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    ASSAY TOOLS AND METHODS OF USE
    23.
    发明申请
    ASSAY TOOLS AND METHODS OF USE 审中-公开
    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

    Applicant: Mark S. Chee ,  Igor A. Kozlov

    Inventor： Mark S. Chee ,  Igor A. Kozlov

    IPC: G01N33/53 ,  C12M1/40

    CPC classification number: G01N33/54366 ,  C12Q1/34 ,  C12Q1/37 ,  G01N33/573

    Abstract: 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.

    Abstract translation: 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。

    METHODS OF ENZYMATIC DISCRIMINATION ENHANCEMENT AND SURFACE-BOUND DOUBLE-STRANDED DNA
    24.
    发明申请
    METHODS OF ENZYMATIC DISCRIMINATION ENHANCEMENT AND SURFACE-BOUND DOUBLE-STRANDED DNA 有权
    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

    Applicant: David J. Lockhart ,  Mark S. Chee ,  Dirk Vetter ,  Martin Digglemann

    Inventor： David J. Lockhart ,  Mark S. Chee ,  Dirk Vetter ,  Martin Digglemann

    IPC: C40B30/04 ,  C40B60/12

    CPC classification number: C40B60/12 ,  B01J2219/00427 ,  B01J2219/00529 ,  B01J2219/00596 ,  B01J2219/00608 ,  B01J2219/00659 ,  B01J2219/00722 ,  C12Q1/6837 ,  C12Q1/6869 ,  C12Q2565/507 ,  C12Q2521/501

    Abstract: 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.

    Abstract translation: 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。

    Nucleic acid affinity columns
    29.
    发明授权
    Nucleic acid affinity columns 有权
    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

    Applicant: Robert J. Lipshutz ,  MacDonald S. Morris ,  Mark S. Chee ,  Thomas R. Gingeras

    Inventor： Robert J. Lipshutz ,  MacDonald S. Morris ,  Mark S. Chee ,  Thomas R. Gingeras

    IPC: C12Q168

    CPC classification number: 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

    Abstract: 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.

    Abstract translation: 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。

    Nucleic acid affinity columns
    30.
    发明授权
    Nucleic acid affinity columns 有权
    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

    Applicant: Robert J. Lipshutz ,  MacDonald S. Morris ,  Mark S. Chee ,  Thomas R. Gingeras

    Inventor： Robert J. Lipshutz ,  MacDonald S. Morris ,  Mark S. Chee ,  Thomas R. Gingeras

    IPC: C12Q168

    CPC classification number: 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

    Abstract: 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.

    Abstract translation: 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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