CA2567591C - Method for nucleic acid sequencing in the absence of divalent metal ion - Google Patents
Method for nucleic acid sequencing in the absence of divalent metal ion Download PDFInfo
- Publication number
- CA2567591C CA2567591C CA2567591A CA2567591A CA2567591C CA 2567591 C CA2567591 C CA 2567591C CA 2567591 A CA2567591 A CA 2567591A CA 2567591 A CA2567591 A CA 2567591A CA 2567591 C CA2567591 C CA 2567591C
- Authority
- CA
- Canada
- Prior art keywords
- nucleic acid
- reaction mixture
- nucleotide
- template
- labeled
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 264
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 261
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 261
- 238000000034 method Methods 0.000 title claims abstract description 93
- 229910021645 metal ion Inorganic materials 0.000 title abstract description 9
- 238000012163 sequencing technique Methods 0.000 title description 27
- 239000002773 nucleotide Substances 0.000 claims abstract description 298
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 295
- 230000000295 complement effect Effects 0.000 claims abstract description 57
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 13
- 238000004458 analytical method Methods 0.000 claims abstract description 10
- 239000011541 reaction mixture Substances 0.000 claims description 149
- 238000006116 polymerization reaction Methods 0.000 claims description 108
- 102000004190 Enzymes Human genes 0.000 claims description 84
- 108090000790 Enzymes Proteins 0.000 claims description 84
- 230000000379 polymerizing effect Effects 0.000 claims description 80
- 229910019142 PO4 Inorganic materials 0.000 claims description 66
- 239000010452 phosphate Substances 0.000 claims description 66
- 150000001768 cations Chemical class 0.000 claims description 58
- 239000000975 dye Substances 0.000 claims description 34
- 230000000977 initiatory effect Effects 0.000 claims description 28
- 238000013500 data storage Methods 0.000 claims description 17
- 230000003100 immobilizing effect Effects 0.000 claims description 15
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 claims description 13
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 claims description 13
- 239000011324 bead Substances 0.000 claims description 12
- 238000012512 characterization method Methods 0.000 claims description 10
- 230000002250 progressing effect Effects 0.000 claims description 9
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 8
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 claims description 8
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 claims description 5
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 claims description 5
- 239000007850 fluorescent dye Substances 0.000 claims description 5
- 239000000987 azo dye Substances 0.000 claims description 4
- 229960000956 coumarin Drugs 0.000 claims description 4
- 235000001671 coumarin Nutrition 0.000 claims description 4
- 239000011777 magnesium Substances 0.000 claims description 4
- 150000004032 porphyrins Chemical class 0.000 claims description 4
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 claims description 4
- 239000001018 xanthene dye Substances 0.000 claims description 4
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- 108010092799 RNA-directed DNA polymerase Proteins 0.000 claims description 3
- 102000016559 DNA Primase Human genes 0.000 claims description 2
- 108010092681 DNA Primase Proteins 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 2
- 108010017842 Telomerase Proteins 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 229910052748 manganese Inorganic materials 0.000 claims description 2
- 239000011572 manganese Substances 0.000 claims description 2
- 108090000119 Nucleotidyltransferases Proteins 0.000 claims 1
- 102000003832 Nucleotidyltransferases Human genes 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 33
- 108020004414 DNA Proteins 0.000 abstract description 13
- 238000001514 detection method Methods 0.000 abstract description 12
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 239000002777 nucleoside Substances 0.000 description 9
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 6
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- 235000011176 polyphosphates Nutrition 0.000 description 6
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- 238000005406 washing Methods 0.000 description 6
- OAKPWEUQDVLTCN-NKWVEPMBSA-N 2',3'-Dideoxyadenosine-5-triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1CC[C@@H](CO[P@@](O)(=O)O[P@](O)(=O)OP(O)(O)=O)O1 OAKPWEUQDVLTCN-NKWVEPMBSA-N 0.000 description 5
- -1 deazapurine Chemical compound 0.000 description 5
- 150000003833 nucleoside derivatives Chemical class 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 239000002738 chelating agent Substances 0.000 description 4
- 239000000872 buffer Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000001351 cycling effect Effects 0.000 description 3
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 3
- 235000011180 diphosphates Nutrition 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical compound NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000003491 array Methods 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000009918 complex formation Effects 0.000 description 2
- 230000008876 conformational transition Effects 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 230000009919 sequestration Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 239000001226 triphosphate Substances 0.000 description 2
- 235000011178 triphosphate Nutrition 0.000 description 2
- FBMZEITWVNHWJW-UHFFFAOYSA-N 1,7-dihydropyrrolo[2,3-d]pyrimidin-4-one Chemical compound OC1=NC=NC2=C1C=CN2 FBMZEITWVNHWJW-UHFFFAOYSA-N 0.000 description 1
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 description 1
- CKTSBUTUHBMZGZ-ULQXZJNLSA-N 4-amino-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-tritiopyrimidin-2-one Chemical compound O=C1N=C(N)C([3H])=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-ULQXZJNLSA-N 0.000 description 1
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 1
- LOSIULRWFAEMFL-UHFFFAOYSA-N 7-deazaguanine Chemical compound O=C1NC(N)=NC2=C1CC=N2 LOSIULRWFAEMFL-UHFFFAOYSA-N 0.000 description 1
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 108010063113 DNA Polymerase II Proteins 0.000 description 1
- 108010071146 DNA Polymerase III Proteins 0.000 description 1
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 1
- 108050009160 DNA polymerase 1 Proteins 0.000 description 1
- 108090000725 DNA polymerase A Proteins 0.000 description 1
- 102000004214 DNA polymerase A Human genes 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 230000006819 RNA synthesis Effects 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- HDRRAMINWIWTNU-NTSWFWBYSA-N [[(2s,5r)-5-(2-amino-6-oxo-3h-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1CC[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HDRRAMINWIWTNU-NTSWFWBYSA-N 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
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- 239000005549 deoxyribonucleoside Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 125000001805 pentosyl group Chemical group 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 239000002342 ribonucleoside Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000021092 sugar substitutes Nutrition 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6834—Enzymatic or biochemical coupling of nucleic acids to a solid phase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US57878904P | 2004-06-10 | 2004-06-10 | |
| US60/578,789 | 2004-06-10 | ||
| PCT/US2005/020378 WO2005123957A2 (en) | 2004-06-10 | 2005-06-09 | Method for nucleic acid analysis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2567591A1 CA2567591A1 (en) | 2005-12-29 |
| CA2567591C true CA2567591C (en) | 2011-08-02 |
Family
ID=35510340
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2567591A Expired - Fee Related CA2567591C (en) | 2004-06-10 | 2005-06-09 | Method for nucleic acid sequencing in the absence of divalent metal ion |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US7871771B2 (https=) |
| EP (1) | EP1766075B1 (https=) |
| JP (1) | JP5037343B2 (https=) |
| CN (1) | CN101120098A (https=) |
| AT (1) | ATE461293T1 (https=) |
| AU (1) | AU2005254984B2 (https=) |
| CA (1) | CA2567591C (https=) |
| DE (1) | DE602005020011D1 (https=) |
| WO (1) | WO2005123957A2 (https=) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7264934B2 (en) * | 2004-06-10 | 2007-09-04 | Ge Healthcare Bio-Sciences Corp. | Rapid parallel nucleic acid analysis |
| US20100227327A1 (en) * | 2008-08-08 | 2010-09-09 | Xiaoliang Sunney Xie | Methods and compositions for continuous single-molecule nucleic acid sequencing by synthesis with fluorogenic nucleotides |
| US20100036110A1 (en) * | 2008-08-08 | 2010-02-11 | Xiaoliang Sunney Xie | Methods and compositions for continuous single-molecule nucleic acid sequencing by synthesis with fluorogenic nucleotides |
| WO2010141391A2 (en) | 2009-06-05 | 2010-12-09 | Life Technologies Corporation | Mutant dna polymerases |
| US9399217B2 (en) | 2010-10-04 | 2016-07-26 | Genapsys, Inc. | Chamber free nanoreactor system |
| NZ610129A (en) | 2010-10-04 | 2014-08-29 | Genapsys Inc | Systems and methods for automated reusable parallel biological reactions |
| US9184099B2 (en) | 2010-10-04 | 2015-11-10 | The Board Of Trustees Of The Leland Stanford Junior University | Biosensor devices, systems and methods therefor |
| US8585973B2 (en) | 2011-05-27 | 2013-11-19 | The Board Of Trustees Of The Leland Stanford Junior University | Nano-sensor array |
| KR101940833B1 (ko) * | 2011-05-27 | 2019-01-21 | 제납시스 인크. | 유전자 및 생물학적 분석을 위한 시스템 및 방법 |
| US9926596B2 (en) | 2011-05-27 | 2018-03-27 | Genapsys, Inc. | Systems and methods for genetic and biological analysis |
| US10093975B2 (en) | 2011-12-01 | 2018-10-09 | Genapsys, Inc. | Systems and methods for high efficiency electronic sequencing and detection |
| WO2013096692A1 (en) | 2011-12-21 | 2013-06-27 | Illumina, Inc. | Apparatus and methods for kinetic analysis and determination of nucleic acid sequences |
| EP2844774B1 (en) | 2012-05-02 | 2018-07-18 | Ibis Biosciences, Inc. | Dna sequencing |
| EP2844775B1 (en) | 2012-05-02 | 2018-07-18 | Ibis Biosciences, Inc. | Dna sequencing |
| WO2013166303A1 (en) | 2012-05-02 | 2013-11-07 | Ibis Biosciences, Inc. | Dna sequencing |
| EP2971141B1 (en) | 2013-03-15 | 2018-11-28 | Genapsys, Inc. | Systems for biological analysis |
| WO2015089238A1 (en) | 2013-12-11 | 2015-06-18 | Genapsys, Inc. | Systems and methods for biological analysis and computation |
| US9822401B2 (en) | 2014-04-18 | 2017-11-21 | Genapsys, Inc. | Methods and systems for nucleic acid amplification |
| US10077470B2 (en) | 2015-07-21 | 2018-09-18 | Omniome, Inc. | Nucleic acid sequencing methods and systems |
| KR102254451B1 (ko) * | 2016-04-22 | 2021-05-20 | 옴니옴 인코포레이티드 | 뉴클레오타이드-특이적 삼원 복합체 형성의 향상된 검출을 사용하는 핵산 서열 결정 방법 및 시스템 |
| CA3022431C (en) | 2016-04-29 | 2023-03-21 | Omniome, Inc. | Method of nucleic acid sequence determination |
| EP3449012B1 (en) | 2016-04-29 | 2020-12-23 | Omniome, Inc. | Sequencing method employing ternary complex destabilization to identify cognate nucleotides |
| WO2018017884A1 (en) | 2016-07-20 | 2018-01-25 | Genapsys, Inc. | Systems and methods for nucleic acid sequencing |
| US10428378B2 (en) | 2016-08-15 | 2019-10-01 | Omniome, Inc. | Sequencing method for rapid identification and processing of cognate nucleotide pairs |
| KR102230444B1 (ko) | 2016-08-15 | 2021-03-23 | 옴니옴 인코포레이티드 | 핵산을 시퀀싱하기 위한 방법 및 시스템 |
| WO2018065299A1 (en) * | 2016-10-05 | 2018-04-12 | F. Hoffmann-La Roche Ag | Nucleic acid sequencing using nanotransistors |
| EP3564387A4 (en) * | 2016-12-27 | 2020-10-07 | EGI Tech (Shen Zhen) Co., Limited | UNIQUE FLUORESCENT DYE SEQUENCING PROCESS |
| US11248254B2 (en) | 2016-12-30 | 2022-02-15 | Omniome, Inc. | Method and system employing distinguishable polymerases for detecting ternary complexes and identifying cognate nucleotides |
| US10975427B2 (en) | 2017-01-20 | 2021-04-13 | Omniome, Inc. | Process for cognate nucleotide detection in a nucleic acid sequencing workflow |
| US10737267B2 (en) | 2017-04-04 | 2020-08-11 | Omniome, Inc. | Fluidic apparatus and methods useful for chemical and biological reactions |
| US9951385B1 (en) | 2017-04-25 | 2018-04-24 | Omniome, Inc. | Methods and apparatus that increase sequencing-by-binding efficiency |
| US10161003B2 (en) | 2017-04-25 | 2018-12-25 | Omniome, Inc. | Methods and apparatus that increase sequencing-by-binding efficiency |
| WO2019060628A1 (en) | 2017-09-21 | 2019-03-28 | Genapsys, Inc. | SYSTEMS AND METHODS FOR NUCLEIC ACID SEQUENCING |
| WO2019079593A1 (en) | 2017-10-19 | 2019-04-25 | Omniome, Inc. | BACKGROUND NOISE REDUCTION AND STABILIZATION OF SIMULTANEOUS COMPLEXES IN LINKED ASSAY WORKFLOWS |
| CN112567048B (zh) | 2018-07-24 | 2026-01-23 | 加利福尼亚太平洋生物科学股份有限公司 | 三元复合物种类的连续形成 |
| EP3853358A1 (en) | 2018-09-17 | 2021-07-28 | Omniome, Inc. | Engineered polymerases for improved sequencing |
| GB2613480B (en) | 2018-11-15 | 2023-11-22 | Element Biosciences Inc | Methods for generating circular nucleic acid molecules |
| US12391929B2 (en) | 2019-05-24 | 2025-08-19 | Element Biosciences, Inc. | Polymerase-nucleotide conjugates for sequencing by trapping |
| US20220251638A1 (en) * | 2019-05-27 | 2022-08-11 | Universal Sequencing Technology Corporation | Methods to Identify Components in Nucleic Acid Sequences |
| WO2021092431A1 (en) | 2019-11-08 | 2021-05-14 | Omniome, Inc. | Engineered polymerases for improved sequencing by binding |
| CA3178970A1 (en) * | 2020-05-20 | 2021-11-25 | Sinan ARSLAN | Methods for paired-end sequencing library preparation |
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| WO1998045474A1 (en) * | 1997-04-04 | 1998-10-15 | Innogenetics N.V. | Isothermal polymerase chain reaction by cycling the concentration of divalent metal ions |
| ATE371022T1 (de) * | 1998-06-17 | 2007-09-15 | Ge Healthcare Bio Sciences | Fy7 polymerase |
| CN1197975C (zh) * | 1998-08-19 | 2005-04-20 | 生物风险公司 | 测定多核苷酸序列变异的方法 |
| GB9901475D0 (en) * | 1999-01-22 | 1999-03-17 | Pyrosequencing Ab | A method of DNA sequencing |
| US20030108867A1 (en) | 1999-04-20 | 2003-06-12 | Chee Mark S | Nucleic acid sequencing using microsphere arrays |
| US6274320B1 (en) * | 1999-09-16 | 2001-08-14 | Curagen Corporation | Method of sequencing a nucleic acid |
| EP1368497A4 (en) * | 2001-03-12 | 2007-08-15 | California Inst Of Techn | METHODS AND APPARATUS FOR ANALYZING ASYNCHRONOUS BASE EXTENSION POLYNUCLEOTIDE SEQUENCES |
| US6613523B2 (en) * | 2001-06-29 | 2003-09-02 | Agilent Technologies, Inc. | Method of DNA sequencing using cleavable tags |
| US7169560B2 (en) * | 2003-11-12 | 2007-01-30 | Helicos Biosciences Corporation | Short cycle methods for sequencing polynucleotides |
| US7264934B2 (en) * | 2004-06-10 | 2007-09-04 | Ge Healthcare Bio-Sciences Corp. | Rapid parallel nucleic acid analysis |
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- 2005-06-09 EP EP05759349A patent/EP1766075B1/en not_active Expired - Lifetime
- 2005-06-09 AT AT05759349T patent/ATE461293T1/de not_active IP Right Cessation
- 2005-06-09 WO PCT/US2005/020378 patent/WO2005123957A2/en not_active Ceased
- 2005-06-09 AU AU2005254984A patent/AU2005254984B2/en not_active Ceased
- 2005-06-09 JP JP2007527745A patent/JP5037343B2/ja not_active Expired - Lifetime
- 2005-06-09 DE DE602005020011T patent/DE602005020011D1/de not_active Expired - Lifetime
- 2005-06-09 CA CA2567591A patent/CA2567591C/en not_active Expired - Fee Related
- 2005-06-09 US US11/570,347 patent/US7871771B2/en active Active
- 2005-06-09 CN CNA2005800191648A patent/CN101120098A/zh active Pending
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| EP1766075A2 (en) | 2007-03-28 |
| WO2005123957A3 (en) | 2006-05-18 |
| CN101120098A (zh) | 2008-02-06 |
| DE602005020011D1 (de) | 2010-04-29 |
| CA2567591A1 (en) | 2005-12-29 |
| US7871771B2 (en) | 2011-01-18 |
| WO2005123957A2 (en) | 2005-12-29 |
| ATE461293T1 (de) | 2010-04-15 |
| US20080287305A1 (en) | 2008-11-20 |
| EP1766075B1 (en) | 2010-03-17 |
| AU2005254984A1 (en) | 2005-12-29 |
| JP5037343B2 (ja) | 2012-09-26 |
| JP2008502369A (ja) | 2008-01-31 |
| EP1766075A4 (en) | 2008-05-21 |
| AU2005254984B2 (en) | 2008-10-16 |
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