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1. 发明授权

US09868945B2 Linking methods, compositions, systems, kits and apparatuses 有权
公开(公告)号：US09868945B2
公开(公告)日：2018-01-16
申请号：US13984346
申请日：2012-02-08
申请人： John Davidson , Theo Nikiforov , Guobin Luo
发明人： John Davidson , Theo Nikiforov , Guobin Luo
IPC分类号： C12N11/10 , C12N9/12 , C12Q1/68
CPC分类号： C12N11/10 , C12N9/1241 , C12Q1/68 , G01N2333/9126
摘要： In some embodiments, the disclosure relates generally to methods as well as related compositions, systems, kits and apparatus comprising linking proteins to target compounds and/or to locations of interest using tethers. For example, the tether can be used to link the protein to a target compound, for example, to link an enzyme to a substrate. Similarly, the tether can be used to link the protein at or near a desired location on a surface. In one group of embodiments, the tether includes a polynucleotide and the target compound or location on the surface includes another polynucleotide that is capable of hybridizing to the tether. In such embodiments, the tether can be used to link the protein to the target compound or location using nucleic acid hybridization.

2. 发明申请

US20130344561A1 LINKING METHODS, COMPOSITIONS, SYSTEMS, KITS AND APPARATUSES 有权
标题翻译：链接方法，组合，系统，工具和设备
公开(公告)号：US20130344561A1
公开(公告)日：2013-12-26
申请号：US13984346
申请日：2012-02-08
申请人： John Davidson , Theo Nikiforov , Guobin Luo
发明人： John Davidson , Theo Nikiforov , Guobin Luo
IPC分类号： C12N11/10
CPC分类号： C12N11/10 , C12N9/1241 , C12Q1/68 , G01N2333/9126
摘要： In some embodiments, the disclosure relates generally to methods as well as related compositions, systems, kits and apparatus comprising linking proteins to target compounds and/or to locations of interest using tethers. For example, the tether can used to link the protein to a target compound, for example, to link an enzyme to a substrate. Similarly, the tether can be used to link the protein at or near a desired location on a surface. In one group of embodiments, the tether includes a polynucleotide and the target compound or location on the surface includes another polynucleotide that is capable of hybridizing to the tether. In such bodiments, the tether can be used to link the protein to the target compound or location using nucleic acid hybridization.
摘要翻译：在一些实施方案中，本公开一般涉及方法以及相关组合物，系统，试剂盒和装置，其包括使用系链将蛋白质与靶化合物和/或感兴趣的位置连接。例如，系链可以用于将蛋白质连接到目标化合物，例如将酶连接到底物上。类似地，系链可用于将蛋白质链接在表面上的期望位置处或附近。在一组实施方案中，系链包括多核苷酸，并且目标化合物或表面上的位置包括能够与系链杂交的另一多核苷酸。在这样的实验中，系链可用于使用核酸杂交将蛋白质与靶化合物或位置连接。

3. 发明授权

US08632975B2 Nucleotide transient binding for sequencing methods 有权
标题翻译：测序方法的核苷酸瞬变结合
公开(公告)号：US08632975B2
公开(公告)日：2014-01-21
申请号：US12790760
申请日：2010-05-28
申请人： Peter B. Vander Horn , Cheng-Yao Chen , Guobin Luo , Michael Previte , Jamshid Temirov , Theo Nikiforov , Zhaohui Zhou , Hongye Sun , Yufang Wang , Stefanie Yukiko Nishimura , Hongyi Wang , Marian Peris , Barnett B. Rosenblum , Michael Phelan
发明人： Peter B. Vander Horn , Cheng-Yao Chen , Guobin Luo , Michael Previte , Jamshid Temirov , Theo Nikiforov , Zhaohui Zhou , Hongye Sun , Yufang Wang , Stefanie Yukiko Nishimura , Hongyi Wang , Marian Peris , Barnett B. Rosenblum , Michael Phelan
IPC分类号： C12Q1/68
CPC分类号： C12N9/1252 , C12Q1/68 , C12Q1/6804 , C12Q1/6818 , C12Q1/6827 , C12Q1/6869 , C12Q1/6872 , C12Y207/07007 , G01N2500/00 , C12Q2565/632 , C12Q2563/137 , C12Q2563/107 , C12Q2565/30 , C12Q2537/157
摘要： Provided herein are compositions and systems for use in polymerase-dependent, nucleotide transient-binding methods. The methods are useful for deducing the sequence of a template nucleic acid molecule and single nucleotide polymorphism (SNP) analyses. The methods rely on the fact that the polymerase transient-binding time for a complementary nucleotide is longer compared to that of a non-complementary nucleotide. The labeled nucleotides transiently-binds the polymerase in a template-dependent manner, but does not incorporate. The methods are conducted under any reaction condition that permits transient binding of a complementary or non-complementary nucleotide to a polymerase, and inhibits nucleotide incorporation.
摘要翻译：本文提供了用于聚合酶依赖性核苷酸瞬变结合方法的组合物和系统。该方法可用于推导模板核酸分子和单核苷酸多态性（SNP）分析的序列。该方法依赖于与非互补核苷酸相比，互补核苷酸的聚合酶瞬时结合时间更长的事实。标记的核苷酸以模板依赖的方式瞬时结合聚合酶，但不包括在内。所述方法在允许互补或非互补核苷酸与聚合酶短暂结合并且抑制核苷酸掺入的任何反应条件下进行。

4. 发明授权

US08999674B2 Methods and apparatus for single molecule sequencing using energy transfer detection 有权
标题翻译：使用能量转移检测的单分子测序的方法和装置
公开(公告)号：US08999674B2
公开(公告)日：2015-04-07
申请号：US13562159
申请日：2012-07-30
申请人： Joseph Beechem , Theo Nikiforov , Vi-En Choong , Xinzhan Peng , Guobin Luo , Cheng-Yao Chen , Michael Previte
发明人： Joseph Beechem , Theo Nikiforov , Vi-En Choong , Xinzhan Peng , Guobin Luo , Cheng-Yao Chen , Michael Previte
IPC分类号： C12P19/34 , C12N9/12 , C07H19/20
CPC分类号： C12Q1/6869 , C07H19/20 , C12N9/1241 , C12N9/1252 , C12N9/96 , C12Q1/6818 , C12Y207/07 , C12Y207/07007 , G01N21/6428 , G01N33/582 , G01N2021/6432
摘要： Provided herein are systems and methods for nucleotide incorporation reactions. The systems comprise polymerases having altered nucleotide incorporation kinetics and are linked to an energy transfer donor moiety, and nucleotide molecules linked with at least one energy transfer acceptor moiety. The donor and acceptor moieties undergo energy transfer when the polymerase and nucleotide are proximal to each other during nucleotide binding and/or nucleotide incorporation. As the donor and acceptor moieties undergo energy transfer, they generate an energy transfer signal which can be associated with nucleotide binding or incorporation. Detecting a time sequence of the generated signals, or the change in the signals, can be used to determine the order of the incorporated nucleotides, and can therefore be used to deduce the sequence of the target molecule.
摘要翻译：本文提供了用于核苷酸掺入反应的系统和方法。该系统包含具有改变的核苷酸掺入动力学并且与能量转移供体部分连接的聚合酶，以及与至少一个能量转移受体部分连接的核苷酸分子。当核苷酸结合和/或核苷酸掺入期间聚合酶和核苷酸彼此接近时，供体和受体部分进行能量转移。当供体和受体部分进行能量转移时，它们产生可与核苷酸结合或掺入相关联的能量转移信号。检测所产生的信号的时间序列或信号的变化可用于确定掺入的核苷酸的顺序，因此可用于推导靶分子的序列。

5. 发明申请

US20100330570A1 NUCLEOTIDE TRANSIENT BINDING FOR SEQUENCING METHODS 有权
标题翻译：用于测序方法的核心瞬态绑定
公开(公告)号：US20100330570A1
公开(公告)日：2010-12-30
申请号：US12790760
申请日：2010-05-28
申请人： Peter B. VANDER HORN , Cheng-Yao Chen , Guobin Luo , Michael Previte , Jamshid Temirov , Theo Nikiforov , Zhaohui Zhou , Hongye Sun , Yufang Wang , Stefanie Yukiko Nishimura , Hongyi Wang , Marian Peris , Barnett B. Rosenblum , Michael Phelan
发明人： Peter B. VANDER HORN , Cheng-Yao Chen , Guobin Luo , Michael Previte , Jamshid Temirov , Theo Nikiforov , Zhaohui Zhou , Hongye Sun , Yufang Wang , Stefanie Yukiko Nishimura , Hongyi Wang , Marian Peris , Barnett B. Rosenblum , Michael Phelan
IPC分类号： C12Q1/68 , C12N9/96
CPC分类号： C12N9/1252 , C12Q1/68 , C12Q1/6804 , C12Q1/6818 , C12Q1/6827 , C12Q1/6869 , C12Q1/6872 , C12Y207/07007 , G01N2500/00 , C12Q2565/632 , C12Q2563/137 , C12Q2563/107 , C12Q2565/30 , C12Q2537/157
摘要： Provided herein are compositions and systems for use in polymerase-dependent, nucleotide transient-binding methods. The methods are useful for deducing the sequence of a template nucleic acid molecule and single nucleotide polymorphism (SNP) analyses. The methods rely on the fact that the polymerase transient-binding time for a complementary nucleotide is longer compared to that of a non-complementary nucleotide. The labeled nucleotides transiently-binds the polymerase in a template-dependent manner, but does not incorporate. The methods are conducted under any reaction condition that permits transient binding of a complementary or non-complementary nucleotide to a polymerase, and inhibits nucleotide incorporation.
摘要翻译：本文提供了用于聚合酶依赖性核苷酸瞬变结合方法的组合物和系统。该方法可用于推导模板核酸分子和单核苷酸多态性（SNP）分析的序列。该方法依赖于与非互补核苷酸相比，互补核苷酸的聚合酶瞬时结合时间更长的事实。标记的核苷酸以模板依赖的方式瞬时结合聚合酶，但不包括在内。所述方法在允许互补或非互补核苷酸与聚合酶短暂结合并且抑制核苷酸掺入的任何反应条件下进行。

6. 发明申请

US20070161071A1 Assay methods and systems 审中-公开
标题翻译：测定方法和系统
公开(公告)号：US20070161071A1
公开(公告)日：2007-07-12
申请号：US11595271
申请日：2006-11-10
申请人： Theo Nikiforov
发明人： Theo Nikiforov
IPC分类号： C12Q1/48
CPC分类号： G01N33/542 , C12Q1/37 , C12Q1/42 , C12Q1/48 , C12Q1/485 , C12Q1/6816 , G01N2333/9121 , C12Q2565/107 , C12Q2563/107
摘要： Methods, systems, kits for carrying out a wide variety of different assays that comprise providing a first reagent mixture which comprises a first reagent having a fluorescent label. A second reagent is introduced into the first reagent mixture to produce a second reagent mixture, where the second reagent reacts with the first reagent to produce a fluorescently labeled product having a substantially different charge than the first reagent. A polyion is introduced into at least one of the first and second reagent mixtures, and the fluorescent polarization in the second reagent mixture relative to the first reagent mixture is determined, this fluorescent polarization being indicative of the rate or extent of the reaction.
摘要翻译：用于进行各种不同测定的方法，系统，试剂盒，其包括提供包含具有荧光标记的第一试剂的第一试剂混合物。将第二试剂引入第一试剂混合物中以产生第二试剂混合物，其中第二试剂与第一试剂反应以产生具有与第一试剂基本不同的电荷的荧光标记产物。将聚离子引入第一和第二试剂混合物中的至少一种，并且确定第二试剂混合物中相对于第一试剂混合物的荧光偏振，该荧光偏振指示反应的速率或程度。

7. 发明申请

US20060254503A1 Seed layers, cap layers, and thin films and methods of making thereof 有权
标题翻译：种子层，盖层和薄膜及其制造方法
公开(公告)号：US20060254503A1
公开(公告)日：2006-11-16
申请号：US11433824
申请日：2006-05-15
申请人： Haixia Dai , Khashayar Pakbaz , Michael Spaid , Theo Nikiforov
发明人： Haixia Dai , Khashayar Pakbaz , Michael Spaid , Theo Nikiforov
IPC分类号： C30B23/00
CPC分类号： C23C18/1608 , B82Y30/00 , C23C18/1844 , C23C18/50 , H01L21/288 , H01L21/76814 , H01L21/76843 , H01L21/76849 , H01L21/7685 , H01L21/76861 , H01L21/76864 , H01L21/76867 , H01L21/76868 , H01L21/76871 , H01L21/76874 , H01L21/76879
摘要： A seed layer is formed on a substrate using a first biological agent. The seed layer may comprise densified nanoparticles which are bound to the biological agent. The seed layer is then used for a deposition of a metal layer, such as a barrier layer, an interconnect layer, a cap layer and/or a bus line for a solid state device.
摘要翻译：使用第一生物试剂在基材上形成种子层。种子层可以包含与生物制剂结合的致密化纳米颗粒。然后种子层用于沉积用于固态器件的金属层，例如阻挡层，互连层，盖层和/或总线。

8. 发明申请

US20060068410A1 Methods and systems for monitoring intracellular binding reactions 审中-公开
公开(公告)号：US20060068410A1
公开(公告)日：2006-03-30
申请号：US11070155
申请日：2005-03-01
申请人： H. Wada , Javier Farinas , Theo Nikiforov
发明人： H. Wada , Javier Farinas , Theo Nikiforov
IPC分类号： C12Q1/68 , C12M1/34
CPC分类号： C12Q1/6841 , G01N21/6428 , G01N21/6445 , G01N21/6458 , G01N33/5008 , G01N33/5041 , G01N33/542 , G01N33/582 , G01N33/6872 , C12Q2561/119
摘要： Intracellular binding reactions, and particularly DNA/DNA binding protein reactions are detected in situ, using intracellular fluorescence polarization detection. The methods comprise providing a biological cell having at least a first component of a binding reaction disposed therein. The cell is contacted with a second component of the binding reaction whereby the second component is internalized within the biological cell. At least one of the first and second components has a fluorescent label. The amount of binding between the first and second components within the cell is determined by measuring a level of polarized and/or depolarized fluorescence emitted from within the biological cell.

9. 发明申请

US20060219557A1 Methods and systems for reducing background signal in assays 审中-公开
公开(公告)号：US20060219557A1
公开(公告)日：2006-10-05
申请号：US11411992
申请日：2006-04-25
申请人： Theo Nikiforov , Aileen Zhou
发明人： Theo Nikiforov , Aileen Zhou
IPC分类号： C07K1/26
CPC分类号： G01N27/44726
摘要： Methods and systems of monitoring reactions, e.g., assays, that filter out background signal from substrate, in detecting the product. The methods and systems controllably move detectable reaction product from a first location to a second location at which the product is detected while controllably moving potentially interfering substrate materials away from or not toward the second location. Controllable movement of the different species is accomplished through the controlled combination of bulk fluid flow and differential electrophoresis of substrate and product to move the product, but not the substrate past the detection region.

10. 发明申请

US20050176071A1 Homogeneous assay methods 审中-公开
标题翻译：均相测定方法
公开(公告)号：US20050176071A1
公开(公告)日：2005-08-11
申请号：US10855657
申请日：2004-05-27
申请人： Theo Nikiforov , Sang Jeong
发明人： Theo Nikiforov , Sang Jeong
IPC分类号： C12Q1/48 , G01N33/542 , G01N33/543 , G01N33/53
CPC分类号： C12Q1/485 , G01N33/542 , G01N33/54306
摘要： The present invention provides a method of assaying for kinase activity, comprising contacting a fluorescently labeled phosphorylatable peptide substrate with an ATP analog in the presence of a kinase enzyme to yield a first product; contacting the first product with a reactant that comprises a biotin derivative to yield a second product; contacting the second product with a biotin-binding protein; and detecting a difference in a fluorescence polarization level from the second product as compared to a fluorescence polarization of the peptide substrate.
摘要翻译：本发明提供了测定激酶活性的方法，包括在激酶的存在下使荧光标记的可磷酸化肽底物与ATP类似物接触以产生第一产物; 使第一产物与包含生物素衍生物的反应物接触以产生第二产物; 使第二产物与生物素结合蛋白接触; 并且与肽基板的荧光偏振相比，检测来自第二产物的荧光偏振电平的差异。

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