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    Separation of charged particles by a spatially and temporally varying electric field
    1.
    发明授权
    Separation of charged particles by a spatially and temporally varying electric field 失效
    通过空间和时间变化的电场分离带电粒子

    公开(公告)号：US06193866B1

    公开(公告)日：2001-02-27

    申请号：US09212622

    申请日：1998-12-16

    申请人： Joel S. Bader ,  Jonathan M. Rothberg ,  Michael W. Deem ,  Gregory T. Mulhern ,  Gregory T. Went ,  John Simpson ,  Steven Henck

    发明人： Joel S. Bader ,  Jonathan M. Rothberg ,  Michael W. Deem ,  Gregory T. Mulhern ,  Gregory T. Went ,  John Simpson ,  Steven Henck

    IPC分类号： G01N2726

    CPC分类号： B82Y30/00 ,  G01N27/44773

    摘要： This invention relates to a method and device for separating charged particles according to their diffusivities in a separation medium by means of a spatially and temporally varying electric potential. The method is particularly suited to sizing and separating DNA fragments, to generating DNA fragment length polymorphism patterns, and to sequencing DNA through the separation of DNA sequencing reaction products. The method takes advantage of the transport of charged particles subject to an electric potential that is cycled between an off-state (in which the potential is flat) and one or more on-states, in which the potential is preferably spatially periodic with a plurality of eccentrically shaped stationary potential wells. The potential wells are at constant spatial positions in the on-state. Differences in liquid-phase diffusivities lead to charged particle separation. A preferred embodiment of the device is microfabricated. A separation medium fills physically defined separation lanes in the device. Electrodes deposited substantially transverse to the lanes create the required electric potentials. Advantageously, injection ports allow sample loading, and special gating electrodes focus the sample prior to separation. The effects of thermal gradients are minimized by placing the device in contact with a thermal control module, preferably a plurality of Peltier-effect heat transfer devices. The small size of a microfabricated device permits rapid separation in a plurality of separation lanes.

    摘要翻译： 本发明涉及一种通过空间和时间上变化的电势根据其在分离介质中的扩散性分离带电粒子的方法和装置。 该方法特别适用于分选DNA片段，产生DNA片段长度多态性模式，并通过分离DNA测序反应产物对DNA进行测序。 该方法利用带电粒子的传输，该带电粒子经历在关闭状态（其中电位为平坦）和一个或多个导通状态之间循环的电位，其中电位优选为空间周期性的多个 偏心固定势阱。 势阱在导通状态下处于恒定的空间位置。 液相扩散性的差异导致带电粒子分离。 装置的优选实施例是微制造的。 分离介质填充设备中物理定义的分离通道。 基本横向于通道沉积的电极产生所需的电位。 有利地，注射端口允许样品加载，并且特殊门电极在分离之前聚焦样品。 通过将设备与热控制模块（优选多个珀耳帖效应传热装置）接触来使热梯度的影响最小化。 微型加工装置的小尺寸允许在多个分离通道中快速分离。

    Separation of charged particles by a spatially and temporally varying electric field
    2.
    发明授权
    Separation of charged particles by a spatially and temporally varying electric field 失效
    通过空间和时间变化的电场分离带电粒子

    公开(公告)号：US5938904A

    公开(公告)日：1999-08-17

    申请号：US623346

    申请日：1996-03-27

    申请人： Joel S. Bader ,  Jonathan M. Rothberg ,  Michael W. Deem ,  Gregory T. Mulhern ,  Gregory T. Went

    发明人： Joel S. Bader ,  Jonathan M. Rothberg ,  Michael W. Deem ,  Gregory T. Mulhern ,  Gregory T. Went

    IPC分类号： B01D57/02 ,  G01N27/26 ,  G01N27/447

    CPC分类号： B82Y30/00 ,  G01N27/44773

    摘要： This invention relates to a method and device for separating charged particles according to their diffusivities in a separation medium by means of a spatially and temporarily varying electric potential. The method is particularly suited to sizing and separating DNA fragments, to generating DNA fragment length polymorphism patterns, and to sequencing DNA through the separation of DNA sequencing reaction products. The method takes advantage of the transport of charged particles subject to an electric potential that is cycled between an off-state (in which the potential is flat) and one or more on-states, in which the potential is preferably spatially periodic with a plurality of eccentrically shaped stationary potential wells. The potential wells are at constant spatial positions in the on-state. Differences in liquid-phase diffusivities lead to charged particle separation. A preferred embodiment of the device is microfabricated. A separation medium fills physically defined separation lanes in the device. Electrodes deposited substantially transverse to the lanes create the required electric potentials. Advantageously, injection ports allow sample loading, and special gating electrodes focus the sample prior to separation. The effects of thermal gradients are minimized by placing the device in contact with a thermal control module, preferably a plurality of Peltier-effect heat transfer devices. The small size of a microfabricated device permits rapid separation in a plurality of separation lanes.

    摘要翻译： 本发明涉及一种通过空间和暂时变化的电位根据其在分离介质中的扩散性分离带电粒子的方法和装置。 该方法特别适用于分选DNA片段，产生DNA片段长度多态性模式，并通过分离DNA测序反应产物对DNA进行测序。 该方法利用带电粒子的传输，该带电粒子经历在关闭状态（其中电位为平坦）和一个或多个导通状态之间循环的电位，其中电位优选为空间周期性的多个 偏心固定势阱。 势阱在导通状态下处于恒定的空间位置。 液相扩散性的差异导致带电粒子分离。 装置的优选实施例是微制造的。 分离介质填充设备中物理定义的分离通道。 基本横向于通道沉积的电极产生所需的电位。 有利地，注射端口允许样品加载，并且特殊门电极在分离之前聚焦样品。 通过将设备与热控制模块（优选多个珀耳帖效应传热装置）接触来使热梯度的影响最小化。 微型加工装置的小尺寸允许在多个分离通道中快速分离。

    Method for distance measurements with solid-state NMR
    3.
    发明授权
    Method for distance measurements with solid-state NMR 失效
    使用固态NMR进行距离测量的方法

    公开(公告)号：US6027941A

    公开(公告)日：2000-02-22

    申请号：US648609

    申请日：1996-05-15

    申请人： Thomas P. Jarvie ,  Joel S. Bader ,  Gregory T. Went

    发明人： Thomas P. Jarvie ,  Joel S. Bader ,  Gregory T. Went

    IPC分类号： G01R33/32 ,  G01N24/08 ,  G01N33/483 ,  G01R33/46 ,  G01N24/00 ,  G01V3/00

    CPC分类号： G01R33/4625 ,  G01R33/4641 ,  Y10T436/24

    摘要： This invention includes methods for analyzing data generated by various solid-state NMR experiments, including rotational echo double resonance (REDOR), transferred echo double resonance (TEDOR), dipolar recoupling at the magic angle (DRAMA), dipolar recoupling with a windowless sequence (DRAWS), and melding of spin-locking and DRAMA (MELODRAMA). The methods are based alternately on a new analytical transform or the maximum entropy method and their multi-dimensional extensions. They permit simultaneous, multiple distance measurements of high accuracy and precision, even from nuclei with identical chemical shifts. By providing high quality easily obtained distance measurement from disordered solid state materials, this invention also improves drug discovery and design through fast determination of structures of pharmaceutical lead compounds, drug molecules, or their targets.

    摘要翻译： 本发明包括用于分析由各种固态NMR实验产生的数据的方法，包括旋转回波双共振（REDOR），传输回波双共振（TEDOR），魔角（DRAMA）的偶极重耦合，无窗序列的偶极重耦合 DRAWS），以及自旋锁定和DRAMA（MELODRAMA）的融合。 该方法交替地基于新的分析变换或最大熵方法及其多维扩展。 它们允许同时进行高精度和高精度的多距离测量，即使是具有相同化学位移的原子核。 通过从无序固体材料提供高质量的容易获得的距离测量，本发明还通过快速测定药物铅化合物，药物分子或其靶标的结构来改进药物发现和设计。

    Method of sequencing a nucleic acid
    8.
    发明授权
    Method of sequencing a nucleic acid 有权
    核酸测序方法

    公开(公告)号：US06274320B1

    公开(公告)日：2001-08-14

    申请号：US09398833

    申请日：1999-09-16

    申请人： Jonathan M. Rothberg ,  Joel S. Bader

    发明人： Jonathan M. Rothberg ,  Joel S. Bader

    IPC分类号： C12Q168

    CPC分类号： C12Q1/6837 ,  C12Q1/6827 ,  C12Q1/6869 ,  C12Q1/6874 ,  C12Q2531/125 ,  C12Q2535/101 ,  C12Q2565/301

    摘要： Disclosed herein are methods and apparatuses for sequencing a nucleic acid. The method includes annealing a population of circular nucleic acid molecules to a plurality of anchor primers linked to a solid support, and amplifying those members of the population of circular nucleic acid molecules which anneal to the target nucleic acid, and then sequencing the amplified molecules by detecting the presence of a sequence byproduct.

    摘要翻译： 本文公开了用于测序核酸的方法和装置。 该方法包括将多个环状核酸分子退火至与固体支持物连接的多个锚定引物，并扩增与靶核酸退火的环状核酸分子群体的那些成员，然后通过 检测序列副产物的存在。