公开(公告)号：US20030061687A1

公开(公告)日：2003-04-03

申请号：US10117978

申请日：2002-04-05

Applicant: California Institute of Technology, A California Corporation

Inventor： Carl L. Hansen ,  Stephen R. Quake ,  James M. Berger

IPC: B01D009/02

CPC classification number: C30B7/08 ,  B01J2219/00274 ,  B01L3/06 ,  B01L3/502707 ,  B01L3/50273 ,  B01L3/502738 ,  B01L3/502761 ,  B01L7/54 ,  B01L9/527 ,  B01L2200/025 ,  B01L2200/027 ,  B01L2200/0605 ,  B01L2200/0642 ,  B01L2200/10 ,  B01L2300/0681 ,  B01L2300/0816 ,  B01L2300/0861 ,  B01L2300/0864 ,  B01L2300/0887 ,  B01L2300/123 ,  B01L2300/14 ,  B01L2300/18 ,  B01L2300/1827 ,  B01L2400/0481 ,  B01L2400/049 ,  B01L2400/0638 ,  B01L2400/0655 ,  B01L2400/0688 ,  C12Q1/6874 ,  C30B7/14 ,  F04B43/043 ,  F16K99/0001 ,  F16K99/0015 ,  F16K99/0026 ,  F16K99/0034 ,  F16K99/0059 ,  F16K2099/0074 ,  F16K2099/0078 ,  F16K2099/008 ,  F16K2099/0084 ,  F16K2099/0094 ,  Y10T117/1004 ,  Y10T117/1008 ,  Y10T137/0318 ,  Y10T137/0396 ,  C12Q2535/125

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 of a microfabricated fluidic device. The microfabricated fluidic device is then manipulated to vary the solution condition in the chambers, 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细加工的流体装置的多个室来实现的。 然后对微制造的流体装置进行操作以改变室中的溶液状态，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，通过捕获通过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：US20040115731A1

公开(公告)日：2004-06-17

申请号：US10637847

申请日：2003-08-07

Applicant: California Institute of Technology ,  The Regents of the University of California

Inventor： Carl L. Hansen ,  Morten Sommer ,  Stephen R. Quake

IPC: G01N033/53 ,  C12M001/34

CPC classification number: C30B29/54 ,  B01J19/0046 ,  B01J2219/00286 ,  B01J2219/00355 ,  B01J2219/00378 ,  B01J2219/00396 ,  B01J2219/00398 ,  B01J2219/00439 ,  B01J2219/005 ,  B01J2219/00527 ,  B01J2219/0059 ,  B01J2219/00605 ,  B01J2219/0061 ,  B01J2219/00612 ,  B01J2219/00659 ,  B01J2219/00704 ,  B01J2219/00707 ,  B01J2219/00722 ,  B01J2219/00725 ,  B01J2219/00756 ,  B01L3/06 ,  B01L3/5027 ,  B01L3/50273 ,  B01L3/502738 ,  B01L7/54 ,  B01L9/527 ,  B01L2200/025 ,  B01L2200/027 ,  B01L2200/0605 ,  B01L2200/0673 ,  B01L2200/10 ,  B01L2300/0681 ,  B01L2300/0861 ,  B01L2300/123 ,  B01L2300/14 ,  B01L2300/18 ,  B01L2400/0472 ,  B01L2400/0481 ,  B01L2400/0655 ,  B01L2400/0688 ,  C30B7/00 ,  C30B29/58 ,  C40B40/10 ,  F04B43/043 ,  F16K99/0001 ,  F16K99/0015 ,  F16K99/0028 ,  F16K99/0057 ,  F16K2099/0074 ,  F16K2099/0078 ,  F16K2099/008 ,  F16K2099/0094 ,  G01N2013/003

Abstract: The use of microfluidic structures enables high throughput screening of protein crystallization. In one embodiment, an integrated combinatoric mixing chip allows for precise metering of reagents to rapidly create a large number of potential crystallization conditions, with possible crystal formations observed on chip. In an alternative embodiment, the microfluidic structures may be utilized to explore phase space conditions of a particular protein crystallizing agent combination, thereby identifying promising conditions and allowing for subsequent focused attempts to obtain crystal growth.

Abstract translation: 使用微流体结构可实现蛋白质结晶的高通量筛选。 在一个实施方案中，集成的组合混合芯片允许精确计量试剂以快速产生大量潜在的结晶条件，并在芯片上观察到可能的晶体形成。 在替代实施方案中，微流体结构可用于探索特定蛋白质结晶剂组合的相空间条件，从而确定有希望的条件并允许随后的聚焦尝试以获得晶体生长。

公开(公告)号：US20030096310A1

公开(公告)日：2003-05-22

申请号：US10265473

申请日：2002-10-04

Applicant: California Institute of Technology

Inventor： Carl L. Hansen ,  Stephen R. Quake ,  James M. Berger

IPC: G01N033/536

CPC classification number: C30B7/14 ,  B01F5/00 ,  B01F13/0093 ,  B01J2219/00355 ,  B01J2219/00378 ,  B01J2219/00396 ,  B01J2219/00398 ,  B01J2219/00439 ,  B01J2219/005 ,  B01J2219/00527 ,  B01J2219/00605 ,  B01J2219/0061 ,  B01J2219/00612 ,  B01J2219/00619 ,  B01J2219/00621 ,  B01J2219/00635 ,  B01J2219/00637 ,  B01J2219/00659 ,  B01J2219/00707 ,  B01J2219/00722 ,  B01J2219/00725 ,  B01L3/502738 ,  B01L3/502746 ,  B01L3/502769 ,  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 ,  B81B1/00 ,  C30B29/02 ,  F04B43/043 ,  F16K99/0001 ,  F16K99/0015 ,  F16K99/0017 ,  F16K99/0059 ,  F16K2099/0074 ,  F16K2099/0078 ,  F16K2099/008 ,  F16K2099/0084 ,  F16K2099/0086 ,  Y10T117/1004 ,  Y10T117/1008 ,  Y10T117/1012 ,  Y10T137/0318 ,  Y10T137/0324 ,  Y10T137/2224 ,  Y10T436/25

Abstract: A static fluid and a second fluid are placed into contact along a microfluidic free interface and allowed to mix by diffusion without convective flow across the interface. In accordance with one embodiment of the present invention, the fluids are static and initially positioned on either side of a closed valve structure in a microfluidic channel having a width that is tightly constrained in at least one dimension. The valve is then opened, and no-slip layers at the sides of the microfluidic channel suppress convective mixing between the two fluids along the resulting interface. Applications for microfluidic free interfaces in accordance with embodiments of the present invention include, but are not limited to, protein crystallization studies, protein solubility studies, determination of properties of fluidics systems, and a variety of biological assays such as diffusive immunoassays, substrate turnover assays, and competitive binding assays.

Abstract translation: 将静态流体和第二流体沿微流体界面放置接触，并允许通过扩散混合而不对流流过该界面。 根据本发明的一个实施例，流体是静态的，并且最初位于微流体通道中的封闭阀结构的任一侧上，该微流体通道的宽度被紧紧地约束在至少一个维度上。 然后打开阀门，并且微流体通道两侧的防滑层抑制沿着所得界面的两种流体之间的对流混合。 根据本发明的实施方案的用于微流体自由界面的应用包括但不限于蛋白质结晶研究，蛋白质溶解度研究，流体系统的性质的确定以及各种生物测定如扩散免疫测定，底物转换测定 和竞争性结合测定。

公开(公告)号：US20030008308A1

公开(公告)日：2003-01-09

申请号：US10118466

申请日：2002-04-05

Applicant: California Institute of Technology

Inventor： Markus M. Enzelberger ,  Carl L. Hansen ,  Jian Liu ,  Stephen R. Quake ,  Chiem Ma

IPC: C12Q001/68 ,  G01N033/53 ,  G01N033/542 ,  C12M001/34

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：US20020144738A1

公开(公告)日：2002-10-10

申请号：US09997205

申请日：2001-11-28

Applicant: California Institute of Technology

Inventor： Marc A. Unger ,  Hou-Pu Chou ,  Todd A. Thorsen ,  Axel Scherer ,  Stephen R. Quake ,  Jian Liu ,  Mark L. Adams ,  Carl L. Hansen

IPC: F15C001/20

CPC classification number: B29C39/02 ,  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 ,  B01L2400/0655 ,  B01L2400/0688 ,  B32B2037/1081 ,  B81B2201/036 ,  B81B2201/054 ,  B81C1/00119 ,  B81C2201/019 ,  C12Q1/6874 ,  F04B43/043 ,  F15C5/00 ,  F16K31/126 ,  F16K99/0001 ,  F16K99/0015 ,  F16K99/0026 ,  F16K99/0046 ,  F16K99/0051 ,  F16K99/0055 ,  F16K99/0059 ,  F16K2099/0074 ,  F16K2099/0076 ,  F16K2099/0078 ,  F16K2099/008 ,  F16K2099/0094 ,  Y10T137/2174 ,  Y10T137/2224 ,  Y10T137/7879 ,  Y10T137/87877 ,  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.