically reactive irregular surface and open channels that extend below the surface and up to essentially the length of the radius of the particles resulting in increased surface area and decreased density. The particles have pendant functional groups produced by the oxidation and/or by subsequent chemical reaction. The pendant functional groups may be attached to spacer arms that are attached to the surface of the particles. Biological material such as proteins, enzymes and whole cells may be immobilized on the particles.
摘要翻译：聚烯烃颗粒通过氧化进行化学改性以提供大的表面积和高负载量。颗粒在柱系统中导致低背压，并且制造经济。该颗粒可用作广泛应用的载体，包括一般有机物以及生物聚合物合成，文库方法，纯化方法和酶介导的方法。在优选的实施方案中，聚乙烯或聚丙烯颗粒在含有三氟乙酸或三氟甲磺酸，三氧化铬和硫酸的溶液中被氧化，以使颗粒具有化学反应性不规则表面和在表面下方延伸至基本上为颗粒半径的长度导致表面积增加和密度降低。颗粒具有通过氧化和/或随后的化学反应产生的侧链官能团。侧链官能团可以连接到附着到颗粒表面的间隔臂上。生物材料如蛋白质，酶和全细胞可以固定在颗粒上。

4. 发明授权

US08674094B2 Stabilized nucleic acid dark quencher-fluorophore probes 有权
标题翻译：稳定的核酸暗猝灭剂 - 荧光团探针
公开(公告)号：US08674094B2
公开(公告)日：2014-03-18
申请号：US13193517
申请日：2011-07-28
申请人： Ronald M. Cook , Matt Lyttle
发明人： Ronald M. Cook , Matt Lyttle
IPC分类号： C07F9/6512 , C07F9/655
CPC分类号： C12Q1/6876 , C07D219/04 , C07H19/06 , C07H19/073 , C09B31/02
摘要： The present invention provides a new class of solids supports for synthesis of modified oligomers of nucleic acids, and nucleic acid probes that have a format expediently synthesized on the new supports. Exemplary solid supports include at least one quencher bound through a linker to the solid support. Various exemplary embodiments include a moiety that stabilizes a duplex, triplex or higher order aggregation (e.g., hybridization) of nucleic acids of which the oligomer of the invention is a component. Other components of the solid support include moieties that stabilize aggregations of nucleic acids, e.g., intercalators, minor groove binding moieties, bases modified with a stabilizing moiety (e.g., alkynyl moieties, and fluoroalkyl moieties), and conformational stabilizing moieties, such as those described in commonly owned U.S. Patent Application Publication No. 2007/0059752.
摘要翻译：本发明提供了用于合成核酸修饰低聚物的新类固体支持物，以及具有在新载体上方便合成的形式的核酸探针。示例性的固体支持物包括通过连接体与固体支持物结合的至少一种猝灭剂。各种示例性实施方案包括稳定其本发明的低聚物是组分的核酸的双链体，三链体或更高级聚集（例如杂交）的部分。固体支持物的其它组分包括稳定核酸聚集的部分，例如嵌入剂，小槽结合部分，用稳定部分修饰的碱基（例如炔基部分和氟烷基部分）和构象稳定部分，例如描述的那些在共同拥有的美国专利申请公开No.2007 / 0059752中。

5. 发明授权

US08604184B2 Chemically programmable immunity 有权
标题翻译：化学可编程免疫
公开(公告)号：US08604184B2
公开(公告)日：2013-12-10
申请号：US12774194
申请日：2010-05-05
申请人： Kary B. Mullis , Jeevalatha Vivekananda , Johnathan Lloyd Kiel , Ronald M. Cook
发明人： Kary B. Mullis , Jeevalatha Vivekananda , Johnathan Lloyd Kiel , Ronald M. Cook
IPC分类号： A61K48/00 , C07H21/04
CPC分类号： A61K31/7088 , Y02A50/471 , Y02A50/473
摘要： Methods and compositions for immediately immunizing an individual against any molecule or compound are provided. The present invention is directed to an immunity linker with at least two sites; (1) at least one first binding site that binds to an immune response component in an individual, and (2) at least one second binding site that binds specifically to a desired compound or molecule, the target. The second binding sites are preferably thiolated aptamers that have the benefit of increased stability, resistance to degradation and longer circulating half life. Methods of making and using pharmaceutical compositions including immunity linker molecules having a thiolated aptamer are also provided.
摘要翻译：提供了立即将个体免疫任何分子或化合物的方法和组合物。本发明涉及具有至少两个位点的免疫接头; （1）结合个体中的免疫应答组分的至少一个第一结合位点，和（2）至少一个第二结合位点，其特异性结合所需化合物或分子，靶标。第二结合位点优选为具有增加的稳定性，耐降解性和更长的循环半衰期益处的硫醇化适体。还提供了制备和使用药物组合物的方法，包括具有巯基适体的免疫接头分子。

6. 发明授权

US06696298B2 Multi-channel reagent dispensing apparatus 有权
标题翻译：多通道试剂分注装置
公开(公告)号：US06696298B2
公开(公告)日：2004-02-24
申请号：US10012729
申请日：2001-12-07
申请人： Ronald M. Cook , Rand Dill , Arnie Baltzley
发明人： Ronald M. Cook , Rand Dill , Arnie Baltzley
IPC分类号： G01N110
CPC分类号： G01N35/1002 , B01J19/0046 , B01J2219/00315 , B01J2219/00317 , B01J2219/0036 , B01J2219/00389 , B01J2219/00414 , B01J2219/00423 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00689 , B01J2219/00722 , B01L3/0203 , C40B40/06 , C40B60/14 , G01N35/1065 , Y10T436/11 , Y10T436/114165 , Y10T436/119163 , Y10T436/2575
摘要： Embodiments of the present invention are directed to an improved chemical synthesis apparatus for performing chemical synthesis such as nuclei acid synthesis in a plurality of reaction wells or cells in an efficient manner. The apparatus employs dispenser heads that each include a cluster of nozzles which are fluidicly coupled to a plurality of reagent sources for dispensing different reagents through the single dispenser head. Because each dispenser head is capable of dispensing a plurality of different reagents, the apparatus can perform simultaneous synthesis in a plurality of cells at a high throughput without complex and elaborate control of movement of the dispenser heads relative to the cells.
摘要翻译：本发明的实施方案涉及一种用于在多个反应孔或细胞中以有效的方式进行化学合成如核酸合成的改进的化学合成装置。该设备使用分配器头，每个分配器头包括一组喷嘴，其流体耦合到多个试剂源，用于通过单个分配头分配不同的试剂。因为每个分配器头部能够分配多个不同的试剂，所以该设备可以以高通量在多个单元中执行同时合成，而无需对分配器头相对于单元的运动进行复杂和精细的控制。

7. 发明授权

US4474948A Benzazolides and their employment in phosphite ester oligonucleotide synthesis processes 失效
标题翻译：苯唑酸及其在亚磷酸酯寡核苷酸合成过程中的应用
公开(公告)号：US4474948A
公开(公告)日：1984-10-02
申请号：US366538
申请日：1982-04-08
申请人： Derek Hudson , Ronald M. Cook
发明人： Derek Hudson , Ronald M. Cook
IPC分类号： C07H19/04 , C07H21/00 , C07H19/18 , C07H19/20
CPC分类号： C07H21/00 , C07H19/04
摘要： Benzotriazoles are employed in phosphite triester oligonucleotide synthesis. The benzotriazoles also form phosphinedibenzazolides. Processes employing these reagents are also disclosed.
摘要翻译：苯并三唑用于亚磷酸三酯寡核苷酸合成。苯并三唑也形成膦酰基二苯唑。还公开了使用这些试剂的方法。

8. 发明授权

US08466266B2 Stabilized nucleic acid dark quencher-fluorophore probes 有权
标题翻译：稳定的核酸暗猝灭剂 - 荧光团探针
公开(公告)号：US08466266B2
公开(公告)日：2013-06-18
申请号：US12416901
申请日：2009-04-01
申请人： Ronald M. Cook , Matt Lyttle
发明人： Ronald M. Cook , Matt Lyttle
IPC分类号： C07C245/02
CPC分类号： C12Q1/6876 , C07D219/04 , C07H19/06 , C07H19/073 , C09B31/02
摘要： The present invention provides a new class of solids supports for synthesis of modified oligomers of nucleic acids, and nucleic acid probes that have a format expediently synthesized on the new supports. Exemplary solid supports include at least one quencher bound through a linker to the solid support. Various exemplary embodiments include a moiety that stabilizes a duplex, triplex or higher order aggregation (e.g., hybridization) of nucleic acids of which the oligomer of the invention is a component. Other components of the solid support include moieties that stabilize aggregations of nucleic acids, e.g., intercalators, minor groove binding moieties, bases modified with a stabilizing moiety (e.g., alkynyl moieties, and fluoroalkyl moieties), and conformational stabilizing moieties, such as those described in commonly owned U.S. Patent Application Publication No. 2007/0059752.
摘要翻译：本发明提供了用于合成核酸修饰低聚物的新类固体支持物，以及具有在新载体上方便合成的形式的核酸探针。示例性的固体支持物包括通过连接体与固体支持物结合的至少一种猝灭剂。各种示例性实施方案包括稳定其本发明的低聚物是组分的核酸的双链体，三链体或更高级聚集（例如杂交）的部分。固体支持物的其它组分包括稳定核酸聚集的部分，例如嵌入剂，小槽结合部分，用稳定部分修饰的碱基（例如炔基部分和氟烷基部分）和构象稳定部分，例如描述的那些在共同拥有的美国专利申请公开No.2007 / 0059752中。

9. 发明申请

US20120208190A1 LUMINESCENT METAL ION COMPLEXES 审中-公开
标题翻译：发光金属离子复合物
公开(公告)号：US20120208190A1
公开(公告)日：2012-08-16
申请号：US13356451
申请日：2012-01-23
申请人： Ronald M. Cook , Matt Lyttle , Mary Katherine Johannson
发明人： Ronald M. Cook , Matt Lyttle , Mary Katherine Johannson
IPC分类号： C12Q1/68 , G01N33/50 , G01N33/573 , G01N33/566 , C07H21/04 , G01N33/48
CPC分类号： C07F15/0053 , C07B2200/11 , C09B56/00 , C09B57/10 , Y10T436/143333
摘要： The present invention provides luminescent metal ion complexes for use in a wide range of biological and chemical studies. The luminescent metal ion complexes of the invention comprise a metal ion chelating component covalently bound to a carrier molecule. Also provided are methods of making and using the luminescent metal ion complexes.
摘要翻译：本发明提供用于广泛的生物和化学研究的发光金属离子络合物。本发明的发光金属离子络合物包含与载体分子共价结合的金属离子螯合组分。还提供了制造和使用发光金属离子络合物的方法。

10. 发明申请

US20090259030A1 STABILIZED NUCLEIC ACID DARK QUENCHER-FLUOROPHORE PROBES 有权
标题翻译：稳定的核酸深色探针 - 荧光探针
公开(公告)号：US20090259030A1
公开(公告)日：2009-10-15
申请号：US12416901
申请日：2009-04-01
申请人： Ronald M. Cook , Matt Lyttle
发明人： Ronald M. Cook , Matt Lyttle
IPC分类号： C07C245/02 , C07H21/00 , C07D241/46
CPC分类号： C12Q1/6876 , C07D219/04 , C07H19/06 , C07H19/073 , C09B31/02
摘要： The present invention provides a new class of solids supports for synthesis of modified oligomers of nucleic acids, and nucleic acid probes that have a format expediently synthesized on the new supports. Exemplary solid supports include at least one quencher bound through a linker to the solid support. Various exemplary embodiments include a moiety that stabilizes a duplex, triplex or higher order aggregation (e.g., hybridization) of nucleic acids of which the oligomer of the invention is a component. Other components of the solid support include moieties that stabilize aggregations of nucleic acids, e.g., intercalators, minor groove binding moieties, bases modified with a stabilizing moiety (e.g., alkynyl moieties, and fluoroalkyl moieties), and conformational stabilizing moieties, such as those described in commonly owned U.S. Patent Application Publication No. 2007/0059752.
摘要翻译：本发明提供了用于合成核酸修饰低聚物的新类固体支持物，以及具有在新载体上方便合成的形式的核酸探针。示例性的固体支持物包括通过连接体与固体支持物结合的至少一种猝灭剂。各种示例性实施方案包括稳定其本发明的低聚物是组分的核酸的双链体，三链体或更高级聚集（例如杂交）的部分。固体支持物的其它组分包括稳定核酸聚集的部分，例如嵌入剂，小槽结合部分，用稳定部分修饰的碱基（例如炔基部分和氟烷基部分）和构象稳定部分，例如描述的那些在共同拥有的美国专利申请公开No.2007 / 0059752中。

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