公开(公告)号：US09029085B2

公开(公告)日：2015-05-12

申请号：US12529926

申请日：2008-03-07

申请人： Jeremy Agresti ,  Liang-Yin Chu ,  David A. Weitz ,  Jin-Woong Kim ,  Amy Rowat ,  Morten Sommer ,  Gautam Dantas ,  George Church

发明人： Jeremy Agresti ,  Liang-Yin Chu ,  David A. Weitz ,  Jin-Woong Kim ,  Amy Rowat ,  Morten Sommer ,  Gautam Dantas ,  George Church

IPC分类号： C12Q1/68 ,  C12P19/34 ,  B01J13/00 ,  B01F3/08 ,  B01F13/00

CPC分类号： C12P19/34 ,  B01F3/0807 ,  B01F3/0811 ,  B01F13/0062 ,  B01F13/0071 ,  B01F2215/0037 ,  B01J13/0052 ,  B01J13/0065 ,  B01L3/502784 ,  C12Q1/6834 ,  C12Q1/6848 ,  C12Q1/686 ,  G01N15/1404 ,  G01N2015/1006

摘要： The present invention generally relates to droplets and/or emulsions, such as multiple emulsions. In some cases, the droplets and/or emulsions may be used in assays, and in certain embodiments, the droplet or emulsion may be hardened to form a gel. In some aspects, a heterogeneous assay can be performed using a gel. For example, a droplet may be hardened to form a gel, where the droplet contains a cell, DNA, or other suitable species. The gel may be exposed to a reactant, and the reactant may interact with the gel and/or with the cell, DNA, etc., in some fashion. For example, the reactant may diffuse through the gel, or the hardened particle may liquefy to form a liquid state, allowing the reactant to interact with the cell. As a specific example, DNA contained within a gel particle may be subjected to PCR (polymerase chain reaction) amplification, e.g., by using PCR primers able to bind to the gel as it forms. As the DNA is amplified using PCR, some of the DNA will be bound to the gel via the PCR primer. After the PCR reaction, unbound DNA may be removed from the gel, e.g., via diffusion or washing. Thus, a gel particle having bound DNA may be formed in one embodiment of the invention.

摘要翻译： 本发明通常涉及液滴和/或乳液，例如多重乳液。 在一些情况下，液滴和/或乳液可用于测定中，并且在某些实施方案中，液滴或乳液可被硬化以形成凝胶。 在一些方面，可以使用凝胶进行异质测定。 例如，液滴可以被硬化以形成凝胶，其中液滴包含细胞，DNA或其它合适的物质。 凝胶可以暴露于反应物，并且反应物可以以某种方式与凝胶和/或与细胞，DNA等相互作用。 例如，反应物可以扩散通过凝胶，或者硬化的颗粒可以液化以形成液体状态，允许反应物与细胞相互作用。 作为具体实例，包含在凝胶颗粒内的DNA可以进行PCR（聚合酶链式反应）扩增，例如通过使用能够在形成凝胶时结合凝胶的PCR引物。 当使用PCR扩增DNA时，一些DNA将通过PCR引物与凝胶结合。 PCR反应后，未结合的DNA可以从凝胶中去除，例如通过扩散或洗涤。 因此，可以在本发明的一个实施方案中形成具有结合DNA的凝胶颗粒。

公开(公告)号：US20140026968A1

公开(公告)日：2014-01-30

申请号：US13979984

申请日：2012-02-06

申请人： Adam R. Abate ,  David A. Weitz

发明人： Adam R. Abate ,  David A. Weitz

IPC分类号： B01L3/00

CPC分类号： B01L3/5027 ,  B01L3/502784 ,  B01L2200/0673 ,  B01L2200/12 ,  B01L2300/0816 ,  B01L2300/0864 ,  B01L2300/123 ,  Y10T137/0318 ,  Y10T137/85938

摘要： The present invention generally relates to fluidics and microfluidics and, in particular, to creating droplets in a fluidic system. In some aspects, the present invention is generally directed to systems and methods for splitting a parent droplet into two or more droplets, e.g., by urging the parent droplet towards an obstacle to split the parent droplet. In some cases, the parent droplet is split into at least first and second droplets which each are directed to separate channels. In some cases, the channels may be constructed and arranged such that the droplet velocities of the first and second droplets are substantially the same as the velocity of the parent droplet. In some cases, such droplets may be repeatedly split, e.g., a parent droplet is divided into 2 daughter droplets, then each droplet split again, etc., for example, such that one parent droplet may eventually be split into 22, 23, 24, 25, 26, etc. daughter droplets. In some cases, the daughter droplets may be substantially monodisperse.

摘要翻译： 本发明一般涉及流体和微流体，特别是涉及在流体系统中产生液滴。 在一些方面，本发明一般涉及用于将母液滴分解为两个或更多个液滴的系统和方法，例如通过将母液滴向障碍物推动以分离母液滴。 在一些情况下，母液滴被分成至少第一和第二液滴，每个液滴被引导到分离的通道。 在一些情况下，可以构造和布置通道，使得第一和第二液滴的液滴速度基本上与母液滴的速度相同。 在一些情况下，这样的液滴可以被重复地分开，例如，母液滴被分成2个子液滴，然后每个液滴再次分离等，例如使得一个亲液滴最终可以分成22,23,24 ，25,26等子液滴。 在一些情况下，子液滴可以是基本上单分散的。

公开(公告)号：US08592221B2

公开(公告)日：2013-11-26

申请号：US12595107

申请日：2008-04-18

申请人： Seth Fraden ,  Hakim Boukellal ,  Yanwei Jia ,  Seila Selimovic ,  Amy Rowat ,  Jeremy Agresti ,  David A. Weitz

发明人： Seth Fraden ,  Hakim Boukellal ,  Yanwei Jia ,  Seila Selimovic ,  Amy Rowat ,  Jeremy Agresti ,  David A. Weitz

IPC分类号： G01F11/00

CPC分类号： B01L3/502784 ,  B01L3/502746 ,  B01L2200/0673 ,  B01L2300/0861 ,  B01L2300/087 ,  B01L2300/0877 ,  B01L2400/0487 ,  B01L2400/0688 ,  B01L2400/0694 ,  B01L2400/082 ,  F17D1/12 ,  G01N1/28 ,  G01N15/0272 ,  G01N15/1484 ,  G01N2015/0092 ,  Y10T137/0324 ,  Y10T137/0391 ,  Y10T137/0396 ,  Y10T137/2082 ,  Y10T137/218 ,  Y10T436/2575

摘要： Microfluidic structures and methods for manipulating fluids, fluid components, and reactions are provided. In one aspect, such structures and methods can allow production of droplets of a precise volume, which can be stored/maintained at precise regions of the device. In another aspect, microfluidic structures and methods described herein are designed for containing and positioning components in an arrangement such that the components can be manipulated and then tracked even after manipulation. For example, cells may be constrained in an arrangement in microfluidic structures described herein to facilitate tracking during their growth and/or after they multiply.

公开(公告)号：US20130046030A1

公开(公告)日：2013-02-21

申请号：US13477636

申请日：2012-05-22

申请人： Assaf Rotem ,  David A. Weitz ,  Adam R. Abate ,  Christian Holtze

发明人： Assaf Rotem ,  David A. Weitz ,  Adam R. Abate ,  Christian Holtze

IPC分类号： B01J13/00 ,  B01F5/00

CPC分类号： B01F3/0811 ,  B01F3/0807 ,  B01F13/0062 ,  B01F13/0084 ,  Y10T137/87571

摘要： The present invention generally relates to emulsions, and more particularly, to double and other multiple emulsions. Certain aspects of the present invention are generally directed to the creation of double emulsions and other multiple emulsions at a common junction of microfluidic channels. In some cases, the microfluidic channels at the common junction may have substantially the same hydrophobicity. In one set of embodiments, a device may include a common junction of six or more channels, where a first fluid flows through one channel, a second fluid flows through two channels, and a third or carrying fluid flows through two more channels, such that a double emulsion of a first droplet of the first fluid, contained in a second droplet of the second fluid, contained by the carrying fluid, flows away from the common junction through a sixth channel.

摘要翻译： 本发明一般涉及乳液，更具体地说涉及双重和其它多重乳液。 本发明的某些方面通常涉及在微流体通道的共同连接处产生双重乳液和其它多重乳液。 在一些情况下，共同连接处的微流体通道可具有基本上相同的疏水性。 在一组实施例中，装置可以包括六个或更多个通道的公共接头，其中第一流体流过一个通道，第二流体流过两个通道，并且第三或承载流体流过两个以上通道，使得 包含在第二流体的第二液滴中的第一流体的第一液滴的双重乳液由携带流体包含，通过第六通道从公共接头流出。

公开(公告)号：US20120015382A1

公开(公告)日：2012-01-19

申请号：US13195468

申请日：2011-08-01

申请人： David A. Weitz ,  Andrew Griffiths ,  Sarah Koester ,  Vamsi K. Mootha ,  Honey Duan ,  Jeremy Agresti ,  Christoph Merten ,  John Heyman ,  John R. Gilbert

发明人： David A. Weitz ,  Andrew Griffiths ,  Sarah Koester ,  Vamsi K. Mootha ,  Honey Duan ,  Jeremy Agresti ,  Christoph Merten ,  John Heyman ,  John R. Gilbert

IPC分类号： G01N33/53 ,  G01N21/64

CPC分类号： G01N33/505 ,  B01F13/0071 ,  B01F13/0076 ,  B01L3/502784 ,  G01N15/1459 ,  G01N33/5052 ,  G01N33/5436 ,  G01N33/6854 ,  G01N2015/149

摘要： The present invention generally relates to fluidic droplets, and techniques for screening or sorting such fluidic droplets. In some embodiments, the fluidic droplets may contain cells (e.g., hybridoma cells) that can secrete various species, such as antibodies, for example. In one aspect, a plurality of fluidic droplets containing cells is screened to determine proteins, antibodies, polypeptides, peptides, nucleic acids, or the like. For example, cells able to secrete species such as antibodies may be selected according to certain embodiments of the invention. Examples of such cells include, for instance, immortal cells such as hybridomas, or non-immortal cells such as B-cells. For instance, blood cells may be encapsulated within a plurality of fluidic droplets, and the cells able to produce antibodies may be determined. In some cases, expression or secretion levels may be determined using signaling entities, for example, determinable microparticles present within the fluidic droplet. Other aspects of the invention relate to kits involving such fluidic droplets, methods of promoting the making or use of such fluidic droplets, and the like.

摘要翻译： 本发明一般涉及流体液滴，以及用于筛选或分类这种流体液滴的技术。 在一些实施方案中，流体液滴可以含有可分泌各种物质例如抗体的细胞（例如，杂交瘤细胞）。 在一个方面，筛选含有细胞的多个流体液滴以确定蛋白质，抗体，多肽，肽，核酸等。 例如，可以根据本发明的某些实施方案来选择能够分泌诸如抗体的物质的细胞。 这些细胞的实例包括，例如，诸如杂交瘤的永生细胞，或非永生细胞如B细胞。 例如，血细胞可以被包封在多个流体液滴中，并且可以确定能产生抗体的细胞。 在一些情况下，表达或分泌水平可以使用信号实体来确定，例如存在于流体液滴内的可测定的微粒。 本发明的其它方面涉及涉及这种流体液滴的试剂盒，促进制造或使用这种流体液滴的方法等。

公开(公告)号：US20110267457A1

公开(公告)日：2011-11-03

申请号：US12809120

申请日：2008-12-19

申请人： David A Weitz ,  Jeremy Agresti ,  Michael P. Weiner ,  Adam R. Abate ,  Tony Hung

发明人： David A Weitz ,  Jeremy Agresti ,  Michael P. Weiner ,  Adam R. Abate ,  Tony Hung

IPC分类号： C40B30/04 ,  C07H1/00 ,  H04N7/18 ,  G01N33/53

CPC分类号： C12Q1/6874 ,  C12Q2537/143 ,  C12Q2563/149

摘要： The present invention relates to systems and methods for sequencing nucleic acids, including sequencing nucleic acids in fluidic droplets. In one set of embodiments, the method employs sequencing by hybridization using droplets such as microfluidic droplets. In some embodiments, droplets are formed which include a target nucleic acid, a nucleic acid probe, and at least one identification element, such as a fluorescent particle. The nucleic acid probes that hybridize to the target nucleic acid are determined, in some instances, by determining the at least one identification element. The nucleic acid probes that hybridize to the target nucleic acid may be used to determine the sequence of the target nucleic acid. In certain instances, the microfluidic droplets are provided with reagents that modify the nucleic acid probe. In some cases, a droplet, such as those described above, is deformed such that the components of the droplets individually pass a target area.

摘要翻译： 本发明涉及用于测序核酸的系统和方法，包括以流体液滴测序核酸。 在一组实施方案中，该方法采用使用微滴（例如微流控液滴）的杂交进行测序。 在一些实施方案中，形成液滴，其包括靶核酸，核酸探针和至少一种识别元件，例如荧光颗粒。 在某些情况下，通过确定至少一个识别元件来确定与靶核酸杂交的核酸探针。 与靶核酸杂交的核酸探针可用于测定靶核酸的序列。 在某些情况下，向微流体液滴提供修饰核酸探针的试剂。 在一些情况下，诸如上述那些的液滴变形，使得液滴的组分分别通过目标区域。

公开(公告)号：US20110151578A1

公开(公告)日：2011-06-23

申请号：US12992376

申请日：2009-05-15

申请人： Adam R. Abate ,  David A. Weitz

发明人： Adam R. Abate ,  David A. Weitz

IPC分类号： G01N1/10 ,  B01L3/00

CPC分类号： B01L3/502738 ,  B01L3/0268 ,  B01L3/502746 ,  B01L3/502784 ,  B01L2200/0605 ,  B01L2200/0636 ,  B01L2200/146 ,  B01L2300/0816 ,  B01L2300/0864 ,  B01L2300/0867 ,  B01L2400/0487 ,  B01L2400/0655 ,  B01L2400/082 ,  F16K99/0017 ,  F16K99/0026 ,  F16K99/0055 ,  Y10T436/2575

摘要： Articles and methods for controlling flow in fluidic Systems, especially in microfluidic Systems, are provided. A microfluidic System includes a configuration such that the actuation of a single valve can allow the switching of fluids from a first fluid path (e.g., a first channel section) to a second fluid path (e.g., a second channel section). This may be achieved by incorporating a valve (38) with a first channel section (24), which may have a lower hydrodynamic resistance than a second channel section (28) prior to actuation of the valve. Actuation of the valve (38) can cause only the hydrodynamic resistance of the first channel section (24) to increase, thereby redirecting fluid flow into the second channel section (28) (which now has a relatively lower hydrodynamic resistance). The valve comprises a control channel (40) for introducing a positive or reduced pressure, and is adapted to modulate fluid flow in an adjacent channel section by constricting or expanding the channel section (24).

摘要翻译： 提供了用于控制流体系统流动的文章和方法，特别是在微流体系统中。 微流体系统包括使得单个阀的致动允许流体从第一流体路径（例如，第一通道部分）切换到第二流体路径（例如，第二通道部分）的构造。 这可以通过在阀致动之前并入具有第一通道部分（24）的阀（38）来实现，其可以具有比第二通道部分（28）更低的流体动力阻力。 阀（38）的致动可以仅使第一通道部分（24）的流体动力阻力增加，从而将流体流转向第二通道部分（28）（其现在具有相对较低的流体动力阻力）。 阀包括用于引入正压或减压的控制通道（40），并且适于通过收缩或扩大通道部分（24）来调制相邻通道部分中的流体流动。

公开(公告)号：US20100172803A1

公开(公告)日：2010-07-08

申请号：US12726223

申请日：2010-03-17

申请人： Howard A. Stone ,  Shelley L. Anna ,  Nathalie Bontoux ,  Darren R. Link ,  David A. Weitz ,  Irina Gitlin ,  Eugenia Kumacheva ,  Piotr Garstecki ,  Willow Diluzio ,  George M. Whitesides

发明人： Howard A. Stone ,  Shelley L. Anna ,  Nathalie Bontoux ,  Darren R. Link ,  David A. Weitz ,  Irina Gitlin ,  Eugenia Kumacheva ,  Piotr Garstecki ,  Willow Diluzio ,  George M. Whitesides

IPC分类号： B01L3/00

CPC分类号： B01L3/5027 ,  B01F3/0807 ,  B01F5/0682 ,  B01F5/0688 ,  B01F13/0062 ,  B01F2215/0431 ,  B01F2215/045 ,  B05B7/0408 ,  B05B7/0416 ,  B05B7/0441 ,  Y10S516/924 ,  Y10S516/927 ,  Y10T29/49002 ,  Y10T137/0324 ,  Y10T137/0329 ,  Y10T137/206 ,  Y10T137/87346 ,  Y10T436/2575

摘要： A microfluidic method and device for focusing and/or forming discontinuous sections of similar or dissimilar size in a fluid is provided. The device can be fabricated simply from readily-available, inexpensive material using simple techniques.

摘要翻译： 提供了用于在流体中聚焦和/或形成类似或不同尺寸的不连续部分的微流体方法和装置。 该装置可以简单地使用简单的技术从容易获得的廉价材料制造。

公开(公告)号：US20100136544A1

公开(公告)日：2010-06-03

申请号：US12529926

申请日：2008-03-07

申请人： Jeremy Agresti ,  Liang-Yin Chu ,  David A. Weitz ,  Jin-Woong Kim ,  Amy Rowat ,  Morten Sommer ,  Gautam Dantas ,  George Church

发明人： Jeremy Agresti ,  Liang-Yin Chu ,  David A. Weitz ,  Jin-Woong Kim ,  Amy Rowat ,  Morten Sommer ,  Gautam Dantas ,  George Church

IPC分类号： C12Q1/68 ,  C12Q1/04

CPC分类号： C12P19/34 ,  B01F3/0807 ,  B01F3/0811 ,  B01F13/0062 ,  B01F13/0071 ,  B01F2215/0037 ,  B01J13/0052 ,  B01J13/0065 ,  B01L3/502784 ,  C12Q1/6834 ,  C12Q1/6848 ,  C12Q1/686 ,  G01N15/1404 ,  G01N2015/1006

摘要： The present invention generally relates to droplets and/or emulsions, such as multiple emulsions. In some cases, the droplets and/or emulsions may be used in assays, and in certain embodiments, the droplet or emulsion may be hardened to form a gel. In some aspects, a heterogeneous assay can be performed using a gel. For example, a droplet may be hardened to form a gel, where the droplet contains a cell, DNA, or other suitable species. The gel may be exposed to a reactant, and the reactant may interact with the gel and/or with the cell, DNA, etc., in some fashion. For example, the reactant may diffuse through the gel, or the hardened particle may liquefy to form a liquid state, allowing the reactant to interact with the cell. As a specific example, DNA contained within a gel particle may be subjected to PCR (polymerase chain reaction) amplification, e.g., by using PCR primers able to bind to the gel as it forms. As the DNA is amplified using PCR, some of the DNA will be bound to the gel via the PCR primer. After the PCR reaction, unbound DNA may be removed from the gel, e.g., via diffusion or washing. Thus, a gel particle having bound DNA may be formed in one embodiment of the invention.

摘要翻译： 本发明通常涉及液滴和/或乳液，例如多重乳液。 在一些情况下，液滴和/或乳液可用于测定中，并且在某些实施方案中，液滴或乳液可被硬化以形成凝胶。 在一些方面，可以使用凝胶进行异质测定。 例如，液滴可以被硬化以形成凝胶，其中液滴包含细胞，DNA或其它合适的物质。 凝胶可以暴露于反应物，并且反应物可以以某种方式与凝胶和/或与细胞，DNA等相互作用。 例如，反应物可以扩散通过凝胶，或者硬化的颗粒可以液化以形成液体状态，允许反应物与细胞相互作用。 作为具体实例，包含在凝胶颗粒内的DNA可以进行PCR（聚合酶链式反应）扩增，例如通过使用能够在形成凝胶时结合凝胶的PCR引物。 当使用PCR扩增DNA时，一些DNA将通过PCR引物与凝胶结合。 PCR反应后，未结合的DNA可以从凝胶中去除，例如通过扩散或洗涤。 因此，可以在本发明的一个实施方案中形成具有结合DNA的凝胶颗粒。

公开(公告)号：US20100124759A1

公开(公告)日：2010-05-20

申请号：US12492830

申请日：2009-06-26

申请人： Benjamin L. Wang ,  Katherine J. Humphry ,  David A. Weitz ,  Gregory Stephanopoulos

发明人： Benjamin L. Wang ,  Katherine J. Humphry ,  David A. Weitz ,  Gregory Stephanopoulos

IPC分类号： C12Q1/28 ,  C12N1/18 ,  C12Q1/26 ,  C12N1/20

CPC分类号： B01L3/502715 ,  B01L3/502753 ,  B01L3/502761 ,  B01L2200/0647 ,  B01L2200/0652 ,  B01L2200/10 ,  B01L2300/0681 ,  B01L2300/0816 ,  B01L2300/087 ,  B01L2400/0421

摘要： The present invention relates generally to the use of droplets to culture and/or assay cells or other species. In some cases, the cells or other species may be sorted based upon the results of the culture and/or assay. In some embodiments, cells other species can be encapsulated in droplets and exposed to one or more agents (e.g., a sugar, an indicator dye, etc.). For instance, in some cases, exposure of cells to the agents may result in the production of metabolites or other compounds (e.g., amino acids, proteins, organic acids, etc.) which may be, for example, assayed or otherwise determined. In some embodiments, the reaction of an agent with cells and/or other species within a droplet may reveal a property of the cells or other species (e.g., sugar consumption, growth rate, ability to withstand exposure to the agent, etc.). As an example, cells that produce desired metabolites or exhibit certain properties may be separated from the other cells via sorting techniques. Other aspects of the invention relate to devices or kits for implementing such sorts, methods of promoting such techniques, or the like.

摘要翻译： 本发明一般涉及使用液滴来培养和/或测定细胞或其它物种。 在一些情况下，可以基于培养和/或测定的结果对细胞或其它物种进行分类。 在一些实施方案中，细胞其他物质可以被包封在液滴中并暴露于一种或多种试剂（例如，糖，指示剂染料等）。 例如，在一些情况下，细胞暴露于试剂可导致生成代谢物或其它化合物（例如，氨基酸，蛋白质，有机酸等），其可以例如被测定或以其他方式测定。 在一些实施方案中，药剂与细胞和/或液滴内的其它物质的反应可以揭示细胞或其他物种的性质（例如，糖消耗，生长速率，耐受试剂暴露的能力等）。 作为实例，产生所需代谢物或显示某些特性的细胞可以通过分选技术与其他细胞分离。 本发明的其他方面涉及用于实现这种类型的装置或套件，促进这种技术的方法等。