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    DNA sequencing by mass spectrometry
    3.
    发明授权
    DNA sequencing by mass spectrometry 失效
    通过质谱法进行DNA测序

    公开(公告)号：US5691141A

    公开(公告)日：1997-11-25

    申请号：US470123

    申请日：1995-06-06

    Applicant: Hubert Koster

    Inventor： Hubert Koster

    IPC: C12N15/09 ,  C07H19/20 ,  C07H21/04 ,  C12P19/34 ,  C12Q1/68 ,  G01N27/62 ,  G01N33/483 ,  G01N33/50 ,  G01N35/10 ,  C07H21/02

    CPC classification number: C12Q1/6827 ,  C12Q1/6816 ,  C12Q1/6872 ,  G01N35/1067 ,  Y10S435/81 ,  Y10T436/143333 ,  Y10T436/24 ,  Y10T436/25

    Abstract: The invention describes a new method to sequence DNA. The improvements over the existing DNA sequencing technologies are high speed, high throughput, no electrophoresis and gel reading artifacts due to the complete absence of an electrophoretic step, and no costly reagents involving various substitutions with stable isotopes. The invention utilizes the Sanger sequencing strategy and assembles the sequence information by analysis of the nested fragments obtained by base-specific chain termination via their different molecular masses using mass spectrometry, as for example, MALDI or ES mass spectrometry. A further increase in throughput can be obtained by introducing mass-modifications in the oligonucleotide primer, chain-terminating nucleoside triphosphates and/or in the chain-elongating nucleoside triphosphates, as well as using integrated tag sequences which allow multiplexing by hybridization of tag specific probes with mass differentiated molecular weights.

    Abstract translation: 本发明描述了一种新的DNA序列化方法。 由于完全不存在电泳步骤，现有DNA测序技术的改进是高速度，高通量，无电泳和凝胶阅读伪像，并且没有昂贵的试剂涉及具有稳定同位素的各种取代。 本发明利用Sanger测序策略，并通过使用质谱法（例如MALDI或ES质谱法）通过分析通过其不同分子量通过碱基特异性链终止获得的嵌套片段来组装序列信息。 通过在寡核苷酸引物，链终止的三磷酸核苷和/或在延伸链的三磷酸的链中引入质量修饰，以及使用允许通过标签特异性探针的杂交进行多重复合的整合的标签序列，可以获得通量的进一步增加 具有质量差异分子量。

    Solid phase sequencing of double-stranded nucleic acids
    4.
    发明申请
    Solid phase sequencing of double-stranded nucleic acids 审中-公开
    双链核酸的固相测序

    公开(公告)号：US20060063193A1

    公开(公告)日：2006-03-23

    申请号：US11259426

    申请日：2005-10-25

    Applicant: Dong-Jing Fu ,  Charles Canton ,  Hubert Koster ,  Cassandra Smith

    Inventor： Dong-Jing Fu ,  Charles Canton ,  Hubert Koster ,  Cassandra Smith

    IPC: C12Q1/68

    CPC classification number: C12Q1/6872 ,  C12Q2565/501

    Abstract: Methods for detecting target nucleic acid molecules in a sample are provided. The methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probes include a double-stranded portion, a single-stranded portion and a variable sequence within the single-stranded portion, where the single-stranded region of the probes includes a sequence complementary or homologous to a sequence of the target nucleic acid to be detected. The molecular weights of the hybridized nucleic acids of the set are determined by mass spectroscopy, and from the molecular weights of the hybridized probes, the presence of the target nucleic acid is detected by the presence of its sequence in the sample.

    Abstract translation: 提供了检测样品中靶核酸分子的方法。 所述方法包括将表示所述靶的互补序列或同源序列的核酸或核酸与核酸探针阵列进行杂交。 这些探针包括单链部分中的双链部分，单链部分和可变序列，其中探针的单链区域包含与待靶核酸序列互补或同源的序列 检测到。 通过质谱法测定该组杂交核酸的分子量，并且通过杂交探针的分子量，通过样品中其序列的存在来检测靶核酸的存在。

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