公开(公告)号：US20140045184A1

公开(公告)日：2014-02-13

申请号：US13784736

申请日：2013-03-04

Applicant: Fluidigm Corporation

Inventor： Martin Pieprzyk ,  Geoff Facer ,  Timothy Woudenberg ,  Brian Fowler

IPC: C12Q1/68

CPC classification number: G01N1/28 ,  B01L3/502738 ,  B01L7/52 ,  B01L2200/16 ,  B01L2300/0867 ,  B01L2300/0874 ,  B01L2300/123 ,  B01L2400/0481 ,  B01L2400/0655 ,  B33Y80/00 ,  C12Q1/686 ,  G01N21/05 ,  G01N21/6452 ,  G01N2021/0346 ,  Y10T137/7793 ,  Y10T436/2575

Abstract: Embodiments of the present invention provide improved microfluidic devices and related apparatus, systems, and methods. Methods are provided for reducing mixing times during use of microfluidic devices. Microfluidic devices and related methods of manufacturing are provided with increased manufacturing yield rates. Improved apparatus and related systems are provided for supplying controlled pressure to microfluidic devices. Methods and related microfluidic devices are provided for reducing dehydration of microfluidic devices during use. Microfluidic devices and related methods are provided with improved sample to reagent mixture ratio control. Microfluidic devices and systems are provided with improved resistance to compression fixture pressure induced failures. Methods and systems for conducting temperature controlled reactions using microfluidic devices are provided that reduce condensation levels within the microfluidic device. Methods and systems are provided for improved fluorescent imaging of microfluidic devices.

Abstract translation: 本发明的实施例提供了改进的微流体装置和相关装置，系统和方法。 提供了减少使用微流体装置期间的混合时间的方法。 微流控装置和相关的制造方法具有提高的制造产率。 提供改进的装置和相关系统用于向微流体装置提供受控的压力。 提供了方法和相关的微流体装置，用于在使用过程中减少微流体装置的脱水。 微流控装置和相关方法提供了改进的样品与试剂混合比控制。 微流体装置和系统具有改进的抗压缩夹具压力引起的故障的阻力。 提供了使用微流体装置进行温度控制反应的方法和系统，其减少微流体装置内的冷凝水平。 提供了用于改进微流体装置的荧光成像的方法和系统。

公开(公告)号：US20130302883A1

公开(公告)日：2013-11-14

申请号：US13781292

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: G01N1/34

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。

公开(公告)号：US10578633B2

公开(公告)日：2020-03-03

申请号：US14775685

申请日：2014-03-14

Applicant: Fluidigm Corporation

Inventor： Jason A. A. West ,  Brian Fowler

IPC: G01N35/08 ,  G01N33/50 ,  G01N15/10 ,  G01N15/14 ,  C12M1/00 ,  G01N33/569 ,  B01L3/00 ,  C12M1/04

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.

公开(公告)号：US09840732B2

公开(公告)日：2017-12-12

申请号：US13899397

申请日：2013-05-21

Applicant: Fluidigm Corporation

Inventor： Megan Anderson ,  Peilin Chen ,  Brian Fowler ,  Fiona Kaper ,  Ronald Lebofsky ,  Andrew May

IPC: C12Q1/68 ,  C12P19/34 ,  C12M1/34 ,  C12M3/00 ,  C07H21/02 ,  C07H21/04 ,  C07H21/00 ,  B01D15/08

CPC classification number: C12Q1/6813 ,  B01D15/08 ,  C12Q1/6806 ,  C12Q2563/159 ,  C12Q2563/179 ,  C12Q2565/629

Abstract: In certain embodiments, the invention provides methods and devices for assaying single particles in a population of particles, wherein at least two parameters are measured for each particle. One or more parameters can be measured while the particles are in the separate reaction volumes. Alternatively or in addition, one or more parameters can be measured in a later analytic step, e.g., where reactions are carried out in the separate reaction volumes and the reaction products are recovered and analyzed. In particular embodiments, one or more parameter measurements are carried out “in parallel,” i.e., essentially simultaneously in the separate reaction volumes.

公开(公告)号：US09316331B2

公开(公告)日：2016-04-19

申请号：US14091342

申请日：2013-11-27

Applicant: Fluidigm Corporation

Inventor： Geoffrey Facer ,  Brian Fowler ,  Emerson Cheung Quan ,  Marc Unger

IPC: B01L3/00 ,  G05D11/02 ,  F16K99/00 ,  B01F5/02 ,  B01F13/00 ,  C12Q1/68 ,  G01N21/75 ,  F16K3/00 ,  G01N21/03

CPC classification number: F16K99/0015 ,  B01F5/02 ,  B01F13/0059 ,  B01L3/502707 ,  B01L3/502738 ,  B01L2200/10 ,  B01L2200/12 ,  B01L2200/16 ,  B01L2300/0627 ,  B01L2300/0816 ,  B01L2300/0874 ,  B01L2300/0887 ,  B01L2300/123 ,  B01L2400/0481 ,  B01L2400/0638 ,  B33Y80/00 ,  C12Q1/686 ,  F16K99/0026 ,  F16K99/0059 ,  F16K2099/008 ,  F16K2099/0084 ,  G01N2021/0346 ,  Y10T137/0329 ,  Y10T137/2164 ,  Y10T137/2169 ,  Y10T137/2559 ,  Y10T137/2655 ,  Y10T137/2688 ,  Y10T137/87249

Abstract: Multilevel microfluidic devices include a control line that can simultaneously actuate valves for both sample and reagent lines. Microfluidic devices are configured to contain a first reagent in a first chamber and a second reagent in a second chamber, where either or both of the first and second reagents are contained at a desired or selected pressure. Operation of a microfluidic device includes transmitting second reagent from the second chamber to the first chamber, for mixing or contact with the first reagent. Microfluidic device features such as channels, valves, chambers, can be at least partially contained, embedded, or formed by or within one or more layers or levels of an elastomeric block.

公开(公告)号：US20150185118A1

公开(公告)日：2015-07-02

申请号：US14477642

申请日：2014-09-04

Applicant: Fluidigm Corporation

Inventor： Martin Pieprzyk ,  Geoff Facer ,  Timothy Woudenberg ,  Brian Fowler

IPC: G01N1/28

CPC classification number: G01N1/28 ,  B01L3/502738 ,  B01L7/52 ,  B01L2200/16 ,  B01L2300/0867 ,  B01L2300/0874 ,  B01L2300/123 ,  B01L2400/0481 ,  B01L2400/0655 ,  B33Y80/00 ,  C12Q1/686 ,  G01N21/05 ,  G01N21/6452 ,  G01N2021/0346 ,  Y10T137/7793 ,  Y10T436/2575

Abstract: Embodiments of the present invention provide improved microfluidic devices and related apparatus, systems, and methods. Methods are provided for reducing mixing times during use of microfluidic devices. Microfluidic devices and related methods of manufacturing are provided with increased manufacturing yield rates. Improved apparatus and related systems are provided for supplying controlled pressure to microfluidic devices. Methods and related microfluidic devices are provided for reducing dehydration of microfluidic devices during use. Microfluidic devices and related methods are provided with improved sample to reagent mixture ratio control. Microfluidic devices and systems are provided with improved resistance to compression fixture pressure induced failures. Methods and systems for conducting temperature controlled reactions using microfluidic devices are provided that reduce condensation levels within the microfluidic device. Methods and systems are provided for improved fluorescent imaging of microfluidic devices.

Abstract translation: 本发明的实施例提供了改进的微流体装置和相关装置，系统和方法。 提供了减少使用微流体装置期间的混合时间的方法。 微流控装置和相关的制造方法具有提高的制造产率。 提供改进的装置和相关系统用于向微流体装置提供受控的压力。 提供了方法和相关的微流体装置，用于在使用过程中减少微流体装置的脱水。 微流控装置和相关方法提供了改进的样品与试剂混合比控制。 微流体装置和系统具有改进的抗压缩夹具压力引起的故障的阻力。 提供了使用微流体装置进行温度控制反应的方法和系统，其减少微流体装置内的冷凝水平。 提供了用于改进微流体装置的荧光成像的方法和系统。

公开(公告)号：US08616227B1

公开(公告)日：2013-12-31

申请号：US13909000

申请日：2013-06-03

Applicant: Fluidigm Corporation

Inventor： Geoffrey Facer ,  Brian Fowler ,  Emerson Cheung Quan ,  Marc Unger

IPC: F17D1/00 ,  F16K11/20 ,  F16K3/00 ,  F04B19/00 ,  G01N21/75 ,  B01L3/00 ,  F17D3/00

CPC classification number: F16K99/0015 ,  B01F5/02 ,  B01F13/0059 ,  B01L3/502707 ,  B01L3/502738 ,  B01L2200/10 ,  B01L2200/12 ,  B01L2200/16 ,  B01L2300/0627 ,  B01L2300/0816 ,  B01L2300/0874 ,  B01L2300/0887 ,  B01L2300/123 ,  B01L2400/0481 ,  B01L2400/0638 ,  B33Y80/00 ,  C12Q1/686 ,  F16K99/0026 ,  F16K99/0059 ,  F16K2099/008 ,  F16K2099/0084 ,  G01N2021/0346 ,  Y10T137/0329 ,  Y10T137/2164 ,  Y10T137/2169 ,  Y10T137/2559 ,  Y10T137/2655 ,  Y10T137/2688 ,  Y10T137/87249

Abstract: Multilevel microfluidic devices include a control line that can simultaneously actuate valves for both sample and reagent lines. Microfluidic devices are configured to contain a first reagent in a first chamber and a second reagent in a second chamber, where either or both of the first and second reagents are contained at a desired or selected pressure. Operation of a microfluidic device includes transmitting second reagent from the second chamber to the first chamber, for mixing or contact with the first reagent. Microfluidic device features such as channels, valves, chambers, can be at least partially contained, embedded, or formed by or within one or more layers or levels of an elastomeric block.

Abstract translation: 多级微流体装置包括一个控制管线，可同时为样品和试剂管线起动阀门。 微流体装置被配置为在第二室中的第一室和第二试剂中含有第一试剂，其中第一试剂和第二试剂中的任一种或两者以所需或选择的压力包含。 微流体装置的操作包括将第二试剂从第二室传输到第一室，用于与第一试剂混合或接触。 诸如通道，阀，腔室的微流体装置特征可以至少部分地包含，嵌入或由弹性体块的一个或多个层或层形成或形成。

公开(公告)号：US20130337457A1

公开(公告)日：2013-12-19

申请号：US13909000

申请日：2013-06-03

Applicant: Fluidigm Corporation

Inventor： Geoffrey Facer ,  Brian Fowler ,  Emerson Cheung Quan ,  Marc Unger

IPC: C12Q1/68

CPC classification number: F16K99/0015 ,  B01F5/02 ,  B01F13/0059 ,  B01L3/502707 ,  B01L3/502738 ,  B01L2200/10 ,  B01L2200/12 ,  B01L2200/16 ,  B01L2300/0627 ,  B01L2300/0816 ,  B01L2300/0874 ,  B01L2300/0887 ,  B01L2300/123 ,  B01L2400/0481 ,  B01L2400/0638 ,  B33Y80/00 ,  C12Q1/686 ,  F16K99/0026 ,  F16K99/0059 ,  F16K2099/008 ,  F16K2099/0084 ,  G01N2021/0346 ,  Y10T137/0329 ,  Y10T137/2164 ,  Y10T137/2169 ,  Y10T137/2559 ,  Y10T137/2655 ,  Y10T137/2688 ,  Y10T137/87249

Abstract: Multilevel microfluidic devices include a control line that can simultaneously actuate valves for both sample and reagent lines. Microfluidic devices are configured to contain a first reagent in a first chamber and a second reagent in a second chamber, where either or both of the first and second reagents are contained at a desired or selected pressure. Operation of a microfluidic device includes transmitting second reagent from the second chamber to the first chamber, for mixing or contact with the first reagent. Microfluidic device features such as channels, valves, chambers, can be at least partially contained, embedded, or formed by or within one or more layers or levels of an elastomeric block.

Abstract translation: 多级微流体装置包括一个控制管线，可同时为样品和试剂管线起动阀门。 微流体装置被配置为在第二室中的第一室和第二试剂中含有第一试剂，其中第一试剂和第二试剂中的任一种或两者以所需或选择的压力包含。 微流体装置的操作包括将第二试剂从第二室传输到第一室，用于与第一试剂混合或接触。 诸如通道，阀，腔室的微流体装置特征可以至少部分地包含，嵌入或由弹性体块的一个或多个层或层形成或形成。

公开(公告)号：US20130323732A1

公开(公告)日：2013-12-05

申请号：US13899397

申请日：2013-05-21

Applicant: Fluidigm Corporation

Inventor： Megan Anderson ,  Peilin Chen ,  Brian Fowler ,  Fiona Kaper ,  Ronald Lebofsky ,  Andrew May

IPC: C12Q1/68 ,  B01D15/08

CPC classification number: C12Q1/6813 ,  B01D15/08 ,  C12Q1/6806 ,  C12Q2563/159 ,  C12Q2563/179 ,  C12Q2565/629

Abstract: In certain embodiments, the invention provides methods and devices for assaying single particles in a population of particles, wherein at least two parameters are measured for each particle. One or more parameters can be measured while the particles are in the separate reaction volumes. Alternatively or in addition, one or more parameters can be measured in a later analytic step, e.g., where reactions are carried out in the separate reaction volumes and the reaction products are recovered and analyzed. In particular embodiments, one or more parameter measurements are carried out “in parallel,” i.e., essentially simultaneously in the separate reaction volumes.

Abstract translation: 在某些实施方案中，本发明提供用于测定颗粒群体中的单个颗粒的方法和装置，其中针对每个颗粒测量至少两个参数。 可以在颗粒处于分开的反应体积中时测量一个或多个参数。 或者或另外，可以在稍后的分析步骤中测量一个或多个参数，例如其中在分开的反应体积中进行反应并回收和分析反应产物。 在具体实施方案中，一个或多个参数测量“并行地进行”，即基本上同时在单独的反应体积中进行。

公开(公告)号：US20130296196A1

公开(公告)日：2013-11-07

申请号：US13781318

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: C12Q1/68

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.