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    Systems and methods for nucleic acid sequencing
    1.
    发明授权
    Systems and methods for nucleic acid sequencing 有权

    公开(公告)号：US09797010B2

    公开(公告)日：2017-10-24

    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： C12Q1/68

    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.

    ACOUSTIC WAVES IN MICROFLUIDICS
    4.
    发明申请
    ACOUSTIC WAVES IN MICROFLUIDICS 有权
    微波中的声波

    公开(公告)号：US20130213488A1

    公开(公告)日：2013-08-22

    申请号：US13818146

    申请日：2011-08-23

    申请人： David A. Weitz ,  Thomas Franke ,  Achim Wixforth ,  Lothar Schmid ,  Jeremy Agresti ,  Adam R. Abate

    发明人： David A. Weitz ,  Thomas Franke ,  Achim Wixforth ,  Lothar Schmid ,  Jeremy Agresti ,  Adam R. Abate

    IPC分类号： C12M3/06 ,  F17D3/01

    CPC分类号： C12M23/16 ,  B01L3/502761 ,  B01L3/502776 ,  B01L2200/0636 ,  B01L2200/0652 ,  B01L2300/0816 ,  B01L2400/0421 ,  B01L2400/0436 ,  B01L2400/0487 ,  B01L2400/0496 ,  C12M47/04 ,  F17D3/01 ,  G01N2015/1006 ,  G01N2015/1081 ,  Y10T137/0391

    摘要： Various aspects of the present invention relate to the control and manipulation of fluidic species, for example, in microfluidic systems. In one set of embodiments, droplets may be sorted using surface acoustic waves. The droplets may contain cells or other species. In some cases, the surface acoustic waves may be created using a surface acoustic wave generator such as an interdigitated transducer, and/or a material such as a piezoelectric substrate. The piezoelectric substrate may be isolated from the microfluidic substrate except at or proximate the location where the droplets are sorted, e.g., into first or second microfluidic channels. At such locations, the microfluidic substrate may be coupled to the piezoelectric substrate (or other material) by one or more coupling regions. In some cases, relatively high sorting rates may be achieved, e.g., at rates of at least about 1,000 Hz, at least about 10,000 Hz, or at least about 100,000 Hz, and in some embodiments, with high cell viability after sorting.

    摘要翻译： 本发明的各个方面涉及流体物质的控制和操作，例如在微流体系统中。 在一组实施例中，可以使用表面声波对液滴进行分类。 液滴可能含有细胞或其他物种。 在一些情况下，表面声波可以使用表面声波发生器（例如交叉换能器）和/或诸如压电基板的材料来产生。 压电衬底可以与微流体衬底隔离，除了在液滴被分类的位置处或附近，例如，进入第一或第二微流体通道。 在这样的位置处，微流体衬底可以通过一个或多个耦合区域耦合到压电衬底（或其它材料）。 在一些情况下，可以例如以至少约1000Hz，至少约10,000Hz或至少约100,000Hz的速率实现相对较高的分选率，并且在一些实施方案中，分选后具有高的细胞活力。

    CREATION OF LIBRARIES OF DROPLETS AND RELATED SPECIES
    5.
    发明申请
    CREATION OF LIBRARIES OF DROPLETS AND RELATED SPECIES 审中-公开
    创作图书馆和相关物种

    公开(公告)号：US20110218123A1

    公开(公告)日：2011-09-08

    申请号：US13119470

    申请日：2009-09-17

    申请人： David A. Weitz ,  Jeremy Agresti

    发明人： David A. Weitz ,  Jeremy Agresti

    IPC分类号： C40B50/08

    CPC分类号： C12Q1/6876 ,  B01J13/04 ,  B01J19/0046 ,  B01J2219/00599 ,  B01J2219/00709 ,  B01J2219/00711 ,  B01J2219/00716 ,  B01J2219/00722 ,  C12Q1/6874

    摘要： The present invention is generally related to systems and methods for producing a plurality of droplets. The droplets may contain varying species, e.g., for use as a library. In some cases, the fluidic droplets may be rigidified to form rigidified droplets (e.g., gel droplets). In certain embodiments, the droplets may undergo a phase change (e.g., from rigidified droplets to fluidized droplets), as discussed more herein. In some cases, a species may be added internally to a droplet by exposing the droplet to a fluid comprising a plurality of species.

    摘要翻译： 本发明通常涉及用于生产多个液滴的系统和方法。 液滴可以包含不同的物种，例如用作文库。 在一些情况下，流体液滴可以被硬化以形成刚性液滴（例如凝胶液滴）。 在某些实施方案中，液滴可能经历相变（例如，从刚性液滴到流化液滴），如本文更多地讨论的。 在一些情况下，通过将液滴暴露于包含多种物质的流体，物质可以内部添加到液滴中。

    Assays and other reactions involving droplets
    8.
    发明授权
    Assays and other reactions involving droplets 有权
    测定和其他涉及液滴的反应

    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。

    GEL-ENCAPSULATED MICROCOLONY SCREENING
    10.
    发明申请
    GEL-ENCAPSULATED MICROCOLONY SCREENING 审中-公开
    凝胶微孔筛选

    公开(公告)号：US20120196770A1

    公开(公告)日：2012-08-02

    申请号：US13360620

    申请日：2012-01-27

    申请人： Jeremy Agresti

    发明人： Jeremy Agresti

    IPC分类号： G01N21/64 ,  C40B30/10

    CPC分类号： C12Q1/02 ,  C12N11/04 ,  C12N11/10 ,  C12P5/007 ,  C12P7/02 ,  G01N33/5005

    摘要： Provided herein are methods and compositions useful for detecting the production of industrially useful compounds (e.g., isoprenoids, polyketides, and fatty acids) in a cell, for example, a microbial cell genetically modified to produce one or more such compounds. In some embodiments, the methods comprise encapsulating the cell in a hydrogel particle, and detecting the compound within the hydrogel particle.

    摘要翻译： 本文提供了可用于检测细胞中工业上有用的化合物（例如类异戊二烯，聚酮化合物和脂肪酸）的生产的方法和组合物，例如经遗传修饰以产生一种或多种这样的化合物的微生物细胞。 在一些实施方案中，所述方法包括将细胞包封在水凝胶颗粒中，并检测水凝胶颗粒内的化合物。