公开(公告)号：WO02081729A3

公开(公告)日：2002-12-05

申请号：PCT/US0210815

申请日：2002-04-05

Applicant: CALIFORNIA INST OF TECHN ,  ENZELBERGER MARKUS M ,  HANSEN CARL L ,  LIU JIAN ,  QUAKE STEPHEN R ,  MA CHIEM

Inventor： ENZELBERGER MARKUS M ,  HANSEN CARL L ,  LIU JIAN ,  QUAKE STEPHEN R ,  MA CHIEM

IPC: B01F5/10 ,  B01F13/00 ,  B01F15/06 ,  B01L3/00 ,  B01L7/00 ,  C12Q1/68 ,  F16K17/00 ,  B01J19/00 ,  C07K1/04 ,  C07K17/06 ,  C07K17/14 ,  C12M1/00 ,  C12P19/34 ,  C23C16/00 ,  F04B17/00 ,  F04B19/24 ,  F27B5/14 ,  F28D21/00 ,  G01N21/01 ,  G01N27/26 ,  G01N27/447

CPC classification number: C12Q1/68 ,  B01F5/102 ,  B01F5/108 ,  B01F13/0059 ,  B01F15/06 ,  B01L3/50273 ,  B01L3/502738 ,  B01L7/525 ,  B01L9/527 ,  B01L2300/0861 ,  B01L2300/088 ,  B01L2300/0883 ,  B01L2300/0887 ,  B01L2300/123 ,  B01L2300/1822 ,  B01L2300/1827 ,  B01L2300/1838 ,  B01L2400/0481 ,  B01L2400/0655 ,  C12Q1/6844 ,  C12Q3/00 ,  C12Q2565/629

Abstract: The present invention provides microfluidic devices and methods using the same in various types of thermal cycling reactions. Certaom devices include a rotary microfluidic channel and a plurality of temperature regions at different locations along the rotary microfluidic channel at which temperature is regulated. Solution can be repeatedly passed through the temperature regions such that the solution is exposed to different temperatures. Other microfluidic devices include an array of reaction chambers formed by intersecting vertical and horizontal flow channels, with the ability to regulate temperature at the reaction chambers. The microfluidic devices can be used to conduct a number of different analyses, including various primer extension reactions and nucleic acid amplification reactions.

Abstract translation: 本发明提供了在各种类型的热循环反应中使用该微流体装置和方法的微流体装置和方法。 Certaom设备包括旋转微流体通道和沿着旋转微流体通道的不同位置处的多个温度区域，在该温度区域调节温度。 溶液可以重复通过温度区域，使得溶液暴露于不同的温度。 其他微流体装置包括通过垂直和水平流动通道相交形成的反应室阵列，具有调节反应室温度的能力。 微流体装置可用于进行许多不同的分析，包括各种引物延伸反应和核酸扩增反应。

公开(公告)号：WO2005030925A2

公开(公告)日：2005-04-07

申请号：PCT/US2004019982

申请日：2004-06-21

Applicant: CALIFORNIA INST OF TECHN ,  LIU JIAN ,  HANSEN CARL L ,  QUAKE STEPHEN R

Inventor： LIU JIAN ,  HANSEN CARL L ,  QUAKE STEPHEN R

IPC: B01J19/00 ,  B01L3/00 ,  B01L7/00 ,  C12M1/36 ,  C12N20060101 ,  C12P19/34 ,  F04B43/04 ,  C12N

CPC classification number: B81B3/00 ,  B01J19/0093 ,  B01J2219/00783 ,  B01J2219/00828 ,  B01J2219/00833 ,  B01J2219/00891 ,  B01J2219/0095 ,  B01L3/5025 ,  B01L3/502707 ,  B01L3/502715 ,  B01L3/50273 ,  B01L3/502738 ,  B01L7/52 ,  B01L2200/10 ,  B01L2300/0816 ,  B01L2300/0819 ,  B01L2300/0861 ,  B01L2300/088 ,  B01L2300/123 ,  B01L2300/1827 ,  B01L2400/0481 ,  B01L2400/0655 ,  C12Q1/68 ,  F04B43/043 ,  G01N2035/00158

Abstract: A microfluidic device comprises a matrix of rotary flow reactors. The microfluidic matrix device offers a solution to the "world-to-chip" interface problem by accomplishing two important goals simultaneously: an economy of scale in reagent consumption is achieved, while simultaneously minimizing pipetting steps. N2 independent assays can be performed with only 2N+1 pipetting steps, using a single aliquot of enzyme amortized over all reactors. The chip reduces labor relative to conventional fluid handling techniques by using an order of magnitude less pipetting steps, and reduces cost by consuming two to three orders of magnitude less reagents per reaction. A PCR format has immediate applications in medical diagnosis and gene testing. Beyond PCR, the microfluidic matrix chip provides a universal and flexible platform for biological and chemical assays requiring parsimonious use of precious reagents and highly automated processing.

Abstract translation: 微流体装置包括旋转流动反应器的矩阵。 微流控矩阵设备通过同时完成两个重要目标提供了“全球到芯片”接口问题的解决方案：实现了试剂消耗的规模经济，同时最大限度地减少了移液步骤。 只需2N + 1的移液步骤就可以进行N2独立测定，使用在所有反应器中分摊的单等份酶。 该芯片相对于传统流体处理技术通过使用少量移液步骤减少了劳动力，并且通过每反应消耗2-3个数量级的试剂来降低成本。 PCR格式可直接用于医疗诊断和基因检测。 除了PCR之外，微流控芯片芯片还为生物和化学分析提供了一个通用且灵活的平台，需要简化使用贵重试剂和高度自动化处理。

公开(公告)号：WO2005069980A3

公开(公告)日：2005-09-29

申请号：PCT/US2005000211

申请日：2005-01-05

Applicant: CALIFORNIA INST OF TECHN ,  BALAGADDE FREDERICK ,  HANSEN CARL L ,  KARTALOV EMIL ,  QUAKE STEPHEN R

Inventor： BALAGADDE FREDERICK ,  HANSEN CARL L ,  KARTALOV EMIL ,  QUAKE STEPHEN R

IPC: B01L3/00 ,  C12M1/00 ,  C12M1/113 ,  C12M1/18 ,  C12M3/00 ,  C12P19/04 ,  C12P19/34 ,  C12Q1/02 ,  C12Q1/68

CPC classification number: C12P19/04 ,  B01L3/5027 ,  B01L3/502738 ,  B01L2300/0861 ,  B01L2300/0877 ,  B01L2300/10 ,  B01L2300/163 ,  B01L2400/0481 ,  B01L2400/0655 ,  C12M23/16 ,  C12M23/34 ,  C12M39/00 ,  C12P1/00

Abstract: A chemostat (Figure 1) that includes a growth chamber having a plurality of compartments, where each of the compartments may be fluidly isolated from the rest of the growth chamber by one or more actuatable valves. The chemostat may also include a nutrient supply-line to supply growth medium to the growth chamber (s), and an output port to remove fluids from the growth chamber. Also, presented is a method to prevent biofilm formation in a growth chamber of the chemostat. The method may include the step of adding a lytic agent to an isolated portion of the growth chamber and re-uniting the isolated portion with the rest of the growth chamber.

Abstract translation: 一种恒温器（图1），其包括具有多个室的生长室，其中每个室可以通过一个或多个可致动阀与生长室的其余部分流体隔离。 恒化器还可以包括向生长室供应生长培养基的营养供应线以及从生长室去除流体的输出端口。 还提出了防止生长膜在恒化器生长室中形成的方法。 该方法可以包括将溶解剂添加到生长室的分离部分并将分离的部分与生长室的其余部分重新结合的步骤。

公开(公告)号：EP1711650A4

公开(公告)日：2011-03-30

申请号：EP04817978

申请日：2004-12-06

Applicant: CALIFORNIA INST OF TECHN ,  UNIV CALIFORNIA

Inventor： HANSEN CARL L ,  SOMMER MORTEN ,  QUAKE STEPHEN R ,  BERGER JAMES M

IPC: C30B35/00 ,  B01L3/00 ,  B29C33/40 ,  B81C1/00 ,  C12Q20060101 ,  C30B7/00 ,  C30B7/02 ,  C30B29/54

CPC classification number: C30B29/16 ,  B01F5/10 ,  B01F5/108 ,  B01F13/0059 ,  B01L3/06 ,  B01L3/50273 ,  B01L3/502738 ,  B01L3/502784 ,  B01L2200/0605 ,  B01L2300/0816 ,  B01L2300/0864 ,  B01L2300/0867 ,  B01L2300/088 ,  B01L2300/123 ,  B01L2400/0481 ,  B01L2400/0655 ,  C30B7/00 ,  C30B7/14 ,  C30B29/58

Abstract: The present invention relates to microfluidic devices and methods facilitating the growth and analysis of crystallized materials such as proteins. In accordance with one embodiment, a crystal growth architecture is separated by a permeable membrane from an adjacent well having a much larger volume. The well may be configured to contain a fluid having an identity and concentration similar to the solvent and crystallizing agent employed in crystal growth, with diffusion across the membrane stabilizing that process. Alternatively, the well may be configured to contain a fluid having an identity calculated to affect the crystallization process. In accordance with the still other embodiment, the well may be configured to contain a material such as a cryo-protectant, which is useful in protecting the crystalline material once formed.

Abstract translation: 本发明涉及促进结晶物质如蛋白质生长和分析的微流体装置和方法。 根据一个实施例，晶体生长结构由具有大得多体积的相邻阱的可渗透膜分离。 该孔可以被配置成包含具有与在晶体生长中使用的溶剂和结晶剂相似的同一性和浓度的流体，其中通过膜的扩散稳定了该过程。 或者，井可以被配置成包含具有计算以影响结晶过程的同一性的流体。 根据另外的实施例，井可以被配置为容纳诸如冷冻保护剂的材料，其可用于保护一旦形成的结晶材料。

公开(公告)号：WO2005056813A3

公开(公告)日：2006-08-10

申请号：PCT/US2004040864

申请日：2004-12-06

Applicant: CALIFORNIA INST OF TECHN ,  UNIV CALIFORNIA ,  HANSEN CARL L ,  SOMMER MORTEN ,  QUAKE STEPHEN R ,  BERGER JAMES M

Inventor： HANSEN CARL L ,  SOMMER MORTEN ,  QUAKE STEPHEN R ,  BERGER JAMES M

IPC: C30B35/00 ,  B29C33/40 ,  C12Q20060101 ,  C30B7/00 ,  C30B7/02 ,  C30B29/54

CPC classification number: C30B29/16 ,  B01F5/10 ,  B01F5/108 ,  B01F13/0059 ,  B01L3/06 ,  B01L3/50273 ,  B01L3/502738 ,  B01L3/502784 ,  B01L2200/0605 ,  B01L2300/0816 ,  B01L2300/0864 ,  B01L2300/0867 ,  B01L2300/088 ,  B01L2300/123 ,  B01L2400/0481 ,  B01L2400/0655 ,  C30B7/00 ,  C30B7/14 ,  C30B29/58

Abstract: The present invention relates to microfluidic devices and methods facilitating the growth and analysis of crystallized materials such as proteins. In accordance with one embodiment, a crystal growth architecture is separated by a permeable membrane from an adjacent well having a much larger volume. The well may be configured to contain a fluid having an identity and concentration similar to the solvent and crystallizing agent employed in crystal growth, with diffusion across the membrane stabilizing that process. Alternatively, the well may be configured to contain a fluid having an identity calculated to affect the crystallization process. In accordance with the still other embodiment, the well may be configured to contain a material such as a cryo-protectant, which is useful in protecting the crystalline material once formed.

Abstract translation: 本发明涉及促进结晶物质如蛋白质生长和分析的微流体装置和方法。 根据一个实施例，晶体生长结构由具有大得多体积的相邻阱的可渗透膜分离。 该孔可以被配置成包含具有与晶体生长中使用的溶剂和结晶剂相似的特性和浓度的流体，并且通过膜的扩散稳定了该过程。 或者，孔可以被配置为包含具有计算以影响结晶过程的同一性的流体。 根据另外的实施例，井可以被配置为容纳诸如冷冻保护剂的材料，其可用于一旦形成时保护结晶材料。

公开(公告)号：WO2005030925A9

公开(公告)日：2005-08-25

申请号：PCT/US2004019982

申请日：2004-06-21

Applicant: CALIFORNIA INST OF TECHN ,  LIU JIAN ,  HANSEN CARL L ,  QUAKE STEPHEN R

Inventor： LIU JIAN ,  HANSEN CARL L ,  QUAKE STEPHEN R

IPC: B01L3/02 ,  B01J19/00 ,  B01L3/00 ,  B01L7/00 ,  B32B27/04 ,  C07H21/00 ,  C12M1/36 ,  C12N20060101 ,  C12P19/34 ,  C12Q1/68 ,  F04B43/04 ,  G01N15/06 ,  C12N

CPC classification number: B81B3/00 ,  B01J19/0093 ,  B01J2219/00783 ,  B01J2219/00828 ,  B01J2219/00833 ,  B01J2219/00891 ,  B01J2219/0095 ,  B01L3/5025 ,  B01L3/502707 ,  B01L3/502715 ,  B01L3/50273 ,  B01L3/502738 ,  B01L7/52 ,  B01L2200/10 ,  B01L2300/0816 ,  B01L2300/0819 ,  B01L2300/0861 ,  B01L2300/088 ,  B01L2300/123 ,  B01L2300/1827 ,  B01L2400/0481 ,  B01L2400/0655 ,  C12Q1/68 ,  F04B43/043 ,  G01N2035/00158

Abstract: A microfluidic device comprises a matrix of rotary flow reactors. The microfluidic matrix device offers a solution to the "world-to-chip" interface problem by accomplishing two important goals simultaneously: an economy of scale in reagent consumption is achieved, while simultaneously minimizing pipetting steps. N2 independent assays can be performed with only 2N+1 pipetting steps, using a single aliquot of enzyme amortized over all reactors. The chip reduces labor relative to conventional fluid handling techniques by using an order of magnitude less pipetting steps, and reduces cost by consuming two to three orders of magnitude less reagents per reaction. A PCR format has immediate applications in medical diagnosis and gene testing. Beyond PCR, the microfluidic matrix chip provides a universal and flexible platform for biological and chemical assays requiring parsimonious use of precious reagents and highly automated processing.

Abstract translation: 微流体装置包括旋转流反应器的基质。 微流体矩阵器件通过同时实现两个重要目标来提供“世界到芯片”接口问题的解决方案：实现了试剂消耗的规模经济，同时最大限度地减少了移液步骤。 可以使用仅在2N + 1移液步骤进行N2独立测定，使用在所有反应器中摊销的单一等分试样。 该芯片相对于常规流体处理技术通过使用少量的移液步骤来减少劳动，并且通过每次反应消耗两到三个数量级的试剂来降低成本。 PCR格式可以在医学诊断和基因检测中立即应用。 除了PCR之外，微流体芯片芯片为生物和化学测定提供了通用和灵活的平台，需要简约地使用贵重的试剂和高度自动化的处理。

公开(公告)号：EP1743019A4

公开(公告)日：2009-09-23

申请号：EP05722383

申请日：2005-01-05

Applicant: CALIFORNIA INST OF TECHN

Inventor： BALAGADDE FREDERICK ,  HANSEN CARL L ,  KARTALOV EMIL ,  QUAKE STEPHEN R

IPC: C12M3/00 ,  B01J19/00 ,  B01L3/00 ,  C12M1/00 ,  C12M1/113 ,  C12M1/18 ,  C12P19/04 ,  C12P19/34 ,  C12Q1/02 ,  C12Q1/68

CPC classification number: C12P19/04 ,  B01L3/5027 ,  B01L3/502738 ,  B01L2300/0861 ,  B01L2300/0877 ,  B01L2300/10 ,  B01L2300/163 ,  B01L2400/0481 ,  B01L2400/0655 ,  C12M23/16 ,  C12M23/34 ,  C12M39/00 ,  C12P1/00

公开(公告)号：EP1392484A4

公开(公告)日：2004-07-28

申请号：EP02763974

申请日：2002-04-05

Applicant: CALIFORNIA INST OF TECHN

Inventor： HANSEN CARL L ,  QUAKE STEPHEN R ,  BERGER JAMES M

IPC: C30B29/54 ,  B01L3/00 ,  B01L7/00 ,  B01L9/00 ,  B81B3/00 ,  B81C1/00 ,  C30B7/00 ,  B81B1/00 ,  C30B29/58

CPC classification number: B01L3/502738 ,  B01J2219/00274 ,  B01L3/06 ,  B01L7/54 ,  B01L9/527 ,  B01L2200/025 ,  B01L2200/027 ,  B01L2200/0605 ,  B01L2200/10 ,  B01L2300/0681 ,  B01L2300/0861 ,  B01L2300/123 ,  B01L2300/14 ,  B01L2300/18 ,  B01L2400/0481 ,  B01L2400/0655 ,  B01L2400/0688 ,  C30B7/00

Abstract: High throughput screening of crystallization of a target material is accomplished by simultaneously introducing a solution of the target material into a plurality of chambers (9102a, 9102b) of a microfabricated fluidic device. The microfabricated fluidic device is then manipulated to vary the solution condition in the chambers (9102a, 9102b), thereby simultaneously providing a large number of crystallization environments. Control over changed solution conditions may result from a variety of techniques, including but not limited to metering volumes of crystallizing agent into the chamber by volume exclusion, by entrapment of volumes of crystallizing agent determined by the dimensions of the microfabricated structure, or by cross-channel injection of sample and crystallizing agent into an array of junctions defined by intersecting orthogonal flow channels.

Abstract translation: 目标材料的结晶的高通量筛选通过将目标材料的溶液同时引入微制造的流体装置的多个腔室（9102a，9102b）中来完成。 然后操纵微制造的流体装置以改变腔室（9102a，9102b）中的溶液状态，从而同时提供大量的结晶环境。 对改变后的溶液条件的控制可由多种技术产生，包括但不限于通过体积排阻计量进入室的结晶剂体积，通过截留由微制造结构的尺寸确定的结晶剂体积， 将样品和结晶剂通道注入由相交的正交流动通道限定的结的阵列中。

公开(公告)号：WO02082047A8

公开(公告)日：2004-08-19

申请号：PCT/US0210875

申请日：2002-04-05

Applicant: CALIFORNIA INST OF TECHN ,  UNIV CALIFORNIA

Inventor： HANSEN CARL L ,  QUAKE STEPHEN R ,  BERGER JAMES M

IPC: C30B29/54 ,  B01L3/00 ,  B01L7/00 ,  B01L9/00 ,  B81B3/00 ,  B81C1/00 ,  C30B7/00 ,  B29C39/00 ,  B29C45/00 ,  C30B35/00

CPC classification number: B01L3/502738 ,  B01J2219/00274 ,  B01L3/06 ,  B01L7/54 ,  B01L9/527 ,  B01L2200/025 ,  B01L2200/027 ,  B01L2200/0605 ,  B01L2200/10 ,  B01L2300/0681 ,  B01L2300/0861 ,  B01L2300/123 ,  B01L2300/14 ,  B01L2300/18 ,  B01L2400/0481 ,  B01L2400/0655 ,  B01L2400/0688 ,  C30B7/00

Abstract: High throughput screening of crystallization of a target material is accomplished by simultaneously introducing a solution of the target material into a plurality of chambers (9102a, 9102b) of a microfabricated fluidic device. The microfabricated fluidic device is then manipulated to vary the solution condition in the chambers (9102a, 9102b), thereby simultaneously providing a large number of crystallization environments. Control over changed solution conditions may result from a variety of techniques, including but not limited to metering volumes of crystallizing agent into the chamber by volume exclusion, by entrapment of volumes of crystallizing agent determined by the dimensions of the microfabricated structure, or by cross-channel injection of sample and crystallizing agent into an array of junctions defined by intersecting orthogonal flow channels.

Abstract translation: 目标材料的结晶化的高通量筛选是通过将目标材料的溶液同时引入微制造流体装置的多个腔室（9102a，9102b）中来实现的。 然后操纵微制造的流体装置以改变腔室（9102a，9102b）中的溶液状态，从而同时提供大量的结晶环境。 改变的溶液条件的控制可以由各种技术产生，包括但不限于通过体积排阻将结晶剂计量到室中的体积，通过捕获由微结构结构的尺寸确定的结晶剂的体积， 将样品和结晶剂通道注入由相交的正交流动通道限定的连接阵列。

公开(公告)号：WO0243615A3

公开(公告)日：2003-03-13

申请号：PCT/US0144549

申请日：2001-11-28

Applicant: CALIFORNIA INST OF TECHN

Inventor： UNGER MARC A ,  CHOU HOU-PU ,  THORSEN TODD A ,  SCHERER AXEL ,  QUAKE STEPHEN R ,  LIU JIAN ,  ADAMS MARK L ,  HANSEN CARL L

IPC: B01L3/00 ,  B01L7/00 ,  B01L9/00 ,  B67D99/00 ,  B81B1/00 ,  B81B3/00 ,  B81C1/00 ,  C12Q1/68 ,  F04B43/04 ,  F15C5/00 ,  F16K7/00 ,  F16K31/126 ,  F16K99/00 ,  A61F2/00

CPC classification number: B05D3/04 ,  B01J2219/00355 ,  B01J2219/00378 ,  B01J2219/00396 ,  B01J2219/00398 ,  B01J2219/00439 ,  B01J2219/005 ,  B01J2219/00527 ,  B01J2219/00605 ,  B01J2219/00612 ,  B01J2219/00621 ,  B01J2219/00659 ,  B01J2219/00707 ,  B01J2219/00722 ,  B01J2219/00725 ,  B01L3/502707 ,  B01L3/50273 ,  B01L3/502738 ,  B01L7/54 ,  B01L9/527 ,  B01L2200/025 ,  B01L2200/027 ,  B01L2200/0605 ,  B01L2200/10 ,  B01L2300/0681 ,  B01L2300/0861 ,  B01L2300/0887 ,  B01L2300/123 ,  B01L2300/14 ,  B01L2300/18 ,  B01L2400/046 ,  B01L2400/0481 ,  B01L2400/06 ,  B01L2400/0655 ,  B01L2400/0688 ,  B32B2037/1081 ,  B65B31/00 ,  B81B2201/036 ,  B81B2201/054 ,  B81C1/00119 ,  B81C2201/019 ,  C12Q1/6832 ,  C12Q1/6874 ,  C30B29/54 ,  F04B43/043 ,  F15C1/06 ,  F15C3/00 ,  F15C5/00 ,  F16K99/0001 ,  F16K99/0015 ,  F16K99/0046 ,  F16K99/0051 ,  F16K99/0059 ,  F16K2099/0074 ,  F16K2099/0076 ,  F16K2099/0078 ,  F16K2099/008 ,  F16K2099/0084 ,  F16K2099/0094 ,  Y10T137/0324 ,  Y10T137/0379 ,  Y10T137/0424 ,  Y10T137/206 ,  Y10T137/2082 ,  Y10T137/2164 ,  Y10T137/2169 ,  Y10T137/2174 ,  Y10T137/2202 ,  Y10T137/2224 ,  Y10T137/3084 ,  Y10T137/7837 ,  Y10T137/86027 ,  Y10T156/10 ,  Y10T428/24479 ,  Y10T428/24612 ,  C12Q2535/125

Abstract: A method of fabricating an elastomeric structure, comprising: forming a first elastomeric layer on top of a first micromachined mold, the first micromachined mold having a first raised protrusion which forms a first recess extending along a bottom surface of the first elastomeric layer; forming a second elastomeric layer on top of a second micromachined mold, the second micromachined mold having a second raised protrusion which forms a second recess extending along a bottom surface of the second elastomeric layer; bonding the bottom surface of the second elastomeric layer onto a top surface of the first elastomeric layer such that a control channel forms in the second recess between the first and second elastomeric layers; and positioning the first elastomeric layer on top of a planar substrate such that a flow channel forms in the first recess between the first elastomeric layer and the planar substrate.

Abstract translation: 一种制造弹性体结构的方法，包括：在第一微加工模具的顶部上形成第一弹性体层，所述第一微加工模具具有形成沿所述第一弹性体层的底表面延伸的第一凹槽的第一凸起突起; 在第二微加工模具的顶部上形成第二弹性体层，所述第二微加工模具具有第二凸起突起，所述第二凸起突起形成沿所述第二弹性体层的底表面延伸的第二凹槽; 将第二弹性体层的底表面粘合到第一弹性体层的顶表面上，使得控制通道在第一和第二弹性体层之间的第二凹部中形成; 以及将第一弹性体层定位在平面基底的顶部上，使得流动通道在第一弹性体层和平面基底之间的第一凹部中形成。