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：US20020164816A1

公开(公告)日：2002-11-07

申请号：US10118461

申请日：2002-04-05

Applicant: California Institute of Technology

Inventor： Stephen R. Quake

IPC: G01N030/02

CPC classification number: G01N30/6095 ,  G01N30/38 ,  G01N30/44 ,  G01N2030/205 ,  G01N2030/565 ,  Y10T436/25 ,  Y10T436/25375 ,  Y10T436/255 ,  Y10T436/2575

Abstract: The present invention provides microfluidic chromatography devices for separating an analyte from a sample solution, and methods for producing and using the same. In particular, the present invention relates to microfluidic devices which comprise a microfabricated flow channel and a material delivery system for transporting a material through the flow channel. The flow channel comprises a chromatography column portion having a solid stationary phase which is capable of separating at least a portion of the analyte from the sample solution.

Abstract translation: 本发明提供了用于从样品溶液中分离分析物的微流体色谱装置及其制备和使用方法。 特别地，本发明涉及微流体装置，其包括微加料流动通道和用于输送材料通过流动通道的材料输送系统。 流动通道包括具有固体固定相的色谱柱部分，其能够将至少一部分分析物与样品溶液分离。

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.

公开(公告)号：US20040089816A1

公开(公告)日：2004-05-13

申请号：US10616896

申请日：2003-07-09

Applicant: California Institute of Technology

Inventor： Stephen R. Quake ,  Guillaume Lessard ,  Lawrence A. Wade ,  Jordan M. Gerton

IPC: G01N021/64

CPC classification number: G01Q60/20 ,  G01Q30/025 ,  G01Q30/04 ,  G01Q30/18 ,  G01Q40/00 ,  G01Q60/06 ,  G01Q70/12 ,  G02B21/16 ,  Y10S977/862

Abstract: Methods and systems for operating an apertureless microscope for observing one or more features to a molecular sensitivity on objects are described. More particularly, the method includes moving a tip of a probe coupled to a cantilever in a vicinity of a feature of a sample, which emits one or more photons at a detected rate relative to a background rate of the sample based upon the presence of the tip of the probe in the vicinity of the feature. The method modifies the detected rate of the feature of the sample, whereupon the modifying of the detected rate causes the feature of the sample to enhance relative to background rate of the feature.

Abstract translation: 描述了用于操作无孔显微镜以观察一个或多个特征以使物体上的分子灵敏度的方法和系统。 更具体地，该方法包括将耦合到悬臂的探针的尖端移动到样品特征附近，基于样品的存在以相对于样品的背景速率以检测的速率发射一个或多个光子 探头尖端附近的特征。 该方法修改检测到的样本特征的速率，因此修改检测到的速率导致样本的特征相对于特征的背景速率增强。

公开(公告)号：US20040027707A1

公开(公告)日：2004-02-12

申请号：US10465526

申请日：2003-06-18

Applicant: California Institute of Technology

Inventor： Olivier Legrand ,  Stephen R. Quake

IPC: G02B005/22

CPC classification number: B29D11/00394 ,  B29C33/50 ,  B29C39/02 ,  B29C39/021 ,  B29C39/36 ,  B29D11/00432 ,  G02B3/00 ,  G02B21/00 ,  Y10S359/90

Abstract: A microlens structure such as a solid immersion lens structure is a radiation transmissive pliant elastomer cast to a desired shape and smoothness. A method for construction of a solid immersion lens structure includes providing a mold defining a lens shaped cavity in which a solid immersion lens is cast, casting a translucent liquid elastomeric material into the lens cavity, permitting the elastomeric material to set to form the solid immersion lens portion and removing the solid immersion lens portion from the mold. A specific material for use as the solid immersion lens is a translucent silicone elastomer of a refractive index greater than nnull1.4, such as General Electric RTV 615.

公开(公告)号：US20030123155A1

公开(公告)日：2003-07-03

申请号：US10265291

申请日：2002-10-04

Applicant: California Institute of Technology

Inventor： Stephen R. Quake ,  Yann Gambin

IPC: G02B003/00 ,  G02B009/00

CPC classification number: B29D11/00394 ,  B01L3/502707 ,  B01L3/502715 ,  B01L2300/0654 ,  B01L2300/0816 ,  B01L2300/0887 ,  B29D11/00365 ,  G02B21/02 ,  G11B7/1374 ,  Y10S425/808

Abstract: Microfabricated lenses, e.g., solid immersion lens (SIL) structures, are provided along with techniques for constructing these lens structures, as well as selected applications of such lens structures.

Abstract translation: 提供微型镜片，例如固体浸没透镜（SIL）结构，以及用于构造这些透镜结构的技术以及这种透镜结构的选择应用。

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：US20020109114A1

公开(公告)日：2002-08-15

申请号：US10045132

申请日：2001-10-23

Applicant: California Institute of Technology

Inventor： B. Scott Driggs ,  Markus M. Enzelberger ,  Stephen R. Quake

IPC: F16K031/02 ,  C23F001/00

CPC classification number: F16K31/02 ,  B33Y80/00 ,  F15C5/00 ,  F16K99/0001 ,  F16K99/0011 ,  F16K99/0051 ,  F16K2099/0074 ,  F16K2099/0078 ,  F16K2099/008

Abstract: Valve structures formed in elastomer material are electrostatically actuated by applying voltage to a flexible, electrically conductive wire pattern. An actuation force generated between the patterned wire structure and an electrode result in closure of a flow channel formed in elastomer material underlying the wire. In one embodiment of a valve structure in accordance with the present invention, the wire structure is patterned by lithography and etching of a copper/polyimide laminate, with an underlying gold plate positioned on the opposite side of the flow channel serving as an electrode. In an alternative embodiment, a first wire structure is patterned by physically cutting out a first pattern of strips from an Aluminum/Mylar laminate sheet. A second patterned wire structure serving as the electrode is formed by the same method, and positioned on the opposite side of a control channel. Application of an actuation force between the first and second patterned strips closes the control channel and an associated flow channel underlying the control channel.

Abstract translation: 弹性体材料中形成的阀结构通过将电压施加到柔性导电的导线图案而被静电致动。 在图案化的线结构和电极之间产生的致动力导致在线下方的弹性体材料中形成的流动通道的封闭。 在根据本发明的阀结构的一个实施例中，通过光刻和铜/聚酰亚胺层压板的蚀刻来对线结构进行图案化，其中下面的金板位于用作电极的流动通道的相对侧上。 在替代实施例中，通过从铝/聚酯薄膜层压板物理切割第一图案条，对第一线结构图案化。 用作电极的第二图案化线结构通过相同的方法形成，并且位于控制通道的相对侧上。 在第一和第二图案化带之间的致动力的施加关闭控制通道和控制通道下方的相关联的流动通道。

公开(公告)号：US20030235924A1

公开(公告)日：2003-12-25

申请号：US10351294

申请日：2003-01-23

Applicant: California Institute of Technology ,  Office of Technology Transfer

Inventor： Mark L. Adams ,  Stephen R. Quake ,  Axel Scherer

IPC: G01N021/76

CPC classification number: G01N21/6454 ,  B01L3/502715 ,  B01L2300/0654

Abstract: Techniques for integrating optoelectronic system and microfluidic system. An apparatus for optical analysis includes a detector system and a microfluidic system on the detector system. The apparatus is free from any lens system between the microfluidic system and the detector system. Methods of making such an apparatus and using such an apparatus are also disclosed.

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。