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1. 发明申请

WO2022235794A1 ARRAYS OF INTEGRATED ANALYTICAL DEVICES WITH REDUCED-SCALE UNIT CELL 审中-公开
公开(公告)号：WO2022235794A1
公开(公告)日：2022-11-10
申请号：PCT/US2022/027664
申请日：2022-05-04
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
发明人： CALLEBAUT, Hans , MCDONALD, Mark , ARJMAND, Arghavan , GROT, Annette , FOQUET, Mathieu , SAXENA, Ravi , RU, Michael Tzu
IPC分类号： C12Q1/6825 , C12Q1/6874 , B82Y15/00 , G01J3/28 , G01N21/01
摘要： Arrays of integrated analytical devices are provided. The arrays are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. In particular, the arrays provide increased efficiency of optical collection and decreased background signal as the lateral dimensions of the unit cell of devices within the array are decreased, for example as they are decreased to 2 µm, or even less.

2. 发明申请

WO2017087975A1 LABELED NUCLEOTIDE ANALOGS, REACTION MIXTURES, AND METHODS AND SYSTEMS FOR SEQUENCING 审中-公开
标题翻译：标记的核苷酸类似物，反应混合物以及用于测序的方法和系统
公开(公告)号：WO2017087975A1
公开(公告)日：2017-05-26
申请号：PCT/US2016/063178
申请日：2016-11-21
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
发明人： SEBO, Lubomir , SHEN, Gene , YUE, Stephen , OSUNA, Honey , LAPIN, Yuri , BROGLEY, Louis , FEDOROV, Andrei
IPC分类号： A61F2/06 , A61F2/82 , A61L31/08 , C08L67/02 , C08L67/04 , C08L67/06
CPC分类号： C12Q1/6869 , C07H19/10 , C07K19/00 , C12Q2563/107
摘要： Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.
摘要翻译：提供了包含至少一种抗生物素蛋白，至少一种染料标记的化合物和至少一种核苷酸化合物的标记的核苷酸类似物。这些类似物可用于各种基于荧光的分析方法，包括高密度分析大量高度多重光学反应，如单分子实时核酸测序反应。类似物在理想的波长处以高灵敏度可检测。它们含有调节类似物与DNA聚合酶相互作用的结构成分，从而减少光损伤并改善测序反应中类似物的动力学和其他性质。还提供了主题类似物的核苷酸和染料标记的化合物，以及可用于制备化合物和类似物的中间体。还提供了包含所述化合物的组合物，所述中间体，化合物和类似物的合成方法以及突变型DNA聚合酶。

3. 发明申请

WO2016126941A1 MULTIMERIC PROTECTED FLUORESCENT REAGENTS 审中-公开
标题翻译：多元保护荧光试剂
公开(公告)号：WO2016126941A1
公开(公告)日：2016-08-11
申请号：PCT/US2016/016564
申请日：2016-02-04
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
发明人： ZHENG, Frank , HANES, Jeremiah , SHEN, Gene , BROGLEY, Louis , YUE, Stephen , LAPIN, Yuri , LYLE, John , OSUNA, Honey , FEDOROV, Andrei , SEBO, Lubomir
IPC分类号： A61K38/00 , A61K38/02 , C07K14/435 , C12Q1/68 , G01N33/58
CPC分类号： C09B23/105 , C09B23/06 , C09B69/00 , C09B69/105 , G01N33/533
摘要： Multimeric protected fluorescent reagents and their methods of synthesis are provided. The reagents are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The reagents contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements. The reagents also contain coupling elements connect monomeric compounds into multimeric forms, thereby increasing brightness.
摘要翻译：提供了多聚体保护的荧光试剂及其合成方法。这些试剂可用于各种基于荧光的分析方法，包括以高密度大量多重光学反应的分析，如单分子实时核酸测序反应。试剂含有荧光染料元素，其允许以期望波长的高灵敏度检测化合物，允许化合物被目标生物分子特异性识别的结合元件以及减少荧光染料元件之间不希望的接触的保护屏蔽元件和结合的靶生物分子，因此由荧光染料元素降低结合的靶生物分子的光损伤。试剂还含有偶联元件将单体化合物连接成多聚体形式，从而增加亮度。

4. 发明申请

WO2014150392A1 METHODS AND COMPOSITIONS FOR NUCLEIC ACID SEQUENCING USING ELECTRONIC SENSING ELEMENTS 审中-公开
标题翻译：使用电子感应元件的核酸序列的方法和组合物
公开(公告)号：WO2014150392A1
公开(公告)日：2014-09-25
申请号：PCT/US2014/023132
申请日：2014-03-11
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
发明人： HANES, Jeremiah , KORLACH, Jonas , TURNER, Stephen
IPC分类号： C12Q1/68 , G01N27/26
CPC分类号： C12Q1/6869 , C12Q2521/525 , C12Q2525/113 , C12Q2565/607
摘要： The present invention is directed to methods, devices, compositions and systems for obtaining sequence data from nucleic acid templates by utilizing electronic sensing elements.
摘要翻译：本发明涉及通过利用电子感测元件从核酸模板获得序列数据的方法，装置，组合物和系统。

5. 发明申请

WO2013185137A1 MODIFIED BASE DETECTION WITH NANOPORE SEQUENCING 审中-公开
标题翻译：用纳米级序列改性基底检测
公开(公告)号：WO2013185137A1
公开(公告)日：2013-12-12
申请号：PCT/US2013/045009
申请日：2013-06-10
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC.
发明人： TURNER, Stephen , KORLACH, Jonas
IPC分类号： C12Q1/68 , C12N15/09
CPC分类号： C12Q1/6869 , C12Q1/68 , C12Q1/6874 , G01N27/447 , G01N33/48721 , C12Q1/6827 , C12Q2521/513 , C12Q2521/543 , C12Q2565/631
摘要： Methods, compositions, and systems are provided for characterization of modified nucleic acids. Nanopore sequencing is performed using a processive enzyme to control the rate of translation of a single strand of a nucleic acid through a nanopore. The presence and identity of a modified base can be determined by monitoring the kinetics of translation through the pore even though the events that lead to the kinetic changes are separated in time and space from the translation of the modified base or it's compliment through the nanopore. The invention also comprises the use of hemi-genomic DNA in nanopore sequencing.
摘要翻译：提供了方法，组合物和系统用于表征修饰的核酸。使用过程酶进行纳米孔测序以控制核酸的单链通过纳米孔的翻译速率。即使导致动力学变化的事件在时间和空间上与经修饰的碱基的翻译或通过纳米孔的补充分离，也可以通过监测通过孔的翻译的动力学来确定改性碱基的存在和特性。本发明还包括在半纳米孔测序中使用半基因组DNA。

6. 发明申请

WO2012065043A2 CLASSIFICATION OF NUCLEIC ACID TEMPLATES 审中-公开
标题翻译：核酸模板的分类
公开(公告)号：WO2012065043A2
公开(公告)日：2012-05-18
申请号：PCT/US2011/060338
申请日：2011-11-11
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC. , FLUSBERG, Benjamin , KORLACH, Jonas , WEGENER, Jeffrey , CLARK, Tyson, A. , VILFAN, Igor , KISLYUK, Andrey , TURNER, Stephen , SORENSON, Jon , TRAVERS, Kevin , HEINER, Cheryl , TOMANEY, Austin, B. , MARKS, Patrick , LEE, Jessica , JIA, Lei , WEBSTER, Dale , LYLE, John , HANES, Jeremiah , PUGLISI, Joseph
发明人： FLUSBERG, Benjamin , KORLACH, Jonas , WEGENER, Jeffrey , CLARK, Tyson, A. , VILFAN, Igor , KISLYUK, Andrey , TURNER, Stephen , SORENSON, Jon , TRAVERS, Kevin , HEINER, Cheryl , TOMANEY, Austin, B. , MARKS, Patrick , LEE, Jessica , JIA, Lei , WEBSTER, Dale , LYLE, John , HANES, Jeremiah , PUGLISI, Joseph
IPC分类号： C12Q1/68 , C12N15/11 , C12Q1/34 , C12Q1/48 , C12Q1/25
CPC分类号： C12Q1/6869 , C12Q1/6837 , C12Q1/6858 , C12Q1/6874 , C12Q1/689 , C12Q2600/154 , C12Q2537/164 , C12Q2527/113 , C12Q2521/101 , C12Q2525/307 , C12Q2525/117
摘要： Methods, compositions, and systems are provided for characterization of modified nucleic acids. In certain preferred embodiments, single molecule sequencing methods are provided for identification of modified nucleotides within nucleic acid sequences. Modifications detectable by the methods provided herein include chemically modified bases, enzymatically modified bases, abasic sites, non-natural bases, secondary structures, and agents bound to a template nucleic acid.
摘要翻译：提供了用于表征修饰的核酸的方法，组合物和系统。在某些优选的实施方案中，提供单分子测序方法用于鉴定核酸序列内的修饰的核苷酸。通过本文提供的方法可检测的修饰包括化学修饰的碱基，酶修饰的碱基，无碱基位点，非天然碱基，二级结构和与模板核酸结合的试剂。

7. 发明申请

WO2011112260A2 MICROMIRROR ARRAYS HAVING SELF ALIGNED FEATURES 审中-公开
标题翻译：具有自对准特征的MICROMIRROR ARRAYS
公开(公告)号：WO2011112260A2
公开(公告)日：2011-09-15
申请号：PCT/US2011/000452
申请日：2011-03-10
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC. , MONADGEMI, Pezhman
发明人： MONADGEMI, Pezhman
IPC分类号： G02B26/00 , G01N21/00
CPC分类号： B29D11/00596 , B82Y20/00 , G02B1/118 , G02B5/09 , G02B5/26 , G02B6/3512 , G02B6/3556 , G02B6/3584 , G02B2207/101
摘要： Methods, arrays, and systems for the optical analysis of multiple chemical, biological, or biochemical reactions are provided. The invention includes methods for producing arrays of micromirrors on transparent substrates, each micromirror comprising a nanostructure or optical confinement on its top. The arrays are produced by a process in which lateral dimensions of both the nanostructures and micromirrors are defined in a single step, allowing for control of the relative placement of the features on the substrate, minimizing the process-related defects, allowing for improved optical performance and consistency. In some aspects, the invention provides methods of selectively etching large features on a substrate while not concurrently etching small features. In some aspects, the invention provides methods of etching large features on a substrate using hard mask materials.
摘要翻译：提供了用于多种化学，生物或生化反应的光学分析的方法，阵列和系统。本发明包括在透明衬底上产生微镜阵列的方法，每个微反射镜在其顶部包括纳米结构或光学限制。阵列是通过一个方法制造的，其中纳米结构和微反射镜的横向尺寸在单个步骤中被限定，允许控制特征在基底上的相对放置，最小化与工艺相关的缺陷，允许改进的光学性能和一致性。在一些方面，本发明提供了选择性地蚀刻衬底上的大特征而不同时蚀刻小特征的方法。在一些方面，本发明提供了使用硬掩模材料在基底上蚀刻大特征的方法。

8. 发明申请

WO2011103504A1 INTEGRATED ANALYTICAL SYSTEM AND METHOD 审中-公开
标题翻译：综合分析系统与方法
公开(公告)号：WO2011103504A1
公开(公告)日：2011-08-25
申请号：PCT/US2011/025537
申请日：2011-02-18
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC. , MCCAFFREY, Nathaniel, Joseph , TURNER, Stephen , SAXENA, Ravi , HELGESEN, Scott, Edward
发明人： MCCAFFREY, Nathaniel, Joseph , TURNER, Stephen , SAXENA, Ravi , HELGESEN, Scott, Edward
IPC分类号： G01N21/00
CPC分类号： C12Q1/6874 , B01L3/502707 , B01L3/502715 , B01L2300/0654 , B01L2300/0663 , B01L2300/0816 , B01L2300/168 , B82Y20/00 , C12Q1/6825 , C12Q1/6869 , G01N21/03 , G01N21/0303 , G01N21/05 , G01N21/64 , G01N21/6428 , G01N21/645 , G01N21/6452 , G01N21/6454 , G01N21/6456 , G01N21/648 , G01N21/75 , G01N21/77 , G01N33/54373 , G01N2021/0346 , G01N2021/6434 , G01N2021/6439 , G01N2021/6441 , G01N2021/6463 , G01N2021/757 , G01N2021/7786 , G01N2201/067 , G01N2201/068 , G01N2201/08 , G02B6/1226 , Y10T436/143333
摘要： An analytical assembly within a unified device structure for integration into an analytical system. The analytical assembly is scalable and includes a plurality of analytical devices, each of which includes a reaction cell, an optical sensor, and at least one optical element positioned in optical communication with both the reaction cell and the sensor and which delivers optical signals from the cell to the sensor. Additional elements are optionally integrated into the analytical assembly. Methods for forming and operating the analytical system are also disclosed.
摘要翻译：用于集成到分析系统中的统一设备结构内的分析组件。分析组件是可扩展的，并且包括多个分析装置，每个分析装置包括反应池，光学传感器和定位成与反应池和传感器两者光学通信的至少一个光学元件，电池到传感器。额外的元件可选地集成到分析组件中。还公开了形成和操作分析系统的方法。

9. 发明申请

WO2010144151A2 SINGLE-MOLECULE REAL-TIME ANALYSIS OF PROTEIN SYNTHESIS 审中-公开
标题翻译：单分子实时分析蛋白质合成
公开(公告)号：WO2010144151A2
公开(公告)日：2010-12-16
申请号：PCT/US2010/001692
申请日：2010-06-11
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC. , FLUSBERG, Benjamin , TURNER, Stephen , KORLACH, Jonas , SCHADT, Eric
发明人： FLUSBERG, Benjamin , TURNER, Stephen , KORLACH, Jonas , SCHADT, Eric
IPC分类号： C12Q1/68
CPC分类号： G01N33/542 , G01N33/6818 , Y10T436/13 , Y10T436/143333
摘要： The present invention is generally directed to compositions, methods, and systems for performing single-molecule, real-time analysis of analytical reactions in which protein synthesis is occurring. The ability to analyze such reactions provides an opportunity to study those reactions as well as to potentially identify factors and/or approaches for impacting such reactions, e.g., to either enhance, inhibit, or otherwise affect such reactions including, but not limited to, affecting the reaction rate, processivity, fidelity, duration, and the like.
摘要翻译：本发明一般涉及用于进行蛋白质合成发生的分析反应的单分子实时分析的组合物，方法和系统。分析这些反应的能力提供了研究这些反应的机会，并且潜在地鉴定影响这些反应的因素和/或方法，例如增强，抑制或以其他方式影响这些反应，包括但不限于影响反应速度，持续性，持续时间等。

10. 发明申请

WO2010117470A2 NANOPORE SEQUENCING DEVICES AND METHODS 审中-公开
标题翻译： NANOPORE顺序设备和方法
公开(公告)号：WO2010117470A2
公开(公告)日：2010-10-14
申请号：PCT/US2010/001072
申请日：2010-04-09
申请人： PACIFIC BIOSCIENCES OF CALIFORNIA, INC. , TURNER, Stephen , FLUSBERG, Benjamin , FOQUET, Mathieu , CALLEBAUT, Hans , SEBRA, Robert , CHAUDHURI, Bidhan , SORENSON, Jon , BJORNSON, Keith , FEHR, Adrian , KORLACH, Jonas , EMIG, Robin
发明人： TURNER, Stephen , FLUSBERG, Benjamin , FOQUET, Mathieu , CALLEBAUT, Hans , SEBRA, Robert , CHAUDHURI, Bidhan , SORENSON, Jon , BJORNSON, Keith , FEHR, Adrian , KORLACH, Jonas , EMIG, Robin
IPC分类号： C12Q1/68 , B82B3/00 , G01N33/48
CPC分类号： G01N33/48721 , B82Y5/00 , B82Y15/00 , C12Q1/6869 , C12Q1/6874 , C12Q2565/631 , G01N27/447 , G01N27/44791 , C12Q2563/116 , C12Q2527/113
摘要： The invention relates to devices and methods for nanopore sequencing. The invention includes arrays of nanopores having incorporated electronic circuits, for example, in CMOS. In some cases, the arrays of nanopores comprise resistive openings for isolating the electronic signals for improved sequencing. Methods for controlling translocation of through the nanopore are disclosed.
摘要翻译：本发明涉及纳米孔测序的装置和方法。本发明包括纳入电子电路的纳米孔阵列，例如在CMOS中。在一些情况下，纳米孔阵列包括用于隔离电子信号的电阻开口以改善测序。公开了通过纳米孔控制易位的方法。

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