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11. 发明申请

US20050205005A1 Microfluidic protein crystallography 有权
标题翻译：微流体蛋白晶体学
公开(公告)号：US20050205005A1
公开(公告)日：2005-09-22
申请号：US11006522
申请日：2004-12-06
申请人： Carl Hansen , Morten Sommer , Stephen Quake
发明人： Carl Hansen , Morten Sommer , Stephen Quake
IPC分类号： C30B1/00 , C30B7/00 , C30B35/00
CPC分类号： C30B7/14 , 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 , C30B7/10 , C30B29/58 , C30B35/00 , C40B40/10 , F04B43/043 , F16K99/0001 , F16K99/0015 , F16K99/0028 , F16K99/0057 , F16K2099/0074 , F16K2099/0078 , F16K2099/008 , F16K2099/0094 , G01N2013/003 , Y10T117/10 , Y10T117/1004 , Y10T117/1008 , Y10T117/1024
摘要： 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.
摘要翻译：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。

12. 发明申请

US20050037471A1 Microfluidic rotary flow reactor matrix 有权
标题翻译：微流控旋流反应器基体
公开(公告)号：US20050037471A1
公开(公告)日：2005-02-17
申请号：US10837025
申请日：2004-04-30
申请人： Jian Liu , Carl Hansen , Stephen Quake
发明人： Jian Liu , Carl Hansen , Stephen Quake
IPC分类号： B01J19/00 , B01L3/00 , B01L7/00 , C12M1/36 , C12N20060101 , C12P19/34 , F04B43/04
CPC分类号： 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
摘要： 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.
摘要翻译：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。 N 2独立测定可以仅使用2N + 1移液步骤，使用在所有反应器中摊销的酶的单等分试样。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。

13. 发明授权

US08104497B2 Microfabricated elastomeric valve and pump systems 有权
公开(公告)号：US08104497B2
公开(公告)日：2012-01-31
申请号：US11685654
申请日：2007-03-13
申请人： Marc Unger , Hou-Pu Chou , Todd Thorsen , Axel Scherer , Stephen Quake , Markus Enzelberger , Mark Adams , Carl Hansen
发明人： Marc Unger , Hou-Pu Chou , Todd Thorsen , Axel Scherer , Stephen Quake , Markus Enzelberger , Mark Adams , Carl Hansen
IPC分类号： B08B3/04
CPC分类号： 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
摘要： 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.

14. 发明申请

US20060054228A1 Microfabricated elastomeric valve and pump systems 有权
公开(公告)号：US20060054228A1
公开(公告)日：2006-03-16
申请号：US11111264
申请日：2005-04-20
申请人： Marc Unger , Hou-Pu Chou , Todd Thorsen , Axel Scherer , Stephen Quake , Jian Liu , Mark Adams , Carl Hansen
发明人： Marc Unger , Hou-Pu Chou , Todd Thorsen , Axel Scherer , Stephen Quake , Jian Liu , Mark Adams , Carl Hansen
IPC分类号： F15C1/06
CPC分类号： 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
摘要： 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.

15. 发明申请

US20050166980A1 Microfabricated elastomeric valve and pump systems 有权
公开(公告)号：US20050166980A1
公开(公告)日：2005-08-04
申请号：US11056451
申请日：2005-02-10
申请人： Marc Unger , Hou-Pu Chou , Todd Thorsen , Axel Scherer , Stephen Quake , Markus Enzelberger , Mark Adams , Carl Hansen
发明人： Marc Unger , Hou-Pu Chou , Todd Thorsen , Axel Scherer , Stephen Quake , Markus Enzelberger , Mark Adams , Carl Hansen
IPC分类号： 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 , B32B3/00
CPC分类号： 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
摘要： 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.

16. 发明申请

US20120156731A1 Improved Methods for Rapid Gene Synthesis 审中-公开
标题翻译：改进的快速基因合成方法
公开(公告)号：US20120156731A1
公开(公告)日：2012-06-21
申请号：US12052156
申请日：2008-03-20
申请人： Yanyi Huang , James Berger , Stephen Quake
发明人： Yanyi Huang , James Berger , Stephen Quake
IPC分类号： C12P19/34 , C07H21/04 , C12M1/00 , C12N9/00
CPC分类号： C12Y605/01001 , C12P19/34 , C12Y605/01002
摘要： Disclosed are methods and materials for assembling long polynucleotides from synthetic oligonucleotides. The use of synthetic oligonucleotides permits non-natural design of sequences. The oligonucleotides used for construction may be relatively short, according to practicalities of nucleotide synthesis. They are assembled using a ligase which is operative over a range of temperatures, i.e., is thermostable. The method and oligonucleotides are designed such that the melting temperature of the strands to be hybridized is set at a number of selected specific temperatures for each group of oligonucleotides to be hybridized and ligated. Hybridization and ligation take place at or near the melting temperature, so that each succeeding ligation is governed by a temperature that will prevent hybridization if any mismatches are present.
摘要翻译：公开了用于从合成寡核苷酸组装长多核苷酸的方法和材料。合成寡核苷酸的使用允许序列的非自然设计。根据核苷酸合成的实用性，用于构建的寡核苷酸可能相对较短。它们使用在一定温度范围内操作的连接酶组装，即是耐热的。设计该方法和寡核苷酸使待杂交的链的解链温度被设定为要混合并连接的每组寡核苷酸的选定的特定温度的数目。杂交和连接在熔融温度或接近熔化温度下进行，因此每次后续连接都由温度控制，如果存在任何错配，将会阻止杂交。

17. 发明授权

US09441273B2 Non-invasive fetal genetic screening by digital analysis 有权
标题翻译：通过数字分析进行非侵入性胎儿遗传筛选
公开(公告)号：US09441273B2
公开(公告)日：2016-09-13
申请号：US12816043
申请日：2010-06-15
申请人： Stephen Quake , Hei-Mun Christina Fan
发明人： Stephen Quake , Hei-Mun Christina Fan
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6883 , C12Q1/6809 , C12Q1/6851 , C12Q1/6858 , C12Q1/6881 , C12Q2600/156 , C12Q2600/158 , Y10T436/143333 , C12Q2565/629 , C12Q2537/143 , C12Q2531/113 , C12Q2537/157 , C12Q2527/125 , C12Q2545/114 , C12Q2527/137
摘要： The present methods are exemplified by a process in which maternal blood containing fetal DNA is diluted to a nominal value of approximately 0.5 genome equivalent of DNA per reaction sample. Digital PCR is then be used to detect aneuploidy, such as the trisomy that causes Down Syndrome. Since aneuploidies do not present a mutational change in sequence, and are merely a change in the number of chromosomes, it has not been possible to detect them in a fetus without resorting to invasive techniques such as amniocentesis or chorionic villi sampling. Digital amplification allows the detection of aneuploidy using massively parallel amplification and detection methods, examining, e.g., 10,000 genome equivalents.
摘要翻译：本方法的例子是一种方法，其中将含有胎儿DNA的母体血液稀释成每反应样品约0.5个基因组当量DNA的标称值。然后使用数字PCR来检测非整倍体，例如导致唐氏综合征的三体性。由于非整倍体并不表现出序列变异，仅仅是染色体数量的变化，所以不可能在胎儿中检测它们，而不需要采用诸如羊膜穿刺或绒毛膜绒毛取样等侵入性技术。数字扩增允许使用大规模并行扩增和检测方法检测非整倍体，检查例如10,000个基因组等同物。

18. 发明申请

US20130001083A1 METHOD AND APPARATUS FOR ANALYSIS AND SORTING OF POLYNUCLEOTIDES BASED ON SIZE 有权
标题翻译：基于尺寸的多核苷酸分析与分选方法与装置
公开(公告)号：US20130001083A1
公开(公告)日：2013-01-03
申请号：US13427815
申请日：2012-03-22
申请人： Stephen Quake , Wayne D. Volksmuth
发明人： Stephen Quake , Wayne D. Volksmuth
IPC分类号： G01N27/447
CPC分类号： G01N27/44791 , B01L3/502707 , B01L3/502738 , B01L3/502761 , B01L2200/0647 , B01L2200/0652 , B01L2300/0654 , B01L2300/0816 , B01L2300/0864 , B01L2400/0415 , B01L2400/0421 , B01L2400/0484 , B01L2400/0487 , C12Q1/6816 , G01N2015/149 , Y10S366/03 , C12Q2565/629
摘要： The invention relates to a microfabricated device and methods of using the device for analyzing and sorting polynucleotide molecules by size.
摘要翻译：本发明涉及一种微加工装置以及使用该装置用于按尺寸分析和分选多核苷酸分子的方法。

19. 发明申请

US20120165203A1 SIMULTANEOUS DETERMINATION OF ANEUPLOIDY AND FETAL FRACTION 审中-公开
标题翻译：同时确定骨质疏松症和骨质疏松症
公开(公告)号：US20120165203A1
公开(公告)日：2012-06-28
申请号：US13365240
申请日：2012-02-02
申请人： Stephen Quake , Richard P. Rava , Manjula Chinnappa , David A. Comstock , Gabrielle Heilek
发明人： Stephen Quake , Richard P. Rava , Manjula Chinnappa , David A. Comstock , Gabrielle Heilek
IPC分类号： C12Q1/68 , C40B20/00
CPC分类号： C12Q1/6869 , C12Q1/6806 , C12Q1/6809 , C12Q1/6883 , C12Q2600/106 , C12Q2537/16 , C12Q2537/165 , C12Q2545/101
摘要： The invention provides compositions and methods for simultaneously determining the presence or absence of fetal aneuploidy and the relative amount of fetal nucleic acids in a sample obtained form a pregnant female. The method encompasses the use of sequencing technologies and exploits the occurrence of polymorphisms to provide a streamlined noninvasive process applicable to the practice of prenatal diagnostics.
摘要翻译：本发明提供用于同时确定胎儿非整倍性的存在或不存在的组合物和方法以及从孕妇获得的样品中的胎儿核酸的相对量。该方法包括使用测序技术，并利用多态性的发生来提供适用于产前诊断实践的流线型非侵入性过程。

20. 发明授权

US07888017B2 Non-invasive fetal genetic screening by digital analysis 有权
标题翻译：通过数字分析进行非侵入性胎儿遗传筛选
公开(公告)号：US07888017B2
公开(公告)日：2011-02-15
申请号：US11701686
申请日：2007-02-02
申请人： Stephen Quake , Hei-Mun Christina Fan
发明人： Stephen Quake , Hei-Mun Christina Fan
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6883 , C12Q1/6809 , C12Q1/6851 , C12Q1/6858 , C12Q1/6881 , C12Q2600/156 , C12Q2600/158 , Y10T436/143333 , C12Q2565/629 , C12Q2537/143 , C12Q2531/113 , C12Q2537/157 , C12Q2527/125 , C12Q2545/114 , C12Q2527/137
摘要： The present methods are exemplified by a process in which maternal blood containing fetal DNA is diluted to a nominal value of approximately 0.5 genome equivalent of DNA per reaction sample. Digital PCR is then be used to detect aneuploidy, such as the trisomy that causes Down Syndrome. Since aneuploidies do not present a mutational change in sequence, and are merely a change in the number of chromosomes, it has not been possible to detect them in a fetus without resorting to invasive techniques such as amniocentesis or chorionic villi sampling. Digital amplification allows the detection of aneuploidy using massively parallel amplification and detection methods, examining, e.g., 10,000 genome equivalents.
摘要翻译：本方法的例子是一种方法，其中将含有胎儿DNA的母体血液稀释成每反应样品约0.5个基因组当量DNA的标称值。然后使用数字PCR来检测非整倍体，例如导致唐氏综合征的三体性。由于非整倍体并不表现出序列变异，仅仅是染色体数量的变化，所以不可能在胎儿中检测它们，而不需要采用诸如羊膜穿刺或绒毛膜绒毛取样等侵入性技术。数字扩增允许使用大规模并行扩增和检测方法检测非整倍体，检查例如10,000个基因组等同物。

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