公开(公告)号：WO2008141183A3

公开(公告)日：2008-11-20

申请号：PCT/US2008/063247

申请日：2008-05-09

Applicant: FLUIDIGM CORPORATION ,  FOWLER, Brian ,  MAY, Andrew

Inventor： FOWLER, Brian ,  MAY, Andrew

IPC: H05G1/00

Abstract: An integrated fluidic circuit includes a substrate layer and a first structure coupled to the substrate layer and including a plurality of channels. The first structure is configured to provide for flow of one or more materials through the plurality of channels. The integrated fluidic circuit also includes a second structure coupled to the substrate layer. The second structure includes a plurality of control channels configured to receive an actuation pressure. The integrated fluidic circuit is characterized by a thickness of less than 1.5 mm.

公开(公告)号：WO2003085379A2

公开(公告)日：2003-10-16

申请号：PCT/US2003/009997

申请日：2003-04-01

Applicant: FLUIDIGM CORPORATION ,  CHOU, Hou-Pu ,  DARIDON, Antoine ,  FARRELL, Kevin ,  FOWLER, Brian ,  HAO, Cunsheng (Casey) ,  JAVADI, Shervin ,  LIAU, Yish-Hann ,  MANGER, Ian, D. ,  NASSEF, Hany, Ramez ,  NORTON, Pierce ,  THRONDSET, William

Inventor： CHOU, Hou-Pu ,  DARIDON, Antoine ,  FARRELL, Kevin ,  FOWLER, Brian ,  HAO, Cunsheng (Casey) ,  JAVADI, Shervin ,  LIAU, Yish-Hann ,  MANGER, Ian, D. ,  NASSEF, Hany, Ramez ,  NORTON, Pierce ,  THRONDSET, William

IPC: G01N

CPC classification number: C12M1/34 ,  B01L3/502738 ,  B01L3/502746 ,  B01L3/502753 ,  B01L3/502761 ,  B01L2200/0636 ,  B01L2200/0647 ,  B01L2200/0652 ,  B01L2200/0668 ,  B01L2200/10 ,  B01L2200/12 ,  B01L2200/16 ,  B01L2300/06 ,  B01L2300/0636 ,  B01L2300/0645 ,  B01L2300/0681 ,  B01L2300/0861 ,  B01L2300/0867 ,  B01L2300/087 ,  B01L2300/088 ,  B01L2300/0887 ,  B01L2300/0893 ,  B01L2300/123 ,  B01L2400/0409 ,  B01L2400/0415 ,  B01L2400/0481 ,  B01L2400/0622 ,  B01L2400/0655 ,  C12M21/06 ,  C12M23/16 ,  G01N15/1484 ,  G01N33/4833 ,  G01N2015/008 ,  G01N2015/0288 ,  G01N2015/149 ,  G01N2015/1493 ,  G02B21/32

Abstract: The invention provides systems, including apparatus, methods, and kits, for the microfluidic manipulation and/or detection of particles, such as cells and/or beads. The invention provides systems, including apparatus, methods, and kits, for the microfluidic manipulation and/or analysis of particles, such as cells, viruses, organelles, beads, and/or vesicles. The invention also provides microfluidic mechanisms for carrying out these manipulations and analyses. These mechanisms may enable controlled input, movement/positioning, retention/localization, treatment, measurement, release, and/or output of particles. Furthermore, these mechanisms may be combined in any suitable order and/or employed for any suitable number of times within a system. Accordingly, these combinations may allow particles to be sorted, cultured, mixed, treated, and/or assayed, among others, as single particles, mixed groups of particles, arrays of particles, heterogeneous particle sets, and/or homogeneous particle sets, among others, in series and/or in parallel. In addition, these combinations may enable microfluidic systems to be reused. Furthermore, these combinations may allow the response of particles to treatment to be measured on a shorter time scale than was previously possible. Therefore, systems of the invention may allow a broad range of cell and particle assays, such as drug screens, cell characterizations, research studies, and/or clinical analyses, among others, to be scaled down to microfluidic size. Such scaled-down assays may use less sample and reagent, may be less labor intensive, and/or may be more informative than comparable macrofluidic assays.

Abstract translation: 本发明提供了用于微流体操纵和/或检测诸如细胞和/或珠粒的装置，方法和试剂盒的系统。 本发明提供了用于微粒操作和/或分析颗粒例如细胞，病毒，细胞器，珠粒和/或囊泡的装置，方法和试剂盒的系统。 本发明还提供用于进行这些操作和分析的微流体机理。 这些机制可以实现颗粒的控制输入，运动/定位，保留/定位，处理，测量，释放和/或输出。 此外，这些机构可以以任何合适的顺序组合和/或在系统内使用任何合适的次数。 因此，这些组合可以允许将粒子分类，培养，混合，处理和/或测定为单粒子，粒子的混合组，粒子阵列，非均匀粒子组和/或均匀粒子组，其中 其他，串联和/或并行。 此外，这些组合可以使微流体系统能够重复使用。 此外，这些组合可以允许在比以前可能的更短的时间尺度上测量颗粒对治疗的反应。 因此，本发明的系统可以允许广泛范围的细胞和颗粒测定，例如药物筛选，细胞特征化，研究研究和/或临床分析等，以缩小到微流体大小。 这种按比例缩小的测定可能使用较少的样品和试剂，可能较少的劳动密集型和/或可能比可比较的大流控测定更具信息性。

公开(公告)号：EP2970849B1

公开(公告)日：2019-08-21

申请号：EP14763560.1

申请日：2014-03-14

Applicant: Fluidigm Corporation

Inventor： WEST, Jason A. A. ,  FOWLER, Brian

IPC: C12M1/22 ,  G01N33/50 ,  G01N33/569

公开(公告)号：EP2820394B1

公开(公告)日：2017-07-12

申请号：EP13754093.6

申请日：2013-02-28

Applicant: Fluidigm Corporation

Inventor： FOWLER, Brian ,  KIMBALL, Jake ,  MAUNG, Myo Thu ,  MAY, Andrew ,  NORRIS, Michael C. ,  TOPPANI, Dominique G. ,  UNGER, Marc A. ,  WANG, Jing ,  WEST, Jason A. A.

IPC: G01N15/10

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.

公开(公告)号：EP2970849A2

公开(公告)日：2016-01-20

申请号：EP14763560.1

申请日：2014-03-14

Applicant: Fluidigm Corporation

Inventor： WEST, Jason A. A. ,  FOWLER, Brian

IPC: C12M1/22

CPC classification number: G01N35/08 ,  B01L3/502738 ,  B01L2200/027 ,  B01L2200/0652 ,  B01L2200/0668 ,  B01L2200/10 ,  B01L2300/0816 ,  B01L2300/0864 ,  B01L2300/0867 ,  B01L2300/10 ,  B01L2300/12 ,  B01L2400/0487 ,  C12M23/24 ,  C12M29/04 ,  G01N15/1056 ,  G01N15/1484 ,  G01N33/5005 ,  G01N33/5097 ,  G01N33/56961 ,  G01N33/56966 ,  G01N2015/1081

Abstract: Methods for cell analysis are provided, comprising cell capturing, characterization, transport, and culture. In an exemplary method individual cells (and/or cellular units) are flowed into a microfluidic channel, the channel is partitioned into a plurality of contiguous segments, capturing at least one cell in at least one segment, A characteristic of one or more captured cells is determined and the cell(s) and combinations of cells are transported to specified cell holding chamber(s) based on the determined characteristic(s). Also provided are devices and systems for cell analysis.

Abstract translation: 提供了用于细胞分析的方法，包括细胞捕获，表征，运输和培养。 在示例性方法中，将单个细胞（和/或细胞单位）流入微流体通道，将该通道划分成多个连续片段，在至少一个片段中捕获至少一个细胞。一个或多个捕获细胞的特征 并且基于确定的特征将细胞和细胞的组合传输到指定的细胞容纳室。 还提供了用于细胞分析的装置和系统。

公开(公告)号：EP3285062B1

公开(公告)日：2019-08-07

申请号：EP17180284.6

申请日：2013-02-28

Applicant: Fluidigm Corporation

Inventor： FOWLER, Brian ,  KIMBALL, Jake ,  MAUNG, Myo Thu ,  MAY, Andrew ,  NORRIS, Michael C. ,  TOPPANI, Dominique G. ,  UNGER, Marc A. ,  WANG, Jing ,  WEST, Jason A. A.

IPC: G01N15/10

公开(公告)号：EP3140428A1

公开(公告)日：2017-03-15

申请号：EP15789313.2

申请日：2015-05-08

Applicant: Fluidigm Corporation

Inventor： WEST, Jason A. A. ,  FOWLER, Brian ,  CHARN, Tze-Howe ,  JOHNSON, Christian F. ,  UNGER, Marc A.

IPC: 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，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。

公开(公告)号：EP2820394A1

公开(公告)日：2015-01-07

申请号：EP13754093.6

申请日：2013-02-28

Applicant: Fluidigm Corporation

Inventor： FOWLER, Brian ,  KIMBALL, Jake ,  MAUNG, Myo Thu ,  MAY, Andrew ,  NORRIS, Michael C. ,  TOPPANI, Dominique G. ,  UNGER, Marc A. ,  WANG, Jing ,  WEST, Jason A. A.

IPC: G01N15/10

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.

公开(公告)号：EP2710172A2

公开(公告)日：2014-03-26

申请号：EP12789957.3

申请日：2012-05-21

Applicant: Fluidigm Corporation

Inventor： ANDERSON, Megan ,  CHEN, Peilin ,  FOWLER, Brian ,  JONES, Robert C. ,  KAPER, Fiona ,  LEBOFSKY, Ronald ,  MAY, Andrew

IPC: C40B20/00 ,  C40B50/06 ,  C40B40/06 ,  C40B30/04 ,  C12P19/34 ,  C12Q1/68

CPC classification number: C12Q1/6855 ,  C12N15/10 ,  C12N15/1065 ,  C12N15/65 ,  C12N15/66 ,  C12Q1/686 ,  C12Q1/6874

Abstract: Described herein are methods useful for incorporating one or more adaptors and/or nucleotide tag(s) and/or barcode nucleotide sequence(s) one, or typically more, target nucleotide sequences. In particular embodiments, nucleic acid fragments having adaptors, e.g., suitable for use in high-throughput DNA sequencing are generated. In other embodiments, information about a reaction mixture is encoded into a reaction product. Also described herein are methods and kits useful for amplifying one or more target nucleic acids in preparation for applications such as bidirectional nucleic acid sequencing. In particular embodiments, methods of the invention entail additionally carrying out bidirectional DNA sequencing. Also described herein are methods for encoding and detecting and/or quantifying alleles by primer extension.

Abstract translation: 本文描述的方法可用于掺入一个或多个衔接子和/或核苷酸标签和/或条形码核苷酸序列，一个或多个靶核苷酸序列。 在具体实施方案中，产生具有适配器（例如适合用于高通量DNA测序）的核酸片段。 在其它实施方案中，关于反应混合物的信息被编码成反应产物。 本文还描述了可用于扩增一种或多种靶核酸以准备应用如双向核酸测序的方法和试剂盒。 在具体实施方案中，本发明的方法还需要进行双向DNA测序。 本文还描述了通过引物延伸来编码和检测和/或定量等位基因的方法。

公开(公告)号：EP3285062A1

公开(公告)日：2018-02-21

申请号：EP17180284.6

申请日：2013-02-28

Applicant: Fluidigm Corporation

Inventor： FOWLER, Brian ,  KIMBALL, Jake ,  MAUNG, Myo Thu ,  MAY, Andrew ,  NORRIS, Michael C. ,  TOPPANI, Dominique G. ,  UNGER, Marc A. ,  WANG, Jing ,  WEST, Jason A. A.

IPC: G01N15/10

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: 描述了使用微流体的多个单细胞捕获和处理的方法，系统和设备。 提供了用于捕获，分配和/或操纵来自更大细胞群体的个体细胞以及产生与每个个体细胞相关的遗传信息和/或反应的工具和技术。 可以使用不同的捕获配置来捕获单个细胞，然后在多腔室反应配置中处理每个单独的细胞。 一些实施例可以提供特定目标扩增，全基因组扩增，全转录扩增，实时PCR制备，拷贝数变异，预扩增的mRNA的测序，和/或单倍型分析已经从较大人口划分的多个单个细胞的 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用于将单独的单元或相关联的反应产物成像为处理的一部分。 反应产物可能在一些情况下收获和/或进一步分析。