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    • 1. 发明申请
    • FLUIDIC DROPLET COALESCENCE
    • 流体滴灌技术
    • WO2007089541A3
    • 2007-11-15
    • PCT/US2007002063
    • 2007-01-24
    • HARVARD COLLEGEAHN KEUNHOCHONG HENRYAGRESTI JEREMYWEITZ DAVID ALINK DARREN ROY
    • AHN KEUNHOCHONG HENRYAGRESTI JEREMYWEITZ DAVID ALINK DARREN ROY
    • B01F13/00B01J19/00
    • B01F13/0071B01F13/0076B01J19/0093B01J2219/00272B01J2219/00828B01J2219/00833B01J2219/00835B01J2219/00853B01J2219/00889B01J2219/0093B01L3/5027B01L3/502784B01L2200/0673B01L2300/0867B01L2400/0415B01L2400/0487
    • The present invention generally relates to methods for the control of fluidic species and, in particular, to the coalescence of fluidic droplets. In certain instances, the methods are microf luidic. In one aspect, the invention relates to methods for causing two or more fluidic droplets within a channel to coalescence. The fluidic droplets may be of unequal size in certain cases. In some embodiments, a first fluidic droplet (21) may be caused to move at a first velocity, and a second fluidic droplet (22) may be caused to move at a second velocity different from the first velocity, for instance, substantially greater than the first velocity. The droplets may then coalesce, for example, upon application of an electric field. In the absence of an electric field, in some cases, the droplets may be unable to coalesce. In some cases, two series of fluidic droplets may coalesce, one or both series being substantially uniform. For instance, one series of droplets may have a distribution of diameters such that no more than about 5% of the droplets have a diameter greater than about 10% of the average diameter. In certain cases, one or more series of droplets may each consist essentially of a substantially uniform number of entities of a species therein (i.e., molecules, cells, particles, etc.). The fluidic droplets may be coalesced to start a reaction, and/or to stop a reaction, in some cases. For instance, a reaction may be initiated when a species in a first droplet contacts a species in a second droplet after the droplets coalesce, or a first droplet may contain an ongoing reaction and a second droplet may contain a species that inhibits the reaction.
    • 本发明一般涉及用于控制流体物种的方法,尤其涉及流体液滴聚结的方法。 在某些情况下,该方法是微流感。 一方面,本发明涉及使通道内的两个或多个流体液滴聚结的方法。 在某些情况下,流体液滴的尺寸可能不相等。 在一些实施例中,可以使第一流体液滴(21)以第一速度移动,并且可以使第二流体液滴(22)以不同于第一速度的第二速度移动,例如基本上大于 第一速度。 例如,当施加电场时,液滴可以聚结。 在没有电场的情况下,在一些情况下,液滴可能不能聚结。 在一些情况下,两系列流体液滴可以聚结,一个或两个串联基本均匀。 例如,一系列液滴可以具有直径分布,使得不超过约5%的液滴具有大于平均直径的约10%的直径。 在某些情况下,一个或多个液滴系列可以各自基本上由基本上一致数量的物质实体(即分子,细胞,颗粒等)组成。 在某些情况下,流体液滴可能被聚结起始反应,和/或停止反应。 例如,当液滴聚结之后,当第一液滴中的物质接触第二液滴中的物质时,或者第一液滴可能含有正在进行的反应,并且第二液滴可以含有抑制反应的物质时,反应可以开始。
    • 8. 发明申请
    • ASSAYS AND OTHER REACTIONS INVOLVING DROPLETS
    • 测定和涉及滴剂的其他反应
    • WO2008109176A8
    • 2008-11-13
    • PCT/US2008003185
    • 2008-03-07
    • HARVARD COLLEGEAGRESTI JEREMYCHU LIANG-YINWEITZ DAVID AKIM JIN-WOONGROWAT AMYSOMMER MORTENDANTAS GAUTAMCHURCH GEORGE
    • AGRESTI JEREMYCHU LIANG-YINWEITZ DAVID AKIM JIN-WOONGROWAT AMYSOMMER MORTENDANTAS GAUTAMCHURCH GEORGE
    • C12Q1/68B01J13/00
    • C12Q1/6848B01F3/0807B01F3/0811B01F13/0062B01F13/0071B01F2215/0037B01J13/0052B01J13/0065C12P19/34C12Q1/6834C12Q1/686
    • 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.
    • 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。
    • 9. 发明申请
    • ASSAYS AND OTHER REACTIONS INVOLVING DROPLETS
    • 测量和其他涉及倾销的反应
    • WO2008109176A2
    • 2008-09-12
    • PCT/US2008003185
    • 2008-03-07
    • HARVARD COLLEGEAGRESTI JEREMYCHU LIANG-YINWEITZ DAVID AKIM JIN-WOONGROWAT AMYSOMMER MORTENDANTAS GUATAMCHURCH GEORGE
    • AGRESTI JEREMYCHU LIANG-YINWEITZ DAVID AKIM JIN-WOONGROWAT AMYSOMMER MORTENDANTAS GUATAMCHURCH GEORGE
    • C12Q1/6848B01F3/0807B01F3/0811B01F13/0062B01F13/0071B01F2215/0037B01J13/0052B01J13/0065C12P19/34C12Q1/6834C12Q1/686
    • 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.
    • 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。