CA2373385A1 - Method for sequencing nucleic acid molecules - Google Patents

Method for sequencing nucleic acid molecules Download PDF

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Publication number
CA2373385A1
CA2373385A1 CA002373385A CA2373385A CA2373385A1 CA 2373385 A1 CA2373385 A1 CA 2373385A1 CA 002373385 A CA002373385 A CA 002373385A CA 2373385 A CA2373385 A CA 2373385A CA 2373385 A1 CA2373385 A1 CA 2373385A1
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Prior art keywords
nucleic acid
target nucleic
nucleotide
acid molecule
identifying
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Granted
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CA002373385A
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French (fr)
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CA2373385C (en
Inventor
Jonas Korlach
Watt W. Webb
Michael Levene
Stephen Turner
Harold G. Craighead
Mathieu Foquet
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Cornell Research Foundation Inc
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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
    • 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
    • C12Q1/6869—Methods for sequencing
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/80—Fluorescent dyes, e.g. rhodamine
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/805—Optical property
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
    • Y10T436/142222—Hetero-O [e.g., ascorbic acid, etc.]
    • Y10T436/143333—Saccharide [e.g., DNA, etc.]

Abstract

The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the templage nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic aci d by the catalytic activity of the nucleic acid polymerizing enzyme at each st ep in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active sit e. A plurality of labelled types of nucleotide analogs are provided proximate t o the active site, with each distinguishable type of nucleotide analog being complementary to a different nucleotide in the target nucleic acid sequence. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand at the active site, where the nucleotide analog being added is complementary to the nucleotide of the targ et nucleic acidat the active site. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. T he steps of providing labelled nucleotide analogs, polymerizing the growing nucleic acid strand, and identifying the added nucleotide analog are repeate d so that the nucleic acid strand is further extended and the sequence of the target nucleic acid is determined.

Claims (61)

1. A method of sequencing a target nucleic acid molecule having a plurality of nucleotide bases comprising:
providing a complex of a nucleic acid polymerizing enzyme and the target nucleic acid molecule oriented with respect to each other in a position suitable to add a nucleotide analog at an active site complementary to the target nucleic acid;
providing a plurality of types of nucleotide analogs proximate to the active site, wherein each type of nucleotide analog is complementary to a different nucleotide in the target nucleic acid sequence;
polymerizing a nucleotide analog at an active site, wherein the nucleotide analog being added is complementary to the nucleotide of the target nucleic acid, leaving the added nucleotide analog ready for subsequent addition of nucleotide analogs;
identifying the nucleotide analog added at the active site as a result of said polymerizing; and repeating said providing a plurality of types of nucleotide analogs, said polymerizing, and said identifying so that the sequence of the target nucleic acid is determined.
2. A method according to claim 1, wherein the nucleic acid polymerizing enzyme is selected from the group consisting of a DNA polymerase, an RNA polymerase, reverse transcriptase, and mixtures thereof.
3. A method according to claim 1, wherein the nucleic acid polymerizing enzyme is a thermostable polymerase.
4. A method according to claim 1, wherein the nucleic acid polymerizing enzyme is a thermodegradable polymerase.
5. A method according to claim 1, wherein the target nucleic acid molecule is selected from the group consisting of double-stranded DNA, single-stranded DNA, single stranded DNA hairpins, DNA/RNA hybrids, RNA with a recognition site for binding of the polymerase, and RNA hairpins.
6. A method according to claim 1, wherein the nucleic acid polymerizing enzyme is bound to the target nucleic acid molecule complex at an origin of replication, a nick or gap in a double-stranded target nucleic acid, a secondary structure in a single-stranded target nucleic acid, a binding site created by an accessory protein, or a primed single stranded nucleic acid.
7. A method according to claim 1, wherein the nucleic acid polymerizing enzyme is provided with one or more accessory proteins to modify its activity.
8. A method according to claim 7, wherein the accessory protein is selected from the group consisting of a single-stranded binding protein, a primase, and helicase.
9. A method according to claim 1, wherein the nucleic acid polymerizing enzyme is processive.
10. A method according to claim 1, wherein the nucleic acid polymerizing enzyme is non-processive.
11. A method according to claim 1, wherein the nucleotide analogs are selected from the group consisting of a ribonucleotide, a deoxyribonucleotide, a modified ribonucleotide, a modified deoxyribonucleotide, a peptide nucleotide, a modified peptide nucleotide, and a modified phosphate-sugar backbone nucleotide.
12. A method according to claim 1 further comprising:

hybridizing an oligonucleotide primer to the target nucleic acid molecule prior to or during said providing a plurality of nucleotide analogs.
13. A method according to claim 12, wherein the oligonucleotide primer comprises nucleotides selected from the group consisting of ribonucleotides, deoxyribonucleotides, modified ribonucleotides, modified deoxyribonucleotides, peptide nucleic acids, modified peptide nucleic acids, and modified phosphate-sugar backbone nucleotides.
14. A method according to claim 1, wherein the nucleotide analogs are provided with a label.
15. A method according to claim 14, wherein the label is selected from the group consisting of chromophores, fluorescent moieties, enzymes, antigens, heavy metals, magnetic probes, dyes, phosphorescent groups, radioactive materials, chemiluminescent moieties, scattering or fluorescent nanoparticles, Raman signal generating moieties, and electrochemical detection moieties.
16. A method according to claim 14, wherein the label is attached to the nucleotide analog at its base, sugar moiety, alpha phosphate, beta phosphate, or gamma phosphate.
17. A method according to claim 14, wherein the label is attached to the nucleotide analog with a linker.
18. A method according to claim 14, wherein the label is attached to the nucleotide analog without a linker.
19. A method according to claim 14 further comprising:
removing the label from the nucleotide analog during or after said identifying and before said polymerizing many further nucleotide analogs at the active site.
20. A method according to claim 19, wherein said removing is carried out by bleaching the label.
21. A method according to claim 20, wherein said bleaching is carried out by photobleaching with radiation which is adjusted to induce and control label removal.
22. A method according to claim 19, wherein said removing is carried out by cleaving the label from the nucleotide analog.
23. A method according to claim 22, wherein beta- or gamma-labeled nucleotide analogs are enzymatically cleaved.
24. A method according to claim 14, wherein each of the plurality of types of nucleotide analogs have different labels which are distinguished from one another during said identifying.
25. A method according to claim 14, wherein three or less of the plurality of types of nucleotide analogs have a different label.
26. A method according to claim 14, wherein the different types of nucleotide analogs have the same label but are distinguished by different properties due to the presence of base fluorophores, quenched fluorophores, or fluorogenic nucleotide analogs.
27. A method according to claim 1, wherein the nucleic acid polymerizing enzyme carries a label and said identifying is carried out by detecting interaction between the label and the nucleotide analog.
28. A method according to claim 27, wherein the label is a fluorescence resonance energy transfer donor or acceptor.
29. A method according to claim 1, wherein said identifying is carried out by non-optical procedures.
30. A method according to claim 1, wherein said identifying is carried out by optical procedures selected from the group consisting of far-field microspectroscopy, near-field microspectroscopy, evanescent wave or wave guided illumination, nanostructure enhancement, and combinations thereof.
31. A method according to claim 1, wherein said identifying is carried out by utilizing single and/or multiphoton excitation, fluorescence resonance energy transfer, or photoconversion.
32. A method according to claim 1, wherein said identifying is achieved by spectral wavelength discrimination, measurement and separation of fluorescence lifetimes, fluorophore identification and/or background suppression.
33. A method according to claim 32, wherein fluorophore identification and/or background suppression utilizes fast switching between excitation modes and illumination sources, and combinations thereof.
34. A method according to claim 1, wherein said providing a complex comprises:
positioning either (1) an oligonucleotide primer or (2) the target nucleic acid molecule on a support;
hybridizing either (1) the target nucleic acid molecule to the positioned oligonucleotide primer or (2) an oligonucleotide primer to the positioned target nucleic acid molecule, to form a primed target nucleic acid molecule complex;
and providing the nucleic acid polymerizing enzyme on the primed target nucleic acid molecule complex in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site.
35. A method according to claim 34, wherein said hybridizing is carried out by additionally binding the end of the target nucleic acid molecule opposite to that bound to the oligonucleotide primer to a second oligonucleotide primer positioned on the support.
36. A method according to claim 34, wherein the support and either the oligonucleotide primer or the target nucleic acid molecule are bound reversibly or irreversibly with corresponding components of a covalent or non-covalent binding pair selected from the group consisting of an antigen-antibody binding pair, a streptavidin-biotin binding pair, photoactivated coupling molecules, and a pair of complementary nucleic acids.
37. A method according to claim 34, where the oligonucleotide primer is positioned on the support and the target nucleic acid molecule is hybridized to the positioned oligonucleotide primer.
38. A method according to claim 34, wherein the target nucleic acid molecule is positioned on the support and the oligonucleotide primer is hybridized to the positioned target nucleic acid molecule.
39. A method according to claim 1, wherein said providing a complex comprises:
positioning, on a support, a double stranded nucleic acid molecule comprising the target nucleic acid and having a recognition site proximate the active site, and providing the nucleic acid polymerizing enzyme on the target nucleic acid molecule in a position suitable to move along the target nucleic acid molecule.
40. A method according to claim 1, wherein said providing a complex comprises:

positioning a nucleic acid polymerizing enzyme on a support in a position suitable for the target nucleic acid complex to move relative to the nucleic acid polymerizing enzyme.
41. A method according to claim 40, wherein the support and the nucleic acid polymerizing enzyme are bound reversibly or irreversibly with corresponding components of a covalent or non-covalent binding pair selected from the group consisting of an antigen-antibody binding pair, a streptavidin-biotin binding pair, photoactivated coupling molecules, and a pair of complementary nucleic acids.
42. A method according to claim 1, wherein the nucleic acid polymerizing enzyme or the target nucleic acid is positioned on an adjustable support.
43. A method according to claim 1, wherein the nucleic acid polymerizing enzyme or the target nucleic acid is positioned in a gel with pores.
44. A method according to claim 1, wherein the target nucleic acid and the nucleic acid polymerizing enzyme are positioned on a solid support proximate to each other.
45. A method according to claim 1, wherein said identifying is carried out by reducing background noise resulting from free nucleotide analogs.
46. A method according to claim 45, wherein said identifying comprises:
directing activating radiation to a region substantially corresponding to the active site and detecting the nucleotide analog polymerized at the active site.
47. A method according to claim 45, wherein said identifying distinguishes nucleotide analogs polymerized at the active site from free nucleotide analogs.
48. A method according to claim 45, wherein said identifying is carried out in a confined region proximate to the active site.
49. A method according to claim 48, wherein said identifying is carried out in a nanostructure.
50. A method according to claim 49, wherein the nanostructure is a punctuate, acicular, or resonant nanostructure which enhances said detecting.
51. A method according to claim 48, wherein nucleotide analogs that are not polymerized at the active site move rapidly through a microstructure to and from the confined region.
52. A method according to claim 51, wherein the microstructure comprises:
a plurality of channels to direct different nucleotide analogs to the confined region and a discharge channel to permit materials to be removed from the confined region, and the nanostructure comprises:
a housing defining the confined region and constructed to facilitate said identifying.
53. A method according to claim 45, wherein said identifying is carried out by electromagnetic field enhancement with electromagnetic radiation being enhanced proximate to an object with a small radius of curvature adjacent to the active site.
54. A method according to claim 45, wherein said identifying is carried out by near-field illumination of cavities in which the primed target nucleic acid molecule is positioned.
55. A method according to claim 45, wherein said identifying is carried out with optical fibers proximate to the complex.
56. A method according to claim 45, wherein said identifying and said reducing background is carried out by time gated delay of photon detection.
57. A method according to claim 1, wherein said method is carried out by sequencing different target nucleic acid molecules at a plurality of different locations on an array.
58. A method according to claim 1, wherein said method is carried out by simultaneously or sequentially sequencing the same target nucleic acid and combining output from such sequencing.
59. An apparatus suitable for sequencing a target nucleic acid molecule comprising:
a support;
a nucleic acid polymerizing enzyme or oligonucleotide primer suitable to bind to a target nucleic acid molecule, wherein said nucleic acid polymerizing enzyme or said oligonucleotide primer is positioned on said support;
and a microstructure defining a confined region containing said support and said nucleic acid polymerizing enzyme or said oligonucleotide primer and configured to permit labeled nucleotide analogs that are not positioned on the support to move rapidly through the confined region.
60. An apparatus according to claim 59, wherein the microstructure comprises:
a plurality of channels to direct different types of nucleotide analogs to the confined region and a discharge channel to permit materials to be removed from the confined region and a nanostructure constructed to facilitate identification of nucleotide analogs positioned on the support.
61. An apparatus suitable for sequencing a target nucleic acid molecule comprising:
a support;
a nucleic acid polymerizing enzyme or oligonucleotide primer suitable to hybridize to a target nucleic acid molecule, wherein said nucleic acid polymerizing enzyme or said oligonucleotide primer is positioned on said support;
a housing defining a confined region containing said support and said nucleic acid polymerizing enzyme or said oligonucleotide primer and constructed to facilitate identification of labeled nucleotide analogs positioned on the support; and optical waveguides proximate to the confined region to focus activating radiation on the confined region and to collect radiation from the confined region.
CA2373385A 1999-05-19 2000-05-18 Method for sequencing nucleic acid molecules Expired - Lifetime CA2373385C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US13482799P 1999-05-19 1999-05-19
US60/134,827 1999-05-19
PCT/US2000/013677 WO2000070073A1 (en) 1999-05-19 2000-05-18 Method for sequencing nucleic acid molecules

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CA2373385A1 true CA2373385A1 (en) 2000-11-23
CA2373385C CA2373385C (en) 2012-07-03

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EP (2) EP1179085B2 (en)
JP (2) JP5535415B2 (en)
AT (2) ATE466951T1 (en)
AU (1) AU5027600A (en)
CA (1) CA2373385C (en)
DE (1) DE60044348D1 (en)
DK (1) DK1179085T4 (en)
ES (1) ES2345137T5 (en)
PT (1) PT1179085E (en)
WO (1) WO2000070073A1 (en)

Families Citing this family (517)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6221654B1 (en) 1996-09-25 2001-04-24 California Institute Of Technology Method and apparatus for analysis and sorting of polynucleotides based on size
RU2198221C2 (en) * 1997-07-28 2003-02-10 Медикал Биосистемз Лтд. Method of polynucleotide sequencing and device for its realization
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
US20040106110A1 (en) * 1998-07-30 2004-06-03 Solexa, Ltd. Preparation of polynucleotide arrays
US20100130368A1 (en) * 1998-07-30 2010-05-27 Shankar Balasubramanian Method and system for sequencing polynucleotides
US20030022207A1 (en) * 1998-10-16 2003-01-30 Solexa, Ltd. Arrayed polynucleotides and their use in genome analysis
US7056661B2 (en) * 1999-05-19 2006-06-06 Cornell Research Foundation, Inc. Method for sequencing nucleic acid molecules
US7501245B2 (en) * 1999-06-28 2009-03-10 Helicos Biosciences Corp. Methods and apparatuses for analyzing polynucleotide sequences
US6818395B1 (en) 1999-06-28 2004-11-16 California Institute Of Technology Methods and apparatus for analyzing polynucleotide sequences
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
US6908736B1 (en) * 1999-10-06 2005-06-21 Medical Biosystems, Ltd. DNA sequencing method
GB9923644D0 (en) * 1999-10-06 1999-12-08 Medical Biosystems Ltd DNA sequencing
US6432290B1 (en) 1999-11-26 2002-08-13 The Governors Of The University Of Alberta Apparatus and method for trapping bead based reagents within microfluidic analysis systems
US6917726B2 (en) * 2001-09-27 2005-07-12 Cornell Research Foundation, Inc. Zero-mode clad waveguides for performing spectroscopy with confined effective observation volumes
US6869764B2 (en) 2000-06-07 2005-03-22 L--Cor, Inc. Nucleic acid sequencing using charge-switch nucleotides
US6936702B2 (en) * 2000-06-07 2005-08-30 Li-Cor, Inc. Charge-switch nucleotides
DE10031028B4 (en) * 2000-06-26 2008-09-04 Gnothis Holding Sa Method for the selection of particles
CN100462433C (en) * 2000-07-07 2009-02-18 维西根生物技术公司 Real-time sequence determination
US20070172866A1 (en) * 2000-07-07 2007-07-26 Susan Hardin Methods for sequence determination using depolymerizing agent
DE20122767U1 (en) 2000-10-06 2007-08-09 The Trustees Of Columbia University In The City Of New York Massive parallel method for the decoding of 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
EP1354064A2 (en) * 2000-12-01 2003-10-22 Visigen Biotechnologies, Inc. Enzymatic nucleic acid synthesis: compositions and methods for altering monomer incorporation fidelity
GB0102568D0 (en) * 2001-02-01 2001-03-21 Magnetic Biosolutions Sweden A Method
EP1368497A4 (en) * 2001-03-12 2007-08-15 California Inst Of Techn Methods and apparatus for analyzing polynucleotide sequences by asynchronous base extension
DE10120797B4 (en) * 2001-04-27 2005-12-22 Genovoxx Gmbh Method for analyzing nucleic acid chains
DE10120798B4 (en) * 2001-04-27 2005-12-29 Genovoxx Gmbh Method for determining gene expression
GB0112238D0 (en) 2001-05-18 2001-07-11 Medical Biosystems Ltd Sequencing method
US7118907B2 (en) 2001-06-06 2006-10-10 Li-Cor, Inc. Single molecule detection systems and methods
US7668697B2 (en) * 2006-02-06 2010-02-23 Andrei Volkov Method for analyzing dynamic detectable events at the single molecule level
US7670770B2 (en) 2001-07-25 2010-03-02 The Trustees Of Princeton University Nanochannel arrays and their preparation and use for high throughput macromolecular analysis
US9678038B2 (en) 2001-07-25 2017-06-13 The Trustees Of Princeton University Nanochannel arrays and their preparation and use for high throughput macromolecular analysis
US7560254B2 (en) 2001-08-29 2009-07-14 Ge Healthcare Bio-Sciences Corp. Allele specific primer extension
US6982165B2 (en) 2001-09-24 2006-01-03 Intel Corporation Nucleic acid sequencing by raman monitoring of molecular deconstruction
US6972173B2 (en) 2002-03-14 2005-12-06 Intel Corporation Methods to increase nucleotide signals by raman scattering
US6852492B2 (en) * 2001-09-24 2005-02-08 Intel Corporation Nucleic acid sequencing by raman monitoring of uptake of precursors during molecular replication
US20050227231A1 (en) * 2001-10-04 2005-10-13 Dimitri Tcherkassov Device for sequencing nucleic acid molecules
JP2005508196A (en) 2001-11-07 2005-03-31 アプレラ コーポレイション General purpose nucleotides for nucleic acid analysis
GB0129012D0 (en) 2001-12-04 2002-01-23 Solexa Ltd Labelled nucleotides
US7057026B2 (en) 2001-12-04 2006-06-06 Solexa Limited Labelled nucleotides
US20030148391A1 (en) * 2002-01-24 2003-08-07 Salafsky Joshua S. Method using a nonlinear optical technique for detection of interactions involving a conformational change
DE10214395A1 (en) * 2002-03-30 2003-10-23 Dmitri Tcherkassov Parallel sequencing of nucleic acid segments, useful for detecting single-nucleotide polymorphisms, by single-base extensions with labeled nucleotide
US20030215816A1 (en) * 2002-05-20 2003-11-20 Narayan Sundararajan Method for sequencing nucleic acids by observing the uptake of nucleotides modified with bulky groups
US6952651B2 (en) * 2002-06-17 2005-10-04 Intel Corporation Methods and apparatus for nucleic acid sequencing by signal stretching and data integration
US11008359B2 (en) 2002-08-23 2021-05-18 Illumina Cambridge Limited Labelled nucleotides
US7414116B2 (en) 2002-08-23 2008-08-19 Illumina Cambridge Limited Labelled nucleotides
AU2003259350A1 (en) 2002-08-23 2004-03-11 Solexa Limited Modified nucleotides for polynucleotide sequencing
WO2004020604A2 (en) * 2002-08-29 2004-03-11 Amersham Biosciences Corp Allele specific primer extension
JP2005538735A (en) * 2002-09-17 2005-12-22 パーキネルマー ラス インコーポレイテッド Real-time detection method of nucleic acid reaction
AU2002363822A1 (en) * 2002-11-20 2004-06-15 Richard Fritz Sauter Method for analyzing molecules for molecule sequencing and spectrometer therefor
WO2004050916A1 (en) * 2002-12-02 2004-06-17 Solexa Limited Recovery of original template
TWI342395B (en) * 2002-12-20 2011-05-21 Ibm Method for producing a monolayer of molecules on a surface and biosensor with such a monolayer
US20090186343A1 (en) * 2003-01-28 2009-07-23 Visigen Biotechnologies, Inc. Methods for preparing modified biomolecules, modified biomolecules and methods for using same
DE60335144D1 (en) * 2003-02-05 2011-01-05 Ge Healthcare Bio Sciences nucleic acid amplification
WO2004074503A2 (en) * 2003-02-21 2004-09-02 Hoser Mark J Nucleic acid sequencing methods, kits and reagents
US7745116B2 (en) * 2003-04-08 2010-06-29 Pacific Biosciences Of California, Inc. Composition and method for nucleic acid sequencing
GB0308852D0 (en) * 2003-04-16 2003-05-21 Lingvitae As Method
US20050170367A1 (en) * 2003-06-10 2005-08-04 Quake Stephen R. Fluorescently labeled nucleoside triphosphates and analogs thereof for sequencing nucleic acids
US20100190151A1 (en) * 2003-06-10 2010-07-29 Quake Stephen R Fluorescently labeled nucleoside triphosphates and analogs thereof for sequencing nucleic acids
GB0317343D0 (en) 2003-07-24 2003-08-27 Medical Biosystems Ltd Polynucleotide sequencing
GB0324456D0 (en) * 2003-10-20 2003-11-19 Isis Innovation Parallel DNA sequencing methods
US7169560B2 (en) 2003-11-12 2007-01-30 Helicos Biosciences Corporation Short cycle methods for sequencing polynucleotides
US20060172408A1 (en) * 2003-12-01 2006-08-03 Quake Steven R Device for immobilizing chemical and biochemical species and methods of using same
US10337054B2 (en) 2004-02-02 2019-07-02 Quantum-Si Incorporated Enrichment of nucleic acid targets
EP1716254B1 (en) * 2004-02-19 2010-04-07 Helicos Biosciences Corporation Methods for analyzing polynucleotide sequences
US20060046258A1 (en) * 2004-02-27 2006-03-02 Lapidus Stanley N Applications of single molecule sequencing
US20050239085A1 (en) * 2004-04-23 2005-10-27 Buzby Philip R Methods for nucleic acid sequence determination
US7462452B2 (en) 2004-04-30 2008-12-09 Pacific Biosciences Of California, Inc. Field-switch sequencing
BR122016013290B1 (en) * 2004-05-13 2021-04-20 Anita Goel nucleic acid molecule amplification device, microfluidic device for applying tension to nucleic acid molecules and kits for nucleic acid molecule processing
US20050260609A1 (en) * 2004-05-24 2005-11-24 Lapidus Stanley N Methods and devices for sequencing nucleic acids
US7476734B2 (en) * 2005-12-06 2009-01-13 Helicos Biosciences Corporation Nucleotide analogs
US20070117103A1 (en) * 2005-11-22 2007-05-24 Buzby Philip R Nucleotide analogs
ATE507305T1 (en) * 2004-05-25 2011-05-15 Helicos Biosciences Corp METHOD FOR NUCLEIC ACID IMMOBILIZATION
US20070117104A1 (en) * 2005-11-22 2007-05-24 Buzby Philip R Nucleotide analogs
US20060024678A1 (en) * 2004-07-28 2006-02-02 Helicos Biosciences Corporation Use of single-stranded nucleic acid binding proteins in sequencing
DE102004038359A1 (en) 2004-08-06 2006-03-16 Rudolf Rigler Sequencing nucleic acids for e.g. analyzing genomes, comprises contacting nucleic acid-degrading enzymes with free fluorescent labeled nucleic acids, and determining base sequence
CN102759466A (en) 2004-09-15 2012-10-31 英特基因有限公司 Microfluidic devices
US7170050B2 (en) 2004-09-17 2007-01-30 Pacific Biosciences Of California, Inc. Apparatus and methods for optical analysis of molecules
EP1790202A4 (en) * 2004-09-17 2013-02-20 Pacific Biosciences California Apparatus and method for analysis of molecules
US20060118754A1 (en) * 2004-12-08 2006-06-08 Lapen Daniel C Stabilizing a polyelectrolyte multilayer
EP1828412B2 (en) * 2004-12-13 2019-01-09 Illumina Cambridge Limited Improved method of nucleotide detection
GB0427236D0 (en) * 2004-12-13 2005-01-12 Solexa Ltd Improved method of nucleotide detection
US7220549B2 (en) * 2004-12-30 2007-05-22 Helicos Biosciences Corporation Stabilizing a nucleic acid for nucleic acid sequencing
US20060172328A1 (en) * 2005-01-05 2006-08-03 Buzby Philip R Methods and compositions for correcting misincorporation in a nucleic acid synthesis reaction
US7482120B2 (en) * 2005-01-28 2009-01-27 Helicos Biosciences Corporation Methods and compositions for improving fidelity in a nucleic acid synthesis reaction
CA2593855A1 (en) * 2005-01-31 2006-08-10 Pacific Biosciences Of California, Inc. Use of reversible extension terminator in nucleic acid sequencing
US20070141598A1 (en) * 2005-02-09 2007-06-21 Pacific Biosciences Of California, Inc. Nucleotide Compositions and Uses Thereof
US7767394B2 (en) * 2005-02-09 2010-08-03 Pacific Biosciences Of California, Inc. Nucleotide compositions and uses thereof
US20060263790A1 (en) * 2005-05-20 2006-11-23 Timothy Harris Methods for improving fidelity in a nucleic acid synthesis reaction
US9410889B2 (en) 2005-06-10 2016-08-09 Applied Biosystem, Llc Method and system for multiplex genetic analysis
GB0514935D0 (en) 2005-07-20 2005-08-24 Solexa Ltd Methods for sequencing a polynucleotide template
CA2616433A1 (en) * 2005-07-28 2007-02-01 Helicos Biosciences Corporation Consecutive base single molecule sequencing
EP1917346A2 (en) * 2005-08-05 2008-05-07 Helicos Biosciences Corporation Signal pattern compositions and methods
US7805081B2 (en) * 2005-08-11 2010-09-28 Pacific Biosciences Of California, Inc. Methods and systems for monitoring multiple optical signals from a single source
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
JP2009507229A (en) * 2005-09-02 2009-02-19 ザ・ユニバーシティ・オブ・トレド Methods and compositions for identifying biomarkers useful for diagnosis and / or treatment of biological conditions
US7405281B2 (en) * 2005-09-29 2008-07-29 Pacific Biosciences Of California, Inc. Fluorescent nucleotide analogs and uses therefor
US7763423B2 (en) 2005-09-30 2010-07-27 Pacific Biosciences Of California, Inc. Substrates having low density reactive groups for monitoring enzyme activity
US20070117102A1 (en) * 2005-11-22 2007-05-24 Buzby Philip R Nucleotide analogs
EP1969153A2 (en) * 2005-11-28 2008-09-17 Pacific Biosciences of California, Inc. Uniform surfaces for hybrid material substrates and methods for making and using same
US7998717B2 (en) 2005-12-02 2011-08-16 Pacific Biosciences Of California, Inc. Mitigation of photodamage in analytical reactions
US20070128610A1 (en) * 2005-12-02 2007-06-07 Buzby Philip R Sample preparation method and apparatus for nucleic acid sequencing
DE602006016984D1 (en) * 2005-12-12 2010-10-28 Us Gov Health & Human Serv PROBE FOR SEQUENCING NUCLEIC ACID AND USE PROCESS
US8703734B2 (en) 2005-12-12 2014-04-22 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Nanoprobes for detection or modification of molecules
US20090305248A1 (en) * 2005-12-15 2009-12-10 Lander Eric G Methods for increasing accuracy of nucleic acid sequencing
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
WO2007075873A2 (en) * 2005-12-22 2007-07-05 Pacific Biosciences Of California, Inc. Protein engineering strategies to optimize activity of surface attached proteins
WO2007076057A2 (en) 2005-12-22 2007-07-05 Pacific Biosciences Of California, Inc. Polymerases for nucleotide analogue incorporation
CA2633476C (en) * 2005-12-22 2015-04-21 Pacific Biosciences Of California, Inc. Active surface coupled polymerases
US20070148636A1 (en) * 2005-12-23 2007-06-28 Song Min-Sun Method, compositions and kits for preparation of nucleic acids
WO2007077952A1 (en) * 2005-12-28 2007-07-12 Canon Kabushiki Kaisha Method and device for determining a nucleic acid allele or base sequence
EP1979079A4 (en) 2006-02-03 2012-11-28 Integenx Inc Microfluidic devices
US7715001B2 (en) * 2006-02-13 2010-05-11 Pacific Biosciences Of California, Inc. Methods and systems for simultaneous real-time monitoring of optical signals from multiple sources
US7692783B2 (en) * 2006-02-13 2010-04-06 Pacific Biosciences Of California Methods and systems for simultaneous real-time monitoring of optical signals from multiple sources
US7995202B2 (en) 2006-02-13 2011-08-09 Pacific Biosciences Of California, Inc. Methods and systems for simultaneous real-time monitoring of optical signals from multiple sources
US20070196832A1 (en) * 2006-02-22 2007-08-23 Efcavitch J William Methods for mutation detection
US7397546B2 (en) * 2006-03-08 2008-07-08 Helicos Biosciences Corporation Systems and methods for reducing detected intensity non-uniformity in a laser beam
US20080309926A1 (en) * 2006-03-08 2008-12-18 Aaron Weber Systems and methods for reducing detected intensity non uniformity in a laser beam
KR101151486B1 (en) * 2006-03-20 2012-05-30 미쓰이 가가쿠 가부시키가이샤 Optical film and method for producing same
US20080050747A1 (en) * 2006-03-30 2008-02-28 Pacific Biosciences Of California, Inc. Articles having localized molecules disposed thereon and methods of producing and using same
US8975216B2 (en) * 2006-03-30 2015-03-10 Pacific Biosciences Of California Articles having localized molecules disposed thereon and methods of producing same
US7563574B2 (en) 2006-03-31 2009-07-21 Pacific Biosciences Of California, Inc. Methods, systems and compositions for monitoring enzyme activity and applications thereof
EP2016415B1 (en) 2006-04-21 2013-08-14 Nanobiosym, Inc. Single-molecule platform for drug discovery: methods for drug discovery, including discovery of anticancer and antiviral agents
US7709808B2 (en) * 2006-05-16 2010-05-04 Applied Biosystems, Llc Systems, methods and apparatus for single molecule sequencing
AU2007260676A1 (en) 2006-06-14 2007-12-21 Artemis Health, Inc. Rare cell analysis using sample splitting and DNA tags
EP3406736B1 (en) 2006-06-14 2022-09-07 Verinata Health, Inc. Methods for the diagnosis of fetal abnormalities
EP2589668A1 (en) 2006-06-14 2013-05-08 Verinata Health, Inc Rare cell analysis using sample splitting and DNA tags
US20080050739A1 (en) 2006-06-14 2008-02-28 Roland Stoughton Diagnosis of fetal abnormalities using polymorphisms including short tandem repeats
US20080070792A1 (en) 2006-06-14 2008-03-20 Roland Stoughton Use of highly parallel snp genotyping for fetal diagnosis
WO2007147110A2 (en) * 2006-06-16 2007-12-21 Pacific Biosciences Of California, Inc. Controlled initiation of primer extension
US20080241951A1 (en) * 2006-07-20 2008-10-02 Visigen Biotechnologies, Inc. Method and apparatus for moving stage detection of single molecular events
US20080241938A1 (en) * 2006-07-20 2008-10-02 Visigen Biotechnologies, Inc. Automated synthesis or sequencing apparatus and method for making and using same
US20080091005A1 (en) * 2006-07-20 2008-04-17 Visigen Biotechnologies, Inc. Modified nucleotides, methods for making and using same
AU2007289057C1 (en) 2006-09-01 2014-01-16 Pacific Biosciences Of California, Inc. Substrates, systems and methods for analyzing materials
US8207509B2 (en) 2006-09-01 2012-06-26 Pacific Biosciences Of California, Inc. Substrates, systems and methods for analyzing materials
US20080076123A1 (en) * 2006-09-27 2008-03-27 Helicos Biosciences Corporation Polymerase variants for DNA sequencing
US20080080059A1 (en) * 2006-09-28 2008-04-03 Pacific Biosciences Of California, Inc. Modular optical components and systems incorporating same
US8399188B2 (en) 2006-09-28 2013-03-19 Illumina, Inc. Compositions and methods for nucleotide sequencing
WO2008051530A2 (en) * 2006-10-23 2008-05-02 Pacific Biosciences Of California, Inc. Polymerase enzymes and reagents for enhanced nucleic acid sequencing
WO2008069973A2 (en) 2006-12-01 2008-06-12 The Trustees Of Columbia University In The City Of New York Four-color dna sequencing by synthesis using cleavable fluorescent nucleotide reversible terminators
US8315817B2 (en) 2007-01-26 2012-11-20 Illumina, Inc. Independently removable nucleic acid sequencing system and method
WO2008092155A2 (en) * 2007-01-26 2008-07-31 Illumina, Inc. Image data efficient genetic sequencing method and system
EP2121983A2 (en) 2007-02-02 2009-11-25 Illumina Cambridge Limited Methods for indexing samples and sequencing multiple nucleotide templates
US11940413B2 (en) 2007-02-05 2024-03-26 IsoPlexis Corporation Methods and devices for sequencing nucleic acids in smaller batches
CN101715483A (en) 2007-02-05 2010-05-26 微芯片生物工艺学股份有限公司 microfluidic and nanofluidic devices, systems, and applications
US8551704B2 (en) 2007-02-16 2013-10-08 Pacific Biosciences Of California, Inc. Controllable strand scission of mini circle DNA
JP2010518862A (en) * 2007-02-21 2010-06-03 ライフ テクノロジーズ コーポレーション Materials and methods for single molecule nucleic acid sequencing
US20080220537A1 (en) * 2007-03-07 2008-09-11 Pacific Biosciences Of California, Inc. Substrates and methods for selective immobilization of active molecules
US20080234143A1 (en) * 2007-03-23 2008-09-25 Pacific Biosciences Of California, Inc. Mechanical methods for producing substrates having selectively immobilized molecules
US8722327B2 (en) * 2007-03-28 2014-05-13 Bionano Genomics, Inc. Methods of macromolecular analysis using nanochannel arrays
ATE548643T1 (en) * 2007-03-30 2012-03-15 Pacific Biosciences California SYSTEM AND METHOD FOR AMPLIFYING FLUORESCENT SIGNALS
EP3543357A1 (en) 2007-05-08 2019-09-25 Trustees of Boston University Chemical functionalization of solid-state nanopores and nanopore arrays and applications thereof
US20080277595A1 (en) * 2007-05-10 2008-11-13 Pacific Biosciences Of California, Inc. Highly multiplexed confocal detection systems and methods of using same
US20100167413A1 (en) * 2007-05-10 2010-07-01 Paul Lundquist Methods and systems for analyzing fluorescent materials with reduced autofluorescence
US8703422B2 (en) * 2007-06-06 2014-04-22 Pacific Biosciences Of California, Inc. Methods and processes for calling bases in sequence by incorporation methods
EP2155855B1 (en) * 2007-06-06 2016-10-12 Pacific Biosciences of California, Inc. Methods and processes for calling bases in sequence by incorporation methods
JP5222599B2 (en) * 2007-07-20 2013-06-26 株式会社日立ハイテクノロジーズ Nucleic acid analysis device and nucleic acid analysis apparatus using the same
WO2009017678A2 (en) 2007-07-26 2009-02-05 Pacific Biosciences Of California, Inc. Molecular redundant sequencing
AU2008307617B2 (en) 2007-09-28 2013-05-23 Pacific Biosciences Of California, Inc. Error-free amplification of DNA for clonal sequencing
US7960116B2 (en) 2007-09-28 2011-06-14 Pacific Biosciences Of California, Inc. Nucleic acid sequencing methods and systems
EP3181228B1 (en) 2007-10-02 2020-07-29 Labrador Diagnostics LLC Modular point-of-care devices and uses thereof
EP2940029B1 (en) 2007-10-19 2023-11-29 The Trustees of Columbia University in the City of New York Design and synthesis of cleavable fluorescent nucleotides as reversible terminators for dna sequencing by synthesis
EP3431615A3 (en) 2007-10-19 2019-02-20 The Trustees of Columbia University in the City of New York Dna sequencing with non-fluorescent nucleotide reversible terminators cleavable label modified nucleotide terminators
EP2203568A1 (en) * 2007-10-22 2010-07-07 Life Technologies Corporation A method and system for obtaining ordered, segmented sequence fragments along a nucleic acid molecule
US7767441B2 (en) 2007-10-25 2010-08-03 Industrial Technology Research Institute Bioassay system including optical detection apparatuses, and method for detecting biomolecules
US7811810B2 (en) 2007-10-25 2010-10-12 Industrial Technology Research Institute Bioassay system including optical detection apparatuses, and method for detecting biomolecules
US8617811B2 (en) 2008-01-28 2013-12-31 Complete Genomics, Inc. Methods and compositions for efficient base calling in sequencing reactions
US8722437B2 (en) 2007-11-01 2014-05-13 Mogul Solutions Llc Method of component assembly on a substrate
US20090117339A1 (en) * 2007-11-01 2009-05-07 Till Bocking Method of component assembly on a substrate
EP2245444A4 (en) 2008-01-10 2014-04-16 Pacific Biosciences California Methods and systems for analysis of fluorescent reactions with modulated excitation
US20090181390A1 (en) * 2008-01-11 2009-07-16 Signosis, Inc. A California Corporation High throughput detection of micrornas and use for disease diagnosis
WO2009108260A2 (en) 2008-01-22 2009-09-03 Microchip Biotechnologies, Inc. Universal sample preparation system and use in an integrated analysis system
WO2009100382A1 (en) * 2008-02-07 2009-08-13 Pacific Biosciences Of California, Inc. Cis reactive oxygen quenchers integrated into linkers
CA2715385A1 (en) * 2008-02-12 2009-08-20 Pacific Biosciences Of California, Inc. Compositions and methods for use in analytical reactions
US7973146B2 (en) * 2008-03-26 2011-07-05 Pacific Biosciences Of California, Inc. Engineered fluorescent dye labeled nucleotide analogs for DNA sequencing
EP4230747A3 (en) 2008-03-28 2023-11-15 Pacific Biosciences Of California, Inc. Compositions and methods for nucleic acid sequencing
US8628940B2 (en) 2008-09-24 2014-01-14 Pacific Biosciences Of California, Inc. Intermittent detection during analytical reactions
US8236499B2 (en) * 2008-03-28 2012-08-07 Pacific Biosciences Of California, Inc. Methods and compositions for nucleic acid sample preparation
US8420366B2 (en) * 2008-03-31 2013-04-16 Pacific Biosciences Of California, Inc. Generation of modified polymerases for improved accuracy in single molecule sequencing
US8999676B2 (en) 2008-03-31 2015-04-07 Pacific Biosciences Of California, Inc. Recombinant polymerases for improved single molecule sequencing
US20090247426A1 (en) * 2008-03-31 2009-10-01 Pacific Biosciences Of California, Inc. Focused library generation
US8906831B2 (en) * 2008-03-31 2014-12-09 Pacific Biosciences Of California, Inc. Single molecule loading methods and compositions
ES2614078T3 (en) * 2008-03-31 2017-05-29 Pacific Biosciences Of California, Inc. Generation of modified polymerases for improved accuracy in single molecule sequencing
US9127259B2 (en) 2008-03-31 2015-09-08 Pacific Biosciences Of California, Inc. Enzymes resistant to photodamage
US20100049445A1 (en) * 2008-06-20 2010-02-25 Eureka Genomics Corporation Method and apparatus for sequencing data samples
WO2010002939A2 (en) * 2008-06-30 2010-01-07 Life Technologies Corporation Methods for real time single molecule sequencing
EP2682460B1 (en) 2008-07-07 2017-04-26 Oxford Nanopore Technologies Limited Enzyme-pore constructs
US9182406B2 (en) 2008-08-04 2015-11-10 Biodesy, Inc. Nonlinear optical detection of molecules comprising an unnatural amino acid possessing a hyperpolarizability
US8198023B2 (en) 2008-08-05 2012-06-12 Pacific Biosciences Of California, Inc. Prevention and alleviation of steric hindrance during single molecule nucleic acid synthesis by a polymerase
US20100227327A1 (en) * 2008-08-08 2010-09-09 Xiaoliang Sunney Xie Methods and compositions for continuous single-molecule nucleic acid sequencing by synthesis with fluorogenic nucleotides
US20100036110A1 (en) * 2008-08-08 2010-02-11 Xiaoliang Sunney Xie Methods and compositions for continuous single-molecule nucleic acid sequencing by synthesis with fluorogenic nucleotides
WO2010027497A2 (en) 2008-09-05 2010-03-11 Pacific Biosciences Of California, Inc Preparations, compositions, and methods for nucleic acid sequencing
EP4325209A2 (en) 2008-09-16 2024-02-21 Pacific Biosciences Of California, Inc. Integrated optical device
US8921046B2 (en) 2008-09-19 2014-12-30 Pacific Biosciences Of California, Inc. Nucleic acid sequence analysis
US8481264B2 (en) * 2008-09-19 2013-07-09 Pacific Biosciences Of California, Inc. Immobilized nucleic acid complexes for sequence analysis
US8383369B2 (en) 2008-09-24 2013-02-26 Pacific Biosciences Of California, Inc. Intermittent detection during analytical reactions
WO2010036287A1 (en) 2008-09-24 2010-04-01 Pacific Biosciences Of California, Inc. Intermittent detection during analytical reactions
WO2010057185A1 (en) 2008-11-17 2010-05-20 Pacific Biosciences Of California, Inc. Phospholink nucleotides for sequencing applications
WO2010059206A2 (en) * 2008-11-19 2010-05-27 Pacific Biosciences Of California, Inc. Modular nucleotide compositions and uses therefor
US8370079B2 (en) 2008-11-20 2013-02-05 Pacific Biosciences Of California, Inc. Algorithms for sequence determination
US8993230B2 (en) * 2008-12-04 2015-03-31 Pacific Biosciences of Californ, Inc. Asynchronous sequencing of biological polymers
BRPI0922411A2 (en) 2008-12-11 2018-06-05 Pacific Biosciences California Inc nucleic acid template classification
US9175338B2 (en) 2008-12-11 2015-11-03 Pacific Biosciences Of California, Inc. Methods for identifying nucleic acid modifications
CN102317471A (en) 2008-12-11 2012-01-11 加利福尼亚大学董事会 Methods and systems for direct sequencing of single dna molecules
US20230148447A9 (en) 2008-12-11 2023-05-11 Pacific Biosciences Of California, Inc. Classification of nucleic acid templates
EP2607496B1 (en) 2008-12-23 2014-07-16 Illumina, Inc. Methods useful in nucleic acid sequencing protocols
CN102341691A (en) * 2008-12-31 2012-02-01 尹特根埃克斯有限公司 Instrument with microfluidic chip
JP5843614B2 (en) 2009-01-30 2016-01-13 オックスフォード ナノポア テクノロジーズ リミテッド Adapters for nucleic acid constructs in transmembrane sequencing
JP5292118B2 (en) * 2009-01-30 2013-09-18 富士フイルム株式会社 Fluorescence endoscope system and method for operating the fluorescence endoscope system
US9212995B2 (en) 2009-03-02 2015-12-15 Mbio Diagnostics, Inc. System and method for detecting multiple molecules in one assay
US9658222B2 (en) 2009-03-02 2017-05-23 Mbio Diagnostics, Inc. Planar waveguide based cartridges and associated methods for detecting target analyte
US8300993B2 (en) * 2009-03-02 2012-10-30 Mbio Diagnostics, Inc. Waveguide with integrated lens
US8331751B2 (en) * 2009-03-02 2012-12-11 mBio Diagnositcs, Inc. Planar optical waveguide with core of low-index-of-refraction interrogation medium
US9778188B2 (en) * 2009-03-11 2017-10-03 Industrial Technology Research Institute Apparatus and method for detection and discrimination molecular object
WO2010111674A2 (en) 2009-03-27 2010-09-30 Life Technologies Corporation Methods and apparatus for single molecule sequencing using energy transfer detection
WO2010117420A2 (en) 2009-03-30 2010-10-14 Pacific Biosciences Of California, Inc. Fret-labeled compounds and uses therefor
WO2010129019A2 (en) * 2009-04-27 2010-11-11 Pacific Biosciences Of California, Inc. Real-time sequencing methods and systems
EP2427572B1 (en) * 2009-05-01 2013-08-28 Illumina, Inc. Sequencing methods
JP5618497B2 (en) * 2009-05-15 2014-11-05 株式会社日立ハイテクノロジーズ Nucleic acid analysis method and nucleic acid analyzer
US20120064527A1 (en) * 2009-05-27 2012-03-15 Akira Maekawa Nucleic acid analysis device, nucleic acid analysis apparatus, and nucleic acid analysis method
CN102459565A (en) * 2009-06-02 2012-05-16 尹特根埃克斯有限公司 Fluidic devices with diaphragm valves
US20100311144A1 (en) * 2009-06-05 2010-12-09 Life Technologies Corporation Mutant dna polymerases
WO2010141921A1 (en) 2009-06-05 2010-12-09 Integenx Inc. Universal sample preparation system and use in an integrated analysis system
US8609421B2 (en) * 2009-06-12 2013-12-17 Pacific Biosciences Of California, Inc. Single-molecule real-time analysis of protein synthesis
WO2010144150A2 (en) 2009-06-12 2010-12-16 Pacific Biosciences Of California, Inc. Real-time analytical methods and systems
US8501406B1 (en) 2009-07-14 2013-08-06 Pacific Biosciences Of California, Inc. Selectively functionalized arrays
US20110059864A1 (en) * 2009-09-07 2011-03-10 Caerus Molecular Diagnostics Incorporated Sequence Determination By Use Of Opposing Forces
WO2011032040A1 (en) 2009-09-10 2011-03-17 Centrillion Technology Holding Corporation Methods of targeted sequencing
US10174368B2 (en) 2009-09-10 2019-01-08 Centrillion Technology Holdings Corporation Methods and systems for sequencing long nucleic acids
US8367159B2 (en) 2009-09-11 2013-02-05 Pacific Biosciences Of California, Inc. Methods for producing ZMWs with islands of functionality
US8906670B2 (en) 2009-09-11 2014-12-09 Pacific Bioscience Of California, Inc. Zero-mode waveguides with non-reflecting walls
WO2011038241A1 (en) * 2009-09-25 2011-03-31 President And Fellows Of Harvard College Nucleic acid amplification and sequencing by synthesis with fluorogenic nucleotides
US9566335B1 (en) 2009-09-25 2017-02-14 The Governing Council Of The University Of Toronto Protein sequencing method and reagents
AU2010301128B2 (en) 2009-09-30 2014-09-18 Quantapore, Inc. Ultrafast sequencing of biological polymers using a labeled nanopore
ES2821500T3 (en) 2009-11-06 2021-04-26 Univ Leland Stanford Junior Non-invasive diagnosis of graft rejection in organ transplant patients
US8772016B2 (en) 2009-11-13 2014-07-08 Pacific Biosciences Of California, Inc. Sealed chip package
US8584703B2 (en) * 2009-12-01 2013-11-19 Integenx Inc. Device with diaphragm valve
WO2011090710A2 (en) * 2009-12-28 2011-07-28 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Composite probes and use thereof in super resolution methods
WO2011091043A1 (en) 2010-01-19 2011-07-28 Life Technologies Corporation Single molecule nucleic acid sequencing using multiphoton fluorescence excitation
US8518643B2 (en) * 2010-02-04 2013-08-27 Pacific Biosciences Of California, Inc. Method to improve single molecule analyses
EP2537019B1 (en) 2010-02-19 2016-09-07 Pacific Biosciences Of California, Inc. Device for measuring analytical reactions
US8994946B2 (en) 2010-02-19 2015-03-31 Pacific Biosciences Of California, Inc. Integrated analytical system and method
US9482615B2 (en) 2010-03-15 2016-11-01 Industrial Technology Research Institute Single-molecule detection system and methods
WO2011139344A2 (en) 2010-04-28 2011-11-10 Pacific Biosciences Of California, Inc Nanoscale apertures having islands of functionality
US8512538B2 (en) 2010-05-28 2013-08-20 Integenx Inc. Capillary electrophoresis device
US9670243B2 (en) 2010-06-02 2017-06-06 Industrial Technology Research Institute Compositions and methods for sequencing nucleic acids
US8865078B2 (en) * 2010-06-11 2014-10-21 Industrial Technology Research Institute Apparatus for single-molecule detection
US8865077B2 (en) 2010-06-11 2014-10-21 Industrial Technology Research Institute Apparatus for single-molecule detection
US8318094B1 (en) 2010-06-18 2012-11-27 Pacific Biosciences Of California, Inc. Substrate analysis systems
US8986930B2 (en) 2010-07-12 2015-03-24 Pacific Biosciences Of California, Inc. Sequencing reactions with alkali metal cations for pulse width control
US8834847B2 (en) 2010-08-12 2014-09-16 Pacific Biosciences Of California, Inc. Photodamage mitigation compounds and systems
EP2606154B1 (en) 2010-08-20 2019-09-25 Integenx Inc. Integrated analysis system
WO2012024657A1 (en) 2010-08-20 2012-02-23 IntegenX, Inc. Microfluidic devices with mechanically-sealed diaphragm valves
WO2012027623A2 (en) 2010-08-25 2012-03-01 Pacific Biosciences Of California, Inc. Cyanine dyes
US8465922B2 (en) 2010-08-26 2013-06-18 Pacific Biosciences Of California, Inc. Methods and systems for monitoring reactions
WO2012031008A2 (en) 2010-08-31 2012-03-08 The General Hospital Corporation Cancer-related biological materials in microvesicles
TW201217783A (en) 2010-09-15 2012-05-01 Mbio Diagnostics Inc System and method for detecting multiple molecules in one assay
EP3327140A1 (en) 2010-09-16 2018-05-30 Gen-Probe Incorporated Capture probes immobilizable via l-nucleotide tail
US8936911B2 (en) 2010-09-22 2015-01-20 Pacific Biosciences Of California, Inc. Purified extended polymerase/template complex for sequencing
AU2011312218B2 (en) 2010-10-04 2015-11-05 Sequencing Health, Inc. Systems and methods for automated reusable parallel biological reactions
US9399217B2 (en) 2010-10-04 2016-07-26 Genapsys, Inc. Chamber free nanoreactor system
US9184099B2 (en) 2010-10-04 2015-11-10 The Board Of Trustees Of The Leland Stanford Junior University Biosensor devices, systems and methods therefor
WO2012055929A1 (en) 2010-10-26 2012-05-03 Illumina, Inc. Sequencing methods
WO2012061412A1 (en) 2010-11-01 2012-05-10 Gen-Probe Incorporated Integrated capture and amplification of target nucleic acid for sequencing
EP2643045A4 (en) 2010-11-23 2016-01-13 Presage Biosciences Inc Therapeutic methods and compositions for solid delivery
US8845880B2 (en) 2010-12-22 2014-09-30 Genia Technologies, Inc. Nanopore-based single DNA molecule characterization, identification and isolation using speed bumps
JP5581228B2 (en) * 2011-01-07 2014-08-27 株式会社日立ハイテクノロジーズ Fluorescence detection device
BR112013018656B1 (en) 2011-01-21 2021-03-02 Labrador Diagnostics Llc method for detecting the presence or concentration of an analyte in a sample of fluid contained in a container, and, method of measuring the concentration of analyte in a sample of fluid
ES2687761T3 (en) 2011-01-31 2018-10-29 F. Hoffmann-La Roche Ag Methods of identification of multiple epitopes in cells
US20120202702A1 (en) * 2011-02-07 2012-08-09 The Regents Of The University Of California Detection of low concentration biological agents
GB2503604B (en) 2011-03-21 2020-04-22 Biodesy Llc Classification of kinase inhibitors using second harmonic optical techniques
EP2689028B1 (en) 2011-03-23 2017-08-30 Pacific Biosciences Of California, Inc. Isolation of polymerase-nucleic acid complexes and loading onto substrates
US20120252682A1 (en) 2011-04-01 2012-10-04 Maples Corporate Services Limited Methods and systems for sequencing nucleic acids
US9611510B2 (en) 2011-04-06 2017-04-04 The University Of Chicago Composition and methods related to modification of 5-methylcytosine (5-mC)
WO2012162429A2 (en) 2011-05-23 2012-11-29 The Trustees Of Columbia University In The City Of New York Dna sequencing by synthesis using raman and infrared spectroscopy detection
US8585973B2 (en) 2011-05-27 2013-11-19 The Board Of Trustees Of The Leland Stanford Junior University Nano-sensor array
US9926596B2 (en) 2011-05-27 2018-03-27 Genapsys, Inc. Systems and methods for genetic and biological analysis
CN103717753B (en) 2011-05-27 2016-12-07 吉纳普赛斯股份有限公司 For heredity and the system and method for bioanalysis
CA2843136C (en) 2011-07-25 2020-12-29 Oxford Nanopore Technologies Limited Hairpin loop method for double strand polynucleotide sequencing using transmembrane pores
CN107326079B (en) 2011-08-10 2021-04-20 生命技术公司 Polymerase compositions, methods of making and using the same
US8435738B2 (en) 2011-09-25 2013-05-07 Theranos, Inc. Systems and methods for multi-analysis
US9632102B2 (en) 2011-09-25 2017-04-25 Theranos, Inc. Systems and methods for multi-purpose analysis
US8840838B2 (en) 2011-09-25 2014-09-23 Theranos, Inc. Centrifuge configurations
US20140170735A1 (en) 2011-09-25 2014-06-19 Elizabeth A. Holmes Systems and methods for multi-analysis
US9268915B2 (en) 2011-09-25 2016-02-23 Theranos, Inc. Systems and methods for diagnosis or treatment
US9664702B2 (en) 2011-09-25 2017-05-30 Theranos, Inc. Fluid handling apparatus and configurations
US9619627B2 (en) 2011-09-25 2017-04-11 Theranos, Inc. Systems and methods for collecting and transmitting assay results
US8475739B2 (en) 2011-09-25 2013-07-02 Theranos, Inc. Systems and methods for fluid handling
WO2013043922A1 (en) 2011-09-22 2013-03-28 ImmuMetrix, LLC Compositions and methods for analyzing heterogeneous samples
US9250229B2 (en) 2011-09-25 2016-02-02 Theranos, Inc. Systems and methods for multi-analysis
US9810704B2 (en) 2013-02-18 2017-11-07 Theranos, Inc. Systems and methods for multi-analysis
US10012664B2 (en) 2011-09-25 2018-07-03 Theranos Ip Company, Llc Systems and methods for fluid and component handling
US9347900B2 (en) 2011-10-14 2016-05-24 Pacific Biosciences Of California, Inc. Real-time redox sequencing
SG10201510189WA (en) 2011-10-19 2016-01-28 Nugen Technologies Inc Compositions And Methods For Directional Nucleic Acid Amplification And Sequencing
US10865440B2 (en) 2011-10-21 2020-12-15 IntegenX, Inc. Sample preparation, processing and analysis systems
US20150136604A1 (en) 2011-10-21 2015-05-21 Integenx Inc. Sample preparation, processing and analysis systems
US9267917B2 (en) 2011-11-04 2016-02-23 Pacific Biosciences Of California, Inc. Nanopores in zero mode waveguides
WO2013070634A1 (en) 2011-11-07 2013-05-16 Ingenuity Systems, Inc. Methods and systems for identification of causal genomic variants
JP6193252B2 (en) 2011-12-01 2017-09-06 ジナプシス インコーポレイテッド System and method for high efficiency electronic sequencing and detection
US9279154B2 (en) 2011-12-21 2016-03-08 Illumina, Inc. Apparatus and methods for kinetic analysis and determination of nucleic acid sequences
SG10201504490QA (en) 2012-01-26 2015-07-30 Nugen Technologies Inc Compositions And Methods For Targeted Nucleic Acid Sequence Enrichment And High Efficiency Library Generation
US9528107B2 (en) 2012-01-31 2016-12-27 Pacific Biosciences Of California, Inc. Compositions and methods for selection of nucleic acids
US9238836B2 (en) 2012-03-30 2016-01-19 Pacific Biosciences Of California, Inc. Methods and compositions for sequencing modified nucleic acids
US8906660B2 (en) 2012-02-01 2014-12-09 Pacific Biosciences Of California, Inc. Recombinant polymerases with increased phototolerance
EP2809807B1 (en) 2012-02-01 2019-04-10 Gen-Probe Incorporated Asymmetric hairpin target capture oligomers
EP2814953B1 (en) 2012-02-15 2017-06-07 Pacific Biosciences Of California, Inc. Polymerase enzyme substrates with protein shield
US9173910B2 (en) 2012-02-29 2015-11-03 The General Hospital Corporation Compositions of microbiota and methods related thereto
WO2013131888A1 (en) * 2012-03-06 2013-09-12 Rudolf Rigler Cyclic single molecule sequencing process
WO2013148400A1 (en) 2012-03-30 2013-10-03 Pacific Biosciences Of California, Inc. Methods and composition for sequencing modified nucleic acids
US9175348B2 (en) 2012-04-24 2015-11-03 Pacific Biosciences Of California, Inc. Identification of 5-methyl-C in nucleic acid templates
US20130302794A1 (en) * 2012-05-09 2013-11-14 Samsung Techwin Co., Ltd. Nucleic acid detection by oligonucleotide probes cleaved by both exonuclease and endonuclease
US9315864B2 (en) 2012-05-18 2016-04-19 Pacific Biosciences Of California, Inc. Heteroarylcyanine dyes with sulfonic acid substituents
WO2013173844A1 (en) 2012-05-18 2013-11-21 Pacific Biosciences Of California, Inc. Heteroarylcyanine dyes
US8956816B2 (en) 2012-06-05 2015-02-17 Pacific Biosciences Of California, Inc. Methods and compositions for performing analytical operations
WO2013185137A1 (en) 2012-06-08 2013-12-12 Pacific Biosciences Of California, Inc. Modified base detection with nanopore sequencing
US9267168B2 (en) 2012-06-12 2016-02-23 Pacific Biosciences Of California, Inc. Methods and compositions for isolating template nucleic acids
WO2013188841A1 (en) 2012-06-15 2013-12-19 Genia Technologies, Inc. Chip set-up and high-accuracy nucleic acid sequencing
WO2013192106A1 (en) 2012-06-17 2013-12-27 Pacific Biosciences Of California, Inc. Filter architecture for analytical devices
US9372308B1 (en) 2012-06-17 2016-06-21 Pacific Biosciences Of California, Inc. Arrays of integrated analytical devices and methods for production
SG11201408478QA (en) 2012-06-18 2015-02-27 Nugen Technologies Inc Compositions and methods for negative selection of non-desired nucleic acid sequences
US20150011396A1 (en) 2012-07-09 2015-01-08 Benjamin G. Schroeder Methods for creating directional bisulfite-converted nucleic acid libraries for next generation sequencing
US10777301B2 (en) 2012-07-13 2020-09-15 Pacific Biosciences For California, Inc. Hierarchical genome assembly method using single long insert library
CN104812947B (en) 2012-07-17 2018-04-27 考希尔股份有限公司 The system and method for detecting hereditary variation
US9092401B2 (en) 2012-10-31 2015-07-28 Counsyl, Inc. System and methods for detecting genetic variation
CN108875312A (en) 2012-07-19 2018-11-23 哈佛大学校长及研究员协会 Utilize the method for nucleic acid storage information
EP2875154B1 (en) 2012-07-19 2017-08-23 Oxford Nanopore Technologies Limited SSB method for characterising a nucleic acid
EP2882868B1 (en) 2012-08-08 2019-07-31 H. Hoffnabb-La Roche Ag Increasing dynamic range for identifying multiple epitopes in cells
JP2015535173A (en) 2012-09-11 2015-12-10 セラノス， インコーポレイテッド Information management system and method using biological signatures
US9637782B2 (en) 2012-09-28 2017-05-02 Pacific Biosciences Of California, Inc. Charged triplet-state quenchers for mitigation of photo-induced damage
US9399766B2 (en) 2012-10-01 2016-07-26 Pacific Biosciences Of California, Inc. Recombinant polymerases for incorporation of protein shield nucleotide analogs
US9651539B2 (en) 2012-10-28 2017-05-16 Quantapore, Inc. Reducing background fluorescence in MEMS materials by low energy ion beam treatment
US9605309B2 (en) 2012-11-09 2017-03-28 Genia Technologies, Inc. Nucleic acid sequencing using tags
EP3524964B1 (en) 2012-12-18 2020-07-15 Pacific Biosciences Of California, Inc. An optical analytical device
WO2014108850A2 (en) 2013-01-09 2014-07-17 Yeda Research And Development Co. Ltd. High throughput transcriptome analysis
CN108624668B (en) 2013-02-01 2022-12-02 加利福尼亚大学董事会 Methods for genome assembly and haplotype phasing
US9411930B2 (en) 2013-02-01 2016-08-09 The Regents Of The University Of California Methods for genome assembly and haplotype phasing
DE102013202721A1 (en) * 2013-02-20 2014-08-21 Siemens Aktiengesellschaft A sequencing device for sequencing at least one nucleic acid single strand and methods for sequencing at least one nucleic acid single strand
US9624540B2 (en) 2013-02-22 2017-04-18 Pacific Biosciences Of California, Inc. Integrated illumination of optical analytical devices
GB201314695D0 (en) 2013-08-16 2013-10-02 Oxford Nanopore Tech Ltd Method
CA2901545C (en) 2013-03-08 2019-10-08 Oxford Nanopore Technologies Limited Use of spacer elements in a nucleic acid to control movement of a helicase
US9146248B2 (en) 2013-03-14 2015-09-29 Intelligent Bio-Systems, Inc. Apparatus and methods for purging flow cells in nucleic acid sequencing instruments
WO2014144883A1 (en) * 2013-03-15 2014-09-18 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
US9290800B2 (en) 2013-03-15 2016-03-22 Pacific Biosciences Of California, Inc. Targeted rolling circle amplification
WO2014152625A1 (en) 2013-03-15 2014-09-25 Genapsys, Inc. Systems and methods for biological analysis
ES2946689T3 (en) 2013-03-15 2023-07-24 Univ Leland Stanford Junior Identification and use of circulating nucleic acid tumor markers
US10933417B2 (en) 2013-03-15 2021-03-02 Nanobiosym, Inc. Systems and methods for mobile device analysis of nucleic acids and proteins
DK2971080T3 (en) * 2013-03-15 2018-02-12 Expedeon S L METHODS FOR AMPLIFICATION AND SEQUENCE USING THERMOSTABLE TTHPRIMPOL
KR102230831B1 (en) 2013-03-15 2021-03-22 일루미나 케임브리지 리미티드 Modified nucleosides or nucleotides
CN105189748B (en) 2013-03-15 2021-06-08 血统生物科学公司 Method for sequencing an immune repertoire
WO2014144092A1 (en) 2013-03-15 2014-09-18 Nugen Technologies, Inc. Sequential sequencing
CN105378113B (en) 2013-05-06 2020-02-21 加利福尼亚太平洋生物科学股份有限公司 Real-time electronic sequencing
WO2014190322A2 (en) 2013-05-24 2014-11-27 Quantapore, Inc. Nanopore-based nucleic acid analysis with mixed fret detection
WO2014194028A1 (en) 2013-05-31 2014-12-04 Pacific Biosciences Of California, Inc Analytical devices having compact lens train arrays
US10544449B2 (en) 2013-06-14 2020-01-28 Pacific Biosciences Of California, Inc. Bis-biotinylation tags
US9678080B2 (en) 2013-06-14 2017-06-13 Pacific Biosciences Of California, Inc. Bis-biotinylation tags
US9938567B2 (en) * 2013-06-15 2018-04-10 Cornell University High-throughput RNA interaction assay
ES2628485T3 (en) * 2013-07-03 2017-08-03 Illumina, Inc. Sequencing by orthogonal synthesis
US10633714B2 (en) 2013-07-21 2020-04-28 Pendulum Therapeutics, Inc. Methods and systems for microbiome characterization, monitoring and treatment
US9957291B2 (en) 2013-08-05 2018-05-01 Pacific Biosciences Of California, Inc. Protected fluorescent reagent compounds
TWI695067B (en) 2013-08-05 2020-06-01 美商扭轉生物科技有限公司 De novo synthesized gene libraries
US9879318B2 (en) 2013-09-06 2018-01-30 Pacific Biosciences Of California, Inc. Methods and compositions for nucleic acid sample preparation
WO2015048763A1 (en) 2013-09-30 2015-04-02 Life Technologies Corporation Polymerase compositions, methods of making and using same
CA2926138A1 (en) 2013-10-23 2015-04-30 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
US9416414B2 (en) 2013-10-24 2016-08-16 Pacific Biosciences Of California, Inc. Delaying real-time sequencing
BR112016010095A2 (en) 2013-11-07 2017-09-12 Univ Leland Stanford Junior free cell nucleic acids for human microbiome analysis and components thereof.
WO2015073711A1 (en) 2013-11-13 2015-05-21 Nugen Technologies, Inc. Compositions and methods for identification of a duplicate sequencing read
JP6673843B2 (en) 2013-11-17 2020-03-25 クアンタム−エスアイ インコーポレイテッドＱｕａｎｔｕｍ−Ｓｉ Ｉｎｃｏｒｐｏｒａｔｅｄ Optical systems and assay chips for probing, detecting and analyzing molecules
US10191071B2 (en) 2013-11-18 2019-01-29 IntegenX, Inc. Cartridges and instruments for sample analysis
DE102014208425A1 (en) * 2013-11-28 2015-05-28 Continental Teves Ag & Co. Ohg Method for producing a sensor
WO2015089238A1 (en) 2013-12-11 2015-06-18 Genapsys, Inc. Systems and methods for biological analysis and computation
US11859246B2 (en) 2013-12-11 2024-01-02 Accuragen Holdings Limited Methods and compositions for enrichment of amplification products
US11286519B2 (en) 2013-12-11 2022-03-29 Accuragen Holdings Limited Methods and compositions for enrichment of amplification products
SG11201604737VA (en) 2013-12-11 2016-07-28 Accuragen Inc Compositions and methods for detecting rare sequence variants
US11091758B2 (en) 2013-12-11 2021-08-17 The Regents Of The University Of California Methods for labeling DNAa fragments to reconstruct physical linkage and phase
GB201403096D0 (en) 2014-02-21 2014-04-09 Oxford Nanopore Tech Ltd Sample preparation method
WO2015131107A1 (en) 2014-02-28 2015-09-03 Nugen Technologies, Inc. Reduced representation bisulfite sequencing with diversity adaptors
EP3132060B1 (en) 2014-04-18 2019-03-13 Genapsys Inc. Methods and systems for nucleic acid amplification
GB2544198B (en) 2014-05-21 2021-01-13 Integenx Inc Fluidic cartridge with valve mechanism
US10526641B2 (en) 2014-08-01 2020-01-07 Dovetail Genomics, Llc Tagging nucleic acids for sequence assembly
JP6707520B2 (en) 2014-08-08 2020-06-10 クアンタム−エスアイ インコーポレイテッドＱｕａｎｔｕｍ−Ｓｉ Ｉｎｃｏｒｐｏｒａｔｅｄ Integrated device for time binning of received photons
BR112017002489B1 (en) 2014-08-08 2023-02-14 Quantum-Si Incorporated INSTRUMENT CONFIGURED TO INTERFACE A TEST CHIP, APPARATUS, METHOD OF ANALYZING A SPECIMEN, METHOD OF SEQUENCING A TARGET MOLECULE OF NUCLEIC ACID, AND METHOD OF SEQUENCING NUCLEIC ACID
CA2957546A1 (en) 2014-08-08 2016-02-11 Quantum-Si Incorporated Integrated device with external light source for probing, detecting, and analyzing molecules
WO2016028887A1 (en) 2014-08-19 2016-02-25 Pacific Biosciences Of California, Inc. Compositions and methods for enrichment of nucleic acids
US10435685B2 (en) 2014-08-19 2019-10-08 Pacific Biosciences Of California, Inc. Compositions and methods for enrichment of nucleic acids
US9606068B2 (en) 2014-08-27 2017-03-28 Pacific Biosciences Of California, Inc. Arrays of integrated analytical devices
WO2016153999A1 (en) 2015-03-25 2016-09-29 Life Technologies Corporation Modified nucleotides and uses thereof
US9885079B2 (en) 2014-10-10 2018-02-06 Quantapore, Inc. Nanopore-based polymer analysis with mutually-quenching fluorescent labels
GB201418159D0 (en) 2014-10-14 2014-11-26 Oxford Nanopore Tech Ltd Method
EP3209410A4 (en) 2014-10-22 2018-05-02 IntegenX Inc. Systems and methods for sample preparation, processing and analysis
CN107074904B (en) 2014-10-23 2022-12-23 深圳华大智造科技股份有限公司 Signal-constrained sequencing (SCS) and nucleotide analogs for signal-constrained sequencing
WO2016065339A1 (en) 2014-10-24 2016-04-28 Quantapore, Inc. Efficient optical analysis of polymers using arrays of nanostructures
GB2551642B (en) 2014-10-31 2020-09-23 Pendulum Therapeutics Inc Methods and compositions relating to microbial treatment and diagnosis of disorders
RU2582198C1 (en) * 2014-11-20 2016-04-20 Федеральное государственное бюджетное учреждение науки Лимнологический институт Сибирского отделения Российской академии наук (ЛИН СО РАН) Analogues of natural deoxyribonucleoside triphosphates and ribonucleoside triphosphates containing reporter fluorescent groups, for use in analytical bioorganic chemistry
EP3234115B1 (en) 2014-12-16 2020-07-22 Life Technologies Corporation Polymerase compositions and methods of making and using same
EP3237906B8 (en) 2014-12-23 2020-10-28 Bluelight Therapeutics, Inc. Attachment of proteins to interfaces for use in nonlinear optical detection
US10302972B2 (en) 2015-01-23 2019-05-28 Pacific Biosciences Of California, Inc. Waveguide transmission
WO2016126941A1 (en) 2015-02-04 2016-08-11 Pacific Biosciences Of California, Inc. Multimeric protected fluorescent reagents
US10669304B2 (en) 2015-02-04 2020-06-02 Twist Bioscience Corporation Methods and devices for de novo oligonucleic acid assembly
CA2975855A1 (en) 2015-02-04 2016-08-11 Twist Bioscience Corporation Compositions and methods for synthetic gene assembly
JP6777966B2 (en) 2015-02-17 2020-10-28 ダブテイル ゲノミクス エルエルシー Nucleic acid sequence assembly
EP4220256A1 (en) 2015-03-16 2023-08-02 Pacific Biosciences of California, Inc. Analytical system comprising integrated devices and systems for free-space optical coupling
WO2016154345A1 (en) 2015-03-24 2016-09-29 Pacific Biosciences Of California, Inc. Methods and compositions for single molecule composition loading
GB2554572B (en) 2015-03-26 2021-06-23 Dovetail Genomics Llc Physical linkage preservation in DNA storage
US10385387B2 (en) 2015-04-20 2019-08-20 Pacific Biosciences Of California, Inc. Methods for selectively amplifying and tagging nucleic acids
US9981239B2 (en) 2015-04-21 2018-05-29 Twist Bioscience Corporation Devices and methods for oligonucleic acid library synthesis
CA2981496C (en) 2015-04-23 2023-09-05 The Board Of Trustees Of The Leland Stanford Junior University Method for multiplexed sample analysis by photoionizing secondary sputtered neutrals
US10246742B2 (en) 2015-05-20 2019-04-02 Quantum-Si Incorporated Pulsed laser and bioanalytic system
US11466316B2 (en) 2015-05-20 2022-10-11 Quantum-Si Incorporated Pulsed laser and bioanalytic system
US10605730B2 (en) 2015-05-20 2020-03-31 Quantum-Si Incorporated Optical sources for fluorescent lifetime analysis
WO2016185284A1 (en) 2015-05-20 2016-11-24 Boreal Genomics, Inc. Method for isolating target nucleic acid using heteroduplex binding proteins
US10174363B2 (en) 2015-05-20 2019-01-08 Quantum-Si Incorporated Methods for nucleic acid sequencing
JP6936736B2 (en) * 2015-05-20 2021-09-22 クアンタム−エスアイ インコーポレイテッドＱｕａｎｔｕｍ−Ｓｉ Ｉｎｃｏｒｐｏｒａｔｅｄ A method for sequencing nucleic acids using time-resolved luminescence
CN107615283B (en) 2015-05-26 2022-07-05 加利福尼亚太平洋生物科学股份有限公司 Methods, software and systems for diploid genome assembly and haplotype sequence reconstruction
AU2016276980B2 (en) 2015-06-12 2021-09-23 Pacific Biosciences Of California, Inc. Integrated target waveguide devices and systems for optical coupling
US20180180567A1 (en) * 2015-06-23 2018-06-28 Bgi Shenzhen Microwell electrode and method for analysis of a chemical substance
EP3322812B1 (en) * 2015-07-13 2022-05-18 President and Fellows of Harvard College Methods for retrievable information storage using nucleic acids
WO2017024049A1 (en) 2015-08-06 2017-02-09 Pacific Biosciences Of California, Inc. Single-molecule nanofet sequencing systems and methods
CN105112516A (en) * 2015-08-14 2015-12-02 深圳市瀚海基因生物科技有限公司 Single-molecule targeted sequencing method, device and system and application
KR20180050411A (en) 2015-09-18 2018-05-14 트위스트 바이오사이언스 코포레이션 Oligonucleotide mutant library and its synthesis
CN108698012A (en) 2015-09-22 2018-10-23 特韦斯特生物科学公司 Flexible substrates for nucleic acid synthesis
CN108350496B (en) 2015-10-01 2023-04-18 生命技术公司 Polymerase compositions and kits, and methods of use and manufacture thereof
KR20180055905A (en) 2015-10-09 2018-05-25 아큐라젠 홀딩스 리미티드 Methods and compositions for the enrichment of amplification products
JP7300831B2 (en) 2015-10-19 2023-06-30 ダブテイル ゲノミクス エルエルシー Methods for Genome Assembly, Haplotype Phasing, and Target-Independent Nucleic Acid Detection
US10280411B2 (en) 2015-10-27 2019-05-07 Pacific Biosciences of California, In.c Methods, systems, and reagents for direct RNA sequencing
EP3377656A4 (en) 2015-11-18 2019-03-27 Pacific Biosciences of California, Inc. Loading nucleic acids onto substrates
WO2017087696A1 (en) 2015-11-18 2017-05-26 Pacific Biosciences Of California, Inc. Methods and compositions for loading of polymerase complexes
WO2017087974A1 (en) 2015-11-20 2017-05-26 Pacific Biosciences Of California, Inc. Protected dye-labeled reagents
CN113321943A (en) 2015-11-20 2021-08-31 加利福尼亚太平洋生物科学股份有限公司 Labeled nucleotide analogs, reaction mixtures, and sequencing methods and systems
US10676788B2 (en) 2015-11-20 2020-06-09 Pacific Biosciences Of California, Inc. Modified nucleotide reagents
EP3384077A4 (en) 2015-12-01 2019-05-08 Twist Bioscience Corporation Functionalized surfaces and preparation thereof
CN115927547A (en) 2015-12-03 2023-04-07 安可济控股有限公司 Methods and compositions for forming ligation products
EP3402903B1 (en) 2016-01-15 2022-03-02 Quantapore, Inc. Optically-based nanopore analysis with reduced background
TWI734748B (en) 2016-02-17 2021-08-01 美商太斯萊特健康股份有限公司 Sensor and device for lifetime imaging and detection applications
JP7441003B2 (en) 2016-02-23 2024-02-29 ダブテイル ゲノミクス エルエルシー Generation of phased read sets and haplotype phasing for genome assembly
EP3455628A4 (en) 2016-05-09 2019-12-04 Biodesy, Inc. Methods and devices for detection of peripheral membrane protein interactions using nonlinear optical techniques
SG11201810088SA (en) 2016-05-13 2018-12-28 Dovetail Genomics Llc Recovering long-range linkage information from preserved samples
EP3458586B1 (en) 2016-05-16 2022-12-28 Accuragen Holdings Limited Method of improved sequencing by strand identification
EP3458465A1 (en) * 2016-05-20 2019-03-27 Quantum-si Incorporated Labeled nucleotide compositions and methods for nucleic acid sequencing
GB201609220D0 (en) 2016-05-25 2016-07-06 Oxford Nanopore Tech Ltd Method
US10655174B2 (en) 2016-05-27 2020-05-19 Roche Sequencing Solutions, Inc. Tagged multi-nucleotides useful for nucleic acid sequencing
US10711299B2 (en) * 2016-06-01 2020-07-14 Quantum-Si Incorporated Pulse caller and base caller
US10544457B2 (en) 2016-06-14 2020-01-28 Pacific Biosciences Of California, Inc. Methods and compositions for enriching compositions for polymerase enzyme complexes
JP2019522983A (en) 2016-07-05 2019-08-22 クアンタポール， インコーポレイテッド Optical-based nanopore sequencing
CN116397014A (en) 2016-07-20 2023-07-07 测序健康公司 Systems and methods for nucleic acid sequencing
US10711300B2 (en) 2016-07-22 2020-07-14 Pacific Biosciences Of California, Inc. Methods and compositions for delivery of molecules and complexes to reaction sites
SG11201901296TA (en) 2016-08-15 2019-03-28 Accuragen Holdings Ltd Compositions and methods for detecting rare sequence variants
AU2017315294B2 (en) 2016-08-22 2023-12-21 Twist Bioscience Corporation De novo synthesized nucleic acid libraries
US10669580B2 (en) 2016-08-26 2020-06-02 Roche Sequencing Solutions, Inc. Tagged nucleotides useful for nanopore detection
US10417457B2 (en) 2016-09-21 2019-09-17 Twist Bioscience Corporation Nucleic acid based data storage
ES2870639T3 (en) 2016-10-24 2021-10-27 Geneinfosec Inc Hiding information present in nucleic acids
TWI658139B (en) 2016-11-01 2019-05-01 體學生物科技股份有限公司 Recombinant dna polymerase for improved incorporation of nucleotide analogues
JP7050068B2 (en) 2016-12-16 2022-04-07 クアンタム－エスアイ インコーポレイテッド Compact beam forming and steering assembly
EP3555972A1 (en) 2016-12-16 2019-10-23 Quantum-si Incorporated Compact mode-locked laser module
CN110366613A (en) 2016-12-16 2019-10-22 特韦斯特生物科学公司 The Mutant libraries of immunological synapse and its synthesis
AU2017378990A1 (en) 2016-12-19 2019-06-20 Quantum-Si Incorporated Polymerizing enzymes for sequencing reactions
JP7149275B2 (en) 2016-12-22 2022-10-06 クアンタム－エスアイ インコーポレイテッド Integrated photodetector with direct binning pixels
AU2017385424A1 (en) * 2016-12-27 2019-08-01 Qingdao MGI Tech Co., Ltd. Single fluorescent dye based sequencing method
US11550939B2 (en) 2017-02-22 2023-01-10 Twist Bioscience Corporation Nucleic acid based data storage using enzymatic bioencryption
CN110913865A (en) 2017-03-15 2020-03-24 特韦斯特生物科学公司 Library of variants of immune synapses and synthesis thereof
AU2018256358A1 (en) 2017-04-18 2019-11-07 Dovetail Genomics, Llc Nucleic acid characteristics as guides for sequence assembly
JP7356909B2 (en) 2017-05-05 2023-10-05 クアンタム－エスアイ インコーポレイテッド Substrates with modified surface reactivity and antifouling properties in biological reactions
WO2018231864A1 (en) 2017-06-12 2018-12-20 Twist Bioscience Corporation Methods for seamless nucleic acid assembly
KR102628876B1 (en) 2017-06-12 2024-01-23 트위스트 바이오사이언스 코포레이션 Methods for seamless nucleic acid assembly
CA3068273A1 (en) 2017-06-21 2018-12-27 Bluedot Llc Systems and methods for identification of nucleic acids in a sample
US11655504B2 (en) 2017-07-24 2023-05-23 Quantum-Si Incorporated High intensity labeled reactant compositions and methods for sequencing
JP2020532515A (en) 2017-08-30 2020-11-12 ペンデュラム セラピューティクス， インコーポレイテッド Methods and compositions for the treatment of microbiome-related disorders
CN111566125A (en) 2017-09-11 2020-08-21 特韦斯特生物科学公司 GPCR binding proteins and synthesis thereof
GB201714748D0 (en) * 2017-09-13 2017-10-25 Univ Oxford Innovation Ltd Single-molecule phenotyping and sequencing of nucleic acid molecules
CA3076378A1 (en) 2017-09-21 2019-03-28 Genapsys, Inc. Systems and methods for nucleic acid sequencing
WO2019060716A1 (en) 2017-09-25 2019-03-28 Freenome Holdings, Inc. Methods and systems for sample extraction
GB201715684D0 (en) 2017-09-28 2017-11-15 Univ Gent Means and methods for single molecule peptide sequencing
US11099202B2 (en) 2017-10-20 2021-08-24 Tecan Genomics, Inc. Reagent delivery system
CA3079613A1 (en) 2017-10-20 2019-04-25 Twist Bioscience Corporation Heated nanowells for polynucleotide synthesis
US11162138B2 (en) 2017-10-30 2021-11-02 Pacific Biosciences Of California, Inc. Multi-amplitude modular labeled compounds
EP3704521A4 (en) 2017-11-03 2021-07-07 Pacific Biosciences of California, Inc. Systems, devices, and methods for improved optical waveguide transmission and alignment
CN108034699A (en) * 2017-11-22 2018-05-15 深圳市瀚海基因生物科技有限公司 A kind of method for detecting polynucleotide and/or non-specific adsorption
US10655168B2 (en) 2017-12-22 2020-05-19 Pacific Biosciences Of California, Inc. Modified biotin-binding proteins for immobilization
CA3088911A1 (en) 2018-01-04 2019-07-11 Twist Bioscience Corporation Dna-based digital information storage
NL2020618B1 (en) * 2018-01-12 2019-07-18 Illumina Inc Real time controller switching
CN111971748A (en) 2018-01-26 2020-11-20 宽腾矽公司 Machine learning enabled pulses and base calls for sequencing devices
AU2019214956A1 (en) 2018-01-31 2020-08-27 Dovetail Genomics, Llc Sample prep for DNA linkage recovery
CN112368397A (en) * 2018-03-13 2021-02-12 萨摩尔股份有限公司 Method for single molecule sequencing
US11203782B2 (en) 2018-03-29 2021-12-21 Accuragen Holdings Limited Compositions and methods comprising asymmetric barcoding
GB201807793D0 (en) 2018-05-14 2018-06-27 Oxford Nanopore Tech Ltd Method
AU2019270243A1 (en) 2018-05-18 2021-01-07 Twist Bioscience Corporation Polynucleotides, reagents, and methods for nucleic acid hybridization
WO2019241733A1 (en) 2018-06-15 2019-12-19 Quantum-Si Incorporated Data acquisition control for advanced analytic instruments having pulsed optical sources
US11391626B2 (en) 2018-06-22 2022-07-19 Quantum-Si Incorporated Integrated photodetector with charge storage bin of varied detection time
EP3814531A4 (en) 2018-06-29 2022-04-06 Pacific Biosciences Of California, Inc. Methods and compositions for delivery of molecules and complexes to reaction sites
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
US10704094B1 (en) 2018-11-14 2020-07-07 Element Biosciences, Inc. Multipart reagents having increased avidity for polymerase binding
US20200149095A1 (en) * 2018-11-14 2020-05-14 Element Biosciences, Inc. Low binding supports for improved solid-phase dna hybridization and amplification
AU2019392932B2 (en) 2018-12-07 2023-11-02 Element Biosciences, Inc. Flow cell device and use thereof
US11166996B2 (en) 2018-12-12 2021-11-09 Flagship Pioneering Innovations V, Inc. Anellovirus compositions and methods of use
US11613772B2 (en) 2019-01-23 2023-03-28 Quantum-Si Incorporated High intensity labeled reactant compositions and methods for sequencing
CA3130693A1 (en) 2019-02-19 2020-08-27 Ultima Genomics, Inc. Linkers and methods for optical detection and sequencing
KR20210143766A (en) 2019-02-26 2021-11-29 트위스트 바이오사이언스 코포레이션 Variant Nucleic Acid Libraries for the GLP1 Receptor
KR20210144698A (en) 2019-02-26 2021-11-30 트위스트 바이오사이언스 코포레이션 Variant Nucleic Acid Libraries for Antibody Optimization
EP3956469A4 (en) * 2019-04-15 2023-01-25 Universal Sequencing Technology Corporation Nanogap device for biopolymer identification
US11272132B2 (en) 2019-06-07 2022-03-08 Pacific Biosciences Of California, Inc. Temporal differential active pixel sensor
EP3966611B1 (en) 2019-06-14 2024-03-06 Quantum-Si Incorporated Grating coupler with increased beam alignment sensitivity
US11332738B2 (en) 2019-06-21 2022-05-17 Twist Bioscience Corporation Barcode-based nucleic acid sequence assembly
US11287422B2 (en) 2019-09-23 2022-03-29 Element Biosciences, Inc. Multivalent binding composition for nucleic acid analysis
KR20220079943A (en) 2019-10-11 2022-06-14 퀀텀-에스아이 인코포레이티드 Surface modification in vapor phase
KR102358418B1 (en) * 2019-12-31 2022-02-04 주식회사 제노헬릭스 A METHOD OF DETECTING small RNA
KR20220143847A (en) 2020-01-21 2022-10-25 퀀텀-에스아이 인코포레이티드 Compounds and methods for selective C-terminal labeling
US11807851B1 (en) 2020-02-18 2023-11-07 Ultima Genomics, Inc. Modified polynucleotides and uses thereof
CN111235248B (en) * 2020-03-26 2022-11-29 北京博奥汇玖生物科技有限公司 Base-balanced amplicon molecular labeling method
WO2022204321A1 (en) 2021-03-24 2022-09-29 Ambry Genetics Corporation Conservative concurrent evaluation of dna modifications
WO2022271701A2 (en) * 2021-06-23 2022-12-29 Reticula, Inc. Methods and compositions for nucleic acid sequencing
CN114958995B (en) * 2022-04-27 2023-07-18 深圳赛陆医疗科技有限公司 Gene sequencing method
WO2023245203A1 (en) * 2022-06-18 2023-12-21 Reticula, Inc. Methods for single cell sequencing and error rate reduction
CN115232867B (en) * 2022-07-21 2024-01-30 深圳赛陆医疗科技有限公司 Rapid second-generation gene sequencing method

Family Cites Families (124)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US14850A (en) * 1856-05-13 Improved cartridge-opener
US4994373A (en) 1983-01-27 1991-02-19 Enzo Biochem, Inc. Method and structures employing chemically-labelled polynucleotide probes
US5200313A (en) * 1983-08-05 1993-04-06 Miles Inc. Nucleic acid hybridization assay employing detectable anti-hybrid antibodies
DE3477271D1 (en) * 1984-12-28 1989-04-20 Ibm Waveguide for an optical near-field microscope
US5849478A (en) * 1986-08-14 1998-12-15 Cashman; Daniel P. Blocked-polymerase polynucleotide immunoassay method and kit
CA1338457C (en) 1986-08-22 1996-07-16 Henry A. Erlich Purified thermostable enzyme
US4795699A (en) * 1987-01-14 1989-01-03 President And Fellows Of Harvard College T7 DNA polymerase
DE3841565C2 (en) * 1988-12-09 1998-07-09 Europ Lab Molekularbiolog Methods for sequencing nucleic acids
GB8910880D0 (en) 1989-05-11 1989-06-28 Amersham Int Plc Sequencing method
US5547839A (en) * 1989-06-07 1996-08-20 Affymax Technologies N.V. Sequencing of surface immobilized polymers utilizing microflourescence detection
US5541099A (en) * 1989-08-10 1996-07-30 Life Technologies, Inc. Cloning and expression of T5 DNA polymerase reduced in 3'-to-5' exonuclease activity
US5302509A (en) 1989-08-14 1994-04-12 Beckman Instruments, Inc. Method for sequencing polynucleotides
US5545522A (en) * 1989-09-22 1996-08-13 Van Gelder; Russell N. Process for amplifying a target polynucleotide sequence using a single primer-promoter complex
IL97222A (en) * 1990-02-16 1995-08-31 Orion Yhtymae Oy Method and reagent for determining specific nucleotide variations
US5401847A (en) 1990-03-14 1995-03-28 Regents Of The University Of California DNA complexes with dyes designed for energy transfer as fluorescent markers
US5079169A (en) * 1990-05-22 1992-01-07 The Regents Of The Stanford Leland Junior University Method for optically manipulating polymer filaments
EP0834576B1 (en) 1990-12-06 2002-01-16 Affymetrix, Inc. (a Delaware Corporation) Detection of nucleic acid sequences
ATE286971T1 (en) * 1991-01-21 2005-01-15 Elan Pharm Inc TEST AND MODEL FOR ALZHEIMERS DISEASE
US6004744A (en) * 1991-03-05 1999-12-21 Molecular Tool, Inc. Method for determining nucleotide identity through extension of immobilized primer
US5405747A (en) 1991-09-25 1995-04-11 The Regents Of The University Of California Office Of Technology Transfer Method for rapid base sequencing in DNA and RNA with two base labeling
US6048690A (en) 1991-11-07 2000-04-11 Nanogen, Inc. Methods for electronic fluorescent perturbation for analysis and electronic perturbation catalysis for synthesis
US5612188A (en) * 1991-11-25 1997-03-18 Cornell Research Foundation, Inc. Automated, multicompartmental cell culture system
FR2685346B1 (en) * 1991-12-18 1994-02-11 Cis Bio International PROCESS FOR THE PREPARATION OF DOUBLE-STRANDED RNA, AND ITS APPLICATIONS.
DE4203983A1 (en) 1992-02-11 1992-08-20 Ulf Greufe DEVICE AND METHOD FOR IMPROVING THE PERFORMANCE DIGIT IN THE REFRIGERANT CIRCUIT
US5470705A (en) * 1992-04-03 1995-11-28 Applied Biosystems, Inc. Probe composition containing a binding domain and polymer chain and methods of use
GB9208733D0 (en) 1992-04-22 1992-06-10 Medical Res Council Dna sequencing method
US5403708A (en) 1992-07-06 1995-04-04 Brennan; Thomas M. Methods and compositions for determining the sequence of nucleic acids
AU4190893A (en) * 1992-07-17 1994-01-20 Suntory Limited Megakaryocyte differentiation factor
US5503980A (en) 1992-11-06 1996-04-02 Trustees Of Boston University Positional sequencing by hybridization
EP1262564A3 (en) * 1993-01-07 2004-03-31 Sequenom, Inc. Dna sequencing by mass spectrometry
US5677196A (en) * 1993-05-18 1997-10-14 University Of Utah Research Foundation Apparatus and methods for multi-analyte homogeneous fluoro-immunoassays
WO1995006138A1 (en) 1993-08-25 1995-03-02 The Regents Of The University Of California Microscopic method for detecting micromotions
US5470710A (en) 1993-10-22 1995-11-28 University Of Utah Automated hybridization/imaging device for fluorescent multiplex DNA sequencing
US5538848A (en) * 1994-11-16 1996-07-23 Applied Biosystems Division, Perkin-Elmer Corp. Method for detecting nucleic acid amplification using self-quenching fluorescence probe
US5654419A (en) * 1994-02-01 1997-08-05 The Regents Of The University Of California Fluorescent labels and their use in separations
JP3175110B2 (en) * 1994-02-07 2001-06-11 オーキッド・バイオサイエンシーズ・インコーポレイテッド Genetic bit analysis of ligase / polymerase mediated single nucleotide polymorphisms and their use in genetic analysis
US5681699A (en) * 1994-02-11 1997-10-28 Cedars-Sinai Medical Center Methods of diagnosing ulcerative colitis and Crohn's disease
US5695934A (en) 1994-10-13 1997-12-09 Lynx Therapeutics, Inc. Massively parallel sequencing of sorted polynucleotides
US5664036A (en) * 1994-10-13 1997-09-02 Accuphotonics, Inc. High resolution fiber optic probe for near field optical microscopy and method of making same
EP0803058B1 (en) * 1994-12-30 2008-11-05 Georgetown University Fluorometric assay for detecting nucleic acid cleavage
US5601982A (en) 1995-02-07 1997-02-11 Sargent; Jeannine P. Method and apparatus for determining the sequence of polynucleotides
AU5171696A (en) 1995-02-27 1996-09-18 Ely Michael Rabani Device, compounds, algorithms, and methods of molecular characterization and manipulation with molecular parallelism
US5624845A (en) * 1995-03-16 1997-04-29 International Business Machines Corporation Assembly and a method suitable for identifying a code
EP0732584A3 (en) * 1995-03-16 1999-06-30 International Business Machines Corporation An assembly and a method suitable for identifying a code sequence of a biomolecule
US5961923A (en) 1995-04-25 1999-10-05 Irori Matrices with memories and uses thereof
DE19515552A1 (en) 1995-04-27 1996-10-31 Europ Lab Molekularbiolog Simultaneous sequencing of nucleic acids
EP0745686A1 (en) 1995-06-01 1996-12-04 Roche Diagnostics GmbH The use of DNA polymerase 3'-intrinsic editing activity
US6399355B1 (en) * 1995-06-07 2002-06-04 The Trustees Of Columbia University In The City Of New York Non-naturally occurring targeted lipolytic compounds and related compositions and methods
JPH0954103A (en) * 1995-06-08 1997-02-25 Nikon Corp Probe and its manufacture, and scanning probe microscope using the probe
US5856174A (en) * 1995-06-29 1999-01-05 Affymetrix, Inc. Integrated nucleic acid diagnostic device
WO1997005156A1 (en) * 1995-07-27 1997-02-13 Carsten Behrens A new achiral linker reagent for the incorporation of multiple amino groups into oligonucleotides
US5661028A (en) 1995-09-29 1997-08-26 Lockheed Martin Energy Systems, Inc. Large scale DNA microsequencing device
US6027890A (en) 1996-01-23 2000-02-22 Rapigene, Inc. Methods and compositions for enhancing sensitivity in the analysis of biological-based assays
JP3327112B2 (en) * 1996-04-19 2002-09-24 松下電器産業株式会社 Anisotropic graphite thin film substrate and applied device using the same
EP0912761A4 (en) * 1996-05-29 2004-06-09 Cornell Res Foundation Inc Detection of nucleic acid sequence differences using coupled ligase detection and polymerase chain reactions
US5846727A (en) * 1996-06-06 1998-12-08 Board Of Supervisors Of Louisiana State University And Agricultural & Mechanical College Microsystem for rapid DNA sequencing
CA2410120A1 (en) * 1996-08-28 1998-03-05 The Johns Hopkins University School Of Medicine Method for detecting cell proliferative disorders
US6258533B1 (en) * 1996-11-01 2001-07-10 The University Of Iowa Research Foundation Iterative and regenerative DNA sequencing method
US5858671A (en) * 1996-11-01 1999-01-12 The University Of Iowa Research Foundation Iterative and regenerative DNA sequencing method
US5963923A (en) * 1996-11-12 1999-10-05 Garber; Howard B. System and method for trading having a principal market maker
GB9626815D0 (en) 1996-12-23 1997-02-12 Cemu Bioteknik Ab Method of sequencing DNA
US6066245A (en) * 1996-12-27 2000-05-23 Genetic Biosystems, Inc. Method and apparatus for scanning fluorescently labeled particles
US6136543A (en) * 1997-01-31 2000-10-24 Hitachi, Ltd. Method for determining nucleic acids base sequence and apparatus therefor
US6206607B1 (en) * 1997-02-10 2001-03-27 John, J. Medico, Jr. Christine Meoli Medico Family Trust Environmental porous pavement construction, and method for manufacturing pavement construction
US5773308A (en) * 1997-02-10 1998-06-30 The United States Of America As Represented By The Secretary Of The Navy Photoactivatable o-nitrobenzyl polyethylene glycol-silane for the production of patterned biomolecular arrays
IL156002A0 (en) 1997-02-12 2003-12-23 Eugene Y Chan Methods and products for analyzing polymers
US6403311B1 (en) 1997-02-12 2002-06-11 Us Genomics Methods of analyzing polymers using ordered label strategies
EP1498494A3 (en) 1997-04-01 2007-06-20 Solexa Ltd. Method of nucleic acid sequencing
EP0972082A4 (en) * 1997-04-04 2007-04-25 Caliper Life Sciences Inc Closed-loop biochemical analyzers
US5888778A (en) * 1997-06-16 1999-03-30 Exact Laboratories, Inc. High-throughput screening method for identification of genetic mutations or disease-causing microorganisms using segmented primers
RU2198221C2 (en) * 1997-07-28 2003-02-10 Медикал Биосистемз Лтд. Method of polynucleotide sequencing and device for its realization
JP3889134B2 (en) * 1997-09-29 2007-03-07 日本分光株式会社 Near-field optical microspectrophotometer
CA2305449A1 (en) 1997-10-10 1999-04-22 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
US5958694A (en) * 1997-10-16 1999-09-28 Caliper Technologies Corp. Apparatus and methods for sequencing nucleic acids in microfluidic systems
US6200752B1 (en) * 1998-01-14 2001-03-13 Joseph R. Lakowicz Method and composition for detecting the presence of a nucleic acid sequence in a sample
CA2330673C (en) * 1998-05-01 2009-05-26 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
US6326725B1 (en) 1998-05-26 2001-12-04 Micron Technology, Inc. Focusing electrode for field emission displays and method
GB0002310D0 (en) 2000-02-01 2000-03-22 Solexa Ltd Polynucleotide sequencing
IL141148A0 (en) 1998-07-30 2002-02-10 Solexa Ltd Arrayed biomolecules and their use in sequencing
CA2340228A1 (en) 1998-08-13 2000-02-24 U.S. Genomics, Inc. Optically characterizing polymers
US6210896B1 (en) 1998-08-13 2001-04-03 Us Genomics Molecular motors
US6263286B1 (en) 1998-08-13 2001-07-17 U.S. Genomics, Inc. Methods of analyzing polymers using a spatial network of fluorophores and fluorescence resonance energy transfer
US6280939B1 (en) * 1998-09-01 2001-08-28 Veeco Instruments, Inc. Method and apparatus for DNA sequencing using a local sensitive force detector
DE19844931C1 (en) † 1998-09-30 2000-06-15 Stefan Seeger Procedures for DNA or RNA sequencing
US6221592B1 (en) * 1998-10-20 2001-04-24 Wisconsin Alumi Research Foundation Computer-based methods and systems for sequencing of individual nucleic acid molecules
CA2355816C (en) * 1998-12-14 2007-10-30 Li-Cor, Inc. A system and methods for nucleic acid sequencing of single molecules by polymerase synthesis
GB9828785D0 (en) 1998-12-30 1999-02-17 Amersham Pharm Biotech Ab Sequencing systems
ATE556149T1 (en) * 1999-02-23 2012-05-15 Caliper Life Sciences Inc MANIPULATION OF MICROPARTICLES IN MICROFLUIDIC SYSTEMS
JP2002537858A (en) 1999-03-10 2002-11-12 エーエスエム サイエンティフィック， インコーポレイテッド Methods for direct sequencing of nucleic acids
AU3567900A (en) 1999-03-30 2000-10-16 Solexa Ltd. Polynucleotide sequencing
GB9907813D0 (en) 1999-04-06 1999-06-02 Medical Biosystems Ltd Synthesis
GB9907812D0 (en) 1999-04-06 1999-06-02 Medical Biosystems Ltd Sequencing
US7056661B2 (en) * 1999-05-19 2006-06-06 Cornell Research Foundation, Inc. Method for sequencing nucleic acid molecules
US6818395B1 (en) 1999-06-28 2004-11-16 California Institute Of Technology Methods and apparatus for analyzing polynucleotide sequences
JP2001013056A (en) * 1999-07-02 2001-01-19 Minolta Co Ltd Formation method for very small opening
CA2381361A1 (en) 1999-08-13 2001-02-22 U.S. Genomics, Inc. Methods and apparatuses for stretching polymers
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
WO2001023610A2 (en) 1999-09-29 2001-04-05 Solexa Ltd. Polynucleotide sequencing
GB9923644D0 (en) 1999-10-06 1999-12-08 Medical Biosystems Ltd DNA sequencing
AU1471001A (en) 1999-11-04 2001-05-14 California Institute Of Technology Methods and apparatus for analyzing polynucleotide sequences
US6399335B1 (en) 1999-11-16 2002-06-04 Advanced Research And Technology Institute, Inc. γ-phosphoester nucleoside triphosphates
GB0002389D0 (en) 2000-02-02 2000-03-22 Solexa Ltd Molecular arrays
CA2412567A1 (en) 2000-06-07 2001-12-13 Li-Cor, Inc. Charge-switch nucleotides
US6936702B2 (en) * 2000-06-07 2005-08-30 Li-Cor, Inc. Charge-switch nucleotides
GB0016472D0 (en) 2000-07-05 2000-08-23 Amersham Pharm Biotech Uk Ltd Sequencing method and apparatus
GB0016473D0 (en) 2000-07-05 2000-08-23 Amersham Pharm Biotech Uk Ltd Sequencing method
CN100462433C (en) * 2000-07-07 2009-02-18 维西根生物技术公司 Real-time sequence determination
AU2002211389A1 (en) 2000-10-03 2002-04-15 California Institute Of Technology Microfluidic devices and methods of use
ATE374259T1 (en) 2001-01-30 2007-10-15 Solexa Ltd PRODUCTION OF MATRICES FROM POLYNUCLEOTIDES
EP1368497A4 (en) 2001-03-12 2007-08-15 California Inst Of Techn Methods and apparatus for analyzing polynucleotide sequences by asynchronous base extension
GB0112238D0 (en) 2001-05-18 2001-07-11 Medical Biosystems Ltd Sequencing method
US7118907B2 (en) 2001-06-06 2006-10-10 Li-Cor, Inc. Single molecule detection systems and methods
WO2002101095A1 (en) 2001-06-08 2002-12-19 U.S. Genomics, Inc. Methods and products for analyzing nucleic acids using nick translation
GB0119719D0 (en) 2001-08-13 2001-10-03 Solexa Ltd DNA sequence analysis
US7244566B2 (en) * 2001-08-29 2007-07-17 Ge Healthcare Bio-Sciences Corp. Analyte detection
US7041812B2 (en) 2001-08-29 2006-05-09 Amersham Biosciences Corp Labeled nucleoside polyphosphates
ATE458832T1 (en) * 2001-11-28 2010-03-15 Bio Rad Laboratories PARALLEL SCORING OF POLYMORPHISMS USING AMPLIFICATION AND ERROR CORRECTION
JP4355210B2 (en) * 2001-11-30 2009-10-28 フルイディグム コーポレイション Microfluidic device and method of using microfluidic device
US7919235B2 (en) 2002-09-30 2011-04-05 F. Hoffman-La Roche Ag Oligonucleotides for genotyping thymidylate synthase gene
US7354706B2 (en) * 2003-09-09 2008-04-08 The Regents Of The University Of Colorado, A Body Corporate Use of photopolymerization for amplification and detection of a molecular recognition event
WO2005047521A2 (en) * 2003-11-10 2005-05-26 Investigen, Inc. Methods of preparing nucleic acid for detection
EP3169805B1 (en) * 2014-07-15 2018-08-29 Illumina, Inc. Biochemically activated electronic device

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