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1. 发明申请

US20050136414A1 Methods and compositions for making locus-specific arrays 审中-公开
标题翻译：用于制作位点特异性阵列的方法和组合物
公开(公告)号：US20050136414A1
公开(公告)日：2005-06-23
申请号：US10746249
申请日：2003-12-23
申请人： Kevin Gunderson , David Barker , Mark Chee , Tim McDaniel , Robert Yang
发明人： Kevin Gunderson , David Barker , Mark Chee , Tim McDaniel , Robert Yang
IPC分类号： C12Q1/68 , C12M1/34 , C12P19/34
CPC分类号： C12Q1/6837 , C12Q2525/161
摘要： The present invention includes methods and compositions relating to locus-specific arrays. More specifically, this invention includes methods for making locus-specific arrays from universal arrays in situ, the custom arrays made using those methods, and methods of using the custom arrays to detect target nucleotides.
摘要翻译：本发明包括与轨迹特异性阵列相关的方法和组合物。更具体地，本发明包括用于从现场通用阵列制备位点特异性阵列的方法，使用这些方法制备的定制阵列，以及使用定制阵列检测靶核苷酸的方法。

2. 发明申请

US20070184456A1 Use of microfluidic systems in the detection of target analytes using microsphere arrays 有权
标题翻译：使用微流体系统检测目标分析物使用微球阵列
公开(公告)号：US20070184456A1
公开(公告)日：2007-08-09
申请号：US10897899
申请日：2004-07-23
申请人： Mark Chee , Todd Dickinson , Kevin Gunderson , Don O'Neil , John Stuelpnagel
发明人： Mark Chee , Todd Dickinson , Kevin Gunderson , Don O'Neil , John Stuelpnagel
IPC分类号： C12Q1/68 , C12M3/00
CPC分类号： C12Q1/6816 , B01L3/502761 , B01L2200/0668 , B01L2300/0816 , B01L2300/0867 , B01L2400/0415 , C12Q2565/629 , C12Q2563/149
摘要： The invention relates generally to methods and apparatus for conducting analyses, particularly microfluidic devices for the detection of target analytes.
摘要翻译：本发明一般涉及用于进行分析的方法和装置，特别是用于检测目标分析物的微流体装置。

3. 发明申请

US20060275782A1 Detection of nucleic acid reactions on bead arrays 审中-公开
公开(公告)号：US20060275782A1
公开(公告)日：2006-12-07
申请号：US11238826
申请日：2005-09-28
申请人： Kevin Gunderson , John Stuelpnagel , Mark Chee
发明人： Kevin Gunderson , John Stuelpnagel , Mark Chee
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6837 , C12Q1/6858 , C12Q1/6874 , C12Q2535/131 , C12Q2525/191 , C12Q2531/137 , C12Q2563/149
摘要： The present invention is directed to methods and compositions for the use of microsphere arrays to detect and quantify a number of nucleic acid reactions. The invention finds use in genotyping, i.e. the determination of the sequence of nucleic acids, particularly alterations such as nucleotide substitutions (mismatches) and single nucleotide polymorphisms (SNPs). Similarly, the invention finds use in the detection and quantification of a nucleic acid target using a variety of amplification techniques, including both signal amplification and target amplification. The methods and compositions of the invention can be used in nucleic acid sequencing reactions as well. All applications can include the use of adapter sequences to allow for universal arrays.

4. 发明申请

US20050191646A1 Nucleic acid analysis techniques 审中-公开
标题翻译：核酸分析技术
公开(公告)号：US20050191646A1
公开(公告)日：2005-09-01
申请号：US10961341
申请日：2004-10-07
申请人： David Lockhart , Mark Chee , Kevin Gunderson , Lai Chaoqiang , Lisa Wodicka , Maureen Cronin , Danny Lee , Huu Tran , Hajime Matsuzaki , Glenn McGall , Anthony Barone
发明人： David Lockhart , Mark Chee , Kevin Gunderson , Lai Chaoqiang , Lisa Wodicka , Maureen Cronin , Danny Lee , Huu Tran , Hajime Matsuzaki , Glenn McGall , Anthony Barone
IPC分类号： C07B61/00 , C07H19/052 , C07H19/12 , C07H21/00 , C12Q1/00 , C12Q1/68
CPC分类号： C07H19/052 , C07H19/12 , C07H21/00 , C12Q1/6809 , C12Q1/6837 , C12Q2600/156 , C40B40/00 , G16B25/00 , G16B30/00 , C12Q2525/161 , C12Q2565/501 , C12Q2561/125
摘要： The present invention provides a simplified method for identifying differences in nucleic acid abundances (e.g., expression levels) between two or more samples. The methods involve providing an array containing a large number (e.g. greater than 1,000) of arbitrarily selected different oligonucleotide probes where the sequence and location of each different probe is known. Nucleic acid samples (e.g. mRNA) from two or more samples are hybridized to the probe arrays and the pattern of hybridization is detected. Differences in the hybridization patterns between the samples indicates differences in expression of various genes between those samples. This invention also provides a method of end-labeling a nucleic acid. In one embodiment, the method involves providing a nucleic acid, providing a labeled oligonucleotide and then enzymatically ligating the oligonucleotide to the nucleic acid. Thus, for example, where the nucleic acid is an RNA, a labeled oligoribonucleotide can be ligated using an RNA ligase. In another embodiment, the end labeling can be accomplished by providing a nucleic acid, providing labeled nucleoside triphosphates, and attaching the nucleoside triphosphates to the nucleic acid using a terminal transferase.
摘要翻译：本发明提供用于鉴定两个或多个样品之间的核酸丰度差异（例如，表达水平）的简化方法。所述方法包括提供包含大量（例如大于1,000个）任意选择的不同寡核苷酸探针的阵列，其中每个不同探针的序列和位置是已知的。来自两个或更多个样品的核酸样品（例如mRNA）与探针阵列杂交，并检测杂交模式。样本之间的杂交模式的差异表明这些样品之间各种基因的表达差异。本发明还提供了一种终止标记核酸的方法。在一个实施方案中，该方法包括提供核酸，提供标记的寡核苷酸，然后将寡核苷酸酶连接到核酸上。因此，例如，当核酸是RNA时，可以使用RNA连接酶连接标记的寡核糖核苷酸。在另一个实施方案中，末端标记可以通过提供核酸，提供标记的核苷三磷酸和使用末端转移酶将核苷三磷酸与核酸连接来实现。

5. 发明申请

US20050100893A1 Detection of nucleic acid reactions on bead arrays 审中-公开
标题翻译：检测珠阵列上的核酸反应
公开(公告)号：US20050100893A1
公开(公告)日：2005-05-12
申请号：US10272384
申请日：2002-10-15
申请人： Kevin Gunderson , John Stuelpnagel , Mark Chee
发明人： Kevin Gunderson , John Stuelpnagel , Mark Chee
IPC分类号： C12P19/34 , C12Q1/68
CPC分类号： C12Q1/6874 , C12Q2565/537 , C12Q2565/518 , C12Q2521/501
摘要： The present invention is directed to methods and compositions for the use of microsphere arrays to detect and quantify a number of nucleic acid reactions. The invention finds use in genotyping, i.e. the determination of the sequence of nucleic acids, particularly alterations such as nucleotide substitutions (mismatches) and single nucleotide polymorphisms (SNPs). Similarly, the invention finds use in the detection and quantification of a nucleic acid target using a variety of amplification techniques, including both signal amplification and target amplification. The methods and compositions of the invention can be used in nucleic acid sequencing reactions as well. All applications can include the use of adapter sequences to allow for universal arrays.
摘要翻译：本发明涉及使用微球阵列来检测和定量许多核酸反应的方法和组合物。本发明用于基因分型，即确定核酸序列，特别是改变，例如核苷酸取代（错配）和单核苷酸多态性（SNP）。类似地，本发明用于使用多种扩增技术检测和定量核酸靶，包括信号放大和靶扩增两者。本发明的方法和组合物也可用于核酸测序反应。所有应用程序可以包括使用适配器序列来允许通用阵列。

6. 发明申请

US20050158772A1 Nucleic acid analysis techniques 审中-公开
公开(公告)号：US20050158772A1
公开(公告)日：2005-07-21
申请号：US11021367
申请日：2004-12-23
申请人： David Lockhart , Mark Chee , Kevin Gunderson , Lai Chaoqiang , Lisa Wodicka , Maureen Cronin , Danny Lee , Huu Tran , Hajime Matsuzaki , Glenn McGall , Anthony Barone
发明人： David Lockhart , Mark Chee , Kevin Gunderson , Lai Chaoqiang , Lisa Wodicka , Maureen Cronin , Danny Lee , Huu Tran , Hajime Matsuzaki , Glenn McGall , Anthony Barone
IPC分类号： C07B61/00 , C07H19/052 , C07H19/12 , C07H21/00 , C12Q1/00 , C12Q1/68
CPC分类号： C07H19/052 , C07H19/12 , C07H21/00 , C12Q1/6809 , C12Q1/6837 , C12Q2600/156 , C40B40/00 , G16B25/00 , G16B30/00 , C12Q2525/161 , C12Q2565/501 , C12Q2561/125
摘要： The present invention provides a simplified method for identifying differences in nucleic acid abundances (e.g., expression levels) between two or more samples. The methods involve providing an array containing a large number (e.g. greater than 1,000) of arbitrarily selected different oligonucleotide probes where the sequence and location of each different probe is known. Nucleic acid samples (e.g. mRNA) from two or more samples are hybridized to the probe arrays and the pattern of hybridization is detected. Differences in the hybridization patterns between the samples indicates differences in expression of various genes between those samples. This invention also provides a method of end-labeling a nucleic acid. In one embodiment, the method involves providing a nucleic acid, providing a labeled oligonucleotide and then enzymatically ligating the oligonucleotide to the nucleic acid. Thus, for example, where the nucleic acid is an RNA, a labeled oligoribonucleotide can be ligated using an RNA ligase. In another embodiment, the end labeling can be accomplished by providing a nucleic acid, providing labeled nucleoside triphosphates, and attaching the nucleoside triphosphates to the nucleic acid using a terminal transferase.

7. 发明授权

US06344316B1 Nucleic acid analysis techniques 失效
标题翻译：核酸分析技术
公开(公告)号：US06344316B1
公开(公告)日：2002-02-05
申请号：US08882649
申请日：1997-06-25
申请人： David J. Lockhart , Mark Chee , Kevin Gunderson , Lai Chaoqiang , Lisa Wodicka , Maureen T. Cronin , Danny Lee , Huu M. Tran , Hajime Matsuzaki
发明人： David J. Lockhart , Mark Chee , Kevin Gunderson , Lai Chaoqiang , Lisa Wodicka , Maureen T. Cronin , Danny Lee , Huu M. Tran , Hajime Matsuzaki
IPC分类号： C12Q168
CPC分类号： C07H19/052 , C07H19/12 , C07H21/00 , C12Q1/6809 , C12Q1/6837 , C12Q2600/156 , C40B40/00 , G06F19/20 , G06F19/22 , C12Q2525/161 , C12Q2565/501 , C12Q2561/125
摘要： The present invention provides a simplified method for identifying differences in nucleic acid abundances (e.g., expression levels) between two or more samples. The methods involve providing an array containing a large number (e.g. greater than 1,000) of arbitrarily selected different oligonucleotide probes where the sequence and location of each different probe is known. Nucleic acid samples (e.g. mRNA) from two or more samples are hybridized to the probe arrays and the pattern of hybridization is detected. Differences in the hybridization patterns between the samples indicates differences in expression of various genes between those samples. This invention also provides a method of end-labeling a nucleic acid. In one embodiment, the method involves providing a nucleic acid, providing a labeled oligonucleotide and then enzymatically ligating the oligonucleotide to the nucleic acid. Thus, for example, where the nucleic acid is an RNA, a labeled oligoribonucleotide can be ligated using an RNA ligase. In another embodiment, the end labeling can be accomplished by providing a nucleic acid, providing labeled nucleoside triphosphates, and attaching the nucleoside triphosphates to the nucleic acid using a terminal transferase.
摘要翻译：本发明提供用于鉴定两个或多个样品之间的核酸丰度差异（例如，表达水平）的简化方法。所述方法包括提供包含大量（例如大于1,000个）任意选择的不同寡核苷酸探针的阵列，其中每个不同探针的序列和位置是已知的。来自两个或更多个样品的核酸样品（例如mRNA）与探针阵列杂交，并检测杂交模式。样本之间的杂交模式的差异表明这些样品之间各种基因的表达差异。本发明还提供了一种终止标记核酸的方法。在一个实施方案中，该方法包括提供核酸，提供标记的寡核苷酸，然后将寡核苷酸酶连接到核酸上。因此，例如，当核酸是RNA时，可以使用RNA连接酶连接标记的寡核糖核苷酸。在另一个实施方案中，末端标记可以通过提供核酸，提供标记的核苷三磷酸和使用末端转移酶将核苷三磷酸与核酸连接来实现。

8. 发明授权

US08951940B2 Solid-phase clonal amplification and related methods 有权
标题翻译：固相克隆扩增及相关方法
公开(公告)号：US08951940B2
公开(公告)日：2015-02-10
申请号：US13637770
申请日：2011-03-16
申请人： Neil A. Straus , Shengrong Lin , Helmy A. Eltoukhy , Kevin Gunderson
发明人： Neil A. Straus , Shengrong Lin , Helmy A. Eltoukhy , Kevin Gunderson
IPC分类号： C40B50/06 , C12Q1/68 , C07H21/04
CPC分类号： C12Q1/6874 , C12Q1/6834 , C12Q1/6837 , C12Q2531/125 , C12Q2563/149
摘要： The present invention provides methods and compositions for analyzing nucleic acid sequences. In some aspects, the methods utilize clonal objects, such as DNA balls, that have been captured on beads. Using the methods described here, compositions are fabricated wherein a bead and one clonal object are affinity bound or hybridized to each other through an affinity binding patch or hybridization patch on the surface of the bead. The invention also provides a population of beads having affinity bound or hybridized clonal objects at a ratio of 1:1. The invention additionally provides methods for amplifying a target nucleic acid molecule utilizing the compositions described herein.
摘要翻译：本发明提供了用于分析核酸序列的方法和组合物。在某些方面，该方法利用已被捕获在珠上的克隆物体，例如DNA球。使用本文描述的方法，制备组合物，其中珠粒和一个克隆物体通过珠粒表面上的亲和结合片段或杂交片段彼此亲和地结合或杂交。本发明还提供了以1:1的比例具有亲和结合或杂交的克隆物体的珠群。本发明另外提供了利用本文所述组合物扩增靶核酸分子的方法。

9. 发明授权

US08914241B2 Nucleic acid sequencing system and method 有权
标题翻译：核酸测序系统及方法
公开(公告)号：US08914241B2
公开(公告)日：2014-12-16
申请号：US12878687
申请日：2010-09-09
申请人： Robert C. Kain , David L. Heiner , Chanfeng Zhao , Kevin Gunderson
发明人： Robert C. Kain , David L. Heiner , Chanfeng Zhao , Kevin Gunderson
IPC分类号： G06F19/20 , C12Q1/68 , C12M1/34 , C12M3/00 , G06F19/22
CPC分类号： C12Q1/6874 , C12Q1/686 , C12Q1/6869 , G06F19/20 , G06F19/22 , C12Q2565/501 , C12Q2537/143
摘要： A technique for sequencing nucleic acids in an automated or semi-automated manner is disclosed. Sample arrays of a multitude of nucleic acid sites are processed in multiple cycles to add nucleotides to the material to be sequenced, detect the nucleotides added to sites, and to de-block the added nucleotides of blocking agents and tags used to identify the last added nucleotide. Multiple parameters of the system are monitored to enable diagnosis and correction of problems as they occur during sequencing of the samples. Quality control routines are run during sequencing to determine quality of samples, and quality of the data collected.
摘要翻译：公开了以自动或半自动方式测序核酸的技术。多个核酸位点的样品阵列在多个周期内进行处理以向要测序的材料添加核苷酸，检测添加到位点的核苷酸，以及去除阻断剂的添加核苷酸和用于鉴定最后添加的标签核苷酸。对系统的多个参数进行监控，以便在样品排序期间发生问题的诊断和纠正。质量控制程序在排序过程中运行，以确定样品的质量和收集的数据的质量。

10. 发明申请

US20120202704A1 MULTI-SAMPLE INDEXING FOR MULTIPLEX GENOTYPING 审中-公开
标题翻译：多重基因多样性指数
公开(公告)号：US20120202704A1
公开(公告)日：2012-08-09
申请号：US13501502
申请日：2010-12-07
申请人： Jian-Bing Fan , Kevin Gunderson
发明人： Jian-Bing Fan , Kevin Gunderson
IPC分类号： C40B30/04
CPC分类号： C12N15/1065 , C12Q1/6816 , C12Q1/6827 , C12Q2521/501 , C12Q2525/155 , C12Q2533/101 , C12Q2533/107 , C12Q2537/143 , C12Q2563/179 , C12Q2565/102 , C12Q2525/186
摘要： A method for determining the presence of multiple nucleotide sequences of interest in multiple samples while preserving the identity of each sample, by contacting the samples with a plurality of probe sets. The probes are designed to indicate the presence of the sequences of interest and the identity of the sample containing the sequence of interest in complex mixtures. Applications of the method include genotyping, expression analysis, and identification of individual species in complex samples. Kits of probe sets for use in the methods are also provided.
摘要翻译：通过使样本与多个探针组接触，确定多个样品中多个核苷酸序列的存在同时保持每个样品的身份的方法。探针被设计为指示感兴趣的序列的存在和在复杂混合物中含有感兴趣的序列的样品的身份。该方法的应用包括基因分型，表达分析和复杂样本中个体物种的鉴定。还提供了用于方法的探针组的套件。

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