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    METHODS, COMPOSITIONS, AND KITS FOR DETECTING PROTEIN AGGREGATES
    1.
    发明申请
    METHODS, COMPOSITIONS, AND KITS FOR DETECTING PROTEIN AGGREGATES 有权
    用于检测蛋白质聚集体的方法，组合物和试剂盒

    公开(公告)号：US20080003604A1

    公开(公告)日：2008-01-03

    申请号：US11743517

    申请日：2007-05-02

    申请人： David Ruff ,  Mark Shannon ,  Kenneth Livak ,  Karl Guegler ,  Kevin Hennessy

    发明人： David Ruff ,  Mark Shannon ,  Kenneth Livak ,  Karl Guegler ,  Kevin Hennessy

    IPC分类号： C12Q1/68

    CPC分类号： C12Q1/6876 ,  C07K14/47 ,  C07K14/4711 ,  C12Q1/6816 ,  C12Q2533/107

    摘要： The present teachings provide methods, compositions, and kits for detecting the presence of protein aggregates. In some embodiments, the protein aggregate is treated with a labeled precursor, and the labeled precursor is incorporated into the protein aggregate to form a labeled protein aggregate. The labeled protein aggregate is then measured, thus detecting the presence of the protein aggregate. In some embodiments, the labeled protein aggregate is detected by interaction of labeled precursors, for example by a proximity ligation assay.

    摘要翻译： 本教导提供了用于检测蛋白质聚集体的存在的方法，组合物和试剂盒。 在一些实施方案中，用标记的前体处理蛋白质聚集体，并将标记的前体掺入蛋白质聚集体中以形成标记的蛋白质聚集体。 然后测量标记的蛋白质聚集体，从而检测蛋白质聚集体的存在。 在一些实施方案中，标记的蛋白质聚集体通过标记的前体的相互作用来检测，例如通过邻近连接测定。

    METHODS FOR RNA PROFILING
    2.
    发明申请
    METHODS FOR RNA PROFILING 审中-公开
    RNA分析方法

    公开(公告)号：US20070015187A1

    公开(公告)日：2007-01-18

    申请号：US11458086

    申请日：2006-07-17

    申请人： Kai Lao ,  Kenneth Livak

    发明人： Kai Lao ,  Kenneth Livak

    IPC分类号： C12Q1/68 ,  C12P19/34

    CPC分类号： C12Q1/6883 ,  C12Q1/6809 ,  C12Q1/6876 ,  C12Q2600/158 ,  C12Q2600/178 ,  C12Q2525/207

    摘要： The present teachings provide methods, compositions, and kits for detecting micro RNAs (miRNAs). In some embodiments, the miRNAs are quantified from formalin-fixed paraffin-embedded tissue samples in which messenger RNA is degraded. The present teachings take advantage of the observation that most mature miRNAs in vivo are protected by degradation as a result of their association with RISC. Thus, novel methods of studying nucleic acids in archived tissues containing degraded messenger RNA are provided, wherein RISC-protected miRNAs are liberated, and analyzed.

    摘要翻译： 本教导提供了用于检测微RNA（miRNA）的方法，组合物和试剂盒。 在一些实施方案中，从福尔马林固定的石蜡包埋的组织样品中定量miRNA，其中信使RNA被降解。 本教导利用观察结果，其中大多数成熟的miRNA在体内受到与RISC结合的降解的保护。 因此，提供了在含有降解的信使RNA的存档组织中研究核酸的新方法，其中RISC保护的miRNA被释放并分析。

    BINARY PROBE AND CLAMP COMPOSITION.
    3.
    发明申请
    BINARY PROBE AND CLAMP COMPOSITION. 有权
    二进制和夹子组成。

    公开(公告)号：US20060035217A1

    公开(公告)日：2006-02-16

    申请号：US10112677

    申请日：2002-03-28

    申请人： Kenneth Livak ,  Michael Egholm ,  Michael Hunkapiller

    发明人： Kenneth Livak ,  Michael Egholm ,  Michael Hunkapiller

    IPC分类号： C12Q1/68 ,  C07H21/04

    CPC分类号： C12Q1/6816 ,  C12Q1/6818 ,  C12Q2549/126 ,  C12Q2537/119 ,  C12Q2525/179

    摘要： Binary probe and clamp compositions conduct methods for target hybridization detection. Where the probe is a substrate for exonuclease cleavage, the composition provides quantitation and detection of PCR products, by real-time and end-point measurements. Where the probe is an amplification primer, the composition provides an improved method for labelling and detection of PCR products. Probes and clamps may be labelled with fluorescent dyes, quenchers, hybridization-stabilizing moieties, chemiluminescent dyes, and affinity ligands. Clamps may be nucleic acid analogs, such as 2-aminoethylglycine PNA.

    摘要翻译： 二进制探针和夹具组合物进行靶杂交检测的方法。 当探针是外切核酸酶切割的底物时，组合物通过实时和终点测量提供PCR产物的定量和检测。 当探针是扩增引物时，组合物提供了PCR产物的标记和检测的改进方法。 探针和夹具可以用荧光染料，猝灭剂，杂交稳定部分，化学发光染料和亲和配体标记。 夹具可以是核酸类似物，例如2-氨基乙基甘氨酸PNA。

    MULTIPLEXED AMPLIFICATION OF SHORT NUCLEIC ACIDS
    5.
    发明申请
    MULTIPLEXED AMPLIFICATION OF SHORT NUCLEIC ACIDS 审中-公开
    短期核酸的多重放大

    公开(公告)号：US20070077570A1

    公开(公告)日：2007-04-05

    申请号：US11421449

    申请日：2006-05-31

    申请人： Kai Lao ,  Kenneth Livak ,  Neil Straus

    发明人： Kai Lao ,  Kenneth Livak ,  Neil Straus

    IPC分类号： C12Q1/68 ,  C12P19/34

    CPC分类号： C12N15/1065 ,  C12Q1/6851 ,  C12Q1/686 ,  C12Q2525/301 ,  C12Q2525/161 ,  C12Q2563/179 ,  C12Q2537/143 ,  C12Q2525/207

    摘要： The present teachings provide methods, compositions, and kits for reverse transcribing and amplifying small nucleic acids such as micro RNAs. High levels of multiplexing are provided by the use of a zip-coded stem-loop reverse transcription primer, along with a PCR-based pre-amplification reaction that comprises a zip-coded forward primer. Detector probes in downstream decoding PCRs can take advantage of the zip-code introduced by the stem-loop reverse transcription primer. In some embodiments, further amplification is achieved by cycling the reverse transcription reaction. The present teachings also provide compositions and kits useful for performing the reverse transcription and amplification reactions described herein.

    摘要翻译： 本教导提供用于逆转录和扩增小核酸如微RNA的方法，组合物和试剂盒。 通过使用zip编码的茎 - 环逆转录引物以及包含经翻译的正向引物的基于PCR的预扩增反应来提供高水平的复用。 下游解码PCR中的检测器探针可以利用茎环逆转录引物引入的zip码。 在一些实施方案中，通过循环逆转录反应来实现进一步的扩增。 本教导还提供可用于进行本文所述的逆转录和扩增反应的组合物和试剂盒。

    BINARY PROBE AND CLAMP COMPOSITION AND METHODS FOR TARGET HYBRIDIZATION DETECTION
    6.
    发明申请
    BINARY PROBE AND CLAMP COMPOSITION AND METHODS FOR TARGET HYBRIDIZATION DETECTION 审中-公开
    二次探针和夹钳组合物和方法进行目标杂交检测

    公开(公告)号：US20070026429A1

    公开(公告)日：2007-02-01

    申请号：US11422211

    申请日：2006-06-05

    申请人： Kenneth Livak ,  Michael Egholm ,  Michael Hunkapiller

    发明人： Kenneth Livak ,  Michael Egholm ,  Michael Hunkapiller

    IPC分类号： C12Q1/68 ,  C07H21/04

    CPC分类号： C12Q1/6816 ,  C12Q1/6818 ,  C12Q2549/126 ,  C12Q2537/119 ,  C12Q2525/179

    摘要： Binary probe and clamp compositions conduct methods for target hybridization detection. Where the probe is a substrate for exonuclease cleavage, the composition provides quantitation and detection of PCR products, by real-time and end-point measurements. Where the probe is an amplification primer, the composition provides an improved method for labelling and detection of PCR products. Probes and clamps may be labelled with fluorescent dyes, quenchers, hybridization-stabilizing moieties, chemiluminescent dyes, and affinity ligands. Clamps may be nucleic acid analogs, such as 2-aminoethylglycine PNA.

    摘要翻译： 二进制探针和夹具组合物进行靶杂交检测的方法。 当探针是外切核酸酶切割的底物时，组合物通过实时和终点测量提供PCR产物的定量和检测。 当探针是扩增引物时，组合物提供了PCR产物的标记和检测的改进方法。 探针和夹具可以用荧光染料，猝灭剂，杂交稳定部分，化学发光染料和亲和配体标记。 夹具可以是核酸类似物，例如2-氨基乙基甘氨酸PNA。

    Encoding and decoding reactions for determining target molecules
    7.
    发明申请
    Encoding and decoding reactions for determining target molecules 失效
    用于确定靶分子的编码和解码反应

    公开(公告)号：US20050260640A1

    公开(公告)日：2005-11-24

    申请号：US11090830

    申请日：2005-03-24

    申请人： Mark Andersen ,  Kenneth Livak ,  Adam Broomer ,  Caifu Chen

    发明人： Mark Andersen ,  Kenneth Livak ,  Adam Broomer ,  Caifu Chen

    IPC分类号： C12Q1/68

    CPC分类号： C12Q1/6869 ,  C12Q1/6851 ,  C12Q2525/191 ,  C12Q2525/185 ,  C12Q2521/501 ,  C12Q2525/155 ,  C12Q2521/313 ,  C12Q2537/143 ,  C12Q2525/161

    摘要： The present invention is directed to methods, reagents, and kits for detecting the presence or absence of (or quantifying) target polynucleotide sequences and proteins in at least one sample using encoding and decoding reactions. When a particular target polynucleotide is present in a sample for example, a reaction product is formed in the encoding reaction that includes addressable primer portions. At least one labeling probe and at least one address primer can be employed in the decoding amplification reaction thereby providing a detectable signal value depending upon whether a sequence is present or absent. In some embodiments, the encoding comprises a ligation reaction with linker probes, and single nucleotide polymorphisms (SNPs) are analyzed.

    摘要翻译： 本发明涉及用于使用编码和解码反应检测至少一个样品中靶多核苷酸序列和蛋白质的存在或不存在（或定量）的方法，试剂和试剂盒。 当特定靶多核苷酸例如存在于样品中时，在包含可寻址引物部分的编码反应中形成反应产物。 可以在解码扩增反应中使用至少一个标记探针和至少一个地址引物，从而根据序列是否存在提供可检测的信号值。 在一些实施方案中，编码包含与接头探针的连接反应，并分析单核苷酸多态性（SNP）。

    METHODS OF ANALYZING BINDING INTERACTIONS
    8.
    发明申请
    METHODS OF ANALYZING BINDING INTERACTIONS 审中-公开
    分析结合相互作用的方法

    公开(公告)号：US20080050752A1

    公开(公告)日：2008-02-28

    申请号：US11763406

    申请日：2007-06-14

    申请人： Hongye SUN ,  Kenneth Livak

    发明人： Hongye SUN ,  Kenneth Livak

    IPC分类号： G01N33/53 ,  C40B30/04

    CPC分类号： G01N33/566 ,  G01N33/48721

    摘要： The present disclosure relates to methods of analyzing binding interactions between a binding component and a receptor component by translocating unbound and any bound components through a pore and detecting the unbound and bound components.

    摘要翻译： 本公开内容涉及通过将未结合的组分和任何结合的组分通过孔移位并检测未结合和结合的组分来分析结合组分和受体组分之间的结合相互作用的方法。

    High density sequence detection methods and apparatus
    9.
    发明申请
    High density sequence detection methods and apparatus 审中-公开
    高密度序列检测方法和装置

    公开(公告)号：US20050112634A1

    公开(公告)日：2005-05-26

    申请号：US10944686

    申请日：2004-09-17

    申请人： Timothy Woudenberg ,  Robert Jones ,  Kenneth Livak

    发明人： Timothy Woudenberg ,  Robert Jones ,  Kenneth Livak

    IPC分类号： C12N20060101 ,  C12P19/34 ,  C12Q1/68 ,  G01N20060101

    CPC分类号： B01L3/50851 ,  B01L3/50853 ,  B01L3/50857 ,  B01L2200/0642 ,  B01L2300/044 ,  B01L2300/0819 ,  B01L2300/0829 ,  B01L2400/0409 ,  B01L2400/0487 ,  C12Q1/6837

    摘要： Methods for amplifying polynucleotides, e.g., by PCR, in a sample comprising polynucleotide targets present at very low concentration, comprising: (a) applying amplification reactants to the surface of a substrate comprising reaction spots, wherein the reactants comprise the sample and an amplification reagent; (b) forming a sealed reaction chamber, having a volume less than about 120 nanoliters, preferably less than about 20 nanoliters, over each of said reaction spots; and (c) thermal cycling the substrate and reactants. In one embodiment, the forming step comprises loading a sealing fluid, e.g., mineral oil, on the surface so as to cover the reaction spots. The present invention also provides microplates, comprising: (a) a substrate having at least about 10,000 reaction spots, each comprising a primer and a droplet of reagent having a volume less than about 120 nanoliters, preferably less then about 20 nanoliters; and (b) a sealing liquid isolating each of the spots.

    摘要翻译： 在包含以非常低浓度存在的多核苷酸靶标的样品中通过PCR扩增多核苷酸的方法包括：（a）将扩增反应物施加到包含反应点的底物表面，其中反应物包含样品和扩增试剂 ; （b）在每个所述反应点上形成体积小于约120纳升，优选小于约20纳升的密封反应室; 和（c）使底物和反应物热循环。 在一个实施例中，成形步骤包括在表面上装载密封流体，例如矿物油，以便覆盖反应点。 本发明还提供了微孔板，其包括：（a）具有至少约10,000个反应点的底物，每个底物包含体积小于约120纳升，优选小于约20纳升的底漆和试剂滴; 和（b）隔离每个斑点的密封液体。

    Combinatorial nucleobase oligomers comprising universal base analogues and methods for making and using same
    10.
    发明申请
    Combinatorial nucleobase oligomers comprising universal base analogues and methods for making and using same 审中-公开
    包含通用碱基类似物的组合核碱基寡聚体及其制备和使用方法

    公开(公告)号：US20050053979A1

    公开(公告)日：2005-03-10

    申请号：US10866523

    申请日：2004-06-10

    申请人： Kenneth Livak ,  Khairuzzaman Mullah

    发明人： Kenneth Livak ,  Khairuzzaman Mullah

    IPC分类号： B01J19/00 ,  C07H21/00 ,  C07H21/04 ,  C07K1/04 ,  C07K14/00 ,  C12N15/11 ,  C12P19/34 ,  C12Q1/68 ,  C40B40/06 ,  C40B50/00

    CPC分类号： C12Q1/6811 ,  C07H21/00 ,  C07H21/04 ,  C12Q2525/197 ,  C12Q2525/117

    摘要： The invention relates to insulating combinatorial nucleobase oligomers that comprise universal base analogs, where the oligomers are formed by the ligation of two or more oligomer “blocks” via a covalent linkage. Universal bases may serve to insulate specifically binding nucleobases from the effects of the covalent linker region joining two oligomer blocks together, so that the universal bases at least partially negate the Tm penalty caused by the covalent linkage, effective to reduce the required minimal length of the oligomer blocks and the combinatorial oligomer. The resulting insulating nucleobase combinatorial oligomers find use in any hybridization-based application, including use as probes and primers. The combinatorial oligomers of the present invention provide advantages over existing combinatorial oligomer systems currently known in the art.

    摘要翻译： 本发明涉及包含通用碱基类似物的绝缘组合核碱基寡聚体，其中通过共价键连接两个或多个低聚物“嵌段”形成低聚物。 通用碱基可以用于将特异性结合的核碱基与连接两个低聚物嵌段的共价连接体区域的作用绝缘，使得通用碱基至少部分地消除由共价键引起的Tm损失，有效地减少所需的最小长度 低聚物嵌段和组合低聚物。 所得到的绝缘核碱基组合寡聚体可用于任何基于杂交的应用，包括用作探针和引物。 本发明的组合寡聚体提供优于现有技术中已知的组合式低聚物体系的优点。