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21. 发明授权

US08486625B2 Detection of nucleic acid reactions on bead arrays 有权
公开(公告)号：US08486625B2
公开(公告)日：2013-07-16
申请号：US12212585
申请日：2008-09-17
申请人： Kevin Gunderson , John R. Stuelpnagel , Mark S. Chee
发明人： Kevin Gunderson , John R. Stuelpnagel , Mark S. Chee
IPC分类号： C12Q1/68 , C12M1/36 , C12P19/34 , C07H21/04
CPC分类号： C12Q1/6837 , C12Q1/6858 , C12Q1/6874 , C12Q2535/131 , C12Q2525/191 , C12Q2531/137 , C12Q2563/149
摘要： The present invention is directed to methods and compositions for the use of microsphere arrays to detect and quantify a number of nucleic acid reactions. The invention finds use in genotyping, i.e. the determination of the sequence of nucleic acids, particularly alterations such as nucleotide substitutions (mismatches) and single nucleotide polymorphisms (SNPs). Similarly, the invention finds use in the detection and quantification of a nucleic acid target using a variety of amplification techniques, including both signal amplification and target amplification. The methods and compositions of the invention can be used in nucleic acid sequencing reactions as well. All applications can include the use of adapter sequences to allow for universal arrays.

22. 发明授权

US08465694B2 Oligonucleotide synthesizer 有权
标题翻译：寡核苷酸合成仪
公开(公告)号：US08465694B2
公开(公告)日：2013-06-18
申请号：US13023406
申请日：2011-02-08
申请人： Michal Lebl , Mark S. Chee , Steven M. Barnard , David L. Heiner , Vit Pokorny , Mark J. Nibbe , Aaron Christopher Jones
发明人： Michal Lebl , Mark S. Chee , Steven M. Barnard , David L. Heiner , Vit Pokorny , Mark J. Nibbe , Aaron Christopher Jones
IPC分类号： G01N33/00
CPC分类号： B01J19/0046 , B01J2219/00283 , B01J2219/00286 , B01J2219/00295 , B01J2219/00308 , B01J2219/00315 , B01J2219/00326 , B01J2219/00328 , B01J2219/00369 , B01J2219/00389 , B01J2219/00412 , B01J2219/00421 , B01J2219/00423 , B01J2219/00454 , B01J2219/0049 , B01J2219/005 , B01J2219/00585 , B01J2219/0059 , B01J2219/00689 , B01J2219/0072 , B01J2219/00722 , C40B40/06 , C40B50/14 , C40B60/14 , G01N35/025 , G01N35/028 , G01N35/1067 , G01N2035/00504 , G01N2035/1037 , G01N2035/1069 , Y10T436/111666 , Y10T436/12 , Y10T436/2575
摘要： An apparatus for high-throughput combinatorial synthesis of organic molecules including a reaction vessel for containing a combinatorial chemistry synthetic reaction, a liquid dispenser for dispensing the liquid, a liquid aspirator and an adjustment mechanism. The reaction vessel includes an ingress aperture allowing a liquid to enter into an interior of the vessel and an egress aperture for aspirating the liquid from the vessel. The liquid dispenser dispenses liquid through the ingress aperture. The liquid aspirator aspirates liquid through the egress aperture and includes a rotor for carrying the vessel and orbiting the vessel about an axis of rotation. The rotor is oriented generally in a horizontal plane and includes an adjustment mechanism for adjusting the angle of the vessel relative to the horizontal plane in response to the centrifugal force generated by orbiting the vessel about the axis or rotation. A method of combinatorial synthesis of organic molecules is also disclosed.
摘要翻译：一种用于高通量组合合成有机分子的装置，包括用于包含组合化学合成反应的反应容器，用于分配液体的液体分配器，液体抽吸器和调节机构。反应容器包括允许液体进入容器内部的入口孔和用于从容器吸出液体的出口孔。液体分配器通过入口孔分配液体。液体吸入器通过出口孔吸出液体，并且包括用于承载容器并绕容器围绕旋转轴线运动的转子。转子通常在水平面定向，并且包括调节机构，用于响应于通过围绕轴线或旋转绕过容器而产生的离心力来调节容器相对于水平面的角度。还公开了组合合成有机分子的方法。

23. 发明申请

US20120129248A1 ASSAY TOOLS AND METHODS OF USE 审中-公开
标题翻译：测定工具和使用方法
公开(公告)号：US20120129248A1
公开(公告)日：2012-05-24
申请号：US13388229
申请日：2010-08-02
申请人： Mark S. Chee , Igor A. Kozlov
发明人： Mark S. Chee , Igor A. Kozlov
IPC分类号： G01N33/53 , C12M1/40
CPC分类号： G01N33/54366 , C12Q1/34 , C12Q1/37 , G01N33/573
摘要： The present invention provides assay tools for the detection of biological or chemical activity in a sample. The assay tools of the invention provide direct detection using a positive signal generated on a surface of the assay tool. These assay tools provide improved methods for detection and/or identification of multiple agents (e.g., enzymes) in a sample, analysis of substrate specificity of such agents, and binding affinities and specificities of such agents. Upon activity a component is released from a first immobilised construct and then captured by a capture surface. At least two different immobilised constructs are used.
摘要翻译：本发明提供了用于检测样品中生物或化学活性的测定工具。本发明的测定工具使用在测定工具的表面上产生的阳性信号提供直接检测。这些测定工具提供了用于样品中多个试剂（例如酶）的检测和/或鉴定的改进方法，这些试剂的底物特异性的分析以及这些试剂的结合亲和力和特异性。在活动时，将组分从第一固定化构建物释放，然后由捕获表面捕获。使用至少两种不同的固定化构建体。

24. 发明申请

US20100216656A1 METHODS OF ENZYMATIC DISCRIMINATION ENHANCEMENT AND SURFACE-BOUND DOUBLE-STRANDED DNA 有权
标题翻译：酶切鉴定增强和表面双重双链DNA的方法
公开(公告)号：US20100216656A1
公开(公告)日：2010-08-26
申请号：US12187503
申请日：2008-08-07
申请人： David J. Lockhart , Mark S. Chee , Dirk Vetter , Martin Digglemann
发明人： David J. Lockhart , Mark S. Chee , Dirk Vetter , Martin Digglemann
IPC分类号： C40B30/04 , C40B60/12
CPC分类号： C40B60/12 , B01J2219/00427 , B01J2219/00529 , B01J2219/00596 , B01J2219/00608 , B01J2219/00659 , B01J2219/00722 , C12Q1/6837 , C12Q1/6869 , C12Q2565/507 , C12Q2521/501
摘要： Methods for discriminating between fully complementary hybrids and those that differ by one or more base pairs and libraries of unimolecular, double-stranded oligonucleotides on a solid support. In one embodiment, the present invention provides methods of using nuclease treatment to improve the quality of hybridization signals on high density oligonucleotide arrays. In another embodiment, the present invention provides methods of using ligation reactions to improve the quality of hybridization signals on high density oligonucleotide arrays. In yet another embodiment, the present invention provides libraries of unimolecular or intermolecular, double-stranded oligonucleotides on a solid support. These libraries are useful in pharmaceutical discovery for the screening of numerous biological samples for specific interactions between the double-stranded oligonucleotides, and peptides, proteins, drugs and RNA. In a related aspect, the present invention provides libraries of conformationally restricted probes on a solid support. The probes are restricted in their movement and flexibility using double-stranded oligonucleotides as scaffolding. The probes are also useful in various screening procedures associated with drug discovery and diagnosis. The present invention further provides methods for the preparation and screening of the above libraries.
摘要翻译：用于区分完全互补的杂交体与通过一个或多个碱基对不同的那些的方法和在固体支持物上的单分子双链寡核苷酸的文库。在一个实施方案中，本发明提供了使用核酸酶处理来提高高密度寡核苷酸阵列上杂交信号质量的方法。在另一个实施方案中，本发明提供了使用连接反应来提高高密度寡核苷酸阵列上杂交信号质量的方法。在另一个实施方案中，本发明提供了在固体支持物上的单分子或分子间双链寡核苷酸的文库。这些文库在药物发现中可用于筛选许多生物样品，用于双链寡核苷酸与肽，蛋白质，药物和RNA之间的特异性相互作用。在相关方面，本发明提供了在固体支持物上的构象限制探针的文库。使用双链寡核苷酸作为脚手架，探针的运动和灵活性受到限制。探针也可用于与药物发现和诊断相关的各种筛选程序。本发明还提供了制备和筛选上述文库的方法。

25. 发明授权

US07604996B1 Compositions and methods for preparing oligonucleotide solutions 有权
标题翻译：制备寡核苷酸溶液的组合物和方法
公开(公告)号：US07604996B1
公开(公告)日：2009-10-20
申请号：US09642068
申请日：2000-08-18
申请人： John R. Stuelpnagel , Mark S. Chee
发明人： John R. Stuelpnagel , Mark S. Chee
IPC分类号： C12Q1/68 , C12P19/34 , C12M1/34 , C12M3/00 , C07H21/02 , C07H21/04
CPC分类号： C12N15/1093 , C12Q1/6806 , C12Q1/6834 , C12Q1/6837 , C12Q1/686 , C12Q1/6876 , G11C7/1048 , H03K19/0966 , Y10S977/792 , C12Q2525/197 , C12Q2523/107
摘要： The present invention is directed to methods and compositions for generating a pool of oligonucleotides. The invention finds use in preparing a population or subpopulations of oligonucleotides in solution. The pool of oligonucleotides finds use in a variety of nucleic acid detection and/or amplification assays.
摘要翻译：本发明涉及用于产生寡核苷酸库的方法和组合物。本发明用于制备溶液中寡核苷酸的群体或亚群。寡核苷酸库可用于各种核酸检测和/或扩增测定。

26. 发明申请

US20090227472A1 ARRAY SYSTEMS AND COMPONENTS 审中-公开
标题翻译：阵列系统和组件
公开(公告)号：US20090227472A1
公开(公告)日：2009-09-10
申请号：US12405170
申请日：2009-03-16
申请人： John R. Stuelpnagel , Mark S. Chee , Steven R. Auger , Gan G. Wang , Laura S. Casas , Shawn Christopher Baker , Robert C. Kain
发明人： John R. Stuelpnagel , Mark S. Chee , Steven R. Auger , Gan G. Wang , Laura S. Casas , Shawn Christopher Baker , Robert C. Kain
IPC分类号： C40B40/06
CPC分类号： B01J19/0046 , B01J2219/00315 , B01J2219/00317 , B01J2219/00382 , B01J2219/005 , B01J2219/00511 , B01J2219/00524 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/00612 , B01J2219/00621 , B01J2219/00626 , B01J2219/00637 , B01J2219/00648 , B01J2219/00659 , B01J2219/00704 , B01J2219/0072 , B01J2219/00722 , C40B40/06 , G01N33/54393
摘要： The invention relates to sensor compositions comprising a composite array of individual arrays, to allow for simultaneous processing of a number of samples. The invention further provides methods of making and using the composite arrays. The invention further provides a hybridization chamber for use with a composite array.
摘要翻译：本发明涉及包括单独阵列的复合阵列的传感器组合物，以允许同时处理多个样品。本发明还提供了制备和使用复合阵列的方法。本发明还提供了一种与复合阵列一起使用的杂交室。

27. 发明授权

US07455971B2 Multiplex decoding of array sensors with microspheres 有权
标题翻译：阵列传感器与微球的多路解码
公开(公告)号：US07455971B2
公开(公告)日：2008-11-25
申请号：US11285722
申请日：2005-11-22
申请人： Mark S. Chee , John R. Stuelpnagel , Anthony W. Czarnik
发明人： Mark S. Chee , John R. Stuelpnagel , Anthony W. Czarnik
IPC分类号： C12Q1/68 , G01N33/53 , C12M1/00 , C12M1/34 , C07H21/04
CPC分类号： C12Q1/6837 , B01J19/0046 , B01J2219/00317 , B01J2219/00459 , B01J2219/00466 , B01J2219/005 , B01J2219/00572 , B01J2219/00576 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00619 , B01J2219/00621 , B01J2219/00626 , B01J2219/0063 , B01J2219/00637 , B01J2219/00641 , B01J2219/00644 , B01J2219/00648 , B01J2219/00659 , B01J2219/00677 , B01J2219/00702 , B01J2219/00722 , B01L3/5085 , B82Y30/00 , C12Q1/6816 , C12Q1/6825 , C12Q1/6834 , C40B40/06 , C40B60/14 , C40B70/00 , G01N33/54313 , G06K9/6202 , Y10S977/924 , C12Q2563/155 , C12Q2563/179 , C12Q2563/107 , C12Q2527/137 , C12Q2521/313 , C12Q2537/143
摘要： The invention relates to compositions and methods for multiplex decoding of microsphere array sensors.
摘要翻译：本发明涉及微球阵列传感器的复用解码的组合物和方法。

28. 发明授权

US06924094B1 Chip-based species identification and phenotypic characterization of microorganisms 失效
标题翻译：基于芯片的物种鉴定和微生物的表型表征
公开(公告)号：US06924094B1
公开(公告)日：2005-08-02
申请号：US09724938
申请日：2000-11-28
申请人： Thomas R. Gingeras , David Mack , Mark S. Chee , Anthony J. Berno , Lubert Stryer , Ghassan Ghandour , Ching Wang
发明人： Thomas R. Gingeras , David Mack , Mark S. Chee , Anthony J. Berno , Lubert Stryer , Ghassan Ghandour , Ching Wang
IPC分类号： C12Q1/68 , C12Q1/70
CPC分类号： C40B80/00 , B01J2219/00529 , B01J2219/00608 , B01J2219/00612 , C12Q1/6809 , C12Q1/6837 , C12Q1/6888 , C12Q1/689 , C12Q2600/156 , G01N33/54386 , G06F19/20 , C12Q2565/501
摘要： This invention provides oligonucleotide based arrays and methods for speciating and phenotyping organisms, for example, using oligonucleotide sequences based on the Mycobacterium tubercluosis rpoB gene. The groups or species to which an organism belongs may be determined by comparing hybridization patterns of target nucleic acid from the organism to hybridization patterns in a database.
摘要翻译：本发明提供了基于寡核苷酸的阵列和用于指定和表型生物的方法，例如使用基于结核分枝杆菌rpoB基因的寡核苷酸序列。可以通过将来自生物体的靶核酸的杂交模式与数据库中的杂交模式进行比较来确定生物体所属的组或物种。

29. 发明授权

US06828104B2 Nucleic acid affinity columns 有权
标题翻译：核酸亲和柱
公开(公告)号：US06828104B2
公开(公告)日：2004-12-07
申请号：US10219006
申请日：2002-08-14
申请人： Robert J. Lipshutz , MacDonald S. Morris , Mark S. Chee , Thomas R. Gingeras
发明人： Robert J. Lipshutz , MacDonald S. Morris , Mark S. Chee , Thomas R. Gingeras
IPC分类号： C12Q168
CPC分类号： C12Q1/6806 , B01J2219/00608 , B01J2219/0061 , B01J2219/00612 , B01J2219/00619 , B01J2219/00621 , B01J2219/00626 , B01J2219/0063 , B01J2219/00637 , B01J2219/00641 , B01J2219/00659 , B01J2219/00722 , C12Q1/6809 , C12Q1/6837 , C40B40/06 , C12Q2565/107 , C12Q2525/155
摘要： This invention provides nucleic acid affinity matrices that bear a large number of different nucleic acid affinity ligands allowing the simultaneous selection and removal of a large number of preselected nucleic acids from the sample. Methods of producing such affinity matrices are also provided. In general the methods involve the steps of a) providing a nucleic acid amplification template array comprising a surface to which are attached at least 50 oligonucleotides having different nucleic acid sequences, and wherein each different oligonucleotide is localized in a predetermined region of said surface, the density of said oligonucleotides is greater than about 60 different oligonucleotides per 1 cm2, and all of said different oligonucleotides have an identical terminal 3′ nucleic acid sequence and an identical terminal 5′ nucleic acid sequence. b) amplifying said multiplicity of oligonucleotides to provide a pool of amplified nucleic acids; and c) attaching the pool of nucleic acids to a solid support.
摘要翻译：本发明提供了携带大量不同核酸亲和配体的核酸亲和基质，允许同时从样品中选择和除去大量预选核酸。还提供了生产这种亲和基质的方法。通常，所述方法包括以下步骤：a）提供核酸扩增模板阵列，其包含与至少50个具有不同核酸序列的寡核苷酸连接的表面，并且其中每个不同的寡核苷酸定位在所述表面的预定区域中，所述寡核苷酸的密度大于每1cm 2大约60个不同的寡核苷酸，并且所有所述不同寡核苷酸具有相同的末端3'核酸序列和相同的末端5'核酸序列。 b）扩增所述多重寡核苷酸以提供扩增核酸的库; 和c）将核酸池连接到固体支持物上。

30. 发明授权

US06440677B2 Nucleic acid affinity columns 有权
标题翻译：核酸亲和柱
公开(公告)号：US06440677B2
公开(公告)日：2002-08-27
申请号：US09910223
申请日：2001-07-20
申请人： Robert J. Lipshutz , MacDonald S. Morris , Mark S. Chee , Thomas R. Gingeras
发明人： Robert J. Lipshutz , MacDonald S. Morris , Mark S. Chee , Thomas R. Gingeras
IPC分类号： C12Q168
CPC分类号： C12Q1/6806 , B01J2219/00608 , B01J2219/0061 , B01J2219/00612 , B01J2219/00619 , B01J2219/00621 , B01J2219/00626 , B01J2219/0063 , B01J2219/00637 , B01J2219/00641 , B01J2219/00659 , B01J2219/00722 , C12Q1/6809 , C12Q1/6837 , C40B40/06 , C12Q2565/107 , C12Q2525/155
摘要： Nucleic acid affinity matrices that bear a large number of different nucleic acid affinity ligands allowing the simultaneous selection and removal of a large number of preselected nucleic acids from the sample. Methods of producing such affinity matrices are also provided. In general the methods involve the steps of a) providing a nucleic acid amplification template array comprising a surface to which are attached at least 50 oligonucleotides having different nucleic acid sequences, and wherein each different oligonucleotide is localized in a predetermined region of the surface, the density of the oligonucleotides is greater than about 60 different oligonucleotides per 1 cm2, and all of the different oligonucleotides have an identical terminal 3′ nucleic acid sequence and an identical terminal 5′ nucleic acid sequence. b) amplifying the multiplicity of oligonucleotides to provide a pool of amplified nucleic acids; and c) attaching the pool of nucleic acids to a solid support.
摘要翻译：具有大量不同核酸亲和配体的核酸亲和基质，允许从样品中同时选择和除去大量预选核酸。还提供了生产这种亲和基质的方法。通常，所述方法包括以下步骤：a）提供核酸扩增模板阵列，其包含与至少50个具有不同核酸序列的寡核苷酸连接的表面，并且其中每个不同的寡核苷酸定位在表面的预定区域中，每1cm 2寡核苷酸的密度大于约60个不同寡核苷酸，并且所有不同的寡核苷酸具有相同的末端3'核酸序列和相同的末端5'核酸序列。 b）扩增多重寡核苷酸以提供扩增的核酸库; 和c）将核酸池连接到固体支持物上。

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