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1. 发明申请

WO2010033200A2 CREATION OF LIBRARIES OF DROPLETS AND RELATED SPECIES 审中-公开
标题翻译：创作画卷和相关物种的图书馆
公开(公告)号：WO2010033200A2
公开(公告)日：2010-03-25
申请号：PCT/US2009/005184
申请日：2009-09-17
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , WEITZ, David, A. , AGRESTI, Jeremy
发明人： WEITZ, David, A. , AGRESTI, Jeremy
IPC分类号： C40B30/04
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。液滴可以含有不同的物质，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，液滴可以经历相变（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，可以通过将液滴暴露于包含多种物质的流体，将物质内部加入到液滴中。

2. 发明申请

WO2009134395A2 MICROFLUIDIC DEVICE FOR STORAGE AND WELL-DEFINED ARRANGEMENT OF DROPLETS 审中-公开
标题翻译：用于储存和定义错误布置的微流体装置
公开(公告)号：WO2009134395A2
公开(公告)日：2009-11-05
申请号：PCT/US2009/002644
申请日：2009-04-28
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , SCHMITZ, Christian , ROWAT, Amy , KOESTER, Sarah , AGRESTI, Jeremy , WEITZ, David, A.
发明人： SCHMITZ, Christian , ROWAT, Amy , KOESTER, Sarah , AGRESTI, Jeremy , WEITZ, David, A.
IPC分类号： G01N35/00 , G01N21/64 , G01N33/50 , C12Q1/02
CPC分类号： G01N21/6452 , B01L3/502784 , B01L7/525 , B01L2200/0621 , B01L2300/0816 , B01L2300/0819 , B01L2300/087 , B01L2300/1827 , B01L2400/0487 , B01L2400/086 , G01N33/5008
摘要： The present invention relates to systems and methods for the arrangement of droplets in pre-determined locations. Many applications require the collection of time- resolved data. Examples include the screening of cells based on their growth characteristics or the observation of enzymatic reactions. The present invention provides a tool and related techniques which addresses this need, and which can be used in many other situations. The invention provides, in one aspect, a tool that allows for stable storage and indexing of individual droplets. The invention can interface not only with microfluidic/microscale equipment, but with macroscopic equipment to allow for the easy injection of liquids and extraction of sample droplets, etc.
摘要翻译：本发明涉及用于在预定位置中布置液滴的系统和方法。许多应用程序需要收集时间分辨数据。实例包括基于其生长特征或观察酶反应来筛选细胞。本发明提供了一种解决该需求的工具和相关技术，并且可以在许多其它情况下使用。本发明在一个方面提供一种允许单个液滴的稳定储存和分度的工具。本发明不仅可以与微流体/微型设备连接，而且可以与宏观设备相接合，以便容易地注入液体和提取样品液滴等。

3. 发明申请

WO2008109176A8 ASSAYS AND OTHER REACTIONS INVOLVING DROPLETS 审中-公开
标题翻译：测定和涉及滴剂的其他反应
公开(公告)号：WO2008109176A8
公开(公告)日：2008-11-13
申请号：PCT/US2008003185
申请日：2008-03-07
申请人： HARVARD COLLEGE , AGRESTI JEREMY , CHU LIANG-YIN , WEITZ DAVID A , KIM JIN-WOONG , ROWAT AMY , SOMMER MORTEN , DANTAS GAUTAM , CHURCH GEORGE
发明人： AGRESTI JEREMY , CHU LIANG-YIN , WEITZ DAVID A , KIM JIN-WOONG , ROWAT AMY , SOMMER MORTEN , DANTAS GAUTAM , CHURCH GEORGE
IPC分类号： C12Q1/68 , B01J13/00
CPC分类号： C12Q1/6848 , B01F3/0807 , B01F3/0811 , B01F13/0062 , B01F13/0071 , B01F2215/0037 , B01J13/0052 , B01J13/0065 , C12P19/34 , C12Q1/6834 , C12Q1/686
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：本发明一般涉及液滴和/或乳液，例如多重乳液。在一些情况下，液滴和/或乳液可以用于测定中，并且在某些实施方案中，液滴或乳液可以被硬化以形成凝胶。在一些方面，可以使用凝胶进行非均相测定。例如，可以使小滴硬化以形成凝胶，其中小滴含有细胞，DNA或其他合适的物质。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，反应物可以通过凝胶扩散，或者硬化的颗粒可以液化以形成液体状态，从而允许反应物与细胞相互作用。作为具体例子，可以对凝胶颗粒内包含的DNA进行PCR（聚合酶链式反应）扩增，例如通过使用能够在凝胶形成时结合到凝胶上的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。

4. 发明申请

WO2008109176A2 ASSAYS AND OTHER REACTIONS INVOLVING DROPLETS 审中-公开
标题翻译：测量和其他涉及倾销的反应
公开(公告)号：WO2008109176A2
公开(公告)日：2008-09-12
申请号：PCT/US2008003185
申请日：2008-03-07
申请人： HARVARD COLLEGE , AGRESTI JEREMY , CHU LIANG-YIN , WEITZ DAVID A , KIM JIN-WOONG , ROWAT AMY , SOMMER MORTEN , DANTAS GUATAM , CHURCH GEORGE
发明人： AGRESTI JEREMY , CHU LIANG-YIN , WEITZ DAVID A , KIM JIN-WOONG , ROWAT AMY , SOMMER MORTEN , DANTAS GUATAM , CHURCH GEORGE
CPC分类号： C12Q1/6848 , B01F3/0807 , B01F3/0811 , B01F13/0062 , B01F13/0071 , B01F2215/0037 , B01J13/0052 , B01J13/0065 , C12P19/34 , C12Q1/6834 , C12Q1/686
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。

5. 发明申请

WO2012027366A3 ACOUSTIC WAVES IN MICROFLUIDICS 审中-公开
标题翻译： MICROFLUIDICS中的声波
公开(公告)号：WO2012027366A3
公开(公告)日：2012-08-16
申请号：PCT/US2011048804
申请日：2011-08-23
申请人： HARVARD COLLEGE , UNIV AUGSBURG , WEITZ DAVID A , FRANKE THOMAS , WIXFORTH ACHIM , SCHMID LOTHAR , AGRESTI JEREMY , ABATE ADAM R
发明人： WEITZ DAVID A , FRANKE THOMAS , WIXFORTH ACHIM , SCHMID LOTHAR , AGRESTI JEREMY , ABATE ADAM R
IPC分类号： B01J19/10 , C12M1/42
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例如在微流体系统中的流体物质的控制和操纵。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，表面声波可以使用诸如叉指换能器的表面声波发生器和/或诸如压电基板的材料来产生。除了在液滴分选位置处或附近之外，压电基底可以与微流体基底分离，例如分离成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（或其他材料）。在一些情况下，可以实现相对高的分选速率，例如以至少约1,000Hz，至少约10,000Hz或至少约100,000Hz的速率，并且在一些实施方式中，在分选后具有高细胞存活力。

6. 发明申请

WO2012103516A1 GEL-ENCAPSULATED MICROCOLONY SCREENING 审中-公开
标题翻译：凝胶微孔筛选
公开(公告)号：WO2012103516A1
公开(公告)日：2012-08-02
申请号：PCT/US2012/023024
申请日：2012-01-27
申请人： AMYRIS, INC. , AGRESTI, Jeremy
发明人： AGRESTI, Jeremy
IPC分类号： C12Q1/02 , G01N33/50 , C12P5/00
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。

7. 发明申请

WO2012027366A2 ACOUSTIC WAVES IN MICROFLUIDICS 审中-公开
标题翻译：微波中的声波
公开(公告)号：WO2012027366A2
公开(公告)日：2012-03-01
申请号：PCT/US2011/048804
申请日：2011-08-23
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , UNIVERSITÄT AUGSBURG , WEITZ, David, A. , FRANKE, Thomas , WIXFORTH, Achim , SCHMID, Lothar , AGRESTI, Jeremy , ABATE, Adam, R.
发明人： WEITZ, David, A. , FRANKE, Thomas , WIXFORTH, Achim , SCHMID, Lothar , AGRESTI, Jeremy , ABATE, Adam, R.
IPC分类号： B01J19/10 , C12M1/42
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。

8. 发明申请

WO2008109176A3 ASSAYS AND OTHER REACTIONS INVOLVING DROPLETS 审中-公开
公开(公告)号：WO2008109176A3
公开(公告)日：2008-09-12
申请号：PCT/US2008/003185
申请日：2008-03-07
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , AGRESTI, Jeremy , CHU, Liang-yin , WEITZ, David, A. , KIM, Jin-woong , ROWAT, Amy , SOMMER, Morten , DANTAS, Gautam , CHURCH, George
发明人： AGRESTI, Jeremy , CHU, Liang-yin , WEITZ, David, A. , KIM, Jin-woong , ROWAT, Amy , SOMMER, Morten , DANTAS, Gautam , CHURCH, George
IPC分类号： B01J13/00
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.

9. 发明申请

WO2009011808A1 DROPLET-BASED SELECTION 审中-公开
标题翻译：基于DROPLET的选择
公开(公告)号：WO2009011808A1
公开(公告)日：2009-01-22
申请号：PCT/US2008/008563
申请日：2008-07-11
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , WEITZ, David, A. , GRIFFITHS, Andrew , KOESTER, Sarah , MOOTHA, Vamsi, K. , DUAN, Honey , AGRESTI, Jeremy , MERTEN, Christoph , HEYMAN, John , GILBERT, John, R.
发明人： WEITZ, David, A. , GRIFFITHS, Andrew , KOESTER, Sarah , MOOTHA, Vamsi, K. , DUAN, Honey , AGRESTI, Jeremy , MERTEN, Christoph , HEYMAN, John , GILBERT, John, R.
IPC分类号： G01N33/50 , G01N33/543
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。

10. 发明申请

WO2008130623A1 MANIPULATION OF FLUIDS, FLUID COMPONENTS AND REACTIONS IN MICROFLUIDIC SYSTEMS 审中-公开
标题翻译：微流控系统中流体，流体组分和反应的操作
公开(公告)号：WO2008130623A1
公开(公告)日：2008-10-30
申请号：PCT/US2008/005009
申请日：2008-04-18
申请人： BRANDEIS UNIVERSITY , PRESIDENT AND FELLOWS OF HARVARD COLLEGE , FRADEN, Seth , BOUKELLAL, Hakim , JIA, Yanwei , SELIMOVIC, Seila , ROWAT, Amy , AGRESTI, Jeremy , WEITZ, David, A.
发明人： FRADEN, Seth , BOUKELLAL, Hakim , JIA, Yanwei , SELIMOVIC, Seila , ROWAT, Amy , AGRESTI, Jeremy , WEITZ, David, A.
IPC分类号： B01L3/00 , G01N15/14
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.
摘要翻译：提供了用于操纵流体，流体组分和反应的微流体结构和方法。在一个方面，这种结构和方法可以允许产生精确体积的液滴，其可被存储/保持在装置的精确区域。在另一方面，本文所述的微流体结构和方法被设计用于在组件中容纳和定位组件，使得即使在操作之后也可以操纵组件并随后进行跟踪。例如，细胞可以以本文所述的微流体结构的排列约束，以便于在其生长期间和/或在它们繁殖之后进行跟踪。

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