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1. 发明申请

WO2013006661A3 MULTIPLE EMULSIONS AND TECHNIQUES FOR THE FORMATION OF MULTIPLE EMULSIONS 审中-公开
公开(公告)号：WO2013006661A3
公开(公告)日：2013-01-10
申请号：PCT/US2012/045481
申请日：2012-07-05
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , KIM, Shin-Hyn , ABBASPOURRAD, Alireza , WEITZ, David, A.
发明人： KIM, Shin-Hyn , ABBASPOURRAD, Alireza , WEITZ, David, A.
IPC分类号： B01F3/08 , B01F5/04 , B01F13/00
摘要： Multiple emulsions and techniques for the formation of multiple emulsions are generally described. A multiple emulsion, as used herein, describes larger droplets that contain one or more smaller droplets therein. In some embodiments, the larger droplet or droplets may be suspended in a carrying fluid containing the larger droplets that, in turn, contain the smaller droplets. As described below, multiple emulsions can be formed in one step in certain embodiments, with generally precise repeatability, and can be tailored in some embodiments to include a relatively thin layer of fluid separating two other fluids.

2. 发明申请

WO2010080134A1 PARTICLE-ASSISTED NUCLEIC ACID SEQUENCING 审中-公开
标题翻译：颗粒辅助核酸序列
公开(公告)号：WO2010080134A1
公开(公告)日：2010-07-15
申请号：PCT/US2009/006649
申请日：2009-12-18
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , WEITZ, David, A. , ABATE, Adam, R.
发明人： WEITZ, David, A. , ABATE, Adam, R.
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6809 , B01L3/502761 , B01L2200/10 , C12Q1/6834 , C12Q1/6869 , C12Q1/6874 , C12Q2525/204 , C12Q2563/149 , C12Q2563/159 , C12Q2565/629
摘要： This invention generally relates to particle-assisted nucleic acid sequencing. In some embodiments, sequencing may be performed in a microfluidic device, which can offer desirable properties, for example, minimal use of reagents, facile scale-up, and/or high throughput. In one embodiment, a target nucleic acid may be exposed to particles having nucleic acid probes. By determining the binding of the particles to the target nucleic acid, the sequence of the target nucleic acid (or at least a portion of the target nucleic acid) can be determined. The target nucleic acid may be encapsulated within a fluidic droplet with the particles having nucleic acid probes, in certain instances. In some cases, the sequence of the target nucleic acid may be determined, based on binding of the particles, using sequencing by hybridization (SBH) algorithms or other known techniques.
摘要翻译：本发明一般涉及颗粒辅助核酸测序。在一些实施方案中，可以在微流体装置中进行测序，所述微流体装置可以提供期望的性质，例如，最少使用试剂，容易的放大和/或高通量。在一个实施方案中，靶核酸可以暴露于具有核酸探针的颗粒。通过确定颗粒与靶核酸的结合，可以确定靶核酸（或目标核酸的至少一部分）的序列。在某些情况下，靶核酸可以包封在具有核酸探针的颗粒的流体液滴内。在一些情况下，可以通过使用通过杂交（SBH）算法或其他已知技术的测序，基于颗粒的结合来确定靶核酸的序列。

3. 发明申请

WO2009139898A2 VALVES AND OTHER FLOW CONTROL IN FLUIDIC SYSTEMS INCLUDING MICROFLUIDIC SYSTEMS 审中-公开
标题翻译：流体系统中的阀门和其他流量控制，包括微流体系统
公开(公告)号：WO2009139898A2
公开(公告)日：2009-11-19
申请号：PCT/US2009/003024
申请日：2009-05-15
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , ABATE, Adam, R. , WEITZ, David, A.
发明人： ABATE, Adam, R. , WEITZ, David, A.
IPC分类号： B01J14/00
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. In one aspect, a microfluidic system described herein 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, for example, by incorporating a valve with a first channel section, which may have a lower hydrodynamic resistance than a second channel section prior to actuation of the valve. Actuation of the valve can cause only the hydrodynamic resistance of the first channel section to increase, thereby redirecting fluid flow into the second channel section (which now has a relatively lower hydrodynamic resistance). In some embodiments, the valve comprises a control channel 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. For example, the valve and/or the channel section may be formed in a flexible material and actuation of the valve may be achieved by applying a positive or reduced pressure to the valve to cause deformation of both the valve and the channel section. Another aspect of the invention includes articles and methods associated with manipulation of multiphase materials (e.g., dispersions). For instance, one or more valves may be combined with a flow focusing system so as to form droplets of different volumes and/or frequencies without the need to vary flow rates of the fluids when they are introduced into the fluidic system.
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。在一个方面，本文描述的微流体系统包括使得单个阀的致动可以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）。这可以通过例如通过结合具有第一通道部分的阀来实现，该阀在致动阀之前可具有比第二通道部分更低的流体动力阻力。阀的致动可以仅使第一通道部分的流体动力阻力增加，从而将流体流转向第二通道部分（其现在具有相对较低的流体动力阻力）。在一些实施例中，阀包括用于引入正压或减压的控制通道，并且适于通过收缩或扩大通道部分来调制相邻通道部分中的流体流动。例如，阀和/或通道部分可以形成为柔性材料，并且可以通过向阀施加正压或减压以使阀和通道部分变形来实现阀的致动。本发明的另一方面包括与多相材料（例如分散体）的操作有关的制品和方法。例如，一个或多个阀可以与流动聚焦系统组合，以便形成不同体积和/或频率的液滴，而不需要在将流体引入流体系统时改变流体流速。

4. 发明申请

WO2006096571A2 METHOD AND APPARATUS FOR FORMING MULTIPLE EMULSIONS 审中-公开
标题翻译：用于形成多种乳液的方法和装置
公开(公告)号：WO2006096571A2
公开(公告)日：2006-09-14
申请号：PCT/US2006/007772
申请日：2006-03-03
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , WEITZ, David, A. , LINK, Darren, Roy , UTADA, Andrew, S.
发明人： WEITZ, David, A. , LINK, Darren, Roy , UTADA, Andrew, S.
IPC分类号： B01F13/00 , B01F3/08 , B01F5/04 , B01J13/02
CPC分类号： F15D1/008 , A61K9/113 , A61K9/1273 , A61K9/5089 , B01F3/0807 , B01F5/045 , B01F5/046 , B01F13/0059 , B01F13/0062 , B01F2005/0022 , B82Y10/00 , B82Y30/00 , Y10S516/924 , Y10T137/0391
摘要： The present invention generally relates to multiple emulsions, and to methods and apparatuses for making multiple emulsions. A multiple emulsion generally describes larger droplets that contain one or more smaller droplets therein. The larger droplets may be suspended in a third fluid in some cases. These can be useful for encapsulating species such as pharmaceutical agents, cells, chemicals, or the like. In some cases, one or more of the droplets can change form, for instance, to become solidified to form a microcapsule, a liposome, a polymerosome, or a colloidosome. Multiple emulsions can be formed in one step in certain embodiments, with generally precise repeatability, and can be tailored to include one, two, three, or more inner droplets within a single outer droplet (which droplets may all be nested in some cases).
摘要翻译：本发明一般涉及多重乳液，以及制备多重乳液的方法和装置。多重乳液通常描述在其中含有一个或多个较小液滴的较大液滴。在一些情况下，较大的液滴可以悬浮在第三流体中。这些可用于包封物质如药剂，细胞，化学品等。在一些情况下，一个或多个液滴可以改变形式，例如变得固化以形成微胶囊，脂质体，聚合物体或胶体体。在某些实施方案中，多个乳液可以在一个实施方案中形成，具有大致精确的重复性，并且可以调整为在单个外部液滴内包含一个，两个，三个或更多个内部液滴（在一些情况下，这些液滴可以嵌套）。

5. 发明申请

WO2017075297A1 HIGH-THROUGHPUT DYNAMIC REAGENT DELIVERY SYSTEM 审中-公开
公开(公告)号：WO2017075297A1
公开(公告)日：2017-05-04
申请号：PCT/US2016/059236
申请日：2016-10-27
申请人： THE BROAD INSTITUTE INC. , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , PRESIDENT AND FELLOWS OF HARVARD COLLEGE , FORD, Christopher , WEITZ, David, A.
发明人： FORD, Christopher , WEITZ, David, A. , BASU, Anindita , REGEV, Aviv
IPC分类号： B01L3/00 , C12M1/00 , C12M1/34 , C12M3/00
CPC分类号： B01L3/502746 , B01L3/0241 , B01L2300/0864 , B01L2300/0867 , B01L2400/086 , C12M23/16
摘要： The present invention generally relates to a controlled fluidic device to develop spatially complex environments to enhance the rate of evolution in cell populations. The method further provides an enhanced understanding in the emergence, for example, drug resistance during cancer chemotherapy.

6. 发明申请

WO2013032709A3 SYSTEMS AND METHODS FOR SHELL ENCAPSULATION 审中-公开
公开(公告)号：WO2013032709A3
公开(公告)日：2013-03-07
申请号：PCT/US2012/050916
申请日：2012-08-15
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , BASF SE , WEITZ, David, A. , SHUM, Ho, Cheung , ZHAO, Yuanjin , SUN, Bingjie , HOLTZE, Christian
发明人： WEITZ, David, A. , SHUM, Ho, Cheung , ZHAO, Yuanjin , SUN, Bingjie , HOLTZE, Christian
IPC分类号： B01J13/20 , A01N25/28 , A23P1/04 , A61K9/50 , C09B67/00 , C11D3/50 , C11D17/00
摘要： The present invention generally relates to particles, including particles for drug delivery and other applications. Certain aspects of the invention are generally directed to particles comprising a shell and an interior at least partially contained by the shell. In some embodiments, the particles may be treated to enhance the containment of the interior, for example to reduce transport of an agent into or out of the interior. Such particles may exhibit increased ability to encapsulate agents and/or increased storage life (e.g., due to reduced leakage). For instance, in certain embodiments, any defects, such as cracks, pores, etc. within the shell may be sealed or otherwise treated to reduce transport therethrough, for example, with a solid. In some embodiments, for instance, a first reactant in the interior of a particle may come into contact with a second reactant outside of the particle to form a solid, or other suitable product. The shell may also be treated, e.g., at a later point in time, to cause release of an agent contained within the interior, in certain aspects. For example, the shell may be heated to cause the release of the agent from the particle, or the shell may be exposed to chemical or enzymatic degradation, or a change in osmolarity, to cause release of an agent. Still other aspects of the present invention are generally directed to methods of making or using such particles, kits or devices including such particles, or the like.

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

WO2011146858A2 FOAMS, INCLUDING MICROCELLULAR FOAMS, CONTAINING COLLOIDAL PARTICULATES 审中-公开
标题翻译： FOAMS，包括微胶囊，含有胶体颗粒
公开(公告)号：WO2011146858A2
公开(公告)日：2011-11-24
申请号：PCT/US2011/037377
申请日：2011-05-20
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , BASF SE , LADAVAC, Kosta , GUERRA, Rodrigo, E. , KAZ, David , MANOHARAN, Vinothan , RIEGER, Jens, B. , KOLTZENBURG, Roland, Sebastian , WEITZ, David, A.
发明人： LADAVAC, Kosta , GUERRA, Rodrigo, E. , KAZ, David , MANOHARAN, Vinothan , RIEGER, Jens, B. , KOLTZENBURG, Roland, Sebastian , WEITZ, David, A.
IPC分类号： A61K9/12 , A61K9/14 , A61K9/51
CPC分类号： A61K9/122 , A61K9/143 , A61K9/146 , A61K9/5115
摘要： The present invention generally relates to foams and particles made from such foams, for applications such as drug delivery. The foams or particles may comprise a pharmaceutically acceptable polymeric carrier. In some cases, the foams may include colloidal particulates. A first aspect of the present invention is generally related to polymer-based foams or particles containing pharmaceutically active agents. In some cases, the foam or particle may contain smaller colloidal particulates therein. Such colloidal particulates may be used, for example, to limit the amount of material within certain regions of the foam, or exclude pharmaceutically active agents from being located within certain portions of the foam, which may useful for enhancing release of pharmaceutically active agents from the foam. In some cases, the colloidal particulates may cause the foam or particle to have an unexpectedly high specific surface area. The foam, in certain embodiments, can exhibit a relatively high loading of the pharmaceutically active agent. The foam may be microcellular in certain instances. The foam may also be created using a supercritical fluid, for example, supercritical C0 2 . For instance, a precursor to the foam, containing a pharmaceutically active agent, a pharmaceutically acceptable polymeric carrier, and colloidal particulates, can be mixed with a foaming agent. The pressure may then be decreased, thereby causing the foaming agent to expand and causing a foam to form. The foam may also be ground or milled, or otherwise processed, to form particles such as nanoparticles.
摘要翻译：本发明一般涉及由这种泡沫制成的泡沫和颗粒，用于诸如药物递送的应用。泡沫或颗粒可以包含药学上可接受的聚合物载体。在一些情况下，泡沫可以包括胶体颗粒。本发明的第一方面通常涉及基于聚合物的泡沫或含有药物活性剂的颗粒。在一些情况下，泡沫或颗粒中可含有较小的胶体颗粒。这种胶体颗粒可以用于例如限制泡沫的某些区域内的物质的量，或者不排除药物活性剂位于泡沫的某些部分内，其可用于增强药物活性剂从泡沫。在一些情况下，胶体颗粒可能导致泡沫或颗粒具有出乎意料的高比表面积。在某些实施方案中，泡沫体可以表现出相对高的药物活性剂的负载量。泡沫在某些情况下可能是微孔的。泡沫也可以使用超临界流体，例如超临界CO 2来产生。例如，含有药物活性剂，药学上可接受的聚合物载体和胶体颗粒的泡沫的前体可与发泡剂混合。然后可以降低压力，从而使发泡剂膨胀并形成泡沫。泡沫也可以研磨或研磨或以其它方式处理，以形成颗粒如纳米颗粒。

9. 发明申请

WO2011028764A2 MULTIPLE EMULSIONS CREATED USING JETTING AND OTHER TECHNIQUES 审中-公开
标题翻译：使用喷嘴和其他技术生产的多种乳液
公开(公告)号：WO2011028764A2
公开(公告)日：2011-03-10
申请号：PCT/US2010/047467
申请日：2010-09-01
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , WEITZ, David, A. , THIELE, Julian, W.P. , ABATE, Adam, R.
发明人： WEITZ, David, A. , THIELE, Julian, W.P. , ABATE, Adam, R.
IPC分类号： B01F5/02 , B01F5/26 , B01F3/08 , B01F15/04
CPC分类号： B01F3/0807 , B01F13/0062 , B01F13/0084 , B01F2003/0838 , B01F2215/045 , B01F2215/0459 , Y10T137/0318 , Y10T137/85938
摘要： The present invention generally relates to emulsions, and more particularly, to multiple emulsions. In one aspect, multiple emulsions are formed by urging a fluid into a channel, e.g., by causing the fluid to enter the channel as a "jet." Side channels can be used to encapsulate the fluid with a surrounding fluid. In some cases, multiple fluids may flow through a channel collinearly before multiple emulsion droplets are formed. The fluidic channels may also, in certain embodiments, include varying degrees of hydrophilicity or hydrophobicity. As examples, the fluidic channel may be relatively hydrophilic upstream of an intersection (or other region within the channel) and relatively hydrophobic downstream of the intersection, or vice versa. In some cases, the average cross-sectional dimension may change, e.g., at an intersection. For instance, the average cross-sectional dimension may increase at the intersection. Surprisingly, a relatively small increase in dimension, in combination with a change in hydrophilicity of the fluidic channel, may delay droplet formation of a stream of collinearly-flowing multiple fluids under certain flow conditions; accordingly, the point at which multiple emulsion droplets are formed can be readily controlled within the fluidic channel. In some cases, the multiple droplet may be formed from the collinear flow of fluids at (or near) a single location within the fluidic channel. In addition, unexpectedly, systems such as those described herein may be used to encapsulate fluids in single or multiple emulsions that are difficult or impossible to encapsulate using other techniques, such as fluids with low surface tension, viscous fluids, or viscoelastic fluids. Other aspects of the invention are generally directed to methods of making and using such systems, kits involving such systems, emulsions created using such systems, or the like.
摘要翻译：本发明一般涉及乳液，更特别地涉及多种乳液。在一个方面，通过将流体推进通道形成多个乳液，例如通过使流体作为“射流”进入通道。侧通道可用于将流体与周围的流体包封。在一些情况下，多个流体可以在形成多个乳液液滴之前共线地流过通道。在某些实施方案中，流体通道也可以包括不同程度的亲水性或疏水性。作为示例，流体通道可以在交叉点（或通道内的其他区域）和交叉口的相对疏水的下游的上游相对亲水，或反之亦然。在一些情况下，平均横截面尺寸可以改变，例如在交叉点处。例如，平均横截面尺寸可能在交叉点处增加。令人惊奇的是，与流体通道的亲水性变化相结合的尺寸相对小的增加可能延迟在某些流动条件下共线流动的多种流体流的液滴形成; 因此，可以容易地在流体通道内控制形成多个乳液液滴的点。在一些情况下，多个液滴可以由流体通道内的（或接近）单个位置处的共流流动形成。此外，意想不到的是，诸如本文所述的那些系统可用于将流体封装在使用其它技术（例如具有低表面张力的流体，粘性流体或粘弹性流体）难以或不可能封装的单个或多个乳液中。本发明的其它方面通常涉及制造和使用这种系统的方法，涉及这种系统的试剂盒，使用这种系统产生的乳液等。

10. 发明申请

WO2010104604A1 METHOD FOR THE CONTROLLED CREATION OF EMULSIONS, INCLUDING MULTIPLE EMULSIONS 审中-公开
标题翻译：用于控制乳液的方法，包括多种乳剂
公开(公告)号：WO2010104604A1
公开(公告)日：2010-09-16
申请号：PCT/US2010/000763
申请日：2010-03-12
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , WEITZ, David, A. , ABATE, Adam, R.
发明人： WEITZ, David, A. , ABATE, Adam, R.
IPC分类号： B01F3/08
CPC分类号： B01F3/0807 , B01F13/0062
摘要： The present invention generally relates to systems and methods for creating emulsions, including multiple emulsions. In some cases, emulsions, including multiple emulsions, may be created through a "triggering" process, where a fluidic droplet or other entity is used to create one or more nestings of droplets containing the fluidic droplet or other entity. In such a manner, multiple emulsions may be formed in some cases, e.g., triple emulsions, quadruple emulsions, quintuple emulsions, etc. In certain embodiments, a first droplet (or other entity) is used to "plug" a channel; fluid pooling behind the droplet pushes the droplet through the channel to form the emulsion. This process may be repeated to create multiple emulsions in some cases. Other aspects of the present invention generally relate to systems for producing such emulsions, methods of using such emulsions, methods of promoting such emulsions, or the like.
摘要翻译：本发明一般涉及用于产生包括多重乳液的乳液的系统和方法。在一些情况下，可以通过“触发”过程产生包括多重乳液的乳液，其中使用流体液滴或其它实体来产生包含流体液滴或其他实体的一个或多个液滴嵌套。以这种方式，在一些情况下可以形成多种乳液，例如三重乳液，四重乳液，五元乳液等。在某些实施方案中，第一液滴（或其他实体）用于“堵塞”通道; 液滴后面的液体汇集通过通道推动液滴形成乳液。在某些情况下可重复该过程以产生多种乳液。本发明的其它方面通常涉及用于生产这种乳液的系统，使用这种乳液的方法，促进这种乳液的方法等。

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