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1. 发明申请

WO2010009463A2 DROPLET OPERATIONS DEVICE 审中-公开
标题翻译： DROPLET操作设备
公开(公告)号：WO2010009463A2
公开(公告)日：2010-01-21
申请号：PCT/US2009/051128
申请日：2009-07-20
申请人： ADVANCED LIQUID LOGIC, INC. , SRINIVASAN, Vijay , SUDARSAN, Arjun , PAMULA, Vamsee , POLLACK, Michael , SISTA, Ramakrishna , KOZIKOWSKI, Raymond , BELL, Nicole
发明人： SRINIVASAN, Vijay , SUDARSAN, Arjun , PAMULA, Vamsee , POLLACK, Michael , SISTA, Ramakrishna , KOZIKOWSKI, Raymond , BELL, Nicole
IPC分类号： G01N27/00 , G01N35/10 , B01J19/00 , B41J2/14 , B01L3/02
CPC分类号： G01N27/44756 , B01F13/0071 , B01F13/0076 , B01L3/502707 , B01L3/502792 , B01L2300/0816 , B01L2300/0819 , B01L2400/0427 , B01L2400/0688 , B01L2400/086 , B29C59/02 , B41J2/1601 , B81B7/0061 , B81B2201/058 , B81B2201/13 , F04B17/00 , F04B19/006
摘要： The invention provides droplet actuators with droplet operations surfaces for manipulating droplets, e.g., by conducting droplet operations. The droplet operations surfaces are typically exposed to a droplet operations gap. One or more regions of a droplet operation surface may include patterned topographic features. The invention also provides a droplet actuator in which one or both gap-facing droplet operations surfaces is formed using a removable film. The removable film may, in various embodiments, also include other components ordinarily associated with the droplet actuator substrate, such as the dielectric layer and the electrodes. Further, the invention provides droplet actuator devices and methods for coupling and/or sealing substrates of a droplet actuator, such as techniques for self-aligning assembly of droplet actuator substrates. The invention provides droplet actuators and methods of disassembling the droplet actuator in order to provide access for cleaning and/or recycling of droplet actuator surfaces.
摘要翻译：本发明提供液滴致动器，其具有用于操纵液滴的液滴操作表面，例如通过进行液滴操作。液滴操作表面通常暴露于液滴操作间隙。液滴操作表面的一个或多个区域可以包括图案化的地形特征。本发明还提供一种液滴致动器，其中使用可除去膜形成一个或两个面向间隙的液滴操作表面。在各种实施例中，可移除膜还可以包括通常与液滴致动器基底（例如介电层和电极）相关联的其它部件。此外，本发明提供了液滴致动器装置和用于联接和/或密封液滴致动器的基板的方法，例如用于液滴致动器基板的自对准组装的技术。本发明提供了液滴致动器和拆卸液滴致动器的方法，以提供用于清洁和/或再循环液滴致动器表面的通路。

2. 发明申请

WO2009140671A3 DROPLET ACTUATOR DEVICES AND METHODS FOR MANIPULATING BEADS 审中-公开
公开(公告)号：WO2009140671A3
公开(公告)日：2009-11-19
申请号：PCT/US2009/044305
申请日：2009-05-18
申请人： ADVANCED LIQUID LOGIC, INC. , SISTA, Ramakrishnan , PAMULA, Vamsee , SUDARSAN, Arjun , SRINIVASAN, Vijay , THWAR, Prasanna
发明人： SISTA, Ramakrishnan , PAMULA, Vamsee , SUDARSAN, Arjun , SRINIVASAN, Vijay , THWAR, Prasanna
IPC分类号： G01N33/543 , C12Q1/00 , C12Q1/68 , C12M1/34
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.

3. 发明申请

WO2008116221A1 BEAD SORTING ON A DROPLET ACTUATOR 审中-公开
标题翻译：珠子致动器上的珠子
公开(公告)号：WO2008116221A1
公开(公告)日：2008-09-25
申请号：PCT/US2008/058047
申请日：2008-03-24
申请人： ADVANCED LIQUID LOGIC, INC. , SHENDEROV, Alexander , PAMULA, Vamsee , ECKHARDT, Allen
发明人： SHENDEROV, Alexander , PAMULA, Vamsee , ECKHARDT, Allen
IPC分类号： C40B50/08
CPC分类号： G01N33/54366 , G01N33/54326 , G01N35/0098
摘要： A method of sorting beads on a droplet actuator. The method may, for example, include the following steps: (a) providing a droplet actuator comprising a substrate comprising electrodes arranged for conducting droplet operations on a substrate surface; (b) providing an assay droplet on the substrate surface, the droplet comprising two or more target-capture bead populations comprising target-capture beads comprising: (i) a capture probe bound to a target substance; and (ii) a unique bar binding element which binds to a corresponding binder; (c) using droplet operations to combine the assay droplet with a bead-capture droplet comprising one or more bead-capture beads having affinity for the binding element; (d) immobilizing the one or more bead-capture beads while conducting droplet operations to separate the bead-capture beads from unbound target-capture beads; (e) resuspending the one or more bead-capture beads in a droplet, thereby providing a droplet comprising a substantially pure substance-capture bead population; and (f) using droplet operations to conduct one or more protocol steps for an assay protocol.
摘要翻译：一种在液滴致动器上分选珠粒的方法。该方法可以例如包括以下步骤：（a）提供液滴致动器，其包括基板，该基板包括布置成用于在基板表面上进行液滴操作的电极; （b）在基底表面上提供测定液滴，所述液滴包含两个或更多个目标捕获珠群，包含目标捕获珠，其包含：（i）与靶物质结合的捕获探针; 和（ii）结合相应的粘合剂的独特的棒结合元件; （c）使用液滴操作将测定液滴与包含对结合元件具有亲和性的一个或多个珠粒捕获珠粒的珠粒捕获液滴组合; （d）固定所述一个或多个珠粒捕获珠粒，同时进行液滴操作以将珠粒捕获珠粒与未结合的靶捕获珠粒分离; （e）将一个或多个珠粒捕获珠重新悬浮在液滴中，由此提供包含基本上纯的物质捕获珠粒的液滴; 和（f）使用液滴操作为测定方案进行一个或多个方案步骤。

4. 发明申请

WO2010042637A2 BEAD INCUBATION AND WASHING ON A DROPLET ACTUATOR 审中-公开
标题翻译：珠滴培养和清洗滴落执行器
公开(公告)号：WO2010042637A2
公开(公告)日：2010-04-15
申请号：PCT/US2009/059868
申请日：2009-10-07
申请人： ADVANCED LIQUID LOGIC, INC. , SISTA, Ramakrishna , SUDARSAN, Arjun , PAMULA, Vamsee
发明人： SISTA, Ramakrishna , SUDARSAN, Arjun , PAMULA, Vamsee
IPC分类号： G01N33/543 , G01N27/00 , C12Q1/68
CPC分类号： G01N33/5308
摘要： The present invention relates to bead incubating and washing on a droplet actuator. Methods for incubating magnetically responsive beads that are labeled with primary antibody, a sample (i.e., analyte), and secondary reporter antibodies on a magnet, on and off a magnet, and completely off a magnet are provided. Also provided are methods for washing magnetically responsive beads using shape-assisted merging of droplets. Also provided are methods for shape-mediated splitting, transporting, and dispensing of a sample droplet that contains magnetically responsive beads. The apparatuses and methods of the invention provide for rapid time to result and optimum detection of an analyte in an immunoassay.
摘要翻译：本发明涉及在液滴致动器上的珠子孵育和洗涤。提供了用一级抗体，样品（即分析物）和二级报道抗体在磁体上，在磁体上和离开磁体并且完全离开磁体来标记磁响应珠的方法。还提供了使用形状辅助的液滴合并来洗涤磁响应珠的方法。还提供了用于形状介导的分裂，运输和分配含有磁性响应珠的样品液滴的方法。本发明的设备和方法提供了快速的结果和免疫测定中分析物的最佳检测。

5. 发明申请

WO2010006166A2 BEAD MANIPULATION TECHNIQUES 审中-公开
标题翻译：珠子操纵技术
公开(公告)号：WO2010006166A2
公开(公告)日：2010-01-14
申请号：PCT/US2009/050101
申请日：2009-07-09
申请人： ADVANCED LIQUID LOGIC, INC. , PAMULA, Vamsee , THWAR, Prasanna , SUDARSAN, Arjun , SISTA, Ramakrishna , SULLIVAN, Michael , NORTON, Scott
发明人： PAMULA, Vamsee , THWAR, Prasanna , SUDARSAN, Arjun , SISTA, Ramakrishna , SULLIVAN, Michael , NORTON, Scott
CPC分类号： B03C5/028 , B03C5/005
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。液滴操作在某些情况下可能是电极介导的。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靶分析物结合到磁响应珠。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。

6. 发明申请

WO2009137415A3 REAGENT AND SAMPLE PREPARATION, LOADING, AND STORAGE 审中-公开
公开(公告)号：WO2009137415A3
公开(公告)日：2009-11-12
申请号：PCT/US2009/042731
申请日：2009-05-04
申请人： ADVANCED LIQUID LOGIC, INC. , POLLACK, Michael , THWAR, Prasanna , PAMULA, Vamsee , SRINIVASAN, Vijay , ECKHARDT, Allen , SHENDEROV, Alexander , ALLEN, Dwayne
发明人： POLLACK, Michael , THWAR, Prasanna , PAMULA, Vamsee , SRINIVASAN, Vijay , ECKHARDT, Allen , SHENDEROV, Alexander , ALLEN, Dwayne
IPC分类号： G01N35/00 , G01N33/00 , G01N1/28 , G01N27/26
摘要： The invention provides droplet actuators and droplet actuator cassettes including reagent storage capabilities, as well as methods of making and using the droplet actuators and cassettes. The invention also provides continuous flow channel elements and techniques for using electrodes to manipulate droplets in flowing streams. The invention also discloses methods of separating compounds on a droplet actuator. Various other aspects of the invention are also disclosed.

7. 发明申请

WO2009052321A3 DROPLET ACTUATORS, SYSTEMS AND METHODS 审中-公开
公开(公告)号：WO2009052321A3
公开(公告)日：2009-04-23
申请号：PCT/US2008/080216
申请日：2008-10-16
申请人： ADVANCED LIQUID LOGIC, INC. , DUKE UNIVERSITY , POLLACK, Michael , PAMULA, Vamsee , SRINIVASAN, Vijay , CHAKRABARTY, Krishnendu , XU, Tao
发明人： POLLACK, Michael , PAMULA, Vamsee , SRINIVASAN, Vijay , CHAKRABARTY, Krishnendu , XU, Tao
IPC分类号： G01N27/26 , G01N33/53
摘要： A droplet actuator with arrays of electrodes electrically coupled to a number of controllable voltage sources that is less than the number of electrodes. A method of defining partitions for pin layouts in a droplet actuator for a specific assay, the method including: defining droplet traces for the assay; and defining a guard ring along the traces. Other methods, systems, droplet actuators, and algorithms are also provided.

8. 发明申请

WO2009052123A2 MULTIPLEXED DETECTION SCHEMES FOR A DROPLET ACTUATOR 审中-公开
标题翻译：一种液滴驱动器的复合检测方案
公开(公告)号：WO2009052123A2
公开(公告)日：2009-04-23
申请号：PCT/US2008/079899
申请日：2008-10-15
申请人： ADVANCED LIQUID LOGIC, INC. , SRINIVASAN, Vijay , PAMULA, Vamsee , SISTA, Ramakrishna , POLLACK, Michael
发明人： SRINIVASAN, Vijay , PAMULA, Vamsee , SISTA, Ramakrishna , POLLACK, Michael
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：具有被配置用于喷射在表面上传输液滴的液滴操作的电极的液滴实现器以及被布置为接近一个或多个电极的传感器，所述传感器在表面上建立检测窗口用于检测一个或多个在表面上的一个或多个液滴的性质，其中电极建立至少两条路径用于将液滴传输到检测窗口中。还提供了一种检测目标液滴的性质的方法，包括使用液滴操作来调制来自包括目标液滴的液滴集合的信号，检测液滴集合的调制信号，解调调制信号以识别由

9. 发明申请

WO2012068055A2 CAPACITANCE DETECTION IN A DROPLET ACTUATOR 审中-公开
标题翻译：电动执行器中的电容检测
公开(公告)号：WO2012068055A2
公开(公告)日：2012-05-24
申请号：PCT/US2011/060714
申请日：2011-11-15
申请人： ADVANCED LIQUID LOGIC, INC. , POLLACK, Michael , STURMER, Ryan , PAIK, Philip , PAMULA, Vamsee , SRINIVASAN, Vijay
发明人： POLLACK, Michael , STURMER, Ryan , PAIK, Philip , PAMULA, Vamsee , SRINIVASAN, Vijay
IPC分类号： G01R27/26
CPC分类号： G01N27/221 , B01L3/502784 , B01L3/502792 , B01L2200/14 , B01L2300/0645 , B01L2300/0816 , B01L2300/089 , B01L2400/0427 , B41J2/04541 , B41J2/04555 , B41J2/0458 , G01K7/34
摘要： The invention provides for a method of performing capacitance detection on a droplet actuator. A capacitor may be formed by the combination of a conductive droplet, an insulator layer, and one or more transport electrodes within a droplet actuator. At any given electrode, the capacitance measured is proportional to the footprint area of a droplet thereon. Capacitance detection methods of the invention herein may be used as a real-time verification tool in order to detect the absence, presence, and/or partial presence of a droplet at an electrode; analysis of droplet properties; measurement of droplet size or volume; optimization of the speed of droplet operations; and detection of air bubbles. The method may include applying a base oscillation frequency at the position and detecting a deviation from the base oscillation frequency.
摘要翻译：本发明提供了一种在液滴致动器上执行电容检测的方法。可以通过导电液滴，绝缘体层和液滴致动器内的一个或多个输送电极的组合来形成电容器。在任何给定的电极处，测量的电容与其上的液滴的占地面积成比例。本发明的电容检测方法可用作实时验证工具，以便检测液滴在电极处的不存在，存在和/或部分存在; 液滴性质分析; 液滴尺寸或体积的测量; 液滴操作速度的优化; 并检测气泡。该方法可以包括在该位置处施加基本振荡频率并检测与基本振荡频率的偏差。

10. 发明申请

WO2009140373A3 DROPLET ACTUATOR DEVICES, SYSTEMS, AND METHODS 审中-公开
公开(公告)号：WO2009140373A3
公开(公告)日：2009-11-19
申请号：PCT/US2009/043774
申请日：2009-05-13
申请人： ADVANCED LIQUID LOGIC, INC. , POLLACK, Michael , HUA, Zhishan , ECKHARDT, Allen , THWAR, Prasanna , SRINIVASAN, Vijay , PAMULA, Vamsee
发明人： POLLACK, Michael , HUA, Zhishan , ECKHARDT, Allen , THWAR, Prasanna , SRINIVASAN, Vijay , PAMULA, Vamsee
IPC分类号： G01N27/26 , C12Q1/68 , B41J2/01
摘要： The invention relates to certain novel approaches to reducing or eliminating the movement of contaminants from one droplet to another on a droplet actuator via liquid filler fluid. In one application, droplet actuators are used to conduct genetic analysis using polymerase chain reaction (PCR) techniques. The invention addresses the need for improved methods of performing PCR on a droplet actuator that provide for optimum amplification and detection of a sample target.

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