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    Microfluidic Devices With Removable Cover and Methods of Fabrication and Application
    41.
    发明申请
    Microfluidic Devices With Removable Cover and Methods of Fabrication and Application 有权
    具有可拆卸盖的微流体装置及其制造和应用方法

    公开(公告)号：US20160016164A1

    公开(公告)日：2016-01-21

    申请号：US14720305

    申请日：2015-05-22

    Applicant: Fluidigm Corporation

    Inventor： David Cohen ,  Andrew May ,  Martin Pieprzyk ,  Kim Huat Lee ,  Jun Yan ,  Ming Fang Zhou ,  Seng Beng Ng

    IPC: B01L3/00

    CPC classification number: B01L3/5027 ,  B01L3/502738 ,  B01L7/52 ,  B01L9/527 ,  B01L2200/12 ,  B01L2300/045 ,  B01L2300/0887 ,  B01L2300/123 ,  B01L2400/0655 ,  G01N1/405

    Abstract: The present invention includes microfluidic systems having a microfabricated cavity that may be covered with a removable cover, where the removable cover allows at least part of the opening of the microfabricated cavity to be exposed or directly accessed by an operator. The microfluidic systems comprise chambers, flow and control channels formed in elastomeric layers that may comprise PDMS. The removable cover comprises a thermoplastic base film bonded to an elastomer layer by an adhesive layer. When the removable cover is peeled off, the chamber is at least partially open to allow sample extraction from the chamber. The chamber may have macromolecular crystals formed inside or resulting contents from a PCR reaction. The invention also includes a method for making vias in elastomeric layers by using the removable cover. The invention further includes methods and devices for peeling the peelable cover or a removable component such as Integrated Heater Spreader.

    Abstract translation: 本发明包括具有微型空腔的​​微流体系统，其可以被可移除的盖覆盖，其中可移除的盖允许微加工腔的至少一部分开口被操作者暴露或直接访问。 微流体系统包括在可包括PDMS的弹性体层中形成的腔室，流动和控制通道。 可移除的盖包括通过粘合剂层结合到弹性体层的热塑性基底膜。 当可移除的盖被剥离时，室至少部分地打开以允许从室中取样。 该室可能在PCR反应内部形成大分子晶体或产生内含物。 本发明还包括通过使用可移除盖制造弹性体层中的通孔的方法。 本发明还包括用于剥离可剥离盖或诸如集成式加热器撒布机的可移除部件的方法和装置。

    INTEGRATED SINGLE CELL SEQUENCING
    42.
    发明申请
    INTEGRATED SINGLE CELL SEQUENCING 审中-公开
    集成单个细胞序列

    公开(公告)号：US20150337295A1

    公开(公告)日：2015-11-26

    申请号：US14708048

    申请日：2015-05-08

    Applicant: FLUIDIGM CORPORATION

    Inventor： JASON A.A. WEST ,  BRIAN FOWLER ,  TZE-HOWE CHARN ,  CHRISTIAN F. JOHNSON ,  MARC A. UNGER

    IPC: C12N15/10 ,  C12Q1/68

    CPC classification number: C12Q1/6855 ,  C12N15/1065 ,  C12Q1/6806 ,  C12Q2565/501 ,  C12Q2521/301 ,  C12Q2521/501 ,  C12Q2525/155 ,  C12Q2537/162 ,  C12Q2565/543 ,  C12Q2535/122

    Abstract: This disclosure provides a method of forming tagged nucleic acid sequences. A target polynucleotide is immobilized on a solid support; a recognition-oligonucleotide is hybridized thereto; the recognition-oligonucleotide-target polynucleotide hybrid is cleaved; and an adapter nucleic acid is ligated to the cleaved target polynucleotide, thereby forming a tagged nucleic acid sequence. Also provided is a method of forming a tagged single stranded cDNA; a method of forming a plurality of tagged heterogeneous nucleic acid sequences; a library of recognition-oligonucleotides; and methods for amplifying a cDNA sequence immobilized on a solid support. These methods and products can be used alone or in combination for integrated single cell sequencing, and can be adapted for use in a microfluidic apparatus or device.

    Abstract translation: 本公开提供了形成标记的核酸序列的方法。 靶多核苷酸固定在固体支持物上; 识别寡核苷酸与其杂交; 识别寡核苷酸靶多核苷酸杂交体被切割; 并将衔接子核酸连接到切割的靶多核苷酸上，从而形成标记的核酸序列。 还提供了形成标记的单链cDNA的方法; 形成多个标记的异源核酸序列的方法; 识别寡核苷酸文库; 以及用于扩增固定在固体支持物上的cDNA序列的方法。 这些方法和产品可以单独使用或组合使用以用于集成的单细胞测序，并且可以适用于微流体装置或装置。

    Methods and devices for electronic sensing
    44.
    发明授权
    Methods and devices for electronic sensing 有权
    电子感应的方法和装置

    公开(公告)号：US09103761B2

    公开(公告)日：2015-08-11

    申请号：US13867555

    申请日：2013-04-22

    Applicant: Fluidigm Corporation

    Inventor： Hany Nassef ,  Geoffrey Facer ,  Marc Unger

    IPC: C03C25/68 ,  G01N1/00 ,  G01N27/00 ,  B01L3/00 ,  G01N27/60

    CPC classification number: C03C25/68 ,  B01L3/502707 ,  B01L2300/0645 ,  B01L2300/0816 ,  B01L2300/123 ,  B01L2400/0481 ,  B01L2400/0655 ,  G01N15/1031 ,  G01N15/12 ,  G01N27/00 ,  G01N27/60 ,  G01N33/48707 ,  G01N33/48721 ,  G01N2015/1087 ,  Y10T436/2575

    Abstract: The presence of a detectable entity within a detection volume of a microfabricated elastomeric structure is sensed through a change in the electrical or magnetic environment of the detection volume. In embodiments utilizing electronic detection, an electric field is applied to the detection volume and a change in impedance, current, or combined impedance and current due to the presence of the detectable entity is measured. In embodiments utilizing magnetic detection, the magnetic properties of a magnetized detected entity alter the magnetic field of the detection volume. This changed magnetic field induces a current which can reveal the detectable entity. The change in resistance of a magnetoresistive element may also reveal the passage of a magnetized detectable entity.

    Abstract translation: 通过检测体积的电气或磁环境的变化来检测在微制造弹性体结构的检测体积内的可检测实体的存在。 在利用电子检测的实施例中，对检测体积施加电场，并且测量由于可检测实体的存在引起的阻抗，电流或组合阻抗和电流的变化。 在利用磁检测的实施例中，磁化检测实体的磁性改变了检测体积的磁场。 这种改变的磁场诱发可以揭示可检测实体的电流。 磁阻元件的电阻变化也可以揭示磁化的可检测实体的通过。

    METHODS, SYSTEMS, AND DEVICES FOR MULTIPLE SINGLE-CELL CAPTURING AND PROCESSING USING MICROFLUIDICS
    48.
    发明申请
    METHODS, SYSTEMS, AND DEVICES FOR MULTIPLE SINGLE-CELL CAPTURING AND PROCESSING USING MICROFLUIDICS 有权
    用于多单细胞捕获和使用微流控的处理的方法，系统和设备

    公开(公告)号：US20130302807A1

    公开(公告)日：2013-11-14

    申请号：US13781313

    申请日：2013-02-28

    Applicant: Fluidigm Corporation

    Inventor： Brian Fowler ,  Jake Kimball ,  Myo Thu Maung ,  Andrew May ,  Michael C. Norris ,  Dominique G. Toppani ,  Marc A. Unger ,  Jing Wang ,  Jason A.A. West

    IPC: G01N1/28

    CPC classification number: G01N1/28 ,  B01L3/502761 ,  B01L7/52 ,  B01L2200/0668 ,  B01L2300/0864 ,  B01L2400/0409 ,  B01L2400/0415 ,  B01L2400/043 ,  B01L2400/0487 ,  B01L2400/086 ,  B01L2400/088 ,  C12P19/34 ,  C12Q1/6813 ,  C12Q1/6844 ,  C12Q1/686 ,  C12Q1/6869 ,  G01N1/34 ,  G01N15/1484 ,  C12Q2565/629

    Abstract: Methods, systems, and devices are described for multiple single-cell capturing and processing utilizing microfluidics. Tools and techniques are provided for capturing, partitioning, and/or manipulating individual cells from a larger population of cells along with generating genetic information and/or reactions related to each individual cell. Different capture configurations may be utilized to capture individual cells and then processing each individual cell in a multi-chamber reaction configuration. Some embodiments may provide for specific target amplification, whole genome amplification, whole transcriptome amplification, real-time PCR preparation, copy number variation, preamplification, mRNA sequencing, and/or haplotyping of the multiple individual cells that have been partitioned from the larger population of cells. Some embodiments may provide for other applications. Some embodiments may be configured for imaging the individual cells or associated reaction products as part of the processing. Reaction products may be harvested and/or further analyzed in some cases.

    Abstract translation: 描述了利用微流体的多单细胞捕获和处理的方法，系统和装置。 提供的工具和技术用于捕获，分配和/或操纵来自较大群体的细胞的单个细胞以及产生与每个单个细胞相关的遗传信息和/或反应。 可以使用不同的捕获配置来捕获单个细胞，然后在多室反应配置中处理每个单独的细胞。 一些实施方案可以提供已经从较大群体中划分的多个单个细胞的特异性靶扩增，全基因组扩增，全转录组扩增，实时PCR制备，拷贝数变异，预扩增，mRNA测序和/或单倍型 细胞。 一些实施例可以提供其他应用。 一些实施例可以被配置为用于对作为处理的一部分的各个单元或相关联的反应产物进行成像。 在某些情况下可以收获和/或进一步分析反应产物。

    METHODS AND DEVICES FOR ELECTRONIC SENSING
    49.
    发明申请
    METHODS AND DEVICES FOR ELECTRONIC SENSING 有权
    电子感应的方法和装置

    公开(公告)号：US20130302785A1

    公开(公告)日：2013-11-14

    申请号：US13867555

    申请日：2013-04-22

    Applicant: Fluidigm Corporation

    Inventor： Hany Nassef ,  Geoffrey Facer ,  Marc Unger

    IPC: G01N27/00

    CPC classification number: C03C25/68 ,  B01L3/502707 ,  B01L2300/0645 ,  B01L2300/0816 ,  B01L2300/123 ,  B01L2400/0481 ,  B01L2400/0655 ,  G01N15/1031 ,  G01N15/12 ,  G01N27/00 ,  G01N27/60 ,  G01N33/48707 ,  G01N33/48721 ,  G01N2015/1087 ,  Y10T436/2575

    Abstract: The presence of a detectable entity within a detection volume of a microfabricated elastomeric structure is sensed through a change in the electrical or magnetic environment of the detection volume. In embodiments utilizing electronic detection, an electric field is applied to the detection volume and a change in impedance, current, or combined impedance and current due to the presence of the detectable entity is measured. In embodiments utilizing magnetic detection, the magnetic properties of a magnetized detected entity alter the magnetic field of the detection volume. This changed magnetic field induces a current which can reveal the detectable entity. The change in resistance of a magnetoresistive element may also reveal the passage of a magnetized detectable entity.

    Abstract translation: 通过检测体积的电气或磁环境的变化来检测在微制造弹性体结构的检测体积内的可检测实体的存在。 在利用电子检测的实施例中，对检测体积施加电场，并且测量由于可检测实体的存在引起的阻抗，电流或组合阻抗和电流的变化。 在利用磁检测的实施例中，磁化检测实体的磁性改变了检测体积的磁场。 这种改变的磁场诱发可以揭示可检测实体的电流。 磁阻元件的电阻变化也可以揭示磁化的可检测实体的通过。

    COPY NUMBER VARIATION DETERMINATION, METHODS AND SYSTEMS
    50.
    发明申请
    COPY NUMBER VARIATION DETERMINATION, METHODS AND SYSTEMS 审中-公开

    公开(公告)号：US20130260381A1

    公开(公告)日：2013-10-03

    申请号：US13902667

    申请日：2013-05-24

    Applicant: Fluidigm Corporation

    Inventor： Ramesh Ramakrishnan

    IPC: C12Q1/68

    CPC classification number: C12Q1/6869 ,  C12Q1/6851 ,  C12Q2545/101 ,  C12Q2527/143

    Abstract: The present invention methods and systems for determining copy number variation of a target polynucleotide in a genome of a subject including amplification based techniques. Methods can include pre-amplification of the sample followed by distribution of sample and a plurality of reaction volumes, quantitative detection of a target polynucleotide and a reference polynucleotide, and analysis so as to determine the relative copy number of the target polynucleotide sequence in the genome of the subject.

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