公开(公告)号：US09643136B2

公开(公告)日：2017-05-09

申请号：US14262424

申请日：2014-04-25

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

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

IPC: C30B7/14 ,  B01F5/00 ,  B01L3/00 ,  B01L9/00 ,  F04B43/04 ,  F16K99/00 ,  B81B1/00 ,  B01F13/00 ,  B01L7/00

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.

公开(公告)号：US20170001195A1

公开(公告)日：2017-01-05

申请号：US15173262

申请日：2016-06-03

Applicant: California Institute of Technology

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

IPC: B01L3/00 ,  C12Q1/68 ,  F16K99/00

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。

公开(公告)号：US09205423B2

公开(公告)日：2015-12-08

申请号：US13776646

申请日：2013-02-25

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

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

IPC: C30B7/14 ,  B01L3/06 ,  B01L3/00 ,  B01L9/00 ,  C12Q1/68 ,  F04B43/04 ,  F16K99/00 ,  B01L7/00

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.

公开(公告)号：US10940473B2

公开(公告)日：2021-03-09

申请号：US16396137

申请日：2019-04-26

Applicant: California Institute of Technology

Inventor： Jong Wook Hong ,  Vincent Studer ,  W. French Anderson ,  Stephen R. Quake ,  Jared Leadbetter

IPC: C12Q1/68 ,  B01L3/00 ,  C12Q1/6806

Abstract: Nucleic acid from cells and viruses sampled from a variety of environments may purified and expressed utilizing microfluidic techniques. Individual or small groups of cells or viruses may be isolated in microfluidic chambers by dilution, sorting, and/or segmentation. The isolated cells or viruses may be lysed directly in the microfluidic chamber, and the resulting nucleic acid purified by exposure to affinity beads. Subsequent elution of the purified nucleic acid may be followed by ligation and cell transformation, all within the same microfluidic chip. Cell isolation, lysis, and nucleic acid purification may be performed utilizing a highly parallelized microfluidic architecture to construct gDNA and cDNA libraries.

公开(公告)号：US09932687B2

公开(公告)日：2018-04-03

申请号：US14880168

申请日：2015-10-09

Applicant: California Institute of Technology

Inventor： Carl L. Hansen ,  Stephen R. Quake

IPC: C30B7/08 ,  C30B7/14 ,  B01L3/00 ,  B01L9/00 ,  C12Q1/68 ,  F04B43/04 ,  F16K99/00 ,  B01L3/06 ,  B01L7/00

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.

公开(公告)号：US20170096713A1

公开(公告)日：2017-04-06

申请号：US15266787

申请日：2016-09-15

Applicant: California Institute of Technology ,  Fluidigm Corporation

Inventor： Stanley N. Lapidus ,  Stephen R. Quake

IPC: C12Q1/68

CPC classification number: C12Q1/6886 ,  C12Q1/6869 ,  C12Q2600/156

Abstract: The invention provides methods for determining the presence of a disease by comparing a sequence from a single target molecule with a predetermined sequence that is associated with a specific disease.

公开(公告)号：US20160339423A1

公开(公告)日：2016-11-24

申请号：US15078884

申请日：2016-03-23

Applicant: California Institute of Technology

Inventor： Stephen R. Quake ,  Hou-Pu Chou

IPC: B01L3/00

CPC classification number: B01L3/02 ,  B01F5/0646 ,  B01F5/0647 ,  B01F13/0072 ,  B01F13/0093 ,  B01F15/0201 ,  B01F15/024 ,  B01L3/5027 ,  B01L3/502707 ,  B01L3/50273 ,  B01L3/502738 ,  B01L3/502753 ,  B01L3/502761 ,  B01L2200/0647 ,  B01L2200/0689 ,  B01L2200/10 ,  B01L2300/0636 ,  B01L2300/0816 ,  B01L2300/0829 ,  B01L2300/0861 ,  B01L2300/0867 ,  B01L2300/088 ,  B01L2300/0887 ,  B01L2300/123 ,  B01L2400/0418 ,  B01L2400/043 ,  B01L2400/0481 ,  B01L2400/0638 ,  B01L2400/0655 ,  B01L2400/0694 ,  C12M1/02 ,  C12Q1/6816 ,  G01N33/53 ,  Y10T137/0318 ,  Y10T137/0329 ,  Y10T137/2218 ,  Y10T137/2224 ,  Y10T436/11 ,  Y10T436/145555 ,  Y10T436/173845 ,  Y10T436/2575 ,  C12Q2565/629

Abstract: The invention relates to a microfabricated device for the rapid detection of DNA, proteins or other molecules associated with a particular disease. The devices and methods of the invention can be used for the simultaneous diagnosis of multiple diseases by detecting molecules (e.g. amounts of molecules), such as polynucleotides (e.g., DNA) or proteins (e.g., antibodies), by measuring the signal of a detectable reporter associated with hybridized polynucleotides or antigen/antibody complex. In the microfabricated device according to the invention, detection of the presence of molecules (i.e., polynucleotides, proteins, or antigen/antibody complexes) are correlated to a hybridization signal from an optically-detectable (e.g. fluorescent) reporter associated with the bound molecules. These hybridization signals can be detected by any suitable means, for example optical, and can be stored for example in a computer as a representation of the presence of a particular gene. Hybridization probes can be immobilized on a substrate that forms part of or is exposed to a channel or channels of the device that form a closed loop, for circulation of sample to actively contact complementary probes. Universal chips according to the invention can be fabricated not only with DNA but also with other molecules such as RNA, proteins, peptide nucleic acid (PNA) and polyamide molecules.

公开(公告)号：US20150183633A1

公开(公告)日：2015-07-02

申请号：US14503252

申请日：2014-09-30

Applicant: California Institute of Technology

Inventor： Marc A. Unger ,  Hou-Pu Chou ,  Todd A. Thorsen ,  Axel Scherer ,  Stephen R. Quake

IPC: B81B3/00

CPC classification number: B32B3/00 ,  B01J2219/00355 ,  B01J2219/00378 ,  B01J2219/00396 ,  B01J2219/00398 ,  B01J2219/00439 ,  B01J2219/005 ,  B01J2219/00527 ,  B01J2219/00605 ,  B01J2219/00612 ,  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 ,  B81B3/0032 ,  B81B3/0051 ,  B81B2201/036 ,  B81B2201/054 ,  B81C1/00119 ,  B81C2201/019 ,  C12Q1/6874 ,  F04B43/043 ,  F15C5/00 ,  F16K99/0001 ,  F16K99/0015 ,  F16K99/0046 ,  F16K99/0051 ,  F16K99/0059 ,  F16K2099/0074 ,  F16K2099/0076 ,  F16K2099/0078 ,  F16K2099/008 ,  F16K2099/0094 ,  Y10T137/0491 ,  Y10T137/2224 ,  Y10T137/87716 ,  Y10T137/87804 ,  Y10T137/87812 ,  Y10T137/87893 ,  Y10T156/10 ,  Y10T156/1002 ,  Y10T156/1064 ,  Y10T428/24479 ,  Y10T428/2457 ,  Y10T428/24612 ,  Y10T428/24744 ,  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。

公开(公告)号：US20140322489A1

公开(公告)日：2014-10-30

申请号：US14218872

申请日：2014-03-18

Applicant: California Institute of Technology

Inventor： Marc A. Unger ,  Hou-Pu Chou ,  Todd A. Thorsen ,  Axel Scherer ,  Stephen R. Quake

IPC: F16K13/00

CPC classification number: B29C51/00 ,  B01L3/502707 ,  B01L3/50273 ,  B01L3/502738 ,  B01L2300/0861 ,  B01L2300/0887 ,  B01L2300/123 ,  B01L2400/046 ,  B01L2400/0481 ,  B01L2400/0655 ,  B33Y80/00 ,  B81B5/00 ,  B81B2201/036 ,  B81B2201/054 ,  B81C1/00119 ,  B81C2201/019 ,  B81C2201/034 ,  C12Q1/6874 ,  F04B43/043 ,  F15C1/06 ,  F15C5/00 ,  F16K11/20 ,  F16K13/00 ,  F16K31/126 ,  F16K99/0001 ,  F16K99/0015 ,  F16K99/0046 ,  F16K99/0048 ,  F16K99/0051 ,  F16K99/0059 ,  F16K2099/0074 ,  F16K2099/0076 ,  F16K2099/0078 ,  F16K2099/008 ,  F16K2099/0094 ,  Y10T137/0491 ,  Y10T137/0497 ,  Y10T137/2224 ,  Y10T137/87249 ,  Y10T156/10 ,  Y10T428/24479 ,  Y10T428/24744 ,  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。

公开(公告)号：US20140065653A1

公开(公告)日：2014-03-06

申请号：US13679328

申请日：2012-11-16

Applicant: California Institute of Technology

Inventor： Sebastian J. Maerkl ,  Todd A. Thorsen ,  Xiaoyan Bao ,  Stephen R. Quake ,  Vincent Studer

IPC: C12Q1/28

CPC classification number: C12Q1/28 ,  B01L3/5025 ,  B01L3/50273 ,  B01L3/502738 ,  B01L2300/0861 ,  B01L2300/0887 ,  B01L2400/0481 ,  B01L2400/0655 ,  B81B2201/0214 ,  B81B2201/054 ,  B81B2201/07 ,  B81C1/00119 ,  F15C5/00 ,  F16K11/20 ,  F16K99/0001 ,  F16K99/0015 ,  F16K99/0059 ,  F16K2099/0074 ,  F16K2099/0076 ,  F16K2099/0078 ,  F16K2099/008 ,  F16K2099/0084 ,  F16K2099/0094 ,  Y10T137/0318 ,  Y10T137/0329 ,  Y10T137/2224 ,  Y10T137/85938 ,  Y10T137/87249

Abstract: High-density microfluidic chips contain plumbing networks with thousands of micromechanical valves and hundreds of individually addressable chambers. These fluidic devices are analogous to electronic integrated circuits fabricated using large scale integration (LSI). A component of these networks is the fluidic multiplexor, which is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs. These integrated microfluidic networks can be used to construct a variety of highly complex microfluidic devices, for example the microfluidic analog of a comparator array, and a microfluidic memory storage device resembling electronic random access memories.

Abstract translation: 高密度微流控芯片包含具有数千个微机械阀门和数百个单独可寻址腔室的管道网络。 这些流体装置类似于使用大规模集成（LSI）制造的电子集成电路。 这些网络的一个组件是流体多路复用器，它是二进制阀模式的组合阵列，通过允许使用最少数量的输入的复杂流体操纵来指数地增加网络的处理能力。 这些集成的微流体网络可用于构建各种高度复杂的微流体装置，例如比较器阵列的微流体模拟装置和类似于电子随机存取存储器的微流体存储器存储装置。