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41. 发明申请

US20060019267A1 Methods and kits for analyzing polynucleotide sequences 有权
标题翻译：用于分析多核苷酸序列的方法和试剂盒
公开(公告)号：US20060019267A1
公开(公告)日：2006-01-26
申请号：US11054243
申请日：2005-02-09
申请人： Stephen Quake
发明人： Stephen Quake
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/68 , C12Q1/6869 , C12Q2561/113 , C12Q2533/101 , C12Q2565/507
摘要： The present invention features methods for analyzing a sequence of a target polynucleotide by detecting incorporation of a nucleotide into its complementary strand, where the polynucleotides may be bound at high density and at single molecule resolution. The invention also features labeling moieties and blocking moieties, which facilitate chain termination or choking. Certain aspects provide for temporal detection of the incorporations; some allow for asynchronous analysis of a plurality of target polynucleotides and the use of short sequencing cycles. Surface chemistry aspects of the sequencing methods are also provided. The method may also be used in kits, said kits designed to carry out and facilitate the methods provided herein.
摘要翻译：本发明的特征在于通过检测将核苷酸掺入其互补链中来分析靶多核苷酸的序列的方法，其中多核苷酸可以以高密度和单分子分辨率结合。本发明还具有标记部分和阻断部分，其有助于链终止或阻塞。某些方面提供了公司的时间检测; 一些允许多个靶多核苷酸的异步分析和使用短的测序循环。还提供了测序方法的表面化学方面。该方法也可用于试剂盒中，所述试剂盒旨在实现和促进本文提供的方法。

42. 发明授权

US06964736B2 Method and apparatus for analysis and sorting of polynucleotides based on size 失效
标题翻译：基于大小分析和分选多核苷酸的方法和装置
公开(公告)号：US06964736B2
公开(公告)日：2005-11-15
申请号：US10021850
申请日：2001-12-13
申请人： Stephen Quake , Wayne D. Volkmuth
发明人： Stephen Quake , Wayne D. Volkmuth
IPC分类号： B01L3/00 , G01N15/14 , G01N27/447 , G01N21/05 , G01N27/453
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。

43. 发明申请

US20050123947A1 Methods and systems for molecular fingerprinting 审中-公开
标题翻译：分子指纹图谱的方法和系统
公开(公告)号：US20050123947A1
公开(公告)日：2005-06-09
申请号：US10917665
申请日：2004-08-13
申请人： Stephen Quake , Hou-Pu Chou
发明人： Stephen Quake , Hou-Pu Chou
IPC分类号： B01L3/00 , C12Q1/68 , G01N15/14 , C07H21/04 , C12P19/34
CPC分类号： B01L3/502707 , B01L3/502738 , B01L3/502761 , B01L2200/0647 , B01L2200/0652 , B01L2300/0654 , B01L2300/0816 , B01L2300/0864 , B01L2400/0406 , B01L2400/0415 , B01L2400/0418 , B01L2400/0421 , B01L2400/0484 , B01L2400/0487 , B01L2400/0622 , B01L2400/0633 , C12Q1/6816 , C12Q1/683 , G01N2015/149 , C12Q2565/629
摘要： This invention relates in general to a method for molecular fingerprinting. The method can be used for forensic identification (e.g. DNA fingerprinting, especially by VNTR), bacterial typing, and human/animal pathogen diagnosis. More particularly, molecules such as polynucleotides (e.g. DNA) can be assessed or sorted by size in a microfabricated device that analyzes the polynucleotides according to restriction fragment length polymorphism. In a microfabricated device according to the invention, DNA fragments or other molecules can be rapidly and accurately typed using relatively small samples, by measuring for example the signal of an optically-detectable (e.g., fluorescent) reporter associated with the polynucleotide fragments.
摘要翻译：本发明一般涉及分子指纹图谱的方法。该方法可用于法医鉴定（例如DNA指纹图谱，特别是VNTR），细菌分型和人/动物病原体诊断。更具体地，可以按照限制性片段长度多态性分析多核苷酸的微制造装置中的大小来评估或分类分子，例如多核苷酸（例如DNA）。在根据本发明的微制造装置中，通过测量例如与多核苷酸片段相关的可光学检测（例如，荧光）报告基因的信号，可以使用相对小的样品快速和精确地分型DNA片段或其他分子。

44. 发明申请

US20050036222A1 Solid immersion lens structures and methods for producing solid immersion lens structures 有权
标题翻译：固体浸没透镜结构及其制造方法
公开(公告)号：US20050036222A1
公开(公告)日：2005-02-17
申请号：US10933156
申请日：2004-09-01
申请人： Olivier Legrand , Stephen Quake
发明人： Olivier Legrand , Stephen Quake
IPC分类号： B29C33/50 , B29C39/02 , B29C39/36 , B29D11/00 , B29K19/00 , B29K83/00 , G02B3/00 , G02B21/00 , G11B3/00 , G02B7/00 , G02B9/00 , G02B11/00 , G02B13/00 , G11B7/00 , G11B9/00 , G11B11/00 , G11B13/00
CPC分类号： B29D11/00394 , B29C33/50 , B29C39/02 , B29C39/021 , B29C39/36 , B29D11/00432 , G02B3/00 , G02B21/00 , Y10S359/90
摘要： 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 n=1.4, such as General Electric RTV 615.
摘要翻译：诸如固体浸没透镜结构的微透镜结构是铸造成所需形状和平滑度的辐射透射柔性弹性体。一种用于构造固体浸没透镜结构的方法包括提供限定透镜形腔的模具，其中铸造固体浸没透镜，将半透明液体弹性体材料浇铸到透镜腔中，允许弹性体材料设置以形成固体浸没透镜部分，并将固体浸没透镜部分从模具中取出。用作固体浸没透镜的特定材料是折射率大于n = 1.4的半透明硅氧烷弹性体，例如通用电气RTV 615。

45. 发明授权

US06818395B1 Methods and apparatus for analyzing polynucleotide sequences 有权
标题翻译：分析多核苷酸序列的方法和装置
公开(公告)号：US06818395B1
公开(公告)日：2004-11-16
申请号：US09707737
申请日：2000-11-06
申请人： Stephen Quake , Marc Unger
发明人： Stephen Quake , Marc Unger
IPC分类号： C12Q168
CPC分类号： C12Q1/68 , B01L3/5027 , B01L3/502707 , B01L3/502738 , B01L2200/10 , B01L2300/0861 , B01L2300/0887 , B01L2300/123 , B01L2300/14 , B01L2400/0481 , B01L2400/0655 , C12Q1/6869 , C12Q1/6874 , F04B43/043 , F15C5/00 , F16K99/0001 , F16K99/0015 , F16K99/0051 , F16K99/0059 , F16K2099/0074 , F16K2099/0076 , F16K2099/0078 , F16K2099/008 , F16K2099/0084 , F16K2099/0094 , G01N33/549 , C12Q2535/125 , C12Q2565/629 , C12Q2533/101
摘要： Methods for high speed, high throughput analysis of polynucleotide sequences, and apparatuses with which to carry out the methods are provided in the invention.
摘要翻译：在本发明中提供了用于多核苷酸序列的高速，高通量分析的方法以及用于实施所述方法的装置。

46. 发明授权

US06344325B1 Methods for analysis and sorting of polynucleotides 有权
标题翻译：多核苷酸分析和分选方法
公开(公告)号：US06344325B1
公开(公告)日：2002-02-05
申请号：US09499943
申请日：2000-02-08
申请人： Stephen Quake , Wayne D. Volkmuth
发明人： Stephen Quake , Wayne D. Volkmuth
IPC分类号： G01N118
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 individual polynucleotides, e.g., by size according to an optical signal measured within a detection region of the device. An optical signal such as fluorescence from a reporter molecule associated with the polynucleotide molecules can be used to determine polynucleotide size or to direct selected polynucleotides into one or more selected branch channels of the device.
摘要翻译：本发明涉及一种微制造装置和使用该装置的方法，用于根据在装置的检测区域内测量的光学信号，例如按尺寸分析和分类各个多核苷酸。可以使用诸如与多核苷酸分子相关的报告分子的荧光的光学信号来确定多核苷酸大小或将选择的多核苷酸引导到装置的一个或多个选择的分支通道中。

47. 发明授权

US07981604B2 Methods and kits for analyzing polynucleotide sequences 有权
标题翻译：用于分析多核苷酸序列的方法和试剂盒
公开(公告)号：US07981604B2
公开(公告)日：2011-07-19
申请号：US11054243
申请日：2005-02-09
申请人： Stephen Quake
发明人： Stephen Quake
IPC分类号： C12Q1/68 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/68 , C12Q1/6869 , C12Q2561/113 , C12Q2533/101 , C12Q2565/507
摘要： The present invention features methods for analyzing a sequence of a target polynucleotide by detecting incorporation of a nucleotide into its complementary strand, where the polynucleotides may be bound at high density and at single molecule resolution. The invention also features labeling moieties and blocking moieties, which facilitate chain termination or choking. Certain aspects provide for temporal detection of the incorporations; some allow for asynchronous analysis of a plurality of target polynucleotides and the use of short sequencing cycles. Surface chemistry aspects of the sequencing methods are also provided. The method may also be used in kits, said kits designed to carry out and facilitate the methods provided herein.
摘要翻译：本发明的特征在于通过检测将核苷酸掺入其互补链中来分析靶多核苷酸的序列的方法，其中多核苷酸可以以高密度和单分子分辨率结合。本发明还具有标记部分和阻断部分，其有助于链终止或阻塞。某些方面提供了公司的时间检测; 一些允许多个靶多核苷酸的异步分析和使用短的测序循环。还提供了测序方法的表面化学方面。该方法也可用于试剂盒中，所述试剂盒旨在实现和促进本文提供的方法。

48. 发明申请

US20100124752A1 Non-Invasive Fetal Genetic Screening by Digital Analysis 有权
公开(公告)号：US20100124752A1
公开(公告)日：2010-05-20
申请号：US12689548
申请日：2010-01-19
申请人： Stephen Quake , Hei-Mun Christina Fan
发明人： Stephen Quake , Hei-Mun Christina Fan
IPC分类号： C12Q1/68
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.

49. 发明申请

US20080050283A1 MICROFLUIDIC DEVICES AND METHODS OF USE 有权
标题翻译：微流体装置及其使用方法
公开(公告)号：US20080050283A1
公开(公告)日：2008-02-28
申请号：US11842731
申请日：2007-08-21
申请人： Hou-Pu Chou , Anne Fu , Stephen Quake
发明人： Hou-Pu Chou , Anne Fu , Stephen Quake
IPC分类号： B01L11/00
CPC分类号： F04B43/00 , A61M2206/22 , B01L3/5027 , B01L3/50273 , B01L3/502738 , B01L2200/0647 , B01L2300/0816 , B01L2300/0864 , B01L2300/123 , B01L2400/0418 , B01L2400/0481 , B01L2400/0655 , B01L2400/084 , F04B11/00 , F04B19/006 , F04B43/043 , G01N30/6095 , G01N2015/1081 , G01N2015/149 , G01N2030/205 , G01N2030/322 , Y10T436/2575
摘要： A microfluidic device comprises pumps, valves, and fluid oscillation dampers. In a device employed for sorting, an entity is flowed by the pump along a flow channel through a detection region to a junction. Based upon an identity of the entity determined in the detection region, a waste or collection valve located on opposite branches of the flow channel at the junction are actuated, thereby routing the entity to either a waste pool or a collection pool. A damper structure may be located between the pump and the junction. The damper reduces the amplitude of oscillation pressure in the flow channel due to operation of the pump, thereby lessening oscillation in velocity of the entity during sorting process. The microfluidic device may be formed in a block of elastomer material, with thin membranes of the elastomer material deflectable into the flow channel to provide pump or valve functionality.
摘要翻译：微流体装置包括泵，阀和流体振荡阻尼器。在用于排序的装置中，实体通过泵通过检测区域的流动通道流到结。基于在检测区域中确定的实体的身份，致动位于连接处的流动通道的相对分支上的废物或收集阀，从而将该实体路由到废物池或收集池。阻尼器结构可以位于泵和接头之间。阻尼器由于泵的操作而减小了流动通道中的振荡压力的振幅，从而减少了分离过程中实体的速度振荡。微流体装置可以形成为弹性体材料块，弹性体材料的薄膜可偏转到流动通道中以提供泵或阀的功能。

50. 发明申请

US20070224617A1 Mechanically induced trapping of molecular interactions 有权
标题翻译：机械诱导分子相互作用的捕获
公开(公告)号：US20070224617A1
公开(公告)日：2007-09-27
申请号：US11698757
申请日：2007-01-26
申请人： Stephen Quake , Sebastian Maerkl
发明人： Stephen Quake , Sebastian Maerkl
IPC分类号： C12Q1/68 , G01N33/53
CPC分类号： G01N33/543 , B01J2219/0043 , B01L3/5027 , B01L3/502707 , B01L3/502738 , B01L2300/0816 , B01L2300/0819 , B01L2300/0861 , B01L2300/123 , B01L2400/0481 , B01L2400/0655 , G01N33/5302 , G01N33/54393
摘要： The invention provides devices and methods for surface patterning the substrate of a microfluidic device, and for detection and analysis of interactions between molecules by mechanically trapping a molecular complex while substantially expelling solvent and unbound solute molecules. Examples of molecular complexes include protein-protein complexes and protein-nucleic acid complexes.
摘要翻译：本发明提供用于表面构图微流体装置的基底的装置和方法，以及通过在基本排出溶剂和未结合的溶质分子的同时机械捕获分子复合物来检测和分析分子之间的相互作用。分子复合物的实例包括蛋白质 - 蛋白质复合物和蛋白质 - 核酸复合物。

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