CA2425112A1 - Massive parallel method for decoding dna and rna - Google Patents

Massive parallel method for decoding dna and rna Download PDF

Info

Publication number
CA2425112A1
CA2425112A1 CA002425112A CA2425112A CA2425112A1 CA 2425112 A1 CA2425112 A1 CA 2425112A1 CA 002425112 A CA002425112 A CA 002425112A CA 2425112 A CA2425112 A CA 2425112A CA 2425112 A1 CA2425112 A1 CA 2425112A1
Authority
CA
Canada
Prior art keywords
group
analogue
nucleotide analogue
solid surface
nucleic acid
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.)
Granted
Application number
CA002425112A
Other languages
French (fr)
Other versions
CA2425112C (en
Inventor
Jingyue Ju
Zengmin Li
John Robert Edwards
Yasuhiro Itagaki
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Columbia University of New York
Original Assignee
Individual
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26972030&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2425112(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Individual filed Critical Individual
Publication of CA2425112A1 publication Critical patent/CA2425112A1/en
Application granted granted Critical
Publication of CA2425112C publication Critical patent/CA2425112C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

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
    • C12Q1/6869—Methods for sequencing
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/14—Pyrrolo-pyrimidine radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • 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
    • 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
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/686—Polymerase chain reaction [PCR]
    • 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
    • C12Q1/6872—Methods for sequencing involving mass spectrometry
    • 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
    • C12Q1/6874—Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation
    • 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
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/11—Compounds covalently bound to a solid support
    • 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
    • C12Q2525/00—Reactions involving modified oligonucleotides, nucleic acids, or nucleotides
    • C12Q2525/10—Modifications characterised by
    • C12Q2525/117—Modifications characterised by incorporating modified base
    • 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
    • C12Q2525/00—Reactions involving modified oligonucleotides, nucleic acids, or nucleotides
    • C12Q2525/10—Modifications characterised by
    • C12Q2525/186—Modifications characterised by incorporating a non-extendable or blocking moiety
    • 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
    • C12Q2535/00—Reactions characterised by the assay type for determining the identity of a nucleotide base or a sequence of oligonucleotides
    • C12Q2535/101—Sanger sequencing method, i.e. oligonucleotide sequencing using primer elongation and dideoxynucleotides as chain terminators
    • 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
    • C12Q2535/00—Reactions characterised by the assay type for determining the identity of a nucleotide base or a sequence of oligonucleotides
    • C12Q2535/122—Massive parallel sequencing
    • 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
    • C12Q2563/00—Nucleic acid detection characterized by the use of physical, structural and functional properties
    • C12Q2563/107—Nucleic acid detection characterized by the use of physical, structural and functional properties fluorescence
    • 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
    • C12Q2565/00—Nucleic acid analysis characterised by mode or means of detection
    • C12Q2565/50—Detection characterised by immobilisation to a surface
    • C12Q2565/501—Detection characterised by immobilisation to a surface being an array of oligonucleotides
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures

Abstract

This invention provides methods for attaching a nucleic acid to a solid surface and for sequencing nucleic acid by detecting the identity of each nucleotide analogue after the nucleotide analogue is incorporated into a growing strand of DNA in a polymerase reaction. The invention also provides nucleotide analogues which comprise unique labels attached to the nucleotide analogue through a cleavable linker, and a cleavable chemical group to cap t he -OH group at the 3'-position of the deoxyribose.

Claims (60)

1. A method for sequencing a nucleic acid by detecting the identity of a nucleotide analogue after the nucleotide analogue is incorporated into a growing strand of DNA in a polymerase reaction, which comprises the following steps:
(i) attaching a 5' end of the nucleic acid to a solid surface;
(ii) attaching a primer to the nucleic acid attached to the solid surface;
(iii) adding a polymerase and one or more different nucleotide analogues to the nucleic acid to thereby incorporate a nucleotide analogue into the growing strand of DNA, wherein the incorporated nucleotide analogue terminates the polymerase reaction and wherein each different nucleotide analogue comprises (a) a base selected from the group consisting of adenine, guanine, cytosine, thymine, and uracil, and their analogues; (b) a unique label attached through a cleavable linker to the base or to an analogue of the base; (c) a deoxyribose; and (d) a cleavable chemical group to cap an -OH group at a 3' -position of the deoxyribose;
(iv) washing the solid surface to remove unincorporated nucleotide analogues;

(v) detecting the unique label attached to the nucleotide analogue that has been incorporated into the growing strand of DNA, so as to thereby identify the incorporated nucleotide analogue;
(vi) adding one or more chemical compounds to permanently cap any unreacted -OH group on the primer attached to the nucleic acid or on a primer extension strand formed by adding one or more nucleotides or nucleotide analogues to the primer;
(vii) cleaving the cleavable linker between the nucleotide analogue that was incorporated into the growing strand of DNA and the unique label;
(viii) cleaving the cleavable chemical group capping the -OH group at the 3'-position of the deoxyribose to uncap the -OH group, and washing the solid surface to remove cleaved compounds; and (ix) repeating steps (iii) through (viii) so as to detect the identity of a newly incorporated nucleotide analogue into the growing strand of DNA;

wherein if the unique label is a dye, the order of steps (v) through (vii) is: (v), (vi), and (vii);
and wherein if the unique label is a mass tag, the order of steps (v) through (vii) is: (vi), (vii), and (v).
2. The method of claim 1, wherein the solid surface is glass, silicon, or gold.
3. The method of claim 1, wherein the solid surface is a magnetic bead, a chip, a channel in a chip, or a porous channel in a chip.
4. The method of claim 1, wherein the step of attaching the nucleic acid to the solid surface comprises:
(i) coating the solid surface with a phosphine moiety, (ii) attaching an azido group to the 5' end of the nucleic acid, and (iii) immobilizing the 5' end of the nucleic acid to the solid surface through interaction between the phosphine moiety on the solid surface and the azido group on the 5' end of the nucleic acid.
5. The method of claim 4, wherein the step of coating the solid surface with the phosphine moiety comprises:
(i) coating the surface with a primary amine, and (ii) covalently coupling a N-hydroxysuccinimidyl ester of triarylphosphine with the primary amine.
6. The method of claim 1, wherein the nucleic acid that is attached to the solid surface is a single-stranded DNA.
7. The method of claim 1, wherein the nucleic acid that is attached to the solid surface in step (i) is a double-stranded DNA, wherein only one strand is directly attached to the solid surface, and wherein the strand that is not directly attached to the solid surface is removed by denaturing before proceeding to step (ii).
8. The method of claim 1, wherein the nucleic acid that is attached to the solid surface is a RNA, and the polymerase in step (iii) is reverse transcriptase.
9. The method of claim 1, wherein the primer is attached to a 3' end of the nucleic acid in step (ii) and wherein the attached primer comprises a stable loop and an -OH group at a 3'-position of a deoxyribose capable of self-priming in the polymerase reaction.
10. The method of claim 1, wherein the step of attaching the primer to the nucleic acid comprises hybridizing the primer to the nucleic acid or ligating the primer to the nucleic acid.
11. The method of claim 1, wherein one or more of four different nucleotide analogues is added in step (iii), wherein each different nucleotide analogue comprises a different base selected from the group consisting of thymine or uracil or an analogue of thymine or uracil, adenine or an analogue of adenine, cytosine or an analogue of cytosine, and guanine or an analogue of guanine, and wherein each of the four different nucleotide analogues comprises a unique label.
12. The method of claim 1, wherein the cleavable chemical group that caps the -OH group at the 3'-position of the deoxyribose in the nucleotide analogue is -CH2OCH3 or -CH2CH=CH2.
13. The method of claim 1, wherein the unique label that is attached to the nucleotide analogue is a fluorescent moiety or a fluorescent semiconductor crystal.
14. The method of claim 13, wherein the fluorescent moiety is selected from the group consisting of 5-carboxyfluorescein, 6-carboxyrhodamine-6G, N,N,N',N'-tetramethyl-6-carboxyrhodamine, and 6-carboxy-X-rhodamine.
15. The method of claim 1, wherein the unique label that is attached to the nucleotide analogue is a fluorescence energy transfer tag which comprises an energy transfer donor and an energy transfer acceptor.
16. The method of claim 15, wherein the energy transfer donor is 5-carboxyfluorescein or cyanine, and wherein the energy transfer acceptor is selected from the group consisting of dichlorocarboxyfluorescein, dichloro-6-carboxyrhodamine-6G, dichloro-N,N,N',N'-tetramethyl-6-carboxyrhodamine, and dichloro-6-carboxy-X-rhodamine.
17. The method of claim 1, wherein the unique label that is attached to the nucleotide analogue is a mass tag that can be detected and differentiated by a mass spectrometer.
18. The method of claim 17, wherein the mass tag is selected from the group consisting of a 2-nitro-a-methyl-benzyl group, a 2-nitro-.alpha.-methyl-3-fluorobenzyl group, a 2-nitro-.alpha.-methyl-3,4-difluorobenzyl group, and a 2-nitro-.alpha.-methyl-3,4-dimethoxybenzyl group.
19. The method of claim 1, wherein the unique label is attached through a cleavable linker to a 5-position of cytosine or thymine or to a 7-position of deaza-adenine or deaza-guanine.
20. The method of claim 1, wherein the cleavable linker between the unique label and the nucleotide analogue is cleaved by a means selected from the group consisting of one or more of a physical means, a chemical means, a physical chemical means, heat, and light.
21. The method of claim 20, wherein the cleavable linker is a photocleavable linker which comprises a 2-nitrobenzyl moiety.
22. The method of claim 1, wherein the cleavable chemical group used to cap the -OH group at the 3'-position of the deoxyribose is cleaved by a means selected from the group consisting of one or more of a physical means, a chemical means, a physical chemical means, heat, and light.
23. The method of claim 1, wherein the chemical compounds added in step (vi) to permanently cap any unreacted -OH group on the primer attached to the nucleic acid or on the primer extension strand are a polymerase and one or more different dideoxynucleotides or analogues of dideoxynucleotides.
24. The method of claim 23, wherein the different dideoxynucleotides are selected from the group consisting of 2',3'-dideoxyadenosine 5'-triphosphate, 2',3'-dideoxyguanosine 5'-triphosphate, 2',3'-dideoxycytidine 5'-triphosphate, 2',3'-dideoxythymidine 5'-triphosphate, 2',3'-dideoxyuridine 5'-triphosphase, and their analogues.
25. The method of claim 1, wherein a polymerase and one or more of four different dideoxynucleotides are added in step (vi), and wherein each different dideoxynucleotide is selected from the group consisting of 2',3'-dideoxyadenosine 5'-triphosphate or an analogue of 2',3'-dideoxyadenosine 5'-triphosphate; 2',3'-dideoxyguanosine 5'-triphosphate or an analogue of 2',3'-dideoxyguanosine 5'-triphosphate; 2',3'-dideoxycytidine 5'-triphosphate or an analogue of 2',3'-dideoxycytidine 5'-triphosphate; and 2',3'-dideoxythymidine 5'-triphosphate or 2',3'-dideoxyuridine 5'-triphosphase or an analogue of 2',3'-dideoxythymidine 5'-triphosphate or an analogue of 2',3'-dideoxyuridine 5'-triphosphase.
26. The method of claim 17, wherein the mass tag is detected using a parallel mass spectrometry system which comprises a plurality of atmospheric pressure chemical ionization mass spectrometers for parallel analysis of a plurality of samples comprising mass tags.
27. A method of simultaneously sequencing a plurality of different nucleic acids, which comprises simultaneously applying the method of claim 1 to the plurality of different nucleic acids.
28. Use of the method of claim 1 or 27 for detection of single nucleotide polymorphisms, genetic mutation analysis, serial analysis of gene expression, gene expression analysis, identification in forensics, genetic disease association studies, DNA
sequencing, genomic sequencing, translational analysis, or transcriptional analysis.
29. A method of attaching a nucleic acid to a solid surface which comprises:
(i) coating the solid surface with a phosphine moiety, (ii) attaching an azido group to a 5' end of the nucleic acid, and (iii) immobilizing the 5' end of the nucleic acid to the solid surface through interaction between the phosphine moiety on the solid surface and the azido group on the 5' end of the nucleic acid.
30. The method of claim 29, wherein the step of coating the solid surface with the phosphine moiety comprises:
(i) coating the surface with a primary amine, and (ii) covalently coupling a N-hydroxysuccinimidyl ester of triarylphosphine with the primary amine.
31. The method of claim 29, wherein the solid surface is glass, silicon, or gold.
32. The method of claim 29, wherein the solid surface is a magnetic bead, a chip, a channel in a chip, or a porous channel in a chip.
33. The method of claim 29, wherein the nucleic acid that is attached to the solid surface is a single-stranded DNA, a double-stranded DNA or a RNA.
34. The method of claim 33, wherein the nucleic acid is a double-stranded DNA and only one strand is attached to the solid surface.
35. The method of claim 34, wherein the strand of the double-stranded DNA that is not attached to the solid surface is removed by denaturing.
36. Use of the method of claim 29 for gene expression analysis, microarray based gene expression analysis, mutation detection, translational analysis, or transcriptional analysis.
37. A nucleotide analogue which comprises:

(a) a base selected from the group consisting of adenine or an analogue of adenine, cytosine or an analogue of cytosine, guanine or an analogue of guanine, thymine or an analogue of thymine, and uracil or an analogue of uracil;
(b) a unique label attached through a cleavable linker to the base or to an analogue of the base;
(c) a deoxyribose; and (d) a cleavable chemical group to cap an -OH group at a 3'-position of the deoxyribose.
38. The nucleotide analogue of claim 37, wherein the cleavable chemical group that caps the -OH group at the 3'-position of the deoxyribose is -CH2OCH3 or -CH2CH=CH2.
39. The nucleotide analogue of claim 37, wherein the unique label is a fluorescent moiety or a fluorescent semiconductor crystal.
40. The nucleotide analogue of claim 39, wherein the fluorescent moiety is selected from the group consisting of 5-carboxyfluorescein, 6-carboxyrhodamine-6G, N,N,N',N'-tetramethyl-6-carboxyrhodamine, and 6-carboxy-X-rhodamine.
41. The nucleotide analogue of claim 37, wherein the unique label is a fluorescence energy transfer tag which comprises an energy transfer donor and an energy transfer acceptor.
42. The nucleotide analogue of claim 41, wherein the energy transfer donor is 5-carboxyfluorescein or cyanine, and wherein the energy transfer acceptor is selected from the group consisting of dichlorocarboxyfluorescein, dichloro-6-carboxyrhodamine-6G, dichloro-N,N,N',N'-tetramethyl-6-carboxyrhodamine, and dichloro-6-carboxy-X-rhodamine.
43. The nucleotide analogue of claim 37, wherein the unique label is a mass tag that can be detected and differentiated by a mass spectrometer.
44. The nucleotide analogue of claim 43, wherein the mass tag is selected from the group consisting of a 2-nitro-a-methyl-benzyl group, a 2-nitro-.alpha.-methyl-3-fluorobenzyl group, a 2-nitro-.alpha.-methyl-3,4-difluorobenzyl group, and a 2-nitro-.alpha.-methyl-3,4-dimethoxybenzyl group.
45. The nucleotide analogue of claim 37, wherein the unique label is attached through a cleavable linker to a 5-position of cytosine or thymine or to a 7-position of deaza-adenine or deaza-guanine.
46. The nucleotide analogue of claim 37, wherein the linker between the unique label and the nucleotide analogue is cleavable by a means selected from the group consisting of one or more of a physical means, a chemical means, a physical chemical means, heat, and light.
47. The nucleotide analogue of claim 46, wherein the cleavable linker is a photocleavable linker which comprises a 2-nitrobenzyl moiety.
48. The nucleotide analogue of claim 37, wherein the cleavable chemical group used to cap the -OH group at the 3'-position of the deoxyribose is cleavable by a means selected from the group consisting of one or more of a physical means, a chemical means, a physical chemical means, heat, and light.
49. The nucleotide analogue of claim 37, wherein the nucleotide analogue is selected from the group consisting of:
wherein Dye1, Dye2, Dye3, and Dye4 are four different dye labels and wherein R is a cleavable chemical group used to cap the -OH group at the 3'-position of the deoxyribose.
50. The nucleotide analogue of claim 49, wherein the nucleotide analogue is selected from the group consisting of:
wherein R is -CH2OCH3 or -CH2CH=CH2.
51. The nucleotide analogue of claim 37, wherein the nucleotide analogue is selected from the group consisting of:
wherein Tag1, Tag2, Tag3, and Tag4 are four different mass tag labels; and wherein R is a cleavable chemical group used to cap the -OH group at the 3'-position of the deoxyribose.
52. The nucleotide analogue of claim 51, wherein the nucleotide analogue is selected from the group consisting of:
wherein R is -CH2OCH3 or -CH2CH=CH2.
53. Use of the nucleotide analogue of claim 37 for detection of single nucleotide polymorphisms, genetic mutation analysis, serial analysis of gene expression, gene expression analysis, identification in forensics, genetic disease association studies, DNA sequencing, genomic sequencing, translational analysis, or transcriptional analysis.
54. A parallel mass spectrometry system, which comprises a plurality of atmospheric pressure chemical ionization mass spectrometers for parallel analysis of a plurality of samples comprising mass tags.
55. The system of claim 54, wherein the mass spectrometers are quadrupole mass spectrometers or time-of-flight mass spectrometers.
56. The system of claim 54, wherein the mass spectrometers are contained in one device.
57. The system of claim 54 which further comprises two turbo-pumps, wherein one pump is used to generate a vacuum and a second pump is used to remove undesired elements.
58. The system of claim 54, which comprises at least three mass spectrometers.
59. The system of claim 54, wherein the mass tags have molecular weights between 150 daltons and 250 daltons.
60. Use of the system of claim 54 for DNA sequencing analysis, detection of single nucleotide polymorphisms, genetic mutation analysis, serial analysis of gene expression, gene expression analysis, identification in forensics, genetic disease association studies, DNA sequencing, genomic sequencing, translational analysis, or transcriptional analysis.
CA2425112A 2000-10-06 2001-10-05 Massive parallel method for decoding dna and rna Expired - Lifetime CA2425112C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US68467000A 2000-10-06 2000-10-06
US09/684,670 2000-10-06
US30089401P 2001-06-26 2001-06-26
US60/300,894 2001-06-26
PCT/US2001/031243 WO2002029003A2 (en) 2000-10-06 2001-10-05 Massive parallel method for decoding dna and rna

Publications (2)

Publication Number Publication Date
CA2425112A1 true CA2425112A1 (en) 2002-04-11
CA2425112C CA2425112C (en) 2011-09-27

Family

ID=26972030

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2425112A Expired - Lifetime CA2425112C (en) 2000-10-06 2001-10-05 Massive parallel method for decoding dna and rna

Country Status (9)

Country Link
US (25) US6664079B2 (en)
EP (3) EP1790736A3 (en)
JP (1) JP2004510433A (en)
AT (1) ATE356222T1 (en)
AU (1) AU2001296645A1 (en)
CA (1) CA2425112C (en)
DE (2) DE20122767U1 (en)
HK (1) HK1227441A1 (en)
WO (1) WO2002029003A2 (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9169510B2 (en) 2005-06-21 2015-10-27 The Trustees Of Columbia University In The City Of New York Pyrosequencing methods and related compositions
US9255292B2 (en) 2005-10-31 2016-02-09 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
US9297042B2 (en) 2005-10-31 2016-03-29 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
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
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
US9718852B2 (en) 2000-10-06 2017-08-01 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US11098353B2 (en) 2006-12-01 2021-08-24 The Trustees Of Columbia University In The City Of New York Four-color DNA sequencing by synthesis using cleavable fluorescent nucleotide reversible terminators
US11242561B2 (en) 2007-10-19 2022-02-08 The Trustees Of Columbia University In The City Of New York DNA sequencing with non-fluorescent nucleotide reversible terminators and cleavable label modified nucleotide terminators

Families Citing this family (237)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7153943B2 (en) * 1997-07-14 2006-12-26 Bolder Biotechnology, Inc. Derivatives of growth hormone and related proteins, and methods of use thereof
US7875440B2 (en) 1998-05-01 2011-01-25 Arizona Board Of Regents Method of determining the nucleotide sequence of oligonucleotides and DNA molecules
US6780591B2 (en) 1998-05-01 2004-08-24 Arizona Board Of Regents Method of determining the nucleotide sequence of oligonucleotides and DNA molecules
US6818395B1 (en) 1999-06-28 2004-11-16 California Institute Of Technology Methods and apparatus for analyzing polynucleotide sequences
US7501245B2 (en) * 1999-06-28 2009-03-10 Helicos Biosciences Corp. Methods and apparatuses for analyzing polynucleotide sequences
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
US7297518B2 (en) * 2001-03-12 2007-11-20 California Institute Of Technology Methods and apparatus for analyzing polynucleotide sequences by asynchronous base extension
US7057026B2 (en) 2001-12-04 2006-06-06 Solexa Limited Labelled nucleotides
GB0129012D0 (en) * 2001-12-04 2002-01-23 Solexa Ltd Labelled nucleotides
US7166478B2 (en) * 2002-03-12 2007-01-23 Enzo Life Sciences, Inc., C/O Enzo Biochem, Inc. Labeling reagents and labeled targets, target labeling processes and other processes for using same in nucleic acid determinations and analyses
WO2003087839A1 (en) * 2002-04-04 2003-10-23 Xzillion Gmbh & Co. Kg Method for characterising analytes
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
SI3587433T1 (en) 2002-08-23 2020-08-31 Illumina Cambridge Limited Modified nucleotides
US7414116B2 (en) 2002-08-23 2008-08-19 Illumina Cambridge Limited Labelled nucleotides
US11008359B2 (en) 2002-08-23 2021-05-18 Illumina Cambridge Limited Labelled nucleotides
EP2119722B1 (en) * 2002-08-23 2016-10-26 Illumina Cambridge Limited Labelled nucleotides
US20050032081A1 (en) * 2002-12-13 2005-02-10 Jingyue Ju Biomolecular coupling methods using 1,3-dipolar cycloaddition chemistry
US7414117B2 (en) * 2002-12-26 2008-08-19 Ngk Insulators, Ltd. Nucleotide derivative and DNA microarray
US7323555B2 (en) * 2002-12-26 2008-01-29 Isao Saito Nucleotide derivative and DNA microarray
US8637650B2 (en) 2003-11-05 2014-01-28 Genovoxx Gmbh Macromolecular nucleotide compounds and methods for using the same
US7169560B2 (en) 2003-11-12 2007-01-30 Helicos Biosciences Corporation Short cycle methods for sequencing polynucleotides
DE602005020421D1 (en) 2004-02-19 2010-05-20 Helicos Biosciences Corp METHOD FOR THE ANALYSIS OF POLYNUCLEOTIDE SEQUENCES
WO2005084367A2 (en) 2004-03-03 2005-09-15 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
US7157699B2 (en) * 2004-03-29 2007-01-02 Purdue Research Foundation Multiplexed mass spectrometer
WO2006073436A2 (en) * 2004-04-29 2006-07-13 The Trustees Of Columbia University In The City Of New York Mass tag pcr for multiplex diagnostics
US20070054345A1 (en) 2004-05-19 2007-03-08 Hunter Christie L Expression quantification using mass spectrometry
CA2569491A1 (en) * 2004-06-02 2005-12-15 Asm Scientific, Inc. 2'-nitrobenzyl-modified ribonucleotides
JP2005353340A (en) * 2004-06-09 2005-12-22 Hitachi Ltd Mass spectrometer
US20070048752A1 (en) 2004-07-12 2007-03-01 Applera Corporation Mass tags for quantitative analyses
WO2006017208A1 (en) * 2004-07-12 2006-02-16 Applera Corporation Mass tags for quantitative analyses
GB0421294D0 (en) * 2004-09-24 2004-10-27 Angiogene Pharm Ltd Bioreductively-activated prodrugs
EP1816130A4 (en) * 2004-11-08 2012-04-25 Riken Novel nucleoside or nucleotide derivative and use thereof
WO2006084132A2 (en) 2005-02-01 2006-08-10 Agencourt Bioscience Corp. Reagents, methods, and libraries for bead-based squencing
EP2233582A1 (en) 2005-02-01 2010-09-29 AB Advanced Genetic Analysis Corporation Nucleic acid sequencing by performing successive cycles of duplex extension
US20060183238A1 (en) 2005-02-09 2006-08-17 Applera Corporation Amine-containing compound analysis methods
JP2006241133A (en) * 2005-03-04 2006-09-14 Univ Of Tokyo Photodecomposable protecting group
US8212020B2 (en) * 2005-03-11 2012-07-03 Steven Albert Benner Reagents for reversibly terminating primer extension
US7544794B1 (en) * 2005-03-11 2009-06-09 Steven Albert Benner Method for sequencing DNA and RNA by synthesis
GB0507835D0 (en) * 2005-04-18 2005-05-25 Solexa Ltd Method and device for nucleic acid sequencing using a planar wave guide
CA2616433A1 (en) * 2005-07-28 2007-02-01 Helicos Biosciences Corporation Consecutive base single molecule sequencing
WO2007021757A2 (en) 2005-08-15 2007-02-22 Massachusetts Institute Of Technology Fluorescent sensor and methods
GB0517097D0 (en) 2005-08-19 2005-09-28 Solexa Ltd Modified nucleosides and nucleotides and uses thereof
US7666593B2 (en) 2005-08-26 2010-02-23 Helicos Biosciences Corporation Single molecule sequencing of captured nucleic acids
US7405281B2 (en) * 2005-09-29 2008-07-29 Pacific Biosciences Of California, Inc. Fluorescent nucleotide analogs and uses therefor
EP1937850B1 (en) 2005-10-27 2019-05-29 The President and Fellows of Harvard College Methods and compositions for labeling nucleic acids
AU2006318462A1 (en) * 2005-11-21 2007-05-31 The Trustees Of Columbia University In The City Of New York Multiplex digital immuno-sensing using a library of photocleavable mass tags
JP2009519717A (en) * 2005-12-16 2009-05-21 アプレラ コーポレイション Method and system for fixed phase sequencing
US8716033B2 (en) 2006-02-10 2014-05-06 Life Technologies Corporation Oligosaccharide modification and labeling of proteins
US8114636B2 (en) 2006-02-10 2012-02-14 Life Technologies Corporation Labeling and detection of nucleic acids
US20090062129A1 (en) * 2006-04-19 2009-03-05 Agencourt Personal Genomics, Inc. Reagents, methods, and libraries for gel-free bead-based sequencing
EP2021415B1 (en) 2006-05-18 2017-03-15 Illumina Cambridge Limited Dye compounds and the use of their labelled conjugates
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
WO2008037568A2 (en) * 2006-09-04 2008-04-03 Quiatech Ab Reversible terminators for efficient sequencing by synthesis
WO2008042067A2 (en) 2006-09-28 2008-04-10 Illumina, Inc. Compositions and methods for nucleotide sequencing
US7897737B2 (en) 2006-12-05 2011-03-01 Lasergen, Inc. 3′-OH unblocked, nucleotides and nucleosides, base modified with photocleavable, terminating groups and methods for their use in DNA sequencing
JP5513122B2 (en) 2006-12-05 2014-06-04 レーザーゲン インコーポレイテッド Photocleavable labeled nucleotides and nucleosides and labeled nucleotides and nucleosides and their use in DNA sequencing
US7893227B2 (en) * 2006-12-05 2011-02-22 Lasergen, Inc. 3′-OH unblocked nucleotides and nucleosides base modified with non-cleavable, terminating groups and methods for their use in DNA sequencing
US11035823B2 (en) 2009-03-17 2021-06-15 Qiagen Sciences, Llc Methods and devices for sequencing nucleic acids in smaller batches
US11940413B2 (en) 2007-02-05 2024-03-26 IsoPlexis Corporation Methods and devices for sequencing nucleic acids in smaller batches
US8481259B2 (en) 2007-02-05 2013-07-09 Intelligent Bio-Systems, Inc. Methods and devices for sequencing nucleic acids in smaller batches
US8612161B2 (en) 2008-03-19 2013-12-17 Intelligent Biosystems Inc. Methods and compositions for base calling nucleic acids
JP5750209B2 (en) * 2007-03-16 2015-07-15 アプタ バイオサイエンス リミテッド Functional molecule, amidite for functional molecule synthesis, and target substance analysis method
US9163053B2 (en) * 2007-05-18 2015-10-20 Fluidigm Corporation Nucleotide analogs
JP2010536383A (en) * 2007-08-23 2010-12-02 アプライド バイオシステムズ， エルエルシー Method of modifying support surface for particle immobilization and use of immobilized particles for nucleic acid analysis
JP2010537643A (en) * 2007-08-29 2010-12-09 アプライド バイオシステムズ， エルエルシー Alternative nucleic acid sequencing methods
US20090191553A1 (en) * 2007-10-01 2009-07-30 Applied Biosystems Inc. Chase Ligation Sequencing
WO2009051807A1 (en) 2007-10-19 2009-04-23 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
WO2009067632A1 (en) * 2007-11-20 2009-05-28 Applied Biosystems Inc. Method of sequencing nucleic acids using elaborated nucleotide phosphorothiolate compounds
US8017338B2 (en) * 2007-11-20 2011-09-13 Life Technologies Corporation Reversible di-nucleotide terminator sequencing
JP5498952B2 (en) 2007-11-21 2014-05-21 ユニバーシティ・オブ・ジョージア・リサーチ・ファウンデイション・インコーポレイテッド Process for reacting alkynes with alkynes and 1,3-dipolar functional compounds
CA2718404C (en) 2008-03-13 2018-04-10 Pacific Biosciences Of California, Inc. Labeled reactants and their uses
US9017973B2 (en) 2008-03-19 2015-04-28 Intelligent Biosystems, Inc. Methods and compositions for incorporating nucleotides
US10745740B2 (en) 2008-03-19 2020-08-18 Qiagen Sciences, Llc Sample preparation
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
EP2297344B1 (en) 2008-05-16 2018-03-14 Life Technologies Corporation Dual labeling methods for measuring cellular proliferation
ES2625938T3 (en) 2008-05-27 2017-07-21 Trilink Biotechnologies Chemically modified 5¿-triphosphate nucleosides for thermally initiated nucleic acid replication
CN103588839B (en) 2008-06-11 2017-04-12 激光基因公司 Nucleotides and nucleosides and method for their use in DNA sequencing
WO2010002939A2 (en) * 2008-06-30 2010-01-07 Life Technologies Corporation Methods for real time single molecule sequencing
WO2010003153A2 (en) * 2008-07-03 2010-01-07 Life Technologies Corporation Methylation analysis of mate pairs
US8173198B2 (en) * 2008-07-23 2012-05-08 Life Technologies Corporation Deposition of metal oxides onto surfaces as an immobilization vehicle for carboxylated or phophated particles or polymers
US20100179075A1 (en) * 2008-07-30 2010-07-15 Life Technologies Corporation Particles for use in supported nucleic acid ligation and detection sequencing
US8541207B2 (en) 2008-10-22 2013-09-24 Illumina, Inc. Preservation of information related to genomic DNA methylation
ATE547522T1 (en) 2008-12-23 2012-03-15 Qiagen Gmbh METHOD AND DEVICE FOR CARRYING OUT NUCLEIC ACID PREPARATION AND/OR AMPLIFICATION
KR20100089688A (en) * 2009-02-04 2010-08-12 삼성전자주식회사 Method for analyzing target nucleic acid
WO2010111690A2 (en) 2009-03-27 2010-09-30 Life Technologies Corporation Polymerase compositions and methods
US20100330569A1 (en) * 2009-04-23 2010-12-30 Intelligent Bio-Systems, Inc. Hydroxymethyl Linkers For Labeling Nucleotides
WO2010129019A2 (en) 2009-04-27 2010-11-11 Pacific Biosciences Of California, Inc. Real-time sequencing methods and systems
GB0907372D0 (en) 2009-04-29 2009-06-10 Invitrogen Dynal As Particles
US10174368B2 (en) 2009-09-10 2019-01-08 Centrillion Technology Holdings Corporation Methods and systems for sequencing long nucleic acids
CN102858995B (en) 2009-09-10 2016-10-26 森特瑞隆技术控股公司 Targeting sequence measurement
WO2011050938A1 (en) 2009-10-26 2011-05-05 Genovoxx Gmbh Conjugates of nucleotides and method for the application thereof
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
US9678055B2 (en) 2010-02-08 2017-06-13 Genia Technologies, Inc. Methods for forming a nanopore in a lipid bilayer
US20110192723A1 (en) * 2010-02-08 2011-08-11 Genia Technologies, Inc. Systems and methods for manipulating a molecule in a nanopore
US8603741B2 (en) 2010-02-18 2013-12-10 Pacific Biosciences Of California, Inc. Single molecule sequencing with two distinct chemistry steps
EP2539464B1 (en) 2010-02-23 2016-11-16 Illumina, Inc. Amplification methods to minimise sequence specific bias
WO2011123246A2 (en) 2010-04-01 2011-10-06 Illumina, Inc. Solid-phase clonal amplification and related methods
US9029103B2 (en) 2010-08-27 2015-05-12 Illumina Cambridge Limited Methods for sequencing polynucleotides
WO2012040624A1 (en) * 2010-09-23 2012-03-29 Centrillion Technology Holding Corporation Native-extension parallel sequencing
GB201016484D0 (en) 2010-09-30 2010-11-17 Geneseque As Method
JP6114694B2 (en) 2010-10-04 2017-04-12 ジナプシス インコーポレイテッド Systems and methods for automated reusable parallel biological reactions
WO2013082164A1 (en) 2011-11-28 2013-06-06 Life Technologies Corporation Enhanced ligation reactions
EP2652153B1 (en) 2010-12-17 2017-07-05 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
US9217132B2 (en) 2011-01-20 2015-12-22 Ibis Biosciences, Inc. Microfluidic transducer
US9581563B2 (en) 2011-01-24 2017-02-28 Genia Technologies, Inc. System for communicating information from an array of sensors
US9110478B2 (en) 2011-01-27 2015-08-18 Genia Technologies, Inc. Temperature regulation of measurement arrays
US20120252682A1 (en) 2011-04-01 2012-10-04 Maples Corporate Services Limited Methods and systems for sequencing nucleic acids
WO2012146377A1 (en) 2011-04-27 2012-11-01 Dmitry Cherkasov Method and components for detecting nucleic acid chains
WO2012150035A1 (en) 2011-05-04 2012-11-08 Genovoxx Gmbh Nucleoside-triphosphate conjugate and methods for the use thereof
US9926596B2 (en) 2011-05-27 2018-03-27 Genapsys, Inc. Systems and methods for genetic and biological analysis
MX2014002027A (en) 2011-08-19 2014-11-10 Synthetic Genomics Inc Integrated method for high-throughput identification of novel pesticidal compositions and uses therefor.
US9988680B2 (en) 2011-09-01 2018-06-05 Case Western Reserve University Non-natural nucleosides as theranostic agents
AU2012308518B2 (en) 2011-09-13 2017-08-17 Agilent Technologies, Inc. 5-methoxy, 3'-oh unblocked, fast photocleavable terminating nucleotides and methods for nucleic acid sequencing
US10378051B2 (en) 2011-09-29 2019-08-13 Illumina Cambridge Limited Continuous extension and deblocking in reactions for nucleic acids synthesis and sequencing
CN104105797B (en) 2011-12-01 2016-08-31 吉纳普赛斯股份有限公司 System and method for efficent electronic order-checking with detection
EP3415901A1 (en) 2012-01-20 2018-12-19 Genia Technologies, Inc. Nanopore based molecular detection and sequencing
US8986629B2 (en) 2012-02-27 2015-03-24 Genia Technologies, Inc. Sensor circuit for controlling, detecting, and measuring a molecular complex
US10246479B2 (en) 2012-04-09 2019-04-02 The Trustees Of Columbia University In The City Of New York Method of preparation of nanopore and uses thereof
EP2861768A4 (en) 2012-06-15 2016-03-02 Genia Technologies Inc Chip set-up and high-accuracy nucleic acid sequencing
WO2013191793A1 (en) 2012-06-20 2013-12-27 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
US9759711B2 (en) 2013-02-05 2017-09-12 Genia Technologies, Inc. Nanopore arrays
CN103232489B (en) * 2013-02-18 2016-09-28 常州津坛生物科技有限公司 A kind of fluorescent probe compounds and its production and use
US9146248B2 (en) 2013-03-14 2015-09-29 Intelligent Bio-Systems, Inc. Apparatus and methods for purging flow cells in nucleic acid sequencing instruments
WO2014152625A1 (en) 2013-03-15 2014-09-25 Genapsys, Inc. Systems and methods for biological analysis
WO2014144898A1 (en) 2013-03-15 2014-09-18 The Trustees Of Columbia University In The City Of New York Method for detecting multiple predetermined compounds in a sample
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
US9591268B2 (en) 2013-03-15 2017-03-07 Qiagen Waltham, Inc. Flow cell alignment methods and systems
WO2014139596A1 (en) 2013-03-15 2014-09-18 Illumina Cambridge Limited Modified nucleosides or nucleotides
US9279149B2 (en) 2013-04-02 2016-03-08 Molecular Assemblies, Inc. Methods and apparatus for synthesizing nucleic acids
US11331643B2 (en) 2013-04-02 2022-05-17 Molecular Assemblies, Inc. Reusable initiators for synthesizing nucleic acids
US8808989B1 (en) 2013-04-02 2014-08-19 Molecular Assemblies, Inc. Methods and apparatus for synthesizing nucleic acids
US11384377B2 (en) 2013-04-02 2022-07-12 Molecular Assemblies, Inc. Reusable initiators for synthesizing nucleic acids
US10683536B2 (en) 2013-04-02 2020-06-16 Molecular Assemblies, Inc. Reusable initiators for synthesizing nucleic acids
US9771613B2 (en) 2013-04-02 2017-09-26 Molecular Assemblies, Inc. Methods and apparatus for synthesizing nucleic acid
US10337049B2 (en) 2013-06-17 2019-07-02 The Trustees Of Columbia University In The City Of New York Universal methylation profiling methods
CN103601778A (en) * 2013-10-17 2014-02-26 上海交通大学 Synthetic method of 7-denitrified-7-substituted guanosine
CN103601779B (en) * 2013-10-17 2016-05-04 上海交通大学 The synthetic method of 7-denitrification-2 '-deoxidation-7-halogen 9 substituted guanine nucleosides
US9551697B2 (en) 2013-10-17 2017-01-24 Genia Technologies, Inc. Non-faradaic, capacitively coupled measurement in a nanopore cell array
EP3060918B1 (en) 2013-10-23 2019-09-18 Genia Technologies, Inc. High speed molecular sensing with nanopores
US9322062B2 (en) 2013-10-23 2016-04-26 Genia Technologies, Inc. Process for biosensor well formation
CN103588838A (en) * 2013-10-30 2014-02-19 上海交通大学 Synthesis method of base modified nucleotide and application thereof
CN103819523B (en) * 2014-01-22 2016-02-10 上海交通大学 The synthetic method of 7-denitrification-7-halogen guanosine-
CN106715453B (en) 2014-03-24 2021-04-30 哥伦比亚大学董事会 Chemical process for producing tagged nucleotides
FR3020071B1 (en) 2014-04-17 2017-12-22 Dna Script PROCESS FOR THE SYNTHESIS OF NUCLEIC ACIDS, IN PARTICULAR LARGE NUCLEIC ACIDS, USE OF THE METHOD AND KIT FOR IMPLEMENTING THE METHOD
EP3132060B1 (en) 2014-04-18 2019-03-13 Genapsys Inc. Methods and systems for nucleic acid amplification
US20170218416A1 (en) * 2014-05-16 2017-08-03 The Regents Of The University Of California Compositions and methods for single-molecule construction of dna
WO2016022540A1 (en) * 2014-08-04 2016-02-11 The Trustees Of The University Of Pennsylvania Transcriptome in vivo analysis ( tiva) and transcriptome in situ analysis (tisa)
GB201413929D0 (en) 2014-08-06 2014-09-17 Geneseque As Method
FR3025201B1 (en) 2014-09-02 2018-10-12 Dna Script MODIFIED NUCLEOTIDES FOR THE SYNTHESIS OF NUCLEIC ACIDS, A KIT COMPRISING SUCH NUCLEOTIDES AND THEIR USE FOR GENERATING SYNTHETIC NUCLEIC ACID GENES OR SEQUENCES
US10487357B2 (en) 2014-10-03 2019-11-26 Life Technologies Corporation Methods of nucleic acid analysis using terminator nucleotides
US10544455B2 (en) 2014-10-03 2020-01-28 Life Technologies Corporation Sequencing methods, compositions and systems using terminator nucleotides
WO2016064880A1 (en) 2014-10-20 2016-04-28 Molecular Assemblies, Inc. Modified template-independent enzymes for polydeoxynucleotide systhesis
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
US9856285B2 (en) * 2015-03-17 2018-01-02 Kaohsiung Medical University Reagents for universal site-specific labeling and modifications of nucleic acids
JP6698708B2 (en) 2015-06-09 2020-05-27 ライフ テクノロジーズ コーポレーション Methods, systems, compositions, kits, devices, and computer-readable media for molecular tagging
US10077470B2 (en) 2015-07-21 2018-09-18 Omniome, Inc. Nucleic acid sequencing methods and systems
BR112017023418A2 (en) 2015-07-30 2018-07-24 Illumina, Inc. orthogonal nucleotide unlocking
US11085076B2 (en) 2015-09-28 2021-08-10 The Trustees Of Columbia University In The City Of New York Synthesis of novel disulfide linker based nucleotides as reversible terminators for DNA sequencing by synthesis
EP3368668B1 (en) 2015-10-28 2023-11-29 Silicon Valley Scientific, Inc. Method and apparatus for encoding cellular spatial position information
US11421264B2 (en) 2015-11-06 2022-08-23 IsoPlexis Corporation Thiol-containing cleave reagents and oxidative wash
US10273539B2 (en) 2015-11-06 2019-04-30 Qiagen Sciences, Llc Methods of using nucleotide analogues
DE112016005255B4 (en) 2015-12-17 2023-06-15 Hitachi High-Tech Corporation biomolecule measuring device
WO2017139415A2 (en) 2016-02-11 2017-08-17 Qiagen Waltham, Inc. Scavenger compounds for improved sequencing-by-synthesis
WO2017139418A1 (en) 2016-02-11 2017-08-17 Qiagen Waltham, Inc. Additive to improve sequencing by synthesis performance
CN109196113B (en) 2016-02-11 2022-10-04 奇根科学有限责任公司 Polyphenol additives in sequencing by synthesis
EP3449012B1 (en) 2016-04-29 2020-12-23 Omniome, Inc. Sequencing method employing ternary complex destabilization to identify cognate nucleotides
US11266673B2 (en) 2016-05-23 2022-03-08 The Trustees Of Columbia University In The City Of New York Nucleotide derivatives and methods of use thereof
US11299769B2 (en) 2016-06-06 2022-04-12 Redvault Biosciences, Lp Target reporter constructs and uses thereof
CN109790575A (en) 2016-07-20 2019-05-21 吉纳普赛斯股份有限公司 System and method for nucleic acid sequencing
WO2018034780A1 (en) 2016-08-15 2018-02-22 Omniome, Inc. Sequencing method for rapid identification and processing of cognate nucleotide pairs
EP4039824A1 (en) 2016-08-15 2022-08-10 Pacific Biosciences of California, Inc. Method and system for sequencing nucleic acids
CN110121563A (en) 2016-11-09 2019-08-13 奇根科学有限责任公司 Light in being sequenced in synthesis as imaging agents protects mixture
CA3048415C (en) 2016-12-30 2023-02-28 Omniome, Inc. Method and system employing distinguishable polymerases for detecting ternary complexes and identifying cognate nucleotides
IL267836B2 (en) 2017-01-04 2023-09-01 Complete Genomics Inc Stepwise sequencing by non-labeled reversible terminators or natural nucleotides
GB201700983D0 (en) 2017-01-20 2017-03-08 Life Tech As Polymeric particles
CA3050695C (en) 2017-01-20 2024-02-20 Omniome, Inc. Process for cognate nucleotide detection in a nucleic acid sequencing workflow
EP3596099A4 (en) 2017-03-06 2020-12-09 Singular Genomics Systems, Inc. Nucleic acid sequencing-by-synthesis (sbs) methods that combine sbs cycle steps
US20210285041A1 (en) * 2017-03-28 2021-09-16 The Trustees Of Columbia University In The City Of New York 3'-o-modified nucleotide analogues with different cleavable linkers for attaching fluorescent labels to the base for dna sequencing by synthesis
US10161003B2 (en) 2017-04-25 2018-12-25 Omniome, Inc. Methods and apparatus that increase sequencing-by-binding efficiency
US9951385B1 (en) 2017-04-25 2018-04-24 Omniome, Inc. Methods and apparatus that increase sequencing-by-binding efficiency
GB2578038B (en) 2017-06-16 2022-11-23 Life Technologies Corp Control nucleic acids, and compositions, kits, and uses thereof
US11110114B2 (en) 2017-07-17 2021-09-07 Oxford University Innovation Limited Dinucleotides
US11104700B2 (en) 2017-07-17 2021-08-31 Oxford University Innovation Limited Oligonucleotides
US11692221B2 (en) 2017-08-01 2023-07-04 Mgi Tech Co., Ltd. Nucleic acid sequencing method
SG11202002282TA (en) 2017-09-20 2020-04-29 Regeneron Pharma Immunotherapy methods for patients whose tumors carry a high passenger gene mutation burden
CN111566224A (en) * 2017-09-21 2020-08-21 吉纳普赛斯股份有限公司 Systems and methods for nucleic acid sequencing
US11193166B2 (en) 2017-10-19 2021-12-07 Omniome, Inc. Simultaneous background reduction and complex stabilization in binding assay workflows
WO2019079802A1 (en) * 2017-10-20 2019-04-25 President And Fellows Of Harvard College Methods of encoding and high-throughput decoding of information stored in dna
CN111836904A (en) 2017-12-21 2020-10-27 豪夫迈·罗氏有限公司 Compositions and methods for unidirectional nucleic acid sequencing
US10844430B2 (en) 2018-01-24 2020-11-24 Qiagen Sciences, Llc DNA sequencing reaction additive
US20210189460A1 (en) 2018-04-25 2021-06-24 Qiagen Sciences Llc Sequential paired-end sequencing
JP7100069B2 (en) 2018-05-15 2022-07-12 イルミナ インコーポレイテッド Compositions and Methods for Chemical Cleavage and Deprotection of Surface-Binding Oligonucleotides
EP3793618A4 (en) 2018-05-18 2022-03-02 Singular Genomics Systems, Inc. Silicon containing detectable compounds
WO2019226689A1 (en) 2018-05-22 2019-11-28 Axbio Inc. Methods, systems, and compositions for nucleic acid sequencing
CA3102109A1 (en) 2018-05-30 2019-12-05 Dtx Pharma, Inc. Lipid-modified nucleic acid compounds and methods
CN110818757A (en) * 2018-08-07 2020-02-21 深圳华大生命科学研究院 Nucleotide analogs and method for screening DNA polymerase
US20230011240A1 (en) 2018-09-11 2023-01-12 Singular Genomics Systems, Inc. Modified archaeal family b polymerases
WO2020086834A1 (en) 2018-10-25 2020-04-30 Singular Genomics Systems, Inc. Nucleotide analogues
US20220010370A1 (en) 2018-11-07 2022-01-13 Egi Tech (Shen Zhen) Co., Limited Method for sequencing polynucleotides
US10704094B1 (en) 2018-11-14 2020-07-07 Element Biosciences, Inc. Multipart reagents having increased avidity for polymerase binding
US10876148B2 (en) 2018-11-14 2020-12-29 Element Biosciences, Inc. De novo surface preparation and uses thereof
US10768173B1 (en) * 2019-09-06 2020-09-08 Element Biosciences, Inc. Multivalent binding composition for nucleic acid analysis
EP3894593A2 (en) 2018-12-13 2021-10-20 DNA Script Direct oligonucleotide synthesis on cells and biomolecules
US11293061B2 (en) * 2018-12-26 2022-04-05 Illumina Cambridge Limited Sequencing methods using nucleotides with 3′ AOM blocking group
EP3908286A4 (en) 2019-01-08 2022-10-12 Singular Genomics Systems, Inc. Nucleotide cleavable linkers and uses thereof
KR20210125496A (en) 2019-02-12 2021-10-18 디엔에이 스크립트 Efficient product cleavage in template-free enzymatic synthesis of polynucleotides
JP2022521730A (en) 2019-02-19 2022-04-12 ウルティマ・ゲノミクス・インコーポレーテッド Linkers and methods for photodetection and sequencing
US20220205036A1 (en) 2019-05-15 2022-06-30 EGI Tech (Shenzhen) Co., Limited Single-channel sequencing method based on self-luminescence
EP4047098A4 (en) 2019-08-20 2023-06-07 EGI Tech (Shen Zhen) Co., Limited Method for sequencing polynucleotides on basis of optical signal dynamics of luminescent label and secondary luminescent signal
US11512295B2 (en) 2019-09-12 2022-11-29 Singular Genomics Systems, Inc. Modified thermoccocus polymerases
US11287422B2 (en) 2019-09-23 2022-03-29 Element Biosciences, Inc. Multivalent binding composition for nucleic acid analysis
EP4034669A1 (en) 2019-09-23 2022-08-03 DNA Script Increasing long-sequence yields in template-free enzymatic synthesis of polynucleotides
EP4055023A4 (en) 2019-11-07 2024-01-03 Singular Genomics Systems Inc Silicon containing detectable compounds and uses thereof
AU2020412459B2 (en) 2019-12-23 2022-12-08 Singular Genomics Systems, Inc. Methods for long read sequencing
US11155858B2 (en) 2019-12-31 2021-10-26 Singular Genomics Systems, Inc. Polynucleotide barcodes for long read sequencing
US11807851B1 (en) 2020-02-18 2023-11-07 Ultima Genomics, Inc. Modified polynucleotides and uses thereof
US11034942B1 (en) 2020-02-27 2021-06-15 Singular Genomics Systems, Inc. Modified pyrococcus polymerases and uses thereof
US11359238B2 (en) 2020-03-06 2022-06-14 Singular Genomics Systems, Inc. Linked paired strand sequencing
EP4117682A4 (en) 2020-04-24 2023-09-13 Singular Genomics Systems, Inc. Modified nucleotides and uses thereof
WO2021226327A1 (en) * 2020-05-08 2021-11-11 Singular Genomics Systems, Inc. Nucleotide cleavable linkers with rigid spacers and uses thereof
US11787831B2 (en) 2020-06-22 2023-10-17 Illumina Cambridge Limited Nucleosides and nucleotides with 3′ acetal blocking group
JP2023532231A (en) 2020-06-30 2023-07-27 イルミナ インコーポレイテッド Sequencing by Catalytically Controlled Synthesis to Generate Unblemished DNA
EP4153606A2 (en) 2020-07-13 2023-03-29 Singular Genomics Systems, Inc. Methods of sequencing complementary polynucleotides
GB2605470A (en) * 2020-10-29 2022-10-05 Ambergen Inc Novel photocleavable mass-tags for multiplexed mass spectrometric imaging of tissues using biomolecular probes
WO2022170212A1 (en) 2021-02-08 2022-08-11 Singular Genomics Systems, Inc. Methods and compositions for sequencing complementary polynucleotides
EP4294920A1 (en) 2021-04-27 2023-12-27 Singular Genomics Systems, Inc. High density sequencing and multiplexed priming
EP4089098A1 (en) * 2021-05-10 2022-11-16 Miltenyi Biotec B.V. & Co. KG Fret dye labeled reversible nucleotide terminators and their use in sequencing of dna
US20230047225A1 (en) 2021-08-14 2023-02-16 Illumina, Inc. Polymerases, compositions, and methods of use
CA3231118A1 (en) 2021-09-07 2023-03-16 Meihua Gong Method for analyzing sequence of target polynucleotide
CN115943217A (en) 2021-09-07 2023-04-07 深圳华大智造科技股份有限公司 Method for analyzing sequence of target polynucleotide
WO2023107673A2 (en) 2021-12-10 2023-06-15 Singular Genomics Systems, Inc. Cleavable disulfide linkers and uses thereof
CA3222797A1 (en) 2022-03-31 2023-10-05 Ramesh NEELAKANDAN Nucleosides and nucleotides with 3' vinyl blocking group
US20230383342A1 (en) 2022-05-31 2023-11-30 Illumina Cambridge Limited Compositions and methods for nucleic acid sequencing

Family Cites Families (220)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4711955A (en) 1981-04-17 1987-12-08 Yale University Modified nucleotides and methods of preparing and using same
US5175269A (en) 1984-01-30 1992-12-29 Enzo Diagnostics, Inc. Compound and detectable molecules having an oligo- or polynucleotide with modifiable reactive group
US5118605A (en) * 1984-10-16 1992-06-02 Chiron Corporation Polynucleotide determination with selectable cleavage sites
US4824775A (en) 1985-01-03 1989-04-25 Molecular Diagnostics, Inc. Cells labeled with multiple Fluorophores bound to a nucleic acid carrier
US4772691A (en) 1985-06-05 1988-09-20 The Medical College Of Wisconsin, Inc. Chemically cleavable nucleotides
US4863849A (en) 1985-07-18 1989-09-05 New York Medical College Automatable process for sequencing nucleotide
DE3529478A1 (en) 1985-08-16 1987-02-19 Boehringer Mannheim Gmbh 7-DESAZA-2'DESOXYGUANOSINE NUCLEOTIDES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE FOR NUCLEIC ACID SEQUENCING
US4888274A (en) 1985-09-18 1989-12-19 Yale University RecA nucleoprotein filament and methods
US5242796A (en) 1986-07-02 1993-09-07 E. I. Du Pont De Nemours And Company Method, system and reagents for DNA sequencing
US5151507A (en) 1986-07-02 1992-09-29 E. I. Du Pont De Nemours And Company Alkynylamino-nucleotides
CA1340806C (en) 1986-07-02 1999-11-02 James Merrill Prober Method, system and reagents for dna sequencing
US5047519A (en) 1986-07-02 1991-09-10 E. I. Du Pont De Nemours And Company Alkynylamino-nucleotides
GB8810400D0 (en) 1988-05-03 1988-06-08 Southern E Analysing polynucleotide sequences
SE8801070D0 (en) 1988-03-23 1988-03-23 Pharmacia Ab METHOD FOR IMMOBILIZING A DNA SEQUENCE ON A SOLID SUPPORT
EP0451141B1 (en) 1988-05-20 1998-11-18 F. Hoffmann-La Roche Ag Immobilized sequence-specific probes
US5174962A (en) 1988-06-20 1992-12-29 Genomyx, Inc. Apparatus for determining DNA sequences by mass spectrometry
US5043272A (en) 1989-04-27 1991-08-27 Life Technologies, Incorporated Amplification of nucleic acid sequences using oligonucleotides of random sequence as primers
GB8910880D0 (en) 1989-05-11 1989-06-28 Amersham Int Plc Sequencing method
US5424186A (en) 1989-06-07 1995-06-13 Affymax Technologies N.V. Very large scale immobilized polymer synthesis
US5547839A (en) 1989-06-07 1996-08-20 Affymax Technologies N.V. Sequencing of surface immobilized polymers utilizing microflourescence detection
US5302509A (en) 1989-08-14 1994-04-12 Beckman Instruments, Inc. Method for sequencing polynucleotides
WO1991006678A1 (en) * 1989-10-26 1991-05-16 Sri International Dna sequencing
US5437975A (en) 1991-02-25 1995-08-01 California Institute Of Biological Research Consensus sequence primed polymerase chain reaction method for fingerprinting genomes
JPH04337446A (en) 1991-05-15 1992-11-25 Hitachi Ltd Method and device for measuring fine grain and constant quantity method
US5556748A (en) 1991-07-30 1996-09-17 Xenopore Corporation Methods of sandwich hybridization for the quantitative analysis of oligonucleotides
WO1993005183A1 (en) 1991-09-09 1993-03-18 Baylor College Of Medicine Method and device for rapid dna or rna sequencing determination by a base addition sequencing scheme
DE4141178A1 (en) 1991-12-13 1993-06-17 Europ Lab Molekularbiolog New nucleic acid sequencing method - using one labelled nucleotide at one time in cycles comprising elongation, wash, label detection and removal of the label, then repeating
DE4141698A1 (en) 1991-12-18 1993-07-01 Bosch Gmbh Robert CLOSING TIME CONTROL METHOD
US6555349B1 (en) 1993-01-22 2003-04-29 Cornell Research Foundation, Inc. Methods for amplifying and sequencing nucleic acid molecules using a three component polymerase
GB9208733D0 (en) 1992-04-22 1992-06-10 Medical Res Council Dna sequencing method
US5637469A (en) 1992-05-01 1997-06-10 Trustees Of The University Of Pennsylvania Methods and apparatus for the detection of an analyte utilizing mesoscale flow systems
GB9210176D0 (en) 1992-05-12 1992-06-24 Cemu Bioteknik Ab Chemical method
US5383858B1 (en) 1992-08-17 1996-10-29 Medrad Inc Front-loading medical injector and syringe for use therewith
US5516664A (en) 1992-12-23 1996-05-14 Hyman; Edward D. Enzymatic synthesis of repeat regions of oligonucleotides
US5436143A (en) 1992-12-23 1995-07-25 Hyman; Edward D. Method for enzymatic synthesis of oligonucleotides
US6074823A (en) * 1993-03-19 2000-06-13 Sequenom, Inc. DNA sequencing by mass spectrometry via exonuclease degradation
FR2703052B1 (en) 1993-03-26 1995-06-02 Pasteur Institut New method of nucleic acid sequencing.
US5959089A (en) 1993-07-19 1999-09-28 Hannessian; Stephen Amino-cyclodextrin syntheses
GB9315847D0 (en) * 1993-07-30 1993-09-15 Isis Innovation Tag reagent and assay method
US5547859A (en) 1993-08-02 1996-08-20 Goodman; Myron F. Chain-terminating nucleotides for DNA sequencing methods
CA2170264A1 (en) 1993-09-10 1995-03-16 Michael W. Konrad Optical detection of position of oligonucleotides on large dna molecules
WO1995014108A1 (en) 1993-11-17 1995-05-26 Amersham International Plc Primer extension mass spectroscopy nucleic acid sequencing method
US5654419A (en) 1994-02-01 1997-08-05 The Regents Of The University Of California Fluorescent labels and their use in separations
US5869255A (en) 1994-02-01 1999-02-09 The Regents Of The University Of California Probes labeled with energy transfer couples dyes exemplified with DNA fragment analysis
US6028190A (en) 1994-02-01 2000-02-22 The Regents Of The University Of California Probes labeled with energy transfer coupled dyes
FR2716263B1 (en) 1994-02-11 1997-01-17 Pasteur Institut Method for aligning macromolecules by passing a meniscus and applications in a method for highlighting, separating and / or assaying a macromolecule in a sample.
US5714330A (en) 1994-04-04 1998-02-03 Lynx Therapeutics, Inc. DNA sequencing by stepwise ligation and cleavage
US5552278A (en) * 1994-04-04 1996-09-03 Spectragen, Inc. DNA sequencing by stepwise ligation and cleavage
US6589736B1 (en) 1994-11-22 2003-07-08 The Trustees Of Boston University Photocleavable agents and conjugates for the detection and isolation of biomolecules
US20020168642A1 (en) 1994-06-06 2002-11-14 Andrzej Drukier Sequencing duplex DNA by mass spectroscopy
US5709999A (en) 1994-08-12 1998-01-20 Myriad Genetics Inc. Linked breast and ovarian cancer susceptibility gene
US6232465B1 (en) 1994-09-02 2001-05-15 Andrew C. Hiatt Compositions for enzyme catalyzed template-independent creation of phosphodiester bonds using protected nucleotides
US5808045A (en) 1994-09-02 1998-09-15 Andrew C. Hiatt Compositions for enzyme catalyzed template-independent creation of phosphodiester bonds using protected nucleotides
US5763594A (en) 1994-09-02 1998-06-09 Andrew C. Hiatt 3' protected nucleotides for enzyme catalyzed template-independent creation of phosphodiester bonds
US6214987B1 (en) 1994-09-02 2001-04-10 Andrew C. Hiatt Compositions for enzyme catalyzed template-independent formation of phosphodiester bonds using protected nucleotides
US5872244A (en) 1994-09-02 1999-02-16 Andrew C. Hiatt 3' protected nucleotides for enzyme catalyzed template-independent creation of phosphodiester bonds
US6013445A (en) 1996-06-06 2000-01-11 Lynx Therapeutics, Inc. Massively parallel signature sequencing by ligation of encoded adaptors
US5614365A (en) 1994-10-17 1997-03-25 President & Fellow Of Harvard College DNA polymerase having modified nucleotide binding site for DNA sequencing
WO1997027317A1 (en) 1996-01-23 1997-07-31 Affymetrix, Inc. Nucleic acid analysis techniques
DE4438918A1 (en) 1994-11-04 1996-05-09 Hoechst Ag Modified oligonucleotides, their preparation and their use
SE9500342D0 (en) 1995-01-31 1995-01-31 Marek Kwiatkowski Novel chain terminators, the use thereof for nucleic acid sequencing and synthesis and a method of their preparation
WO1996027025A1 (en) 1995-02-27 1996-09-06 Ely Michael Rabani Device, compounds, algorithms, and methods of molecular characterization and manipulation with molecular parallelism
US5885813A (en) 1995-05-31 1999-03-23 Amersham Life Science, Inc. Thermostable DNA polymerases
EP0745686A1 (en) 1995-06-01 1996-12-04 Roche Diagnostics GmbH The use of DNA polymerase 3'-intrinsic editing activity
US5770365A (en) 1995-08-25 1998-06-23 Tm Technologies, Inc. Nucleic acid capture moieties
US5728528A (en) 1995-09-20 1998-03-17 The Regents Of The University Of California Universal spacer/energy transfer dyes
US5962228A (en) 1995-11-17 1999-10-05 Lynx Therapeutics, Inc. DNA extension and analysis with rolling primers
US5945283A (en) 1995-12-18 1999-08-31 Washington University Methods and kits for nucleic acid analysis using fluorescence resonance energy transfer
US5658736A (en) 1996-01-16 1997-08-19 Genetics Institute, Inc. Oligonucleotide population preparation
US6312893B1 (en) 1996-01-23 2001-11-06 Qiagen Genomics, Inc. Methods and compositions for determining the sequence of nucleic acid molecules
EP0992511B1 (en) 1996-01-23 2009-03-11 Operon Biotechnologies, Inc. Methods and compositions for determining the sequence of nucleic acid molecules
US6613508B1 (en) 1996-01-23 2003-09-02 Qiagen Genomics, Inc. Methods and compositions for analyzing nucleic acid molecules utilizing sizing techniques
AU2320597A (en) 1996-03-19 1997-10-10 Molecular Tool, Inc. Method for determining the nucleotide sequence of a polynucleotide
JP2000512498A (en) 1996-06-14 2000-09-26 サルノフ コーポレーション Polynucleotide sequencing method
US5821356A (en) 1996-08-12 1998-10-13 The Perkin Elmer Corporation Propargylethoxyamino nucleotides
US6361940B1 (en) 1996-09-24 2002-03-26 Qiagen Genomics, Inc. Compositions and methods for enhancing hybridization and priming specificity
GB9620209D0 (en) 1996-09-27 1996-11-13 Cemu Bioteknik Ab Method of sequencing DNA
US5853992A (en) 1996-10-04 1998-12-29 The Regents Of The University Of California Cyanine dyes with high-absorbance cross section as donor chromophores in energy transfer labels
US5885775A (en) 1996-10-04 1999-03-23 Perseptive Biosystems, Inc. Methods for determining sequences information in polynucleotides using mass spectrometry
US5856104A (en) 1996-10-28 1999-01-05 Affymetrix, Inc. Polymorphisms in the glucose-6 phosphate dehydrogenase locus
US5858671A (en) 1996-11-01 1999-01-12 The University Of Iowa Research Foundation Iterative and regenerative DNA sequencing method
DE69735445T2 (en) 1996-12-10 2006-08-10 Sequenom, Inc., San Diego NON-VOLATILE, NON-VOLATILE MOLECULES FOR MASS MARKING
JP2001508657A (en) 1997-01-08 2001-07-03 プロリゴ・エルエルシー Oligonucleotide bioconjugation
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
FR2758822B1 (en) 1997-01-30 1999-07-02 Centre Nat Rech Scient USE OF A POLYPEPTIDE AS A CELLULAR RECEPTOR OF ADENOVIRUS
WO1998033939A1 (en) 1997-01-31 1998-08-06 Hitachi, Ltd. Method for determining nucleic acid base sequence and apparatus therefor
US6197557B1 (en) 1997-03-05 2001-03-06 The Regents Of The University Of Michigan Compositions and methods for analysis of nucleic acids
EP0866071B1 (en) 1997-03-20 2004-10-20 F. Hoffmann-La Roche Ag Modified primers
ES2563643T3 (en) 1997-04-01 2016-03-15 Illumina Cambridge Limited Nucleic acid sequencing method
CA2291180A1 (en) 1997-05-23 1998-11-26 Lynx Therapeutics, Inc. System and apparatus for sequential processing of analytes
US6309829B1 (en) 1997-05-27 2001-10-30 Pe Corporation (Ny) Length determination of nucleic acid repeat sequences by discontinuous primer extension
CN1152140C (en) 1997-07-28 2004-06-02 医疗生物系统有限公司 Nucleic acid sequence analysis
US5834203A (en) 1997-08-25 1998-11-10 Applied Spectral Imaging Method for classification of pixels into groups according to their spectra using a plurality of wide band filters and hardwire therefore
US6008379A (en) 1997-10-01 1999-12-28 The Perkin-Elmer Corporation Aromatic-substituted xanthene dyes
US6511803B1 (en) 1997-10-10 2003-01-28 President And Fellows Of Harvard College Replica amplification of nucleic acid arrays
AU737174B2 (en) 1997-10-10 2001-08-09 President & Fellows Of Harvard College Replica amplification of nucleic acid arrays
US6485944B1 (en) 1997-10-10 2002-11-26 President And Fellows Of Harvard College Replica amplification of nucleic acid arrays
US6227607B1 (en) 1997-10-15 2001-05-08 James E. Dewald, Jr. Latching mechanism for latching a slide out room to main living area
US6627436B2 (en) 1997-10-31 2003-09-30 Stratagene Vector for gene expression in prokaryotic and eukaryotic systems
US5876036A (en) 1997-11-10 1999-03-02 Mathis; Darryl One-on-one basketball game apparatus
US5936087A (en) 1997-11-25 1999-08-10 The Perkin-Elmer Corporation Dibenzorhodamine dyes
GB9815163D0 (en) 1998-07-13 1998-09-09 Brax Genomics Ltd Compounds
WO1999049082A2 (en) 1998-03-23 1999-09-30 Invitrogen Corporation Modified nucleotides and methods useful for nucleic acid sequencing
WO1999057321A1 (en) 1998-05-01 1999-11-11 Arizona Board Of Regents Method of determining the nucleotide sequence of oligonucleotides and dna molecules
US6780591B2 (en) 1998-05-01 2004-08-24 Arizona Board Of Regents Method of determining the nucleotide sequence of oligonucleotides and DNA molecules
US6175107B1 (en) 1998-05-27 2001-01-16 Owens-Brockway Glass Container Inc. Inspection of containers employing a single area array sensor and alternately strobed light sources
US6096875A (en) 1998-05-29 2000-08-01 The Perlein-Elmer Corporation Nucleotide compounds including a rigid linker
US5948648A (en) 1998-05-29 1999-09-07 Khan; Shaheer H. Nucleotide compounds including a rigid linker
US6218530B1 (en) 1998-06-02 2001-04-17 Ambergen Inc. Compounds and methods for detecting biomolecules
US6287821B1 (en) 1998-06-11 2001-09-11 Orchid Biosciences, Inc. Nucleotide analogues with 3'-pro-fluorescent fluorophores in nucleic acid sequence analysis
US6335155B1 (en) 1998-06-26 2002-01-01 Sunesis Pharmaceuticals, Inc. Methods for rapidly identifying small organic molecule ligands for binding to biological target molecules
US6218118B1 (en) 1998-07-09 2001-04-17 Agilent Technologies, Inc. Method and mixture reagents for analyzing the nucleotide sequence of nucleic acids by mass spectrometry
WO2000006770A1 (en) * 1998-07-30 2000-02-10 Solexa Ltd. Arrayed biomolecules and their use in sequencing
US6787308B2 (en) 1998-07-30 2004-09-07 Solexa Ltd. Arrayed biomolecules and their use in sequencing
GB0002310D0 (en) 2000-02-01 2000-03-22 Solexa Ltd Polynucleotide sequencing
AU5479599A (en) 1998-08-11 2000-03-06 Caliper Technologies Corporation Methods and systems for sequencing dna by distinguishing the decay times of fluorescent probes
US6245507B1 (en) 1998-08-18 2001-06-12 Orchid Biosciences, Inc. In-line complete hyperspectral fluorescent imaging of nucleic acid molecules
US20020012913A1 (en) 1998-09-15 2002-01-31 Kevin L. Gunderson Nucleic acid analysis using complete n-mer arrays
DE19844931C1 (en) 1998-09-30 2000-06-15 Stefan Seeger Procedures for DNA or RNA sequencing
US6500650B1 (en) 1998-10-01 2002-12-31 Variagenics, Inc. Method for identifying polymorphisms
US6221592B1 (en) 1998-10-20 2001-04-24 Wisconsin Alumi Research Foundation Computer-based methods and systems for sequencing of individual nucleic acid molecules
WO2000036152A1 (en) 1998-12-14 2000-06-22 Li-Cor, Inc. A system and methods for nucleic acid sequencing of single molecules by polymerase synthesis
US6207831B1 (en) 1998-12-21 2001-03-27 Novartis Ag Fluorescent dyes (AIDA) for solid phase and solution phase screening
US6380378B1 (en) 1998-12-24 2002-04-30 Toagosei Company, Ltd. Nucleotide compound, nucleotide block oligonucleotide, and method for producing them
EP2145963A1 (en) 1999-01-06 2010-01-20 Callida Genomics, Inc. Enhanced sequencing by hybridization using pools of probes
US20030054360A1 (en) 1999-01-19 2003-03-20 Larry Gold Method and apparatus for the automated generation of nucleic acid ligands
DE60044490D1 (en) 1999-02-23 2010-07-15 Caliper Life Sciences Inc MANIPULATION OF MICROTEILS IN MICROFLUID SYSTEMS
DK1159453T3 (en) * 1999-03-10 2008-10-06 Asm Scient Inc Method of Direct Nucleic Acid Sequencing
US7037654B2 (en) 1999-04-30 2006-05-02 Aclara Biosciences, Inc. Methods and compositions for enhancing detection in determinations employing cleavable electrophoretic tag reagents
US7056661B2 (en) 1999-05-19 2006-06-06 Cornell Research Foundation, Inc. Method for sequencing nucleic acid molecules
US6277607B1 (en) 1999-05-24 2001-08-21 Sanjay Tyagi High specificity primers, amplification methods and kits
US6248884B1 (en) 1999-06-03 2001-06-19 The Perkin-Elmer Corporation Extended rhodamine compounds useful as fluorescent labels
EP1077264B1 (en) 1999-06-07 2005-04-20 Fuji Photo Film Co., Ltd. DNA chip, PNA chip, and their preparation methods
US6818395B1 (en) 1999-06-28 2004-11-16 California Institute Of Technology Methods and apparatus for analyzing polynucleotide sequences
US6242193B1 (en) 1999-07-30 2001-06-05 Hitachi, Ltd. Apparatus for determining base sequence of nucleic acid
US6316230B1 (en) 1999-08-13 2001-11-13 Applera Corporation Polymerase extension at 3′ terminus of PNA-DNA chimera
CA2385475A1 (en) 1999-08-16 2001-02-22 Human Genome Sciences, Inc. 18 human secreted proteins
AU7086800A (en) 1999-08-30 2001-03-26 Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The High speed parallel molecular nucleic acid sequencing
US6982146B1 (en) 1999-08-30 2006-01-03 The United States Of America As Represented By The Department Of Health And Human Services High speed parallel molecular nucleic acid sequencing
US6664399B1 (en) 1999-09-02 2003-12-16 E. I. Du Pont De Nemours & Company Triazole linked carbohydrates
US6274320B1 (en) 1999-09-16 2001-08-14 Curagen Corporation Method of sequencing a nucleic acid
AU7537200A (en) 1999-09-29 2001-04-30 Solexa Ltd. Polynucleotide sequencing
US6309836B1 (en) 1999-10-05 2001-10-30 Marek Kwiatkowski Compounds for protecting hydroxyls and methods for their use
DE60044030D1 (en) 1999-10-08 2010-04-29 Robert C Leif MARKER COMPLEXES OF CONJUGATED POLYMERS
WO2001029257A2 (en) 1999-10-22 2001-04-26 Genset Methods of genetic cluster analysis
EP1228244A4 (en) 1999-11-04 2005-02-09 California Inst Of Techn Methods and apparatuses for analyzing polynucleotide sequences
US20030186256A1 (en) 1999-12-23 2003-10-02 Achim Fischer Method for carrying out the parallel sequencing of a nucleic acid mixture on a surface
GB0002389D0 (en) 2000-02-02 2000-03-22 Solexa Ltd Molecular arrays
AU2001241125A1 (en) 2000-03-14 2001-09-24 Itoham Foods Inc. Process for producing polypeptide having disulfide bond
US6495680B1 (en) 2000-03-24 2002-12-17 The University Of Toledo Helices and nanotubes on folding compositions and method of making same
WO2001073121A1 (en) 2000-03-30 2001-10-04 Toyota Jidosha Kabushiki Kaisha Method of determining base sequence of single nucleic acid molecule
GB0013276D0 (en) * 2000-06-01 2000-07-26 Amersham Pharm Biotech Uk Ltd Nucleotide analogues
GB0016473D0 (en) 2000-07-05 2000-08-23 Amersham Pharm Biotech Uk Ltd Sequencing method
CA2416631C (en) 2000-08-03 2011-11-22 F. Hoffmann-La Roche Ag Nucleic acid binding compounds containing pyrazolo[3,4-d]pyrimidine analogues of purin-2,6-diamine and their uses
US20060057565A1 (en) 2000-09-11 2006-03-16 Jingyue Ju Combinatorial fluorescence energy transfer tags and uses thereof
CA2421582A1 (en) 2000-09-11 2002-03-21 The Trustees Of Columbia University In The City Of New York 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
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
EP1790736A3 (en) 2000-10-06 2007-08-15 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US7297518B2 (en) 2001-03-12 2007-11-20 California Institute Of Technology Methods and apparatus for analyzing polynucleotide sequences by asynchronous base extension
US20030027140A1 (en) 2001-03-30 2003-02-06 Jingyue Ju High-fidelity DNA sequencing using solid phase capturable dideoxynucleotides and mass spectrometry
DE10120798B4 (en) 2001-04-27 2005-12-29 Genovoxx Gmbh Method for determining gene expression
DE10120797B4 (en) 2001-04-27 2005-12-22 Genovoxx Gmbh Method for analyzing nucleic acid chains
US6573677B2 (en) * 2001-06-18 2003-06-03 Motorola, Inc. Method of compensating for abrupt load changes in an anti-pinch window control system
US6613523B2 (en) 2001-06-29 2003-09-02 Agilent Technologies, Inc. Method of DNA sequencing using cleavable tags
AU2002354577B2 (en) 2001-07-13 2007-02-08 Ambergen, Inc. Nucleotide compositions comprising photocleavable markers and methods of preparation thereof
US6902904B2 (en) 2001-08-27 2005-06-07 Pharmanetics Incorporated Coagulation assay reagents containing lanthanides
AU2002337030A1 (en) 2001-08-29 2003-03-18 Genovoxx Gmbh Method for analyzing nucleic acid sequences and gene expression
GB0128526D0 (en) 2001-11-29 2002-01-23 Amersham Pharm Biotech Uk Ltd Nucleotide analogues
US7057026B2 (en) 2001-12-04 2006-06-06 Solexa Limited Labelled nucleotides
GB0129012D0 (en) 2001-12-04 2002-01-23 Solexa Ltd Labelled nucleotides
US20030166282A1 (en) 2002-02-01 2003-09-04 David Brown High potency siRNAS for reducing the expression of target genes
WO2003066812A2 (en) 2002-02-05 2003-08-14 Baylor College Of Medecine Substituted 4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene compounds for 8-color dna sequencing
US6858393B1 (en) 2002-03-13 2005-02-22 Stratagene California Chain terminators for DNA synthesis
DE60301622T2 (en) 2002-04-04 2006-06-14 Biotage Ab Uppsala PRIMER EXTENSION BASED PROCESS USING NUCLEOTIDES MARKED OVER COLD LINKERS
US20040014096A1 (en) 2002-04-12 2004-01-22 Stratagene Dual-labeled nucleotides
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
WO2004018492A1 (en) 2002-08-12 2004-03-04 F. Hoffmann-La-Roche Ag Process for producing a ribofuranose
US7414116B2 (en) 2002-08-23 2008-08-19 Illumina Cambridge Limited Labelled nucleotides
EP2119722B1 (en) 2002-08-23 2016-10-26 Illumina Cambridge Limited Labelled nucleotides
SI3587433T1 (en) 2002-08-23 2020-08-31 Illumina Cambridge Limited Modified nucleotides
JP2004085934A (en) * 2002-08-27 2004-03-18 Pentax Corp Extending cam mechanism for zoom lens barrel and extending cam mechanism
US20050032081A1 (en) 2002-12-13 2005-02-10 Jingyue Ju Biomolecular coupling methods using 1,3-dipolar cycloaddition chemistry
US20060252938A1 (en) 2003-04-28 2006-11-09 Basf Aktiengesellschaft Process for the separation of palladium catalyst from crude reaction mixtures of aryl acetic acids obtained by carbonylation
DE10324808B4 (en) 2003-06-02 2005-10-20 Bosch Gmbh Robert Optimized controller configuration for a car parking brake
US20050170367A1 (en) 2003-06-10 2005-08-04 Quake Stephen R. Fluorescently labeled nucleoside triphosphates and analogs thereof for sequencing nucleic acids
GB0321306D0 (en) 2003-09-11 2003-10-15 Solexa Ltd Modified polymerases for improved incorporation of nucleotide analogues
US7622026B2 (en) * 2004-03-02 2009-11-24 Panasonic Corporation Biosensor
WO2005084367A2 (en) 2004-03-03 2005-09-15 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
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
WO2006073436A2 (en) 2004-04-29 2006-07-13 The Trustees Of Columbia University In The City Of New York Mass tag pcr for multiplex diagnostics
US20060105461A1 (en) 2004-10-22 2006-05-18 May Tom-Moy Nanopore analysis system
US7393533B1 (en) 2004-11-08 2008-07-01 La Jolla Institute For Allergy And Immunology H3L envelope protein immunization methods and H3L envelope passive protection methods
US9169510B2 (en) 2005-06-21 2015-10-27 The Trustees Of Columbia University In The City Of New York Pyrosequencing methods and related compositions
GB2446083B (en) 2005-10-31 2011-03-02 Univ Columbia Chemically cleavable 3'-0-allyl-dntp-allyl-fluorophore fluorescent nucleotide analogues and related methods
GB2446084B (en) 2005-10-31 2011-03-02 Univ Columbia Synthesis of four color 3-o-allyl modified photocleavable fluorescent nucleotides and related methods
AU2006318462A1 (en) 2005-11-21 2007-05-31 The Trustees Of Columbia University In The City Of New York Multiplex digital immuno-sensing using a library of photocleavable mass tags
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
WO2008042067A2 (en) 2006-09-28 2008-04-10 Illumina, Inc. Compositions and methods for nucleotide sequencing
GB2457402B (en) 2006-12-01 2011-10-19 Univ Columbia Four-color DNA sequencing by synthesis using cleavable fluorescent nucleotide reversible terminators
US8481259B2 (en) 2007-02-05 2013-07-09 Intelligent Bio-Systems, Inc. Methods and devices for sequencing nucleic acids in smaller batches
US8612161B2 (en) 2008-03-19 2013-12-17 Intelligent Biosystems Inc. Methods and compositions for base calling nucleic acids
WO2009051807A1 (en) 2007-10-19 2009-04-23 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
EP2725107B1 (en) 2007-10-19 2018-08-29 The Trustees of Columbia University in the City of New York DNA sequencing with non-fluorescent nucleotide reversible terminators and cleavable label modified ddNTPs and nucleic acid comprising inosine with reversible terminators
JP5018402B2 (en) 2007-10-31 2012-09-05 ダイキン工業株式会社 Humidity control device
DE102009027275A1 (en) 2009-06-29 2010-12-30 Robert Bosch Gmbh Image processing method for a driver assistance system of a motor vehicle for detecting and classifying at least a part of at least one predetermined picture element
US9309569B2 (en) 2010-08-26 2016-04-12 Intelligent Bio-Systems, Inc. Methods and compositions for sequencing nucleic acid using charge
EP2652153B1 (en) 2010-12-17 2017-07-05 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
US10246479B2 (en) 2012-04-09 2019-04-02 The Trustees Of Columbia University In The City Of New York Method of preparation of nanopore and uses thereof
WO2013191793A1 (en) 2012-06-20 2013-12-27 The Trustees Of Columbia University In The City Of New York Nucleic acid sequencing by nanopore detection of tag molecules
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
WO2014144898A1 (en) 2013-03-15 2014-09-18 The Trustees Of Columbia University In The City Of New York Method for detecting multiple predetermined compounds in a sample
US9159610B2 (en) 2013-10-23 2015-10-13 Globalfoundires, Inc. Hybrid manganese and manganese nitride barriers for back-end-of-line metallization and methods for fabricating the same
EP3105354B1 (en) 2014-02-12 2020-05-06 The Trustees of Columbia University in the City of New York Single molecule electronic multiplex snp assay and pcr analysis
CN106715453B (en) 2014-03-24 2021-04-30 哥伦比亚大学董事会 Chemical process for producing tagged nucleotides
WO2015179284A1 (en) 2014-05-19 2015-11-26 The Trustees Of Columbia University In The City Of New York Ion sensor dna and rna sequencing by synthesis using nucleotide reversible terminators
US10113084B2 (en) 2014-05-22 2018-10-30 Illinois Tool Works, Inc. Mold release agent

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10428380B2 (en) 2000-10-06 2019-10-01 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US10662472B2 (en) 2000-10-06 2020-05-26 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US10435742B2 (en) 2000-10-06 2019-10-08 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US10457984B2 (en) 2000-10-06 2019-10-29 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
US9718852B2 (en) 2000-10-06 2017-08-01 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US9719139B2 (en) 2000-10-06 2017-08-01 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US9725480B2 (en) 2000-10-06 2017-08-08 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US9868985B2 (en) 2000-10-06 2018-01-16 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US10669582B2 (en) 2000-10-06 2020-06-02 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US10407458B2 (en) 2000-10-06 2019-09-10 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US10407459B2 (en) 2000-10-06 2019-09-10 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US10669577B2 (en) 2000-10-06 2020-06-02 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US10648028B2 (en) 2000-10-06 2020-05-12 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US10633700B2 (en) 2000-10-06 2020-04-28 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US10570446B2 (en) 2000-10-06 2020-02-25 The Trustee Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US10577652B2 (en) 2000-10-06 2020-03-03 The Trustees Of Columbia University In The City Of New York Massive parallel method for decoding DNA and RNA
US9909177B2 (en) 2005-06-21 2018-03-06 The Trustees Of Columbia University In The City Of New York Pyrosequencing methods and related compositions
US9169510B2 (en) 2005-06-21 2015-10-27 The Trustees Of Columbia University In The City Of New York Pyrosequencing methods and related compositions
US9297042B2 (en) 2005-10-31 2016-03-29 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
US9255292B2 (en) 2005-10-31 2016-02-09 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
US10907194B2 (en) 2005-10-31 2021-02-02 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
US11939631B2 (en) 2006-12-01 2024-03-26 The Trustees Of Columbia University In The City Of New York Four-color DNA sequencing by synthesis using cleavable fluorescent nucleotide reversible terminators
US11098353B2 (en) 2006-12-01 2021-08-24 The Trustees Of Columbia University In The City Of New York Four-color DNA sequencing by synthesis using cleavable fluorescent nucleotide reversible terminators
US11242561B2 (en) 2007-10-19 2022-02-08 The Trustees Of Columbia University In The City Of New York DNA sequencing with non-fluorescent nucleotide reversible terminators and cleavable label modified nucleotide terminators
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

Also Published As

Publication number Publication date
EP3034627A1 (en) 2016-06-22
US20080131895A1 (en) 2008-06-05
US20190031704A1 (en) 2019-01-31
US20080319179A1 (en) 2008-12-25
US20160264612A1 (en) 2016-09-15
US10570446B2 (en) 2020-02-25
EP1790736A3 (en) 2007-08-15
US20170088575A1 (en) 2017-03-30
US10407458B2 (en) 2019-09-10
US20190092806A1 (en) 2019-03-28
US10435742B2 (en) 2019-10-08
AU2001296645A1 (en) 2002-04-15
US9718852B2 (en) 2017-08-01
US20020102586A1 (en) 2002-08-01
US10407459B2 (en) 2019-09-10
EP1337541A2 (en) 2003-08-27
US7635578B2 (en) 2009-12-22
US20040185466A1 (en) 2004-09-23
US10457984B2 (en) 2019-10-29
US9725480B2 (en) 2017-08-08
CA2425112C (en) 2011-09-27
DE60127162D1 (en) 2007-04-19
WO2002029003A3 (en) 2002-07-18
ATE356222T1 (en) 2007-03-15
US20190085014A1 (en) 2019-03-21
US20190092805A1 (en) 2019-03-28
US9133511B2 (en) 2015-09-15
US20190135851A1 (en) 2019-05-09
US9868985B2 (en) 2018-01-16
DE20122767U1 (en) 2007-08-09
US20190031706A1 (en) 2019-01-31
US10633700B2 (en) 2020-04-28
US7345159B2 (en) 2008-03-18
US9719139B2 (en) 2017-08-01
US6664079B2 (en) 2003-12-16
US10669577B2 (en) 2020-06-02
DE60127162T2 (en) 2008-04-24
US20120142006A1 (en) 2012-06-07
US20150197800A1 (en) 2015-07-16
US10669582B2 (en) 2020-06-02
US20180201642A1 (en) 2018-07-19
US20190085016A1 (en) 2019-03-21
US7790869B2 (en) 2010-09-07
EP1790736A2 (en) 2007-05-30
US10577652B2 (en) 2020-03-03
EP1337541B1 (en) 2007-03-07
US20130096015A1 (en) 2013-04-18
US20170088891A1 (en) 2017-03-30
US20170313737A1 (en) 2017-11-02
US20170190730A2 (en) 2017-07-06
US8088575B2 (en) 2012-01-03
US7713698B2 (en) 2010-05-11
US20100317012A1 (en) 2010-12-16
US20190135850A1 (en) 2019-05-09
JP2004510433A (en) 2004-04-08
US20140206553A1 (en) 2014-07-24
US10648028B2 (en) 2020-05-12
HK1227441A1 (en) 2017-10-20
WO2002029003A2 (en) 2002-04-11
US20190031705A1 (en) 2019-01-31
EP3034627B1 (en) 2019-01-30
US10428380B2 (en) 2019-10-01
EP1337541A4 (en) 2004-07-14
US20080199868A1 (en) 2008-08-21
US10662472B2 (en) 2020-05-26
US20190085015A1 (en) 2019-03-21

Similar Documents

Publication Publication Date Title
CA2425112A1 (en) Massive parallel method for decoding dna and rna
US11939631B2 (en) Four-color DNA sequencing by synthesis using cleavable fluorescent nucleotide reversible terminators
EP0723598B1 (en) Methods and compositions for efficient nucleic acid sequencing
US6401267B1 (en) Methods and compositions for efficient nucleic acid sequencing
US9206476B2 (en) Sequencing and genotyping using reversibly terminating nucleotides
JP5951755B2 (en) Improved quantitative nuclease protection assay (qNPA) and quantitative nuclease protection sequencing (qNPS) methods
US20210285041A1 (en) 3'-o-modified nucleotide analogues with different cleavable linkers for attaching fluorescent labels to the base for dna sequencing by synthesis
US20170088574A1 (en) Massive parallel method for decoding dna and rna
US20120316072A1 (en) Methods for indexing samples and sequencing multiple polynucleotide templates
CN105392902A (en) Digital PCR barcoding
US20040019005A1 (en) Methods for parallel measurement of genetic variations
WO2020093261A1 (en) Method for sequencing polynucleotides
US6083701A (en) Method for determining tandem repeat sequence length
US7001722B1 (en) Parallel primer extension approach to nucleic acid sequence analysis
CN113748216A (en) Single-channel sequencing method based on self-luminescence
CA2754196A1 (en) Massive parallel method for decoding dna and rna

Legal Events

Date Code Title Description
EEER Examination request
MKEX Expiry

Effective date: 20211005