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    Methods of enzymatic discrimination enhancement and surface bound double-stranded DNA
    31.
    发明申请
    Methods of enzymatic discrimination enhancement and surface bound double-stranded DNA 审中-公开
    酶鉴别增强方法和表面结合双链DNA

    公开(公告)号：US20060292579A1

    公开(公告)日：2006-12-28

    申请号：US11176012

    申请日：2005-07-05

    申请人： David Lockhart ,  Mark Chee ,  Dirk Vetter ,  Martin Digglemann

    发明人： David Lockhart ,  Mark Chee ,  Dirk Vetter ,  Martin Digglemann

    IPC分类号： C12Q1/68

    CPC分类号： C12N15/1093 ,  B01J19/0046 ,  B01J2219/00529 ,  B01J2219/00608 ,  B01J2219/00612 ,  B01J2219/00626 ,  B01J2219/0063 ,  B01J2219/00659 ,  B01J2219/00722 ,  C07B2200/11 ,  C07H21/00 ,  C12Q1/6827 ,  C12Q1/683 ,  C12Q1/6837 ,  C12Q1/6874 ,  C40B40/06 ,  C40B80/00 ,  G01N33/5308 ,  G01N33/551

    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。

    Cellular arrays comprising encoded cells
    34.
    发明申请
    Cellular arrays comprising encoded cells 审中-公开
    包含编码细胞的细胞阵列

    公开(公告)号：US20050158702A1

    公开(公告)日：2005-07-21

    申请号：US10363240

    申请日：2001-09-05

    申请人： John Stuelpnagel ,  Mark Chee

    发明人： John Stuelpnagel ,  Mark Chee

    IPC分类号： C07B61/00 ,  G01N33/50 ,  G01N33/543 ,  C12Q1/00 ,  C12M1/34 ,  G01N33/53 ,  G01N33/567

    CPC分类号： G01N33/502 ,  C40B40/00 ,  G01N33/5008 ,  G01N33/54373

    摘要： A biosensor, sensor array, sensing method and sensing apparatus are provided in which individual cells or randomly mixed populations of cells, having unique response characteristics to chemical and biological materials, are deployed in a plurality of discrete sites on a substrate. In a preferred embodiment, the discrete sites comprise microwells formed at the distal end of individual fibers within a fiber optic array. The biosensor array utilizes an optically interrogatable encoding scheme for determining the identity and location of each cell type in the array and provides for simultaneous measurements of large number of individual cell respnses to target analyses. The sensing method utilizes the unique ability of cell populations to respond to biologically significant compounds in a characteristic and detectable manner. The biosensor array and measurement method may be employed in the study of biologically active materials in situ environmental monitoring, monitoring of a variety of bioprocesses, and for high throughput screening of large combinatorial chemical libraries.

    摘要翻译： 提供了生物传感器，传感器阵列，感测方法和感测装置，其中对化学和生物材料具有独特响应特性的单个细胞或随机混合的细胞群体部署在基底上的多个离散位置。 在优选实施例中，离散位置包括在光纤阵列内的各个纤维的远端处形成的微孔。 生物传感器阵列利用光学可询问编码方案来确定阵列中每种细胞类型的身份和位置，并提供大量单个细胞反应同时测量以进行目标分析。 感测方法利用细胞群体以特征和可检测方式对生物学重要化合物的独特能力。 生物传感器阵列和测量方法可用于研究生物活性材料的原位环境监测，各种生物过程的监测以及大量组合化学文库的高通量筛选。

    Method to detect gene polymorphisms and monitor allelic expression employing a probe array
    35.
    发明授权
    Method to detect gene polymorphisms and monitor allelic expression employing a probe array 有权
    使用探针阵列检测基因多态性和监测等位基因表达的方法

    公开(公告)号：US06368799B1

    公开(公告)日：2002-04-09

    申请号：US09445734

    申请日：2000-03-14

    申请人： Mark Chee

    发明人： Mark Chee

    IPC分类号： C12Q168

    CPC分类号： C12Q1/6837 ,  C12Q2600/156 ,  C12Q2600/158 ,  Y10S435/911 ,  C12Q2535/131

    摘要： The invention provides methods of monitoring expression levels of different polymorphic forms of a gene. Such methods entail analyzing genomic DNA from an individual to determine the presence of heterozygous polymorphic forms at a polymorphic site within a transcribed sequence of a gene of interest. RNA from a tissue of the individual in which the gene is expressed is then analyzed to determine relative proportions of polymorphic forms in transcript of the gene. Having identified alleles of a gene that are expressed at different levels, the alleles can be further analyzed to locate a second polymorphism that has a causative role in the different expression levels. The methods are amenable to analyzing large collections of genes simultaneously using arrays of immobilized probes.

    摘要翻译： 本发明提供了监测基因不同多态形式的表达水平的方法。 这样的方法需要分析来自个体的基因组DNA，以确定在感兴趣的基因的转录序列内的多态性位点处存在杂合多态性形式。 然后分析来自表达基因的个体的组织的RNA，以确定基因转录本中多态形式的相对比例。 鉴定了在不同水平表达的基因的等位基因，可以进一步分析等位基因以定位在不同表达水平中起决定作用的第二多态性。 该方法适用于使用固定化探针阵列同时分析大量基因。