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    • 3. 发明申请
    • NANOPORE VOLTAGE METHODS
    • NANOPORE电压方法
    • WO2018069302A1
    • 2018-04-19
    • PCT/EP2017/075782
    • 2017-10-10
    • F. HOFFMANN-LA ROCHE AGROCHE DIAGNOSTICS GMBHROCHE SEQUENCING SOLUTIONS, INC.
    • DAVIS, RandallWALLGREN, Markus
    • G01N33/487
    • A method for sequencing a nucleic acid molecule includes providing a sequencing cell (200) having a nanopore (216) in a membrane (214) that resides over a well (205), a first electrode (202) at a bottom of the well, a second electrode (210) in a chamber (215) above the membrane, and an electrolyte (206, 208) in the well (205) and the chamber (215). The first electrode (202) is configured to facilitate non-Faradaic conduction of ionic current and forms a capacitance with ions in the electrolyte. A first voltage signal (1310) is applied across the first and second electrodes (202, 210), thereby creating a force that moves a nucleic acid molecule in the sequence cell through the nanopore (216). The first voltage signal (1310) increases to compensate for changes in the capacitance at the first electrode (202) during application of the first voltage signal. The method further includes determining signal values measured during the first voltage signal, which correspond to one or more nucleotides in the nucleic acid molecule.
    • 用于对核酸分子进行测序的方法包括:提供在位于孔(205)上方的膜(214)中具有纳米孔(216)的测序单元(200),第一电极(202) ),在膜的上方的腔室(215)中的第二电极(210)以及在阱(205)和腔室(215)中的电解质(206,208)。 第一电极(202)被配置为促进离子电流的非法拉第传导并且与电解质中的离子形成电容。 跨第一和第二电极(202,210)施加第一电压信号(1310),由此产生移动序列细胞中的核酸分子通过纳米孔(216)的力。 第一电压信号(1310)增加以补偿施加第一电压信号期间第一电极(202)处的电容变化。 该方法还包括确定在第一电压信号期间测量的对应于核酸分子中的一个或多个核苷酸的信号值。
    • 5. 发明申请
    • NUCLEIC ACID SAMPLE PREPARATION METHODS
    • 核酸样品制备方法
    • WO2017174572A1
    • 2017-10-12
    • PCT/EP2017/057974
    • 2017-04-04
    • F. HOFFMANN-LA ROCHE AGROCHE DIAGNOSTICS GMBHROCHE SEQUENCING SOLUTIONS, INC.
    • DAVIS, RandallDORWART, MichaelMOK, Janine
    • C12Q1/68
    • Provided are methods of nucleic acid sample preparation for analysis, including analysis using nanopore sequencing applications. In particular provided are methods that allow for the creation of circular and linear DNA samples that contain asymmetric ends to ligate different and desired adaptors to the end of the sample, methods to create single nucleic acid molecules that automatically form concatemers for higher sequencing throughput; methods to create multiple copies (temperature dependent, multi-primed, open-fold replication) of one original nucleic acid sample, or to create single nucleic acid molecules containing multiple copies of more than one original nucleic acid sample (concatemerized samples) for improved accuracy and throughput are described; and methods for improved modified base calling.
    • 提供用于分析的核酸样品制备方法,包括使用纳米孔测序应用的分析。 特别提供了允许产生含有不对称末端以将不同和所需衔接子连接到样品末端的环状和线性DNA样品的方法,产生单一核酸分子的方法,所述单个核酸分子自动形成用于更高测序通量的串联体; 方法来创建一个原始核酸样品的多个拷贝(温度依赖的,多引发的,开放倍数复制),或产生含有多个原始核酸样品的多个拷贝的单个核酸分子(串联样品)以提高精度 并描述吞吐量; 以及改进修饰碱基调用的方法。