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1. 发明申请

WO2010151776A2 FLUID INJECTION 审中-公开
标题翻译：流体注射
公开(公告)号：WO2010151776A2
公开(公告)日：2010-12-29
申请号：PCT/US2010/040006
申请日：2010-06-25
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , WEITZ, David, A. , ABATE, Adam, R. , HUNG, Tony , MARY, Pascaline
发明人： WEITZ, David, A. , ABATE, Adam, R. , HUNG, Tony , MARY, Pascaline
IPC分类号： G01N35/10 , B01J19/00 , B01F13/00 , B01F5/06 , B05C9/00
CPC分类号： B01F5/0471 , B01F13/0071 , B01F13/0076 , B01J19/0093 , B01J2219/00837 , B01J2219/00853 , B01J2219/00862 , B01J2219/00889 , B01L3/50273 , B01L3/502784 , B01L2300/0867 , B01L2400/0415 , F16K99/0042 , F16K99/0051 , G01N27/44791 , G01N2035/1034 , Y10T137/0391 , Y10T137/206
摘要： The present invention generally relates to systems and methods for the control of fluids and, in some cases, to systems and methods for flowing a fluid into and/or out of other fluids. As examples, fluid may be injected into a droplet contained within a fluidic channel, or a fluid may be injected into a fluidic channel to create a droplet. In some embodiments, electrodes may be used to apply an electric field to one or more fluidic channels, e.g., proximate an intersection of at least two fluidic channels. For instance, a first fluid may be urged into and/or out of a second fluid, facilitated by the electric field. The electric field, in some cases, may disrupt an interface between a first fluid and at least one other fluid. Properties such as the volume, flow rate, etc. of a first fluid being urged into and/or out of a second fluid can be controlled by controlling various properties of the fluid and/or a fluidic droplet, for example curvature of the fluidic droplet, and/or controlling the applied electric field.
摘要翻译：本发明一般涉及用于控制流体的系统和方法，并且在一些情况下涉及将流体流入和/或流出其它流体的系统和方法。作为示例，流体可以被注入到包含在流体通道内的液滴中，或者可以将流体注入到流体通道中以产生液滴。在一些实施例中，可以使用电极将电场施加到一个或多个流体通道，例如至少两个流体通道的相交处。例如，可以通过电场促进第一流体进入和/或流出第二流体。在一些情况下，电场可能破坏第一流体和至少一种其它流体之间的界面。可以通过控制流体和/或流体液滴的各种性质（例如流体液滴的曲率）来控制被推入和/或流出第二流体的第一流体的体积，流速等性质，和/或控制所施加的电场。

2. 发明申请

WO2009085215A1 SYSTEMS AND METHODS FOR NUCLEIC ACID SEQUENCING 审中-公开
标题翻译：核酸序列的系统和方法
公开(公告)号：WO2009085215A1
公开(公告)日：2009-07-09
申请号：PCT/US2008/013912
申请日：2008-12-19
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , WEITZ, David, A. , AGRESTI, Jeremy , WEINER, Michael, P. , ABATE, Adam, R. , HUNG, Tony
发明人： WEITZ, David, A. , AGRESTI, Jeremy , WEINER, Michael, P. , ABATE, Adam, R. , HUNG, Tony
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.
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（例如微流体液滴）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。

3. 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。

4. 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。

5. 发明申请

WO2012109138A1 SYSTEMS AND METHODS FOR SPLITTING DROPLETS 审中-公开
标题翻译：用于分割滴液的系统和方法
公开(公告)号：WO2012109138A1
公开(公告)日：2012-08-16
申请号：PCT/US2012/023961
申请日：2012-02-06
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： 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 2 2 , 2 3 , 2 4 , 2 5 , 2 6 , 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。

6. 发明申请

WO2011056546A1 DROPLET CREATION TECHNIQUES 审中-公开
标题翻译： DROPLET创建技术
公开(公告)号：WO2011056546A1
公开(公告)日：2011-05-12
申请号：PCT/US2010/054050
申请日：2010-10-26
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： B01L3/00 , B01F13/00
CPC分类号： B01L3/502761 , B01F3/0807 , B01F13/0062 , B01F13/0071 , B01L3/502784 , B01L2200/0636 , B01L2200/0652 , B01L2300/0681 , Y10T137/0318 , Y10T137/8593
摘要： The present invention is generally related to systems and methods for producing droplets. The droplets may contain varying species, e.g., for use as a library. In some cases, at least one droplet is used to create a plurality of droplets, using techniques such as flow-focusing techniques. In one set of embodiments, a plurality of droplets, containing varying species, can be divided to form a collection of droplets containing the various species therein. A collection of droplets, according to certain embodiments, may contain various subpopulations of droplets that all contain the same species therein. Such a collection of droplets may be used as a library in some cases, or may be used for other purposes.
摘要翻译：本发明通常涉及用于产生液滴的系统和方法。液滴可以包含不同的物种，例如用作文库。在一些情况下，使用诸如流动聚焦技术之类的技术，使用至少一个液滴来产生多个液滴。在一组实施例中，包含不同种类的多个液滴可以被分开以形成其中包含各种物质的液滴的集合。根据某些实施方案，液滴的集合可以包含各种各样的液滴亚组，其中都含有相同的物质。这种液滴的集合在某些情况下可以用作文库，也可以用于其他目的。

7. 发明申请

WO2012087350A3 SPRAY DRYING TECHNIQUES 审中-公开
公开(公告)号：WO2012087350A3
公开(公告)日：2012-06-28
申请号：PCT/US2011/001993
申请日：2011-12-20
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , BASF SE , ABATE, Adam, R. , THIELE, Julian, W.P. , WEITZ, David, A. , WINDBERGS, Maike , HOLTZE, Christian
发明人： ABATE, Adam, R. , THIELE, Julian, W.P. , WEITZ, David, A. , WINDBERGS, Maike , HOLTZE, Christian
IPC分类号： B01J2/04 , B05B7/04
摘要： The present invention generally relates to microfluidics, and to spray drying and other drying techniques. In some aspects, an article containing one or more channels or microfiuidic channels is used to mix one or more fluids prior to spray drying. The mixing may occur immediately before the fluids are expelled through a nozzle or other opening into a drying region of the spray dryer. In one set of embodiments, for example, a first fluid is exposed to a second fluid, then the fluids are exposed to air or other gases before being expelled through a nozzle. In certain instances, the first fluid may contain a dissolved species that may precipitate upon exposure to the second fluid; such precipitation may occur immediately before expulsion through a nozzle or other opening, thereby resulting in controlled precipitation as part of the spray drying process.

8. 发明申请

WO2011008233A1 METHODS AND APPARATUS FOR FLUORESCENCE SENSING EMPLOYING FRESNEL ZONE PLATES 审中-公开
标题翻译：使用FRESNEL区域板进行荧光感测的方法和装置
公开(公告)号：WO2011008233A1
公开(公告)日：2011-01-20
申请号：PCT/US2010/001372
申请日：2010-05-07
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , CROZIER, Kenneth, B. , WEITZ, David, A. , SCHONBRUN, Ethan , ABATE, Adam, R.
发明人： CROZIER, Kenneth, B. , WEITZ, David, A. , SCHONBRUN, Ethan , ABATE, Adam, R.
IPC分类号： A01N31/00
CPC分类号： G01N21/6458 , B01L3/502715 , B01L3/502784 , B01L2300/0654 , B01L2300/0877
摘要： Methods and apparatus for high-throughput fluorescence detection using integrated microfabricated optical element arrays are described. In one example, the optical element arrays may comprise one or more microfabricated Fresnel zone plates, which may be configured to collect light from samples flowing in microfluidic channels. Multiple samples may be inspected in parallel at significantly high rates (e.g., about 200,000 samples per second or higher). A relay lens combined with high numerical aperture integrated microfabricated optical elements provides significant signal enhancement (e.g., on the order of at least 200 times that of conventional fluorescence detection methods).
摘要翻译：描述了使用集成的微制造光学元件阵列进行高通量荧光检测的方法和装置。在一个示例中，光学元件阵列可以包括一个或多个微细加工的菲涅尔区域板，其可被配置为从在微流体通道中流动的样品收集光。可以以非常高的速率并行地检查多个样品（例如，每秒约20万个样品或更高）。与高数值孔径集成微制造光学元件结合的中继透镜提供显着的信号增强（例如，大约是常规荧光检测方法的200倍）。

9. 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。

10. 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。

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