JP6805425B2 - タグ付けされたヌクレオチドを製造するための化学的方法 - Google Patents
タグ付けされたヌクレオチドを製造するための化学的方法 Download PDFInfo
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- JP6805425B2 JP6805425B2 JP2017502763A JP2017502763A JP6805425B2 JP 6805425 B2 JP6805425 B2 JP 6805425B2 JP 2017502763 A JP2017502763 A JP 2017502763A JP 2017502763 A JP2017502763 A JP 2017502763A JP 6805425 B2 JP6805425 B2 JP 6805425B2
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461969628P | 2014-03-24 | 2014-03-24 | |
| US61/969,628 | 2014-03-24 | ||
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11396677B2 (en) | 2014-03-24 | 2022-07-26 | The Trustees Of Columbia University In The City Of New York | Chemical methods for producing tagged nucleotides |
Families Citing this family (80)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6664079B2 (en) | 2000-10-06 | 2003-12-16 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
| US9708358B2 (en) | 2000-10-06 | 2017-07-18 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
| US9169510B2 (en) | 2005-06-21 | 2015-10-27 | The Trustees Of Columbia University In The City Of New York | Pyrosequencing methods and related compositions |
| WO2007053702A2 (en) | 2005-10-31 | 2007-05-10 | The Trustees Of Columbia University In The City Of New York | Synthesis of four color 3'-o-allyl modified photocleavable fluorescent nucleotides and related methods |
| EP3431615A3 (en) | 2007-10-19 | 2019-02-20 | The Trustees of Columbia University in the City of New York | Dna sequencing with non-fluorescent nucleotide reversible terminators cleavable label modified nucleotide terminators |
| US10443096B2 (en) | 2010-12-17 | 2019-10-15 | The Trustees Of Columbia University In The City Of New York | DNA sequencing by synthesis using modified nucleotides and nanopore detection |
| US9624539B2 (en) | 2011-05-23 | 2017-04-18 | The Trustees Of Columbia University In The City Of New York | DNA sequencing by synthesis using Raman and infrared spectroscopy detection |
| WO2013154999A2 (en) | 2012-04-09 | 2013-10-17 | The Trustees Of Columbia University In The City Of New York | Method of preparation of nanopore and uses thereof |
| EP2864502B1 (en) | 2012-06-20 | 2019-10-23 | The Trustees of Columbia University in the City of New York | Nucleic acid sequencing by nanopore detection of tag molecules |
| US9605309B2 (en) | 2012-11-09 | 2017-03-28 | Genia Technologies, Inc. | Nucleic acid sequencing using tags |
| US10648026B2 (en) | 2013-03-15 | 2020-05-12 | The Trustees Of Columbia University In The City Of New York | Raman cluster tagged molecules for biological imaging |
| CN105102627B (zh) | 2013-03-15 | 2018-10-19 | 纽约哥伦比亚大学理事会 | 用于检测样品中多种预定化合物的方法 |
| EP3268050B1 (en) | 2015-03-09 | 2021-07-14 | The Trustees of Columbia University in the City of New York | Pore-forming protein conjugate compositions and methods |
| CN108779138B (zh) | 2015-09-28 | 2022-06-17 | 哥伦比亚大学董事会 | 用作dna合成测序的可逆终止物的基于新的二硫键接头的核苷酸的设计与合成 |
| US20180299400A1 (en) * | 2015-10-21 | 2018-10-18 | Genia Technologies, Inc. | Use of fluoropolymers as a hydrophobic layer to support lipid bilayer formation for nanopore based dna sequencing |
| WO2017087887A1 (en) * | 2015-11-18 | 2017-05-26 | The Trustees Of Columbia University In The City Of New York | Ion sensor dna and rna sequencing by synthesis using nucleotide reversible terminators |
| CA3006233A1 (en) | 2015-11-25 | 2017-06-01 | Helen Franklin | Purification of polymerase complexes |
| WO2017125565A1 (en) * | 2016-01-21 | 2017-07-27 | Genia Technologies, Inc. | Nanopore sequencing complexes |
| CN109071212A (zh) * | 2016-01-28 | 2018-12-21 | 罗斯韦尔生物技术股份有限公司 | 使用大规模分子电子传感器阵列测量分析物的方法和装置 |
| US20170268052A1 (en) * | 2016-02-29 | 2017-09-21 | Genia Technologies, Inc. | Polymerase-template complexes |
| ES2911439T3 (es) * | 2016-03-24 | 2022-05-19 | Genia Tech Inc | Procedimientos y composiciones de bioconjugación específica de sitio útiles para sistemas de nanoporos |
| WO2017184677A1 (en) * | 2016-04-21 | 2017-10-26 | President And Fellows Of Harvard College | Method and system of nanopore-based information encoding |
| CN109661232B (zh) | 2016-05-23 | 2023-03-03 | 纽约哥伦比亚大学董事会 | 核苷酸衍生物及其使用方法 |
| US10655174B2 (en) | 2016-05-27 | 2020-05-19 | Roche Sequencing Solutions, Inc. | Tagged multi-nucleotides useful for nucleic acid sequencing |
| JP7022443B2 (ja) * | 2016-08-01 | 2022-02-18 | ロズウェル バイオテクノロジーズ，インコーポレイテッド | 分子電子センサーのための修飾ヌクレオチド三リン酸 |
| US10669580B2 (en) | 2016-08-26 | 2020-06-02 | Roche Sequencing Solutions, Inc. | Tagged nucleotides useful for nanopore detection |
| US11591647B2 (en) | 2017-03-06 | 2023-02-28 | Singular Genomics Systems, Inc. | Nucleic acid sequencing-by-synthesis (SBS) methods that combine SBS cycle steps |
| EP3600339A4 (en) | 2017-03-28 | 2021-05-19 | The Trustees of Columbia University in the City of New York | 3'-O-MODIFIED NUCLEOTIDE ANALOGUE WITH DIFFERENT FITTING LINKS TO FIX FLUORESCENT MARKERS TO THE BASE FOR DNA SEQUENCING BY SYNTHESIS |
| WO2018189214A1 (en) * | 2017-04-12 | 2018-10-18 | F. Hoffmann-La Roche Ag | A method for labeling of aldehyde containing target molecules |
| CN107190067B (zh) * | 2017-06-13 | 2019-12-13 | 厦门艾德生物医药科技股份有限公司 | 一种改进的二代测序用随机标签接头制作方法 |
| WO2019040546A1 (en) | 2017-08-23 | 2019-02-28 | Roche Sequencing Solutions, Inc | ENZYME SCREENING METHODS |
| CA3232118A1 (en) * | 2017-09-15 | 2019-03-21 | Illumina, Inc. | Sequence-detection system |
| KR102034304B1 (ko) * | 2017-12-29 | 2019-10-18 | 한국과학기술연구원 | 나노포어 구조체를 사용한 폴리펩티드의 아미노산 서열을 분석하는 방법 |
| CN111164222A (zh) * | 2018-02-16 | 2020-05-15 | 伊鲁米纳公司 | 带有电荷标签的核苷酸及其使用方法 |
| WO2019164977A1 (en) | 2018-02-21 | 2019-08-29 | Singular Genomics Systems, Inc. | Fluorinated nucleotides and uses thereof |
| EP3759116A1 (en) | 2018-02-28 | 2021-01-06 | F. Hoffmann-La Roche AG | Tagged nucleoside compounds useful for nanopore detection |
| WO2019178393A1 (en) | 2018-03-15 | 2019-09-19 | The Trustees Of Columbia University In The City Of New York | Nucleotide analogues and use thereof for nucleic acid sequencing and analysis |
| WO2019226689A1 (en) | 2018-05-22 | 2019-11-28 | Axbio Inc. | Methods, systems, and compositions for nucleic acid sequencing |
| US20210381041A1 (en) | 2018-05-28 | 2021-12-09 | Roche Sequencing Solutions, Inc. | Enzymatic Enrichment of DNA-Pore-Polymerase Complexes |
| EP3802823A1 (en) | 2018-06-05 | 2021-04-14 | Technische Universität München | Novel method for stabilizing nucleic acid nanostructures |
| CN113227772B (zh) | 2018-07-23 | 2024-11-01 | 纽约市哥伦比亚大学信托人 | 用于生物标志物检测的单分子电子多重纳米孔免疫测定 |
| EP3844497B1 (en) | 2018-08-28 | 2025-11-12 | F. Hoffmann-La Roche AG | Nanopore sequencing device comprising ruthenium-containing electrodes |
| CN109134541B (zh) * | 2018-09-10 | 2020-10-27 | 伯科生物医学科技（北京）有限公司 | 长链生物素标记物及其制备方法和用途 |
| CN113039191B (zh) | 2018-10-25 | 2024-07-16 | 奇异基因组学系统公司 | 核苷酸类似物 |
| EP3898643B1 (en) | 2018-12-19 | 2024-04-17 | Roche Diagnostics GmbH | 3' reversibly protected nucleotides for sequencing by synthesis using nanopores |
| US11970735B2 (en) | 2019-01-08 | 2024-04-30 | Singular Genomics Systems, Inc. | Nucleotide cleavable linkers and uses thereof |
| CN119662792A (zh) | 2019-02-19 | 2025-03-21 | 阿尔缇玛基因组学公司 | 用于光学检测和测序的接头和方法 |
| WO2020236526A1 (en) * | 2019-05-23 | 2020-11-26 | Stratos Genomics, Inc. | Translocation control elements, reporter codes, and further means for translocation control for use in nanopore sequencing |
| JP2022537069A (ja) | 2019-06-21 | 2022-08-23 | サーモ フィッシャー サイエンティフィック バルティックス ユーエービー | 次世代配列決定ライブラリを調製するための核酸の標識化に有用なオリゴヌクレオチドが連結された三リン酸ヌクレオチド |
| TW202120695A (zh) * | 2019-08-21 | 2021-06-01 | 美商伊路米納有限公司 | 用聚合酶將核苷酸接附至聚核苷酸 |
| US20230061438A1 (en) * | 2019-12-18 | 2023-03-02 | Roche Sequencing Solutions, Inc. | Methods of sequencing by synthesis using a consecutive labeling scheme |
| EP4100415A1 (en) * | 2020-02-06 | 2022-12-14 | F. Hoffmann-La Roche AG | Compositions that reduce template threading into a nanopore |
| US11807851B1 (en) | 2020-02-18 | 2023-11-07 | Ultima Genomics, Inc. | Modified polynucleotides and uses thereof |
| US20230249178A1 (en) | 2020-07-08 | 2023-08-10 | Roche Sequencing Solutions, Inc. | Split-pool synthesis apparatus and methods of performing split-pool synthesis |
| US20220059187A1 (en) | 2020-08-07 | 2022-02-24 | Oxford Nanopore Technologies Limited | Methods of detecting nucleic acid barcodes |
| US20240150824A1 (en) | 2020-08-11 | 2024-05-09 | Roche Sequencing Solutions, Inc. | Nucleoside-5'-oligophosphates tagged with postiviely-charged polymers, nanopores incorporating negative charges, and methods and systems using the same |
| WO2022081741A1 (en) | 2020-10-15 | 2022-04-21 | Roche Sequencing Solutions, Inc. | Electrophoretic devices and methods for next-generation sequencing library preparation |
| EP4308723B1 (en) | 2021-03-15 | 2025-04-23 | F. Hoffmann-La Roche AG | Targeted next-generation sequencing via anchored primer extension |
| WO2022200485A1 (en) | 2021-03-26 | 2022-09-29 | F. Hoffmann-La Roche Ag | Hybridization buffer formulations |
| EP4314337A1 (en) | 2021-04-01 | 2024-02-07 | F. Hoffmann-La Roche AG | Immune cell counting of sars-cov-2 patients based on immune repertoire sequencing |
| WO2022263496A1 (en) | 2021-06-17 | 2022-12-22 | F. Hoffmann-La Roche Ag | Engineered nanopore with a negatively charged polymer threaded through the channel |
| WO2022263489A1 (en) | 2021-06-17 | 2022-12-22 | F. Hoffmann-La Roche Ag | Nucleoside-5 -oligophosphates having a cationically-modified nucleobase |
| US12435369B2 (en) | 2021-08-13 | 2025-10-07 | Singular Genomcis Systems, Inc. | Nucleotide analogs and uses thereof |
| CN113736778B (zh) * | 2021-09-14 | 2025-05-09 | 成都齐碳科技有限公司 | 测序接头、构建方法、纳米孔建库试剂盒及应用 |
| WO2023055752A2 (en) | 2021-09-28 | 2023-04-06 | Axbio Inc. | Methods for processing a nucleic acid sample and compositions thereof |
| WO2023213766A1 (en) | 2022-05-02 | 2023-11-09 | F. Hoffmann-La Roche Ag | Compositions and methods that reduce prussian blue formation during nanopore sequencing |
| CN119497755A (zh) | 2022-06-30 | 2025-02-21 | 卡帕生物系统公司 | 使用古细菌组蛋白样蛋白针对片段化并加标签测序文库插入片段大小进行控制 |
| WO2024046992A1 (en) | 2022-09-02 | 2024-03-07 | F. Hoffmann-La Roche Ag | Improvements to next-generation target enrichment performance |
| WO2024077111A2 (en) * | 2022-10-05 | 2024-04-11 | Axbio Inc. | Compositions, methods, and systems for detecting nucleotides |
| AU2024246785A1 (en) | 2023-03-30 | 2025-09-11 | F. Hoffmann-La Roche Ag | Modulation of target molecule-lipid bilayer interactions |
| WO2024215528A1 (en) | 2023-04-13 | 2024-10-17 | Ventana Medical Systems, Inc. | Proliferation assay for fixed solid tumors |
| CN121057766A (zh) | 2023-05-04 | 2025-12-02 | 豪夫迈·罗氏有限公司 | 经修饰的三嵌段共聚物化合物及其使用方法 |
| WO2024227837A1 (en) | 2023-05-04 | 2024-11-07 | F. Hoffmann-La Roche Ag | Hybrid triblock copolymer membrane compositions and methods for nanopore sequencing |
| WO2024256358A2 (en) | 2023-06-14 | 2024-12-19 | F. Hoffmann-La Roche Ag | Accelerated marking of 5-formyl cytosine and use in nucleic acid methylation sequencing |
| GB202310278D0 (en) * | 2023-07-05 | 2023-08-16 | Navinci Diagnostics Ab | Stabilisation of phi29 polymerase |
| CN118409092B (zh) * | 2023-09-21 | 2024-10-18 | 上海市肺科医院（上海市职业病防治院） | 一种用于干扰素γ检测的核酸适体功能化磁珠及其制备方法和试剂盒 |
| WO2025064405A1 (en) * | 2023-09-22 | 2025-03-27 | Illumina, Inc. | Macromolecule blocks for nanopore sequencing |
| WO2025193604A1 (en) | 2024-03-11 | 2025-09-18 | Ventana Medical Systems, Inc. | Non-enzymatic dissociation of ffpe tissue and generation of single cells with intact cell surface markers |
| WO2025210056A1 (en) | 2024-04-03 | 2025-10-09 | Roche Sequencing Solutions, Inc. | In vitro amplification of dna methylation patterns |
| WO2025240460A2 (en) | 2024-05-14 | 2025-11-20 | Roche Molecular Systems, Inc. | Assay for detection of mutations conferring resistance to treatment with an immunotherapeutic agent |
Family Cites Families (131)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH055425Y2 (enExample) | 1986-05-20 | 1993-02-12 | ||
| US5547839A (en) | 1989-06-07 | 1996-08-20 | Affymax Technologies N.V. | Sequencing of surface immobilized polymers utilizing microflourescence detection |
| EP0637384B1 (en) | 1992-04-22 | 1996-10-02 | Ecole Polytechnique Federale De Lausanne | Lipid membrane sensors |
| GB9315847D0 (en) | 1993-07-30 | 1993-09-15 | Isis Innovation | Tag reagent and assay method |
| US5795782A (en) | 1995-03-17 | 1998-08-18 | President & Fellows Of Harvard College | Characterization of individual polymer molecules based on monomer-interface interactions |
| US6362002B1 (en) | 1995-03-17 | 2002-03-26 | President And Fellows Of Harvard College | Characterization of individual polymer molecules based on monomer-interface interactions |
| US20120160687A1 (en) | 1995-03-17 | 2012-06-28 | President And Fellows Of Harvard College | Characterization of individual polymer molecules based on monomer-interface interactions |
| US5804386A (en) | 1997-01-15 | 1998-09-08 | Incyte Pharmaceuticals, Inc. | Sets of labeled energy transfer fluorescent primers and their use in multi component analysis |
| US5876936A (en) | 1997-01-15 | 1999-03-02 | Incyte Pharmaceuticals, Inc. | Nucleic acid sequencing with solid phase capturable terminators |
| US6046005A (en) | 1997-01-15 | 2000-04-04 | Incyte Pharmaceuticals, Inc. | Nucleic acid sequencing with solid phase capturable terminators comprising a cleavable linking group |
| US6485703B1 (en) | 1998-07-31 | 2002-11-26 | The Texas A&M University System | Compositions and methods for analyte detection |
| US6267872B1 (en) | 1998-11-06 | 2001-07-31 | The Regents Of The University Of California | Miniature support for thin films containing single channels or nanopores and methods for using same |
| US6232075B1 (en) * | 1998-12-14 | 2001-05-15 | Li-Cor, Inc. | Heterogeneous assay for pyrophosphate detection |
| US20030054360A1 (en) | 1999-01-19 | 2003-03-20 | Larry Gold | Method and apparatus for the automated generation of nucleic acid ligands |
| US6399335B1 (en) | 1999-11-16 | 2002-06-04 | Advanced Research And Technology Institute, Inc. | γ-phosphoester nucleoside triphosphates |
| US6383749B2 (en) | 1999-12-02 | 2002-05-07 | Clontech Laboratories, Inc. | Methods of labeling nucleic acids for use in array based hybridization assays |
| AU2001241474A1 (en) | 2000-02-11 | 2001-08-20 | The Texas A And M University System | Biosensor compositions and methods of use |
| US6616895B2 (en) | 2000-03-23 | 2003-09-09 | Advanced Research Corporation | Solid state membrane channel device for the measurement and characterization of atomic and molecular sized samples |
| US6413792B1 (en) | 2000-04-24 | 2002-07-02 | Eagle Research Development, Llc | Ultra-fast nucleic acid sequencing device and a method for making and using the same |
| US6936702B2 (en) | 2000-06-07 | 2005-08-30 | Li-Cor, Inc. | Charge-switch nucleotides |
| JP2004516810A (ja) * | 2000-06-07 | 2004-06-10 | リ−コール インコーポレーティッド | 電荷スイッチヌクレオチド |
| JP4331476B2 (ja) | 2000-08-03 | 2009-09-16 | エフ．ホフマン−ラ ロシュ アーゲー | プリン−２，６−ジアミンのピラゾロ［３，４−ｄ］ピリミジンアナローグを含有する核酸結合性化合物およびそれらの使用 |
| US20060057565A1 (en) | 2000-09-11 | 2006-03-16 | Jingyue Ju | Combinatorial fluorescence energy transfer tags and uses thereof |
| US6627748B1 (en) | 2000-09-11 | 2003-09-30 | The Trustees Of Columbia University In The City Of New York | Combinatorial fluorescence energy transfer tags and their applications for multiplex genetic analyses |
| AU8911101A (en) | 2000-09-11 | 2002-03-26 | Univ Columbia | Combinatorial fluorescence energy transfer tags and uses thereof |
| US6664079B2 (en) | 2000-10-06 | 2003-12-16 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
| US9708358B2 (en) | 2000-10-06 | 2017-07-18 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
| US20030027140A1 (en) | 2001-03-30 | 2003-02-06 | Jingyue Ju | High-fidelity DNA sequencing using solid phase capturable dideoxynucleotides and mass spectrometry |
| US7041812B2 (en) | 2001-08-29 | 2006-05-09 | Amersham Biosciences Corp | Labeled nucleoside polyphosphates |
| ES2346640T4 (es) * | 2001-10-26 | 2011-04-26 | Noxxon Pharma Ag | Ácido l-nucleico modificado. |
| WO2003064621A2 (en) | 2002-02-01 | 2003-08-07 | Ambion, Inc. | HIGH POTENCY siRNAS FOR REDUCING THE EXPRESSION OF TARGET GENES |
| US7074597B2 (en) | 2002-07-12 | 2006-07-11 | The Trustees Of Columbia University In The City Of New York | Multiplex genotyping using solid phase capturable dideoxynucleotides and mass spectrometry |
| US20090186343A1 (en) * | 2003-01-28 | 2009-07-23 | Visigen Biotechnologies, Inc. | Methods for preparing modified biomolecules, modified biomolecules and methods for using same |
| JP4896708B2 (ja) * | 2003-02-05 | 2012-03-14 | ジーイー・ヘルスケア・バイオサイエンス・コーポレイション | 新規リンカー類を有する末端リン酸標識ヌクレオチド類 |
| JP4896707B2 (ja) | 2003-02-05 | 2012-03-14 | ジーイー・ヘルスケア・バイオサイエンス・コーポレイション | 固相配列決定法 |
| US7365178B2 (en) * | 2003-04-01 | 2008-04-29 | Activx Biosciences, Inc. | Acyl-nucleotide probes and methods of their synthesis and use in proteomic analysis |
| US7745116B2 (en) | 2003-04-08 | 2010-06-29 | Pacific Biosciences Of California, Inc. | Composition and method for nucleic acid sequencing |
| US7019346B2 (en) | 2003-12-23 | 2006-03-28 | Intel Corporation | Capacitor having an anodic metal oxide substrate |
| US20050148087A1 (en) | 2004-01-05 | 2005-07-07 | Applera Corporation | Isobarically labeled analytes and fragment ions derived therefrom |
| EP2436778A3 (en) | 2004-03-03 | 2012-07-11 | The Trustees of Columbia University in the City of New York | Photocleavable fluorescent nucleotides for DNA sequencing on chip constructed by site-specific coupling chemistry |
| US7279337B2 (en) | 2004-03-10 | 2007-10-09 | Agilent Technologies, Inc. | Method and apparatus for sequencing polymers through tunneling conductance variation detection |
| WO2006028508A2 (en) | 2004-03-23 | 2006-03-16 | President And Fellows Of Harvard College | Methods and apparatus for characterizing polynucleotides |
| US20050239134A1 (en) | 2004-04-21 | 2005-10-27 | Board Of Regents, The University Of Texas System | Combinatorial selection of phosphorothioate single-stranded DNA aptamers for TGF-beta-1 protein |
| GB2431013B (en) | 2004-07-23 | 2008-05-21 | Electronic Bio Sciences Llc | Method and apparatus for sensing a time varying current passing through an ion channel |
| EP1784754A4 (en) | 2004-08-13 | 2009-05-27 | Harvard College | OPTI-NANOPORE DNA READING PLATFORM WITH ULTRAHOLE THROUGHPUT |
| US20060105461A1 (en) | 2004-10-22 | 2006-05-18 | May Tom-Moy | Nanopore analysis system |
| US7867716B2 (en) | 2004-12-21 | 2011-01-11 | The Texas A&M University System | High temperature ion channels and pores |
| GB0505971D0 (en) | 2005-03-23 | 2005-04-27 | Isis Innovation | Delivery of molecules to a lipid bilayer |
| US9169510B2 (en) | 2005-06-21 | 2015-10-27 | The Trustees Of Columbia University In The City Of New York | Pyrosequencing methods and related compositions |
| US7405281B2 (en) | 2005-09-29 | 2008-07-29 | Pacific Biosciences Of California, Inc. | Fluorescent nucleotide analogs and uses therefor |
| WO2007041621A2 (en) | 2005-10-03 | 2007-04-12 | Xingsheng Sean Ling | Hybridization assisted nanopore sequencing |
| US7397232B2 (en) | 2005-10-21 | 2008-07-08 | The University Of Akron | Coulter counter having a plurality of channels |
| WO2007053719A2 (en) | 2005-10-31 | 2007-05-10 | The Trustees Of Columbia University In The City Of New York | Chemically cleavable 3'-o-allyl-dntp-allyl-fluorophore fluorescent nucleotide analogues and related methods |
| WO2007053702A2 (en) | 2005-10-31 | 2007-05-10 | The Trustees Of Columbia University In The City Of New York | Synthesis of four color 3'-o-allyl modified photocleavable fluorescent nucleotides and related methods |
| AU2006331512B2 (en) | 2005-12-22 | 2012-02-23 | Pacific Biosciences Of California, Inc. | Active surface coupled polymerases |
| US20070298511A1 (en) | 2006-04-27 | 2007-12-27 | The Texas A&M University System | Nanopore sensor system |
| US7777505B2 (en) | 2006-05-05 | 2010-08-17 | University Of Utah Research Foundation | Nanopore platforms for ion channel recordings and single molecule detection and analysis |
| WO2007146158A1 (en) | 2006-06-07 | 2007-12-21 | The Trustees Of Columbia University In The City Of New York | Dna sequencing by nanopore using modified nucleotides |
| EP1867638A1 (de) * | 2006-06-16 | 2007-12-19 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Verfahren zur kovalenten Verknüpfung zweier Moleküle mittels Diels-Alder-Reaktion mit inversem Elektronenbedarf |
| US7883869B2 (en) | 2006-12-01 | 2011-02-08 | The Trustees Of Columbia University In The City Of New York | Four-color DNA sequencing by synthesis using cleavable fluorescent nucleotide reversible terminators |
| US7902345B2 (en) | 2006-12-05 | 2011-03-08 | Sequenom, Inc. | Detection and quantification of biomolecules using mass spectrometry |
| US8003319B2 (en) | 2007-02-02 | 2011-08-23 | International Business Machines Corporation | Systems and methods for controlling position of charged polymer inside nanopore |
| NZ579083A (en) | 2007-02-20 | 2012-07-27 | Oxford Nanopore Tech Ltd | Lipid bilayer sensor system |
| AU2008236694B2 (en) | 2007-04-04 | 2014-01-23 | The Regents Of The University Of California | Compositions, devices, systems, and methods for using a nanopore |
| EP2158476B8 (en) | 2007-05-08 | 2019-10-09 | Trustees of Boston University | Chemical functionalization of solid-state nanopores and nanopore arrays and applications thereof |
| US20090073293A1 (en) | 2007-06-27 | 2009-03-19 | Yoel Yaffe | CMOS image sensors with increased dynamic range and methods of operating the same |
| US8278047B2 (en) | 2007-10-01 | 2012-10-02 | Nabsys, Inc. | Biopolymer sequencing by hybridization of probes to form ternary complexes and variable range alignment |
| EP2205765B1 (en) | 2007-10-02 | 2012-09-12 | President and Fellows of Harvard College | Capture, recapture, and trapping of molecules with a nanopore |
| EP3431615A3 (en) | 2007-10-19 | 2019-02-20 | The Trustees of Columbia University in the City of New York | Dna sequencing with non-fluorescent nucleotide reversible terminators cleavable label modified nucleotide terminators |
| EP2207900B1 (en) | 2007-10-19 | 2015-04-29 | The Trustees of Columbia University in the City of New York | Design and synthesis of cleavable fluorescent nucleotides as reversible terminators for dna sequencing by synthesis |
| CN101939339A (zh) | 2007-11-14 | 2011-01-05 | 阿特瑞斯技术有限公司 | 生物标记的检测 |
| GB0724736D0 (en) | 2007-12-19 | 2008-01-30 | Oxford Nanolabs Ltd | Formation of layers of amphiphilic molecules |
| WO2009091847A2 (en) * | 2008-01-14 | 2009-07-23 | Life Technologies Corporation | Compositions, methods and systems for single molecule sequencing |
| DE102008006990A1 (de) * | 2008-01-31 | 2009-08-06 | Osram Opto Semiconductors Gmbh | Hintergrundbeleuchtungseinheit für eine Hintergrundbeleuchtung eines Bildschirms und Bildschirmeinheit des Bildschirms |
| EP2107040B1 (en) | 2008-03-31 | 2011-10-26 | Sony Deutschland Gmbh | A method of fabricating a membrane having a tapered pore |
| WO2009145828A2 (en) | 2008-03-31 | 2009-12-03 | Pacific Biosciences Of California, Inc. | Two slow-step polymerase enzyme systems and methods |
| US8058414B2 (en) | 2008-04-29 | 2011-11-15 | Life Technologies Corporation | Unnatural polymerase substrates that can sustain enzymatic synthesis of double stranded nucleic acids from a nucleic acid template and methods of use |
| BRPI0911442A2 (pt) | 2008-04-30 | 2019-03-12 | Immunogen, Inc. | conjugados potentes e ligantes hidrofílicos |
| US8940142B2 (en) | 2008-05-05 | 2015-01-27 | The Regents Of The University Of California | Functionalized nanopipette biosensor |
| US20110229877A1 (en) | 2008-07-07 | 2011-09-22 | Oxford Nanopore Technologies Limited | Enzyme-pore constructs |
| JP5596684B2 (ja) | 2008-08-12 | 2014-09-24 | エフ．ホフマン−ラ ロシュ アーゲー | プルーフリーディング・プライマー伸長 |
| US8921046B2 (en) | 2008-09-19 | 2014-12-30 | Pacific Biosciences Of California, Inc. | Nucleic acid sequence analysis |
| US20100148126A1 (en) | 2008-11-26 | 2010-06-17 | Board Of Regents, The University Of Texas System | Genomic sequencing using modified protein pores and ionic liquids |
| US20100227414A1 (en) | 2009-03-05 | 2010-09-09 | Trex Enterprises Corp. | Affinity capture mass spectroscopy with a porous silicon biosensor |
| GB0905140D0 (en) | 2009-03-25 | 2009-05-06 | Isis Innovation | Method |
| EP2239053A1 (en) | 2009-04-09 | 2010-10-13 | baseclick GmbH | Click chemistry on heterogeneous catalysts |
| US8986928B2 (en) | 2009-04-10 | 2015-03-24 | Pacific Biosciences Of California, Inc. | Nanopore sequencing devices and methods |
| WO2011038241A1 (en) | 2009-09-25 | 2011-03-31 | President And Fellows Of Harvard College | Nucleic acid amplification and sequencing by synthesis with fluorogenic nucleotides |
| WO2011079188A2 (en) * | 2009-12-23 | 2011-06-30 | Life Technologies Corporation | Protein modification from the oxidation of clickable polyunsaturated fatty acid analogs |
| EP2360167A1 (en) * | 2010-02-03 | 2011-08-24 | Deutsches Krebsforschungszentrum | Post-synthetic modification of nucleic acids by inverse Diels-Alder reaction |
| US9605307B2 (en) | 2010-02-08 | 2017-03-28 | Genia Technologies, Inc. | Systems and methods for forming a nanopore in a lipid bilayer |
| US8324914B2 (en) | 2010-02-08 | 2012-12-04 | Genia Technologies, Inc. | Systems and methods for characterizing a molecule |
| US20120052188A1 (en) | 2010-02-08 | 2012-03-01 | Genia Technologies, Inc. | Systems and methods for assembling a lipid bilayer on a substantially planar solid surface |
| US20110192723A1 (en) | 2010-02-08 | 2011-08-11 | Genia Technologies, Inc. | Systems and methods for manipulating a molecule in a nanopore |
| US20110287414A1 (en) | 2010-02-08 | 2011-11-24 | Genia Technologies, Inc. | Systems and methods for identifying a portion of a molecule |
| EP2843405B8 (en) | 2010-02-08 | 2023-10-04 | Roche Sequencing Solutions, Inc. | Systems and methods for manipulating a molecule in a nanopore |
| US9234930B2 (en) | 2010-02-10 | 2016-01-12 | Lattice Semiconductor Corporation | Determination of physical connectivity status of devices based on electrical measurement |
| CA2790672C (en) | 2010-02-23 | 2018-05-29 | University Of Washington | Artificial mycolic acid membranes |
| US8652779B2 (en) | 2010-04-09 | 2014-02-18 | Pacific Biosciences Of California, Inc. | Nanopore sequencing using charge blockade labels |
| JP6016792B2 (ja) | 2010-07-14 | 2016-10-26 | ザ キュレイターズ オブ ザ ユニバーシティ オブ ミズーリ | ナノポア促進型の核酸の単分子検出 |
| EP2595967B1 (en) * | 2010-07-23 | 2016-03-23 | University Of Delaware | Tetrazine-trans-cyclooctene ligation for the rapid construction of radionuclide labeled probes |
| US10443096B2 (en) * | 2010-12-17 | 2019-10-15 | The Trustees Of Columbia University In The City Of New York | DNA sequencing by synthesis using modified nucleotides and nanopore detection |
| GB2500360B (en) | 2010-12-22 | 2019-10-23 | Genia Tech Inc | Nanopore-based single DNA molecule characterization, identification and isolation using speed bumps |
| US8962242B2 (en) | 2011-01-24 | 2015-02-24 | Genia Technologies, Inc. | System for detecting electrical properties of a molecular complex |
| US9110478B2 (en) | 2011-01-27 | 2015-08-18 | Genia Technologies, Inc. | Temperature regulation of measurement arrays |
| US11274341B2 (en) | 2011-02-11 | 2022-03-15 | NABsys, 2.0 LLC | Assay methods using DNA binding proteins |
| WO2012152708A1 (en) * | 2011-05-06 | 2012-11-15 | Qiagen Gmbh | Oligonucleotides comprising a label associated through a linker |
| US9624539B2 (en) | 2011-05-23 | 2017-04-18 | The Trustees Of Columbia University In The City Of New York | DNA sequencing by synthesis using Raman and infrared spectroscopy detection |
| JP2014521956A (ja) | 2011-07-27 | 2014-08-28 | ザ ボード オブ トラスティーズ オブ ザ ユニヴァーシティー オブ イリノイ | 生体分子を特徴付けるためのナノ細孔センサー |
| EP3415901A1 (en) | 2012-01-20 | 2018-12-19 | Genia Technologies, Inc. | Nanopore based molecular detection and sequencing |
| US8541849B2 (en) | 2012-02-14 | 2013-09-24 | Genia Technologies, Inc. | Noise shielding techniques for ultra low current measurements in biochemical applications |
| EP2814983B1 (en) | 2012-02-16 | 2019-04-24 | Genia Technologies, Inc. | Methods for creating bilayers for use with nanopore sensors |
| WO2013154999A2 (en) * | 2012-04-09 | 2013-10-17 | The Trustees Of Columbia University In The City Of New York | Method of preparation of nanopore and uses thereof |
| GB2510719A (en) | 2012-06-15 | 2014-08-13 | Genia Technologies Inc | Chip set-up and high-accuracy nucleic acid sequencing |
| EP2864502B1 (en) | 2012-06-20 | 2019-10-23 | The Trustees of Columbia University in the City of New York | Nucleic acid sequencing by nanopore detection of tag molecules |
| US9605309B2 (en) | 2012-11-09 | 2017-03-28 | Genia Technologies, Inc. | Nucleic acid sequencing using tags |
| WO2014081301A1 (en) | 2012-11-22 | 2014-05-30 | Tagworks Pharmaceuticals B.V. | Bio-orthogonal drug activation |
| WO2014117001A1 (en) | 2013-01-25 | 2014-07-31 | Memorial Sloan-Kettering Cancer Center | Tetrazines/trans-cyclooctenes in solid phase synthesis of labeled peptides |
| US10648026B2 (en) | 2013-03-15 | 2020-05-12 | The Trustees Of Columbia University In The City Of New York | Raman cluster tagged molecules for biological imaging |
| CN105102627B (zh) | 2013-03-15 | 2018-10-19 | 纽约哥伦比亚大学理事会 | 用于检测样品中多种预定化合物的方法 |
| CN106164297B (zh) | 2014-02-12 | 2020-09-08 | 纽约哥伦比亚大学理事会 | 单分子电子多重snp试验以及pcr分析 |
| US10240195B2 (en) | 2014-03-24 | 2019-03-26 | The Trustees Of Columbia University In The City Of New York | Chemical methods for producing tagged nucleotides |
| US20170101675A1 (en) | 2014-05-19 | 2017-04-13 | The Trustees Of Columbia University In The City Of New York | Ion sensor dna and rna sequencing by synthesis using nucleotide reversible terminators |
| EP3268050B1 (en) | 2015-03-09 | 2021-07-14 | The Trustees of Columbia University in the City of New York | Pore-forming protein conjugate compositions and methods |
| WO2016154215A1 (en) | 2015-03-23 | 2016-09-29 | The Trustees Of Columbia University In The City Of New York | Polymer tagged nucleotides for single molecule electronic snp assay |
| CN108779138B (zh) | 2015-09-28 | 2022-06-17 | 哥伦比亚大学董事会 | 用作dna合成测序的可逆终止物的基于新的二硫键接头的核苷酸的设计与合成 |
| WO2017087887A1 (en) | 2015-11-18 | 2017-05-26 | The Trustees Of Columbia University In The City Of New York | Ion sensor dna and rna sequencing by synthesis using nucleotide reversible terminators |
| EP3452219A4 (en) | 2016-04-04 | 2020-01-29 | The Trustees of Columbia University in the City of New York | DNA SEQUENCING ON A SINGLE MOLECULE / ASSEMBLY BASED ON SYNTHESIS FLUORESCENCE ENERGY TRANSFER |
| CN109562142B (zh) | 2016-04-04 | 2022-09-13 | 纽约哥伦比亚大学董事会 | 使用核苷酸类似物和拉曼检测的dna合成测序 |
| CN109661232B (zh) | 2016-05-23 | 2023-03-03 | 纽约哥伦比亚大学董事会 | 核苷酸衍生物及其使用方法 |
| EP3600339A4 (en) | 2017-03-28 | 2021-05-19 | The Trustees of Columbia University in the City of New York | 3'-O-MODIFIED NUCLEOTIDE ANALOGUE WITH DIFFERENT FITTING LINKS TO FIX FLUORESCENT MARKERS TO THE BASE FOR DNA SEQUENCING BY SYNTHESIS |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US11396677B2 (en) | 2014-03-24 | 2022-07-26 | The Trustees Of Columbia University In The City Of New York | Chemical methods for producing tagged nucleotides |
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| CN106715453B (zh) | 2021-04-30 |
| CA2943952A1 (en) | 2015-10-01 |
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| US20150368710A1 (en) | 2015-12-24 |
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| CN106715453A (zh) | 2017-05-24 |
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| US20190276887A1 (en) | 2019-09-12 |
| EP3122759A1 (en) | 2017-02-01 |
| EP3122759B1 (en) | 2022-06-01 |
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