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公开(公告)号：US08927296B2
公开(公告)日：2015-01-06
申请号：US12992939
申请日：2009-05-18
CPC分类号： B01L3/502792 , B01L3/502761 , B01L2200/0673 , B01L2300/0816 , B01L2300/0819 , B01L2300/0829 , B01L2300/089 , B01L2400/0406 , B01L2400/0415 , B01L2400/0427 , B01L2400/043 , B01L2400/0487 , G01N1/4077 , G01N35/0098 , G01N2035/00564 , Y10T436/25
摘要： The invention provides droplet actuators and droplet actuator techniques. Among other things, the droplet actuators and methods are useful for manipulating beads on a droplet actuator, such as conducting droplet operations using bead-containing droplets on a droplet actuator. For example, beads may be manipulated on a droplet actuator in the context of executing a sample preparation protocol and/or an assay protocol. An output of the methods of the invention may be beads prepared for execution of an assay protocol. Another output of the methods of the invention may be results of an assay protocol executed using beads. Among the methods described herein are methods of concentrating beads in droplets, methods of washing beads, methods of suspending beads, methods of separating beads, methods of localizing beads within a droplet, methods of forming emulsions in which droplets include beads, methods of loading beads into a droplet operations gap of a droplet actuator, methods of organizing beads in a monolayer, and methods of capturing, trapping or restraining beads.
摘要翻译： 本发明提供了液滴致动器和液滴致动器技术。 除其他之外，液滴致动器和方法可用于操纵液滴致动器上的珠，例如使用液滴致动器上的含珠液滴进行液滴操作。 例如，在执行样品制备方案和/或测定方案的上下文中，珠可以在液滴致动器上操作。 本发明方法的输出可以是准备用于执行测定方案的珠粒。 本发明方法的另一个输出可以是使用珠子执行的测定方案的结果。 在本文描述的方法中，将珠粒集中在液滴中的方法，洗涤珠粒的方法，悬浮珠粒的方法，分离珠粒的方法，在液滴内定位珠粒的方法，形成液滴包括珠粒的乳液的方法，加载珠粒的方法 液滴致动器的液滴操作间隙，单层组织珠粒的方法，以及捕获，捕获或抑制珠粒的方法。
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公开(公告)号：US08809068B2
公开(公告)日：2014-08-19
申请号：US12761066
申请日：2010-04-15
IPC分类号： G01N15/06
CPC分类号： G01N33/54326 , B01F11/0071 , B01F13/0071 , B01F13/0076 , B01F13/0809 , B01L3/50273 , B01L3/502761 , B01L3/502792 , B01L7/52 , B01L7/525 , B01L2200/027 , B01L2200/0647 , B01L2200/0673 , B01L2300/06 , B01L2300/0654 , B01L2300/0816 , B01L2300/0861 , B01L2300/0864 , B01L2300/0867 , B01L2300/089 , B01L2300/1827 , B01L2400/0406 , B01L2400/0415 , B01L2400/0421 , B01L2400/0424 , B01L2400/0427 , B01L2400/043 , B01L2400/0436 , B01L2400/0442 , G01N1/38 , G01N2001/386 , G01N2035/1046 , Y10T436/11 , Y10T436/25 , Y10T436/25625 , Y10T436/2575
摘要： The invention provides a method of dispersing or circulating magnetically responsive beads within a droplet in a droplet actuator. The invention, in one embodiment, makes use of a droplet actuator with a plurality of droplet operations electrodes configured to transport the droplet, and a magnetic field present at a portion of the plurality of droplet operations electrodes. A bead-containing droplet is provided on the droplet actuator in the presence of the uniform magnetic field. Beads are circulated in the droplet during incubation by conducting droplet operations on the droplet within a uniform region of the magnetic field wherein droplet operations do not allow magnetically responsive beads to be introduced into a region of the magnetic field which is sufficiently non-uniform to cause bead clumping resulting in a more homogenous distribution of the beads in the droplet. Other embodiments are also provided.
摘要翻译： 本发明提供了一种在液滴致动器中的液滴内分散或循环磁响应珠的方法。 在一个实施例中，本发明利用具有配置成传送液滴的多个液滴操作电极的液滴致动器和存在于多个液滴操作电极的一部分处的磁场。 在均匀磁场存在的情况下，在液滴致动器上提供含珠的液滴。 在孵育期间，通过在磁场的均匀区域内对液滴进行液滴操作，珠在液滴中循环，其中液滴操作不允许将磁响应的珠引入磁场的区域，该区域足够不均匀，从而导致 珠粒聚集，导致珠粒在液滴中更均匀的分布。 还提供了其他实施例。
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公开(公告)号：US20100279374A1
公开(公告)日：2010-11-04
申请号：US12761066
申请日：2010-04-15
CPC分类号： G01N33/54326 , B01F11/0071 , B01F13/0071 , B01F13/0076 , B01F13/0809 , B01L3/50273 , B01L3/502761 , B01L3/502792 , B01L7/52 , B01L7/525 , B01L2200/027 , B01L2200/0647 , B01L2200/0673 , B01L2300/06 , B01L2300/0654 , B01L2300/0816 , B01L2300/0861 , B01L2300/0864 , B01L2300/0867 , B01L2300/089 , B01L2300/1827 , B01L2400/0406 , B01L2400/0415 , B01L2400/0421 , B01L2400/0424 , B01L2400/0427 , B01L2400/043 , B01L2400/0436 , B01L2400/0442 , G01N1/38 , G01N2001/386 , G01N2035/1046 , Y10T436/11 , Y10T436/25 , Y10T436/25625 , Y10T436/2575
摘要： The invention provides a method of dispersing or circulating magnetically responsive beads within a droplet in a droplet actuator. The invention, in one embodiment, makes use of a droplet actuator with a plurality of droplet operations electrodes configured to transport the droplet, and a magnetic field present at a portion of the plurality of droplet operations electrodes. A bead-containing droplet is provided on the droplet actuator in the presence of the uniform magnetic field. Beads are circulated in the droplet during incubation by conducting droplet operations on the droplet within a uniform region of the magnetic field. Other embodiments are also provided.
摘要翻译： 本发明提供了一种在液滴致动器中的液滴内分散或循环磁响应珠的方法。 在一个实施例中，本发明利用具有配置成传送液滴的多个液滴操作电极的液滴致动器和存在于多个液滴操作电极的一部分处的磁场。 在均匀磁场存在的情况下，在液滴致动器上提供含珠的液滴。 在孵育期间，通过在磁场的均匀区域内的液滴上进行液滴操作，珠子在液滴中循环。 还提供了其他实施例。
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公开(公告)号：US20100068764A1
公开(公告)日：2010-03-18
申请号：US12524495
申请日：2008-02-11
申请人： Ramakrishna Sista , Vamsee K. Pamula , Michael G. Pollack , Vijay Srinivasan , Allen E. Eckhardt
发明人： Ramakrishna Sista , Vamsee K. Pamula , Michael G. Pollack , Vijay Srinivasan , Allen E. Eckhardt
CPC分类号： G01N33/54326 , B01L3/502715 , B01L3/50273 , B01L3/502761 , B01L3/502784 , B01L2200/025 , B01L2200/028 , B01L2200/0647 , B01L2200/0673 , B01L2200/141 , B01L2300/0816 , B01L2300/0864 , B01L2300/0867 , B01L2400/0427 , B01L2400/043 , C12M25/01 , C12M25/16 , G01N27/44717 , G01N27/44786 , G01N33/54386 , G01N35/0098 , G01N2035/1046
摘要： A method of providing a droplet in contact with a magnetically responsive bead and having a reduced quantity of a substance. The method generally includes the steps of (a) providing a droplet actuator (200) comprising: (i) a substrate (210) comprising electrodes (214) arranged for conducting droplet operations on a surface; (ii) a starting droplet (218/222) comprising: (1) one or more magnetically responsive beads (220); (2) a starting quantity of the substance; and (3) a starting volume; (b) magnetically immobilizing the one or more magnetically responsive beads at a location which is at a distance from a target droplet splitting zone, (224); (c) conducting one or more droplet operations comprising droplet dividing operations selected to divide the combined droplet to yield a set of droplets comprising: (i) a droplet (218) comprising substantially all of the one or more magnetically responsive beads and having a decreased quantity of the substance relative to the starting concentration; and (ii) a droplet (222) substantially lacking the magnetically responsive beads.
摘要翻译： 提供与磁响应珠接触并具有减少的物质量的液滴的方法。 该方法通常包括以下步骤：（a）提供液滴致动器（200），包括：（i）包括布置用于在表面上进行液滴操作的电极（214）的基底（210） （ii）起始液滴（218/222），包括：（1）一个或多个磁响应珠（220）; （2）物质的起始量; 和（3）起始体积; （b）将所述一个或多个磁响应珠磁性地固定在距离目标液滴分离区一段距离的位置处（224）; （c）进行一个或多个液滴操作，其包括液滴分割操作，所述液滴分割操作被选择以分割组合的液滴以产生一组液滴，其包括：（i）液滴（218），其基本上包含所有一个或多个磁响应珠粒， 物质的数量相对于起始浓度; 和（ii）基本上不含磁响应珠的液滴（222）。
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公开(公告)号：US09446404B2
公开(公告)日：2016-09-20
申请号：US14234855
申请日：2012-07-25
CPC分类号： B01L3/502715 , B01L3/502792 , B01L2200/025 , B01L2200/04 , B01L2300/0816 , B01L2300/089 , B01L2400/0427 , B01L2400/043 , B23P11/02 , Y10T29/49945
摘要： Droplet actuator apparatus and system are provided. An apparatus comprises: a microfluidics system having an insertion slot for insertion of a droplet actuator; a bottom plate against which the droplet actuator would slide when inserting the droplet actuator into the insertion slot; and means for forcing a substrate in the droplet actuator parallel to the bottom plate, wherein warpage in the substrate is corrected.
摘要翻译： 提供液滴致动器装置和系统。 一种装置包括：具有用于插入液滴致动器的插入口的微流体系统; 当将液滴致动器插入插槽时液滴致动器将滑动的底板; 以及用于强制平行于底板的液滴致动器中的基板的装置，其中校正基板中的翘曲。
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公开(公告)号：US20100258441A1
公开(公告)日：2010-10-14
申请号：US12761147
申请日：2010-04-15
CPC分类号： B01F11/0071 , B01F13/0071 , B01F13/0076 , B01L3/502746 , B01L3/502761 , B01L3/502792 , B01L7/52 , B01L7/525 , B01L2200/027 , B01L2300/0654 , B01L2300/0816 , B01L2300/0861 , B01L2300/0864 , B01L2300/0867 , B01L2300/089 , B01L2300/1827 , B01L2400/0406 , B01L2400/0415 , B01L2400/0421 , B01L2400/0424 , B01L2400/0427 , B01L2400/043 , B01L2400/0436 , B01L2400/0442 , G01N35/0098 , G01N2035/1046 , Y10T436/11 , Y10T436/25 , Y10T436/25625 , Y10T436/2575
摘要： The invention provides a method of circulating magnetically responsive beads within a droplet in a droplet actuator. The invention also provides methods for splitting droplets. The invention, in one embodiment, makes use of a droplet actuator with top and bottom substrates, a plurality of magnetic fields respectively present proximate the top and bottom substrates, wherein at least one of the magnet fields is selectively alterable, and a plurality of droplet operations electrodes positioned along at least one of the top and bottom surfaces. A droplet is positioned between the top and bottom surfaces and at least one of the magnetic fields is selectively altered.
摘要翻译： 本发明提供了一种在液滴致动器中的液滴内循环磁响应珠的方法。 本发明还提供了分裂液滴的方法。 在一个实施例中，本发明利用具有顶部和底部基底的液滴致动器，分别存在于顶部和底部基底附近的多个磁场，其中至少一个磁场可选择性地改变，并且多个液滴 沿着顶表面和底表面中的至少一个定位的操作电极。 液滴位于顶表面和底表面之间，并且至少一个磁场被选择性地改变。
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公开(公告)号：US20100236928A1
公开(公告)日：2010-09-23
申请号：US12681848
申请日：2008-10-15
CPC分类号： B01L3/502792 , B01L3/502761 , B01L2200/0673 , B01L2300/0654 , B01L2300/0816 , B01L2300/0819 , B01L2300/0861 , B01L2300/0864 , B01L2300/0867 , B01L2300/087 , B01L2300/088 , B01L2300/089 , B01L2400/0424 , B01L2400/0427 , B01L2400/0448
摘要： A droplet actualor having electrodes configured for ejecting droplet operations transporting droplets on a surface, and a sensor arranged in proximity to one or more of the electrodes establishing a detection window on the surface for detection of one or more properties of one or more droplets on the surface, wherein the electrodes establish at least two pathways for transport of droplets into the detection window. Also provided is, A method of detecting a property of a target droplet, including using droplet operations to modulate signals from a droplet set comprising the target droplet, detecting the modulated signals of the droplet set, demodulating the modulated signals to identify the signal produced by one or more individual droplets of the set Related methods and alternative embodiments are also provided.
摘要翻译： 具有配置用于喷射在表面上输送液滴的液滴操作的电极的液滴实体，以及布置在一个或多个电极附近的传感器，其在表面上建立检测窗口，用于检测表面上的一个或多个液滴的一个或多个特性 表面，其中电极建立用于将液滴输送到检测窗中的至少两个路径。 还提供了一种检测目标液滴的属性的方法，包括使用液滴操作来调制来自包括目标液滴的液滴组的信号，检测液滴组的调制信号，解调调制信号以识别由 还提供了一组或多个组合的相关方法和替代实施例。
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公开(公告)号：US20140057363A9
公开(公告)日：2014-02-27
申请号：US12992939
申请日：2009-05-18
IPC分类号： G01N1/40
CPC分类号： B01L3/502792 , B01L3/502761 , B01L2200/0673 , B01L2300/0816 , B01L2300/0819 , B01L2300/0829 , B01L2300/089 , B01L2400/0406 , B01L2400/0415 , B01L2400/0427 , B01L2400/043 , B01L2400/0487 , G01N1/4077 , G01N35/0098 , G01N2035/00564 , Y10T436/25
摘要： The invention provides droplet actuators and droplet actuator techniques. Among other things, the droplet actuators and methods are useful for manipulating beads on a droplet actuator, such as conducting droplet operations using bead-containing droplets on a droplet actuator. For example, beads may be manipulated on a droplet actuator in the context of executing a sample preparation protocol and/or an assay protocol. An output of the methods of the invention may be beads prepared for execution of an assay protocol. Another output of the methods of the invention may be results of an assay protocol executed using beads. Among the methods described herein are methods of concentrating beads in droplets, methods of washing beads, methods of suspending beads, methods of separating beads, methods of localizing beads within a droplet, methods of forming emulsions in which droplets include beads, methods of loading beads into a droplet operations gap of a droplet actuator, methods of organizing beads in a monolayer, and methods of capturing, trapping or restraining beads.
摘要翻译： 本发明提供了液滴致动器和液滴致动器技术。 除其他之外，液滴致动器和方法可用于操纵液滴致动器上的珠，例如使用液滴致动器上的含珠液滴进行液滴操作。 例如，在执行样品制备方案和/或测定方案的上下文中，珠可以在液滴致动器上操作。 本发明方法的输出可以是准备用于执行测定方案的珠粒。 本发明方法的另一个输出可以是使用珠子执行的测定方案的结果。 在本文描述的方法中，将珠粒集中在液滴中的方法，洗涤珠粒的方法，悬浮珠粒的方法，分离珠粒的方法，在液滴内定位珠粒的方法，形成液滴包括珠粒的乳液的方法，加载珠粒的方法 液滴致动器的液滴操作间隙，单层组织珠粒的方法，以及捕获，捕获或抑制珠粒的方法。
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9.发明申请公开(公告)号：US20130233425A1
公开(公告)日：2013-09-12
申请号：US13866105
申请日：2013-04-19
IPC分类号： F16L55/00
CPC分类号： F16L55/00 , B01F13/0071 , B01F13/0076 , B01L3/502784 , B01L2200/143 , B01L2300/089 , B01L2300/161 , B01L2400/0427 , B01L2400/086 , Y10T137/206
摘要： The present invention is directed to modified droplet actuators, fluids and methods for enhancing and/or maintaining oil film stability in a droplet actuator. In an exemplary embodiment, the invention provides a droplet actuator with one or more substrates arranged to form a droplet operations gap comprising gap-facing surfaces; droplet operations electrodes configured to conduct droplet operations in the droplet operations gap; at least one barrier included on at least one of the substrate surfaces and having dimensions selected to: permit droplet transport from atop a first droplet operations electrode to a second droplet operations electrode when the second droplet operations electrode is activated; and prevent movement of a droplet from atop a first droplet operations electrode when the first and second droplet operations electrodes are inactive.
摘要翻译： 本发明涉及用于在液滴致动器中增强和/或维持油膜稳定性的改进的液滴致动器，流体和方法。 在示例性实施例中，本发明提供了具有一个或多个基板的液滴致动器，其被布置成形成包括间隙面的表面的液滴操作间隙; 液滴操作电极，被配置为在液滴操作间隙中进行液滴操作; 至少一个屏障包括在至少一个基板表面上，并且具有选定的尺寸：当第二液滴操作电极被激活时允许液滴从第一液滴操作电极顶部传输到第二液滴操作电极; 并且当第一和第二液滴操作电极不活动时，防止液滴从第一液滴操作电极的顶部移动。
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公开(公告)号：US20110114490A1
公开(公告)日：2011-05-19
申请号：US12985409
申请日：2011-01-06
IPC分类号： B01J8/08
CPC分类号： B01F11/0071 , B01F13/0071 , B01F13/0076 , B01L3/502715 , B01L3/502761 , B01L3/502784 , B01L3/502792 , B01L7/52 , B01L7/525 , B01L2200/027 , B01L2300/0654 , B01L2300/0816 , B01L2300/0861 , B01L2300/0864 , B01L2300/0867 , B01L2300/089 , B01L2300/1827 , B01L2400/0406 , B01L2400/0415 , B01L2400/0421 , B01L2400/0424 , B01L2400/0427 , B01L2400/043 , B01L2400/0436 , B01L2400/0442 , B03C1/01 , B03C1/288 , B03C2201/18 , G01N2035/1046
摘要： The invention provides a method of redistributing magnetically responsive beads in a droplet. The method may include providing a droplet including magnetically responsive beads. The droplet may be provided within a region of a magnetic field having sufficient strength to attract the magnetically responsive beads to an edge of the droplet or towards an edge of the droplet, or otherwise regionalize or aggregate beads within the droplet. The method may also include conducting on a droplet operations surface one or more droplet operations using the droplet without removing the magnetically responsive beads from the region of the magnetic field. The droplet operations may in some cases be electrode-mediated. The droplet operations may redistribute and/or circulate the magnetically responsive beads within the droplet. In some cases, the droplet may include a sample droplet may include a target analyte. The redistributing of the magnetically responsive beads may cause target analyte to bind to the magnetically responsive beads. In some cases, the droplet may include unbound substances in a wash buffer. The redistributing of the magnetically responsive beads causes unbound substances to be freed from interstices of an aggregated set or subset of the magnetically responsive beads.
摘要翻译： 本发明提供了一种在液滴中重新分布磁响应珠的方法。 该方法可以包括提供包括磁响应珠的液滴。 液滴可以设置在具有足够强度的磁场的区域内，以将磁响应珠吸引到液滴的边缘或朝向液滴的边缘，或以其他方式区分或聚集液滴内的珠粒。 该方法还可以包括在液滴操作表面上使用液滴进行一个或多个液滴操作，而不从磁场的区域移除磁响应珠。 在某些情况下，液滴操作可能是电极介导的。 液滴操作可以在液滴内重新分布和/或循环磁响应珠。 在一些情况下，液滴可以包括样品液滴可以包括靶分析物。 磁响应珠的重新分布可能导致目标分析物结合磁响应珠。 在一些情况下，液滴可以包括洗涤缓冲液中的未结合物质。 磁响应珠子的重新分布导致未结合物质从磁性响应珠粒的聚集或子集的空隙中释放出来。
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