US20040185484A1 - Method for preparing single-stranded DNA libraries - Google Patents
Method for preparing single-stranded DNA libraries Download PDFInfo
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- US20040185484A1 US20040185484A1 US10/767,894 US76789404A US2004185484A1 US 20040185484 A1 US20040185484 A1 US 20040185484A1 US 76789404 A US76789404 A US 76789404A US 2004185484 A1 US2004185484 A1 US 2004185484A1
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Definitions
- the invention relates to protein chemistry, molecular biology, and methods of preparing single-stranded libraries for sequence analysis. More specifically, this invention includes methods of processing DNA for use in amplification and sequencing reactions.
- PCR polymerase chain reaction
- two primers are designed to hybridize to the template DNA at positions complementary to respective primers that are separated on the DNA template molecule by some number of nucleotides.
- the base sequence of the template DNA between and including the primers is amplified by repetitive complementary strand extension reactions whereby the number of copies of the target DNA fragments is increased by several orders of magnitude.
- Amplification is exponential as 2 n , where n equals the number of amplification cycles.
- the amplified DNA may be sequenced through conventional sequencing methods (see, U.S. Pat. No. 6,274,320).
- Samples comprising large template DNA or whole DNA genomes comprising long nucleotide sequences are not conducive to efficient amplification by PCR. These long molecules do not naturally possess sequences useful for primer hybridization. In addition, if primer hybridization sequences are added to double stranded DNA molecules, it is difficult to ascertain the directionality of the amplified DNA molecules and this frustrates sequencing efforts.
- U.S. Pat. No. 5,508,169 describes that subsets of nucleic acid fragments may be indexed (i.e., selected or targeted) based upon the information contained in non-identical 5′-protruding or 3′-protruding cohesive ends. This includes fragments having 3, 4 or 5 base cohesive ends, such as those revealed by cleavage of DNA by Type II restriction endonucleases and interrupted palindrome recognizing type II restriction endonucleases.
- indexing linkers nucleic acid molecules similar to adaptors (called indexing linkers) which contain protruding single strands complementary to the cohesive ends of cleavage sites of restriction endonucleases (rather than the recognition sequences).
- Various functional groups or specific nucleic acid sequences designed for particular applications may be selectively attached to the aforementioned subsets of fragments. Selective attachment of indexing linkers having known base sequences in their cohesive ends to a subset of fragments bearing the complementary cohesive ends can be used for the detection, identification, isolation, amplification, and manipulation of the subset of fragments.
- U.S. Pat. No. 6,468,748 describes a method of sorting genes and/or gene fragments comprising several steps.
- ds cDNA molecules are prepared from mRNA molecules by reverse transcription, using a poly-T primer optionally having a general primer-template sequence upstream from the poly-T sequence, yielding ds cDNA molecules having the poly-T sequence, optionally having the general primer-template sequence.
- the ds cDNA molecules are digested with a restriction enzyme that produces digested cDNA molecules with cohesive ends having overhanging ssDNA sequences of a constant number of arbitrary nucleotides.
- the digested cDNA molecules are ligated to a set of dsDNA oligonucleotide adaptors, each of which adaptors has at one of its ends a cohesive-end ssDNA adaptor sequence complementary to one of the possible overhanging ssDNA sequences of the digested cDNA, at the opposite end a specific primer-template sequence specific for the ssDNA adaptor complementary sequence, and in between the ends a constant sequence that is the same for all of the different adaptors of the set.
- the ligated cDNA molecules are amplified by separate polymerase chain reactions, utilizing for each separate polymerase chain reaction a primer that anneals to the cDNA poly-T sequence optionally having the cDNA general primer-template, and a primer from a set of different specific primers that anneal to the cDNA specific primer-template sequences.
- the amplified cDNA molecules are sorted into nonoverlapping groups by collecting the amplification products after each separate polymerase chain reaction, each group of amplified cDNA molecules determined by the specific primer that annealed to the specific primer-template sequence and primed the polymerase chain reaction.
- U.S. Pat. No. 5,863,722 describes a method and materials for sorting polynucleotides with oligonucleotide tags.
- the oligonucleotide tags are capable of hybridizing to complementary oligomeric compounds consisting of subunits having enhanced binding strength and specificity as compared to natural oligonucleotides.
- tag complements Such complementary oligomeric compounds are referred to as “tag complements.”
- Subunits of tag complements may consist of monomers of non-natural nucleotide analogs, referred to as “antisense monomers” or they may comprise oligomers having lengths in the range of 3 to 6 nucleotides or analogs thereof, including antisense monomers, the oligomers being selected from a minimally cross-hybridizing set. In such a set, a duplex made up of an oligomer of the set and the complement of any other oligomer of the set contains at least two mismatches.
- an oligomer of a minimally cross-hybridizing set at best forms a duplex having at least two mismatches with the complement of any other oligomer of the same set.
- Tag complements attached to a solid phase support are used to sort polynucleotides from a mixture of polynucleotides each containing a tag. The surface of each support is derivatized by only one type of tag complement which has a particular sequence.
- the polynucleotides to be sorted each comprise an oligonucleotide tag in the repertoire, such that identical polynucleotides have the same tag and different polynucleotides have different tags.
- subpopulations of identical polynucleotides are sorted onto particular beads or regions.
- the subpopulations of polynucleotides can then be manipulated on the solid phase support by micro-biochemical techniques.
- U.S. Pat. No. 5,728,524 describes a process for the categorization of nucleic acid sequences in which these sequences are linked to a population of adaptor molecules, each exhibiting specificity for linking to a sequence including a predetermined nucleotide base. The resulting linked sequences are then categorized based upon selection for the particular base.
- the art does not describe methods for generating libraries of unknown fragment sequences additionally comprising two known sequences, each different than the other, one being adjoined at each end.
- This invention describes a novel method for preparing a library of multiple nucleic acid sequences from a sample where the library is suited to further quantitative and comparative analysis, particularly where the multiple nucleic acid sequences are unknown and derived from large template DNA or whole (or partial) genome DNA.
- sequences of single stranded DNA are prepared from a sample of large template DNA or whole or partial DNA genomes through fragmentation, polishing, adaptor ligation, nick repair, and isolation of ssDNA.
- the present invention provides a method for clonally isolating a library comprising a plurality of ssDNAs, wherein each ssDNA comprises a first single stranded universal adaptor and a second single stranded universal adaptor, the method comprising:
- the single stranded DNA molecules are delivered into droplets in a water-in-oil emulsion (i.e., microreactors), or onto multiwell surfaces (e.g., PicoTiter plates).
- a water-in-oil emulsion i.e., microreactors
- multiwell surfaces e.g., PicoTiter plates
- the single stranded DNA molecules may be delivered via attachment to a solid support (e.g., beads).
- a solid support e.g., beads
- the adaptor ligated DNA molecules comprising a first double stranded universal adaptor and second double stranded universal adaptor is attached to a solid support via one strand of the double stranded universal adaptor (via the first or second universal adaptor).
- the adaptor ligated DNA molecules which have not attached to a solid support are washed away, and one strand of the adaptor ligated DNA molecules is released. This generates a mixture comprising a plurality of ssDNAs comprising a population of single stranded molecules with a first and second universal adaptor pair, thereby generating a library.
- sequence of the fragmented DNA may be known or unknown.
- sequence of the fragmented DNA, particularly the sequence of the ends of the fragmented DNA is unknown.
- the present invention includes a method for generating a ssDNA library linked to solid supports comprising: (a) generating a library of ssDNA templates; (b) attaching the ssDNA templates to solid supports; and (c) isolating the solid supports on which one ssDNA template is attached.
- the present invention includes a library of mobile solid supports made by the method disclosed herein.
- FIG. 1 is a schematic representation of the entire process of library preparation including the steps of template DNA fragmentation (FIG. 1A), end polishing (FIG. 1B), adaptor ligation (FIG. 1C), nick repair, strand extension and gel isolation (FIG. 1D).
- FIG. 1 also depicts a representative agarose gel containing a sample preparation of a 180-350 base pair adenovirus DNA library according to the methods of this invention.
- FIG. 2A is a schematic representation of the universal adaptor design according one embodiment of the present invention.
- Each universal adaptor is generated from two complementary ssDNA oligonucleotides that are designed to contain a 20 bp nucleotide sequence for PCR priming, a 20 bp nucleotide sequence for sequence priming and a unique 4 bp discriminating sequence comprised of a non-repeating nucleotide sequence (i.e., ACGT, CAGT, etc.).
- a non-repeating nucleotide sequence i.e., ACGT, CAGT, etc.
- FIG. 2B depicts a representative universal adaptor sequence pair for use with the invention.
- Adaptor A sense strand SEQ ID NO:1;
- Adaptor A antisense strand SEQ ID NO:2;
- Adaptor B sense strand SEQ ID NO:3;
- Adaptor B antisense strand SEQ ID NO:4.
- FIG. 2C is a schematic representation of universal adaptor design for use with the invention.
- FIG. 3 represents the strand displacement and extension of nicked double-stranded DNA fragments according to the present invention.
- double-stranded DNA fragments will be generated that contain two nicked regions following T4 DNA ligase treatment (FIG. 3A).
- a strand displacing enzyme i.e., Bst DNA polymerase I
- FIG. 3B strand displace the nicked strand and complete nucleotide extension of the strand
- FIG. 3D non-nicked double-stranded DNA fragments
- FIG. 4 represents the isolation of directionally-ligated single-stranded DNA according to the present invention using streptavidin-coated magnetic beads.
- double-stranded DNA will contain adaptors in four possible combinations: AA, BB, AB, and BA.
- universal adaptor B contains a 5′-biotin
- magnetic streptavidin-coated solid supports are used to capture and isolate the AB, BA, and BB populations (population AA is washed away).
- the BB population is retained on the beads as each end of the double-stranded DNA is attached to a bead and is not released.
- FIG. 5 represents an insert flanked by PCR primers and sequencing primers.
- FIG. 6 represents truncated product produced by PCR primer mismatch at cross-hybridization region (CHR).
- FIGS. 7A-7D depict the assembly for the nebulizer used for the methods of the invention.
- a tube cap was placed over the top of the nebulizer (FIG. 7A) and the cap was secured with a nebulizer clamp assembly (FIG. 7B).
- the bottom of the nebulizer was attached to the nitrogen supply (FIG. 7C) and the entire device was wrapped in parafilm (FIG. 7D).
- FIG. 8 depicts representative BioAnalyzer output from analysis of a single stranded DNA library.
- FIG. 9A depicts representative results for LabChip analysis of a single stranded DNA library following nebulization and polishing.
- FIG. 9B depicts representative size distribution results for an adaptor-ligated single stranded DNA library following nebulization, polishing, and gel purification.
- FIG. 10 depicts the calculation for primer candidates based on melting temperature.
- This invention relates to the preparation of sample DNA for amplification and sequencing reactions.
- the invention includes a method for preparing the sample DNA comprised of the following steps: (a) fragmenting large template DNA or whole genomic DNA samples to generate a plurality of digested DNA fragments; (b) creating compatible ends on the plurality of digested DNA samples; (c) ligating a set of universal adaptor sequences onto the ends of fragmented DNA molecules to make a plurality of adaptor-ligated DNA molecules, wherein each universal adaptor sequence comprises a PCR primer sequence, a sequencing primer sequence and a discriminating key sequence and wherein one adaptor is attached to biotin; (d) separating and isolating the plurality of ligated DNA fragments; (e) removing any portion of the plurality of ligated DNA fragments; (f) nick repair and strand extension of the plurality of ligated DNA fragments; (g) attaching each of the ligated DNA fragments to a solid support; and (h) isolating populations
- the term “universal adaptor” refers to two complementary and annealed oligonucleotides that are designed to contain a nucleotide sequence for PCR priming and a nucleotide sequence for sequence priming.
- the universal adaptor may further include a unique discriminating key sequence comprised of a non-repeating nucleotide sequence (i.e., ACGT, CAGT, etc.).
- a set of universal adaptors comprises two unique and distinct double-stranded sequences that can be ligated to the ends of double-stranded DNA. Therefore, the same universal adaptor or different universal adaptors can be ligated to either end of the DNA molecule.
- the universal adaptor may be referred to as a single stranded universal adaptor.
- discriminating key sequence refers to a sequence including a combination of the four deoxyribonucleotides (i.e., A, C, G, T). The same discriminating sequence can be used for an entire library of DNA fragments. Alternatively, different discriminating key sequences can be used to track libraries of DNA fragments derived from different organisms. Longer discriminating key sequences can be used for a mixture of more than one library.
- the term “plurality of molecules” refers to DNA isolated from the same source, whereby different organisms may be prepared separately by the same method.
- the plurality of DNA samples is derived from large segments of DNA, e.g., genomic DNA, cDNA, viral DNA, plasmid DNA, cosmid DNA, artificial chromosome DNA (e.g., BACs, YACs, MACs, PACs), synthetic DNA, phagemid DNA, phasemid DNA, or from reverse transcripts of viral RNA.
- This DNA may be derived from any source, including any mammal (i.e., human, nonhuman primate, rodent, or canine), plant, bird, reptile, fish, fungus, bacteria, or virus.
- library refers to a subset of smaller sized DNA species generated from a larger DNA template, e.g., a segmented or whole genome.
- unique refers to a sequence that does not exist or exists at an extremely low copy level within the DNA molecules to be amplified or sequenced.
- compatible refers to an end of double stranded DNA to which an adaptor molecule may be attached (i.e., blunt end or cohesive end).
- fragmenting refers to a process by which a larger molecule of DNA is converted into smaller pieces of DNA.
- large template DNA would be DNA of more than 5 kb, 10 kb, or 25 kb, preferably more than 500 kb, more preferably more than 1 MB, and most preferably 5 MB or larger.
- stringent hybridization conditions refers to those conditions under which only fully complimentary sequences will hybridize to each other.
- the fragmentation of the DNA sample can be done by any means known to those of ordinary skill in the art.
- the fragmenting is performed by enzymatic, chemical, or mechanical means.
- the mechanical means may include sonication, French press, HPLC, HydroShear (GeneMachines, San Carlos, Calif.), and nebulization.
- the enzymatic means may be performed by digestion with Deoxyribonuclease I (DNase I), nonspecific nucleases, or single or multiple restriction endonucleases.
- DNase I Deoxyribonuclease I
- the fragmentation results in ends for which the sequence adjacent to the end is not known.
- the sequence adjacent to the end may be at least 5 bases, 10 bases, 20 bases, 30 bases, or 50 bases.
- the enzymatic means is DNase I.
- DNase I is a versatile enzyme that nonspecifically cleaves double-stranded DNA (dsDNA) to release 5′-phosphorylated oligonucleotide products.
- DNase I has optimal activity in buffers containing Mn 2+ , Mg 2+ and Ca 2+ .
- the purpose of the DNase I digestion step is to fragment a large DNA genome into smaller species comprising a library.
- the cleavage characteristics of DNase I will result in random digestion of template DNA (i.e., minimal sequence bias) and in the predominance of blunt-ended dsDNA fragments when used in the presence of manganese-based buffers (Melgar, E. and D. A.
- DNase I is used to digest large template DNA or whole genome DNA for 1-2 minutes to generate a population of oligonucleotides that range from 50 to 500 bp, or 50 to 700 bp.
- the DNase I digestion is performed at a temperature of 10° C.-37° C.
- the digested DNA fragments are 50 bp to 700 bp in length.
- nucleic acid fragmentation Another preferred method for nucleic acid fragmentation is mechanical fragmentation.
- Mechanical fragmentation methods include sonication and nebulization, and use of HydroShear, HPLC, and French Press devices.
- Sonication may be performed by a tube containing DNA in a suitable buffer (i.e., 10 mM Tris, 0.1 mM EDTA) and sonicating for a varying number of 10 second bursts using maximum output and continuous power Sonicators are commercially available from, e.g., Misonix Inc. (Farmingdale, N.Y.), and can be used essentially as described by Bankier and Barrell (Bankier, A. T., Weston, K. M., and Barrell, B.
- sonication it is preferred to maintain the nucleic acid at a uniform temperature by keeping the sample on ice. Constant temperature conditions, at 0° C. for example, are preferred to maintain an even fragment distribution.
- the optimal conditions for sonication may be determined empirically for a given DNA sample before preparative sonication is performed. For example, aliquots of DNA can be treated for different times under sonication and the size and quality of DNA can be analyzed by PAGE. Once optimal sonication conditions are determined, the remaining DNA can be sonicated according to those pre-determined conditions.
- nucleic acid fragmentation is treatment by nebulizers (e.g., protocols, and hardware available from GeneMachines, San Carlos, Calif. Also see U.S. Pat. Nos. 5,506,100 and 5,610,010).
- nebulizers e.g., protocols, and hardware available from GeneMachines, San Carlos, Calif. Also see U.S. Pat. Nos. 5,506,100 and 5,610,010).
- hydrodynamic shearing forces are used to fragment DNA strands.
- DNA in a aqueous solution can be passed through a tube with an abrupt contraction. As the solution approaches the contraction, the fluid accelerates to maintain the volumetric flow rate through the smaller area of the contraction. During this acceleration, drag forces stretch the DNA until it snaps.
- the DNA solution can be passed several times (e.g., 15 to 20 cycles) through the contraction until the fragments are too short for further shearing.
- DNA may be suspended in various solutions including, but not limited to, water, Tris buffer, Tris-EDTA buffer, and Tris-EDTA with up to 0.5 M NaCl.
- Polishing digestion of genomic DNA (gDNA) templates with DNase I in the presence of Mn 2+ produces fragments of DNA that are either blunt-ended or have protruding termini with one or two nucleotides in length.
- fragmentation of DNA by mechanical means provides a combination of fragments with blunt-ends or overhanging ends.
- Polishing also called end repair refers to the conversion of non-blunt ended DNA into blunt ended DNA.
- polishing may be performed by treatment with a single strand-specific exonuclease, such as BAL32 nuclease or Mung Bean nuclease. Generally, the nuclease should be calibrated prior to use.
- blunt ends are created with Pfu DNA polymerase.
- blunt ends are created with other DNA polymerases such as T4 DNA polymerase or Klenow DNA polymerase.
- Pfu “polishing” or blunt ending can be used to increase the amount of blunt-ended species generated following genomic template digestion with DNase I.
- Pfu DNA polymerase fills in 5′ overhangs.
- Pfu DNA polymerase exhibits 3′ ⁇ 5′ exonuclease activity.
- the enzyme can be used to remove single and double nucleotide extensions to further increase the amount of blunt-ended DNA fragments available for adaptor ligation (see, e.g., Costa, G. L. and M. P. Weiner. 1994a.
- the universal adaptors can be added to each DNA fragment.
- the universal adaptors are designed to include: 1) a set of unique PCR priming regions that are typically 10-20 bp in length (any suitable size may be used) located adjacent to; 2) a set of unique sequencing priming regions that are typically 10-20 bp in length (any suitable size may be used) optionally followed by; 3) a unique discriminating key sequence (e.g., 1-12 bp in length) including a combination of at least one of each of the four deoxyribonucleotides (i.e., A, C, G, T).
- the discriminating key sequence is 4 bases in length.
- the discriminating key sequence may be combinations of 1-4 bases.
- the key sequence includes one of each of the four nucleotides.
- the key sequence includes one or more ribonucleotides, e.g., U.
- each unique universal adaptor is forty-four bp (44 bp) in length, although any suitable size may be used.
- the universal adaptors are ligated, using T4 DNA ligase, onto each end of the DNA fragment to generate a total nucleotide addition of 88 bp to each DNA fragment, although any suitable size may be used.
- Different universal adaptors can be specifically designed for each DNA library preparation and therefore provide a unique identifier for each organism. For example, different library preparations can employ different key sequences. It is understood that the size and sequence of the universal adaptors may be modified as would be apparent to one of skill in the art. Thus, the adaptors for use with the invention are not limited to the size and sequence described herein.
- first and second single-stranded oligonucleotides may be ordered from a commercial vendor (e.g., Integrated DNA Technologies, IA or Operon Technologies, CA).
- a commercial vendor e.g., Integrated DNA Technologies, IA or Operon Technologies, CA.
- all of the first adaptors for a library share one nucleotide sequence, including a PCR priming sequence, sequencing primer sequence, and discriminating key sequence, while all of the second adaptors share another nucleotide sequence.
- the universal adaptor oligonucleotide sequences are modified during synthesis with one or more phosphorothioate linkages in place of phosphodiester linkages.
- adaptor oligonucleotides can include two or three phosphorothioate linkages at both the 5′ and 3′ ends, or at one end.
- Unmodified oligonucleotides are typically subject to rapid degradation by contaminating nucleases that catalyze the hydrolytic cleavage of the phosphodiester linkage between nucleotide bases.
- nuclease-resistant chemistry available for use in oligonucleotide applications is the phosphorothioate modification. In phosphorothioates, a sulfur atom replaces a non-bridging oxygen in the oligonucleotide backbone making it resistant to all forms of nuclease digestion (i.e.
- Each oligonucleotide is HPLC-purified to ensure there are no contaminating or spurious oligonucleotide sequences in the synthetic oligonucleotide preparation.
- the universal adaptors are designed to allow directional ligation to the fragmented DNA.
- Each set of double-stranded universal adaptors is designed with a PCR priming region that includes non-complementary 5′ four-base overhangs which are unable to ligate to each other or to the blunt-ended DNA fragment.
- binding occurs between the 3′ end of the adaptor and the 5′ end of the DNA fragment or between the 3′ end of the DNA fragment and the 5′ end of the adaptor.
- Double-stranded universal adaptor sequences are generated using single-stranded oligonucleotides that are designed with sequences that allow primarily complimentary oligonucleotides to anneal, and to prevent cross-hybridization between two non-complimentary oligonucleotides.
- 95% of the universal adaptors are formed from the annealing of complimentary oligonucleotides.
- 97% of the universal adaptors are formed from the annealing of complimentary oligonucleotides.
- 99% of the universal adaptors are formed from the annealing of complimentary oligonucleotides.
- 100% of the universal adaptors are formed from the annealing of complimentary oligonucleotides.
- an overhanging nucleotide e.g., T
- a polymerase is used to add an overhanging nucleotide (e.g., A) to the blunt 5′ ends of the template DNA.
- the overhanging nucleotides of the adaptors and template are complementary to allow more efficient adaptor ligation.
- a plasmid capture system is used in accordance with the disclosed methods.
- the double stranded universal adaptors can be inserted into a plasmid.
- the adaptor region can include the following sequences, in order: Restriction Site(s), PCR Primer Sequence 1, Sequencing Primer Sequence 1, Key Sequence 1, Restriction Site(s), Key Sequence 2, Sequencing Primer Sequence 2, PCR Priming Sequence 2, and Restriction Site(s).
- the plasmid is digested with one or more restriction enzymes that cut between Key Sequence 1 and Key Sequence 2.
- the fragmented template DNA is ligated between Key Sequence 1 and Key Sequence 2.
- the ligated construct is then digested to cut after PCR Priming Sequence 2.
- the digested end next to PCR Priming Sequence 2 is filled in with biotinylated nucleotides.
- the biotinylated construct is digested to cut prior to PCR Primer Sequence 1.
- the Adaptor-DNA fragment-Adaptor-biotin segment is excised and isolated, e.g., by binding to a streptavidin magnetic bead.
- Other embodiments of the plasmid capture system are also possible through application of known cloning techniques. These embodiments are also encompassed by the invention.
- One of the two adaptors can be linked to a support binding moiety.
- a 5′ biotin is added to the first universal adaptor to allow subsequent isolation of ssDNA template and noncovalent coupling of the universal adaptor to the surface of a solid support that is saturated with a biotin-binding protein (e.g., streptavidin, NeutrAvidinTM or avidin).
- Suitable supports include but are not limited to magnetic beads, affinity columns, membranes (e.g., PDVF membrane, nitrocellulose, etc.), which can be coated with streptavidin or another member of a binding pair.
- Other linkages are well known in the art and may be used in place of biotin-streptavidin.
- the solid support is a bead, preferably a polystyrene bead.
- the bead has a diameter of about 2.8 ⁇ m, although any suitable size may be used.
- the bead is a paramagnetic bead (e.g., Dynal Biotech, Inc., Lake Success, N.Y.). As used herein, this bead is referred to as a “sample prep bead”.
- Each universal adaptor may be prepared by combining and annealing two ssDNA oligonucleotides, one containing the sense sequence and the second containing the antisense (complementary) sequence. Schematic representation of the universal adaptor design is depicted in FIG. 2.
- the universal adaptor ligation results in the formation of fragmented DNAs with adaptors on each end, unbound single adaptors, and adaptor dimers.
- agarose gel electrophoresis is used as a method to separate and isolate the adapted DNA library population from the unligated single adaptors and adaptor dimer populations.
- the fragments may be separated by size exclusion chromatography, filtration, sucrose sedimentation, or other nucleic acid separation techniques known to those skilled in the art.
- the procedure of DNase I digestion of DNA typically yields a library population that ranges from 50-700 bp.
- the addition of the 88 bp universal adaptor set will shift the DNA library population to a larger size and will result in a migration profile in the size range of approximately 130-800 bp; adaptor dimers will migrate at 88 bp; and adaptors not ligated will migrate at 44 bp. Therefore, numerous double-stranded DNA libraries in sizes ranging from 200-800 bp can be physically isolated from the agarose gel and purified using standard gel extraction techniques. In one embodiment, gel isolation of the adapted ligated DNA library will result in the recovery of a library population ranging in size from 200-500 bp. Other methods of distinguishing adaptor-ligated fragments are known to one of skill in the art.
- gaps will be present at the 3′ junctions of the fragmented DNAs following ligase treatment (see FIG. 3A). These “gaps” or “nicks” can be filled in by using a DNA polymerase enzyme that can bind to, strand displace, and extend the nicked DNA fragments.
- DNA polymerases that lack 3′ ⁇ 5′ exonuclease activity but exhibit 5′ ⁇ 3′ exonuclease activity have the ability to recognize nicks, displace the nicked strands, and extend the strand in a manner that results in the repair of the nicks and in the formation of non-nicked double-stranded DNA (see FIG. 3B and 3C) (Hamilton, S. C., J. W. Farchaus and M. C. Davis. 2001. DNA polymerases as engines for biotechnology. BioTechniques 31:370).
- DNA polymerases that can be used in the methods of the invention include, for example, E. coli DNA polymerase I, Thermoanaerobacter thermohydrosulfuricus polymerase I, and bacteriophage phi 29.
- the strand displacing enzyme Bacillus stearothermophilus polymerase I Bacillus stearothermophilus polymerase I ( Bst DNA polymerase I) is used to repair the nicked dsDNA and results in non-nicked dsDNA (see FIG. 3D).
- the ligase is T4 DNA ligase and the kinase is T4 polynucleotide kinase.
- ssDNAs comprising both the first and second adaptor molecules may be isolated.
- Double-stranded DNA libraries will have adaptors bound in the following configurations:
- a and B correspond to the first and second adaptors.
- the desired populations are designated with asterisks.
- the universal adaptors are designed such that only one universal adaptor has a 5′ biotin moiety.
- universal adaptor B has a 5′ biotin moiety
- streptavidin-coated sample prep beads can be used to bind all double-stranded DNA library species with universal adaptor B.
- Genomic library populations that contain two universal adaptor A species will not contain a 5′ biotin moiety and will not bind to streptavidin-containing sample prep beads and thus can be washed away.
- the only species that will remain attached to beads are those with universal adaptors A and B and those with two universal adaptor B sequences.
- DNA species with two universal adaptor B sequences will be bound to streptavidin-coated sample prep beads at each end, as each strand comprised in the double strand will be bound.
- Double-stranded DNA species with a universal adaptor A and a universal adaptor B will contain a single 5′ biotin moiety and thus will be bound to streptavidin-coated beads at only one end. Where the sample prep beads are magnetic, the beads will remain coupled to a solid support when magnetized.
- ssDNA libraries that are created according to the methods of the invention are quantitated to calculate the number of molecules per unit volume.
- the molecules can be annealed to a solid support that includes oligonucleotide capture primers that are complementary to the PCR priming regions of the universal adaptor ends of the ssDNA species.
- beads comprising capture primers annealed to ssDNA library molecules can be transferred to a thermocycler to allow PCR amplification. Clonal populations of single species of single stranded DNA captured on DNA beads may then sequenced.
- the solid support is a bead, preferably a sepharose bead. As used herein, this bead is referred to as a “DNA capture bead”.
- the beads used herein may be of any convenient size and fabricated from any number of known materials.
- Example of such materials include: inorganics, natural polymers, and synthetic polymers. Specific examples of these materials include: cellulose, cellulose derivatives, acrylic resins, glass; silica gels, polystyrene, gelatin, polyvinyl pyrrolidone, co-polymers of vinyl and acrylamide, polystyrene cross-linked with divinylbenzene or the like (see, Merrifield Biochemistry 1964, 3, 1385-1390), polyacrylamides, latex gels, polystyrene, dextran, rubber, silicon, plastics, nitrocellulose, celluloses, natural sponges, silica gels, glass, metals plastic, cellulose, cross-linked dextrans (e.g., SephadexTM) and agarose gel (SepharoseTM) and solid phase supports known to those of skill in the art.
- cross-linked dextrans e.g., SephadexTM
- the diameter of the DNA capture bead is 20-70 ⁇ m. In a preferred embodiment, the diameter of the DNA capture bead is 20-50 ⁇ m. In a more preferred embodiment, the diameter of the DNA capture bead is about 30 ⁇ m.
- the invention includes a method for generating a library of solid supports comprising: (a) preparing a population of ssDNA templates according to the methods disclosed herein; (b) attaching each DNA template to a solid support such that there is one molecule of DNA per solid support; (c) amplifying the population of single-stranded templates such that the amplification generates a clonal population of each DNA fragment on each solid support; (d) sequencing clonal populations of the ssDNA templates.
- the solid support is a DNA capture bead.
- the DNA is genomic DNA, cDNA, or reverse transcripts of RNA (e.g., viral RNA).
- the DNA may be attached to the solid support, for example, via a biotin-streptavidin linkage, a covalent linkage, or by complementary oligonucleotide hybridization.
- each DNA template is ligated to a set of universal adaptors.
- the universal adaptor pair comprises a PCR primer sequence, a sequencing primer sequence, and a discriminating key sequence. Single-stranded DNAs with unique ends are isolated and then attached to a solid support and exposed to amplification techniques for clonal amplification.
- the DNA may be amplified by PCR.
- the invention provides a library attached to solid supports made by the methods described herein.
- the DNA prepared by this method may be used for many molecular biological procedures, such as linear extension, rolling circle amplification, PCR, and sequencing.
- the linkage reaction can be driven, for example, by using a high molar ratio of bead to DNA.
- the capture of single-stranded DNA molecules follows a Poisson distribution and results in subsets of beads having no DNA attached, one molecule of DNA attached, or more than one molecule of DNA attached.
- a single stranded nucleic acid template to be amplified is attached to a capture bead.
- the nucleic acid template may be attached to the solid support capture bead in any manner known in the art. Numerous methods exist in the art for attaching DNA to a solid support such as the preferred microscopic bead. According to the present invention, covalent chemical attachment of the DNA to the bead can be accomplished by using standard coupling agents, such as water-soluble carbodiimide, to link the 5′-phosphate on the DNA to amine-coated capture beads through a phosphoamidate bond.
- Another alternative is to first couple specific oligonucleotide linkers to the bead using similar chemistry, and to then use DNA ligase to link the DNA to the linker on the bead.
- Other linkage chemistries to join the oligonucleotide to the beads include the use of N-hydroxysuccinamide (NHS) and its derivatives.
- one end of the oligonucleotide may contain a reactive group (such as an amide group) which forms a covalent bond with the solid support, while the other end of the linker contains a second reactive group that can bond with the oligonucleotide to be immobilized.
- the oligonucleotide is bound to the DNA capture bead by covalent linkage.
- non-covalent linkages such as chelation or antigen-antibody complexes, may also be used to join the oligonucleotide to the bead.
- Oligonucleotide linkers can be employed which specifically hybridize to unique sequences at the end of the DNA fragment, such as the overlapping end from a restriction enzyme site or the “sticky ends” of bacteriophage lambda based cloning vectors, but blunt-end ligations can also be used beneficially. These methods are described in detail in U.S. Pat. No. 5,674,743. It is preferred that any method used to immobilize the beads will continue to bind the immobilized oligonucleotide throughout the steps in the methods of the invention.
- each capture bead is designed to have a plurality of nucleic acid primers that recognize (i.e., are complementary to) a portion of the nucleic template, and the nucleic acid template is thus hybridized to the capture bead.
- nucleic acid primers that recognize (i.e., are complementary to) a portion of the nucleic template, and the nucleic acid template is thus hybridized to the capture bead.
- clonal amplification of the template species is desired, so it is preferred that only one unique nucleic acid template is attached to any one capture bead.
- the beads used herein may be of any convenient size and fabricated from any number of known materials.
- Example of such materials include: inorganics, natural polymers, and synthetic polymers. Specific examples of these materials include: cellulose, cellulose derivatives, acrylic resins, glass, silica gels, polystyrene, gelatin, polyvinyl pyrrolidone, co-polymers of vinyl and acrylamide, polystyrene cross-linked with divinylbenzene or the like (as described, e.g., in Merrifield, Biochemistry 1964, 3, 1385-1390), polyacrylamides, latex gels, polystyrene, dextran, rubber, silicon, plastics, nitrocellulose, natural sponges, silica gels, control pore glass, metals, cross-linked dextrans (e.g., SephadexTM) agarose gel (SepharoseTM), and solid phase supports known to those of skill in the art.
- the capture beads are Sepharose beads approximately
- capture beads with or without attached nucleic acid template may be suspended in a heat stable water-in-oil emulsion. It is contemplated that a plurality of the microreactors include only one template and one bead. There may be many droplets that do not contain a template or which do not contain a bead. Likewise there may be droplets that contain more than one copy of a template.
- the emulsion may be formed according to any suitable method known in the art. One method of creating emulsion is described below but any method for making an emulsion may be used. These methods are known in the art and include adjuvant methods, counter-flow methods, cross-current methods, rotating drum methods, and membrane methods.
- the size of the microcapsules may be adjusted by varying the flow rate and speed of the components. For example, in dropwise addition, the size of the drops and the total time of delivery may be varied.
- the emulsion contains a density of about 3,000 beads encapsulated per microliter.
- This method involves compartmentalizing a gene, expressing the gene, and sorting the compartmentalized gene based on the expressed product.
- the microencapsulated sorting method of Griffith is not suitable for parallel analysis of multiple microcapsules because their nucleic acid product is not anchored and cannot be anchored. Since the nucleic acids of Griffiths are not anchored, they would be mixed together during demulsification.
- the emulsion is preferably generated by adding beads to an amplification solution.
- amplification solution means the sufficient mixture of reagents that is necessary to perform amplification of template DNA.
- a PCR amplification solution is provided in the Examples below. It will be appreciated that various modifications may be made to the amplification solution based on the type of amplification being performed and whether the template DNA is attached to the beads or provided in solution.
- the mixture of beads and amplification solution is added dropwise into a spinning mixture of biocompatible oil (e.g., light mineral oil, Sigma) and allowed to emulsify.
- biocompatible oil e.g., light mineral oil, Sigma
- the beads and amplification solution are added dropwise into a cross-flow of biocompatible oil.
- the oil used may be supplemented with one or more biocompatible emulsion stabilizers.
- emulsion stabilizers may include Atlox 4912, Span 80, and other recognized and commercially available suitable stabilizers.
- the emulsion is heat stable to allow thermal cycling, e.g., to at least 94° C., at least 95° C., or at least 96° C.
- the droplets formed range in size from about 5 microns to about 500 microns, more preferably from about 10 microns to about 350 microns, even more preferably from about 50 to 250 microns, and most preferably from about 100 microns to about 200 microns.
- cross-flow fluid mixing allows for control of the droplet formation, and uniformity of droplet size.
- smaller water droplets not containing beads may be present in the emulsion.
- the microreactors should be sufficiently large to encompass sufficient amplification reagents for the degree of amplification required. However, the microreactors should be sufficiently small so that a population of microreactors, each containing a member of a DNA library, can be amplified by conventional laboratory equipment, e.g., PCR thermocycling equipment, test tubes, incubators and the like.
- microreactors allows amplification of complex mixtures of templates (e.g., genomic DNA samples or whole cell RNA) without intermixing of sequences, or domination by one or more templates (e.g., PCR selection bias; see, Wagner et al., 1994, Suzuki and Giovannoni, 1996; Chandler et al., 1997, Polz and Cavanaugh, 1998).
- templates e.g., genomic DNA samples or whole cell RNA
- the optimal size of a microreactor may be on average 100 to 200 microns in diameter. Microreactors of this size would allow amplification of a DNA library comprising about 600,000 members in a suspension of microreactors of less than 10 ml in volume. For example, if PCR is the chosen amplification method, 10 ml of microreactors would fit into 96 tubes of a regular thermocycler with 96 tube capacity. In a preferred embodiment, the suspension of 600,000 microreactors would have a volume of less than 1 ml. A suspension of less than 1 ml may be amplified in about 10 tubes of a conventional PCR thermocycler. In a most preferred embodiment, the suspension of 600,000 microreactors would have a volume of less than 0.5 ml.
- Another embodiment of the invention is directed to a method of performing nucleic acid amplification with a template and a bead, but without attachment of the template to the bead.
- the bead may comprise a linker molecule that can bind the amplified nucleic acid after amplification.
- the linker may be a linker that can be activated.
- Such linkers are well known and include temperature sensitive or salt sensitive binding pairs such as streptavidin/biotin and antibodies/antigen.
- the template nucleic acid may be encapsulated with a bead and amplified. Following amplification, the amplified nucleic acid may be linked to the beads, e.g., by adjustments in temperature or salt concentration.
- the template nucleic acid may be amplified, while attached or unattached to beads, by any suitable method of amplification including transcription-based amplification systems (Kwoh D. et al., Proc. Natl. Acad Sci. (U.S.A.) 86:1173 (1989); Gingeras T. R. et al., WO 88/10315; Davey, C. et al., EP Publication No. 329,822; Miller, H. I. et al., WO 89/06700), “RACE” (Frohman, M.
- a nucleic acid template is amplified after encapsulation with a bead in a microreactor.
- a nucleic acid template is amplified after distribution onto a multiwell surface, e.g., a PicoTiter plate.
- DNA amplification is performed by PCR.
- PCR according to the present invention may be performed by encapsulating the target nucleic acid with a PCR solution comprising all the necessary reagents for PCR. Then, PCR may be accomplished by exposing the emulsion to any suitable thermocycling regimen known in the art. In a preferred embodiment, 30 to 50 cycles, preferably about 40 cycles, of amplification are performed. It is desirable, but not necessary, that following the amplification procedure there be one or more hybridization and extension cycles following the cycles of amplification. In a preferred embodiment, 10 to 30 cycles, preferably about 25 cycles, of hybridization and extension are performed (e.g., as described in the examples).
- the template DNA is amplified until typically at least 10,000 to 50,000,000 copies are immobilized on each bead. It is recognized that for nucleic acid detection applications, fewer copies of template are required. For nucleic acid sequencing applications we prefer that at least two million to fifty million copies, preferably about ten million to thirty million copies of the template DNA are immobilized on each bead. The skilled artisan will recognize that the size of bead (and capture site thereon) determines how many captive primers can be bound (and thus how many amplified templates may be captured onto each bead).
- the invention encompasses a method for clonally isolating a library comprising a plurality of single stranded DNA molecules comprising: a) fragmenting large template DNA molecules to generate a plurality of fragmented DNA molecules; b) attaching a first or second universal double stranded adaptor to a first end of each fragmented DNA molecule and a first or second universal adaptor to a second end of each fragmented DNA molecule to form a mixture of adaptor ligated DNA molecules; c) isolating a plurality of single stranded DNA molecules each comprising a first single stranded universal adaptor and a second single stranded universal adaptor to obtain a library; and d) delivering the single stranded DNA molecules into reactors such that a plurality of the reactors include one DNA molecule, thereby clonally isolating the library.
- the invention encompasses a method for generating a library comprising a plurality of single stranded DNA molecules, comprising: a) fragmenting large or whole genomic template DNA molecules to generate a plurality of fragmented DNA molecules; b) ligating a first universal double stranded adaptor or a second universal adaptor to a first end of each fragmented DNA molecule and a first universal adaptor or second universal adaptor to a second end of each fragmented DNA molecule to produce a mixture of adaptor ligated DNA molecules, wherein the first universal adaptor contains a moiety that binds to a solid support; c) attaching to a solid support those DNA molecules comprising a first double stranded universal adaptor; d) washing away adaptor ligated DNA molecules which have not attached to the solid support; e) strand separating those adaptor ligated DNA molecules that are attached to the solid support to release a plurality of single stranded DNA molecules comprising a first single strand
- (f) can be accomplished by: i) delivering the single stranded DNA molecules onto a location on a reactor array; or ii) delivering the single stranded DNA molecules into droplets in a water-in-oil emulsion.
- the first universal double stranded adaptor or the second universal adaptor can be attached to the fragmented DNA molecules by ligation.
- DNA ligase may be used.
- These methods can further include a step of repairing single stranded nicks in the mixture of adaptor ligated DNA molecules using DNA repair and modifying enzymes, such as a polymerase, ligase, kinase, or combinations thereof.
- the enzymes can include Bacillus stearothermophilus polymerase I, T4 ligase, and T4 polynucleotide kinase.
- the template DNA for these methods can comprise genomic DNA, cDNA, plasmid DNA, cosmid DNA, artificial chromosome DNA, synthetic DNA, phasemid DNA, phagemid DNA, or reverse transcripts. Fragmenting may be performed by enzymatic, chemical, or mechanical means.
- DNase I enzyme can be used in a digestion performed at a temperature of 10-37° C. for 1-2 minutes. Alternatively, a restriction enzyme may be used.
- the mechanical means can be a nebulizer, French Press, sonicator, or a HydroShear.
- the fragmented DNA molecules can be 50 bp to 700 bp in length.
- the compatible ends can be blunt ends, or the compatible ends can include an A or T overhang. Blunt ends can be created with an enzyme such as Pfu polymerase, T4 DNA polymerase, and Klenow fragments.
- the first or second double stranded universal adaptor may comprise one or more phosphorothioate linkages, and may be attached to a biotin moiety.
- the first double stranded universal adaptors or the second double stranded universal adaptors or both double stranded universal adaptors may comprise a discriminating key sequence.
- the discriminating key sequence is 3-12 nucleotides in length and comprise at least one nucleotide selected from the group consisting of A, G, C, U, and T.
- the first and second double stranded universal adaptor may comprise a PCR priming sequence and a sequencing primer sequence.
- the PCR priming sequence is 10-20 base pairs in length
- the sequencing primer sequence is 10-20 base pairs in length.
- the PCR priming sequence and the sequencing primer sequence may overlap.
- the mixture of adaptor ligated DNA molecules is separated by a method selected from the group consisting of gel electrophoresis, filtration, size exclusion chromatography, and sucrose sedimentation.
- the plurality of single stranded DNA molecules may be obtained by a treatment selected from the group consisting of low salt treatment, high pH treatment, and chemical denaturation treatment.
- the plurality of single stranded DNA molecules may be attached to a DNA capture bead.
- the DNA capture bead may comprise a component of a binding pair, such as avidin/biotin, ligand/receptor, antigen/antibody or complementary nucleotides.
- the DNA capture bead is a paramagnetic bead.
- the invention also encompasses a method for generating a single stranded DNA library attached to solid supports comprising: a) generating a plurality of single stranded DNA templates; b) attaching each of the plurality of ssDNA templates to a solid support; and c) isolating the solid supports on which the single stranded DNA templates are attached.
- the invention further encompasses a method for generating a single stranded DNA library attached to solid supports comprising: a) fragmenting large template DNA molecules to generate a plurality of fragmented DNA molecules; b) attaching a first or second universal double stranded adaptor to a first end of each fragmented DNA molecule and a first or second universal adaptor to a second end of each fragmented DNA molecule to make a mixture of adaptor ligated DNA molecules; c) isolating those single stranded DNA molecules which comprise a first single stranded universal adaptor and a second single stranded universal adaptor; and d) attaching the isolated single stranded molecules from (c) to a solid support.
- the solid support may be a DNA capture bead, and the DNA may be genomic DNA, cDNA, plasmid DNA, cosmid DNA, artificial chromosome DNA, synthetic DNA, phasemid DNA, or phagemid DNA.
- the DNA is attached to the solid support via a binding pair such as avidin/biotin, ligand/receptor, antigen/antibody and complementary nucleotides.
- a binding pair such as avidin/biotin, ligand/receptor, antigen/antibody and complementary nucleotides.
- a library of mobile solid supports made by this method.
- the invention comprises a nucleic acid molecule comprising a first adaptor, a fragment of template DNA, and a second adaptor, wherein the first adaptor and second adaptor each comprise a sequencing primer, a PCR primer, and a discriminating key sequence, and wherein the first adaptor and second adaptor, when dissociated, do not cross-hybridize to each other under stringent hybridization conditions.
- the PCR primer may be 10-20 base pairs in length
- the sequencing primer may be 10-20 base pairs in length
- the discriminating key sequence may be 3 to 12 base pairs in length.
- the template DNA can be genomic DNA, cDNA plasmid DNA, cosmid DNA, artificial chromosome DNA, synthetic DNA, phasemid DNA, or phagemid DNA.
- the nucleic acid molecule when dissociated, has minimal cross-hybridization to dissociated template DNA.
- Also encompassed by the invention is a method for preparing single stranded DNA molecules, comprising: a) fragmenting large or whole genomic template DNA molecules to generate a plurality of fragmented DNA molecules; b) ligating a first universal double stranded adaptor or a second universal adaptor to a first end of each fragmented DNA molecule and a first universal adaptor or second universal adaptor to a second end of each fragmented DNA molecule to produce a mixture of adaptor ligated DNA molecules; c) attaching adaptor ligated DNA molecules comprising a first double stranded universal adaptor and a second double stranded adaptor to a solid support via one strand of the first double stranded universal adaptor; d) washing away adaptor ligated DNA molecules which have not attached to the solid support; e) strand separating those adaptor ligated DNA molecules that are attached to the solid support to release a plurality of single stranded DNA molecules comprising a first single stranded universal
- the isolating step may comprise attaching the nucleic acid templates to a bead, or encapsulating the nucleic acid template in an emulsion of a water-in-oil emulsion.
- the nucleic acid template may be encapsulated with a bead that can bind the nucleic acid.
- the delivering step may comprise delivering the sequestered nucleic acid to a plurality of reaction centers, wherein each reaction center is a well on a picotiter plate.
- the method can further comprising the step of attaching the isolated single stranded molecules each individually to a solid support.
- the DNA should be of high quality and free from contaminants such as proteins, nucleases, lipids, and other chemicals (such as residual EDTA from preparation) and salts. It is preferred that genomic DNA should have a 260/280 ratio of 1.8 or higher. If it is desired to sequence the genome of only one organism, then the DNA should be quality checked to ensure that there is no contaminating DNA. For example: a preparation of human DNA may be checked by PCR to ensure that it is not contaminated by bacterial DNA molecules. Another method of checking for contamination is by restriction digestion patterns and especially restriction digestion followed by Southern Blot using suitable probes known to be specific for an organism (e.g., human or mouse) and a second probe known to be specific for a possible contaminating organism (e.g., E. coli ). If it is desired, the DNA should originate from a single clone of the organism (e.g., a colony if from bacteria).
- DNase I The purpose of the DNase I digestion step is to fragment a large stretch of DNA such as a whole genome or a large portion of a genome into smaller species. This population of smaller-sized DNA species generated from a single DNA template is referred to as a “library”.
- DNase I is an endonuclease which cleaves double-stranded template DNA. The cleavage characteristics of DNase I allow random digestion of template DNA (i.e., minimal sequence bias) and will result in the predominance of blunt-ended, double-stranded DNA fragments when used in the presence of manganese-based buffers (Melgar and Goldthwait 1968).
- the digestion of genomic templates by DNase I is dependent on three factors: i) quantity of enzyme used (units); ii) temperature of digestion (° C.); and iii) incubation time (minutes).
- the DNase I digestion conditions outlined below were optimized to yield DNA libraries in a size range from 50-700 base pairs (bp).
- DNA was obtained and prepared to a concentration of 0.3 mg/ml in Tris-HCl (10 mM, pH 7-8). A total of 134 ⁇ l of DNA (15 ⁇ g) was needed for this preparation. It is recommended to not use DNA preparations diluted with buffers containing EDTA (i.e., TE, Tris/EDTA). The presence of EDTA is inhibitory to enzyme digestion with DNase I. If the DNA preparation contains EDTA, it is important that the DNA be “salted” out of solution and reconstituted with the appropriate Tris-HCl buffer (10 mM, pH 7-8) or nanopure H 2 O (pH 7-8).
- Tris-HCl buffer 10 mM, pH 7-8
- nanopure H 2 O pH 7-8
- DNase I Buffer comprising 50 ⁇ l Tris pH 7.5 (1M), 10 ⁇ l MnCl 2 (1M), 1 ⁇ l BSA (100 mg/ml), and 39 ⁇ l water was prepared.
- the digested DNA was purified by using the QiaQuick PCR purification kit. The digestion reaction was then split into four aliquots, and four spin columns were used to purify each aliquot (37.5 ⁇ l per spin column). Each column was eluted with 30 ⁇ l elution buffer (EB) according to the manufacturer's protocol. The eluates were then combined to generate a final reaction volume of 120 ⁇ l.
- EB elution buffer
- Pfu polishing is used to increase the amount of blunt-ended species by fill-in (i.e., “blunting”) of 5′ overhangs. Additionally, Pfu DNA polymerase has 3′ ⁇ 5′ exonuclease activity that will result in the removal of single and double nucleotide extensions. Pfu polishing increases the amount of blunt-ended DNA fragments available for adaptor ligation (Costa 1994a, 1994b, 1994c). The following Pfu polishing protocol was used.
- polishing reaction components were mixed well and incubated at 72° C. for 30 minutes.
- polishing reaction mixture was then split into four aliquots and purified using QiaQuick PCR purification columns (37.5 ⁇ L on each column). Each column was eluted with 30 ⁇ l buffer EB according to the manufacturer's protocol. The eluates were then combined to generate a final reaction volume of 120 ⁇ L.
- Step 3 Ligation of Universal Adaptors to Fragmented DNA Library
- Universal Adaptors are comprised of double-stranded oligonucleotides that contain specific priming regions that afford both PCR amplification and nucleotide sequencing.
- the Universal Adaptors are designed to include a set of unique PCR priming regions that are 20 base pairs in length located adjacent to a set of unique sequencing priming regions that are 20 base pairs in length, followed by a unique 4-base “key” consisting of one of each deoxyribonucleotide (i.e., A, C, G, T).
- Each unique Universal Adaptor (termed “Universal Adaptor A” and “Universal Adaptor B”) is forty-four base pairs (44 bp) in length. Universal Adaptors are ligated, using T4 DNA ligase, onto each end of the DNA fragment to generate a total nucleotide addition of 88 bp to each DNA fragment. Different Universal Adaptors are designed specifically for each genomic DNA library preparation and will therefore provide a unique identifier for each organism.
- Universal Adaptor DNA oligonucleotides are designed with two phosphorothioate linkages at each oligonucleotide end that serve to protect against nuclease activity (Samini, T. D., B. Jolles, and A. Laigle. 2001. Best minimally modified antisense oligonucleotides according to cell nuclease activity. Antisense Nucleic Acid Drug Dev . 11(3):129., the disclosure of which is incorporated in toto herein by reference.). Each oligonucleotide is HPLC-purified to ensure there are no contaminating or spurious DNA oligonucleotide sequences in the final prep.
- the Universal Adaptors are designed to allow directional ligation to the blunt-ended, fragmented genomic DNA.
- the PCR priming region contains a 5′ four-base overhang and a blunt-ended 3′ Key region.
- Directionality is achieved as the blunt-end side of the Universal Adaptor ligates to the blunt-ended DNA fragment while the 5′ overhang of the adaptor cannot ligate to the blunt-ended DNA fragment.
- a 5′ biotin is added to the Universal Adaptor B to allow subsequent isolation of ssDNA template (Step 8).
- Each Universal Adaptor is prepared by annealing, in a single tube, the two single-stranded complementary DNA oligonucleotides (i.e., one oligo containing the sense sequence and the second oligo containing the antisense sequence). The following ligation protocol was used.
- Step 3a Microcon Filtration and Adaptor Construction. Total Preparation Time was Approximately 25 min.
- the Universal Adaptor ligation reaction requires a 100-fold excess of adaptors.
- the double-stranded gDNA library is filtered through a Microcon YM-100 filter device.
- Microcon YM-100 membranes can be used to remove double stranded DNA smaller than 125 bp. Therefore, unbound adaptors (44 bp), as well as adaptor dimers (88 bp) can be removed from the ligated gDNA library population. The following filtration protocol was used:
- Adaptors were HPLC-purified and modified with phosphorothioate linkages prior to use.
- Adaptor “A” (10 ⁇ M)
- the primers were annealed using the ANNEAL program on the Sample Prep Labthermal cycler (see below).
- Adaptor “B” (10 ⁇ M)
- 10 ⁇ l of 100 ⁇ M Adaptor B 40 bp, sense
- 10 ⁇ l of 100 ⁇ M Adaptor B 44 bp, antisense
- the primers were annealed using the ANNEAL program on the Sample Prep Lab thermal cycler.
- Adaptor sets could be stored at ⁇ 20° C. until use.
- Step 4 Gel Electrophoresis and Extraction of Adapted DNA Library
- the Universal Adaptor ligation protocol produces the following: 1) fragmented DNAs with adaptors on either end; 2) unbound single adaptors; or 3) the formation of adaptor dimers.
- Agarose gel electrophoresis is used as a method to separate and isolate the adapted DNA library population from the unligated, single adaptors and adaptor dimer populations.
- the procedure of DNase I digestion of genomic DNA yields a library population that ranges from 50-700 bp (Step 1).
- the addition of the 88-bp Universal Adaptor set will shift the population to a larger size and will result in a migration profile in the size range of approximately 130-800 bp.
- Adaptor dimers will migrate at 88 bp and adaptors unligated will migrate at 44 bp. Therefore, genomic DNA libraries in size ranges >200 bp can be physically isolated from the agarose gel and purified using standard gel extraction techniques. Gel isolation of the adapted DNA library will result in the recovery of a library population in a size range that is ⁇ 200 bp (size range of library can be varied depending on application). The following electrophoresis and extraction protocol was used.
- Step 5 Strand Displacement and Extension of Nicked Double Stranded DNA Library
- DNA oligonucleotides used for the Universal Adaptors are not phosphorylated, gaps are present at the 3′ junctions of the fragmented gDNAs. These two “gaps” or “nicks” can be filled in by using a strand displacing DNA polymerase.
- the polymerase recognizes nicks, displaces the nicked strands, and extends the strand in a manner that results in repair of nicks and in the formation of non-nicked double-stranded DNA.
- the strand displacing enzyme used is the large fragment of Bst DNA polymerase.
- Step 7 Isolation of Single-Stranded DNA Library using Streptavidin Beads
- Double-stranded genomic DNA fragment pools will have adaptors bound in the following possible configurations:
- Genomic DNA species with two Universal Adaptor B sequences with two biotin molecules can bind to the streptavidin-containing beads at both ends.
- Species with A and B adaptors having only a single biotin molecule can bind to the beads only at the “B” end.
- the bead-bound double-stranded DNA is treated with a sodium hydroxide solution that serves to disrupt the hydrogen bonding between the complementary DNA strands. If the DNA fragment has biotin on each end (Universal Adaptor B ends), both resulting single strands remain bound to the beads. If the fragment has only a single biotin (Universal Adaptors A and B), then the complementary strand separates from the DNA-bead complex.
- the resulting single-stranded genomic DNA library is collected from the solution phase and is quantitated, e.g., using pyrophosphate sequencing (PyroSequence) or by using a RNA Pico 6000 LabChip (Agilent, Palo Alto, Calif.).
- Single-stranded genomic DNA libraries are quantitated by calculating the number of molecules per unit volume.
- Single-stranded gDNA molecules are then annealed (at a half copy per bead to obtain one effective copy per bead) to 25-30 ⁇ m sepharose beads containing DNA capture primers (PCR primer B).
- the templates are then amplified using emulsion polymerase chain reaction protocols. Subsequent sequencing may be conducted using known techniques. For isolation of the single stranded library, the following protocol was used.
- Step 8a Single-Stranded gDNA Quantitation using Pyrophosphate Sequencing. Total Preparation Time was Approximately 1 hr.
- Step 8b Single-Stranded gDNA Quantitation using RNA Pico 6000 LabChip. Total Preparation Time was Approximately 30 minutes.
- RNA Pico 6000 LabChip was prepared on the BioAnalyzer according to the manufacturers' guidelines.
- RNA LabChip ladder (RNA 6000 ladder) was prepared according to manufacturer's (Ambion) directions. Briefly, the RNA LabChip ladder, in solution, was heated to 70° C. for 2 minutes. The solution was chilled on ice for 5 minutes to snap cool the ladder. The solution was briefly centrifuged to clear any condensate from tube walls. The RNA LabChip Ladder was stored on ice and used within one day.
- the BioAnalyzer software was used to calculate the concentration of each ssDNA library lane (see the Table below and FIG. 8. The average of all three lanes was used to calculate the DNA concentration of the library using the procedure outlined below.
- the concentration of Library 1 was calculated as 1639 pg/ ⁇ l (Column 5) and the average fragment size was 434 nucleotides (Column 9). These values were obtained from the Agilent 2100 software as described in Steps (a)-(d), above.
- the average molecular weight (MW) of a ribonucleotide is 328.2 g/mole (Column 10).
- the MW of the average library fragment (1.42 ⁇ 10 5 g/mole, Column 11) was calculated by multiplying the average fragment length (434) by the average ribonucleotide (328.2).
- the quantitated library (1639 pg/ ⁇ l) was converted to grams per microliter (1.64 ⁇ 10 ⁇ 9 g/ ⁇ l, Column 12).
- the number of moles per microliter (1.15 ⁇ 10 ⁇ 14 moles/ ⁇ l, Column 14) was calculated by dividing the grams per microliter (1.64 ⁇ 10 ⁇ 9 g/ ⁇ l, Column 12) by the average molecular weight of the library fragments (1.42 ⁇ 10 5 , Column 11). Finally, the number of molecules per microliter (6.93 ⁇ 10 9 molecules/ ⁇ l, Column 15) was derived by multiplying the number of moles per microliter (1.15 ⁇ 10 ⁇ 14 moles/ ⁇ l, Column 14) by Avogadro's number (6.02 ⁇ 10 23 molecules/mole).
- the final library concentration was expected to be greater than 1 ⁇ 10 8 molecules/ ⁇ l.
- a more important factor for library quality was adaptor dimer concentration.
- the height of the library peak was determined approximately 10 fold greater than the adaptor dimer peak (the first peak after the marker).
- a library of good quality is expected to have a peak height at least 2 fold greater than the dimer peak.
- the RNA Pico 6000 LabChip provided estimates within 500% accuracy of the single-stranded gDNA concentration.
- the recommended input DNA is 2.5 cpb, 1 cpb, 0.5 cpb, and 0.1 cpb. This titration was easily checked using the 4slot bead loading chamber on a 14 ⁇ 43 PTP.
- Step 9 Dilution and Storage of Single-Stranded gDNA Library
- the single-stranded gDNA library was eluted and quantitated in Buffer EB. To prevent degradation, the single-stranded gDNA library was stored frozen at ⁇ 20° C. in the presence of EDTA. After quantitation, an equal volume of 10 mM TE was added to the library stock. All subsequent dilutions was in TE. The yield was as follows:
- single-stranded gDNA library was diluted to 100 million molecules/ ⁇ l in 1 ⁇ Library-Grade Elution Buffer. Aliquots of single-stranded gDNA library were prepared for common use. For this, 200,000 molecules/ ⁇ l were diluted in 1 ⁇ Library-Grade Elution Buffer and 20 ⁇ l aliquots were measured. Single-use library aliquots were stored at ⁇ 20° C.
- Step 10 Emulsion Polymerase Chain Reaction.
- the Stop Solution (50 mM EDTA) included 100 ⁇ l of 0.5 M EDTA mixed with 900 ⁇ l of nH 2 O to obtain 1.0 ml of 50 mM EDTA solution.
- 10 mM dNTPs (10 ⁇ l dCTP (100 mM), 10 ⁇ l DATP (100 mM), 10 ⁇ l dGTP (100 mM), and 10 ⁇ l dTTP (100 mM) were mixed with 60 ⁇ l molecular biology grade water. All four 100 mM nucleotide stocks were thawed on ice.
- each nucleotide was combined with 60 ⁇ l of nH 2 O to a final volume of 100 ⁇ l, and mixed thoroughly. Next, 1 ml aliquots were dispensed into 1.5 ml microcentrifuge tubes. The stock solutions could be stored at ⁇ 20° C. for one year.
- the 10 ⁇ Annealing buffer included 200 mM Tris (pH 7.5) and 50 mM magnesium acetate. For this solution, 24.23 g Tris was added to 800 ml nH 2 O and the mixture was adjusted to pH 7.5. To this solution, 10.72 g of magnesium acetate was added and dissolved completely. The solution was brought up to a final volume of 1000 ml and could be stored at 4° C. for 1 month.
- the 10 ⁇ TE included 100 mM Tris-HCl (pH 7.5) and 50 mM EDTA. These reagents were added together and mixed thoroughly. The solution could be stored at room temperature for 6 months.
- the universal adaptors are designed to include: 1) a set of unique PCR priming regions that are typically 20 bp in length (located adjacent to (2)); 2) a set of unique sequencing priming regions that are typically 20 bp in length; and 3) optionally followed by a unique discriminating key sequence consisting of at least one of each of the four deoxyribonucleotides (i.e., A, C, G, T).
- a unique discriminating key sequence consisting of at least one of each of the four deoxyribonucleotides (i.e., A, C, G, T).
- the single-stranded DNA library is utilized for PCR amplification and subsequent sequencing.
- Sequencing methodology requires random digestion of a given genome into 150 to 500 base pair fragments, after which two unique bipartite primers (composed of both a PCR and sequencing region) are ligated onto the 5′ and 3′ ends of the fragments (FIG. 5).
- T m melting temperature
- the disclosed process utilizes synthetic priming sites that necessitates careful de novo primer design.
- PCR/LDR work was particularly relevant and focused on designing oligonucleotide “zipcodes”, 24 base primers comprised of six specifically designed tetramers with a similar final T m . (see, Gerry, N. P., et al., Universal DNA microarray method for multiplex detection of low abundance point mutations. Journal of Molecular Biology, 1999. 292: p. 251-262; U.S. Pat. No. 6,506,594).
- Tetrameric components were chosen based on the following criteria: each tetramer differed from the others by at least two bases, tetramers that induced self-pairing or hairpin formations were excluded, and palindromic (AGCT) or repetitive tetramers (TATA) were omitted as well. Thirty-six of the 256 (4 4 ) possible permutations met the necessary requirements and were then subjected to further restrictions required for acceptable PCR primer design (Table 1).
- Table 1 shows a matrix demonstrating tetrameric primer component selection based on criteria outlined by Gerry et al. 1999 . J. Mol. Bio . 292: 251-262. Each tetramer was required to differ from all others by at least two bases. The tetramers could not be palindromic or complimentary with any other tetramer. Thirty-six tetramers were selected (bold, underlined); italicized sequences signal palindromic tetramers that were excluded from consideration.
- PCR primers were designed to meet specifications common to general primer design (see, Rubin, E. and A. A. Levy, A mathematical model and a computerized simulation of PCR using complex templates. Nucleic Acids Res, 1996. 24(18): p. 3538-45; Buck, G. A., et al., Design strategies and performance of custom DNA sequencing primers. Biotechniques, 1999. 27(3): p. 528-36), and the actual selection was conducted by a computer program, MMP. Primers were limited to a length of 20 bases (5 tetramers) for efficient synthesis of the total bipartite PCR/sequencing primer.
- Each primer contained a two base GC clamp on the 5′ end, and a single GC clamp on the 3′ end (Table 2), and all primers shared similar T m (+/ ⁇ 2° C.) (FIG. 10).
- No hairpinning within the primer (internal hairpin stem ⁇ G> ⁇ 1.9 kcal/mol) was permitted.
- Dimerization was also controlled; a 3 base maximum acceptable dimer was allowed, but it could occur in final six 3′ bases, and the maximum allowable ⁇ G for a 3′ dimer was ⁇ 2.0 kcal/mol. Additionally, a penalty was applied to primers in which the 3′ ends were too similar to others in the group, thus preventing cross-hybridization between one primer and the reverse complement of another.
- Table 2 shows possible permutations of the 36 selected tetrads providing two 5′ and a single 3′ G/C clamp. The internal positions are composed of remaining tetrads. This results in 8 ⁇ 19 ⁇ 19 ⁇ 19 ⁇ 9 permutations, or 493,848 possible combinations.
- FIG. 10 shows first pass, T m based selection of acceptable primers, reducing field of 493,848 primers to 56,246 candidates with T m of 64 to 66° C.
- TABLE 3 The probability of perfect sequence matches for primers increases with decreasing match length requirements and increasing size of the genome of interest.
- the probability of finding a 16 base perfect match is 97% for the sequences in the NCBI database (approximately 100 times larger than the Adenovirus genome).
- the probability of finding a 17 base perfect match to a 20 base primer is 99% for the sequences in the human genome (3 billion bases).
- the immobilized product would lack a sequencing primer binding site, and would result in an empty PicoTiter plate (PTP) well. If the CHR out-competed the bead-bound primer, the sequencing primer would still be present, and the only effect would be a shorter insert. Neither result would unduly compromise the sequencing quality. Given the large amount of genomic material used in the sample preparation process (currently 25 ⁇ g, containing 5.29 ⁇ 10 16 copies of the 35 Kb Adenovirus genome), oversampling can be used to provide fragments that lack the complete CHR, and allow standard PCR amplification of the region in question.
- the purpose of the Nebulization step is to fragment a large stretch of DNA such as a whole genome or a large portion of a genome into smaller molecular species that are amenable to DNA sequencing.
- This population of smaller-sized DNA species generated from a single DNA template is referred to as a library.
- Nebulization shears double-stranded template DNA into fragments ranging from 50 to 900 base pairs.
- the sheared library contains single-stranded ends that are end-repaired by a combination of T4 DNA polymerase, E. coli DNA polymerase I (Klenow fragment), and T4 polynucleotide kinase.
- Both T4 and Klenow DNA polymerases are used to “fill-in” 3′ recessed ends (5′ overhangs) of DNA via their 5′-3′ polymerase activity.
- the single-stranded 3′-5′ exonuclease activity of T4 and Klenow polymerases will remove 3′ overhang ends and the kinase activity of T4 polynucleotide kinase will add phosphates to 5′ hydroxyl termini.
- gDNA genomic DNA
- 10 mM TE 10 mM Tris, 0.1 mM EDTA, pH 7.6; see reagent list at the end of section.
- the DNA was analyzed for contamination by measuring the O.D. 260/280 ratio, which was 1.8 or higher.
- the final gDNA concentration was expected to be approximately 300 ⁇ g/ml.
- reaction mixture was placed in an ice-cold nebulizer (CIS-US, Bedford, Mass.).
- the recovered sample was purified using a QIAquick column (Qiagen Inc., Valencia, Calif.) according to manufacturer's directions. The large volume required the column to be loaded several times.
- the sample was eluted with 30 ⁇ l of Buffer EB (10 mM Tris HCl, pH 8.5; supplied in Qiagen kit) which was pre-warmed at 55° C.
- Nebulization of DNA templates yields many fragments of DNA with frayed ends. These ends are made blunt and ready for ligation to adaptor fragments by using three enzymes, T4 DNA polymerase, E. coli DNA polymerase (Klenow fragment) and T4 polynucleotide kinase.
- step 2 The solution of step 1 was mixed well and incubated at 25° C. for 10 minutes in a MJ thermocycler (any accurate incubator may be used).
- the treated DNA was purified using a QiaQuick column and eluted with 30 ⁇ l of Buffer EB (10 mM Tris HCl, pH 8.5) which was pre-warmed at 55° C.
- genomic DNA libraries isolated in size ranges ⁇ 250 bp can be physically isolated from the agarose gel and purified using standard gel extraction techniques. Gel isolation of the adapted gDNA library will result in the recovery of a library population in a size range that is ⁇ 250 bp (size range of library can be varied depending on application).
- the library size range after ligation of adapters is 130 to 980 bp. It should be noted that the procedure may be adapted for isolation of any band size range, such as, for example, 130 to 200 bp, 200 to 400 bp, 250 to 500 bp, 300 to 600 bp, 500 to 700 bp and the like by cutting different regions of the gel. The procedure described below was used to isolated fragments of 250 bp to 500 bp.
- a 150 ml agarose gel was prepared to include 2% agarose, 1 ⁇ TBE, and 4.5 ⁇ l ethidium bromide (10 mg/ml stock).
- the ligated DNA was mixed with 10 ⁇ Ready Load Dye and loaded onto the gel.
- 10 ⁇ l of a 100-bp ladder (0.1 ⁇ g/ ⁇ l) was loaded on two lanes away from the ligation reaction flanking the sample.
- the gel was electrophoresed at 100 V for 3 hours. When the gel run was complete, the gel was removed from the gel box, transferred to a GelDoc, and covered with plastic wrap.
- the DNA bands were visualized using the Prep UV light.
- the gel slices were placed in a 15 ml falcon tube.
- the agarose-embedded gDNA library was isolated using a Qiagen MinElute Gel Extraction kit. Aliquots of each isolated gDNA library were analyzed using a BioAnalyzer DNA 1000 LabChip to assess the exact distribution of the gDNA library population.
- PB from the QiaQuick Purification kit
- 9 ⁇ l of 20% acetic acid were mixed.
- the beads in 250 ⁇ l Melt Solution were pelleted using a Dynal MPC and the supernatant was carefully removed and transferred to the freshly prepared PB/acetic acid solution.
- DNA from the 1500 ⁇ l solution was purified using a single MinElute purification spin column. This was performed by loading the sample through the same column twice at 750 ⁇ l per load.
- the single stranded gDNA library was eluted with 15 ⁇ l of Buffer EB which was pre-warmed at 55° C.
- Single-stranded gDNA was quantitated using RNA Pico 6000 LabChip as described in Example 1.
- the single stranded library was quantitated by a second assay to ensure the initial Agilent 2100 quantitation was performed accurately.
- RiboGreen quantitation was performed as described (ssDNA Quantitation by Fluorometry) to confirm the Agilent 2100 quantitation. If the two estimates differed by more than 3 fold, each analysis was repeated. If the quantitation showed greater than a 3 fold difference between the two procedures, a broader range of template to bead was used.
- FIG. 9A Typical results from Agilent 2100 DNA 1000 LabChip analysis of 1 ⁇ l of the material following Nebulization and polishing are shown in FIG. 9A. The size range distribution of the majority of the product was expected to fall around 50 to 900 base pairs. The mean size (top of peak) was expected to be approximately 450 bp. Typical results from gel purification of adaptor ligated library fragments are shown in FIG. 9B.
- reagents listed in the Examples represent standard reagents that are commercially available.
- Klenow, T4 DNA polymerase, T4 DNA polymerase buffer, T4 PNK, T4 PNK buffer, Quick T4 DNA Ligase, Quick Ligation Buffer, Bst DNA polymerase (Large Fragment) and ThermoPol reaction buffer are available from New England Biolabs (Beverly, Mass.).
- dNTP mix is available from Pierce (Rockford, Ill.).
- Agarose, UltraPure TBE, BlueJuice gel loading buffer and Ready-Load 100 bp DNA ladder may be purchased from Invitrogen (Carlsbad, Calif.).
- Ethidium Bromide and 2-Propanol may be purchased from Fisher (Hampton, N.H.).
- RNA Ladder may be purchased from Ambion (Austin, Tex.).
- Other reagents are either commonly known and/or are listed below:
- Melt Solution Ingredient Quantity Required Vendor Stock Number NaCl (5 M) 200 ⁇ l Invitrogen 24740-011 NaOH (10 N) 125 ⁇ l Fisher SS255-1 molecular biology 9.675 ml Eppendorf 0032-006-205 grade water
- the Melt Solution included 100 mM NaCl, and 125 mM NaOH. The listed reagents were combined and mixed thoroughly. The solution could be stored at RT for six months.
- the 2 ⁇ B&W buffer included final concentrations of 10 mM Tris-HCl (pH 7.5), 1 mM EDTA, and 2 M NaCl.
- the listed reagents were combined by combined and mixed thoroughly. The solution could be stored at RT for 6 months.
- the 1 ⁇ B&W buffer was prepared by mixing 2 ⁇ B&W buffer with picopure H 2 O, 1:1. The final concentrations was half of that listed the above, i.e., 5 mM Tris-HCl (pH 7.5), 0.5 mM EDTA, and 1 M NaCl.
- T4 DNA Polymerase Buffer 50 mM NaCl, 10 mM Tris-HCl, 10 mM MgCl 2 , 1 mM dithiothreitol (pH 7.9 @ 25° C.).
- TE 10 mM Tris, 1 mM EDTA.
- Nebulization Buffer Ingredient Quantity Required Vendor Stock Number Glycerol 53.1 ml Sigma G5516 molecular biology 42.1 ml Eppendorf 0032-006-205 grade water UltraPure Tris-HCl 3.7 ml Invitrogen 15567-027 (pH 7.5, 1M) EDTA (0.5M) 1.1 ml Sigma M-10228
- ATP 10 mM: Ingredient Quantity Required Vendor Stock Number ATP (100 mM) 10 ⁇ l Roche 1140965 molecular biology 90 ⁇ l Eppendorf 0032-006-205 grade water
- the 10 ⁇ Annealing Buffer included 200 mM Tris (pH 7.5) and 50 mM magnesium acetate.
- 200 ml of Tris was added to 500 ml picopure H 2 O.
- 10.72 g of magnesium acetate was added to the solution and dissolved completely.
- the solution was adjusted to a final volume of 1000 ml.
- the solution could be stored at 4° C. for six months. To avoid the potential for contamination of libraries, the buffer was aliquotted for single or short-term usage.
- Adaptor “A” (400 ⁇ M): Quantity Ingredient Req. Vendor Stock No. Adaptor A (sense; HPLC- 10.0 ⁇ l IDT custom purified, phosphorothioate linkages, 44 bp, 1000 pmol/ ⁇ l) Adaptor A (antisense; HPLC- 10.0 ⁇ l IDT custom purified, Phosphorothioate linkages, 40 bp, 1000 pmol/ ⁇ l) Annealing buffer (10 ⁇ ) 2.5 ⁇ l 454 Corp. previous table molecular biology grade water 2.5 ⁇ l Eppendorf 0032-006-205
- Adaptor “B” (400 ⁇ M): Quantity Ingredient Req. Vendor Stock No. Adaptor B (sense; HPLC- 10 ⁇ l IDT Custom purified, phosphorothioate linkages, 40 bp, 1000 pmol/ ⁇ l)) Adaptor B (anti; HPLC-purified, 10 ⁇ l IDT Custom phosphorothioate linkages, 5′Biotinylated, 44 bp, 1000 pmol/ ⁇ l) Annealing buffer (10X) 2.5 ⁇ l 454 Corp. previous table molecular biology grade water 2.5 ⁇ l Eppendorf 0032-006-205
- Acetic Acid Quantity Ingredient Required Vendor Stock Number acetic acid, glacial 2 ml Fisher A35-500 molecular biology grade water 8 ml Eppendorf 0032-006-205
- MinElute kit hypertext transfer protocol://world wide web.qiagen.com/literature/handbooks/minelute/1016839_HBMinElute_Prot_Gel.pdf.
- BioAnalyzer DNA and RNA LabChip Usage (Agilent): hypertext transfer protocol://world wide web.agilent.com/chem/labonachip
- BioAnalyzer RNA 6000 Ladder (Ambion): hypertext transfer protocol://world wide web.ambion.com/techlib/spec/sp — 7152.pdf
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---|---|---|---|---|
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US20040056018A1 (en) * | 2001-09-25 | 2004-03-25 | Beru Ag | Method for operating a multi-stage electrical heater comprised of several heating elements |
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US20070117121A1 (en) * | 2005-09-16 | 2007-05-24 | Hutchison Stephen K | cDNA library preparation |
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US20090239211A1 (en) * | 2004-02-17 | 2009-09-24 | Nuevolution A/S | Method For Enrichment Involving Elimination By Mismatch Hybridisation |
US7604940B1 (en) | 2005-03-16 | 2009-10-20 | Applied Biosystems, Llc | Compositions and methods for analyzing isolated polynucleotides |
US20090318298A1 (en) * | 2006-09-28 | 2009-12-24 | President And Fellows Of Harvard College | Methods for Sequencing DNA |
US20100016177A1 (en) * | 2001-06-20 | 2010-01-21 | Henrik Pedersen | Templated molecules and methods for using such molecules |
US20100137143A1 (en) * | 2008-10-22 | 2010-06-03 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
US20100136557A1 (en) * | 2007-06-29 | 2010-06-03 | Sydney Brenner | Methods and Compositions for Isolating Nucleic Acid Sequence Variants |
US20100143908A1 (en) * | 2006-11-15 | 2010-06-10 | Biospherex, Llc, A Limited Liability Company | Multitag sequencing ecogenomics analysis-us |
USRE41780E1 (en) | 2003-03-14 | 2010-09-28 | Lawrence Livermore National Security, Llc | Chemical amplification based on fluid partitioning in an immiscible liquid |
US20100261189A1 (en) * | 2008-10-03 | 2010-10-14 | Roche Molecular Systems, Inc. | System and method for detection of HLA Variants |
US20100282617A1 (en) * | 2006-12-14 | 2010-11-11 | Ion Torrent Systems Incorporated | Methods and apparatus for detecting molecular interactions using fet arrays |
US20100301398A1 (en) * | 2009-05-29 | 2010-12-02 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
US7888034B2 (en) | 2008-07-01 | 2011-02-15 | 454 Life Sciences Corporation | System and method for detection of HIV tropism variants |
US20110039303A1 (en) * | 2007-02-05 | 2011-02-17 | Stevan Bogdan Jovanovich | Microfluidic and nanofluidic devices, systems, and applications |
WO2011042189A1 (fr) | 2009-10-09 | 2011-04-14 | Roche Diagnostics Gmbh | Système et procédé pour la rupture d'émulsion et la récupération d'éléments biologiques |
US7948015B2 (en) | 2006-12-14 | 2011-05-24 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US20110126911A1 (en) * | 2009-12-01 | 2011-06-02 | IntegenX Inc., a California Corporation | Composite Plastic Articles |
US20110177587A1 (en) * | 2004-01-28 | 2011-07-21 | 454 Corporation | Nucleic acid amplification with continuous flow emulsion |
US20110217738A1 (en) * | 2010-03-03 | 2011-09-08 | Gen9, Inc. | Methods and Devices for Nucleic Acid Synthesis |
WO2011056872A3 (fr) * | 2009-11-03 | 2011-11-03 | Gen9, Inc. | Procédés et dispositifs microfluidiques pour la manipulation de gouttelettes dans un ensemble polynucléotidique haute fidélité |
WO2011106314A3 (fr) * | 2010-02-25 | 2012-02-23 | Advanced Liquid Logic, Inc. | Procédé de fabrication de banques d'acide nucléique |
US20120135871A1 (en) * | 2006-04-04 | 2012-05-31 | Keygene N.V. | High throughput detection of molecular markers based on aflp and high through-put sequencing |
US8217433B1 (en) | 2010-06-30 | 2012-07-10 | Life Technologies Corporation | One-transistor pixel array |
US8262900B2 (en) | 2006-12-14 | 2012-09-11 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
WO2012130681A1 (fr) | 2011-03-25 | 2012-10-04 | Roche Diagnostics Gmbh | Système et procédé de détection de variants de l'intégrase du vih |
US8388908B2 (en) | 2009-06-02 | 2013-03-05 | Integenx Inc. | Fluidic devices with diaphragm valves |
US8394642B2 (en) | 2009-06-05 | 2013-03-12 | Integenx Inc. | Universal sample preparation system and use in an integrated analysis system |
US8431390B2 (en) | 2004-09-15 | 2013-04-30 | Integenx Inc. | Systems of sample processing having a macro-micro interface |
EP2599877A1 (fr) * | 2010-06-30 | 2013-06-05 | BGI Shenzhen Co., Limited | Nouvelle méthode de séquençage par pcr et son utilisation dans le génotypage hla |
US8470164B2 (en) | 2008-06-25 | 2013-06-25 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8476063B2 (en) | 2004-09-15 | 2013-07-02 | Integenx Inc. | Microfluidic devices |
US8512538B2 (en) | 2010-05-28 | 2013-08-20 | Integenx Inc. | Capillary electrophoresis device |
US8552771B1 (en) | 2012-05-29 | 2013-10-08 | Life Technologies Corporation | System for reducing noise in a chemical sensor array |
US20130309668A1 (en) * | 2004-03-08 | 2013-11-21 | Rubicon Genomics, Inc. | Methods and compositions for generating and amplifying dna libraries for sensitive detection and analysis of dna methylation |
US8653567B2 (en) | 2010-07-03 | 2014-02-18 | Life Technologies Corporation | Chemically sensitive sensor with lightly doped drains |
US8673627B2 (en) | 2009-05-29 | 2014-03-18 | Life Technologies Corporation | Apparatus and methods for performing electrochemical reactions |
US8672532B2 (en) | 2008-12-31 | 2014-03-18 | Integenx Inc. | Microfluidic methods |
WO2014043140A1 (fr) * | 2012-09-12 | 2014-03-20 | The Regents Of The University Of California | Séquençage précis du génome de cellules individuelles par l'amplification et le séquençage d'un seul brin |
US8685324B2 (en) | 2010-09-24 | 2014-04-01 | Life Technologies Corporation | Matched pair transistor circuits |
GB2497912B (en) * | 2010-10-08 | 2014-06-04 | Harvard College | High-throughput single cell barcoding |
US8747748B2 (en) | 2012-01-19 | 2014-06-10 | Life Technologies Corporation | Chemical sensor with conductive cup-shaped sensor surface |
US8748165B2 (en) | 2008-01-22 | 2014-06-10 | Integenx Inc. | Methods for generating short tandem repeat (STR) profiles |
US8753812B2 (en) | 2004-11-12 | 2014-06-17 | The Board Of Trustees Of The Leland Stanford Junior University | Charge perturbation detection method for DNA and other molecules |
WO2014068407A3 (fr) * | 2012-10-26 | 2014-06-26 | Sysmex Corporation | Systèmes d'émulsion et amplification à base d'émulsion d'acide nucléique |
US8763642B2 (en) | 2010-08-20 | 2014-07-01 | Integenx Inc. | Microfluidic devices with mechanically-sealed diaphragm valves |
US8776573B2 (en) | 2009-05-29 | 2014-07-15 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US8808984B2 (en) | 2002-03-15 | 2014-08-19 | Neuvolution A/S | Method for synthesising templated molecules |
US8808986B2 (en) | 2008-08-27 | 2014-08-19 | Gen9, Inc. | Methods and devices for high fidelity polynucleotide synthesis |
US8815512B2 (en) | 2005-12-22 | 2014-08-26 | Keygene N.V. | Method for high-throughput AFLP-based polymorphism detection |
US8821798B2 (en) | 2012-01-19 | 2014-09-02 | Life Technologies Corporation | Titanium nitride as sensing layer for microwell structure |
US8841217B1 (en) | 2013-03-13 | 2014-09-23 | Life Technologies Corporation | Chemical sensor with protruded sensor surface |
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US8963216B2 (en) | 2013-03-13 | 2015-02-24 | Life Technologies Corporation | Chemical sensor with sidewall spacer sensor surface |
US8962366B2 (en) | 2013-01-28 | 2015-02-24 | Life Technologies Corporation | Self-aligned well structures for low-noise chemical sensors |
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US9080968B2 (en) | 2013-01-04 | 2015-07-14 | Life Technologies Corporation | Methods and systems for point of use removal of sacrificial material |
US20150197789A1 (en) * | 2006-02-08 | 2015-07-16 | Illumina Cambridge Limited | End modification to prevent over-representation of fragments |
US9096951B2 (en) | 2003-02-21 | 2015-08-04 | Nuevolution A/S | Method for producing second-generation library |
US9109251B2 (en) | 2004-06-25 | 2015-08-18 | University Of Hawaii | Ultrasensitive biosensors |
US9116117B2 (en) | 2013-03-15 | 2015-08-25 | Life Technologies Corporation | Chemical sensor with sidewall sensor surface |
US9121058B2 (en) | 2010-08-20 | 2015-09-01 | Integenx Inc. | Linear valve arrays |
US9128044B2 (en) | 2013-03-15 | 2015-09-08 | Life Technologies Corporation | Chemical sensors with consistent sensor surface areas |
US9217144B2 (en) | 2010-01-07 | 2015-12-22 | Gen9, Inc. | Assembly of high fidelity polynucleotides |
US9216414B2 (en) | 2009-11-25 | 2015-12-22 | Gen9, Inc. | Microfluidic devices and methods for gene synthesis |
US9376716B2 (en) | 2005-06-23 | 2016-06-28 | Keygene N.V. | Strategies for high throughput identification and detection of polymorphisms |
US9422600B2 (en) | 2009-11-25 | 2016-08-23 | Gen9, Inc. | Methods and apparatuses for chip-based DNA error reduction |
WO2016160965A1 (fr) * | 2015-03-30 | 2016-10-06 | Rubicon Genomics, Inc. | Procédés et compositions permettant la réparation des extrémités de l'adn par de multiples activités enzymatiques |
US9464318B2 (en) * | 2015-02-11 | 2016-10-11 | Paragon Genomics, Inc. | Methods and compositions for reducing non-specific amplification products |
US9486757B2 (en) | 2009-03-13 | 2016-11-08 | President And Fellows Of Harvard College | Scale-up of microfluidic devices |
US9513253B2 (en) | 2011-07-11 | 2016-12-06 | Advanced Liquid Logic, Inc. | Droplet actuators and techniques for droplet-based enzymatic assays |
US9574189B2 (en) | 2005-12-01 | 2017-02-21 | Nuevolution A/S | Enzymatic encoding methods for efficient synthesis of large libraries |
US9618475B2 (en) | 2010-09-15 | 2017-04-11 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US9671363B2 (en) | 2013-03-15 | 2017-06-06 | Life Technologies Corporation | Chemical sensor with consistent sensor surface areas |
EP3175914A1 (fr) * | 2004-01-07 | 2017-06-07 | Illumina Cambridge Limited | Perfectionnements apportés ou se rapportant à des réseaux moléculaires |
US9752176B2 (en) | 2011-06-15 | 2017-09-05 | Ginkgo Bioworks, Inc. | Methods for preparative in vitro cloning |
US9816088B2 (en) | 2013-03-15 | 2017-11-14 | Abvitro Llc | Single cell bar-coding for antibody discovery |
US9823217B2 (en) | 2013-03-15 | 2017-11-21 | Life Technologies Corporation | Chemical device with thin conductive element |
US9835585B2 (en) | 2013-03-15 | 2017-12-05 | Life Technologies Corporation | Chemical sensor with protruded sensor surface |
US9841398B2 (en) | 2013-01-08 | 2017-12-12 | Life Technologies Corporation | Methods for manufacturing well structures for low-noise chemical sensors |
WO2018049260A1 (fr) * | 2016-09-09 | 2018-03-15 | Tl Biolabs Corp . | Compositions de microréseau réutilisables et procédés |
EP3208343A4 (fr) * | 2014-10-13 | 2018-03-21 | BGI Shenzhen Co., Limited | Procédé de fragmentation d'acide nucléique et combinaison de séquences |
US20180080020A1 (en) * | 2006-01-11 | 2018-03-22 | Raindance Technologies, Inc. | Microfluidic devices and methods of use in the formation and control of nanoreactors |
US9951384B2 (en) | 2012-01-13 | 2018-04-24 | Data2Bio | Genotyping by next-generation sequencing |
US9970984B2 (en) | 2011-12-01 | 2018-05-15 | Life Technologies Corporation | Method and apparatus for identifying defects in a chemical sensor array |
US20180148767A1 (en) * | 2015-05-29 | 2018-05-31 | Epicentre Technologies Corporation | Methods of analyzing nucleic acids |
US10077472B2 (en) | 2014-12-18 | 2018-09-18 | Life Technologies Corporation | High data rate integrated circuit with power management |
US10081807B2 (en) | 2012-04-24 | 2018-09-25 | Gen9, Inc. | Methods for sorting nucleic acids and multiplexed preparative in vitro cloning |
CN108588200A (zh) * | 2018-05-06 | 2018-09-28 | 湖南大地同年生物科技有限公司 | 一种R-Loop高通量测序文库构建方法 |
WO2018186930A1 (fr) * | 2017-04-06 | 2018-10-11 | MyOmicsDx, Inc | Procédé et kit de construction d'une bibliothèque d'acides nucléiques |
US10100358B2 (en) | 2017-01-10 | 2018-10-16 | Paragon Genomics, Inc. | Methods and compositions for reducing redundant molecular barcodes created in primer extension reactions |
US10100357B2 (en) | 2013-05-09 | 2018-10-16 | Life Technologies Corporation | Windowed sequencing |
EP3259372A4 (fr) * | 2015-02-17 | 2018-11-07 | Complete Genomics, Inc. | Séquençage de l'adn à l'aide d'un déplacement de brin régulé |
US10192024B2 (en) | 2012-05-18 | 2019-01-29 | 454 Life Sciences Corporation | System and method for generation and use of optimal nucleotide flow orders |
US10191071B2 (en) | 2013-11-18 | 2019-01-29 | IntegenX, Inc. | Cartridges and instruments for sample analysis |
US10202608B2 (en) | 2006-08-31 | 2019-02-12 | Gen9, Inc. | Iterative nucleic acid assembly using activation of vector-encoded traits |
US10208332B2 (en) | 2014-05-21 | 2019-02-19 | Integenx Inc. | Fluidic cartridge with valve mechanism |
US10233494B2 (en) | 2005-09-29 | 2019-03-19 | Keygene N.V. | High throughput screening of populations carrying naturally occurring mutations |
US10308931B2 (en) | 2012-03-21 | 2019-06-04 | Gen9, Inc. | Methods for screening proteins using DNA encoded chemical libraries as templates for enzyme catalysis |
CN109853047A (zh) * | 2019-04-10 | 2019-06-07 | 翌圣生物科技(上海)有限公司 | 一种基因组dna测序文库快速构建方法及配套试剂盒 |
US10316364B2 (en) | 2005-09-29 | 2019-06-11 | Keygene N.V. | Method for identifying the source of an amplicon |
US10344336B2 (en) | 2015-06-09 | 2019-07-09 | Life Technologies Corporation | Methods, systems, compositions, kits, apparatus and computer-readable media for molecular tagging |
CN110062809A (zh) * | 2016-12-20 | 2019-07-26 | 豪夫迈·罗氏有限公司 | 用于环状共有序列测序的单链环状dna文库 |
US10379079B2 (en) | 2014-12-18 | 2019-08-13 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US10421993B2 (en) | 2015-02-11 | 2019-09-24 | Paragon Genomics, Inc. | Methods and compositions for reducing non-specific amplification products |
US10451585B2 (en) | 2009-05-29 | 2019-10-22 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US10457935B2 (en) | 2010-11-12 | 2019-10-29 | Gen9, Inc. | Protein arrays and methods of using and making the same |
US10458942B2 (en) | 2013-06-10 | 2019-10-29 | Life Technologies Corporation | Chemical sensor array having multiple sensors per well |
US10525467B2 (en) | 2011-10-21 | 2020-01-07 | Integenx Inc. | Sample preparation, processing and analysis systems |
US10590483B2 (en) | 2014-09-15 | 2020-03-17 | Abvitro Llc | High-throughput nucleotide library sequencing |
US10605767B2 (en) | 2014-12-18 | 2020-03-31 | Life Technologies Corporation | High data rate integrated circuit with transmitter configuration |
US10612017B2 (en) | 2009-05-29 | 2020-04-07 | Life Technologies Corporation | Scaffolded nucleic acid polymer particles and methods of making and using |
CN111133135A (zh) * | 2017-07-17 | 2020-05-08 | 希昆斯生物科学公司 | 用于高通量测序的快速文库构建 |
US10690627B2 (en) | 2014-10-22 | 2020-06-23 | IntegenX, Inc. | Systems and methods for sample preparation, processing and analysis |
CN111455469A (zh) * | 2020-04-07 | 2020-07-28 | 深圳易倍科华生物科技有限公司 | 一种单链快速建库方法及建库仪器 |
US10865440B2 (en) | 2011-10-21 | 2020-12-15 | IntegenX, Inc. | Sample preparation, processing and analysis systems |
US10941453B1 (en) | 2020-05-20 | 2021-03-09 | Paragon Genomics, Inc. | High throughput detection of pathogen RNA in clinical specimens |
US10960397B2 (en) | 2007-04-19 | 2021-03-30 | President And Fellows Of Harvard College | Manipulation of fluids, fluid components and reactions in microfluidic systems |
EP2971168B1 (fr) | 2013-03-15 | 2021-05-05 | Guardant Health, Inc. | Méthodes pour détecter cancer |
US11072789B2 (en) | 2012-06-25 | 2021-07-27 | Gen9, Inc. | Methods for nucleic acid assembly and high throughput sequencing |
US11077415B2 (en) | 2011-02-11 | 2021-08-03 | Bio-Rad Laboratories, Inc. | Methods for forming mixed droplets |
US11084014B2 (en) | 2010-11-12 | 2021-08-10 | Gen9, Inc. | Methods and devices for nucleic acids synthesis |
EP3901273A1 (fr) * | 2012-08-14 | 2021-10-27 | 10X Genomics, Inc. | Compositions de microcapsule et procédés |
US11168353B2 (en) | 2011-02-18 | 2021-11-09 | Bio-Rad Laboratories, Inc. | Compositions and methods for molecular labeling |
US11174509B2 (en) | 2013-12-12 | 2021-11-16 | Bio-Rad Laboratories, Inc. | Distinguishing rare variations in a nucleic acid sequence from a sample |
US11187702B2 (en) | 2003-03-14 | 2021-11-30 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
US11193121B2 (en) | 2013-02-08 | 2021-12-07 | 10X Genomics, Inc. | Partitioning and processing of analytes and other species |
US11231451B2 (en) | 2010-06-30 | 2022-01-25 | Life Technologies Corporation | Methods and apparatus for testing ISFET arrays |
US11254968B2 (en) | 2010-02-12 | 2022-02-22 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
US11307166B2 (en) | 2010-07-01 | 2022-04-19 | Life Technologies Corporation | Column ADC |
US11339430B2 (en) | 2007-07-10 | 2022-05-24 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US11351510B2 (en) | 2006-05-11 | 2022-06-07 | Bio-Rad Laboratories, Inc. | Microfluidic devices |
US11359239B2 (en) | 2012-08-14 | 2022-06-14 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US11390917B2 (en) | 2010-02-12 | 2022-07-19 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
US11421274B2 (en) | 2012-12-14 | 2022-08-23 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US11434531B2 (en) | 2013-12-28 | 2022-09-06 | Guardant Health, Inc. | Methods and systems for detecting genetic variants |
US11434523B2 (en) | 2012-09-04 | 2022-09-06 | Guardant Health, Inc. | Systems and methods to detect rare mutations and copy number variation |
US11441179B2 (en) | 2012-08-14 | 2022-09-13 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US11473138B2 (en) | 2012-12-14 | 2022-10-18 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US11511242B2 (en) | 2008-07-18 | 2022-11-29 | Bio-Rad Laboratories, Inc. | Droplet libraries |
US11591637B2 (en) | 2012-08-14 | 2023-02-28 | 10X Genomics, Inc. | Compositions and methods for sample processing |
US11629344B2 (en) | 2014-06-26 | 2023-04-18 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US11635427B2 (en) | 2010-09-30 | 2023-04-25 | Bio-Rad Laboratories, Inc. | Sandwich assays in droplets |
US11667952B2 (en) | 2017-08-24 | 2023-06-06 | Takara Bio Usa, Inc. | Methods of producing nucleic acids using oligonucleotides modified by a stimulus |
US11680293B1 (en) | 2022-04-21 | 2023-06-20 | Paragon Genomics, Inc. | Methods and compositions for amplifying DNA and generating DNA sequencing results from target-enriched DNA molecules |
US11702662B2 (en) | 2011-08-26 | 2023-07-18 | Gen9, Inc. | Compositions and methods for high fidelity assembly of nucleic acids |
US11786872B2 (en) | 2004-10-08 | 2023-10-17 | United Kingdom Research And Innovation | Vitro evolution in microfluidic systems |
WO2023175040A3 (fr) * | 2022-03-15 | 2023-11-02 | Illumina, Inc. | Séquençage simultané de brins complémentaires sens et antisens sur des polynucléotides concaténés pour la détection de méthylation |
US11819849B2 (en) | 2007-02-06 | 2023-11-21 | Brandeis University | Manipulation of fluids and reactions in microfluidic systems |
US11898193B2 (en) | 2011-07-20 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Manipulating droplet size |
US11901041B2 (en) | 2013-10-04 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Digital analysis of nucleic acid modification |
US11913065B2 (en) | 2012-09-04 | 2024-02-27 | Guardent Health, Inc. | Systems and methods to detect rare mutations and copy number variation |
Families Citing this family (972)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7622294B2 (en) | 1997-03-14 | 2009-11-24 | Trustees Of Tufts College | Methods for detecting target analytes and enzymatic reactions |
US20030027126A1 (en) | 1997-03-14 | 2003-02-06 | Walt David R. | Methods for detecting target analytes and enzymatic reactions |
DE69826697T2 (de) | 1997-07-07 | 2006-02-16 | Medical Research Council | In vitro selektionsmethode |
GB9900298D0 (en) * | 1999-01-07 | 1999-02-24 | Medical Res Council | Optical sorting method |
CA2290731A1 (fr) * | 1999-11-26 | 2001-05-26 | D. Jed Harrison | Appareil et methode de piegeage de reactifs en forme de perles, dans le cadre d'un systeme d'analyse de microfluides |
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 |
ATE455186T1 (de) * | 2000-06-26 | 2010-01-15 | Nugen Technologies Inc | Methoden und zusammensetzungen zur auf transkription basierenden vervielfältigung von nukleinsäuren |
US7846733B2 (en) | 2000-06-26 | 2010-12-07 | Nugen Technologies, Inc. | Methods and compositions for transcription-based nucleic acid amplification |
DE60142709D1 (de) | 2000-12-13 | 2010-09-09 | Nugen Technologies Inc | Methoden und zusammensetzungen zur generierung einer vielzahl von kopien von nukleinsäuresequenzen und methoden zur detektion derselben |
WO2002072772A2 (fr) | 2001-03-09 | 2002-09-19 | Nugen Technologies, Inc. | Procedes et compositions permettant l'amplification de sequences d'arn |
US20030108664A1 (en) * | 2001-10-05 | 2003-06-12 | Kodas Toivo T. | Methods and compositions for the formation of recessed electrical features on a substrate |
WO2003035824A1 (fr) * | 2001-10-25 | 2003-05-01 | Bar-Ilan University | Processeur de biopuces transparentes interactives pour cellules individuelles |
GB0127564D0 (en) * | 2001-11-16 | 2002-01-09 | Medical Res Council | Emulsion compositions |
US20030217923A1 (en) * | 2002-05-24 | 2003-11-27 | Harrison D. Jed | Apparatus and method for trapping bead based reagents within microfluidic analysis systems |
US7595883B1 (en) | 2002-09-16 | 2009-09-29 | The Board Of Trustees Of The Leland Stanford Junior University | Biological analysis arrangement and approach therefor |
US8791053B2 (en) * | 2002-09-27 | 2014-07-29 | Mpm-Holding Aps | Spatially encoded polymer matrix |
KR101216828B1 (ko) * | 2002-12-30 | 2013-01-04 | 더 리전트 오브 더 유니버시티 오브 캘리포니아 | 병원균 검출과 분석을 위한 방법과 기구 |
US7575865B2 (en) * | 2003-01-29 | 2009-08-18 | 454 Life Sciences Corporation | Methods of amplifying and sequencing nucleic acids |
CA2555962C (fr) | 2003-02-26 | 2015-10-06 | Callida Genomics, Inc. | Analyse de reseau d'adn aleatoire par hybridation |
IL154677A0 (en) * | 2003-02-27 | 2003-09-17 | Univ Bar Ilan | A method and apparatus for manipulating an individual cell |
GB0307403D0 (en) | 2003-03-31 | 2003-05-07 | Medical Res Council | Selection by compartmentalised screening |
GB0307428D0 (en) | 2003-03-31 | 2003-05-07 | Medical Res Council | Compartmentalised combinatorial chemistry |
US20060078893A1 (en) * | 2004-10-12 | 2006-04-13 | Medical Research Council | Compartmentalised combinatorial chemistry by microfluidic control |
JP2006523465A (ja) | 2003-04-14 | 2006-10-19 | ニューゲン テクノロジーズ, インコーポレイテッド | ランダムにプライミングされる複合プライマーを用いる大規模増幅 |
FR2856498B1 (fr) * | 2003-06-19 | 2005-09-30 | Goulven Jean Alain Vernois | Distribution sous atmosphere controlee |
US8597597B2 (en) * | 2003-06-26 | 2013-12-03 | Seng Enterprises Ltd. | Picoliter well holding device and method of making the same |
US9200245B2 (en) | 2003-06-26 | 2015-12-01 | Seng Enterprises Ltd. | Multiwell plate |
US7888110B2 (en) * | 2003-06-26 | 2011-02-15 | Seng Enterprises Ltd. | Pico liter well holding device and method of making the same |
WO2005028110A2 (fr) * | 2003-09-19 | 2005-03-31 | Applera Corporation | Microplaques utilisees pour effectuer une amplification nucleotidique par cyclage thermique |
WO2005054431A2 (fr) * | 2003-12-01 | 2005-06-16 | 454 Corporation | Procede permettant d'isoler des micro-reactions chimiques paralleles independantes au moyen d'un filtre poreux |
US7972994B2 (en) | 2003-12-17 | 2011-07-05 | Glaxosmithkline Llc | Methods for synthesis of encoded libraries |
US20050221339A1 (en) | 2004-03-31 | 2005-10-06 | Medical Research Council Harvard University | Compartmentalised screening by microfluidic control |
US7622281B2 (en) | 2004-05-20 | 2009-11-24 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for clonal amplification of nucleic acid |
WO2005118773A2 (fr) | 2004-05-28 | 2005-12-15 | Wafergen, Inc. | Appareil et procedes pour effectuer des analyses multiplex |
US7799553B2 (en) | 2004-06-01 | 2010-09-21 | The Regents Of The University Of California | Microfabricated integrated DNA analysis system |
US7264934B2 (en) * | 2004-06-10 | 2007-09-04 | Ge Healthcare Bio-Sciences Corp. | Rapid parallel nucleic acid analysis |
WO2006003664A1 (fr) * | 2004-07-07 | 2006-01-12 | Seng Enterprises Ltd. | Procede et dispositif d'identification d'une image d'un puits dans une image de composant porteur de puits |
EP1781404A2 (fr) * | 2004-08-25 | 2007-05-09 | Seng Enterprises Limited | Procede et dispositif destines a isoler des cellules |
US7485451B2 (en) * | 2004-11-18 | 2009-02-03 | Regents Of The University Of California | Storage stable compositions of biological materials |
BRPI0515777A (pt) * | 2004-12-11 | 2008-08-05 | Cytogenix Inc | biossìntese isenta de células de ácido nucléico de alta qualidade e usos dos mesmos |
US8038964B2 (en) * | 2005-01-25 | 2011-10-18 | Seng Enterprises Ltd. | Device for studying individual cells |
EP2272983A1 (fr) * | 2005-02-01 | 2011-01-12 | AB Advanced Genetic Analysis Corporation | Réactifs, méthodes et bibliothèques pour séquencage fondé sur des billes |
JP2006211984A (ja) * | 2005-02-04 | 2006-08-17 | Univ Nagoya | エマルジョンを利用した核酸増幅方法、及び核酸増幅反応用キット |
US8374887B1 (en) | 2005-02-11 | 2013-02-12 | Emily H. Alexander | System and method for remotely supervising and verifying pharmacy functions |
JP2008529538A (ja) * | 2005-02-16 | 2008-08-07 | ジェネティック テクノロジーズ リミテッド | 相補性デュプリコンの増幅を含む遺伝子分析方法 |
EP1861721B1 (fr) * | 2005-03-10 | 2017-05-03 | Gen-Probe Incorporated | Systemes et procedes permettant d'effectuer des dosages afin de detecter ou de quantifier des analytes dans des echantillons |
EP1877576B1 (fr) * | 2005-04-12 | 2013-01-23 | 454 Life Sciences Corporation | Procedes de determination de variantes de sequence utilisant un sequencage des amplicons |
US20060228721A1 (en) | 2005-04-12 | 2006-10-12 | Leamon John H | Methods for determining sequence variants using ultra-deep sequencing |
CA2607532C (fr) * | 2005-04-29 | 2013-03-12 | The J. Craig Venter Institute | Amplification et clonage de molecules d'adn uniques en cercle roulant |
NZ564095A (en) * | 2005-05-10 | 2009-06-26 | Oregon State | Methods of mapping polymorphisms and polymorphism microarrays |
WO2007145612A1 (fr) | 2005-06-06 | 2007-12-21 | 454 Life Sciences Corporation | Séquençage d'extrémités appariées |
DK1910538T3 (da) | 2005-06-09 | 2011-08-08 | Praecis Pharm Inc | Fremgangsmåder til syntese af kodede biblioteker |
WO2006138284A2 (fr) | 2005-06-15 | 2006-12-28 | Callida Genomics, Inc. | Analyse d'acides nucleiques a l'aide de melanges aleatoires de fragments non chevauchants |
ES2344802T3 (es) * | 2005-06-23 | 2010-09-07 | Keygene N.V. | Estrategias mejoradas para la secuenciacion de genomas complejos utilizando tecnologias de secuenciacion de alto rendimiento. |
GB0514935D0 (en) | 2005-07-20 | 2005-08-24 | Solexa Ltd | Methods for sequencing a polynucleotide template |
GB0514910D0 (en) | 2005-07-20 | 2005-08-24 | Solexa Ltd | Method for sequencing a polynucleotide template |
US10083273B2 (en) * | 2005-07-29 | 2018-09-25 | Natera, Inc. | System and method for cleaning noisy genetic data and determining chromosome copy number |
US11111543B2 (en) | 2005-07-29 | 2021-09-07 | Natera, Inc. | System and method for cleaning noisy genetic data and determining chromosome copy number |
US11111544B2 (en) | 2005-07-29 | 2021-09-07 | Natera, Inc. | System and method for cleaning noisy genetic data and determining chromosome copy number |
US9424392B2 (en) | 2005-11-26 | 2016-08-23 | Natera, Inc. | System and method for cleaning noisy genetic data from target individuals using genetic data from genetically related individuals |
US10081839B2 (en) * | 2005-07-29 | 2018-09-25 | Natera, Inc | System and method for cleaning noisy genetic data and determining chromosome copy number |
JP2009505642A (ja) * | 2005-08-19 | 2009-02-12 | コモンウェルス サイエンティフィック アンド インダストリアル リサーチ オーガニゼイション | アラクノカンパのルシフェラーゼ |
CA2621267A1 (fr) * | 2005-09-07 | 2007-03-15 | Nugen Technologies, Inc. | Procedure d'amplication d'acide nucleique amelioree |
WO2007133831A2 (fr) | 2006-02-24 | 2007-11-22 | Callida Genomics, Inc. | Séquençage génomique à haut débit sur des puces à adn |
EP2546360A1 (fr) | 2005-10-07 | 2013-01-16 | Callida Genomics, Inc. | Réseaux de molécules simples auto-assemblées et leurs utilisations |
US20070141555A1 (en) * | 2005-10-11 | 2007-06-21 | Mordechai Deutsch | Current damper for the study of cells |
PT1948816E (pt) * | 2005-10-24 | 2012-03-19 | Univ Johns Hopkins | Processos melhorados de focalização |
KR100828714B1 (ko) | 2005-10-25 | 2008-05-09 | 주식회사 엘지화학 | 리보핵산을 이용한 멀티플렉스 증폭방법 |
JP2009513135A (ja) * | 2005-10-28 | 2009-04-02 | プリーシス・ファーマシューティカルズ・インコーポレイテッド | エンコードされたライブラリーを用いて興味のある化合物を同定する方法 |
GB0522310D0 (en) | 2005-11-01 | 2005-12-07 | Solexa Ltd | Methods of preparing libraries of template polynucleotides |
US8288120B2 (en) * | 2005-11-03 | 2012-10-16 | Seng Enterprises Ltd. | Method for studying floating, living cells |
WO2007056490A2 (fr) * | 2005-11-08 | 2007-05-18 | Incom, Inc. | Lame porte-objet d’examen par fibres optiques, trousses de lames porte-objet et leurs utilisations |
WO2007055568A1 (fr) * | 2005-11-14 | 2007-05-18 | Keygene N.V. | Procede de tri a haut debit de populations de marquage de transposons et d'identification a grande echelle de sequences paralleles de sites d'insertion |
GB0524069D0 (en) | 2005-11-25 | 2006-01-04 | Solexa Ltd | Preparation of templates for solid phase amplification |
US20070128610A1 (en) * | 2005-12-02 | 2007-06-07 | Buzby Philip R | Sample preparation method and apparatus for nucleic acid sequencing |
DK1966394T3 (da) * | 2005-12-22 | 2012-10-29 | Keygene Nv | Forbedrede strategier til transkriptprofilering under anvendelse af high throughput-sekventeringsteknologier |
CA2637974A1 (fr) * | 2006-01-19 | 2007-07-26 | The Research Foundation Of State University Of New York | Procedes et dispositifs destines a la detection et l'identification de billes codees et de molecules biologiques |
WO2007083388A1 (fr) * | 2006-01-20 | 2007-07-26 | Toppan Printing Co., Ltd. | Cuve de réaction et procédé de réaction d'amplification d'adn |
US7749365B2 (en) | 2006-02-01 | 2010-07-06 | IntegenX, Inc. | Optimized sample injection structures in microfluidic separations |
DE102006005287B4 (de) * | 2006-02-06 | 2012-12-27 | Siemens Ag | Verfahren zum Nachweis von Zielnukleinsäuren |
CA2641851A1 (fr) | 2006-02-08 | 2007-08-16 | Eric Hans Vermaas | Procede de sequencage d'une matrice polynucleotidique |
US8301394B2 (en) | 2006-02-16 | 2012-10-30 | 454 Life Sciences Corporation | System and method for correcting primer extension errors in nucleic acid sequence data |
US8364417B2 (en) * | 2007-02-15 | 2013-01-29 | 454 Life Sciences Corporation | System and method to correct out of phase errors in DNA sequencing data by use of a recursive algorithm |
US11237171B2 (en) | 2006-02-21 | 2022-02-01 | Trustees Of Tufts College | Methods and arrays for target analyte detection and determination of target analyte concentration in solution |
US8492098B2 (en) * | 2006-02-21 | 2013-07-23 | The Trustees Of Tufts College | Methods and arrays for target analyte detection and determination of reaction components that affect a reaction |
SG10201405158QA (en) * | 2006-02-24 | 2014-10-30 | Callida Genomics Inc | High throughput genome sequencing on dna arrays |
US7766033B2 (en) * | 2006-03-22 | 2010-08-03 | The Regents Of The University Of California | Multiplexed latching valves for microfluidic devices and processors |
SG170802A1 (en) | 2006-03-31 | 2011-05-30 | Solexa Inc | Systems and devices for sequence by synthesis analysis |
US8809068B2 (en) | 2006-04-18 | 2014-08-19 | Advanced Liquid Logic, Inc. | Manipulation of beads in droplets and methods for manipulating droplets |
US7439014B2 (en) | 2006-04-18 | 2008-10-21 | Advanced Liquid Logic, Inc. | Droplet-based surface modification and washing |
CN101495654A (zh) * | 2006-04-19 | 2009-07-29 | 阿普里拉股份有限公司 | 无凝胶珠基测序的试剂、方法和文库 |
US10522240B2 (en) | 2006-05-03 | 2019-12-31 | Population Bio, Inc. | Evaluating genetic disorders |
US7702468B2 (en) * | 2006-05-03 | 2010-04-20 | Population Diagnostics, Inc. | Evaluating genetic disorders |
US9562837B2 (en) | 2006-05-11 | 2017-02-07 | Raindance Technologies, Inc. | Systems for handling microfludic droplets |
WO2007136736A2 (fr) * | 2006-05-19 | 2007-11-29 | Codon Devices, Inc. | Procédés de tri et de synthèse d'acides nucléiques |
CA2653321A1 (fr) * | 2006-05-26 | 2007-12-06 | Althea Technologies, Inc. | Analyse biochimique de cellules partagees |
US11001881B2 (en) | 2006-08-24 | 2021-05-11 | California Institute Of Technology | Methods for detecting analytes |
US8614278B2 (en) | 2006-06-06 | 2013-12-24 | Dow Corning Corporation | Silicone acrylate hybrid composition and method of making same |
US8569416B2 (en) | 2006-06-06 | 2013-10-29 | Dow Corning Corporation | Single phase silicone acrylate formulation |
JP2009540052A (ja) * | 2006-06-06 | 2009-11-19 | ダウ・コーニング・コーポレイション | シリコーンアクリレートハイブリッド組成物およびその製造方法 |
US20080124707A1 (en) * | 2006-06-09 | 2008-05-29 | Agency For Science, Technology And Research | Nucleic acid concatenation |
EP2548972A1 (fr) | 2006-06-14 | 2013-01-23 | Verinata Health, Inc | Procédés pour le diagnostic dýanomalies fýtales |
US20080009007A1 (en) * | 2006-06-16 | 2008-01-10 | Pacific Biosciences Of California, Inc. | Controlled initiation of primer extension |
EP2038425B1 (fr) | 2006-07-12 | 2010-09-15 | Keygene N.V. | Cartographie physique à haut débit par aflp |
WO2008014485A2 (fr) | 2006-07-28 | 2008-01-31 | California Institute Of Technology | Ensembles de pcr-q multiplex |
US11525156B2 (en) | 2006-07-28 | 2022-12-13 | California Institute Of Technology | Multiplex Q-PCR arrays |
WO2008015396A2 (fr) | 2006-07-31 | 2008-02-07 | Solexa Limited | Procédé de préparation de bibliothèque évitant la formation de dimères d'adaptateur |
EP3536396B1 (fr) | 2006-08-07 | 2022-03-30 | The President and Fellows of Harvard College | Tensioactifs fluorocarbonés stabilisateurs d'émulsions |
US11560588B2 (en) | 2006-08-24 | 2023-01-24 | California Institute Of Technology | Multiplex Q-PCR arrays |
WO2008042067A2 (fr) | 2006-09-28 | 2008-04-10 | Illumina, Inc. | Compositions et procédés de séquencage nucléotidique |
US7754429B2 (en) | 2006-10-06 | 2010-07-13 | Illumina Cambridge Limited | Method for pair-wise sequencing a plurity of target polynucleotides |
WO2008045575A2 (fr) * | 2006-10-13 | 2008-04-17 | J. Craig Venter Institute, Inc. | Procédé de séquençage |
US8841116B2 (en) * | 2006-10-25 | 2014-09-23 | The Regents Of The University Of California | Inline-injection microdevice and microfabricated integrated DNA analysis system using same |
US7910354B2 (en) * | 2006-10-27 | 2011-03-22 | Complete Genomics, Inc. | Efficient arrays of amplified polynucleotides |
US8338109B2 (en) | 2006-11-02 | 2012-12-25 | Mayo Foundation For Medical Education And Research | Predicting cancer outcome |
WO2008055915A2 (fr) * | 2006-11-06 | 2008-05-15 | Clondiag Gmbh | Dosages |
US20090111705A1 (en) | 2006-11-09 | 2009-04-30 | Complete Genomics, Inc. | Selection of dna adaptor orientation by hybrid capture |
US20080242560A1 (en) * | 2006-11-21 | 2008-10-02 | Gunderson Kevin L | Methods for generating amplified nucleic acid arrays |
US7902345B2 (en) | 2006-12-05 | 2011-03-08 | Sequenom, Inc. | Detection and quantification of biomolecules using mass spectrometry |
US7932034B2 (en) * | 2006-12-20 | 2011-04-26 | The Board Of Trustees Of The Leland Stanford Junior University | Heat and pH measurement for sequencing of DNA |
WO2008093098A2 (fr) | 2007-02-02 | 2008-08-07 | Illumina Cambridge Limited | Procedes pour indexer des echantillons et sequencer de multiples matrices nucleotidiques |
US9152150B1 (en) | 2007-02-22 | 2015-10-06 | Applied Biosystems, Llc | Compositions, systems, and methods for immiscible fluid discrete volume manipulation |
US9029085B2 (en) | 2007-03-07 | 2015-05-12 | President And Fellows Of Harvard College | Assays and other reactions involving droplets |
JP2010521156A (ja) | 2007-03-16 | 2010-06-24 | 454 ライフ サイエンシーズ コーポレイション | Hiv薬物耐性バリアントの検出のためのシステムおよび方法 |
US20100151465A1 (en) | 2008-03-27 | 2010-06-17 | Jingyue Ju | Selective Capture and Release of Analytes |
US20080243865A1 (en) * | 2007-03-28 | 2008-10-02 | Oracle International Corporation | Maintaining global state of distributed transaction managed by an external transaction manager for clustered database systems |
US20080239867A1 (en) * | 2007-03-28 | 2008-10-02 | Gilbert Donna J | Adjustable stir |
JP2008245612A (ja) * | 2007-03-30 | 2008-10-16 | Hitachi Ltd | 試料調製法および装置 |
US7883265B2 (en) * | 2007-06-01 | 2011-02-08 | Applied Biosystems, Llc | Devices, systems, and methods for preparing emulsions |
WO2009015296A1 (fr) * | 2007-07-24 | 2009-01-29 | The Regents Of The University Of California | Générateur de gouttelettes microfabriqué |
WO2009012984A1 (fr) | 2007-07-26 | 2009-01-29 | Roche Diagnostics Gmbh | Préparation cible pour le séquençage en parallèle de génomes complexes |
JP5020734B2 (ja) * | 2007-07-31 | 2012-09-05 | 株式会社日立ハイテクノロジーズ | 核酸解析方法及び装置 |
US9404150B2 (en) | 2007-08-29 | 2016-08-02 | Sequenom, Inc. | Methods and compositions for universal size-specific PCR |
EP2201021A4 (fr) | 2007-08-29 | 2012-01-25 | Applied Biosystems Llc | Procédé de séquençage alternatif d'acide nucléique |
EP2191011B1 (fr) * | 2007-08-29 | 2017-03-29 | Illumina Cambridge Limited | Procédé de séquençage d'une matrice de polynucléotides |
CA2734029C (fr) | 2007-08-30 | 2016-03-29 | The Trustees Of Tufts College | Procedes pour determiner la concentration d'un analyte dans une solution |
EP2188027A4 (fr) * | 2007-09-11 | 2011-06-08 | Arryx Inc | Procédé de liaison et appareil pour trier des objets |
JP2010538644A (ja) * | 2007-09-13 | 2010-12-16 | アリックス インク | 法医学的dna分析および医学的診断において対象物を選別するための方法および装置 |
EP2188660B1 (fr) * | 2007-09-13 | 2018-11-14 | GE Healthcare Bio-Sciences Corp. | Liquide d'immersion dispersant pour imagerie à résolution élevée et lithographie |
US8716190B2 (en) | 2007-09-14 | 2014-05-06 | Affymetrix, Inc. | Amplification and analysis of selected targets on solid supports |
US9388457B2 (en) | 2007-09-14 | 2016-07-12 | Affymetrix, Inc. | Locus specific amplification using array probes |
US20100304378A1 (en) * | 2007-09-17 | 2010-12-02 | Universite De Strasbourg | Method for Detecting or Quantifying a Truncating Mutation |
US20090118129A1 (en) * | 2007-09-28 | 2009-05-07 | Pacific Biosciences Of California, Inc. | Virtual reads for readlength enhancement |
JP2010539982A (ja) * | 2007-10-01 | 2010-12-24 | アプライド バイオシステムズ, エルエルシー | チェイスライゲーション配列決定法 |
US20100086914A1 (en) * | 2008-10-03 | 2010-04-08 | Roche Molecular Systems, Inc. | High resolution, high throughput hla genotyping by clonal sequencing |
EP2053132A1 (fr) | 2007-10-23 | 2009-04-29 | Roche Diagnostics GmbH | Enrichissement et analyse de séquence de régions génomiques |
WO2009055597A2 (fr) * | 2007-10-25 | 2009-04-30 | Monsanto Technology Llc | Procédés d'identification d'une liaison génétique |
US9145540B1 (en) | 2007-11-15 | 2015-09-29 | Seng Enterprises Ltd. | Device for the study of living cells |
US8592150B2 (en) | 2007-12-05 | 2013-11-26 | Complete Genomics, Inc. | Methods and compositions for long fragment read sequencing |
US9797010B2 (en) | 2007-12-21 | 2017-10-24 | President And Fellows Of Harvard College | Systems and methods for nucleic acid sequencing |
EP2237887A2 (fr) * | 2007-12-26 | 2010-10-13 | Seng Enterprises Ltd. | Dispositif pour l'étude de cellules vivantes |
US8189186B2 (en) * | 2007-12-27 | 2012-05-29 | Lawrence Livermore National Security, Llc. | Signal enhancement using a switchable magnetic trap |
US20090181390A1 (en) * | 2008-01-11 | 2009-07-16 | Signosis, Inc. A California Corporation | High throughput detection of micrornas and use for disease diagnosis |
WO2009091934A1 (fr) * | 2008-01-17 | 2009-07-23 | Sequenom, Inc. | Procédés et compositions d'analyse de séquence d'acide nucléique à simple molécule |
US7767400B2 (en) * | 2008-02-03 | 2010-08-03 | Helicos Biosciences Corporation | Paired-end reads in sequencing by synthesis |
EP2250283A2 (fr) * | 2008-02-12 | 2010-11-17 | Nugen Technologies, Inc. | Procédés et composition pour amplification isotherme d'acide nucléique |
US20090203531A1 (en) * | 2008-02-12 | 2009-08-13 | Nurith Kurn | Method for Archiving and Clonal Expansion |
CA2717320A1 (fr) * | 2008-03-11 | 2009-09-17 | Sequenom, Inc. | Tests adn pour determiner le sexe d'un bebe avant sa naissance |
AU2009226248B8 (en) | 2008-03-17 | 2014-10-02 | Stichting Genetwister Ip | Expression-linked gene discovery |
US10745740B2 (en) | 2008-03-19 | 2020-08-18 | Qiagen Sciences, Llc | Sample preparation |
GB2470672B (en) * | 2008-03-21 | 2012-09-12 | Nugen Technologies Inc | Methods of RNA amplification in the presence of DNA |
EP3170904B1 (fr) * | 2008-03-28 | 2017-08-16 | Pacific Biosciences Of California, Inc. | Compositions et procédés pour le séquençage d'acide nucléique |
BRPI0911326B1 (pt) * | 2008-04-04 | 2019-11-26 | Allopartis Biotechnologies Inc | método de seleção para atividade enzimática melhorada em um substrato insolúvel |
JP5227062B2 (ja) | 2008-04-08 | 2013-07-03 | 株式会社日立製作所 | Dna分析装置 |
TWI460602B (zh) * | 2008-05-16 | 2014-11-11 | Counsyl Inc | 廣用的懷孕前篩檢裝置 |
AU2009253675A1 (en) | 2008-05-28 | 2009-12-03 | Genomedx Biosciences, Inc. | Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer |
US10407731B2 (en) | 2008-05-30 | 2019-09-10 | Mayo Foundation For Medical Education And Research | Biomarker panels for predicting prostate cancer outcomes |
WO2010003132A1 (fr) | 2008-07-02 | 2010-01-07 | Illumina Cambridge Ltd. | Utilisation de populations de billes dans la fabrication de matrices sur des surfaces |
WO2010009426A2 (fr) * | 2008-07-17 | 2010-01-21 | Life Technologies Corporation | Dispositifs et procédés pour la délivrance de réactif |
ES2532153T3 (es) | 2008-07-18 | 2015-03-24 | Trovagene, Inc. | Métodos para la detección de secuencias de ácidos nucleicos "ultracortos" basados en PCR |
US20100035252A1 (en) * | 2008-08-08 | 2010-02-11 | Ion Torrent Systems Incorporated | Methods for sequencing individual nucleic acids under tension |
EP3216874A1 (fr) | 2008-09-05 | 2017-09-13 | TOMA Biosciences, Inc. | Procédés pour la stratification et l'annotation des options de traitement médicamenteux contre le cancer |
US8795961B2 (en) | 2008-09-05 | 2014-08-05 | Pacific Biosciences Of California, Inc. | Preparations, compositions, and methods for nucleic acid sequencing |
US8476013B2 (en) | 2008-09-16 | 2013-07-02 | Sequenom, Inc. | Processes and compositions for methylation-based acid enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses |
US8962247B2 (en) | 2008-09-16 | 2015-02-24 | Sequenom, Inc. | Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non invasive prenatal diagnoses |
US20110218123A1 (en) | 2008-09-19 | 2011-09-08 | President And Fellows Of Harvard College | Creation of libraries of droplets and related species |
WO2010039189A2 (fr) * | 2008-09-23 | 2010-04-08 | Helicos Biosciences Corporation | Procédés de séquençage d’acides nucléiques dégradés ou modifiés |
US20100075862A1 (en) * | 2008-09-23 | 2010-03-25 | Quanterix Corporation | High sensitivity determination of the concentration of analyte molecules or particles in a fluid sample |
US8663920B2 (en) | 2011-07-29 | 2014-03-04 | Bio-Rad Laboratories, Inc. | Library characterization by digital assay |
US9417190B2 (en) | 2008-09-23 | 2016-08-16 | Bio-Rad Laboratories, Inc. | Calibrations and controls for droplet-based assays |
US9132394B2 (en) | 2008-09-23 | 2015-09-15 | Bio-Rad Laboratories, Inc. | System for detection of spaced droplets |
US20100075439A1 (en) * | 2008-09-23 | 2010-03-25 | Quanterix Corporation | Ultra-sensitive detection of molecules by capture-and-release using reducing agents followed by quantification |
US8951939B2 (en) | 2011-07-12 | 2015-02-10 | Bio-Rad Laboratories, Inc. | Digital assays with multiplexed detection of two or more targets in the same optical channel |
US9492797B2 (en) | 2008-09-23 | 2016-11-15 | Bio-Rad Laboratories, Inc. | System for detection of spaced droplets |
US9598725B2 (en) | 2010-03-02 | 2017-03-21 | Bio-Rad Laboratories, Inc. | Emulsion chemistry for encapsulated droplets |
US9156010B2 (en) | 2008-09-23 | 2015-10-13 | Bio-Rad Laboratories, Inc. | Droplet-based assay system |
US11130128B2 (en) | 2008-09-23 | 2021-09-28 | Bio-Rad Laboratories, Inc. | Detection method for a target nucleic acid |
US8222047B2 (en) * | 2008-09-23 | 2012-07-17 | Quanterix Corporation | Ultra-sensitive detection of molecules on single molecule arrays |
US9764322B2 (en) | 2008-09-23 | 2017-09-19 | Bio-Rad Laboratories, Inc. | System for generating droplets with pressure monitoring |
US8633015B2 (en) | 2008-09-23 | 2014-01-21 | Bio-Rad Laboratories, Inc. | Flow-based thermocycling system with thermoelectric cooler |
US9399215B2 (en) | 2012-04-13 | 2016-07-26 | Bio-Rad Laboratories, Inc. | Sample holder with a well having a wicking promoter |
WO2011120020A1 (fr) | 2010-03-25 | 2011-09-29 | Quantalife, Inc. | Système de transport de gouttelettes à des fins de détection |
US8709762B2 (en) | 2010-03-02 | 2014-04-29 | Bio-Rad Laboratories, Inc. | System for hot-start amplification via a multiple emulsion |
US10512910B2 (en) | 2008-09-23 | 2019-12-24 | Bio-Rad Laboratories, Inc. | Droplet-based analysis method |
US20100087325A1 (en) * | 2008-10-07 | 2010-04-08 | Illumina, Inc. | Biological sample temperature control system and method |
US8541207B2 (en) | 2008-10-22 | 2013-09-24 | Illumina, Inc. | Preservation of information related to genomic DNA methylation |
US9080211B2 (en) | 2008-10-24 | 2015-07-14 | Epicentre Technologies Corporation | Transposon end compositions and methods for modifying nucleic acids |
ES2515065T3 (es) | 2008-10-24 | 2014-10-29 | Epicentre Technologies Corporation | Composiciones de extremo del transposón y métodos para modificar ácidos nucleicos |
US8877436B2 (en) * | 2008-10-27 | 2014-11-04 | Qiagen Gaithersburg, Inc. | Fast results hybrid capture assay on an automated platform |
US8486865B2 (en) | 2008-11-03 | 2013-07-16 | The Regents Of The University Of California | Methods for detecting modification resistant nucleic acids |
JP2010110262A (ja) * | 2008-11-06 | 2010-05-20 | Hitachi Maxell Ltd | ウェルプレートを用いた核酸増幅法 |
US9506119B2 (en) | 2008-11-07 | 2016-11-29 | Adaptive Biotechnologies Corp. | Method of sequence determination using sequence tags |
US9394567B2 (en) | 2008-11-07 | 2016-07-19 | Adaptive Biotechnologies Corporation | Detection and quantification of sample contamination in immune repertoire analysis |
US8748103B2 (en) | 2008-11-07 | 2014-06-10 | Sequenta, Inc. | Monitoring health and disease status using clonotype profiles |
US8628927B2 (en) | 2008-11-07 | 2014-01-14 | Sequenta, Inc. | Monitoring health and disease status using clonotype profiles |
US9528160B2 (en) | 2008-11-07 | 2016-12-27 | Adaptive Biotechnolgies Corp. | Rare clonotypes and uses thereof |
US9365901B2 (en) | 2008-11-07 | 2016-06-14 | Adaptive Biotechnologies Corp. | Monitoring immunoglobulin heavy chain evolution in B-cell acute lymphoblastic leukemia |
SG195652A1 (en) | 2008-11-07 | 2013-12-30 | Sequenta Inc | Methods of monitoring conditions by sequence analysis |
US10236078B2 (en) | 2008-11-17 | 2019-03-19 | Veracyte, Inc. | Methods for processing or analyzing a sample of thyroid tissue |
US9495515B1 (en) | 2009-12-09 | 2016-11-15 | Veracyte, Inc. | Algorithms for disease diagnostics |
GB2512153B (en) | 2008-11-17 | 2014-11-12 | Veracyte Inc | Methods and compositions of molecular profiling for disease diagnostics |
US8674175B2 (en) | 2008-12-05 | 2014-03-18 | Keygene N.V. | Farnesene synthase |
EP3150724A1 (fr) | 2008-12-19 | 2017-04-05 | President and Fellows of Harvard College | Séquençage d'acide nucléique assisté par particules |
WO2010075188A2 (fr) | 2008-12-23 | 2010-07-01 | Illumina Inc. | Libération multibase pour lectures longues dans le séquençage par des protocoles de synthèse |
ES2403312T3 (es) | 2009-01-13 | 2013-05-17 | Keygene N.V. | Nuevas estrategias para la secuenciación del genoma |
US20100179074A1 (en) * | 2009-01-15 | 2010-07-15 | Honeywell International Inc. | Methods and apparatus for fluid delivery and removal of micron scale structures |
HUE029424T2 (en) | 2009-01-15 | 2017-02-28 | Adaptive Biotechnologies Corp | Adaptive immunity profiling and a method for producing monoclonal antibodies |
CN102333891A (zh) * | 2009-01-20 | 2012-01-25 | 利兰·斯坦福青年大学托管委员会 | 用于药靶诊断、预后和鉴别的单细胞基因表达 |
US20100331204A1 (en) | 2009-02-13 | 2010-12-30 | Jeff Jeddeloh | Methods and systems for enrichment of target genomic sequences |
JP5457222B2 (ja) | 2009-02-25 | 2014-04-02 | エフ.ホフマン−ラ ロシュ アーゲー | 小型化ハイスループット核酸分析 |
US9347092B2 (en) | 2009-02-25 | 2016-05-24 | Roche Molecular System, Inc. | Solid support for high-throughput nucleic acid analysis |
US9074258B2 (en) | 2009-03-04 | 2015-07-07 | Genomedx Biosciences Inc. | Compositions and methods for classifying thyroid nodule disease |
WO2010107946A2 (fr) * | 2009-03-18 | 2010-09-23 | Sequenom, Inc. | Utilisation d'endonucléases thermostables pour générer des molécules rapporteuses |
EP2411148B1 (fr) | 2009-03-23 | 2018-02-21 | Raindance Technologies, Inc. | Manipulation de gouttelettes microfluidiques |
GB0904957D0 (en) | 2009-03-23 | 2009-05-06 | Univ Erasmus Medical Ct | Tumour gene profile |
GB0904934D0 (en) | 2009-03-23 | 2009-05-06 | Geneseqe As | Method and apparatus for detecting molecules |
WO2010115100A1 (fr) | 2009-04-03 | 2010-10-07 | L&C Diagment, Inc. | Procédés et systèmes de détection multiplex d'acide nucléique |
WO2010117456A2 (fr) * | 2009-04-08 | 2010-10-14 | Applied Biosystems, Llc | Enrichissement sur colonne de billes de pcr comprenant des amplicons insérés |
JP2012529918A (ja) | 2009-04-19 | 2012-11-29 | セルマティックス, インコーポレイテッド | 不妊症および/または卵の質を評価するための方法および装置 |
US9090663B2 (en) * | 2009-04-21 | 2015-07-28 | The Trustees Of Columbia University In The City Of New York | Systems and methods for the capture and separation of microparticles |
AU2010242073C1 (en) | 2009-04-30 | 2015-12-24 | Good Start Genetics, Inc. | Methods and compositions for evaluating genetic markers |
EP2248914A1 (fr) | 2009-05-05 | 2010-11-10 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Utilisation d'endonucléases à restriction de classe IIB dans des applications de séquençage de 2ème génération |
EP3360978A3 (fr) | 2009-05-07 | 2018-09-26 | Veracyte, Inc. | Procédés pour le diagnostic d'affections thyroïdiennes |
US8003329B2 (en) * | 2009-05-12 | 2011-08-23 | Becton Dickinson & Company | Molecular counting by color-coded micelles |
EP3663750B1 (fr) | 2009-05-29 | 2021-11-03 | Life Technologies Corporation | Particules de polymère d'acide nucléique échafaudées et procédés de fabrication et d'utilisation |
US9524369B2 (en) | 2009-06-15 | 2016-12-20 | Complete Genomics, Inc. | Processing and analysis of complex nucleic acid sequence data |
JP2012531202A (ja) | 2009-06-25 | 2012-12-10 | フレッド ハチンソン キャンサー リサーチ センター | 適応免疫を測定する方法 |
WO2011002319A2 (fr) * | 2009-07-02 | 2011-01-06 | Zygem Corporation Limited | Blocage, extraction et détection combinés d'acide nucléique dans un réceptacle de réaction unique |
JP5099455B2 (ja) * | 2009-07-16 | 2012-12-19 | 独立行政法人科学技術振興機構 | エマルジョンを用いたrnaの選択的増幅法 |
US8825412B2 (en) | 2010-05-18 | 2014-09-02 | Natera, Inc. | Methods for non-invasive prenatal ploidy calling |
EP2456892B1 (fr) * | 2009-07-24 | 2014-10-01 | Illumina, Inc. | Procédé de séquençage d'une matrice polynucléotidique |
JP5795313B2 (ja) * | 2009-07-29 | 2015-10-14 | パイロベット ピーティーイー エルティーディーPyrobett Pte Ltd | アッセイを行うための方法及び装置 |
WO2011014811A1 (fr) * | 2009-07-31 | 2011-02-03 | Ibis Biosciences, Inc. | Amorces de capture et supports solides liés à une séquence de capture pour tests diagnostiques moléculaires |
EP2470669B1 (fr) | 2009-08-25 | 2014-06-18 | Illumina, Inc. | Procédés de sélection et d amplification de polynucléotides |
JP5869482B2 (ja) | 2009-09-02 | 2016-02-24 | プレジデント アンド フェローズ オブ ハーバード カレッジ | ジェッティングおよび他の技術を使用して生成された多重エマルジョン |
EP2473618B1 (fr) | 2009-09-02 | 2015-03-04 | Bio-Rad Laboratories, Inc. | Système de mélange de fluides par coalescence d'émulsions multiples |
US10072287B2 (en) | 2009-09-10 | 2018-09-11 | Centrillion Technology Holdings 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 |
WO2011041485A1 (fr) | 2009-09-30 | 2011-04-07 | Gene Security Network, Inc. | Méthode non invasive de détermination d'une ploïdie prénatale |
US10520500B2 (en) | 2009-10-09 | 2019-12-31 | Abdeslam El Harrak | Labelled silica-based nanomaterial with enhanced properties and uses thereof |
AU2010315580B2 (en) | 2009-10-27 | 2014-11-06 | President And Fellows Of Harvard College | Droplet creation techniques |
EP2494353B1 (fr) | 2009-10-30 | 2017-09-27 | Illumina Inc. | Dispositif comprenant une pluralité de microrécipients codés et une pluralité de compartiments et un procédé de lecture d'une pluralité de microrécipients codés |
EP2494069B1 (fr) | 2009-10-30 | 2013-10-02 | Roche Diagniostics GmbH | Procédé de détection des aberrations chromosomiques équilibrées |
CN102712954A (zh) | 2009-11-06 | 2012-10-03 | 小利兰·斯坦福大学托管委员会 | 器官移植患者移植排斥的非侵入性诊断 |
ES2542426T3 (es) * | 2009-11-16 | 2015-08-05 | Genomictree, Inc. | Método de genotipado |
EP2504448B1 (fr) * | 2009-11-25 | 2016-10-19 | Bio-Rad Laboratories, Inc. | Procédés et compositions destinés à détecter un matériel génétique |
US10446272B2 (en) | 2009-12-09 | 2019-10-15 | Veracyte, Inc. | Methods and compositions for classification of samples |
WO2011071382A1 (fr) | 2009-12-10 | 2011-06-16 | Keygene N.V. | Profilage polymorphique du génome entier |
CN102656279A (zh) | 2009-12-17 | 2012-09-05 | 凯津公司 | 基于全基因组测序的限制性酶 |
CN102791880A (zh) | 2009-12-18 | 2012-11-21 | 凯津公司 | 改进的大突变分析 |
US9926593B2 (en) | 2009-12-22 | 2018-03-27 | Sequenom, Inc. | Processes and kits for identifying aneuploidy |
EP2517025B1 (fr) | 2009-12-23 | 2019-11-27 | Bio-Rad Laboratories, Inc. | Procédés pour réduire l'échange de molécules entre des gouttelettes |
ES2704701T3 (es) | 2010-01-19 | 2019-03-19 | Verinata Health Inc | Nuevo protocolo de preparación de bibliotecas de secuenciación |
US20120100548A1 (en) | 2010-10-26 | 2012-04-26 | Verinata Health, Inc. | Method for determining copy number variations |
PL2531880T3 (pl) | 2010-02-01 | 2017-09-29 | Illumina Inc. | Sposoby ogniskowania oraz układy optyczne i zespoły optyczne realizujące te sposoby |
US20110195457A1 (en) * | 2010-02-09 | 2011-08-11 | General Electric Company | Isothermal amplification of nucleic acid using primers comprising a randomized sequence and specific primers and uses thereof |
US9366632B2 (en) | 2010-02-12 | 2016-06-14 | Raindance Technologies, Inc. | Digital analyte analysis |
US10351905B2 (en) | 2010-02-12 | 2019-07-16 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
WO2011103421A1 (fr) | 2010-02-18 | 2011-08-25 | Shuber Anthony P | Compositions et méthodes pour le traitement du cancer |
US20110262903A1 (en) | 2010-02-26 | 2011-10-27 | Life Technologies Corporation | Modified Proteins and Methods of Making and Using Same |
US8415171B2 (en) * | 2010-03-01 | 2013-04-09 | Quanterix Corporation | Methods and systems for extending dynamic range in assays for the detection of molecules or particles |
US8236574B2 (en) | 2010-03-01 | 2012-08-07 | Quanterix Corporation | Ultra-sensitive detection of molecules or particles using beads or other capture objects |
WO2011109379A1 (fr) | 2010-03-01 | 2011-09-09 | Quanterix Corporation | Procédés et systèmes pour étendre la plage dynamique dans des dosages pour la détection de molécules ou de particules |
US9678068B2 (en) * | 2010-03-01 | 2017-06-13 | Quanterix Corporation | Ultra-sensitive detection of molecules using dual detection methods |
CN202281746U (zh) | 2010-03-06 | 2012-06-20 | 伊鲁米那股份有限公司 | 检测来自样品光信号的测定设备及其光学组件和光学系统 |
US20110311963A1 (en) * | 2010-03-16 | 2011-12-22 | Life Technologies Corporation | Method and Apparatus for Addressable Flow Cells in Single Molecule Sequencing |
EP2550351A4 (fr) | 2010-03-25 | 2014-07-09 | Quantalife Inc | Système de détection pour analyses à base de gouttelettes |
EP2550528B1 (fr) | 2010-03-25 | 2019-09-11 | Bio-Rad Laboratories, Inc. | Génération de gouttelettes pour dosages sur gouttelettes |
US8951940B2 (en) | 2010-04-01 | 2015-02-10 | Illumina, Inc. | Solid-phase clonal amplification and related methods |
PT2556171E (pt) | 2010-04-05 | 2015-12-21 | Prognosys Biosciences Inc | Ensaios biológicos codificados espacialmente |
US10787701B2 (en) | 2010-04-05 | 2020-09-29 | Prognosys Biosciences, Inc. | Spatially encoded biological assays |
US20190300945A1 (en) | 2010-04-05 | 2019-10-03 | Prognosys Biosciences, Inc. | Spatially Encoded Biological Assays |
SI2558577T1 (sl) | 2010-04-16 | 2019-05-31 | Nuevolution A/S | Bifunkcionalni kompleksi in metode za pripravo in uporabo takšnih kompleksov |
US20110269194A1 (en) * | 2010-04-20 | 2011-11-03 | Swift Biosciences, Inc. | Materials and methods for nucleic acid fractionation by solid phase entrapment and enzyme-mediated detachment |
WO2011135041A1 (fr) | 2010-04-30 | 2011-11-03 | Roche Diagnostics Gmbh | Système et procédé de purification et d'utilisation de la pyrophosphatase inorganique provenant d'aquifex aeolicus |
US9930297B2 (en) * | 2010-04-30 | 2018-03-27 | Becton, Dickinson And Company | System and method for acquiring images of medication preparations |
EP2388337B1 (fr) | 2010-04-30 | 2014-07-02 | Nxp B.V. | Dispositif de détection et son procédé de fabrication |
EP2566985A4 (fr) * | 2010-05-06 | 2014-08-06 | Ibis Biosciences Inc | Systèmes intégrés de préparation d'échantillons et mélanges d'enzymes stabilisées |
DK2567226T3 (en) | 2010-05-06 | 2016-10-10 | Adaptive Biotechnologies Corp | Monitoring the health and disease status using klonotypeprofiler |
WO2011140433A2 (fr) | 2010-05-07 | 2011-11-10 | The Board Of Trustees Of The Leland Stanford Junior University | Mesure et comparaison de diversité immunitaire par séquençage à haut débit |
WO2011143194A2 (fr) | 2010-05-10 | 2011-11-17 | Life Technologies Corporation | Système et procédé de traitement d'un échantillon biologique |
WO2011143361A2 (fr) | 2010-05-11 | 2011-11-17 | Veracyte, Inc. | Méthodes et compositions utilisées dans le cadre du diagnostic de maladies |
US11322224B2 (en) | 2010-05-18 | 2022-05-03 | Natera, Inc. | Methods for non-invasive prenatal ploidy calling |
US20190010543A1 (en) | 2010-05-18 | 2019-01-10 | Natera, Inc. | Methods for simultaneous amplification of target loci |
US11408031B2 (en) | 2010-05-18 | 2022-08-09 | Natera, Inc. | Methods for non-invasive prenatal paternity testing |
US11326208B2 (en) | 2010-05-18 | 2022-05-10 | Natera, Inc. | Methods for nested PCR amplification of cell-free DNA |
US11332785B2 (en) | 2010-05-18 | 2022-05-17 | Natera, Inc. | Methods for non-invasive prenatal ploidy calling |
US11939634B2 (en) | 2010-05-18 | 2024-03-26 | Natera, Inc. | Methods for simultaneous amplification of target loci |
US9677118B2 (en) | 2014-04-21 | 2017-06-13 | Natera, Inc. | Methods for simultaneous amplification of target loci |
US11332793B2 (en) | 2010-05-18 | 2022-05-17 | Natera, Inc. | Methods for simultaneous amplification of target loci |
US10316362B2 (en) | 2010-05-18 | 2019-06-11 | Natera, Inc. | Methods for simultaneous amplification of target loci |
US11339429B2 (en) | 2010-05-18 | 2022-05-24 | Natera, Inc. | Methods for non-invasive prenatal ploidy calling |
US20110287432A1 (en) | 2010-05-21 | 2011-11-24 | 454 Life Science Corporation | System and method for tailoring nucleotide concentration to enzymatic efficiencies in dna sequencing technologies |
US20120035062A1 (en) | 2010-06-11 | 2012-02-09 | Life Technologies Corporation | Alternative nucleotide flows in sequencing-by-synthesis methods |
US9353412B2 (en) | 2010-06-18 | 2016-05-31 | Illumina, Inc. | Conformational probes and methods for sequencing nucleic acids |
US9650629B2 (en) * | 2010-07-07 | 2017-05-16 | Roche Molecular Systems, Inc. | Clonal pre-amplification in emulsion |
WO2012008831A1 (fr) | 2010-07-13 | 2012-01-19 | Keygene N.V. | Génération simplifiée de cartes physiques de novo à partir de banques de clones |
CN105964312A (zh) | 2010-07-22 | 2016-09-28 | 基因细胞生物系统有限公司 | 复合液体池 |
CN103392182B (zh) | 2010-08-02 | 2017-07-04 | 众有生物有限公司 | 用于发现遗传疾病中致病突变的系统和方法 |
US20120034603A1 (en) | 2010-08-06 | 2012-02-09 | Tandem Diagnostics, Inc. | Ligation-based detection of genetic variants |
US10533223B2 (en) | 2010-08-06 | 2020-01-14 | Ariosa Diagnostics, Inc. | Detection of target nucleic acids using hybridization |
US11203786B2 (en) | 2010-08-06 | 2021-12-21 | Ariosa Diagnostics, Inc. | Detection of target nucleic acids using hybridization |
US20130040375A1 (en) | 2011-08-08 | 2013-02-14 | Tandem Diagnotics, Inc. | Assay systems for genetic analysis |
US11031095B2 (en) | 2010-08-06 | 2021-06-08 | Ariosa Diagnostics, Inc. | Assay systems for determination of fetal copy number variation |
US8700338B2 (en) | 2011-01-25 | 2014-04-15 | Ariosa Diagnosis, Inc. | Risk calculation for evaluation of fetal aneuploidy |
US20130261003A1 (en) | 2010-08-06 | 2013-10-03 | Ariosa Diagnostics, In. | Ligation-based detection of genetic variants |
US10167508B2 (en) | 2010-08-06 | 2019-01-01 | Ariosa Diagnostics, Inc. | Detection of genetic abnormalities |
US20140342940A1 (en) | 2011-01-25 | 2014-11-20 | Ariosa Diagnostics, Inc. | Detection of Target Nucleic Acids using Hybridization |
JP5917519B2 (ja) | 2010-09-10 | 2016-05-18 | バイオ−ラッド ラボラトリーズ インコーポレーティッド | クロマチン分析のためのdnaのサイズ選択 |
EP3572528A1 (fr) | 2010-09-24 | 2019-11-27 | The Board of Trustees of the Leland Stanford Junior University | Capture directe, amplification et séquençage d'adn cible à l'aide d'amorces immobilisées |
US20120077716A1 (en) | 2010-09-29 | 2012-03-29 | 454 Life Sciences Corporation | System and method for producing functionally distinct nucleic acid library ends through use of deoxyinosine |
US8759038B2 (en) | 2010-09-29 | 2014-06-24 | Illumina Cambridge Limited | Compositions and methods for sequencing nucleic acids |
GB201016484D0 (en) | 2010-09-30 | 2010-11-17 | Geneseque As | Method |
US9399217B2 (en) | 2010-10-04 | 2016-07-26 | Genapsys, Inc. | Chamber free nanoreactor system |
US9187783B2 (en) | 2010-10-04 | 2015-11-17 | Genapsys, Inc. | Systems and methods for automated reusable parallel biological reactions |
US9184099B2 (en) | 2010-10-04 | 2015-11-10 | The Board Of Trustees Of The Leland Stanford Junior University | Biosensor devices, systems and methods therefor |
US20120322665A1 (en) | 2010-10-08 | 2012-12-20 | 454 Life Sciences Corporation | System and method for detection of hiv-1 clades and recombinants of the reverse transcriptase and protease regions |
US9689012B2 (en) | 2010-10-12 | 2017-06-27 | Cornell University | Method of dual-adapter recombination for efficient concatenation of multiple DNA fragments in shuffled or specified arrangements |
US20150225792A1 (en) | 2014-01-17 | 2015-08-13 | Northwestern University | Compositions and methods for identifying depressive disorders |
US10233501B2 (en) | 2010-10-19 | 2019-03-19 | Northwestern University | Biomarkers predictive of predisposition to depression and response to treatment |
US10093981B2 (en) | 2010-10-19 | 2018-10-09 | Northwestern University | Compositions and methods for identifying depressive disorders |
US20150218639A1 (en) | 2014-01-17 | 2015-08-06 | Northwestern University | Biomarkers predictive of predisposition to depression and response to treatment |
EP2633069B1 (fr) | 2010-10-26 | 2015-07-01 | Illumina, Inc. | Procédés de séquençage |
EP3141614B1 (fr) | 2010-10-27 | 2018-11-28 | Life Technologies Corporation | Modèle prédictif destiné à être utilisé dans le séquençage par synthèse |
US9387476B2 (en) | 2010-10-27 | 2016-07-12 | Illumina, Inc. | Flow cells for biological or chemical analysis |
US10273540B2 (en) | 2010-10-27 | 2019-04-30 | Life Technologies Corporation | Methods and apparatuses for estimating parameters in a predictive model for use in sequencing-by-synthesis |
WO2012058096A1 (fr) * | 2010-10-27 | 2012-05-03 | Illumina, Inc. | Microdispositifs et cartouches de biocapteurs pour analyse biologique ou chimique et systèmes et procédés associés |
EP4016086A1 (fr) | 2010-11-01 | 2022-06-22 | Bio-Rad Laboratories, Inc. | Système de formation d'émulsions |
WO2012074855A2 (fr) | 2010-11-22 | 2012-06-07 | The Regents Of The University Of California | Procédés d'identification d'un transcrit cellulaire naissant d'arn |
EP2646573A1 (fr) | 2010-12-01 | 2013-10-09 | MorphoSys AG | Détection simultanée de biomolécules dans des cellules uniques |
EP3709303A1 (fr) | 2010-12-14 | 2020-09-16 | Life Technologies Corporation | Systèmes et procédés permettant la surveillance de la qualité d'exécution de séquençage du temps d'exécution |
ES2770342T3 (es) | 2010-12-22 | 2020-07-01 | Natera Inc | Procedimientos para pruebas prenatales no invasivas de paternidad |
US9163281B2 (en) | 2010-12-23 | 2015-10-20 | Good Start Genetics, Inc. | Methods for maintaining the integrity and identification of a nucleic acid template in a multiplex sequencing reaction |
US9594870B2 (en) | 2010-12-29 | 2017-03-14 | Life Technologies Corporation | Time-warped background signal for sequencing-by-synthesis operations |
US20130060482A1 (en) | 2010-12-30 | 2013-03-07 | Life Technologies Corporation | Methods, systems, and computer readable media for making base calls in nucleic acid sequencing |
US10241075B2 (en) | 2010-12-30 | 2019-03-26 | Life Technologies Corporation | Methods, systems, and computer readable media for nucleic acid sequencing |
KR20210131432A (ko) | 2010-12-30 | 2021-11-02 | 파운데이션 메디신 인코포레이티드 | 종양 샘플의 다유전자 분석의 최적화 |
WO2012092455A2 (fr) | 2010-12-30 | 2012-07-05 | Life Technologies Corporation | Modèles pour analyser des données issues d'opérations de séquençage par synthèse |
US8951781B2 (en) | 2011-01-10 | 2015-02-10 | Illumina, Inc. | Systems, methods, and apparatuses to image a sample for biological or chemical analysis |
US20130005591A1 (en) * | 2011-01-13 | 2013-01-03 | Halgen Corporation | Method for parallel amplification of nucleic acids |
CA2823815A1 (fr) | 2011-01-14 | 2012-07-19 | Keygene N.V. | Genotypage fonde sur des sequences aleatoires a extremites appariees |
WO2012100194A1 (fr) | 2011-01-20 | 2012-07-26 | Ibis Biosciences, Inc. | Transducteur microfluidique |
US10131947B2 (en) | 2011-01-25 | 2018-11-20 | Ariosa Diagnostics, Inc. | Noninvasive detection of fetal aneuploidy in egg donor pregnancies |
US8756020B2 (en) | 2011-01-25 | 2014-06-17 | Ariosa Diagnostics, Inc. | Enhanced risk probabilities using biomolecule estimations |
US11270781B2 (en) | 2011-01-25 | 2022-03-08 | Ariosa Diagnostics, Inc. | Statistical analysis for non-invasive sex chromosome aneuploidy determination |
US9994897B2 (en) | 2013-03-08 | 2018-06-12 | Ariosa Diagnostics, Inc. | Non-invasive fetal sex determination |
US9952237B2 (en) | 2011-01-28 | 2018-04-24 | Quanterix Corporation | Systems, devices, and methods for ultra-sensitive detection of molecules or particles |
US10144950B2 (en) | 2011-01-31 | 2018-12-04 | Roche Sequencing Solutions, Inc. | Methods of identifying multiple epitopes in cells |
US20130316358A1 (en) | 2011-01-31 | 2013-11-28 | Yeda Research And Development Co. Ltd. | Methods of diagnosing disease using overlap extension pcr |
WO2012108920A1 (fr) | 2011-02-09 | 2012-08-16 | Natera, Inc | Procédés de classification de ploïdie prénatale non invasive |
WO2012129187A1 (fr) | 2011-03-18 | 2012-09-27 | Bio-Rad Laboratories, Inc. | Essais numériques multiplexés avec utilisation combinée de signaux |
US20120252682A1 (en) | 2011-04-01 | 2012-10-04 | Maples Corporate Services Limited | Methods and systems for sequencing nucleic acids |
WO2012139125A2 (fr) | 2011-04-07 | 2012-10-11 | Life Technologies Corporation | Système et procédés de fabrication et de traitement d'émulsions |
US9121047B2 (en) | 2011-04-07 | 2015-09-01 | Life Technologies Corporation | System and methods for making and processing emulsions |
EP3878975A1 (fr) | 2011-04-08 | 2021-09-15 | Life Technologies Corporation | Ordonnancements d'écoulement de réactif de protection de phase pour utilisation dans un séquençage-par-synthèse |
WO2012142301A2 (fr) | 2011-04-12 | 2012-10-18 | Quanterix Corporation | Procédé de détermination d'un protocole de traitement et/ou d'un pronostic de rétablissement d'un patient à la suite d'un traumatisme cérébral |
GB201106254D0 (en) | 2011-04-13 | 2011-05-25 | Frisen Jonas | Method and product |
ES2625288T3 (es) | 2011-04-15 | 2017-07-19 | The Johns Hopkins University | Sistema de secuenciación segura |
AU2012249759A1 (en) | 2011-04-25 | 2013-11-07 | Bio-Rad Laboratories, Inc. | Methods and compositions for nucleic acid analysis |
CA2834218C (fr) | 2011-04-29 | 2021-02-16 | Sequenom, Inc. | Quantification d'une minorite d'especes d'acide nucleique utilisant des oligonucleotides inhibiteurs |
US9487825B2 (en) | 2011-05-13 | 2016-11-08 | Mount Sinai School Of Medicine | Pooled adapter strategy for reducing bias in small RNA characterization |
SG10201605049QA (en) * | 2011-05-20 | 2016-07-28 | Fluidigm Corp | Nucleic acid encoding reactions |
EP2714254B1 (fr) | 2011-05-23 | 2017-09-06 | President and Fellows of Harvard College | Génération d'émulsions et, notamment, d'émulsions multiples |
US9926596B2 (en) | 2011-05-27 | 2018-03-27 | Genapsys, Inc. | Systems and methods for genetic and biological analysis |
US8585973B2 (en) | 2011-05-27 | 2013-11-19 | The Board Of Trustees Of The Leland Stanford Junior University | Nano-sensor array |
EP2714928B1 (fr) * | 2011-05-27 | 2017-08-02 | Life Technologies Corporation | Procédés de manipulation de biomolécules |
US8841071B2 (en) | 2011-06-02 | 2014-09-23 | Raindance Technologies, Inc. | Sample multiplexing |
US9598473B2 (en) | 2011-06-10 | 2017-03-21 | Keygene N.V. | Trichome-specific transcription factor modulating terpene biosynthesis |
CN103732744A (zh) | 2011-06-15 | 2014-04-16 | Gen9股份有限公司 | 制备性体外克隆的方法 |
DK2729580T3 (en) | 2011-07-08 | 2015-12-14 | Keygene Nv | SEQUENCE BASED genotyping BASED ON OLIGONUKLEOTIDLIGERINGSASSAYS |
US8920751B2 (en) | 2011-07-08 | 2014-12-30 | Life Technologies Corporation | Automated enrichment for nucleic acid sequencing |
WO2013019714A1 (fr) | 2011-07-29 | 2013-02-07 | The Trustees Of Columbia University In The City Of New York | Capteur d'affinité mems pour surveillance ininterrompue de substances à analyser |
WO2013022778A1 (fr) | 2011-08-05 | 2013-02-14 | Ibis Biosciences, Inc. | Séquençage d'acide nucléique par une détection électrochimique |
EP4324935A3 (fr) | 2011-08-18 | 2024-05-08 | Life Technologies Corporation | Procédés, systèmes et supports lisibles par ordinateur pour effectuer des appels de base dans le séquençage d'acides nucléiques |
EP3564261A1 (fr) | 2011-08-23 | 2019-11-06 | Foundation Medicine, Inc. | Molécules de fusion kif5b-ret et leurs utilisations |
US10704164B2 (en) | 2011-08-31 | 2020-07-07 | Life Technologies Corporation | Methods, systems, computer readable media, and kits for sample identification |
US8712697B2 (en) | 2011-09-07 | 2014-04-29 | Ariosa Diagnostics, Inc. | Determination of copy number variations using binomial probability calculations |
GB2496016B (en) | 2011-09-09 | 2016-03-16 | Univ Leland Stanford Junior | Methods for obtaining a sequence |
US10385475B2 (en) | 2011-09-12 | 2019-08-20 | Adaptive Biotechnologies Corp. | Random array sequencing of low-complexity libraries |
EP2758552A4 (fr) * | 2011-09-23 | 2015-09-09 | Univ Columbia | Isolement et enrichissement en acides nucléiques sur puce |
DK3623481T3 (da) | 2011-09-23 | 2021-11-15 | Illumina Inc | Sammensætninger til nukleinsyresekventering |
US10152569B2 (en) | 2011-09-26 | 2018-12-11 | Gen-Probe Incorporated | Algorithms for sequence determinations |
US10378051B2 (en) | 2011-09-29 | 2019-08-13 | Illumina Cambridge Limited | Continuous extension and deblocking in reactions for nucleic acids synthesis and sequencing |
DE102011054101A1 (de) | 2011-09-30 | 2013-04-04 | Albert-Ludwigs-Universität Freiburg | Verfahren zur räumlichen Anordnung von Probenfragmenten zur Amplifikation und Immobilisierung für weitere Derivatisierungen |
US11008611B2 (en) | 2011-09-30 | 2021-05-18 | Unm Rainforest Innovations | Double gate ion sensitive field effect transistor |
US10221454B2 (en) | 2011-10-10 | 2019-03-05 | The Hospital For Sick Children | Methods and compositions for screening and treating developmental disorders |
CN102329876B (zh) * | 2011-10-14 | 2014-04-02 | 深圳华大基因科技有限公司 | 一种测定待检测样本中疾病相关核酸分子的核苷酸序列的方法 |
WO2013055995A2 (fr) | 2011-10-14 | 2013-04-18 | President And Fellows Of Harvard College | Séquençage par assemblage structurel |
CA2852665A1 (fr) | 2011-10-17 | 2013-04-25 | Good Start Genetics, Inc. | Methodes d'identification de mutations associees a des maladies |
US9206418B2 (en) | 2011-10-19 | 2015-12-08 | Nugen Technologies, Inc. | Compositions and methods for directional nucleic acid amplification and sequencing |
EP2768982A4 (fr) | 2011-10-21 | 2015-06-03 | Adaptive Biotechnologies Corp | Quantification de génomes de cellules immunitaires adaptatives dans un mélange complexe de cellules |
DE102011085473A1 (de) | 2011-10-28 | 2013-05-02 | Albert-Ludwigs-Universität Freiburg | Verfahren zur Identifikation von Aptameren |
US11180807B2 (en) | 2011-11-04 | 2021-11-23 | Population Bio, Inc. | Methods for detecting a genetic variation in attractin-like 1 (ATRNL1) gene in subject with Parkinson's disease |
EP2776962A4 (fr) | 2011-11-07 | 2015-12-02 | Ingenuity Systems Inc | Procédés et systèmes pour l'identification de variants génomiques causals |
AU2012336040B2 (en) | 2011-11-07 | 2015-12-10 | Illumina, Inc. | Integrated sequencing apparatuses and methods of use |
GB201120711D0 (en) | 2011-12-01 | 2012-01-11 | Univ Erasmus Medical Ct | Method for classifying tumour cells |
JP6193252B2 (ja) | 2011-12-01 | 2017-09-06 | ジナプシス インコーポレイテッド | 高効率電子配列決定及び検出のためのシステム並びに方法 |
WO2013085918A1 (fr) * | 2011-12-05 | 2013-06-13 | The Regents Of The University Of California | Procédés et compositions pour générer des fragments d'acides polynucléiques |
EP2788509B1 (fr) | 2011-12-09 | 2018-07-11 | Adaptive Biotechnologies Corporation | Diagnostic des malignités lymphoïdes et détection de maladie résiduelle minimale |
KR101830778B1 (ko) | 2011-12-09 | 2018-02-22 | 삼성전자주식회사 | 발열 입자를 포함하는 오일 층을 이용하는 핵산 증폭 장치 및 방법 |
EP2788499B1 (fr) | 2011-12-09 | 2016-01-13 | Illumina, Inc. | Base de numération étendue pour étiquettes polymères |
US9499865B2 (en) | 2011-12-13 | 2016-11-22 | Adaptive Biotechnologies Corp. | Detection and measurement of tissue-infiltrating lymphocytes |
US10513737B2 (en) | 2011-12-13 | 2019-12-24 | Decipher Biosciences, Inc. | Cancer diagnostics using non-coding transcripts |
US20130189679A1 (en) | 2011-12-20 | 2013-07-25 | The Regents Of The University Of Michigan | Pseudogenes and uses thereof |
WO2013096838A2 (fr) | 2011-12-22 | 2013-06-27 | Ibis Biosciences, Inc. | Systèmes et procédés d'isolation d'acides nucléiques |
US11021737B2 (en) | 2011-12-22 | 2021-06-01 | President And Fellows Of Harvard College | Compositions and methods for analyte detection |
US10150993B2 (en) | 2011-12-22 | 2018-12-11 | Ibis Biosciences, Inc. | Macromolecule positioning by electrical potential |
ES2953308T3 (es) | 2011-12-22 | 2023-11-10 | Harvard College | Composiciones y métodos para la detección de analitos |
WO2013096799A1 (fr) | 2011-12-22 | 2013-06-27 | Ibis Biosciences, Inc. | Systèmes et procédés d'isolement d'acides nucléiques à partir d'échantillons cellulaires |
US9823246B2 (en) | 2011-12-28 | 2017-11-21 | The Board Of Trustees Of The Leland Stanford Junior University | Fluorescence enhancing plasmonic nanoscopic gold films and assays based thereon |
US9506113B2 (en) | 2011-12-28 | 2016-11-29 | Ibis Biosciences, Inc. | Nucleic acid ligation systems and methods |
WO2013102081A2 (fr) | 2011-12-29 | 2013-07-04 | Ibis Biosciences, Inc. | Distribution de macromolécule à des nanopuits |
US9222115B2 (en) | 2011-12-30 | 2015-12-29 | Abbott Molecular, Inc. | Channels with cross-sectional thermal gradients |
WO2013104990A1 (fr) | 2012-01-09 | 2013-07-18 | Oslo Universitetssykehus Hf | Procédés et biomarqueurs pour l'analyse d'un cancer colorectal |
US9777269B2 (en) | 2012-01-25 | 2017-10-03 | Gencell Biosystems Ltd. | Biomolecule isolation |
CA2862552A1 (fr) | 2012-01-26 | 2013-08-01 | Nugen Technologies, Inc. | Compositions et procedes pour l'enrichissement en sequence d'acide nucleique ciblee et la generation d'une banque a efficacite elevee |
US9701959B2 (en) | 2012-02-02 | 2017-07-11 | Invenra Inc. | High throughput screen for biologically active polypeptides |
US8597882B2 (en) | 2012-02-03 | 2013-12-03 | Pyrobett Pte. Ltd. | Method and apparatus for conducting an assay |
WO2013117595A2 (fr) * | 2012-02-07 | 2013-08-15 | Illumina Cambridge Limited | Enrichissement et amplification ciblés d'acides nucléiques sur un support |
CA2863887C (fr) | 2012-02-09 | 2023-01-03 | Population Diagnostics, Inc. | Methode de selection de biomarqueurs de variation de l'adn genomique basse frequence pour le trouble envahissant du developpement (ted) ou letrouble envahissant du developpement non specifie ailleurs (ted_nos) |
CN104220876A (zh) | 2012-02-21 | 2014-12-17 | 奥斯陆大学医院 | 用于宫颈癌的检测和预后的方法和生物标志物 |
US20130217023A1 (en) | 2012-02-22 | 2013-08-22 | 454 Life Sciences Corporation | System And Method For Generation And Use Of Compact Clonally Amplified Products |
ES2930180T3 (es) | 2012-03-02 | 2022-12-07 | Sequenom Inc | Métodos para enriquecer ácido nucleico canceroso a partir de una muestra biológica |
EP2823060B1 (fr) | 2012-03-05 | 2018-02-14 | Adaptive Biotechnologies Corporation | Détermination de chaînes appariées de récepteurs immuns à partir de sous-unités présentant une fréquence correspondante |
IN2014DN08312A (fr) | 2012-03-06 | 2015-05-15 | Univ Oslo Hf | |
NO2694769T3 (fr) | 2012-03-06 | 2018-03-03 | ||
US20130261984A1 (en) | 2012-03-30 | 2013-10-03 | Illumina, Inc. | Methods and systems for determining fetal chromosomal abnormalities |
US9193996B2 (en) | 2012-04-03 | 2015-11-24 | Illumina, Inc. | Integrated optoelectronic read head and fluidic cartridge useful for nucleic acid sequencing |
US9732387B2 (en) | 2012-04-03 | 2017-08-15 | The Regents Of The University Of Michigan | Biomarker associated with irritable bowel syndrome and Crohn's disease |
US8209130B1 (en) | 2012-04-04 | 2012-06-26 | Good Start Genetics, Inc. | Sequence assembly |
US8812422B2 (en) | 2012-04-09 | 2014-08-19 | Good Start Genetics, Inc. | Variant database |
US20130274148A1 (en) | 2012-04-11 | 2013-10-17 | Illumina, Inc. | Portable genetic detection and analysis system and method |
CN107435070A (zh) * | 2012-04-12 | 2017-12-05 | 维里纳塔健康公司 | 拷贝数变异的检测和分类 |
US10227635B2 (en) | 2012-04-16 | 2019-03-12 | Molecular Loop Biosolutions, Llc | Capture reactions |
CN104471075B (zh) | 2012-04-19 | 2018-06-22 | 生命技术公司 | 核酸扩增 |
EP3095879B1 (fr) | 2012-04-19 | 2018-09-19 | Life Technologies Corporation | Amplification d'acides nucléiques |
WO2013163210A1 (fr) * | 2012-04-23 | 2013-10-31 | Philip Alexander Rolfe | Procédé et système pour la détection d'un organisme |
WO2013165594A1 (fr) * | 2012-04-30 | 2013-11-07 | Life Technologies Corporation | Modules et procédé d'étalonnage pour un système de préparation robotisé d'échantillons de polynucléotidiques |
US20150133310A1 (en) | 2012-05-02 | 2015-05-14 | Ibis Biosciences, Inc. | Nucleic acid sequencing systems and methods |
DK2831276T3 (da) | 2012-05-08 | 2016-08-01 | Adaptive Biotechnologies Corp | Sammensætninger og fremgangsmåde til at måle og kalibrere amplifikations-bias i multipleks-PCR-reaktioner |
US9646132B2 (en) | 2012-05-11 | 2017-05-09 | Life Technologies Corporation | Models for analyzing data from sequencing-by-synthesis operations |
US10289800B2 (en) | 2012-05-21 | 2019-05-14 | Ariosa Diagnostics, Inc. | Processes for calculating phased fetal genomic sequences |
WO2013177220A1 (fr) * | 2012-05-21 | 2013-11-28 | The Scripps Research Institute | Procédés de préparation d'un échantillon |
US9920361B2 (en) | 2012-05-21 | 2018-03-20 | Sequenom, Inc. | Methods and compositions for analyzing nucleic acid |
CN102766574B (zh) * | 2012-05-24 | 2013-12-25 | 中国科学院北京基因组研究所 | 用于dna测序仪的反应仓 |
EP2856177B1 (fr) * | 2012-05-25 | 2020-11-18 | The University of North Carolina At Chapel Hill | Dispositifs microfluidiques, supports solides pour réactifs et procédés associés |
WO2013184754A2 (fr) | 2012-06-05 | 2013-12-12 | President And Fellows Of Harvard College | Séquençage spatial d'acides nucléiques à l'aide de sondes d'origami d'adn |
US9012022B2 (en) | 2012-06-08 | 2015-04-21 | Illumina, Inc. | Polymer coatings |
US8895249B2 (en) | 2012-06-15 | 2014-11-25 | Illumina, Inc. | Kinetic exclusion amplification of nucleic acid libraries |
CN104619894B (zh) | 2012-06-18 | 2017-06-06 | 纽亘技术公司 | 用于非期望核酸序列的阴性选择的组合物和方法 |
WO2014005076A2 (fr) | 2012-06-29 | 2014-01-03 | The Regents Of The University Of Michigan | Procédés et biomarqueurs pour la détection de troubles rénaux |
WO2014008448A1 (fr) | 2012-07-03 | 2014-01-09 | Sloan Kettering Institute For Cancer Research | Évaluation quantitative de la reconstitution du répertoire des cellules t chez l'homme après une greffe allogénique de cellules souches hématopoïétiques |
US20150011396A1 (en) | 2012-07-09 | 2015-01-08 | Benjamin G. Schroeder | Methods for creating directional bisulfite-converted nucleic acid libraries for next generation sequencing |
EP2872648B1 (fr) | 2012-07-13 | 2019-09-04 | Sequenom, Inc. | Procédés et compositions pour l'enrichissement basé sur la méthylation d'un échantillon maternel en acide nucléique foetal, utiles pour les diagnostics prénatals non invasifs |
US9092401B2 (en) | 2012-10-31 | 2015-07-28 | Counsyl, Inc. | System and methods for detecting genetic variation |
GB201212775D0 (en) | 2012-07-18 | 2012-08-29 | Dna Electronics Ltd | Sensing apparatus and method |
US9977861B2 (en) | 2012-07-18 | 2018-05-22 | Illumina Cambridge Limited | Methods and systems for determining haplotypes and phasing of haplotypes |
CA2878280A1 (fr) | 2012-07-19 | 2014-01-23 | Ariosa Diagnostics, Inc. | Detection a base de ligature sequentielle multiplexe de variants genetiques |
CA2877493C (fr) * | 2012-07-24 | 2020-08-25 | Natera, Inc. | Procedes de pcr hautement multiplex et compositions |
US8673972B2 (en) | 2012-08-03 | 2014-03-18 | Foundation Medicine, Inc. | Human papilloma virus as predictor of cancer prognosis |
JP6525872B2 (ja) | 2012-08-08 | 2019-06-05 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 細胞中の複数のエピトープを同定するためのダイナミックレンジを高めること |
AU2013302867A1 (en) | 2012-08-13 | 2015-02-26 | The Regents Of The University Of California | Methods and systems for detecting biological components |
US9951386B2 (en) | 2014-06-26 | 2018-04-24 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US20140378345A1 (en) * | 2012-08-14 | 2014-12-25 | 10X Technologies, Inc. | Compositions and methods for sample processing |
US20140378322A1 (en) * | 2012-08-14 | 2014-12-25 | 10X Technologies, Inc. | Compositions and methods for sample processing |
US20150005199A1 (en) * | 2012-08-14 | 2015-01-01 | 10X Technologies, Inc. | Compositions and methods for sample processing |
US9567631B2 (en) | 2012-12-14 | 2017-02-14 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10221442B2 (en) | 2012-08-14 | 2019-03-05 | 10X Genomics, Inc. | Compositions and methods for sample processing |
US10752949B2 (en) | 2012-08-14 | 2020-08-25 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10273541B2 (en) | 2012-08-14 | 2019-04-30 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US20150005200A1 (en) * | 2012-08-14 | 2015-01-01 | 10X Technologies, Inc. | Compositions and methods for sample processing |
DK3435084T3 (da) | 2012-08-16 | 2023-05-30 | Mayo Found Medical Education & Res | Prostatakræftprognose under anvendelse af biomarkører |
NL2017959B1 (en) | 2016-12-08 | 2018-06-19 | Illumina Inc | Cartridge assembly |
EP2895620B1 (fr) | 2012-09-11 | 2017-08-02 | Life Technologies Corporation | Amplification d'acides nucléiques |
WO2014043143A1 (fr) | 2012-09-11 | 2014-03-20 | Life Technologies Corporation | Amplification d'acides nucléiques |
DK2895621T3 (da) | 2012-09-14 | 2020-11-30 | Population Bio Inc | Fremgangsmåder og sammensætning til diagnosticering, prognose og behandling af neurologiske tilstande |
US10233495B2 (en) | 2012-09-27 | 2019-03-19 | The Hospital For Sick Children | Methods and compositions for screening and treating developmental disorders |
ES2749118T3 (es) | 2012-10-01 | 2020-03-19 | Adaptive Biotechnologies Corp | Evaluación de la inmunocompetencia por la diversidad de los receptores de inmunidad adaptativa y caracterización de la clonalidad |
US10329608B2 (en) | 2012-10-10 | 2019-06-25 | Life Technologies Corporation | Methods, systems, and computer readable media for repeat sequencing |
US9177098B2 (en) | 2012-10-17 | 2015-11-03 | Celmatix Inc. | Systems and methods for determining the probability of a pregnancy at a selected point in time |
US10162800B2 (en) | 2012-10-17 | 2018-12-25 | Celmatix Inc. | Systems and methods for determining the probability of a pregnancy at a selected point in time |
WO2015160439A2 (fr) | 2014-04-17 | 2015-10-22 | Adaptive Biotechnologies Corporation | Quantification de génomes de cellules de l'immunité acquise dans un mélange complexe de cellules |
US9651539B2 (en) | 2012-10-28 | 2017-05-16 | Quantapore, Inc. | Reducing background fluorescence in MEMS materials by low energy ion beam treatment |
AU2013338393B2 (en) | 2012-10-29 | 2017-05-11 | The Johns Hopkins University | Papanicolaou test for ovarian and endometrial cancers |
EP2914621B1 (fr) | 2012-11-05 | 2023-06-07 | Foundation Medicine, Inc. | Nouvelles molécules de fusion de ntrk1 et leurs utilisations |
US9776182B2 (en) | 2012-11-27 | 2017-10-03 | Gencell Biosystems Ltd. | Handling liquid samples |
CN105189780A (zh) * | 2012-12-03 | 2015-12-23 | 以琳生物药物有限公司 | 核酸制备和分析的组合物和方法 |
US9836577B2 (en) | 2012-12-14 | 2017-12-05 | Celmatix, Inc. | Methods and devices for assessing risk of female infertility |
EP2746405B1 (fr) | 2012-12-23 | 2015-11-04 | HS Diagnomics GmbH | Procédés et ensembles d'amorces de séquençage de PCR à haut rendement |
WO2014113502A1 (fr) | 2013-01-15 | 2014-07-24 | Quanterix Corporation | Détection de l'adn ou de l'arn au moyen de matrices de molécules simples et d'autres techniques |
US9128861B2 (en) | 2013-01-17 | 2015-09-08 | Personalis, Inc. | Methods and systems for genetic analysis |
WO2014113729A2 (fr) | 2013-01-18 | 2014-07-24 | Foundation Mecicine, Inc. | Méthodes de traitement du cholangiocarcinome |
WO2014116729A2 (fr) | 2013-01-22 | 2014-07-31 | The Board Of Trustees Of The Leland Stanford Junior University | Haplotypage de loci hla par séquençage ultra-profond à l'aveugle |
CA3209385A1 (fr) | 2013-02-01 | 2014-08-07 | The Regents Of The University Of California | Procedes pour assemblage du genome et phasage d'haplotype |
US9411930B2 (en) | 2013-02-01 | 2016-08-09 | The Regents Of The University Of California | Methods for genome assembly and haplotype phasing |
US9512422B2 (en) | 2013-02-26 | 2016-12-06 | Illumina, Inc. | Gel patterned surfaces |
ES2662598T3 (es) | 2013-03-08 | 2018-04-09 | F. Hoffmann-La Roche Ag | Análisis de sangre para la detección de mutaciones de EGFR |
EP3578666A1 (fr) * | 2013-03-12 | 2019-12-11 | President and Fellows of Harvard College | Procédé de génération d'une matrice contenant un acide nucléique tridimensionnel |
EP2971169A4 (fr) | 2013-03-13 | 2016-10-26 | Abbott Molecular Inc | Systèmes et méthodes permettant d'isoler les acides nucléiques |
WO2014164716A1 (fr) * | 2013-03-13 | 2014-10-09 | President And Fellows Of Harvard College | Procédés d'élongation de l'adn |
US11060145B2 (en) | 2013-03-13 | 2021-07-13 | Sequenom, Inc. | Methods and compositions for identifying presence or absence of hypermethylation or hypomethylation locus |
US8778609B1 (en) | 2013-03-14 | 2014-07-15 | Good Start Genetics, Inc. | Methods for analyzing nucleic acids |
US20140287946A1 (en) | 2013-03-14 | 2014-09-25 | Ibis Biosciences, Inc. | Nucleic acid control panels |
JP2016512437A (ja) | 2013-03-14 | 2016-04-28 | アボツト・モレキユラー・インコーポレイテツド | 多重メチル化特異的増幅システムおよび方法 |
US9146248B2 (en) | 2013-03-14 | 2015-09-29 | Intelligent Bio-Systems, Inc. | Apparatus and methods for purging flow cells in nucleic acid sequencing instruments |
US20140296080A1 (en) | 2013-03-14 | 2014-10-02 | Life Technologies Corporation | Methods, Systems, and Computer Readable Media for Evaluating Variant Likelihood |
WO2014151764A2 (fr) | 2013-03-15 | 2014-09-25 | Veracyte, Inc. | Procédés et compositions pour classification d'échantillons |
US9591268B2 (en) | 2013-03-15 | 2017-03-07 | Qiagen Waltham, Inc. | Flow cell alignment methods and systems |
CN105358709B (zh) | 2013-03-15 | 2018-12-07 | 雅培分子公司 | 用于检测基因组拷贝数变化的系统和方法 |
US9822408B2 (en) * | 2013-03-15 | 2017-11-21 | Nugen Technologies, Inc. | Sequential sequencing |
US10767221B2 (en) | 2013-03-15 | 2020-09-08 | Illumina, Inc. | Enzyme-linked nucleotides |
US9809852B2 (en) | 2013-03-15 | 2017-11-07 | Genapsys, Inc. | Systems and methods for biological analysis |
WO2014144822A2 (fr) | 2013-03-15 | 2014-09-18 | Immumetrix, Inc. | Procédés et compositions d'étiquetage et d'analyse d'échantillons |
EP2971152B1 (fr) | 2013-03-15 | 2018-08-01 | The Board Of Trustees Of The Leland Stanford Junior University | Identification et utilisation de marqueurs tumoraux acides nucléiques circulants |
ES2716094T3 (es) | 2013-03-15 | 2019-06-10 | Ibis Biosciences Inc | Métodos para analizar la contaminación en la secuenciación del ADN |
US11976329B2 (en) | 2013-03-15 | 2024-05-07 | Veracyte, Inc. | Methods and systems for detecting usual interstitial pneumonia |
US9708658B2 (en) * | 2013-03-19 | 2017-07-18 | New England Biolabs, Inc. | Enrichment of target sequences |
US11859171B2 (en) | 2013-04-17 | 2024-01-02 | Agency For Science, Technology And Research | Method for generating extended sequence reads |
JP6433982B2 (ja) * | 2013-04-19 | 2018-12-05 | シーメンス・ヘルスケア・ダイアグノスティックス・インコーポレーテッドSiemens Healthcare Diagnostics Inc. | 無接触微小滴ディスペンサおよび方法 |
RU2578009C2 (ru) * | 2013-05-08 | 2016-03-20 | Закрытое акционерное общество "ЕВРОГЕН" | Способ идентификации нативных пар фрагментов днк или рнк, присутствующих в одних и тех же живых клетках |
US10160995B2 (en) * | 2013-05-13 | 2018-12-25 | Qiagen Waltham, Inc. | Analyte enrichment methods and compositions |
EP3004385B1 (fr) | 2013-05-24 | 2018-11-28 | Quantapore Inc. | Analyse d'acides nucléiques basés sur des nanopores avec une détection par fret mixte |
WO2014197377A2 (fr) | 2013-06-03 | 2014-12-11 | Good Start Genetics, Inc. | Procédés et systèmes pour stocker des données de lecture de séquence |
EP3603679B1 (fr) | 2013-06-04 | 2022-08-10 | President and Fellows of Harvard College | Régulation transcriptionnelle guidée par arn |
US10526640B2 (en) | 2013-06-19 | 2020-01-07 | Industry-Academic Cooperation Foundation, Yonsei University | Methods for retrieving sequence-verified nucleic acid fragments and apparatuses for amplifying sequence verified nucleic acid fragments |
KR101648252B1 (ko) * | 2014-01-28 | 2016-08-16 | 연세대학교 산학협력단 | 염기서열 확인 과정에서 분리된 핵산 단편들을 회수하는 방법 |
CN105849275B (zh) | 2013-06-25 | 2020-03-17 | 普罗格诺西斯生物科学公司 | 检测样品中生物靶标的空间分布的方法和系统 |
US9708657B2 (en) * | 2013-07-01 | 2017-07-18 | Adaptive Biotechnologies Corp. | Method for generating clonotype profiles using sequence tags |
EP3919624A3 (fr) | 2013-07-01 | 2021-12-29 | Illumina, Inc. | Fonctionnalisation de surface exempte de catalyseurs et greffage de polymères |
ES2719579T3 (es) | 2013-07-03 | 2019-07-11 | Illumina Inc | Sistema para secuenciación por síntesis ortogonal |
US9926597B2 (en) | 2013-07-26 | 2018-03-27 | Life Technologies Corporation | Control nucleic acid sequences for use in sequencing-by-synthesis and methods for designing the same |
JP6656733B2 (ja) | 2013-08-05 | 2020-03-04 | ツイスト バイオサイエンス コーポレーション | 新規合成した遺伝子ライブラリ |
FI3030645T3 (fi) | 2013-08-08 | 2023-02-10 | Fluidijärjestelmä reagenssien toimittamiseen virtauskennoon | |
US20150051117A1 (en) * | 2013-08-16 | 2015-02-19 | President And Fellows Of Harvard College | Assembly of Nucleic Acid Sequences in Emulsions |
US20160199832A1 (en) | 2013-08-30 | 2016-07-14 | Advanced Liquid Logic France Sas | Manipulation of droplets on hydrophilic or variegated-hydrophilic surfaces |
WO2015031689A1 (fr) | 2013-08-30 | 2015-03-05 | Personalis, Inc. | Méthodes et systèmes d'analyse génomique |
US10395758B2 (en) | 2013-08-30 | 2019-08-27 | 10X Genomics, Inc. | Sequencing methods |
CA2959978A1 (fr) * | 2013-09-24 | 2015-04-02 | The Regents Of The University Of California | Capteurs et systemes de capteurs encapsules pour biodosages et diagnostics et leurs procedes de fabrication et d'utilisation |
US10577655B2 (en) | 2013-09-27 | 2020-03-03 | Natera, Inc. | Cell free DNA diagnostic testing standards |
US10262755B2 (en) | 2014-04-21 | 2019-04-16 | Natera, Inc. | Detecting cancer mutations and aneuploidy in chromosomal segments |
WO2015051275A1 (fr) | 2013-10-03 | 2015-04-09 | Personalis, Inc. | Procédés d'analyse de génotypes |
JP6532456B2 (ja) | 2013-10-04 | 2019-06-19 | ライフ テクノロジーズ コーポレーション | 終止化学を用いる配列決定における整相効果(phasing effects)をモデル化するための方法及びシステム |
EP3572527B1 (fr) | 2013-10-17 | 2021-05-26 | Illumina, Inc. | Procédés et compositions pour préparer des bibliothèques d'acides nucléiques |
US10851414B2 (en) | 2013-10-18 | 2020-12-01 | Good Start Genetics, Inc. | Methods for determining carrier status |
US11041203B2 (en) | 2013-10-18 | 2021-06-22 | Molecular Loop Biosolutions, Inc. | Methods for assessing a genomic region of a subject |
US9897986B2 (en) | 2013-10-29 | 2018-02-20 | Regal Beloit America, Inc. | System and method for enabling a motor controller to communicate using multiple different communication protocols |
CN103540672B (zh) * | 2013-10-29 | 2015-04-08 | 中国科学技术大学 | 一种亲和核酸分子的快速鉴定和分离方法 |
WO2015069798A1 (fr) * | 2013-11-05 | 2015-05-14 | The Regents Of The University Of California | Typage médico-légal par microsatellites d'une cellule isolée présente dans des gouttelettes microfluidiques |
CN105829589B (zh) | 2013-11-07 | 2021-02-02 | 小利兰·斯坦福大学理事会 | 用于分析人体微生物组及其组分的无细胞核酸 |
WO2015069634A1 (fr) | 2013-11-08 | 2015-05-14 | President And Fellows Of Harvard College | Microparticules, procédés pour leur préparation et leur utilisation |
WO2015073332A1 (fr) | 2013-11-12 | 2015-05-21 | Life Technologies Corporation | Système et procédé de rupture d'une émulsion |
EP3511422B1 (fr) | 2013-11-12 | 2022-12-28 | Population Bio, Inc. | Procédés et compositions de diagnostic, pronostic et traitement de l'endométriose |
CN104630202A (zh) * | 2013-11-13 | 2015-05-20 | 北京大学 | 一种能够减小微量核酸物质整体扩增时产生偏倚的扩增方法 |
WO2015073711A1 (fr) | 2013-11-13 | 2015-05-21 | Nugen Technologies, Inc. | Compositions et procédés pour l'identification d'une lecture de séquençage en double |
EP3077543B1 (fr) | 2013-12-05 | 2019-09-25 | Centrillion Technology Holdings Corporation | Fabrication de réseaux structurés |
EP3077545B1 (fr) | 2013-12-05 | 2020-09-16 | Centrillion Technology Holdings Corporation | Procédés de séquençage d'acides nucléiques |
US10385335B2 (en) | 2013-12-05 | 2019-08-20 | Centrillion Technology Holdings Corporation | Modified surfaces |
AU2014364180B2 (en) | 2013-12-09 | 2021-03-04 | Illumina, Inc. | Methods and compositions for targeted nucleic acid sequencing |
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 |
EP3080300B1 (fr) | 2013-12-11 | 2020-09-02 | Genapsys Inc. | Systèmes et procédés d'analyse et d'informatique biologiques |
WO2015089438A1 (fr) | 2013-12-13 | 2015-06-18 | Northwestern University | Biomarqueurs pour les états de stress post-traumatique |
US9824068B2 (en) | 2013-12-16 | 2017-11-21 | 10X Genomics, Inc. | Methods and apparatus for sorting data |
US10768181B2 (en) | 2013-12-17 | 2020-09-08 | The Brigham And Women's Hospital, Inc. | Detection of an antibody against a pathogen |
US11193176B2 (en) | 2013-12-31 | 2021-12-07 | Bio-Rad Laboratories, Inc. | Method for detecting and quantifying latent retroviral RNA species |
WO2015103225A1 (fr) | 2013-12-31 | 2015-07-09 | Illumina, Inc. | Cuve à circulation adressable utilisant des électrodes à motif |
WO2015107430A2 (fr) | 2014-01-16 | 2015-07-23 | Oslo Universitetssykehus Hf | Méthodes et biomarqueurs pour la détection et le pronostic du cancer du col de l'utérus |
US9587268B2 (en) | 2014-01-29 | 2017-03-07 | Agilent Technologies Inc. | Fast hybridization for next generation sequencing target enrichment |
US9387451B2 (en) | 2014-02-03 | 2016-07-12 | International Business Machines Corporation | Flow cell array and uses thereof |
EP3105326A4 (fr) | 2014-02-10 | 2018-01-10 | Gencell Biosystems Limited | Dispositif de préparation de banque d'acides nucléiques médiée par des cellules à liquides composites (clc), et ses procédés d'utilisation |
US9745614B2 (en) | 2014-02-28 | 2017-08-29 | Nugen Technologies, Inc. | Reduced representation bisulfite sequencing with diversity adaptors |
WO2015134787A2 (fr) | 2014-03-05 | 2015-09-11 | Adaptive Biotechnologies Corporation | Procédés dans lesquels on utilise des molécules synthétiques contenant des randomères |
EP3736344A1 (fr) | 2014-03-13 | 2020-11-11 | Sequenom, Inc. | Méthodes et procédés d'évaluation non invasive de variations génétiques |
WO2015141649A1 (fr) * | 2014-03-20 | 2015-09-24 | ユニバーサル・バイオ・リサーチ株式会社 | Dispositif d'automatisation de l'amplification d'acide nucléique et dispositif d'automatisation de l'analyse d'une amplification d'acide nucléique |
US11060139B2 (en) | 2014-03-28 | 2021-07-13 | Centrillion Technology Holdings Corporation | Methods for sequencing nucleic acids |
US10066265B2 (en) | 2014-04-01 | 2018-09-04 | Adaptive Biotechnologies Corp. | Determining antigen-specific t-cells |
US11390921B2 (en) | 2014-04-01 | 2022-07-19 | Adaptive Biotechnologies Corporation | Determining WT-1 specific T cells and WT-1 specific T cell receptors (TCRs) |
US20150284715A1 (en) * | 2014-04-07 | 2015-10-08 | Qiagen Gmbh | Enrichment Methods |
CN106413896B (zh) | 2014-04-10 | 2019-07-05 | 10X基因组学有限公司 | 用于封装和分割试剂的流体装置、系统和方法及其应用 |
WO2015161054A2 (fr) | 2014-04-18 | 2015-10-22 | Genapsys, Inc. | Procédés et systèmes pour l'amplification d'acide nucléique |
EP3957749A1 (fr) | 2014-04-21 | 2022-02-23 | Natera, Inc. | Détection de mutations spécifiques d'un tumeur dans les biopsies par séquençage exome entier et dans les échantillons acellulaires |
US11053548B2 (en) | 2014-05-12 | 2021-07-06 | Good Start Genetics, Inc. | Methods for detecting aneuploidy |
US10760109B2 (en) | 2014-06-06 | 2020-09-01 | The Regents Of The University Of Michigan | Compositions and methods for characterizing and diagnosing periodontal disease |
WO2015191877A1 (fr) * | 2014-06-11 | 2015-12-17 | Life Technologies Corporation | Systèmes et procédés d'enrichissement d'un substrat |
EP3155127B1 (fr) * | 2014-06-13 | 2020-07-22 | Life Technologies Corporation | Amplification multiplex d'acides nucléiques |
CN105392902B (zh) | 2014-06-24 | 2021-10-29 | 生物辐射实验室股份有限公司 | 数字式pcr条码化 |
CN110211637B (zh) | 2014-06-26 | 2023-10-27 | 10X基因组学有限公司 | 核酸序列装配的方法和系统 |
EP3160654A4 (fr) | 2014-06-27 | 2017-11-15 | The Regents of The University of California | Tri activé par pcr (pas) |
MX2016017136A (es) | 2014-06-27 | 2017-05-10 | Abbott Lab | Composiciones y metodos para detectar pegivirus 2 de humano (hpgv-2). |
WO2016007839A1 (fr) | 2014-07-11 | 2016-01-14 | President And Fellows Of Harvard College | Méthodes de marquage et de détection à haut rendement de caractéristiques biologiques in situ à l'aide de microscopie |
CA2954895A1 (fr) | 2014-07-17 | 2016-01-21 | Celmatix Inc. | Procedes et systemes pour evaluer l'infertilite et des pathologies apparentees |
EP3578668B1 (fr) | 2014-07-24 | 2020-12-30 | Abbott Molecular Inc. | Procédés pour la détection et l'analyse de mycobacterium tuberculosis |
US10526641B2 (en) | 2014-08-01 | 2020-01-07 | Dovetail Genomics, Llc | Tagging nucleic acids for sequence assembly |
WO2016022696A1 (fr) | 2014-08-05 | 2016-02-11 | The Trustees Of Columbia University In The City Of New York | Procédé d'isolement d'aptamères pour détecter une maladie résiduelle minimale |
US10102337B2 (en) | 2014-08-06 | 2018-10-16 | Nugen Technologies, Inc. | Digital measurements from targeted sequencing |
GB201413929D0 (en) | 2014-08-06 | 2014-09-17 | Geneseque As | Method |
CA2956812C (fr) | 2014-08-11 | 2023-04-11 | Luminex Corporation | Sondes pour une discrimination de fusion et un multiplexage ameliores dans des analyses d'acides nucleiques |
GB2543728B (en) | 2014-08-12 | 2019-04-17 | Nextgen Jane Inc | Medical kit and method for processing a biological sample |
US10435685B2 (en) * | 2014-08-19 | 2019-10-08 | Pacific Biosciences Of California, Inc. | Compositions and methods for enrichment of nucleic acids |
EP3183577B1 (fr) | 2014-08-21 | 2020-08-19 | Illumina Cambridge Limited | Fonctionnalisation de surface réversible |
WO2016036403A1 (fr) | 2014-09-05 | 2016-03-10 | Population Diagnostics Inc. | Méthodes et compositions destinées à inhiber et à traiter des états neurologiques |
CA3180239A1 (fr) | 2014-09-08 | 2016-03-17 | Becton, Dickinson And Company | Plateau ameliore pour malaxage pharmaceutique |
US11408024B2 (en) | 2014-09-10 | 2022-08-09 | Molecular Loop Biosciences, Inc. | Methods for selectively suppressing non-target sequences |
CN105400864B (zh) * | 2014-09-12 | 2020-04-14 | 深圳华大基因股份有限公司 | 用于基于血液样品构建测序文库的方法及其在确定胎儿遗传异常中的用途 |
CN106715713B (zh) * | 2014-09-12 | 2020-11-03 | 深圳华大智造科技有限公司 | 试剂盒及其在核酸测序中的用途 |
EP3192869B1 (fr) * | 2014-09-12 | 2019-03-27 | MGI Tech Co., Ltd. | Oligonucléotide isolé et son utilisation dans le séquençage d'acide nucléique |
US10550428B2 (en) | 2014-09-17 | 2020-02-04 | Ibis Biosciences, Inc. | Sequencing by synthesis using pulse read optics |
CN107002121B (zh) | 2014-09-18 | 2020-11-13 | 亿明达股份有限公司 | 用于分析核酸测序数据的方法和系统 |
JP2017536087A (ja) | 2014-09-24 | 2017-12-07 | グッド スタート ジェネティクス, インコーポレイテッド | 遺伝子アッセイのロバストネスを増大させるためのプロセス制御 |
CA2963604C (fr) | 2014-10-10 | 2023-02-14 | Quantapore, Inc. | Analyse de polymeres, a base de nanopore, a l'aide de marqueurs fluorescents a desactivation mutuelle |
WO2016060974A1 (fr) | 2014-10-13 | 2016-04-21 | Life Technologies Corporation | Procédés, systèmes, et supports lisibles par ordinateur pour appel de bases accéléré |
EP3209419A4 (fr) | 2014-10-22 | 2018-10-03 | The Regents of The University of California | Imprimante à microgouttelettes haute définition |
CN107002126B (zh) * | 2014-10-24 | 2021-05-25 | 昆塔波尔公司 | 使用纳米结构阵列的聚合物的高效光学分析 |
US20160122817A1 (en) | 2014-10-29 | 2016-05-05 | 10X Genomics, Inc. | Methods and compositions for targeted nucleic acid sequencing |
CA2966201A1 (fr) | 2014-10-29 | 2016-05-06 | Adaptive Biotechnologies Corp. | Detection simultanee hautement multiplexee d'acides nucleiques codant pour des heterodimeres de recepteurs de l'immunite adaptative apparies a partir de nombreux echantillons |
EP4026913A1 (fr) | 2014-10-30 | 2022-07-13 | Personalis, Inc. | Procédés d'utilisation du mosaïcisme dans des acides nucléiques prélevés de façon distale par rapport à leur origine |
CN114805710B (zh) | 2014-10-31 | 2023-11-17 | 伊鲁米纳剑桥有限公司 | 聚合物以及dna共聚物涂层 |
JP6812797B2 (ja) * | 2014-11-04 | 2021-01-13 | 凸版印刷株式会社 | 核酸導入方法、核酸検出方法、生体成分解析方法、生体成分定量用アレイデバイス、及び生体成分解析キット |
EP3770274A1 (fr) | 2014-11-05 | 2021-01-27 | Veracyte, Inc. | Systèmes et procédés de diagnostic de la fibrose pulmonaire idiopathique sur des biopsies transbronchiques à l'aide de l'apprentissage automatique et de données de transcription dimensionnelle élevée |
CN111024936A (zh) | 2014-11-05 | 2020-04-17 | 纳迈达斯生物科技中心 | 用于增强成像的金属复合物 |
CN107250358B (zh) | 2014-11-05 | 2021-03-30 | 伊卢米纳剑桥有限公司 | 在样品制备和测序期间使用铁载体螯合剂减少dna损伤 |
US9975122B2 (en) | 2014-11-05 | 2018-05-22 | 10X Genomics, Inc. | Instrument systems for integrated sample processing |
US10246701B2 (en) | 2014-11-14 | 2019-04-02 | Adaptive Biotechnologies Corp. | Multiplexed digital quantitation of rearranged lymphoid receptors in a complex mixture |
US11789906B2 (en) | 2014-11-19 | 2023-10-17 | Arc Bio, Llc | Systems and methods for genomic manipulations and analysis |
WO2016081549A1 (fr) | 2014-11-20 | 2016-05-26 | Ampliwise Inc. | Compositions, méthodes, systèmes et kits d'amplification et d'analyse d'acides nucléiques |
US10233490B2 (en) | 2014-11-21 | 2019-03-19 | Metabiotech Corporation | Methods for assembling and reading nucleic acid sequences from mixed populations |
US11066705B2 (en) | 2014-11-25 | 2021-07-20 | Adaptive Biotechnologies Corporation | Characterization of adaptive immune response to vaccination or infection using immune repertoire sequencing |
EP3227464B1 (fr) | 2014-12-05 | 2022-04-20 | Foundation Medicine, Inc. | Analyse multigénique de prélèvements tumoraux |
US20160177386A1 (en) | 2014-12-18 | 2016-06-23 | Life Technologies Corporation | Calibration panels and methods for designing the same |
US20180016631A1 (en) | 2014-12-24 | 2018-01-18 | Keygene N.V. | Backbone mediated mate pair sequencing |
US10066259B2 (en) | 2015-01-06 | 2018-09-04 | Good Start Genetics, Inc. | Screening for structural variants |
CN112126675B (zh) | 2015-01-12 | 2022-09-09 | 10X基因组学有限公司 | 用于制备核酸测序文库的方法和系统以及用其制备的文库 |
SG11201705425SA (en) | 2015-01-13 | 2017-08-30 | 10X Genomics Inc | Systems and methods for visualizing structural variation and phasing information |
GB201501012D0 (en) * | 2015-01-21 | 2015-03-04 | Base4 Innovation Ltd | Improved droplet sequencing apparatus and method |
WO2016122582A1 (fr) * | 2015-01-30 | 2016-08-04 | Hewlett Packard Enterprise Development Lp | Projection préservant la relation entre des objets numériques |
WO2016125236A1 (fr) | 2015-02-02 | 2016-08-11 | 株式会社日立ハイテクノロジーズ | Dispositif d'analyse par fluorescence multicolore |
US10646869B2 (en) * | 2015-02-03 | 2020-05-12 | Hitachi, Ltd. | Flow cell device for single cell analysis, and single cell analysis device |
US10669304B2 (en) | 2015-02-04 | 2020-06-02 | Twist Bioscience Corporation | Methods and devices for de novo oligonucleic acid assembly |
WO2016126987A1 (fr) | 2015-02-04 | 2016-08-11 | Twist Bioscience Corporation | Compositions et méthodes d'assemblage de gène synthétique |
EP3253479B1 (fr) | 2015-02-04 | 2022-09-21 | The Regents of The University of California | Séquençage d'acides nucléiques contenus dans des entités individuelles par barcoding |
CA2975529A1 (fr) | 2015-02-09 | 2016-08-18 | 10X Genomics, Inc. | Systemes et procedes pour determiner la variation structurale et la mise en phase au moyen de donnees d'appel de variant |
WO2016134034A1 (fr) | 2015-02-17 | 2016-08-25 | Dovetail Genomics Llc | Assemblage de séquences d'acide nucléique |
CN107407685B (zh) | 2015-02-20 | 2021-08-03 | 宝生物工程(美国)有限公司 | 快速精确分配、可视化和分析单个细胞的方法 |
KR20170119710A (ko) | 2015-02-24 | 2017-10-27 | 10엑스 제노믹스, 인크. | 표적화된 핵산 서열 커버리지 방법 |
EP4286516A3 (fr) | 2015-02-24 | 2024-03-06 | 10X Genomics, Inc. | Procédés et systèmes de traitement de cloisonnement |
AU2016222788B2 (en) | 2015-02-24 | 2022-03-31 | Adaptive Biotechnologies Corp. | Methods for diagnosing infectious disease and determining HLA status using immune repertoire sequencing |
CN107614096A (zh) | 2015-03-13 | 2018-01-19 | 哈佛学院院长及董事 | 使用扩增测定细胞 |
CA2979850C (fr) | 2015-03-24 | 2020-07-21 | Illumina, Inc. | Procedes, ensembles de support, et systemes pour l'imagerie d'echantillons pour une analyse biologique ou chimique |
US11807896B2 (en) | 2015-03-26 | 2023-11-07 | Dovetail Genomics, Llc | Physical linkage preservation in DNA storage |
US20160287152A1 (en) * | 2015-03-30 | 2016-10-06 | Verily Life Sciences Llc | Functionalized Nanoparticles, Methods and In Vivo Diagnostic System |
AU2016242967B2 (en) | 2015-04-01 | 2021-07-01 | Adaptive Biotechnologies Corp. | Method of identifying human compatible T cell receptors specific for an antigenic target |
CA2980769A1 (fr) | 2015-04-02 | 2016-10-06 | The Jackson Laboratory | Procede pour detecter des variations genomiques a l'aide de banques de paires d'appariement circularisees et d'un sequencage aleatoire |
EP3530752B1 (fr) | 2015-04-10 | 2021-03-24 | Spatial Transcriptomics AB | Analyse de plusieurs acides nucléiques spatialement différenciés de spécimens biologiques |
WO2016172377A1 (fr) | 2015-04-21 | 2016-10-27 | Twist Bioscience Corporation | Dispositifs et procédés pour la synthèse de banques d'acides oligonucléiques |
EP3091026B1 (fr) | 2015-05-08 | 2019-02-20 | Centrillion Technology Holdings Corporation | Terminateurs réversibles à liaison disulfure |
WO2016183106A1 (fr) | 2015-05-11 | 2016-11-17 | Natera, Inc. | Procédés et compositions pour la détermination de la ploïdie |
DK3294911T3 (da) | 2015-05-11 | 2020-11-16 | Illumina Inc | Platform til opdagelse og analyse af terapeutiske midler |
CN107969138B (zh) | 2015-05-14 | 2022-04-12 | 生命科技公司 | 条形码序列和有关系统与方法 |
EP3527672B1 (fr) | 2015-06-09 | 2022-10-05 | Centrillion Technology Holdings Corporation | Matrices aux oligonucleotides pour la séquençage d'acides nucléiques |
WO2017007753A1 (fr) | 2015-07-07 | 2017-01-12 | Illumina, Inc. | Formation de motifs en surface sélective par nanoimpression |
CN108350452B (zh) | 2015-07-14 | 2022-07-19 | 雅培分子公司 | 使用铜-钛氧化物纯化核酸 |
WO2017011565A1 (fr) | 2015-07-14 | 2017-01-19 | Abbott Molecular Inc. | Compositions et méthodes d'identification de tuberculose résistante aux médicaments |
ES2945607T3 (es) | 2015-07-17 | 2023-07-04 | Illumina Inc | Láminas de polímero para aplicaciones de secuenciación |
US10150994B2 (en) | 2015-07-22 | 2018-12-11 | Qiagen Waltham, Inc. | Modular flow cells and methods of sequencing |
BR112017023418A2 (pt) | 2015-07-30 | 2018-07-24 | Illumina, Inc. | desbloqueio ortogonal de nucleotídeos |
EP3332034A4 (fr) | 2015-08-06 | 2019-01-02 | Arc Bio, LLC | Systèmes et procédés d'analyse génomique |
WO2017027653A1 (fr) | 2015-08-11 | 2017-02-16 | The Johns Hopkins University | Analyse du fluide d'un kyste ovarien |
US10976334B2 (en) | 2015-08-24 | 2021-04-13 | Illumina, Inc. | In-line pressure accumulator and flow-control system for biological or chemical assays |
CN107921432A (zh) | 2015-09-02 | 2018-04-17 | 伊卢米纳剑桥有限公司 | 改善流控系统中的液滴操作的系统和方法 |
US10647981B1 (en) | 2015-09-08 | 2020-05-12 | Bio-Rad Laboratories, Inc. | Nucleic acid library generation methods and compositions |
US9938572B1 (en) | 2015-09-08 | 2018-04-10 | Raindance Technologies, Inc. | System and method for forming an emulsion |
JP6982362B2 (ja) | 2015-09-18 | 2021-12-17 | ツイスト バイオサイエンス コーポレーション | オリゴ核酸変異体ライブラリーとその合成 |
CN108698012A (zh) | 2015-09-22 | 2018-10-23 | 特韦斯特生物科学公司 | 用于核酸合成的柔性基底 |
US10465232B1 (en) | 2015-10-08 | 2019-11-05 | Trace Genomics, Inc. | Methods for quantifying efficiency of nucleic acid extraction and detection |
CN108289797B (zh) | 2015-10-13 | 2022-01-28 | 哈佛学院院长及董事 | 用于制备和使用凝胶微球的系统和方法 |
SG11201803289VA (en) | 2015-10-19 | 2018-05-30 | Dovetail Genomics Llc | Methods for genome assembly, haplotype phasing, and target independent nucleic acid detection |
WO2017079406A1 (fr) | 2015-11-03 | 2017-05-11 | President And Fellows Of Harvard College | Procédé et appareil pour imagerie volumétrique d'une matrice tridimensionnelle contenant des acides nucléiques |
US11371094B2 (en) | 2015-11-19 | 2022-06-28 | 10X Genomics, Inc. | Systems and methods for nucleic acid processing using degenerate nucleotides |
US9895673B2 (en) | 2015-12-01 | 2018-02-20 | Twist Bioscience Corporation | Functionalized surfaces and preparation thereof |
WO2017096110A1 (fr) * | 2015-12-04 | 2017-06-08 | Siemens Healthcare Diagnostics Inc. | Procédé et dispositif pour optimiser le processus d'identification de pathogènes |
SG11201804086VA (en) | 2015-12-04 | 2018-06-28 | 10X Genomics Inc | Methods and compositions for nucleic acid analysis |
US10730030B2 (en) | 2016-01-08 | 2020-08-04 | Bio-Rad Laboratories, Inc. | Multiple beads per droplet resolution |
AU2017207259B2 (en) | 2016-01-11 | 2019-06-27 | Illumina Singapore Pte Ltd | Detection apparatus having a microfluorometer, a fluidic system, and a flow cell latch clamp module |
CN108495938B (zh) * | 2016-01-12 | 2023-07-14 | 生物辐射实验室股份有限公司 | 利用相位移区块合成条码化序列及其用途 |
WO2017123758A1 (fr) | 2016-01-12 | 2017-07-20 | Seqwell, Inc. | Compositions et méthodes pour le séquençage d'acides nucléiques |
KR102641264B1 (ko) | 2016-01-22 | 2024-02-26 | 퍼듀 리서치 파운데이션 | 하전된 질량 표지 시스템 |
JP6685138B2 (ja) | 2016-01-27 | 2020-04-22 | シスメックス株式会社 | 核酸増幅の精度管理方法、精度管理用試薬およびその試薬キット |
EP3848457A1 (fr) | 2016-02-08 | 2021-07-14 | Rgene, Inc. | Compositions de ligase multiples, systèmes et procédés |
JP6735348B2 (ja) | 2016-02-11 | 2020-08-05 | 10エックス ジェノミクス, インコーポレイテッド | 全ゲノム配列データのデノボアセンブリのためのシステム、方法及び媒体 |
JP2017143783A (ja) * | 2016-02-17 | 2017-08-24 | 国立大学法人 筑波大学 | 並列反応用懸濁液、並列反応方法、スクリーニング方法および検査方法 |
KR20180116377A (ko) | 2016-02-23 | 2018-10-24 | 더브테일 제노믹스 엘엘씨 | 게놈 어셈블리를 위한 페이징된 판독 세트의 생성 및 반수체형 페이징 |
WO2017155858A1 (fr) | 2016-03-07 | 2017-09-14 | Insilixa, Inc. | Identification de séquence d'acide nucléique à l'aide d'une extension de base unique cyclique en phase solide |
US20190062827A1 (en) | 2016-03-14 | 2019-02-28 | RGENE, Inc. | HYPER-THERMOSTABLE LYSINE-MUTANT ssDNA/RNA LIGASES |
CA3016077A1 (fr) | 2016-03-22 | 2017-09-28 | Counsyl, Inc. | Criblage combinatoire d'adn |
EP4198146A3 (fr) | 2016-03-25 | 2023-08-23 | Karius, Inc. | Procédé utilisant des spike-ins d'acides nucléiques synthétiques |
CN108463287B (zh) | 2016-03-28 | 2021-01-15 | 亿明达股份有限公司 | 多平面微阵列 |
WO2017180909A1 (fr) | 2016-04-13 | 2017-10-19 | Nextgen Jane, Inc. | Dispositifs, systèmes et procédés de collecte et de conservation d'échantillon |
US11355328B2 (en) | 2016-04-13 | 2022-06-07 | Purdue Research Foundation | Systems and methods for isolating a target ion in an ion trap using a dual frequency waveform |
ITUA20162640A1 (it) * | 2016-04-15 | 2017-10-15 | Menarini Silicon Biosystems Spa | Metodo e kit per la generazione di librerie di dna per sequenziamento massivo parallelo |
CA3210120C (fr) | 2016-04-25 | 2024-04-09 | President And Fellows Of Harvard College | Procedes de reaction en chaine d'hybridation pour la detection moleculaire in situ |
CN105821482B (zh) * | 2016-04-29 | 2018-04-10 | 李星军 | 一种生化微反应体系、高通量测序的建库仪及应用 |
US10077459B2 (en) | 2016-05-04 | 2018-09-18 | General Electric Company | Cell-free protein expression using rolling circle amplification product |
US10619205B2 (en) | 2016-05-06 | 2020-04-14 | Life Technologies Corporation | Combinatorial barcode sequences, and related systems and methods |
EP3455356B1 (fr) | 2016-05-13 | 2021-08-04 | Dovetail Genomics LLC | Récupération d'informations de liaison de longue portée à partir d'échantillons conservés |
WO2017197338A1 (fr) | 2016-05-13 | 2017-11-16 | 10X Genomics, Inc. | Systèmes microfluidiques et procédés d'utilisation |
US10900076B2 (en) | 2016-05-18 | 2021-01-26 | Illumina, Inc. | Self assembled patterning using patterned hydrophobic surfaces |
US11299783B2 (en) | 2016-05-27 | 2022-04-12 | Personalis, Inc. | Methods and systems for genetic analysis |
EP3469078B1 (fr) | 2016-06-10 | 2024-03-27 | Life Technologies Corporation | Procédés et compositions d'amplification d'acide nucléique |
EP3469097B1 (fr) * | 2016-06-14 | 2020-02-19 | Base4 Innovation Limited | Procédé de séparation d'un polynucléotide modifié |
WO2018013509A1 (fr) | 2016-07-11 | 2018-01-18 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Compositions et méthodes pour diagnostiquer et traiter des arythmies |
WO2018017884A1 (fr) | 2016-07-20 | 2018-01-25 | Genapsys, Inc. | Systèmes et procédés de séquençage d'acides nucléiques |
JP7075394B2 (ja) | 2016-07-21 | 2022-05-25 | タカラ バイオ ユーエスエー, インコーポレイテッド | マルチウェルデバイスを用いたマルチz撮像及び分注 |
WO2018031691A1 (fr) | 2016-08-10 | 2018-02-15 | The Regents Of The University Of California | Amplification à déplacement multiple et pcr combinées dans une microgouttelette d'émulsion |
EP3500082A1 (fr) | 2016-08-22 | 2019-06-26 | Biolumic Limited | Système, dispositif et méthodes de traitement de semences |
GB2568444A (en) | 2016-08-22 | 2019-05-15 | Twist Bioscience Corp | De novo synthesized nucleic acid libraries |
WO2018039490A1 (fr) | 2016-08-24 | 2018-03-01 | Genomedx Biosciences, Inc. | Utilisation de signatures génomiques en vue d'une prédiction de la réactivité de patients atteints d'un cancer de la prostate à une radiothérapie postopératoire |
EP3507364A4 (fr) | 2016-08-31 | 2020-05-20 | President and Fellows of Harvard College | Procédés de génération de bibliothèques de séquences d'acides nucléiques pour la détection par séquençage fluorescent in situ |
WO2018045186A1 (fr) | 2016-08-31 | 2018-03-08 | President And Fellows Of Harvard College | Procédés de combinaison de la détection de biomolécules dans un dosage unique à l'aide d'un séquençage fluorescent in situ |
WO2018039969A1 (fr) * | 2016-08-31 | 2018-03-08 | President And Fellows Of Harvard College | Procédés d'amplification numérique du génome entier |
WO2018045162A1 (fr) | 2016-09-01 | 2018-03-08 | Biogen Ma Inc. | Biomarqueurs prédictifs de la sclérose en plaques progressive primaire et leurs utilisations |
US10428325B1 (en) | 2016-09-21 | 2019-10-01 | Adaptive Biotechnologies Corporation | Identification of antigen-specific B cell receptors |
KR102217487B1 (ko) | 2016-09-21 | 2021-02-23 | 트위스트 바이오사이언스 코포레이션 | 핵산 기반 데이터 저장 |
WO2018064226A1 (fr) | 2016-09-27 | 2018-04-05 | uBiome, Inc. | Procédé et système de préparation et de séquençage de banque à base de crispr |
WO2018064116A1 (fr) | 2016-09-28 | 2018-04-05 | Illumina, Inc. | Procédés et systèmes de traitement de données |
US11485996B2 (en) | 2016-10-04 | 2022-11-01 | Natera, Inc. | Methods for characterizing copy number variation using proximity-litigation sequencing |
US10190155B2 (en) | 2016-10-14 | 2019-01-29 | Nugen Technologies, Inc. | Molecular tag attachment and transfer |
IL290157B2 (en) | 2016-10-14 | 2023-09-01 | Illumina Inc | cartridge kit |
US11725232B2 (en) | 2016-10-31 | 2023-08-15 | The Hong Kong University Of Science And Technology | Compositions, methods and kits for detection of genetic variants for alzheimer's disease |
US10255990B2 (en) | 2016-11-11 | 2019-04-09 | uBiome, Inc. | Method and system for fragment assembly and sequence identification |
US10011870B2 (en) | 2016-12-07 | 2018-07-03 | Natera, Inc. | Compositions and methods for identifying nucleic acid molecules |
CN110366613A (zh) | 2016-12-16 | 2019-10-22 | 特韦斯特生物科学公司 | 免疫突触的变体文库及其合成 |
WO2018118971A1 (fr) | 2016-12-19 | 2018-06-28 | Bio-Rad Laboratories, Inc. | Adn marqué ayant une contiguïté préservée de marquage par gouttelettes |
CA3047328A1 (fr) | 2016-12-21 | 2018-06-28 | The Regents Of The University Of California | Sequencage genomique de cellules uniques a l'aide de gouttelettes a base d'hydrogel |
US10011872B1 (en) | 2016-12-22 | 2018-07-03 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10815525B2 (en) | 2016-12-22 | 2020-10-27 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10550429B2 (en) | 2016-12-22 | 2020-02-04 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
EP3564387A4 (fr) | 2016-12-27 | 2020-10-07 | EGI Tech (Shen Zhen) Co., Limited | Procédé de séquençage à base de colorant fluorescent unique |
KR102349259B1 (ko) * | 2017-01-04 | 2022-01-07 | 엠쥐아이 테크 컴퍼니 엘티디. | 친화성 시약을 이용한 핵산 시퀀싱 |
GB201704754D0 (en) | 2017-01-05 | 2017-05-10 | Illumina Inc | Kinetic exclusion amplification of nucleic acid libraries |
EP3571322B9 (fr) | 2017-01-20 | 2023-10-04 | VERACYTE SD, Inc. | Sous-typage moléculaire, pronostic et traitement du cancer de la vessie |
WO2018140966A1 (fr) | 2017-01-30 | 2018-08-02 | 10X Genomics, Inc. | Procédés et systèmes de codage à barres de cellules individuelles sur la base de gouttelettes |
GB201701688D0 (en) | 2017-02-01 | 2017-03-15 | Illumia Inc | System and method with fiducials in non-recliner layouts |
GB201701689D0 (en) | 2017-02-01 | 2017-03-15 | Illumia Inc | System and method with fiducials of non-closed shapes |
GB201701686D0 (en) | 2017-02-01 | 2017-03-15 | Illunina Inc | System & method with fiducials having offset layouts |
US10240205B2 (en) | 2017-02-03 | 2019-03-26 | Population Bio, Inc. | Methods for assessing risk of developing a viral disease using a genetic test |
US10995333B2 (en) | 2017-02-06 | 2021-05-04 | 10X Genomics, Inc. | Systems and methods for nucleic acid preparation |
EP3585889A1 (fr) | 2017-02-21 | 2020-01-01 | Natera, Inc. | Compositions, procédés, et kits d'isolement d'acides nucléiques |
CA3054303A1 (fr) | 2017-02-22 | 2018-08-30 | Twist Bioscience Corporation | Stockage de donnees reposant sur un acide nucleique |
EP4218738A1 (fr) | 2017-02-24 | 2023-08-02 | The Regents of The University of California | Structures de particules-gouttes et procédé pour les préparer et les utiliser |
GB201703049D0 (en) * | 2017-02-24 | 2017-04-12 | Univ I Tromsø - Norges Arktiske Univ | Single-strand binding protein |
JP6931540B2 (ja) | 2017-02-27 | 2021-09-08 | シスメックス株式会社 | 検体処理チップを用いた送液方法、検体処理チップの送液装置 |
CA3055925A1 (fr) | 2017-03-09 | 2018-09-13 | Decipher Biosciences, Inc. | Sous-typage du cancer de la prostate pour predire la reponse a une therapie hormonale |
WO2018170169A1 (fr) | 2017-03-15 | 2018-09-20 | Twist Bioscience Corporation | Banques de variants de la synapse immunologique et leur synthèse |
WO2018175399A1 (fr) | 2017-03-24 | 2018-09-27 | Bio-Rad Laboratories, Inc. | Amorces universelles en épingle à cheveux |
US10737267B2 (en) | 2017-04-04 | 2020-08-11 | Omniome, Inc. | Fluidic apparatus and methods useful for chemical and biological reactions |
EP3610034B1 (fr) | 2017-04-12 | 2022-06-08 | Karius, Inc. | Systèmes, procédés et compositions de préparation d'échantillon |
US11185568B2 (en) | 2017-04-14 | 2021-11-30 | President And Fellows Of Harvard College | Methods for generation of cell-derived microfilament network |
US20210371918A1 (en) | 2017-04-18 | 2021-12-02 | Dovetail Genomics, Llc | Nucleic acid characteristics as guides for sequence assembly |
US10161003B2 (en) | 2017-04-25 | 2018-12-25 | Omniome, Inc. | Methods and apparatus that increase sequencing-by-binding efficiency |
JP2018183097A (ja) * | 2017-04-26 | 2018-11-22 | 株式会社エンプラス | 細胞由来の解析用液滴の単離方法、および細胞の解析方法 |
CA3062716A1 (fr) | 2017-05-12 | 2018-11-15 | Decipher Biosciences, Inc. | Signatures genetiques pour predire une metastase du cancer de la prostate et identifier la virulence d'une tumeur |
CN106957842B (zh) * | 2017-05-15 | 2020-05-22 | 青岛安德贝生命科技有限公司 | Bac克隆dna的提取方法 |
WO2018213774A1 (fr) | 2017-05-19 | 2018-11-22 | 10X Genomics, Inc. | Systèmes et procédés d'analyse d'ensembles de données |
US10844372B2 (en) | 2017-05-26 | 2020-11-24 | 10X Genomics, Inc. | Single cell analysis of transposase accessible chromatin |
EP4230746A3 (fr) | 2017-05-26 | 2023-11-01 | 10X Genomics, Inc. | Analyse de cellule unique de chromatine accessible par transposase |
US20200362397A1 (en) * | 2017-05-31 | 2020-11-19 | Centrillion Technology Holdings Corporation | Oligonucleotide probe array with electronic detection system |
CN110997711A (zh) | 2017-06-08 | 2020-04-10 | 布里格姆妇女医院 | 用于鉴定表位的方法和组合物 |
CA3066744A1 (fr) | 2017-06-12 | 2018-12-20 | Twist Bioscience Corporation | Methodes d'assemblage d'acides nucleiques sans joint |
WO2018231864A1 (fr) | 2017-06-12 | 2018-12-20 | Twist Bioscience Corporation | Méthodes d'assemblage d'acides nucléiques continus |
US11001885B2 (en) * | 2017-06-13 | 2021-05-11 | Personal Genomics Taiwan, Inc. | Apparatus for single molecular sequencing and method of sequencing nucleic acid molecules |
US11186862B2 (en) | 2017-06-20 | 2021-11-30 | Bio-Rad Laboratories, Inc. | MDA using bead oligonucleotide |
CA3068273A1 (fr) | 2017-06-21 | 2018-12-27 | Bluedot Llc | Systemes et procedes d'identification d'acides nucleiques dans un echantillon |
US11217329B1 (en) | 2017-06-23 | 2022-01-04 | Veracyte, Inc. | Methods and systems for determining biological sample integrity |
SG11202000964UA (en) | 2017-08-15 | 2020-02-27 | Omniome Inc | Scanning apparatus and methods useful for detection of chemical and biological analytes |
WO2019038594A2 (fr) | 2017-08-21 | 2019-02-28 | Biolumic Limited | Plantes transgéniques à la croissance élevée et à la rusticité élevée |
SG11202002194UA (en) | 2017-09-11 | 2020-04-29 | Twist Bioscience Corp | Gpcr binding proteins and synthesis thereof |
JP2020536051A (ja) | 2017-09-20 | 2020-12-10 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | 腫瘍が高いパッセンジャー遺伝子変異量を担持する患者の免疫療法剤 |
SG11202002516WA (en) | 2017-09-21 | 2020-04-29 | Genapsys Inc | Systems and methods for nucleic acid sequencing |
WO2019060716A1 (fr) | 2017-09-25 | 2019-03-28 | Freenome Holdings, Inc. | Méthodes et systèmes d'extraction d'échantillon |
CN111372574A (zh) * | 2017-09-29 | 2020-07-03 | 加利福尼亚大学董事会 | 单分散乳液的制备方法 |
US10837047B2 (en) | 2017-10-04 | 2020-11-17 | 10X Genomics, Inc. | Compositions, methods, and systems for bead formation using improved polymers |
CN111787930A (zh) | 2017-10-06 | 2020-10-16 | 芝加哥大学 | 针对癌症特异性抗原对t淋巴细胞的筛选 |
US10501739B2 (en) | 2017-10-18 | 2019-12-10 | Mission Bio, Inc. | Method, systems and apparatus for single cell analysis |
WO2019079593A1 (fr) | 2017-10-19 | 2019-04-25 | Omniome, Inc. | Réduction du bruit de fond et stabilisation de complexes simultanées dans des flux de travaux de dosage par liaison |
WO2019079769A1 (fr) | 2017-10-20 | 2019-04-25 | Twist Bioscience Corporation | Nano-puits chauffés pour la synthèse de polynucléotides |
US11099202B2 (en) | 2017-10-20 | 2021-08-24 | Tecan Genomics, Inc. | Reagent delivery system |
WO2019084043A1 (fr) | 2017-10-26 | 2019-05-02 | 10X Genomics, Inc. | Méthodes et systèmes de préparation d'acide nucléique et d'analyse de chromatine |
CN111479631B (zh) | 2017-10-27 | 2022-02-22 | 10X基因组学有限公司 | 用于样品制备和分析的方法和系统 |
CN111295443B (zh) | 2017-11-02 | 2024-04-16 | 生物辐射实验室股份有限公司 | 基于转座酶的基因组分析 |
SG11201913654QA (en) | 2017-11-15 | 2020-01-30 | 10X Genomics Inc | Functionalized gel beads |
US10829815B2 (en) | 2017-11-17 | 2020-11-10 | 10X Genomics, Inc. | Methods and systems for associating physical and genetic properties of biological particles |
WO2019103967A1 (fr) | 2017-11-22 | 2019-05-31 | The Regents Of The University Of Michigan | Compositions et méthodes pour traiter le cancer |
JP2021503969A (ja) | 2017-11-29 | 2021-02-15 | エックスゲノムズ コーポレーション | 出現(emergence)による核酸のシーケンシング |
US11254980B1 (en) | 2017-11-29 | 2022-02-22 | Adaptive Biotechnologies Corporation | Methods of profiling targeted polynucleotides while mitigating sequencing depth requirements |
US11427867B2 (en) | 2017-11-29 | 2022-08-30 | Xgenomes Corp. | Sequencing by emergence |
WO2019108851A1 (fr) | 2017-11-30 | 2019-06-06 | 10X Genomics, Inc. | Systèmes et procédés de préparation et d'analyse d'acides nucléiques |
JP2021509024A (ja) | 2018-01-02 | 2021-03-18 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | 多数の液滴の捕捉 |
US10936953B2 (en) | 2018-01-04 | 2021-03-02 | Twist Bioscience Corporation | DNA-based digital information storage with sidewall electrodes |
US20190237163A1 (en) | 2018-01-12 | 2019-08-01 | Life Technologies Corporation | Methods for flow space quality score prediction by neural networks |
EP4324962A3 (fr) | 2018-01-31 | 2024-05-08 | Bio-Rad Laboratories, Inc. | Procédés et compositions pour déconvolutionner des codes à barres de partition |
US20200370096A1 (en) | 2018-01-31 | 2020-11-26 | Dovetail Genomics, Llc | Sample prep for dna linkage recovery |
EP3752832A1 (fr) | 2018-02-12 | 2020-12-23 | 10X Genomics, Inc. | Procédés de caractérisation d'analytes multiples à partir de cellules individuelles ou de populations cellulaires |
CN110184325A (zh) * | 2018-02-22 | 2019-08-30 | 张家港万众一芯生物科技有限公司 | 基于微孔阵列芯片的单分子文库pcr扩增的基因测序方法 |
US11639928B2 (en) | 2018-02-22 | 2023-05-02 | 10X Genomics, Inc. | Methods and systems for characterizing analytes from individual cells or cell populations |
CN112368397A (zh) * | 2018-03-13 | 2021-02-12 | 萨摩尔股份有限公司 | 用于单分子测序的方法 |
WO2019195346A1 (fr) | 2018-04-02 | 2019-10-10 | Progenity, Inc. | Procédés, systèmes et compositions de comptage de molécules d'acide nucléique |
CN112262218A (zh) | 2018-04-06 | 2021-01-22 | 10X基因组学有限公司 | 用于单细胞处理中的质量控制的系统和方法 |
EP3553182A1 (fr) | 2018-04-11 | 2019-10-16 | Université de Bourgogne | Méthode de détection d'anomalies génétiques somatiques, combinaison de sondes de capture et d'un kit de détection |
CA3097583A1 (fr) | 2018-04-19 | 2019-10-24 | Omniome, Inc. | Amelioration de la precision d'appels de base dans des procedes de sequencage d'acide nucleique |
CA3098296A1 (fr) | 2018-04-26 | 2019-10-31 | Omniome, Inc. | Procedes et compositions destines a stabiliser des complexes acide nucleique-nucleotide-polymerase |
US20210239700A1 (en) | 2018-05-04 | 2021-08-05 | Abbott Laboratories | Hbv diagnostic, prognostic, and therapeutic methods and products |
WO2019222706A1 (fr) | 2018-05-18 | 2019-11-21 | Twist Bioscience Corporation | Polynucléotides, réactifs, et procédés d'hybridation d'acides nucléiques |
EP3802874A1 (fr) | 2018-05-31 | 2021-04-14 | Omniome, Inc. | Augmentation du rapport signal/bruit lors du séquençage d'acides nucléiques |
US11814750B2 (en) | 2018-05-31 | 2023-11-14 | Personalis, Inc. | Compositions, methods and systems for processing or analyzing multi-species nucleic acid samples |
US10801064B2 (en) | 2018-05-31 | 2020-10-13 | Personalis, Inc. | Compositions, methods and systems for processing or analyzing multi-species nucleic acid samples |
US11180794B2 (en) | 2018-05-31 | 2021-11-23 | Omniome, Inc. | Methods and compositions for capping nucleic acids |
US11932899B2 (en) | 2018-06-07 | 2024-03-19 | 10X Genomics, Inc. | Methods and systems for characterizing nucleic acid molecules |
US11703427B2 (en) | 2018-06-25 | 2023-07-18 | 10X Genomics, Inc. | Methods and systems for cell and bead processing |
US11525159B2 (en) | 2018-07-03 | 2022-12-13 | Natera, Inc. | Methods for detection of donor-derived cell-free DNA |
AU2019312152A1 (en) | 2018-07-24 | 2021-02-18 | Pacific Biosciences Of California, Inc. | Serial formation of ternary complex species |
US20200032335A1 (en) | 2018-07-27 | 2020-01-30 | 10X Genomics, Inc. | Systems and methods for metabolome analysis |
EP3836967A4 (fr) | 2018-07-30 | 2022-06-15 | ReadCoor, LLC | Procédés et systèmes de traitement ou d'analyse d'échantillons |
HRP20221504T1 (hr) | 2018-08-08 | 2023-03-31 | Pml Screening, Llc | Postupci procjene rizika od razvoja progresivne multifokalne leukoencefalopatije uzrokovane john cunningham virusom pomoću genetskog testiranja |
WO2020041293A1 (fr) | 2018-08-20 | 2020-02-27 | Bio-Rad Laboratories, Inc. | Génération de séquences nucléotidiques par co-localisation de billes à code-barres dans des partitions |
US11519033B2 (en) | 2018-08-28 | 2022-12-06 | 10X Genomics, Inc. | Method for transposase-mediated spatial tagging and analyzing genomic DNA in a biological sample |
US20220048940A1 (en) | 2018-09-28 | 2022-02-17 | Centrillion Technology Holdings Corporation | Disulfide-linked reversible terminators |
AU2019364418A1 (en) | 2018-10-25 | 2021-04-22 | Illumina, Inc. | Methods and compositions for identifying ligands on arrays using indexes and barcodes |
WO2020101795A1 (fr) | 2018-11-15 | 2020-05-22 | Omniome, Inc. | Détection électronique de structure d'acide nucléique |
EP3887545A4 (fr) * | 2018-11-29 | 2022-08-24 | XGenomes Corp. | Séquencage par coalescence |
GB2585608B (en) | 2018-12-04 | 2021-11-03 | Omniome Inc | Mixed-phase fluids for nucleic acid sequencing and other analytical assays |
CA3121805A1 (fr) | 2018-12-07 | 2020-06-11 | Octant, Inc. | Systemes de criblage d'interactions proteine-proteine |
US11459607B1 (en) | 2018-12-10 | 2022-10-04 | 10X Genomics, Inc. | Systems and methods for processing-nucleic acid molecules from a single cell using sequential co-partitioning and composite barcodes |
WO2020120442A2 (fr) | 2018-12-13 | 2020-06-18 | Dna Script | Synthèse d'oligonucléotides directe sur des cellules et des biomolécules |
SG11202012558VA (en) | 2018-12-19 | 2021-01-28 | Illumina Inc | Methods for improving polynucleotide cluster clonality priority |
US11041199B2 (en) | 2018-12-20 | 2021-06-22 | Omniome, Inc. | Temperature control for analysis of nucleic acids and other analytes |
US11358137B2 (en) | 2018-12-26 | 2022-06-14 | Industrial Technology Research Institute | Tubular structure for producing droplets and method for producing droplets |
CN109738469A (zh) * | 2018-12-29 | 2019-05-10 | 赛纳生物科技(北京)有限公司 | 一种fop表面微坑镀膜的致密性检测方法 |
US20220081714A1 (en) | 2019-01-04 | 2022-03-17 | Northwestern University | Storing temporal data into dna |
US11926867B2 (en) | 2019-01-06 | 2024-03-12 | 10X Genomics, Inc. | Generating capture probes for spatial analysis |
US11649485B2 (en) | 2019-01-06 | 2023-05-16 | 10X Genomics, Inc. | Generating capture probes for spatial analysis |
US11845983B1 (en) | 2019-01-09 | 2023-12-19 | 10X Genomics, Inc. | Methods and systems for multiplexing of droplet based assays |
EP3908678A1 (fr) | 2019-01-10 | 2021-11-17 | Iovance Biotherapeutics, Inc. | Système et procédés de surveillance de la clonalité et de la persistance d'une thérapie cellulaire adoptive |
MX2021009482A (es) * | 2019-02-11 | 2021-11-12 | Ultima Genomics Inc | Metodos para el analisis de acidos nucleicos. |
US11467153B2 (en) | 2019-02-12 | 2022-10-11 | 10X Genomics, Inc. | Methods for processing nucleic acid molecules |
US11851683B1 (en) | 2019-02-12 | 2023-12-26 | 10X Genomics, Inc. | Methods and systems for selective analysis of cellular samples |
SG11202108788TA (en) | 2019-02-12 | 2021-09-29 | 10X Genomics Inc | Methods for processing nucleic acid molecules |
EP3924513B1 (fr) | 2019-02-14 | 2023-04-12 | Pacific Biosciences of California, Inc. | Atténuation d'impacts défavorables de systèmes de détection sur des acides nucléiques et d'autres analytes biologiques |
CN113613787B (zh) | 2019-02-20 | 2023-06-13 | 加利福尼亚太平洋生物科学股份有限公司 | 用于检测化学和生物分析物的扫描装置和方法 |
US11655499B1 (en) | 2019-02-25 | 2023-05-23 | 10X Genomics, Inc. | Detection of sequence elements in nucleic acid molecules |
SG11202109322TA (en) | 2019-02-26 | 2021-09-29 | Twist Bioscience Corp | Variant nucleic acid libraries for glp1 receptor |
JP2022522668A (ja) | 2019-02-26 | 2022-04-20 | ツイスト バイオサイエンス コーポレーション | 抗体を最適化するための変異体核酸ライブラリ |
WO2020185791A1 (fr) | 2019-03-11 | 2020-09-17 | 10X Genomics, Inc. | Systèmes et procédés de traitement de billes marquées optiquement |
EP3937780A4 (fr) | 2019-03-14 | 2022-12-07 | InSilixa, Inc. | Procédés et systèmes pour une détection à base de fluorescence résolue en temps |
NL2023316B1 (en) | 2019-03-21 | 2020-09-28 | Illumina Inc | Artificial intelligence-based sequencing |
WO2020191387A1 (fr) | 2019-03-21 | 2020-09-24 | Illumina, Inc. | Appel de base à base d'intelligence artificielle |
NL2023312B1 (en) | 2019-03-21 | 2020-09-28 | Illumina Inc | Artificial intelligence-based base calling |
NL2023311B9 (en) | 2019-03-21 | 2021-03-12 | Illumina Inc | Artificial intelligence-based generation of sequencing metadata |
US11210554B2 (en) | 2019-03-21 | 2021-12-28 | Illumina, Inc. | Artificial intelligence-based generation of sequencing metadata |
NL2023310B1 (en) | 2019-03-21 | 2020-09-28 | Illumina Inc | Training data generation for artificial intelligence-based sequencing |
NL2023314B1 (en) | 2019-03-21 | 2020-09-28 | Illumina Inc | Artificial intelligence-based quality scoring |
WO2020206170A1 (fr) | 2019-04-02 | 2020-10-08 | Progenity, Inc. | Procédés, systèmes et compositions de comptage de molécules d'acide nucléique |
US11989216B2 (en) | 2019-04-09 | 2024-05-21 | University Of Washington | Systems and methods for providing similarity-based retrieval of information stored in DNA |
MX2021003760A (es) | 2019-04-29 | 2021-09-21 | Illumina Inc | Identificacion y analisis de muestras microbianas por incubacion rapida y enriquecimiento de acido nucleico. |
WO2020227382A1 (fr) * | 2019-05-08 | 2020-11-12 | Qiagen Sciences, Llc | Procédés et compositions de séquençage séquentiel |
US11593649B2 (en) | 2019-05-16 | 2023-02-28 | Illumina, Inc. | Base calling using convolutions |
AU2020280104A1 (en) | 2019-05-22 | 2022-01-20 | Mission Bio, Inc. | Method and apparatus for simultaneous targeted sequencing of DNA, RNA and protein |
AU2020283935A1 (en) | 2019-05-28 | 2021-12-23 | Octant, Inc. | Transcriptional relay system |
EP3976820A1 (fr) | 2019-05-30 | 2022-04-06 | 10X Genomics, Inc. | Procédés de détection de l'hétérogénéité spatiale d'un échantillon biologique |
WO2020252186A1 (fr) | 2019-06-11 | 2020-12-17 | Omniome, Inc. | Détection de mise au point étalonnée |
AU2020298294A1 (en) | 2019-06-21 | 2022-02-17 | Twist Bioscience Corporation | Barcode-based nucleic acid sequence assembly |
WO2021003255A1 (fr) | 2019-07-01 | 2021-01-07 | Mission Bio | Procédé et appareil pour normaliser des lectures quantitatives dans des expériences à cellule unique |
WO2021011803A1 (fr) | 2019-07-16 | 2021-01-21 | Omniome, Inc. | Acides nucléiques synthétiques ayant des structures non naturelles |
US10656368B1 (en) | 2019-07-24 | 2020-05-19 | Omniome, Inc. | Method and system for biological imaging using a wide field objective lens |
CN110499361B (zh) * | 2019-07-31 | 2022-11-25 | 齐鲁工业大学 | 一种末端碱基流式荧光测序微球的制备方法及应用 |
US20230178182A1 (en) | 2019-08-19 | 2023-06-08 | Green Cross Genome Corporation | Method for detecting chromosomal abnormality by using information about distance between nucleic acid fragments |
TW202124406A (zh) | 2019-09-10 | 2021-07-01 | 美商歐姆尼歐美公司 | 核苷酸之可逆修飾 |
BR112021026562A2 (pt) | 2019-09-20 | 2022-11-29 | Illumina Inc | Métodos e composições para identificar ligantes em arranjos com o uso de índices e códigos de barras |
CN114829626A (zh) | 2019-10-10 | 2022-07-29 | 1859公司 | 用于微流体筛选的方法和系统 |
CN114599795A (zh) * | 2019-10-18 | 2022-06-07 | 加利福尼亚太平洋生物科学股份有限公司 | 用于对核酸加帽的方法和组合物 |
CN114556480A (zh) | 2019-11-07 | 2022-05-27 | 欧森纳治疗股份有限公司 | 肿瘤微环境的分类 |
WO2021091611A1 (fr) | 2019-11-08 | 2021-05-14 | 10X Genomics, Inc. | Agents de capture d'analytes marqués spatialement pour le multiplexage d'analytes |
EP4025711A2 (fr) | 2019-11-08 | 2022-07-13 | 10X Genomics, Inc. | Amélioration de la spécificité de la liaison d'un analyte |
CN110951852B (zh) * | 2019-11-25 | 2022-11-25 | 齐鲁工业大学 | 单碱基连续延伸流式靶向测序法 |
US20230028790A1 (en) | 2019-11-29 | 2023-01-26 | GC Genome Corporation | Artificial intelligence-based chromosomal abnormality detection method |
SG11202106899SA (en) | 2019-12-23 | 2021-09-29 | 10X Genomics Inc | Methods for spatial analysis using rna-templated ligation |
JP2023511279A (ja) | 2020-01-13 | 2023-03-17 | フルーエント バイオサイエンシーズ インコーポレイテッド | 単一細胞シーケンシング |
US11827936B2 (en) | 2020-01-13 | 2023-11-28 | Fluent Biosciences Inc. | Methods and systems for single cell gene profiling |
CA3167729A1 (fr) | 2020-01-13 | 2021-07-22 | Fluent Biosciences Inc. | Criblage de medicament par emulsion |
US11702693B2 (en) | 2020-01-21 | 2023-07-18 | 10X Genomics, Inc. | Methods for printing cells and generating arrays of barcoded cells |
US11732299B2 (en) | 2020-01-21 | 2023-08-22 | 10X Genomics, Inc. | Spatial assays with perturbed cells |
US11821035B1 (en) | 2020-01-29 | 2023-11-21 | 10X Genomics, Inc. | Compositions and methods of making gene expression libraries |
WO2021152586A1 (fr) | 2020-01-30 | 2021-08-05 | Yeda Research And Development Co. Ltd. | Procédés d'analyse du microbiome, du profil d'immunoglobuline et de l'état physiologique |
US11898205B2 (en) | 2020-02-03 | 2024-02-13 | 10X Genomics, Inc. | Increasing capture efficiency of spatial assays |
WO2021158511A1 (fr) | 2020-02-04 | 2021-08-12 | Omniome, Inc. | Cuves à circulation et procédés pour leur fabrication et leur utilisation |
US11732300B2 (en) | 2020-02-05 | 2023-08-22 | 10X Genomics, Inc. | Increasing efficiency of spatial analysis in a biological sample |
US11835462B2 (en) | 2020-02-11 | 2023-12-05 | 10X Genomics, Inc. | Methods and compositions for partitioning a biological sample |
WO2021163637A1 (fr) | 2020-02-13 | 2021-08-19 | Zymergen Inc. | Bibliothèque métagénomique et plateforme de découverte de produit naturel |
US20210265018A1 (en) | 2020-02-20 | 2021-08-26 | Illumina, Inc. | Knowledge Distillation and Gradient Pruning-Based Compression of Artificial Intelligence-Based Base Caller |
US11891654B2 (en) | 2020-02-24 | 2024-02-06 | 10X Genomics, Inc. | Methods of making gene expression libraries |
US11926863B1 (en) | 2020-02-27 | 2024-03-12 | 10X Genomics, Inc. | Solid state single cell method for analyzing fixed biological cells |
US11768175B1 (en) | 2020-03-04 | 2023-09-26 | 10X Genomics, Inc. | Electrophoretic methods for spatial analysis |
EP4121016A1 (fr) | 2020-03-16 | 2023-01-25 | Fluent Biosciences Inc. | Analyse multi-omique dans des gouttelettes monodispersées |
WO2021214766A1 (fr) | 2020-04-21 | 2021-10-28 | Yeda Research And Development Co. Ltd. | Procédés de diagnostic d'infections virales et vaccins associés |
EP4242325A3 (fr) | 2020-04-22 | 2023-10-04 | 10X Genomics, Inc. | Procédés d'analyse spatiale utilisant un appauvrissement d'arn ciblée |
US20230183798A1 (en) | 2020-05-05 | 2023-06-15 | Pacific Biosciences Of California, Inc. | Compositions and methods for modifying polymerase-nucleic acid complexes |
US11188778B1 (en) | 2020-05-05 | 2021-11-30 | Illumina, Inc. | Equalization-based image processing and spatial crosstalk attenuator |
US20230203592A1 (en) | 2020-05-05 | 2023-06-29 | Akershus Universitetssykehus Hf | Compositions and methods for characterizing bowel cancer |
US11851700B1 (en) | 2020-05-13 | 2023-12-26 | 10X Genomics, Inc. | Methods, kits, and compositions for processing extracellular molecules |
EP4153775A1 (fr) | 2020-05-22 | 2023-03-29 | 10X Genomics, Inc. | Mesure spatio-temporelle simultanée de l'expression génique et de l'activité cellulaire |
EP4153776A1 (fr) | 2020-05-22 | 2023-03-29 | 10X Genomics, Inc. | Analyse spatiale pour détecter des variants de séquence |
WO2021242834A1 (fr) | 2020-05-26 | 2021-12-02 | 10X Genomics, Inc. | Procédé de réinitialisation d'un réseau |
IL298097A (en) | 2020-05-27 | 2023-01-01 | Genetic Tech Limited | Methods for assessing the risk of the development of an acute reaction to infection with the corona virus |
EP4025692A2 (fr) | 2020-06-02 | 2022-07-13 | 10X Genomics, Inc. | Procédés de banques d'acides nucléiques |
CN116249785A (zh) | 2020-06-02 | 2023-06-09 | 10X基因组学有限公司 | 用于抗原-受体的空间转录组学 |
WO2021252499A1 (fr) | 2020-06-08 | 2021-12-16 | 10X Genomics, Inc. | Méthodes de détermination de marge chirurgicale et méthodes d'utilisation associées |
EP4165207A1 (fr) | 2020-06-10 | 2023-04-19 | 10X Genomics, Inc. | Procédés de détermination d'un emplacement d'un analyte dans un échantillon biologique |
AU2021294334A1 (en) | 2020-06-25 | 2023-02-02 | 10X Genomics, Inc. | Spatial analysis of DNA methylation |
US11761038B1 (en) | 2020-07-06 | 2023-09-19 | 10X Genomics, Inc. | Methods for identifying a location of an RNA in a biological sample |
US11981960B1 (en) | 2020-07-06 | 2024-05-14 | 10X Genomics, Inc. | Spatial analysis utilizing degradable hydrogels |
EP4179113A1 (fr) | 2020-07-08 | 2023-05-17 | F. Hoffmann-La Roche AG | Déplétion ciblée de molécules de bibliothèque non cibles à l'aide d'amorces poison pendant la capture cible de bibliothèques de séquençage de nouvelle génération |
US11981958B1 (en) | 2020-08-20 | 2024-05-14 | 10X Genomics, Inc. | Methods for spatial analysis using DNA capture |
US11926822B1 (en) | 2020-09-23 | 2024-03-12 | 10X Genomics, Inc. | Three-dimensional spatial analysis |
CA3200519A1 (fr) * | 2020-11-03 | 2022-05-12 | Fluent Biosciences Inc. | Procedes et systemes pour la detection de microbes pathogenes chez un patient |
US11827935B1 (en) | 2020-11-19 | 2023-11-28 | 10X Genomics, Inc. | Methods for spatial analysis using rolling circle amplification and detection probes |
KR20220074088A (ko) | 2020-11-27 | 2022-06-03 | 주식회사 지씨지놈 | 인공지능 기반 암 진단 및 암 종 예측방법 |
AU2021409136A1 (en) | 2020-12-21 | 2023-06-29 | 10X Genomics, Inc. | Methods, compositions, and systems for capturing probes and/or barcodes |
CN116997411A (zh) | 2021-01-13 | 2023-11-03 | 加利福尼亚太平洋生物科学股份有限公司 | 使用胶体组装的表面结构化 |
WO2022174054A1 (fr) | 2021-02-13 | 2022-08-18 | The General Hospital Corporation | Procédés et compositions pour la détection de macromolécules in situ et utilisations correspondantes |
AU2022227563A1 (en) | 2021-02-23 | 2023-08-24 | 10X Genomics, Inc. | Probe-based analysis of nucleic acids and proteins |
WO2022198068A1 (fr) | 2021-03-18 | 2022-09-22 | 10X Genomics, Inc. | Capture multiplex de gène et expression de protéines à partir d'un échantillon biologique |
EP4314327A1 (fr) | 2021-03-22 | 2024-02-07 | Illumina Cambridge Limited | Procédés d'amélioration de la clonalité de groupes d'acides nucléiques |
WO2022208171A1 (fr) | 2021-03-31 | 2022-10-06 | UCL Business Ltd. | Procédés de détection d'analytes |
US20220336052A1 (en) * | 2021-04-19 | 2022-10-20 | University Of Utah Research Foundation | Systems and methods for facilitating rapid genome sequence analysis |
KR20220160806A (ko) | 2021-05-28 | 2022-12-06 | 주식회사 지씨지놈 | 세포유리 핵산단편 말단 서열 모티프 빈도 및 크기를 이용한 암 진단 및 암 종 예측방법 |
WO2022265994A1 (fr) | 2021-06-15 | 2022-12-22 | Illumina, Inc. | Fonctionnalisation de surface exempte d'hydrogel pour séquençage |
US11236388B1 (en) | 2021-06-17 | 2022-02-01 | Element Biosciences, Inc. | Compositions and methods for pairwise sequencing |
US11859241B2 (en) | 2021-06-17 | 2024-01-02 | Element Biosciences, Inc. | Compositions and methods for pairwise sequencing |
CN113174388B (zh) * | 2021-06-28 | 2021-09-10 | 中国农业大学 | 一种功能核酸纳米杆与功能核酸纳米花的制备及形貌转换方法 |
US11455487B1 (en) | 2021-10-26 | 2022-09-27 | Illumina Software, Inc. | Intensity extraction and crosstalk attenuation using interpolation and adaptation for base calling |
KR20240031968A (ko) | 2021-07-19 | 2024-03-08 | 일루미나, 인코포레이티드 | 염기 호출에 대한 보간 및 적응을 갖는 강도 추출 |
GB202110479D0 (en) | 2021-07-21 | 2021-09-01 | Dnae Diagnostics Ltd | Compositions, kits and methods for sequencing target polynucleotides |
GB202110485D0 (en) | 2021-07-21 | 2021-09-01 | Dnae Diagnostics Ltd | Compositions, kits and methods for sequencing target polynucleotides |
WO2023002203A1 (fr) | 2021-07-21 | 2023-01-26 | Dnae Diagnostics Limited | Procédé et système comprenant une cartouche pour le séquençage de polynucléotides cibles |
US20230116852A1 (en) | 2021-07-23 | 2023-04-13 | Illumina, Inc. | Methods for preparing substrate surface for dna sequencing |
WO2023034489A1 (fr) | 2021-09-01 | 2023-03-09 | 10X Genomics, Inc. | Procédés, compositions et kits pour bloquer une sonde de capture sur un réseau spatial |
WO2023049215A1 (fr) | 2021-09-22 | 2023-03-30 | Illumina, Inc. | Appel de base basé sur l'état compressé |
CA3234961A1 (fr) | 2021-10-20 | 2023-04-27 | Illumina, Inc. | Procedes de capture d'adn de banque pour le sequencage |
WO2023081300A2 (fr) * | 2021-11-03 | 2023-05-11 | Abbott Laboratories | Systèmes et méthodes pour l'analyse d'échantillons |
US20230348957A1 (en) | 2021-12-07 | 2023-11-02 | Luminex Corporation | Methods and compositions for nucleic acid analysis |
WO2023114190A1 (fr) * | 2021-12-13 | 2023-06-22 | Cz Biohub Sf, Inc. | Établissement de profils épigénomiques unicellulaires à l'aide de la fluidique et des hydrogels |
US20230215515A1 (en) | 2021-12-23 | 2023-07-06 | Illumina Software, Inc. | Facilitating secure execution of external workflows for genomic sequencing diagnostics |
WO2023122363A1 (fr) | 2021-12-23 | 2023-06-29 | Illumina Software, Inc. | Résumés dynamiques d'état graphique pour séquençage de nucléotides |
WO2023129764A1 (fr) | 2021-12-29 | 2023-07-06 | Illumina Software, Inc. | Permutation automatique des versions de modèle d'analyse de variants pour les applications d'analyse génomique |
WO2023135485A1 (fr) | 2022-01-13 | 2023-07-20 | Oslo Universitetssykehus Hf | Marqueurs du cancer de la prostate et leurs utilisations |
WO2023141154A1 (fr) | 2022-01-20 | 2023-07-27 | Illumina Cambridge Limited | Procédés de détection de méthylcytosine et d'hydroxyméthylcytosine par séquençage |
WO2023152568A2 (fr) | 2022-02-10 | 2023-08-17 | Oslo Universitetssykehus Hf | Compositions et méthodes de caractérisation du cancer du poumon |
WO2023183937A1 (fr) | 2022-03-25 | 2023-09-28 | Illumina, Inc. | Appel de bases séquence par séquence |
CN114592023B (zh) * | 2022-03-31 | 2023-03-24 | 杭州优玛达生物科技有限公司 | 一种细胞裂解自组装多肽复合物、自组装方法、自组装多肽制剂及应用 |
EP4253550A1 (fr) | 2022-04-01 | 2023-10-04 | GenCC GmbH 6 Co. KG | Procédé de fabrication d'un système de transport viral, d'un vecteur ou de tout système de transport et complexes crispr spécifiques au cancer |
US20230392201A1 (en) | 2022-06-06 | 2023-12-07 | Element Biosciences, Inc. | Methods for assembling and reading nucleic acid sequences from mixed populations |
WO2023239917A1 (fr) | 2022-06-09 | 2023-12-14 | Illumina, Inc. | Dépendance d'appel de bases envers l'inclinaison de cellule de flux |
WO2024050450A1 (fr) | 2022-08-31 | 2024-03-07 | Gigamune, Inc. | Vecteurs enveloppés modifiés et leurs procédés d'utilisation |
US20240133892A1 (en) | 2022-09-27 | 2024-04-25 | Nautilus Subsidiary, Inc. | Polypeptide capture, in situ fragmentation and identification |
Citations (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5506100A (en) * | 1990-10-11 | 1996-04-09 | Indiana University Foundation | Process and apparatus for fragmenting biomaterials |
US5508169A (en) * | 1990-04-06 | 1996-04-16 | Queen's University At Kingston | Indexing linkers |
US5610010A (en) * | 1990-10-11 | 1997-03-11 | Indiana University Foundation | Process and apparatus for fragmenting biomaterials |
US5629158A (en) * | 1989-03-22 | 1997-05-13 | Cemu Bitecknik Ab | Solid phase diagnosis of medical conditions |
US5728524A (en) * | 1992-07-13 | 1998-03-17 | Medical Research Counsil | Process for categorizing nucleotide sequence populations |
US5814444A (en) * | 1995-06-07 | 1998-09-29 | University Of Washington | Methods for making and using single-chromosome amplfication libraries |
US5863722A (en) * | 1994-10-13 | 1999-01-26 | Lynx Therapeutics, Inc. | Method of sorting polynucleotides |
US5989892A (en) * | 1995-06-14 | 1999-11-23 | Tonen Corporation | Microorganisms, demulsifiers and processes for breaking an emulsion |
US5994068A (en) * | 1997-03-11 | 1999-11-30 | Wisconsin Alumni Research Foundation | Nucleic acid indexing |
US6004783A (en) * | 1994-03-18 | 1999-12-21 | The General Hospital Corporation | Cleaved amplified RFLP detection methods |
US6023540A (en) * | 1997-03-14 | 2000-02-08 | Trustees Of Tufts College | Fiber optic sensor with encoded microspheres |
US6060245A (en) * | 1996-12-13 | 2000-05-09 | Stratagene | Methods and adaptors for generating specific nucleic acid populations |
US6184012B1 (en) * | 1996-04-25 | 2001-02-06 | Medical Research Council | Isolation of enzymes |
US6270966B1 (en) * | 1996-02-09 | 2001-08-07 | The United States Of America As Represented By The Department Of Health And Human Services | Restriction display (RD-PCR) of differentially expressed mRNAs |
US6274320B1 (en) * | 1999-09-16 | 2001-08-14 | Curagen Corporation | Method of sequencing a nucleic acid |
US6287825B1 (en) * | 1998-09-18 | 2001-09-11 | Molecular Staging Inc. | Methods for reducing the complexity of DNA sequences |
US6468748B1 (en) * | 1996-03-04 | 2002-10-22 | Sequenom, Inc. | Methods of screening nucleic acids using volatile salts in mass spectrometry |
US6475736B1 (en) * | 2000-05-23 | 2002-11-05 | Variagenics, Inc. | Methods for genetic analysis of DNA using biased amplification of polymorphic sites |
US6489103B1 (en) * | 1997-07-07 | 2002-12-03 | Medical Research Council | In vitro sorting method |
Family Cites Families (216)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4175054A (en) | 1976-11-11 | 1979-11-20 | Petrolite Corporation | Use of hydrocarbon polymers in demulsification |
US5821058A (en) * | 1984-01-16 | 1998-10-13 | California Institute Of Technology | Automated DNA sequencing technique |
US5171534A (en) * | 1984-01-16 | 1992-12-15 | California Institute Of Technology | Automated DNA sequencing technique |
US4965188A (en) * | 1986-08-22 | 1990-10-23 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme |
US4683202A (en) * | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
US4683195A (en) * | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
US4801529A (en) | 1985-06-18 | 1989-01-31 | Brandeis University | Methods for isolating mutant microoganisms using microcapsules coated with indicator material |
US4863849A (en) | 1985-07-18 | 1989-09-05 | New York Medical College | Automatable process for sequencing nucleotide |
US4811218A (en) * | 1986-06-02 | 1989-03-07 | Applied Biosystems, Inc. | Real time scanning electrophoresis apparatus for DNA sequencing |
US5252494A (en) * | 1986-06-25 | 1993-10-12 | Trustees Of Tufts College | Fiber optic sensors, apparatus, and detection methods using controlled release polymers and reagent formulations held within a polymeric reaction matrix |
US5143853A (en) * | 1986-06-25 | 1992-09-01 | Trustees Of Tufts College | Absorbance modulated fluorescence detection methods and sensors |
US5254477A (en) * | 1986-06-25 | 1993-10-19 | Trustees Of Tufts College | Flourescence intramolecular energy transfer conjugate compositions and detection methods |
US4822746A (en) * | 1986-06-25 | 1989-04-18 | Trustees Of Tufts College | Radiative and non-radiative energy transfer and absorbance modulated fluorescence detection methods and sensors |
US4994372A (en) * | 1987-01-14 | 1991-02-19 | President And Fellows Of Harvard College | DNA sequencing |
US5525464A (en) * | 1987-04-01 | 1996-06-11 | Hyseq, Inc. | Method of sequencing by hybridization of oligonucleotide probes |
IL86724A (en) | 1987-06-19 | 1995-01-24 | Siska Diagnostics Inc | Methods and kits for amplification and testing of nucleic acid sequences |
JP2846018B2 (ja) | 1988-01-21 | 1999-01-13 | ジェネンテク,インコーポレイテッド | 核酸配列の増幅および検出 |
CA1340807C (fr) | 1988-02-24 | 1999-11-02 | Lawrence T. Malek | Procede d'amplification d'une sequence d'acide nucleique |
GB8810400D0 (en) | 1988-05-03 | 1988-06-08 | Southern E | Analysing polynucleotide sequences |
SE8801070D0 (sv) | 1988-03-23 | 1988-03-23 | Pharmacia Ab | Method for immobilizing a dna sequence on a solid support |
US4971903A (en) * | 1988-03-25 | 1990-11-20 | Edward Hyman | Pyrophosphate-based method and apparatus for sequencing nucleic acids |
JPH03503845A (ja) | 1988-04-22 | 1991-08-29 | マサチユセツツ・インスチチユート・オブ・テクノロジー | 微小滴を形成しそして使用する方法 |
US5225332A (en) | 1988-04-22 | 1993-07-06 | Massachusetts Institute Of Technology | Process for manipulation of non-aqueous surrounded microdroplets |
US6054270A (en) * | 1988-05-03 | 2000-04-25 | Oxford Gene Technology Limited | Analying polynucleotide sequences |
US5700637A (en) * | 1988-05-03 | 1997-12-23 | Isis Innovation Limited | Apparatus and method for analyzing polynucleotide sequences and method of generating oligonucleotide arrays |
GB8822228D0 (en) * | 1988-09-21 | 1988-10-26 | Southern E M | Support-bound oligonucleotides |
US5512439A (en) * | 1988-11-21 | 1996-04-30 | Dynal As | Oligonucleotide-linked magnetic particles and uses thereof |
US4938876A (en) | 1989-03-02 | 1990-07-03 | Ohsol Ernest O | Method for separating oil and water emulsions |
EP0392546A3 (fr) | 1989-04-14 | 1991-09-11 | Ro Institut Za Molekularnu Genetiku I Geneticko Inzenjerstvo | Procédé pour déterminer le contenu complet ou partiel de séquences très courtes dans des échantillons de particules discrètes de dimensions microscopiques par hybridation avec des sondes oligonucléotidiques |
US5143854A (en) | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
US5871928A (en) * | 1989-06-07 | 1999-02-16 | Fodor; Stephen P. A. | Methods for nucleic acid analysis |
US5744101A (en) * | 1989-06-07 | 1998-04-28 | Affymax Technologies N.V. | Photolabile nucleoside protecting groups |
US5800992A (en) | 1989-06-07 | 1998-09-01 | Fodor; Stephen P.A. | Method of detecting nucleic acids |
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 |
KR0185192B1 (ko) | 1989-10-05 | 1999-04-01 | 제임스 더블유. 데이비 | 신규의 유전자 및 폴리펩티드의 무세포 합성 및 분리 |
WO1991012342A1 (fr) * | 1990-02-16 | 1991-08-22 | F. Hoffmann-La Roche Ag | Ameliorations apportees a la specificite et a l'applicabilite de la reaction en chaine de polymerases |
JPH04223A (ja) * | 1990-04-16 | 1992-01-06 | Toshiba Corp | 無線電話装置、その充電方法および無線電話充電システム |
US5244636A (en) * | 1991-01-25 | 1993-09-14 | Trustees Of Tufts College | Imaging fiber optic array sensors, apparatus, and methods for concurrently detecting multiple analytes of interest in a fluid sample |
US5320814A (en) * | 1991-01-25 | 1994-06-14 | Trustees Of Tufts College | Fiber optic array sensors, apparatus, and methods for concurrently visualizing and chemically detecting multiple analytes of interest in a fluid sample |
US5250264A (en) * | 1991-01-25 | 1993-10-05 | Trustees Of Tufts College | Method of making imaging fiber optic sensors to concurrently detect multiple analytes of interest in a fluid sample |
US5114984A (en) * | 1991-04-26 | 1992-05-19 | Olin Corporation | Process for producing an antimicrobially effective polyurethane |
WO1993003151A1 (fr) † | 1991-08-10 | 1993-02-18 | Medical Research Council | Traitement de populations de cellules |
US5474796A (en) | 1991-09-04 | 1995-12-12 | Protogene Laboratories, Inc. | Method and apparatus for conducting an array of chemical reactions on a support surface |
WO1993005183A1 (fr) * | 1991-09-09 | 1993-03-18 | Baylor College Of Medicine | Procede et dispositif pour la determination rapide du sequençage d'adn ou d'arn au moyen d'une methode de sequençage par addition de base |
WO1993006239A1 (fr) * | 1991-09-24 | 1993-04-01 | Keygene N.V. | Amplification selective de fragments de restriction: procede general de dactyloscopie genetique |
US5270170A (en) | 1991-10-16 | 1993-12-14 | Affymax Technologies N.V. | Peptide library and screening method |
EP0916396B1 (fr) * | 1991-11-22 | 2005-04-13 | Affymetrix, Inc. (a Delaware Corporation) | Stratégies associées pour la synthèse de polymères |
US5445971A (en) * | 1992-03-20 | 1995-08-29 | Abbott Laboratories | Magnetically assisted binding assays using magnetically labeled binding members |
GB9208733D0 (en) | 1992-04-22 | 1992-06-10 | Medical Res Council | Dna sequencing method |
GB9210176D0 (en) * | 1992-05-12 | 1992-06-24 | Cemu Bioteknik Ab | Chemical method |
DE4223169C1 (de) | 1992-07-10 | 1993-11-25 | Ferring Arzneimittel Gmbh | Verfahren zur Mikroverkapselung wasserlöslicher Wirkstoffe |
US6114114A (en) * | 1992-07-17 | 2000-09-05 | Incyte Pharmaceuticals, Inc. | Comparative gene transcript analysis |
RU2048522C1 (ru) | 1992-10-14 | 1995-11-20 | Институт белка РАН | Способ размножения нуклеиновых кислот, способ их экспрессии и среда для их осуществления |
US5436143A (en) * | 1992-12-23 | 1995-07-25 | Hyman; Edward D. | Method for enzymatic synthesis of oligonucleotides |
IL104384A (en) | 1993-01-13 | 1996-11-14 | Yeda Res & Dev | Method for screening catalytic non-enzyme polypeptides and proteins |
US5298741A (en) * | 1993-01-13 | 1994-03-29 | Trustees Of Tufts College | Thin film fiber optic sensor array and apparatus for concurrent viewing and chemical sensing of a sample |
CA2155186A1 (fr) | 1993-02-01 | 1994-08-18 | Kevin M. Ulmer | Methodes et appareil pour le sequencage de l'adn |
US5436149A (en) | 1993-02-19 | 1995-07-25 | Barnes; Wayne M. | Thermostable DNA polymerase with enhanced thermostability and enhanced length and efficiency of primer extension |
US5714320A (en) | 1993-04-15 | 1998-02-03 | University Of Rochester | Rolling circle synthesis of oligonucleotides and amplification of select randomized circular oligonucleotides |
AU6707194A (en) | 1993-04-19 | 1994-11-08 | Medisorb Technologies International L.P. | Encapsulation of nucleic acids with conjugates that facilitate and target cellular uptake and gene expression |
AU6815894A (en) | 1993-04-19 | 1994-11-08 | Stuart A. Kauffman | Random chemistry for the generation of new compounds |
GB9315847D0 (en) * | 1993-07-30 | 1993-09-15 | Isis Innovation | Tag reagent and assay method |
US5482845A (en) * | 1993-09-24 | 1996-01-09 | The Trustees Of Columbia University In The City Of New York | Method for construction of normalized cDNA libraries |
ATE424927T1 (de) * | 1993-10-28 | 2009-03-15 | Houston Advanced Res Ct | Mikrofabriziertes poröses durchflussgerät zur diskreten bestimmung von bindungsreaktionen |
US5429807A (en) * | 1993-10-28 | 1995-07-04 | Beckman Instruments, Inc. | Method and apparatus for creating biopolymer arrays on a solid support surface |
AU8124694A (en) | 1993-10-29 | 1995-05-22 | Affymax Technologies N.V. | In vitro peptide and antibody display libraries |
GB9401833D0 (en) * | 1994-02-01 | 1994-03-30 | Isis Innovation | Method for discovering ligands |
US5928905A (en) * | 1995-04-18 | 1999-07-27 | Glaxo Group Limited | End-complementary polymerase reaction |
US5834252A (en) * | 1995-04-18 | 1998-11-10 | Glaxo Group Limited | End-complementary polymerase reaction |
AU710504B2 (en) | 1994-03-15 | 1999-09-23 | Brown University Research Foundation | Polymeric gene delivery system |
JP2556293B2 (ja) * | 1994-06-09 | 1996-11-20 | 日本電気株式会社 | Mos ota |
US5512490A (en) * | 1994-08-11 | 1996-04-30 | Trustees Of Tufts College | Optical sensor, optical sensing apparatus, and methods for detecting an analyte of interest using spectral recognition patterns |
US5604097A (en) * | 1994-10-13 | 1997-02-18 | Spectragen, Inc. | Methods for sorting polynucleotides using oligonucleotide tags |
US6013445A (en) * | 1996-06-06 | 2000-01-11 | Lynx Therapeutics, Inc. | Massively parallel signature sequencing by ligation of encoded adaptors |
US5795716A (en) * | 1994-10-21 | 1998-08-18 | Chee; Mark S. | Computer-aided visualization and analysis system for sequence evaluation |
FR2726286B1 (fr) | 1994-10-28 | 1997-01-17 | Genset Sa | Procede d'amplification d'acides nucleiques en phase solide et trousse de reactifs utile pour la mise en oeuvre de ce procede |
US5919673A (en) * | 1995-03-22 | 1999-07-06 | The Scripps Research Institute | One-pot enzymatic sulfation process using 3'-phosphoadenosine-5'-phosphosulfate and recycled phosphorylated adenosine intermediates |
EP0735144B1 (fr) * | 1995-03-28 | 2002-06-05 | Japan Science and Technology Corporation | Procédé pour l'indexation moléculaire de gènes utilisant des enzymes de restriction |
GB9507238D0 (en) * | 1995-04-07 | 1995-05-31 | Isis Innovation | Detecting dna sequence variations |
US5750341A (en) * | 1995-04-17 | 1998-05-12 | Lynx Therapeutics, Inc. | DNA sequencing by parallel oligonucleotide extensions |
KR19990008000A (ko) | 1995-04-24 | 1999-01-25 | 로버트 에스. 화이트 헤드 | 새로운 대사 경로를 만들고 이를 스크리닝하는 방법 |
US5648245A (en) * | 1995-05-09 | 1997-07-15 | Carnegie Institution Of Washington | Method for constructing an oligonucleotide concatamer library by rolling circle replication |
DE19518505A1 (de) * | 1995-05-19 | 1996-11-21 | Max Planck Gesellschaft | Verfahren zur Genexpressionsanalyse |
US5690894A (en) * | 1995-05-23 | 1997-11-25 | The Regents Of The University Of California | High density array fabrication and readout method for a fiber optic biosensor |
US5910408A (en) | 1995-06-07 | 1999-06-08 | The General Hospital Corporation | Catalytic DNA having ligase activity |
US5728529A (en) * | 1995-06-23 | 1998-03-17 | Baylor College Of Medicine | Alternative dye-labeled ribonucleotides, deoxyribonucleotides, and dideoxyribonucleotides for automated DNA analysis |
US6200737B1 (en) * | 1995-08-24 | 2001-03-13 | Trustees Of Tufts College | Photodeposition method for fabricating a three-dimensional, patterned polymer microstructure |
US5843655A (en) * | 1995-09-18 | 1998-12-01 | Affymetrix, Inc. | Methods for testing oligonucleotide arrays |
US5871697A (en) * | 1995-10-24 | 1999-02-16 | Curagen Corporation | Method and apparatus for identifying, classifying, or quantifying DNA sequences in a sample without sequencing |
DE19646372C1 (de) | 1995-11-11 | 1997-06-19 | Evotec Biosystems Gmbh | Genotyp und Phänotyp koppelnde Verbindung |
US5780231A (en) * | 1995-11-17 | 1998-07-14 | Lynx Therapeutics, Inc. | DNA extension and analysis with rolling primers |
US5962228A (en) * | 1995-11-17 | 1999-10-05 | Lynx Therapeutics, Inc. | DNA extension and analysis with rolling primers |
DK0862656T3 (da) | 1995-11-21 | 2001-04-09 | Univ Yale | Unimolekylær segmentamplifikation og -detektering |
US5854033A (en) | 1995-11-21 | 1998-12-29 | Yale University | Rolling circle replication reporter systems |
US5633972A (en) * | 1995-11-29 | 1997-05-27 | Trustees Of Tufts College | Superresolution imaging fiber for subwavelength light energy generation and near-field optical microscopy |
US5814524A (en) * | 1995-12-14 | 1998-09-29 | Trustees Of Tufts College | Optical sensor apparatus for far-field viewing and making optical analytical measurements at remote locations |
US5851772A (en) * | 1996-01-29 | 1998-12-22 | University Of Chicago | Microchip method for the enrichment of specific DNA sequences |
US5770637A (en) * | 1996-05-01 | 1998-06-23 | Johnson & Johnson Vision Products, Inc. | Anti-bacterial, UV absorbable, tinted, metal-chelating polymers |
US6022688A (en) * | 1996-05-13 | 2000-02-08 | Sequenom, Inc. | Method for dissociating biotin complexes |
US5846727A (en) * | 1996-06-06 | 1998-12-08 | Board Of Supervisors Of Louisiana State University And Agricultural & Mechanical College | Microsystem for rapid DNA sequencing |
CZ397998A3 (cs) * | 1996-06-06 | 1999-07-14 | Lynx Therapeutics, Inc. | Způsob sekvenční analýzy ligací kódovaného adaptoru |
US6083693A (en) | 1996-06-14 | 2000-07-04 | Curagen Corporation | Identification and comparison of protein-protein interactions that occur in populations |
US5916524A (en) | 1997-07-23 | 1999-06-29 | Bio-Dot, Inc. | Dispensing apparatus having improved dynamic range |
US5846721A (en) * | 1996-09-19 | 1998-12-08 | The Trustees Of Columbia University In The City Of New York | Efficient and simpler method to construct normalized cDNA libraries with improved representations of full-length cDNAs |
GB9620209D0 (en) | 1996-09-27 | 1996-11-13 | Cemu Bioteknik Ab | Method of sequencing DNA |
WO1998013502A2 (fr) | 1996-09-27 | 1998-04-02 | Icos Corporation | Procedes d'identification de composes pour la rupture des interactions entre proteines |
US6124092A (en) | 1996-10-04 | 2000-09-26 | The Perkin-Elmer Corporation | Multiplex polynucleotide capture methods and compositions |
US5900481A (en) * | 1996-11-06 | 1999-05-04 | Sequenom, Inc. | Bead linkers for immobilizing nucleic acids to solid supports |
US6133436A (en) * | 1996-11-06 | 2000-10-17 | Sequenom, Inc. | Beads bound to a solid support and to nucleic acids |
US6887665B2 (en) * | 1996-11-14 | 2005-05-03 | Affymetrix, Inc. | Methods of array synthesis |
DE19648372A1 (de) | 1996-11-22 | 1998-05-28 | Serck Como Gmbh | Verfahren und Vorrichtung zum Eindampfen von Abwässern |
US6395524B2 (en) | 1996-11-27 | 2002-05-28 | University Of Washington | Thermostable polymerases having altered fidelity and method of identifying and using same |
US6310354B1 (en) | 1996-12-03 | 2001-10-30 | Erkki Soini | Method and a device for monitoring nucleic acid amplification reactions |
US20020172965A1 (en) * | 1996-12-13 | 2002-11-21 | Arcaris, Inc. | Methods for measuring relative amounts of nucleic acids in a complex mixture and retrieval of specific sequences therefrom |
GB9626815D0 (en) | 1996-12-23 | 1997-02-12 | Cemu Bioteknik Ab | Method of sequencing DNA |
EP1712623B1 (fr) | 1997-01-21 | 2011-10-19 | The General Hospital Corporation | Sélection de protéines par fusions de proteénes et d'ARN |
US6136543A (en) * | 1997-01-31 | 2000-10-24 | Hitachi, Ltd. | Method for determining nucleic acids base sequence and apparatus therefor |
CA2196496A1 (fr) | 1997-01-31 | 1998-07-31 | Stephen William Watson Michnick | Epreuve de complementation de fragments de proteines pour la detection d'interactions entre proteines |
ATE273381T1 (de) * | 1997-02-12 | 2004-08-15 | Eugene Y Chan | Verfahren zur analyse von polymeren |
GB9703369D0 (en) | 1997-02-18 | 1997-04-09 | Lindqvist Bjorn H | Process |
AU6571598A (en) | 1997-03-18 | 1998-10-12 | Chromaxome Corporation | Methods for screening compounds using encapsulated cells |
US5891477A (en) | 1997-03-28 | 1999-04-06 | Biohybrid Technologies, Inc. | Non-steroidal anti-inflammatory agents inhibition of fibrotic response to an implanted device |
AU6846698A (en) * | 1997-04-01 | 1998-10-22 | Glaxo Group Limited | Method of nucleic acid amplification |
ATE269908T1 (de) | 1997-04-01 | 2004-07-15 | Manteia S A | Methode zur sequenzierung von nukleinsäuren |
US6143496A (en) | 1997-04-17 | 2000-11-07 | Cytonix Corporation | Method of sampling, amplifying and quantifying segment of nucleic acid, polymerase chain reaction assembly having nanoliter-sized sample chambers, and method of filling assembly |
US6406845B1 (en) | 1997-05-05 | 2002-06-18 | Trustees Of Tuft College | Fiber optic biosensor for selectively detecting oligonucleotide species in a mixed fluid sample |
EP1138764A3 (fr) * | 1997-05-13 | 2001-10-24 | Azign Bioscience A/S | Transcription inverse à deux étapes |
JP3610231B2 (ja) * | 1997-08-01 | 2005-01-12 | キヤノン株式会社 | 反応場アレー、反応場アレーの製造方法、反応場アレーを用いた反応方法及び反応場アレーを用いた試料溶液中の物質の定量方法 |
EP0895083B1 (fr) | 1997-08-01 | 2009-09-23 | Canon Kabushiki Kaisha | Réseau de site de réaction, procédé de son fabrication, procédé de réaction le utilisant, et procédé de détermination quantitatif d'une substance dans un échantillon le utilisant |
US5961228A (en) * | 1997-08-22 | 1999-10-05 | Paxar Corporation | Modular printer |
US20010006630A1 (en) * | 1997-09-02 | 2001-07-05 | Oron Yacoby-Zeevi | Introducing a biological material into a patient |
US6087099A (en) * | 1997-09-08 | 2000-07-11 | Myriad Genetics, Inc. | Method for sequencing both strands of a double stranded DNA in a single sequencing reaction |
US6475722B1 (en) | 1997-12-03 | 2002-11-05 | Curagen Corporation | Surface treatments for DNA processing devices |
NL1007781C2 (nl) | 1997-12-12 | 1999-06-15 | Packard Instr Bv | Microtiterplaat. |
DE69822206T2 (de) | 1997-12-19 | 2005-02-17 | Affymetrix, Inc., Santa Clara | Erkenntnisse der genomforschung für die suche nach neuartigen wirkstoffen |
ATE506449T1 (de) | 1997-12-22 | 2011-05-15 | Hitachi Chemical Co Ltd | Direkte rt-pcr auf oligonukleotid-immobilisierten pcr-mikroplatten |
KR100280219B1 (ko) * | 1998-02-26 | 2001-04-02 | 이수빈 | 삼핵산 반복 서열을 이용한 신경정신 질환의 진단 방법 및 진단 시약 |
US5882874A (en) * | 1998-02-27 | 1999-03-16 | The Trustees Of Columbia University In The City Of New York | Reciprocal subtraction differential display |
US6210910B1 (en) * | 1998-03-02 | 2001-04-03 | Trustees Of Tufts College | Optical fiber biosensor array comprising cell populations confined to microcavities |
US6378527B1 (en) | 1998-04-08 | 2002-04-30 | Chondros, Inc. | Cell-culture and polymer constructs |
WO1999055886A1 (fr) * | 1998-04-24 | 1999-11-04 | Genova Pharmaceuticals Corporation | Decouverte de genes fonctionnels |
JP2981547B1 (ja) | 1998-07-02 | 1999-11-22 | 農林水産省食品総合研究所長 | クロスフロー型マイクロチャネル装置及び同装置を用いたエマルションの生成または分離方法 |
WO2000004139A1 (fr) | 1998-07-17 | 2000-01-27 | Mirus Corporation | Solutions de tensio-actifs |
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 |
GB9820185D0 (en) | 1998-09-15 | 1998-11-11 | Dynal As | Method |
AR021833A1 (es) | 1998-09-30 | 2002-08-07 | Applied Research Systems | Metodos de amplificacion y secuenciacion de acido nucleico |
US6203989B1 (en) * | 1998-09-30 | 2001-03-20 | Affymetrix, Inc. | Methods and compositions for amplifying detectable signals in specific binding assays |
AU2595300A (en) * | 1998-12-31 | 2000-07-31 | City Of Hope | Method for detecting mutations in nucleic acids |
GB9900298D0 (en) * | 1999-01-07 | 1999-02-24 | Medical Res Council | Optical sorting method |
US20020150909A1 (en) | 1999-02-09 | 2002-10-17 | Stuelpnagel John R. | Automated information processing in randomly ordered arrays |
EP1157131A2 (fr) * | 1999-02-22 | 2001-11-28 | Lynx Therapeutics, Inc. | Fragments d'adn polymorphes et leurs utilisations |
US6255476B1 (en) * | 1999-02-22 | 2001-07-03 | Pe Corporation (Ny) | Methods and compositions for synthesis of labelled oligonucleotides and analogs on solid-supports |
US6225061B1 (en) * | 1999-03-10 | 2001-05-01 | Sequenom, Inc. | Systems and methods for performing reactions in an unsealed environment |
DK1159453T3 (da) * | 1999-03-10 | 2008-10-06 | Asm Scient Inc | Fremgangsmåde til direkte nukleinsyresekventering |
US7371851B1 (en) * | 1999-03-18 | 2008-05-13 | Complete Genomics As | Methods of cloning and producing fragment chains with readable information content |
US6506594B1 (en) | 1999-03-19 | 2003-01-14 | Cornell Res Foundation Inc | Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays |
GB9907812D0 (en) | 1999-04-06 | 1999-06-02 | Medical Biosystems Ltd | Sequencing |
US6284465B1 (en) * | 1999-04-15 | 2001-09-04 | Agilent Technologies, Inc. | Apparatus, systems and method for locating nucleic acids bound to surfaces |
ATE413467T1 (de) | 1999-04-20 | 2008-11-15 | Illumina Inc | Detektion von nukleinsäurereaktionen auf kügelchen-arrays |
US20030108867A1 (en) * | 1999-04-20 | 2003-06-12 | Chee Mark S | Nucleic acid sequencing using microsphere arrays |
US6355431B1 (en) * | 1999-04-20 | 2002-03-12 | Illumina, Inc. | Detection of nucleic acid amplification reactions using bead arrays |
US6221653B1 (en) * | 1999-04-27 | 2001-04-24 | Agilent Technologies, Inc. | Method of performing array-based hybridization assays using thermal inkjet deposition of sample fluids |
CA2374390A1 (fr) | 1999-05-20 | 2000-12-14 | Illumina, Inc. | Decodage combinatoire de jeux d'acides nucleiques aleatoires |
US20020051971A1 (en) * | 1999-05-21 | 2002-05-02 | John R. Stuelpnagel | Use of microfluidic systems in the detection of target analytes using microsphere arrays |
US6300070B1 (en) * | 1999-06-04 | 2001-10-09 | Mosaic Technologies, Inc. | Solid phase methods for amplifying multiple nucleic acids |
US6340589B1 (en) | 1999-07-23 | 2002-01-22 | Mj Research, Inc. | Thin-well microplate and methods of making same |
GB9921155D0 (en) | 1999-09-08 | 1999-11-10 | Medical Res Council | Selection system |
US7211390B2 (en) | 1999-09-16 | 2007-05-01 | 454 Life Sciences Corporation | Method of sequencing a nucleic acid |
US7244559B2 (en) | 1999-09-16 | 2007-07-17 | 454 Life Sciences Corporation | Method of sequencing a nucleic acid |
WO2001046471A1 (fr) | 1999-12-21 | 2001-06-28 | The Government Of The United States Of America As Represented By The Secretary Of The Navy | Expression de proteines a partir d'acides nucleiques immobilises et amplifies |
AU2282801A (en) * | 1999-12-29 | 2001-07-09 | Mergen Ltd. | Methods for amplifying and detecting multiple polynucleotides on a solid phase support |
JP2003535576A (ja) | 2000-01-20 | 2003-12-02 | ロゼッタ・インファーマティクス・インコーポレーテッド | 薬物標的を同定するためのバーコード化された合成的致死スクリーニング |
ATE360095T1 (de) | 2000-02-07 | 2007-05-15 | Illumina Inc | Nukleinsäure nachweisverfahren mit universellem priming |
US7582420B2 (en) | 2001-07-12 | 2009-09-01 | Illumina, Inc. | Multiplex nucleic acid reactions |
US6714874B1 (en) | 2000-03-15 | 2004-03-30 | Applera Corporation | Method and system for the assembly of a whole genome using a shot-gun data set |
JP3442338B2 (ja) * | 2000-03-17 | 2003-09-02 | 株式会社日立製作所 | Dna分析装置、dna塩基配列決定装置、dna塩基配列決定方法、および反応モジュール |
CN1189159C (zh) | 2000-05-05 | 2005-02-16 | 欧莱雅 | 含水溶性美容活性组分水性核的微胶囊及含其的组合物 |
US6808874B2 (en) | 2000-06-13 | 2004-10-26 | Cyclacel Ltd. | Methods of monitoring enzyme activity |
CA2419058A1 (fr) | 2000-08-09 | 2002-02-14 | Illumina, Inc. | Traitement automatise de l'information dans des matrices organisees de facon aleatoire |
GB0021977D0 (en) | 2000-09-07 | 2000-10-25 | Pyrosequencing Ab | Method of sequencing DNA |
GB0022069D0 (en) | 2000-09-08 | 2000-10-25 | Pyrosequencing Ab | Method |
GB0022458D0 (en) | 2000-09-13 | 2000-11-01 | Medical Res Council | Directed evolution method |
WO2002027029A2 (fr) * | 2000-09-27 | 2002-04-04 | Lynx Therapeutics, Inc. | Procede de mesure de l'abondance relative de sequences d'acides nucleiques |
US6632610B2 (en) | 2000-10-12 | 2003-10-14 | Gensat S.A. | Methods of identification and isolation of polynucleotides containing nucleic acid differences |
US20020172980A1 (en) * | 2000-11-27 | 2002-11-21 | Phan Brigitte Chau | Methods for decreasing non-specific binding of beads in dual bead assays including related optical biodiscs and disc drive systems |
JP2002257070A (ja) | 2001-02-28 | 2002-09-11 | Toyota Industries Corp | 真空ポンプにおける軸封構造 |
US6936264B2 (en) | 2001-03-05 | 2005-08-30 | The Procter & Gamble Company | Delivery of reactive agents via multiple emulsions for use in shelf stable products |
US6996287B1 (en) | 2001-04-20 | 2006-02-07 | Adobe Systems, Inc. | Method and apparatus for texture cloning |
GB0114856D0 (en) | 2001-06-18 | 2001-08-08 | Medical Res Council | Selection by avidity capture |
GB0114854D0 (en) * | 2001-06-18 | 2001-08-08 | Medical Res Council | Selective gene amplification |
WO2003004690A2 (fr) * | 2001-07-06 | 2003-01-16 | 454$m(3) CORPORATION | Methode utilisant un filtre poreux pour isoler en parallele des micro-reactions chimiques independantes |
US20030064400A1 (en) | 2001-08-24 | 2003-04-03 | Li-Cor, Inc. | Microfluidics system for single molecule DNA sequencing |
US6956114B2 (en) | 2001-10-30 | 2005-10-18 | '454 Corporation | Sulfurylase-luciferase fusion proteins and thermostable sulfurylase |
US6902921B2 (en) | 2001-10-30 | 2005-06-07 | 454 Corporation | Sulfurylase-luciferase fusion proteins and thermostable sulfurylase |
GB0127564D0 (en) | 2001-11-16 | 2002-01-09 | Medical Res Council | Emulsion compositions |
US20030165935A1 (en) | 2001-11-21 | 2003-09-04 | Vann Charles S. | Digital assay |
US7198897B2 (en) * | 2001-12-19 | 2007-04-03 | Brandeis University | Late-PCR |
EP1495137B1 (fr) * | 2002-04-04 | 2005-09-14 | Biotage AB | Procede base sur l'extension d'amorce et employant des nucleotides marques via un element de liaison clivable |
AU2003302770B2 (en) | 2002-12-20 | 2007-07-12 | Caliper Life Sciences, Inc. | Single molecule amplification and detection of DNA |
EP1583831A2 (fr) * | 2003-01-15 | 2005-10-12 | Wyeth | Nouveau procede a haut debit de production et de purification de cibles d'arnc marquees pour l'analyse de l'expression genique |
US7575865B2 (en) | 2003-01-29 | 2009-08-18 | 454 Life Sciences Corporation | Methods of amplifying and sequencing nucleic acids |
WO2004069849A2 (fr) | 2003-01-29 | 2004-08-19 | 454 Corporation | Amplification d'acides nucleiques par emulsion de billes |
US8150627B2 (en) | 2003-05-15 | 2012-04-03 | Illumina, Inc. | Methods and compositions for diagnosing lung cancer with specific DNA methylation patterns |
JP5183063B2 (ja) * | 2003-07-05 | 2013-04-17 | ザ ジョンズ ホプキンス ユニバーシティ | 遺伝的変異の検出および列挙のための方法ならびに組成物 |
CA2553833C (fr) | 2004-01-28 | 2012-10-02 | 454 Corporation | Amplification d'acide nucleique avec emulsion a flux continu |
US7682816B2 (en) | 2005-04-07 | 2010-03-23 | 454 Life Sciences Corporation | Thin film coated microwell arrays and methods of using same |
US7785862B2 (en) | 2005-04-07 | 2010-08-31 | 454 Life Sciences Corporation | Thin film coated microwell arrays |
WO2007145612A1 (fr) | 2005-06-06 | 2007-12-21 | 454 Life Sciences Corporation | Séquençage d'extrémités appariées |
US8301394B2 (en) | 2006-02-16 | 2012-10-30 | 454 Life Sciences Corporation | System and method for correcting primer extension errors in nucleic acid sequence data |
US8364417B2 (en) | 2007-02-15 | 2013-01-29 | 454 Life Sciences Corporation | System and method to correct out of phase errors in DNA sequencing data by use of a recursive algorithm |
EP2038427A4 (fr) | 2006-06-19 | 2010-07-07 | Univ Johns Hopkins | Pcr de molecule unique sur des microparticules dans des emulsions d'eau dans l'huile |
US7585865B2 (en) | 2006-07-21 | 2009-09-08 | The Penn State Research Foundation | Protein kinase C zeta inhibition to treat vascular permeability |
JP2010521156A (ja) | 2007-03-16 | 2010-06-24 | 454 ライフ サイエンシーズ コーポレイション | Hiv薬物耐性バリアントの検出のためのシステムおよび方法 |
EP3404009B1 (fr) | 2017-05-16 | 2019-12-25 | Arkema France | Procédé de fabrication de 1,4-bis(4-phénoxybenzoyle)benzène dans des conditions de sursaturation |
-
2004
- 2004-01-28 WO PCT/US2004/002484 patent/WO2004069849A2/fr active Search and Examination
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- 2004-01-28 ES ES04785758T patent/ES2330339T3/es not_active Expired - Lifetime
- 2004-01-28 JP JP2006503134A patent/JP4480715B2/ja not_active Expired - Fee Related
- 2004-01-28 AT AT09175588T patent/ATE546525T1/de active
- 2004-01-28 AU AU2004209416A patent/AU2004209416B2/en not_active Ceased
- 2004-01-28 JP JP2006503163A patent/JP2007525151A/ja active Pending
-
2007
- 2007-04-20 US US11/788,838 patent/US8790876B2/en not_active Expired - Lifetime
- 2007-10-31 US US11/982,095 patent/US8012690B2/en not_active Expired - Lifetime
-
2008
- 2008-05-27 US US12/154,901 patent/US20090011959A1/en not_active Abandoned
-
2009
- 2009-12-28 JP JP2009297745A patent/JP2010142233A/ja active Pending
-
2010
- 2010-03-10 JP JP2010053827A patent/JP5258822B2/ja not_active Expired - Lifetime
- 2010-06-24 US US12/803,362 patent/US8158359B2/en not_active Expired - Lifetime
-
2011
- 2011-02-23 US US13/033,240 patent/US8748102B2/en active Active
-
2012
- 2012-03-13 US US13/419,241 patent/US20120238475A1/en not_active Abandoned
- 2012-08-20 JP JP2012181295A patent/JP5495399B2/ja not_active Expired - Lifetime
- 2012-09-14 US US13/618,334 patent/US8765380B2/en not_active Expired - Lifetime
- 2012-11-27 JP JP2012258136A patent/JP5726155B2/ja not_active Expired - Lifetime
- 2012-12-26 JP JP2012282220A patent/JP2013090635A/ja active Pending
-
2013
- 2013-09-25 US US14/036,398 patent/US20140162885A1/en not_active Abandoned
-
2014
- 2014-10-20 US US14/518,700 patent/US20150099672A1/en not_active Abandoned
-
2016
- 2016-06-23 US US15/190,886 patent/US10240192B2/en not_active Expired - Lifetime
-
2019
- 2019-01-16 US US16/249,681 patent/US10982274B2/en not_active Expired - Lifetime
Patent Citations (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5629158A (en) * | 1989-03-22 | 1997-05-13 | Cemu Bitecknik Ab | Solid phase diagnosis of medical conditions |
US5508169A (en) * | 1990-04-06 | 1996-04-16 | Queen's University At Kingston | Indexing linkers |
US5506100A (en) * | 1990-10-11 | 1996-04-09 | Indiana University Foundation | Process and apparatus for fragmenting biomaterials |
US5610010A (en) * | 1990-10-11 | 1997-03-11 | Indiana University Foundation | Process and apparatus for fragmenting biomaterials |
US5728524A (en) * | 1992-07-13 | 1998-03-17 | Medical Research Counsil | Process for categorizing nucleotide sequence populations |
US6004783A (en) * | 1994-03-18 | 1999-12-21 | The General Hospital Corporation | Cleaved amplified RFLP detection methods |
US5863722A (en) * | 1994-10-13 | 1999-01-26 | Lynx Therapeutics, Inc. | Method of sorting polynucleotides |
US5814444A (en) * | 1995-06-07 | 1998-09-29 | University Of Washington | Methods for making and using single-chromosome amplfication libraries |
US5989892A (en) * | 1995-06-14 | 1999-11-23 | Tonen Corporation | Microorganisms, demulsifiers and processes for breaking an emulsion |
US6270966B1 (en) * | 1996-02-09 | 2001-08-07 | The United States Of America As Represented By The Department Of Health And Human Services | Restriction display (RD-PCR) of differentially expressed mRNAs |
US6468748B1 (en) * | 1996-03-04 | 2002-10-22 | Sequenom, Inc. | Methods of screening nucleic acids using volatile salts in mass spectrometry |
US6184012B1 (en) * | 1996-04-25 | 2001-02-06 | Medical Research Council | Isolation of enzymes |
US6060245A (en) * | 1996-12-13 | 2000-05-09 | Stratagene | Methods and adaptors for generating specific nucleic acid populations |
US5994068A (en) * | 1997-03-11 | 1999-11-30 | Wisconsin Alumni Research Foundation | Nucleic acid indexing |
US6023540A (en) * | 1997-03-14 | 2000-02-08 | Trustees Of Tufts College | Fiber optic sensor with encoded microspheres |
US6266459B1 (en) * | 1997-03-14 | 2001-07-24 | Trustees Of Tufts College | Fiber optic sensor with encoded microspheres |
US6489103B1 (en) * | 1997-07-07 | 2002-12-03 | Medical Research Council | In vitro sorting method |
US6287825B1 (en) * | 1998-09-18 | 2001-09-11 | Molecular Staging Inc. | Methods for reducing the complexity of DNA sequences |
US6274320B1 (en) * | 1999-09-16 | 2001-08-14 | Curagen Corporation | Method of sequencing a nucleic acid |
US6475736B1 (en) * | 2000-05-23 | 2002-11-05 | Variagenics, Inc. | Methods for genetic analysis of DNA using biased amplification of polymorphic sites |
Cited By (447)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10669538B2 (en) | 2001-06-20 | 2020-06-02 | Nuevolution A/S | Templated molecules and methods for using such molecules |
US8932992B2 (en) | 2001-06-20 | 2015-01-13 | Nuevolution A/S | Templated molecules and methods for using such molecules |
US20100016177A1 (en) * | 2001-06-20 | 2010-01-21 | Henrik Pedersen | Templated molecules and methods for using such molecules |
US20050009022A1 (en) * | 2001-07-06 | 2005-01-13 | Weiner Michael P. | Method for isolation of independent, parallel chemical micro-reactions using a porous filter |
US20030096268A1 (en) * | 2001-07-06 | 2003-05-22 | Michael Weiner | Method for isolation of independent, parallel chemical micro-reactions using a porous filter |
US20040056018A1 (en) * | 2001-09-25 | 2004-03-25 | Beru Ag | Method for operating a multi-stage electrical heater comprised of several heating elements |
US10731151B2 (en) | 2002-03-15 | 2020-08-04 | Nuevolution A/S | Method for synthesising templated molecules |
US8808984B2 (en) | 2002-03-15 | 2014-08-19 | Neuvolution A/S | Method for synthesising templated molecules |
US10730906B2 (en) | 2002-08-01 | 2020-08-04 | Nuevolutions A/S | Multi-step synthesis of templated molecules |
US20060121470A1 (en) * | 2002-08-01 | 2006-06-08 | Henrik Pedersen | Multi-step synthesis of templated molecules |
US20060292603A1 (en) * | 2002-10-30 | 2006-12-28 | Gouliaev Alex H | Method for selecting a chemical entity from a tagged library |
US8206901B2 (en) | 2002-10-30 | 2012-06-26 | Nuevolution A/S | Method for the synthesis of a bifunctional complex |
US10077440B2 (en) | 2002-10-30 | 2018-09-18 | Nuevolution A/S | Method for the synthesis of a bifunctional complex |
US8722583B2 (en) | 2002-10-30 | 2014-05-13 | Nuevolution A/S | Method for selecting a chemical entity from a tagged library |
US9284600B2 (en) | 2002-10-30 | 2016-03-15 | Neuvolution A/S | Method for the synthesis of a bifunctional complex |
US11001835B2 (en) | 2002-10-30 | 2021-05-11 | Nuevolution A/S | Method for the synthesis of a bifunctional complex |
US9109248B2 (en) | 2002-10-30 | 2015-08-18 | Nuevolution A/S | Method for the synthesis of a bifunctional complex |
US20080193983A1 (en) * | 2002-12-19 | 2008-08-14 | Nuevolution A/S | Quasirandom Structure and Function Guided Synthesis Methods |
US9121110B2 (en) | 2002-12-19 | 2015-09-01 | Nuevolution A/S | Quasirandom structure and function guided synthesis methods |
US20080132693A1 (en) * | 2003-01-29 | 2008-06-05 | Jan Berka | Bead emulsion nucleic acid amplification |
US10982274B2 (en) | 2003-01-29 | 2021-04-20 | Roche Molecular Systems, Inc. | Bead emulsion nucleic acid amplification |
US20090011959A1 (en) * | 2003-01-29 | 2009-01-08 | Costa Gina L | Method for preparing single-stranded DNA libraries |
US10240192B2 (en) | 2003-01-29 | 2019-03-26 | 454 Life Sciences Corporation | Bead emulsion nucleic acid amplification |
US8765380B2 (en) | 2003-01-29 | 2014-07-01 | 454 Life Sciences Corporation | Bead emulsion nucleic acid amplification |
US8012690B2 (en) | 2003-01-29 | 2011-09-06 | 454 Life Sciences Corporation | Bead emulsion nucleic acid amplification |
US8748102B2 (en) | 2003-01-29 | 2014-06-10 | 454 Life Sciences Corporation | Bead emulsion nucleic acid amplification |
US9096951B2 (en) | 2003-02-21 | 2015-08-04 | Nuevolution A/S | Method for producing second-generation library |
USRE43365E1 (en) | 2003-03-14 | 2012-05-08 | Lawrence Livermore National Security, Llc | Apparatus for chemical amplification based on fluid partitioning in an immiscible liquid |
USRE48788E1 (en) | 2003-03-14 | 2021-10-26 | Lawrence Livermore National Security, Llc | Chemical amplification based on fluid partitioning |
USRE45539E1 (en) | 2003-03-14 | 2015-06-02 | Lawrence Livermore National Security, Llc | Method for chemical amplification based on fluid partitioning in an immiscible liquid |
US11187702B2 (en) | 2003-03-14 | 2021-11-30 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
USRE47080E1 (en) | 2003-03-14 | 2018-10-09 | Lawrence Livermore National Security, Llc | Chemical amplification based on fluid partitioning |
USRE41780E1 (en) | 2003-03-14 | 2010-09-28 | Lawrence Livermore National Security, Llc | Chemical amplification based on fluid partitioning in an immiscible liquid |
USRE46322E1 (en) | 2003-03-14 | 2017-02-28 | Lawrence Livermore National Security, Llc | Method for chemical amplification based on fluid partitioning in an immiscible liquid |
US8048627B2 (en) | 2003-07-05 | 2011-11-01 | The Johns Hopkins University | Method and compositions for detection and enumeration of genetic variations |
US20070065823A1 (en) * | 2003-07-05 | 2007-03-22 | Devin Dressman | Method and compositions for detection and enumeration of genetic variations |
US9328343B2 (en) | 2003-07-05 | 2016-05-03 | The Johns Hopkins University | Method and compositions for detection and enumeration of genetic variations |
WO2005010145A3 (fr) * | 2003-07-05 | 2005-08-11 | Univ Johns Hopkins | Procede et compositions de detection et d'enumeration de variations genetiques |
US10604797B2 (en) | 2003-07-05 | 2020-03-31 | The Johns Hopkins University | Method and compositions for detection and enumeration of genetic variations |
US20090286687A1 (en) * | 2003-07-05 | 2009-11-19 | The Johns Hopkins University | Method and Compositions for Detection and Enumeration of Genetic Variations |
US20080305957A1 (en) * | 2003-09-18 | 2008-12-11 | Thomas Thisted | Method for Obtaining Structural Information Concerning an Encoded Molecule and Method for Selecting Compounds |
US11965209B2 (en) | 2003-09-18 | 2024-04-23 | Nuevolution A/S | Method for obtaining structural information concerning an encoded molecule and method for selecting compounds |
US11118215B2 (en) | 2003-09-18 | 2021-09-14 | Nuevolution A/S | Method for obtaining structural information concerning an encoded molecule and method for selecting compounds |
US10953379B2 (en) | 2004-01-07 | 2021-03-23 | Illumina Cambridge Limited | Methods and compositions of localizing nucleic acids to arrays |
US9889422B2 (en) | 2004-01-07 | 2018-02-13 | Illumina Cambridge Limited | Methods of localizing nucleic acids to arrays |
US11654411B2 (en) | 2004-01-07 | 2023-05-23 | Illumina Cambridge Limited | Methods and compositions of localizing nucleic acids to arrays |
EP3175914A1 (fr) * | 2004-01-07 | 2017-06-07 | Illumina Cambridge Limited | Perfectionnements apportés ou se rapportant à des réseaux moléculaires |
US10525437B2 (en) | 2004-01-07 | 2020-01-07 | Illumina Cambridge Limited | Methods and compositions of localizing nucleic acids to arrays |
US20110177587A1 (en) * | 2004-01-28 | 2011-07-21 | 454 Corporation | Nucleic acid amplification with continuous flow emulsion |
US20090239211A1 (en) * | 2004-02-17 | 2009-09-24 | Nuevolution A/S | Method For Enrichment Involving Elimination By Mismatch Hybridisation |
US9708652B2 (en) * | 2004-03-08 | 2017-07-18 | Rubicon Genomics, Inc. | Methods and compositions for generating and amplifying DNA libraries for sensitive detection and analysis of DNA methylation |
US20130309668A1 (en) * | 2004-03-08 | 2013-11-21 | Rubicon Genomics, Inc. | Methods and compositions for generating and amplifying dna libraries for sensitive detection and analysis of dna methylation |
US9109251B2 (en) | 2004-06-25 | 2015-08-18 | University Of Hawaii | Ultrasensitive biosensors |
US10563252B2 (en) | 2004-06-25 | 2020-02-18 | University Of Hawaii | Ultrasensitive biosensors |
US9752185B2 (en) | 2004-09-15 | 2017-09-05 | Integenx Inc. | Microfluidic devices |
US8551714B2 (en) | 2004-09-15 | 2013-10-08 | Integenx Inc. | Microfluidic devices |
US8476063B2 (en) | 2004-09-15 | 2013-07-02 | Integenx Inc. | Microfluidic devices |
US8431390B2 (en) | 2004-09-15 | 2013-04-30 | Integenx Inc. | Systems of sample processing having a macro-micro interface |
US8431340B2 (en) | 2004-09-15 | 2013-04-30 | Integenx Inc. | Methods for processing and analyzing nucleic acid samples |
US11786872B2 (en) | 2004-10-08 | 2023-10-17 | United Kingdom Research And Innovation | Vitro evolution in microfluidic systems |
US20060110764A1 (en) * | 2004-10-25 | 2006-05-25 | Tom Tang | Large-scale parallelized DNA sequencing |
US8753812B2 (en) | 2004-11-12 | 2014-06-17 | The Board Of Trustees Of The Leland Stanford Junior University | Charge perturbation detection method for DNA and other molecules |
US9228971B2 (en) | 2004-11-12 | 2016-01-05 | The Board Of Trustees Of The Leland Stanford Junior University | Charge perturbation detection system for DNA and other molecules |
US10822641B2 (en) | 2004-11-12 | 2020-11-03 | The Board Of Trustees Of The Leland Stanford Junior University | Charge perturbation detection system for DNA and other molecules |
US20090325184A1 (en) * | 2005-03-16 | 2009-12-31 | Life Technologies Corporation | Compositions and Methods for Clonal Amplification and Analysis of Polynucleotides |
US7604940B1 (en) | 2005-03-16 | 2009-10-20 | Applied Biosystems, Llc | Compositions and methods for analyzing isolated polynucleotides |
US20060269934A1 (en) * | 2005-03-16 | 2006-11-30 | Applera Corporation | Compositions and methods for clonal amplification and analysis of polynucleotides |
US20090233291A1 (en) * | 2005-06-06 | 2009-09-17 | 454 Life Sciences Corporation | Paired end sequencing |
US9376716B2 (en) | 2005-06-23 | 2016-06-28 | Keygene N.V. | Strategies for high throughput identification and detection of polymorphisms |
US9898576B2 (en) | 2005-06-23 | 2018-02-20 | Keygene N.V. | Strategies for high throughput identification and detection of polymorphisms |
US9896721B2 (en) | 2005-06-23 | 2018-02-20 | Keygene N.V. | Strategies for high throughput identification and detection of polymorphisms |
US9898577B2 (en) | 2005-06-23 | 2018-02-20 | Keygene N.V. | Strategies for high throughput identification and detection of polymorphisms |
US10978175B2 (en) | 2005-06-23 | 2021-04-13 | Keygene N.V. | Strategies for high throughput identification and detection of polymorphisms |
US10095832B2 (en) | 2005-06-23 | 2018-10-09 | Keygene N.V. | Strategies for high throughput identification and detection of polymorphisms |
US9447459B2 (en) | 2005-06-23 | 2016-09-20 | Keygene N.V. | Strategies for high throughput identification and detection of polymorphisms |
US9453256B2 (en) * | 2005-06-23 | 2016-09-27 | Keygene N.V. | Strategies for high throughput identification and detection of polymorphisms |
US9493820B2 (en) * | 2005-06-23 | 2016-11-15 | Keygene N.V. | Strategies for high throughput identification and detection of polymorphisms |
US10235494B2 (en) | 2005-06-23 | 2019-03-19 | Keygene N.V. | Strategies for high throughput identification and detection of polymorphisms |
US20070031865A1 (en) * | 2005-07-07 | 2007-02-08 | David Willoughby | Novel Process for Construction of a DNA Library |
US20110171748A1 (en) * | 2005-08-22 | 2011-07-14 | Life Technologies Corporation | Device And Method For Making Discrete Volumes Of A First Fluid In Contact With A Second Fluid, Which Are Immiscible With Each Other |
US8361807B2 (en) | 2005-08-22 | 2013-01-29 | Applied Biosystems, Llc | Device and method for making discrete volumes of a first fluid in contact with a second fluid, which are immiscible with each other |
US9285297B2 (en) | 2005-08-22 | 2016-03-15 | Applied Biosystems, Llc | Device, system, and method for depositing processed immiscible-fluid-discrete-volumes |
US7955864B2 (en) | 2005-08-22 | 2011-06-07 | Life Technologies Corporation | Device and method for making discrete volumes of a first fluid in contact with a second fluid, which are immiscible with each other |
US20070039866A1 (en) * | 2005-08-22 | 2007-02-22 | Schroeder Benjamin G | Device, system, and method for depositing processed immiscible-fluid-discrete-volumes |
US10041113B2 (en) | 2005-08-22 | 2018-08-07 | Applied Biosystems, Llc | Apparatus, system, and method using immiscible-fluid-discrete-volumes |
US20070062583A1 (en) * | 2005-08-22 | 2007-03-22 | Cox David M | Device and method for making discrete volumes of a first fluid in contact with a second fluid, which are immiscible with each other |
EP2660482B1 (fr) * | 2005-08-22 | 2019-08-07 | Life Technologies Corporation | Appareil, système et procédé utilisant des volumes discrets de fluides non miscibles |
US11162137B2 (en) | 2005-08-22 | 2021-11-02 | Applied Biosystems Llc | Apparatus, system, and method using immiscible-fluid-discrete-volumes |
US20070068573A1 (en) * | 2005-08-22 | 2007-03-29 | Applera Corporation | Device and method for microfluidic control of a first fluid in contact with a second fluid, wherein the first and second fluids are immiscible |
US20070141593A1 (en) * | 2005-08-22 | 2007-06-21 | Lee Linda G | Apparatus, system, and method using immiscible-fluid-discrete-volumes |
EP2660482A1 (fr) | 2005-08-22 | 2013-11-06 | Life Technologies Corporation | Appareil, système et procédé utilisant des volumes discrets de fluides non miscibles |
US11319585B2 (en) | 2005-08-22 | 2022-05-03 | Applied Biosystems, Llc | Device and method for making discrete volumes of a first fluid in contact with a second fluid, which are immiscible with each other |
US20070117121A1 (en) * | 2005-09-16 | 2007-05-24 | Hutchison Stephen K | cDNA library preparation |
US10316364B2 (en) | 2005-09-29 | 2019-06-11 | Keygene N.V. | Method for identifying the source of an amplicon |
US10233494B2 (en) | 2005-09-29 | 2019-03-19 | Keygene N.V. | High throughput screening of populations carrying naturally occurring mutations |
US11649494B2 (en) | 2005-09-29 | 2023-05-16 | Keygene N.V. | High throughput screening of populations carrying naturally occurring mutations |
US10538806B2 (en) | 2005-09-29 | 2020-01-21 | Keygene N.V. | High throughput screening of populations carrying naturally occurring mutations |
US9574189B2 (en) | 2005-12-01 | 2017-02-21 | Nuevolution A/S | Enzymatic encoding methods for efficient synthesis of large libraries |
US11702652B2 (en) | 2005-12-01 | 2023-07-18 | Nuevolution A/S | Enzymatic encoding methods for efficient synthesis of large libraries |
US9334536B2 (en) | 2005-12-22 | 2016-05-10 | Keygene N.V. | Method for high-throughput AFLP-based polymorphism detection |
US9062348B1 (en) | 2005-12-22 | 2015-06-23 | Keygene N.V. | Method for high-throughput AFLP-based polymorphism detection |
US11008615B2 (en) | 2005-12-22 | 2021-05-18 | Keygene N.V. | Method for high-throughput AFLP-based polymorphism detection |
US9777324B2 (en) | 2005-12-22 | 2017-10-03 | Keygene N.V. | Method for high-throughput AFLP-based polymorphism detection |
US8815512B2 (en) | 2005-12-22 | 2014-08-26 | Keygene N.V. | Method for high-throughput AFLP-based polymorphism detection |
US9328383B2 (en) | 2005-12-22 | 2016-05-03 | Keygene N.V. | Method for high-throughput AFLP-based polymorphism detection |
US9702004B2 (en) | 2005-12-22 | 2017-07-11 | Keygene N.V. | Method for high-throughput AFLP-based polymorphism detection |
US8911945B2 (en) | 2005-12-22 | 2014-12-16 | Keygene N.V. | Method for high-throughput AFLP-based polymorphism detection |
US10106850B2 (en) | 2005-12-22 | 2018-10-23 | Keygene N.V. | Method for high-throughput AFLP-based polymorphism detection |
US20180355350A1 (en) * | 2006-01-11 | 2018-12-13 | Raindance Technologies, Inc. | Microfluidic devices and methods of use in the formation and control of nanoreactors |
US10633652B2 (en) * | 2006-01-11 | 2020-04-28 | Bio-Rad Laboratories, Inc. | Microfluidic devices and methods of use in the formation and control of nanoreactors |
US20180080020A1 (en) * | 2006-01-11 | 2018-03-22 | Raindance Technologies, Inc. | Microfluidic devices and methods of use in the formation and control of nanoreactors |
US20070172839A1 (en) * | 2006-01-24 | 2007-07-26 | Smith Douglas R | Asymmetrical adapters and methods of use thereof |
US20150197789A1 (en) * | 2006-02-08 | 2015-07-16 | Illumina Cambridge Limited | End modification to prevent over-representation of fragments |
US10006081B2 (en) * | 2006-02-08 | 2018-06-26 | Illumina Cambridge Limited | End modification to prevent over-representation of fragments |
US7993842B2 (en) | 2006-03-23 | 2011-08-09 | Life Technologies Corporation | Directed enrichment of genomic DNA for high-throughput sequencing |
US20070231823A1 (en) * | 2006-03-23 | 2007-10-04 | Mckernan Kevin J | Directed enrichment of genomic DNA for high-throughput sequencing |
EP2963127A1 (fr) * | 2006-04-04 | 2016-01-06 | Keygene N.V. | Détection à haut débit de marqueurs moléculaires sur la base de fragments de restriction |
EP3239304A1 (fr) * | 2006-04-04 | 2017-11-01 | Keygene N.V. | Détection à haut débit de marqueurs moléculaires sur la base d'aflp et de séquençage à haut débit |
US10023907B2 (en) | 2006-04-04 | 2018-07-17 | Keygene N.V. | High throughput detection of molecular markers based on AFLP and high through-put sequencing |
US20120135871A1 (en) * | 2006-04-04 | 2012-05-31 | Keygene N.V. | High throughput detection of molecular markers based on aflp and high through-put sequencing |
US20120202698A1 (en) * | 2006-04-04 | 2012-08-09 | Keygene N.V. | High throughput detection of molecular markers based on aflp and high through-put sequencing |
US11351510B2 (en) | 2006-05-11 | 2022-06-07 | Bio-Rad Laboratories, Inc. | Microfluidic devices |
US10202608B2 (en) | 2006-08-31 | 2019-02-12 | Gen9, Inc. | Iterative nucleic acid assembly using activation of vector-encoded traits |
US20090318298A1 (en) * | 2006-09-28 | 2009-12-24 | President And Fellows Of Harvard College | Methods for Sequencing DNA |
US20100143908A1 (en) * | 2006-11-15 | 2010-06-10 | Biospherex, Llc, A Limited Liability Company | Multitag sequencing ecogenomics analysis-us |
US8603749B2 (en) * | 2006-11-15 | 2013-12-10 | Biospherex, LLC | Multitag sequencing ecogenomics analysis-US |
US8349167B2 (en) | 2006-12-14 | 2013-01-08 | Life Technologies Corporation | Methods and apparatus for detecting molecular interactions using FET arrays |
US8293082B2 (en) | 2006-12-14 | 2012-10-23 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US20080145898A1 (en) * | 2006-12-14 | 2008-06-19 | Applera Corporation | Sequencing methods |
US8450781B2 (en) | 2006-12-14 | 2013-05-28 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8658017B2 (en) | 2006-12-14 | 2014-02-25 | Life Technologies Corporation | Methods for operating an array of chemically-sensitive sensors |
US8685230B2 (en) | 2006-12-14 | 2014-04-01 | Life Technologies Corporation | Methods and apparatus for high-speed operation of a chemically-sensitive sensor array |
US8692298B2 (en) | 2006-12-14 | 2014-04-08 | Life Technologies Corporation | Chemical sensor array having multiple sensors per well |
US10415079B2 (en) | 2006-12-14 | 2019-09-17 | Life Technologies Corporation | Methods and apparatus for detecting molecular interactions using FET arrays |
US8445945B2 (en) | 2006-12-14 | 2013-05-21 | Life Technologies Corporation | Low noise chemically-sensitive field effect transistors |
US8492800B2 (en) | 2006-12-14 | 2013-07-23 | Life Technologies Corporation | Chemically sensitive sensors with sample and hold capacitors |
US8492799B2 (en) | 2006-12-14 | 2013-07-23 | Life Technologies Corporation | Methods and apparatus for detecting molecular interactions using FET arrays |
US10502708B2 (en) | 2006-12-14 | 2019-12-10 | Life Technologies Corporation | Chemically-sensitive sensor array calibration circuitry |
US10203300B2 (en) | 2006-12-14 | 2019-02-12 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8742472B2 (en) | 2006-12-14 | 2014-06-03 | Life Technologies Corporation | Chemically sensitive sensors with sample and hold capacitors |
US20090325183A1 (en) * | 2006-12-14 | 2009-12-31 | Life Technologies Corporation | Sequencing methods |
US8496802B2 (en) | 2006-12-14 | 2013-07-30 | Life Technologies Corporation | Methods for operating chemically-sensitive sample and hold sensors |
US9269708B2 (en) | 2006-12-14 | 2016-02-23 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8441044B2 (en) | 2006-12-14 | 2013-05-14 | Life Technologies Corporation | Methods for manufacturing low noise chemically-sensitive field effect transistors |
US11732297B2 (en) * | 2006-12-14 | 2023-08-22 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8502278B2 (en) | 2006-12-14 | 2013-08-06 | Life Technologies Corporation | Chemically-sensitive sample and hold sensors |
US20100282617A1 (en) * | 2006-12-14 | 2010-11-11 | Ion Torrent Systems Incorporated | Methods and apparatus for detecting molecular interactions using fet arrays |
US10633699B2 (en) | 2006-12-14 | 2020-04-28 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8766328B2 (en) | 2006-12-14 | 2014-07-01 | Life Technologies Corporation | Chemically-sensitive sample and hold sensors |
US8764969B2 (en) | 2006-12-14 | 2014-07-01 | Life Technologies Corporation | Methods for operating chemically sensitive sensors with sample and hold capacitors |
US8435395B2 (en) | 2006-12-14 | 2013-05-07 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8426898B2 (en) | 2006-12-14 | 2013-04-23 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US7948015B2 (en) | 2006-12-14 | 2011-05-24 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US9989489B2 (en) | 2006-12-14 | 2018-06-05 | Life Technnologies Corporation | Methods for calibrating an array of chemically-sensitive sensors |
US10816506B2 (en) | 2006-12-14 | 2020-10-27 | Life Technologies Corporation | Method for measuring analytes using large scale chemfet arrays |
US9134269B2 (en) | 2006-12-14 | 2015-09-15 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8575664B2 (en) | 2006-12-14 | 2013-11-05 | Life Technologies Corporation | Chemically-sensitive sensor array calibration circuitry |
US8519448B2 (en) | 2006-12-14 | 2013-08-27 | Life Technologies Corporation | Chemically-sensitive array with active and reference sensors |
US8426899B2 (en) | 2006-12-14 | 2013-04-23 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8558288B2 (en) | 2006-12-14 | 2013-10-15 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US9951382B2 (en) | 2006-12-14 | 2018-04-24 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8262900B2 (en) | 2006-12-14 | 2012-09-11 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8415716B2 (en) | 2006-12-14 | 2013-04-09 | Life Technologies Corporation | Chemically sensitive sensors with feedback circuits |
US11435314B2 (en) | 2006-12-14 | 2022-09-06 | Life Technologies Corporation | Chemically-sensitive sensor array device |
US8264014B2 (en) | 2006-12-14 | 2012-09-11 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8890216B2 (en) | 2006-12-14 | 2014-11-18 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8269261B2 (en) | 2006-12-14 | 2012-09-18 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8530941B2 (en) | 2006-12-14 | 2013-09-10 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US9404920B2 (en) | 2006-12-14 | 2016-08-02 | Life Technologies Corporation | Methods and apparatus for detecting molecular interactions using FET arrays |
US8540868B2 (en) | 2006-12-14 | 2013-09-24 | Life Technologies Corporation | Methods and apparatus for detecting molecular interactions using FET arrays |
US8306757B2 (en) | 2006-12-14 | 2012-11-06 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8535513B2 (en) | 2006-12-14 | 2013-09-17 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8313625B2 (en) | 2006-12-14 | 2012-11-20 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8540865B2 (en) | 2006-12-14 | 2013-09-24 | Life Technologies Corporation | Methods and apparatus for detecting molecular interactions using FET arrays |
US8317999B2 (en) | 2006-12-14 | 2012-11-27 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US20220340965A1 (en) * | 2006-12-14 | 2022-10-27 | Life Technologies Corporation | Methods and Apparatus for Measuring Analytes Using Large Scale FET Arrays |
US8313639B2 (en) | 2006-12-14 | 2012-11-20 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8540867B2 (en) | 2006-12-14 | 2013-09-24 | Life Technologies Corporation | Methods and apparatus for detecting molecular interactions using FET arrays |
US9023189B2 (en) | 2006-12-14 | 2015-05-05 | Life Technologies Corporation | High density sensor array without wells |
US9039888B2 (en) | 2006-12-14 | 2015-05-26 | Life Technologies Corporation | Methods and apparatus for detecting molecular interactions using FET arrays |
US8540866B2 (en) | 2006-12-14 | 2013-09-24 | Life Technologies Corporation | Methods and apparatus for detecting molecular interactions using FET arrays |
US8557518B2 (en) | 2007-02-05 | 2013-10-15 | Integenx Inc. | Microfluidic and nanofluidic devices, systems, and applications |
US20110039303A1 (en) * | 2007-02-05 | 2011-02-17 | Stevan Bogdan Jovanovich | Microfluidic and nanofluidic devices, systems, and applications |
US11819849B2 (en) | 2007-02-06 | 2023-11-21 | Brandeis University | Manipulation of fluids and reactions in microfluidic systems |
US11224876B2 (en) | 2007-04-19 | 2022-01-18 | Brandeis University | Manipulation of fluids, fluid components and reactions in microfluidic systems |
US10960397B2 (en) | 2007-04-19 | 2021-03-30 | President And Fellows Of Harvard College | Manipulation of fluids, fluid components and reactions in microfluidic systems |
US11618024B2 (en) | 2007-04-19 | 2023-04-04 | President And Fellows Of Harvard College | Manipulation of fluids, fluid components and reactions in microfluidic systems |
US20100267043A1 (en) * | 2007-06-01 | 2010-10-21 | Braverman Michael S | System and method for identification of individual samples from a multiplex mixture |
US20090105959A1 (en) * | 2007-06-01 | 2009-04-23 | Braverman Michael S | System and method for identification of individual samples from a multiplex mixture |
US20090053724A1 (en) * | 2007-06-28 | 2009-02-26 | 454 Life Sciences Corporation | System and method for adaptive reagent control in nucleic acid sequencing |
US20100136557A1 (en) * | 2007-06-29 | 2010-06-03 | Sydney Brenner | Methods and Compositions for Isolating Nucleic Acid Sequence Variants |
US8241850B2 (en) * | 2007-06-29 | 2012-08-14 | Population Genetics Technologies Ltd. | Methods and compositions for isolating nucleic acid sequence variants |
US11339430B2 (en) | 2007-07-10 | 2022-05-24 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8748165B2 (en) | 2008-01-22 | 2014-06-10 | Integenx Inc. | Methods for generating short tandem repeat (STR) profiles |
US20090203086A1 (en) * | 2008-02-06 | 2009-08-13 | 454 Life Sciences Corporation | System and method for improved signal detection in nucleic acid sequencing |
US9194000B2 (en) | 2008-06-25 | 2015-11-24 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8470164B2 (en) | 2008-06-25 | 2013-06-25 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8524057B2 (en) | 2008-06-25 | 2013-09-03 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8344123B2 (en) | 2008-07-01 | 2013-01-01 | 454 Life Sciences Corporation | System and method for detection of HIV tropism variants |
US7888034B2 (en) | 2008-07-01 | 2011-02-15 | 454 Life Sciences Corporation | System and method for detection of HIV tropism variants |
USRE46293E1 (en) | 2008-07-01 | 2017-01-31 | 454 Life Sciences Corporation | System and method for detection of HIV tropism variants |
US11534727B2 (en) | 2008-07-18 | 2022-12-27 | Bio-Rad Laboratories, Inc. | Droplet libraries |
US11596908B2 (en) | 2008-07-18 | 2023-03-07 | Bio-Rad Laboratories, Inc. | Droplet libraries |
US11511242B2 (en) | 2008-07-18 | 2022-11-29 | Bio-Rad Laboratories, Inc. | Droplet libraries |
US8808986B2 (en) | 2008-08-27 | 2014-08-19 | Gen9, Inc. | Methods and devices for high fidelity polynucleotide synthesis |
US11015191B2 (en) | 2008-08-27 | 2021-05-25 | Gen9, Inc. | Methods and devices for high fidelity polynucleotide synthesis |
US9856471B2 (en) | 2008-08-27 | 2018-01-02 | Gen9, Inc. | Methods and devices for high fidelity polynucleotide synthesis |
US20100261189A1 (en) * | 2008-10-03 | 2010-10-14 | Roche Molecular Systems, Inc. | System and method for detection of HLA Variants |
US9944981B2 (en) | 2008-10-22 | 2018-04-17 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US20100137143A1 (en) * | 2008-10-22 | 2010-06-03 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
US9964515B2 (en) | 2008-10-22 | 2018-05-08 | Life Technologies Corporation | Integrated sensor arrays for biological and chemical analysis |
US11874250B2 (en) | 2008-10-22 | 2024-01-16 | Life Technologies Corporation | Integrated sensor arrays for biological and chemical analysis |
US8936763B2 (en) | 2008-10-22 | 2015-01-20 | Life Technologies Corporation | Integrated sensor arrays for biological and chemical analysis |
US11448613B2 (en) | 2008-10-22 | 2022-09-20 | Life Technologies Corporation | ChemFET sensor array including overlying array of wells |
US11137369B2 (en) | 2008-10-22 | 2021-10-05 | Life Technologies Corporation | Integrated sensor arrays for biological and chemical analysis |
US8672532B2 (en) | 2008-12-31 | 2014-03-18 | Integenx Inc. | Microfluidic methods |
US11517864B2 (en) | 2009-03-13 | 2022-12-06 | President And Fellows Of Harvard College | Scale-up of microfluidic devices |
US9486757B2 (en) | 2009-03-13 | 2016-11-08 | President And Fellows Of Harvard College | Scale-up of microfluidic devices |
US10518230B2 (en) | 2009-03-13 | 2019-12-31 | President And Fellows Of Harvard College | Scale-up of microfluidic devices |
US8263336B2 (en) | 2009-05-29 | 2012-09-11 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US9927393B2 (en) | 2009-05-29 | 2018-03-27 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US8776573B2 (en) | 2009-05-29 | 2014-07-15 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US11768171B2 (en) | 2009-05-29 | 2023-09-26 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US8748947B2 (en) | 2009-05-29 | 2014-06-10 | Life Technologies Corporation | Active chemically-sensitive sensors with reset switch |
US10809226B2 (en) | 2009-05-29 | 2020-10-20 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US8673627B2 (en) | 2009-05-29 | 2014-03-18 | Life Technologies Corporation | Apparatus and methods for performing electrochemical reactions |
US8592154B2 (en) | 2009-05-29 | 2013-11-26 | Life Technologies Corporation | Methods and apparatus for high speed operation of a chemically-sensitive sensor array |
US20100301398A1 (en) * | 2009-05-29 | 2010-12-02 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
US10612017B2 (en) | 2009-05-29 | 2020-04-07 | Life Technologies Corporation | Scaffolded nucleic acid polymer particles and methods of making and using |
US8592153B1 (en) | 2009-05-29 | 2013-11-26 | Life Technologies Corporation | Methods for manufacturing high capacitance microwell structures of chemically-sensitive sensors |
US11692964B2 (en) | 2009-05-29 | 2023-07-04 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US8822205B2 (en) | 2009-05-29 | 2014-09-02 | Life Technologies Corporation | Active chemically-sensitive sensors with source follower amplifier |
US10718733B2 (en) | 2009-05-29 | 2020-07-21 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US8698212B2 (en) | 2009-05-29 | 2014-04-15 | Life Technologies Corporation | Active chemically-sensitive sensors |
US8912580B2 (en) | 2009-05-29 | 2014-12-16 | Life Technologies Corporation | Active chemically-sensitive sensors with in-sensor current sources |
US10451585B2 (en) | 2009-05-29 | 2019-10-22 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US8766327B2 (en) | 2009-05-29 | 2014-07-01 | Life Technologies Corporation | Active chemically-sensitive sensors with in-sensor current sources |
US8742469B2 (en) | 2009-05-29 | 2014-06-03 | Life Technologies Corporation | Active chemically-sensitive sensors with correlated double sampling |
US8994076B2 (en) | 2009-05-29 | 2015-03-31 | Life Technologies Corporation | Chemically-sensitive field effect transistor based pixel array with protection diodes |
US8388908B2 (en) | 2009-06-02 | 2013-03-05 | Integenx Inc. | Fluidic devices with diaphragm valves |
US8562918B2 (en) | 2009-06-05 | 2013-10-22 | Integenx Inc. | Universal sample preparation system and use in an integrated analysis system |
US9012236B2 (en) | 2009-06-05 | 2015-04-21 | Integenx Inc. | Universal sample preparation system and use in an integrated analysis system |
US8394642B2 (en) | 2009-06-05 | 2013-03-12 | Integenx Inc. | Universal sample preparation system and use in an integrated analysis system |
US20110087016A1 (en) * | 2009-10-09 | 2011-04-14 | 454 Life Sciences Corporation | System and Method for Emulsion Breaking and Recovery of Biological Elements |
US8609339B2 (en) | 2009-10-09 | 2013-12-17 | 454 Life Sciences Corporation | System and method for emulsion breaking and recovery of biological elements |
WO2011042189A1 (fr) | 2009-10-09 | 2011-04-14 | Roche Diagnostics Gmbh | Système et procédé pour la rupture d'émulsion et la récupération d'éléments biologiques |
US20120220497A1 (en) * | 2009-11-03 | 2012-08-30 | Gen 9, Inc. | Methods and Microfluidic Devices for the Manipulation of Droplets in High Fidelity Polynucleotide Assembly |
US10207240B2 (en) * | 2009-11-03 | 2019-02-19 | Gen9, Inc. | Methods and microfluidic devices for the manipulation of droplets in high fidelity polynucleotide assembly |
WO2011056872A3 (fr) * | 2009-11-03 | 2011-11-03 | Gen9, Inc. | Procédés et dispositifs microfluidiques pour la manipulation de gouttelettes dans un ensemble polynucléotidique haute fidélité |
US9968902B2 (en) | 2009-11-25 | 2018-05-15 | Gen9, Inc. | Microfluidic devices and methods for gene synthesis |
US9216414B2 (en) | 2009-11-25 | 2015-12-22 | Gen9, Inc. | Microfluidic devices and methods for gene synthesis |
US9422600B2 (en) | 2009-11-25 | 2016-08-23 | Gen9, Inc. | Methods and apparatuses for chip-based DNA error reduction |
US10829759B2 (en) | 2009-11-25 | 2020-11-10 | Gen9, Inc. | Methods and apparatuses for chip-based DNA error reduction |
US8584703B2 (en) | 2009-12-01 | 2013-11-19 | Integenx Inc. | Device with diaphragm valve |
US20110126911A1 (en) * | 2009-12-01 | 2011-06-02 | IntegenX Inc., a California Corporation | Composite Plastic Articles |
US9925510B2 (en) | 2010-01-07 | 2018-03-27 | Gen9, Inc. | Assembly of high fidelity polynucleotides |
US11071963B2 (en) | 2010-01-07 | 2021-07-27 | Gen9, Inc. | Assembly of high fidelity polynucleotides |
US9217144B2 (en) | 2010-01-07 | 2015-12-22 | Gen9, Inc. | Assembly of high fidelity polynucleotides |
US11254968B2 (en) | 2010-02-12 | 2022-02-22 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
US11390917B2 (en) | 2010-02-12 | 2022-07-19 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
WO2011106314A3 (fr) * | 2010-02-25 | 2012-02-23 | Advanced Liquid Logic, Inc. | Procédé de fabrication de banques d'acide nucléique |
AU2011221243B2 (en) * | 2010-02-25 | 2016-06-02 | Advanced Liquid Logic, Inc. | Method of making nucleic acid libraries |
US9938553B2 (en) | 2010-03-03 | 2018-04-10 | Gen9, Inc. | Methods and devices for nucleic acid synthesis |
US20110217738A1 (en) * | 2010-03-03 | 2011-09-08 | Gen9, Inc. | Methods and Devices for Nucleic Acid Synthesis |
US8716467B2 (en) | 2010-03-03 | 2014-05-06 | Gen9, Inc. | Methods and devices for nucleic acid synthesis |
US9388407B2 (en) | 2010-03-03 | 2016-07-12 | Gen9, Inc. | Methods and devices for nucleic acid synthesis |
US8512538B2 (en) | 2010-05-28 | 2013-08-20 | Integenx Inc. | Capillary electrophoresis device |
US8742471B2 (en) | 2010-06-30 | 2014-06-03 | Life Technologies Corporation | Chemical sensor array with leakage compensation circuit |
US9164070B2 (en) | 2010-06-30 | 2015-10-20 | Life Technologies Corporation | Column adc |
US9957564B2 (en) | 2010-06-30 | 2018-05-01 | Bgi Genomics Co., Ltd. | Application of a PCR sequencing method, based on DNA barcoding technique and DNA incomplete shearing strategy, in HLA genotyping |
US8217433B1 (en) | 2010-06-30 | 2012-07-10 | Life Technologies Corporation | One-transistor pixel array |
US8858782B2 (en) | 2010-06-30 | 2014-10-14 | Life Technologies Corporation | Ion-sensing charge-accumulation circuits and methods |
US8983783B2 (en) | 2010-06-30 | 2015-03-17 | Life Technologies Corporation | Chemical detection device having multiple flow channels |
US8524487B2 (en) | 2010-06-30 | 2013-09-03 | Life Technologies Corporation | One-transistor pixel array with cascoded column circuit |
US10641729B2 (en) | 2010-06-30 | 2020-05-05 | Life Technologies Corporation | Column ADC |
EP2599877B1 (fr) * | 2010-06-30 | 2017-09-27 | BGI Genomics Co., Limited | Nouvelle méthode de séquençage par pcr et son utilisation dans le génotypage hla |
US8415177B2 (en) | 2010-06-30 | 2013-04-09 | Life Technologies Corporation | Two-transistor pixel array |
EP2599877A1 (fr) * | 2010-06-30 | 2013-06-05 | BGI Shenzhen Co., Limited | Nouvelle méthode de séquençage par pcr et son utilisation dans le génotypage hla |
US8415176B2 (en) | 2010-06-30 | 2013-04-09 | Life Technologies Corporation | One-transistor pixel array |
US8455927B2 (en) | 2010-06-30 | 2013-06-04 | Life Technologies Corporation | One-transistor pixel array with cascoded column circuit |
US8421437B2 (en) | 2010-06-30 | 2013-04-16 | Life Technologies Corporation | Array column integrator |
US8487790B2 (en) | 2010-06-30 | 2013-07-16 | Life Technologies Corporation | Chemical detection circuit including a serializer circuit |
US8823380B2 (en) | 2010-06-30 | 2014-09-02 | Life Technologies Corporation | Capacitive charge pump |
US11231451B2 (en) | 2010-06-30 | 2022-01-25 | Life Technologies Corporation | Methods and apparatus for testing ISFET arrays |
US8432150B2 (en) | 2010-06-30 | 2013-04-30 | Life Technologies Corporation | Methods for operating an array column integrator |
US8432149B2 (en) | 2010-06-30 | 2013-04-30 | Life Technologies Corporation | Array column integrator |
US8741680B2 (en) | 2010-06-30 | 2014-06-03 | Life Technologies Corporation | Two-transistor pixel array |
US10481123B2 (en) | 2010-06-30 | 2019-11-19 | Life Technologies Corporation | Ion-sensing charge-accumulation circuits and methods |
US8772698B2 (en) | 2010-06-30 | 2014-07-08 | Life Technologies Corporation | CCD-based multi-transistor active pixel sensor array |
US9239313B2 (en) | 2010-06-30 | 2016-01-19 | Life Technologies Corporation | Ion-sensing charge-accumulation circuits and methods |
US8247849B2 (en) | 2010-06-30 | 2012-08-21 | Life Technologies Corporation | Two-transistor pixel array |
US8731847B2 (en) | 2010-06-30 | 2014-05-20 | Life Technologies Corporation | Array configuration and readout scheme |
US11307166B2 (en) | 2010-07-01 | 2022-04-19 | Life Technologies Corporation | Column ADC |
US8653567B2 (en) | 2010-07-03 | 2014-02-18 | Life Technologies Corporation | Chemically sensitive sensor with lightly doped drains |
US9960253B2 (en) | 2010-07-03 | 2018-05-01 | Life Technologies Corporation | Chemically sensitive sensor with lightly doped drains |
US9121058B2 (en) | 2010-08-20 | 2015-09-01 | Integenx Inc. | Linear valve arrays |
US9731266B2 (en) | 2010-08-20 | 2017-08-15 | Integenx Inc. | Linear valve arrays |
US8763642B2 (en) | 2010-08-20 | 2014-07-01 | Integenx Inc. | Microfluidic devices with mechanically-sealed diaphragm valves |
US9618475B2 (en) | 2010-09-15 | 2017-04-11 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US9958414B2 (en) | 2010-09-15 | 2018-05-01 | Life Technologies Corporation | Apparatus for measuring analytes including chemical sensor array |
US9958415B2 (en) | 2010-09-15 | 2018-05-01 | Life Technologies Corporation | ChemFET sensor including floating gate |
US8685324B2 (en) | 2010-09-24 | 2014-04-01 | Life Technologies Corporation | Matched pair transistor circuits |
US9110015B2 (en) | 2010-09-24 | 2015-08-18 | Life Technologies Corporation | Method and system for delta double sampling |
US8796036B2 (en) | 2010-09-24 | 2014-08-05 | Life Technologies Corporation | Method and system for delta double sampling |
US8912005B1 (en) | 2010-09-24 | 2014-12-16 | Life Technologies Corporation | Method and system for delta double sampling |
US11635427B2 (en) | 2010-09-30 | 2023-04-25 | Bio-Rad Laboratories, Inc. | Sandwich assays in droplets |
US11396651B2 (en) | 2010-10-08 | 2022-07-26 | President And Fellows Of Harvard College | High-throughput single cell barcoding |
US10246703B2 (en) | 2010-10-08 | 2019-04-02 | President And Fellows Of Harvard College | High-throughput single cell barcoding |
GB2497912B (en) * | 2010-10-08 | 2014-06-04 | Harvard College | High-throughput single cell barcoding |
US9902950B2 (en) | 2010-10-08 | 2018-02-27 | President And Fellows Of Harvard College | High-throughput single cell barcoding |
US10752895B2 (en) | 2010-10-08 | 2020-08-25 | President And Fellows Of Harvard College | High-throughput single cell barcoding |
US11845054B2 (en) | 2010-11-12 | 2023-12-19 | Gen9, Inc. | Methods and devices for nucleic acids synthesis |
US10457935B2 (en) | 2010-11-12 | 2019-10-29 | Gen9, Inc. | Protein arrays and methods of using and making the same |
US10982208B2 (en) | 2010-11-12 | 2021-04-20 | Gen9, Inc. | Protein arrays and methods of using and making the same |
US11084014B2 (en) | 2010-11-12 | 2021-08-10 | Gen9, Inc. | Methods and devices for nucleic acids synthesis |
US11077415B2 (en) | 2011-02-11 | 2021-08-03 | Bio-Rad Laboratories, Inc. | Methods for forming mixed droplets |
US11768198B2 (en) | 2011-02-18 | 2023-09-26 | Bio-Rad Laboratories, Inc. | Compositions and methods for molecular labeling |
US11965877B2 (en) | 2011-02-18 | 2024-04-23 | Bio-Rad Laboratories, Inc. | Compositions and methods for molecular labeling |
US11747327B2 (en) | 2011-02-18 | 2023-09-05 | Bio-Rad Laboratories, Inc. | Compositions and methods for molecular labeling |
US11168353B2 (en) | 2011-02-18 | 2021-11-09 | Bio-Rad Laboratories, Inc. | Compositions and methods for molecular labeling |
WO2012130681A1 (fr) | 2011-03-25 | 2012-10-04 | Roche Diagnostics Gmbh | Système et procédé de détection de variants de l'intégrase du vih |
US11754499B2 (en) | 2011-06-02 | 2023-09-12 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
US9752176B2 (en) | 2011-06-15 | 2017-09-05 | Ginkgo Bioworks, Inc. | Methods for preparative in vitro cloning |
US9513253B2 (en) | 2011-07-11 | 2016-12-06 | Advanced Liquid Logic, Inc. | Droplet actuators and techniques for droplet-based enzymatic assays |
US11898193B2 (en) | 2011-07-20 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Manipulating droplet size |
US11702662B2 (en) | 2011-08-26 | 2023-07-18 | Gen9, Inc. | Compositions and methods for high fidelity assembly of nucleic acids |
US10865440B2 (en) | 2011-10-21 | 2020-12-15 | IntegenX, Inc. | Sample preparation, processing and analysis systems |
US10525467B2 (en) | 2011-10-21 | 2020-01-07 | Integenx Inc. | Sample preparation, processing and analysis systems |
US11684918B2 (en) | 2011-10-21 | 2023-06-27 | IntegenX, Inc. | Sample preparation, processing and analysis systems |
US10598723B2 (en) | 2011-12-01 | 2020-03-24 | Life Technologies Corporation | Method and apparatus for identifying defects in a chemical sensor array |
US9970984B2 (en) | 2011-12-01 | 2018-05-15 | Life Technologies Corporation | Method and apparatus for identifying defects in a chemical sensor array |
US10365321B2 (en) | 2011-12-01 | 2019-07-30 | Life Technologies Corporation | Method and apparatus for identifying defects in a chemical sensor array |
US9951384B2 (en) | 2012-01-13 | 2018-04-24 | Data2Bio | Genotyping by next-generation sequencing |
US10704091B2 (en) | 2012-01-13 | 2020-07-07 | Data2Bio | Genotyping by next-generation sequencing |
US20180201996A1 (en) * | 2012-01-13 | 2018-07-19 | Data2Bio | Genotyping by next-generation sequencing |
US8821798B2 (en) | 2012-01-19 | 2014-09-02 | Life Technologies Corporation | Titanium nitride as sensing layer for microwell structure |
US8747748B2 (en) | 2012-01-19 | 2014-06-10 | Life Technologies Corporation | Chemical sensor with conductive cup-shaped sensor surface |
US10308931B2 (en) | 2012-03-21 | 2019-06-04 | Gen9, Inc. | Methods for screening proteins using DNA encoded chemical libraries as templates for enzyme catalysis |
US10081807B2 (en) | 2012-04-24 | 2018-09-25 | Gen9, Inc. | Methods for sorting nucleic acids and multiplexed preparative in vitro cloning |
US10927369B2 (en) | 2012-04-24 | 2021-02-23 | Gen9, Inc. | Methods for sorting nucleic acids and multiplexed preparative in vitro cloning |
US10192024B2 (en) | 2012-05-18 | 2019-01-29 | 454 Life Sciences Corporation | System and method for generation and use of optimal nucleotide flow orders |
US10404249B2 (en) | 2012-05-29 | 2019-09-03 | Life Technologies Corporation | System for reducing noise in a chemical sensor array |
US8552771B1 (en) | 2012-05-29 | 2013-10-08 | Life Technologies Corporation | System for reducing noise in a chemical sensor array |
US9270264B2 (en) | 2012-05-29 | 2016-02-23 | Life Technologies Corporation | System for reducing noise in a chemical sensor array |
US8786331B2 (en) | 2012-05-29 | 2014-07-22 | Life Technologies Corporation | System for reducing noise in a chemical sensor array |
US9985624B2 (en) | 2012-05-29 | 2018-05-29 | Life Technologies Corporation | System for reducing noise in a chemical sensor array |
US11072789B2 (en) | 2012-06-25 | 2021-07-27 | Gen9, Inc. | Methods for nucleic acid assembly and high throughput sequencing |
US11591637B2 (en) | 2012-08-14 | 2023-02-28 | 10X Genomics, Inc. | Compositions and methods for sample processing |
US11441179B2 (en) | 2012-08-14 | 2022-09-13 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US11359239B2 (en) | 2012-08-14 | 2022-06-14 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
EP3901273A1 (fr) * | 2012-08-14 | 2021-10-27 | 10X Genomics, Inc. | Compositions de microcapsule et procédés |
US11434523B2 (en) | 2012-09-04 | 2022-09-06 | Guardant Health, Inc. | Systems and methods to detect rare mutations and copy number variation |
US11913065B2 (en) | 2012-09-04 | 2024-02-27 | Guardent Health, Inc. | Systems and methods to detect rare mutations and copy number variation |
WO2014043140A1 (fr) * | 2012-09-12 | 2014-03-20 | The Regents Of The University Of California | Séquençage précis du génome de cellules individuelles par l'amplification et le séquençage d'un seul brin |
US10752945B2 (en) | 2012-09-12 | 2020-08-25 | The Regents Of The University Of California | Accurate genome sequencing of single cells by single-stranded amplification and sequencing |
WO2014068407A3 (fr) * | 2012-10-26 | 2014-06-26 | Sysmex Corporation | Systèmes d'émulsion et amplification à base d'émulsion d'acide nucléique |
US9803226B2 (en) | 2012-10-26 | 2017-10-31 | Sysmex Corporation | Emulsion systems and emulsion-based amplification of nucleic acid |
US11421274B2 (en) | 2012-12-14 | 2022-08-23 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US11473138B2 (en) | 2012-12-14 | 2022-10-18 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US9080968B2 (en) | 2013-01-04 | 2015-07-14 | Life Technologies Corporation | Methods and systems for point of use removal of sacrificial material |
US9852919B2 (en) | 2013-01-04 | 2017-12-26 | Life Technologies Corporation | Methods and systems for point of use removal of sacrificial material |
US9841398B2 (en) | 2013-01-08 | 2017-12-12 | Life Technologies Corporation | Methods for manufacturing well structures for low-noise chemical sensors |
US10436742B2 (en) | 2013-01-08 | 2019-10-08 | Life Technologies Corporation | Methods for manufacturing well structures for low-noise chemical sensors |
US8962366B2 (en) | 2013-01-28 | 2015-02-24 | Life Technologies Corporation | Self-aligned well structures for low-noise chemical sensors |
US11193121B2 (en) | 2013-02-08 | 2021-12-07 | 10X Genomics, Inc. | Partitioning and processing of analytes and other species |
US9995708B2 (en) | 2013-03-13 | 2018-06-12 | Life Technologies Corporation | Chemical sensor with sidewall spacer sensor surface |
US8963216B2 (en) | 2013-03-13 | 2015-02-24 | Life Technologies Corporation | Chemical sensor with sidewall spacer sensor surface |
US8841217B1 (en) | 2013-03-13 | 2014-09-23 | Life Technologies Corporation | Chemical sensor with protruded sensor surface |
US10392614B2 (en) | 2013-03-15 | 2019-08-27 | Abvitro Llc | Methods of single-cell barcoding and sequencing |
US10119134B2 (en) | 2013-03-15 | 2018-11-06 | Abvitro Llc | Single cell bar-coding for antibody discovery |
US9823217B2 (en) | 2013-03-15 | 2017-11-21 | Life Technologies Corporation | Chemical device with thin conductive element |
US11118176B2 (en) | 2013-03-15 | 2021-09-14 | Abvitro Llc | Single cell bar-coding for antibody discovery |
US9128044B2 (en) | 2013-03-15 | 2015-09-08 | Life Technologies Corporation | Chemical sensors with consistent sensor surface areas |
US9816088B2 (en) | 2013-03-15 | 2017-11-14 | Abvitro Llc | Single cell bar-coding for antibody discovery |
US9835585B2 (en) | 2013-03-15 | 2017-12-05 | Life Technologies Corporation | Chemical sensor with protruded sensor surface |
US9116117B2 (en) | 2013-03-15 | 2015-08-25 | Life Technologies Corporation | Chemical sensor with sidewall sensor surface |
EP2971168B1 (fr) | 2013-03-15 | 2021-05-05 | Guardant Health, Inc. | Méthodes pour détecter cancer |
US10422767B2 (en) | 2013-03-15 | 2019-09-24 | Life Technologies Corporation | Chemical sensor with consistent sensor surface areas |
US10876107B2 (en) | 2013-03-15 | 2020-12-29 | Abvitro Llc | Single cell bar-coding for antibody discovery |
US10481124B2 (en) | 2013-03-15 | 2019-11-19 | Life Technologies Corporation | Chemical device with thin conductive element |
US9671363B2 (en) | 2013-03-15 | 2017-06-06 | Life Technologies Corporation | Chemical sensor with consistent sensor surface areas |
US10655175B2 (en) | 2013-05-09 | 2020-05-19 | Life Technologies Corporation | Windowed sequencing |
US10100357B2 (en) | 2013-05-09 | 2018-10-16 | Life Technologies Corporation | Windowed sequencing |
US11028438B2 (en) | 2013-05-09 | 2021-06-08 | Life Technologies Corporation | Windowed sequencing |
US10816504B2 (en) | 2013-06-10 | 2020-10-27 | Life Technologies Corporation | Chemical sensor array having multiple sensors per well |
US11499938B2 (en) | 2013-06-10 | 2022-11-15 | Life Technologies Corporation | Chemical sensor array having multiple sensors per well |
US11774401B2 (en) | 2013-06-10 | 2023-10-03 | Life Technologies Corporation | Chemical sensor array having multiple sensors per well |
US10458942B2 (en) | 2013-06-10 | 2019-10-29 | Life Technologies Corporation | Chemical sensor array having multiple sensors per well |
US9624519B2 (en) | 2013-08-23 | 2017-04-18 | 454 Life Sciences Corporation | System and method for nucleic acid amplification |
EP2840148A1 (fr) | 2013-08-23 | 2015-02-25 | F. Hoffmann-La Roche AG | Procédé et système pour l'amplification d'acides nucléiques |
US9808806B2 (en) | 2013-08-26 | 2017-11-07 | 454 Life Sciences Corporation | System and method for automated nucleic acid amplification |
EP2848698A1 (fr) | 2013-08-26 | 2015-03-18 | F. Hoffmann-La Roche AG | Système et méthode pour une amplification automatisée dacide nucléique |
US11901041B2 (en) | 2013-10-04 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Digital analysis of nucleic acid modification |
US10191071B2 (en) | 2013-11-18 | 2019-01-29 | IntegenX, Inc. | Cartridges and instruments for sample analysis |
US10989723B2 (en) | 2013-11-18 | 2021-04-27 | IntegenX, Inc. | Cartridges and instruments for sample analysis |
US11174509B2 (en) | 2013-12-12 | 2021-11-16 | Bio-Rad Laboratories, Inc. | Distinguishing rare variations in a nucleic acid sequence from a sample |
US11639525B2 (en) | 2013-12-28 | 2023-05-02 | Guardant Health, Inc. | Methods and systems for detecting genetic variants |
US11639526B2 (en) | 2013-12-28 | 2023-05-02 | Guardant Health, Inc. | Methods and systems for detecting genetic variants |
US11767555B2 (en) | 2013-12-28 | 2023-09-26 | Guardant Health, Inc. | Methods and systems for detecting genetic variants |
US11434531B2 (en) | 2013-12-28 | 2022-09-06 | Guardant Health, Inc. | Methods and systems for detecting genetic variants |
US11959139B2 (en) | 2013-12-28 | 2024-04-16 | Guardant Health, Inc. | Methods and systems for detecting genetic variants |
US11767556B2 (en) | 2013-12-28 | 2023-09-26 | Guardant Health, Inc. | Methods and systems for detecting genetic variants |
US11649491B2 (en) | 2013-12-28 | 2023-05-16 | Guardant Health, Inc. | Methods and systems for detecting genetic variants |
US11667959B2 (en) | 2014-03-05 | 2023-06-06 | Guardant Health, Inc. | Systems and methods to detect rare mutations and copy number variation |
US11447813B2 (en) | 2014-03-05 | 2022-09-20 | Guardant Health, Inc. | Systems and methods to detect rare mutations and copy number variation |
US11891650B2 (en) | 2014-05-21 | 2024-02-06 | IntegenX, Inc. | Fluid cartridge with valve mechanism |
US10961561B2 (en) | 2014-05-21 | 2021-03-30 | IntegenX, Inc. | Fluidic cartridge with valve mechanism |
US10208332B2 (en) | 2014-05-21 | 2019-02-19 | Integenx Inc. | Fluidic cartridge with valve mechanism |
US11713457B2 (en) | 2014-06-26 | 2023-08-01 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US11629344B2 (en) | 2014-06-26 | 2023-04-18 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10590483B2 (en) | 2014-09-15 | 2020-03-17 | Abvitro Llc | High-throughput nucleotide library sequencing |
EP3208343A4 (fr) * | 2014-10-13 | 2018-03-21 | BGI Shenzhen Co., Limited | Procédé de fragmentation d'acide nucléique et combinaison de séquences |
US10344317B2 (en) | 2014-10-13 | 2019-07-09 | Mgi Tech Co., Ltd | Method and a sequence combination for producing nucleic acid fragments |
US10690627B2 (en) | 2014-10-22 | 2020-06-23 | IntegenX, Inc. | Systems and methods for sample preparation, processing and analysis |
US10379079B2 (en) | 2014-12-18 | 2019-08-13 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US11536688B2 (en) | 2014-12-18 | 2022-12-27 | Life Technologies Corporation | High data rate integrated circuit with transmitter configuration |
US10077472B2 (en) | 2014-12-18 | 2018-09-18 | Life Technologies Corporation | High data rate integrated circuit with power management |
US10767224B2 (en) | 2014-12-18 | 2020-09-08 | Life Technologies Corporation | High data rate integrated circuit with power management |
US10605767B2 (en) | 2014-12-18 | 2020-03-31 | Life Technologies Corporation | High data rate integrated circuit with transmitter configuration |
US10421993B2 (en) | 2015-02-11 | 2019-09-24 | Paragon Genomics, Inc. | Methods and compositions for reducing non-specific amplification products |
US9464318B2 (en) * | 2015-02-11 | 2016-10-11 | Paragon Genomics, Inc. | Methods and compositions for reducing non-specific amplification products |
US11319588B2 (en) | 2015-02-17 | 2022-05-03 | Mgi Tech Co., Ltd. | DNA sequencing using controlled strand displacement |
US10227647B2 (en) | 2015-02-17 | 2019-03-12 | Complete Genomics, Inc. | DNA sequencing using controlled strand displacement |
AU2016220404B2 (en) * | 2015-02-17 | 2021-05-27 | Mgi Tech Co., Ltd. | DNA sequencing using controlled strand displacement |
EP3259372A4 (fr) * | 2015-02-17 | 2018-11-07 | Complete Genomics, Inc. | Séquençage de l'adn à l'aide d'un déplacement de brin régulé |
US10301660B2 (en) | 2015-03-30 | 2019-05-28 | Takara Bio Usa, Inc. | Methods and compositions for repair of DNA ends by multiple enzymatic activities |
WO2016160965A1 (fr) * | 2015-03-30 | 2016-10-06 | Rubicon Genomics, Inc. | Procédés et compositions permettant la réparation des extrémités de l'adn par de multiples activités enzymatiques |
US10640809B2 (en) * | 2015-05-29 | 2020-05-05 | Epicentre Technologies Corporation | Methods of analyzing nucleic acids |
US20180148767A1 (en) * | 2015-05-29 | 2018-05-31 | Epicentre Technologies Corporation | Methods of analyzing nucleic acids |
US11339422B2 (en) | 2015-05-29 | 2022-05-24 | Illumina, Inc. | Methods of analyzing nucleic acids |
US11795578B2 (en) | 2015-05-29 | 2023-10-24 | Illumina, Inc. | Methods of analyzing nucleic acids |
US10344336B2 (en) | 2015-06-09 | 2019-07-09 | Life Technologies Corporation | Methods, systems, compositions, kits, apparatus and computer-readable media for molecular tagging |
US11124842B2 (en) | 2015-06-09 | 2021-09-21 | Life Technologies Corporation | Methods, systems, compositions, kits, apparatus and computer-readable media for molecular tagging |
WO2018049260A1 (fr) * | 2016-09-09 | 2018-03-15 | Tl Biolabs Corp . | Compositions de microréseau réutilisables et procédés |
CN110062809A (zh) * | 2016-12-20 | 2019-07-26 | 豪夫迈·罗氏有限公司 | 用于环状共有序列测序的单链环状dna文库 |
US10100358B2 (en) | 2017-01-10 | 2018-10-16 | Paragon Genomics, Inc. | Methods and compositions for reducing redundant molecular barcodes created in primer extension reactions |
CN110719958A (zh) * | 2017-04-06 | 2020-01-21 | 王磬 | 构建核酸文库的方法和试剂盒 |
CN110719958B (zh) * | 2017-04-06 | 2023-07-18 | 康博国际有限公司 | 构建核酸文库的方法和试剂盒 |
WO2018186930A1 (fr) * | 2017-04-06 | 2018-10-11 | MyOmicsDx, Inc | Procédé et kit de construction d'une bibliothèque d'acides nucléiques |
CN111133135A (zh) * | 2017-07-17 | 2020-05-08 | 希昆斯生物科学公司 | 用于高通量测序的快速文库构建 |
US11667952B2 (en) | 2017-08-24 | 2023-06-06 | Takara Bio Usa, Inc. | Methods of producing nucleic acids using oligonucleotides modified by a stimulus |
CN108588200A (zh) * | 2018-05-06 | 2018-09-28 | 湖南大地同年生物科技有限公司 | 一种R-Loop高通量测序文库构建方法 |
CN109853047A (zh) * | 2019-04-10 | 2019-06-07 | 翌圣生物科技(上海)有限公司 | 一种基因组dna测序文库快速构建方法及配套试剂盒 |
CN111455469A (zh) * | 2020-04-07 | 2020-07-28 | 深圳易倍科华生物科技有限公司 | 一种单链快速建库方法及建库仪器 |
US10941453B1 (en) | 2020-05-20 | 2021-03-09 | Paragon Genomics, Inc. | High throughput detection of pathogen RNA in clinical specimens |
WO2023175040A3 (fr) * | 2022-03-15 | 2023-11-02 | Illumina, Inc. | Séquençage simultané de brins complémentaires sens et antisens sur des polynucléotides concaténés pour la détection de méthylation |
US11680293B1 (en) | 2022-04-21 | 2023-06-20 | Paragon Genomics, Inc. | Methods and compositions for amplifying DNA and generating DNA sequencing results from target-enriched DNA molecules |
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