The invention provides a novel class of cyanine dyes that are functionalized with sulfonic acid groups and a linker moiety that facilitates their conjugation to other species and substituent groups which increase the water-solubility, and optimize the optical properties of the dyes. Also provided are conjugates of the dyes, methods of using the dyes and their conjugates and kits including the dyes and their conjugates.
C07D 209/14 - Radicaux substitués par des atomes d'azote ne faisant pas partie d'un radical nitro
C07D 401/14 - Composés hétérocycliques contenant plusieurs hétérocycles comportant des atomes d'azote comme uniques hétéro-atomes du cycle, au moins un cycle étant un cycle à six chaînons avec un unique atome d'azote contenant au moins trois hétérocycles
C07D 405/14 - Composés hétérocycliques contenant à la fois un ou plusieurs hétérocycles comportant des atomes d'oxygène comme uniques hétéro-atomes du cycle et un ou plusieurs hétérocycles comportant des atomes d'azote comme uniques hétéro-atomes du cycle contenant au moins trois hétérocycles
C07H 19/10 - Radicaux pyrimidine avec le radical saccharide estérifié par des acides phosphoriques ou polyphosphoriques
C07K 5/09 - Tripeptides la chaîne latérale du premier amino-acide contenant plus de groupes amino que de groupes carboxyle, ou leurs dérivés, p.ex. Lys, Arg
C07K 5/11 - Tétrapeptides la chaîne latérale du premier amino-acide contenant plus de groupes amino que de groupes carboxyle, ou leurs dérivés, p.ex. Lys, Arg
C09B 23/01 - Colorants méthiniques ou polyméthiniques, p.ex. du type cyanine caractérisés par la chaîne méthinique
C09B 23/06 - Colorants méthiniques ou polyméthiniques, p.ex. du type cyanine caractérisés par la chaîne méthinique contenant un nombre impair de groupes CH trois groupes CH, p.ex. carbocyanines
C09B 23/08 - Colorants méthiniques ou polyméthiniques, p.ex. du type cyanine caractérisés par la chaîne méthinique contenant un nombre impair de groupes CH plus de trois groupes CH, p.ex. polycarbocyanines
C09B 23/10 - Colorants méthiniques ou polyméthiniques, p.ex. du type cyanine caractérisés par la chaîne méthinique contenant un nombre pair de groupes CH
C09B 23/16 - Colorants méthiniques ou polyméthiniques, p.ex. du type cyanine la chaîne polyméthinique contenant des hétéro-atomes
C12Q 1/6876 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p.ex. amorces ou sondes
G01N 33/52 - Utilisation de composés ou de compositions pour des recherches colorimétriques, spectrophotométriques ou fluorométriques, p.ex. utilisation de bandes de papier indicateur
G01N 33/58 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des substances marquées
2.
COMPOSITIONS AND TECHNIQUES FOR NUCLEIC ACID PRIMER EXTENSION
A method of characterizing a nucleic acid that includes steps of (a) contacting a primer-template nucleic acid hybrid with a polymerase and a mixture of nucleotides to produce an extended primer hybrid and to form a stabilized ternary complex including the extended primer hybrid, the polymerase and a nucleotide cognate of the next base in the template, wherein the mixture contains nucleotide cognates of four different base types, wherein the nucleotide cognate of the first base type has a reversible terminator, and wherein nucleotide cognates of the second, third and fourth base types are extendable; (b) detecting the stabilized ternary complex to distinguish the next base from other base types in the template; and (c) determining the presence of a base multiplet in the template nucleic acid, the base multiplet including the first base type followed by the next base.
Systems and methods for mapping a plurality of sequence reads to a genomic region are provided. A plurality of sequence reads mappable to the genomic region are obtained. An initial Markov model for the genomic region is obtained. The initial Markov model comprises at least (i) a first repeat for a first repeat region, (ii) a second repeat for a second repeat region, and (iii) an intermediate region linking the first repeat to the second repeat. The initial Markov model is refined using the plurality of sequence reads, thereby obtaining a refined Markov model. For each respective sequence read in the plurality of sequences, the respective sequence read is used to find a highest probability path through the Markov model. This highest probability path is then used to map the respective sequence read to the genomic region.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
05 - Produits pharmaceutiques, vétérinaires et hygièniques
Produits et services
Assays and reagents for scientific or research use; reagent
kits for preparation or performance of single molecule
assays for scientific or research use; buffers, enzymes,
reagents, nucleotides, chemical preparations and/or
biological compounds for scientific or research use. Assays and reagents for medical and diagnostic use; reagent
kits for medical and diagnostic use; buffers, enzymes,
reagents, nucleotides, chemical preparations and/or
biological compounds for medical and diagnostic use.
5.
SUBSTRATES AND OPTICAL SYSTEMS AND METHODS OF USE THEREOF
This invention provides devices for use in various analytical applications including single-molecule analytical reactions. Methods for detecting analytes optically by propagating optical energy by waveguides within a substrate are provided. Analytical devices are provided which have both shallow and deep waveguides in which illumination light is transported through the deep waveguides and coupled into the shallow waveguides. The shallow waveguides provide evanescent field illumination to analytes, such as single-molecule analytes, within nanometer scale wells. Integrated devices including integrated detectors such as CMOS detectors are included.
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismes; Compositions à cet effet; Procédés pour préparer ces compositions faisant intervenir des acides nucléiques
C12Q 1/6825 - Détecteurs faisant intervenir la détection d’acides nucléiques
G01N 21/77 - Systèmes dans lesquels le matériau est soumis à une réaction chimique, le progrès ou le résultat de la réaction étant analysé en observant l'effet sur un réactif chimique
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
6.
DIGITAL ANALYSIS OF MOLECULAR ANALYTES USING SINGLE MOLECULE DETECTION
Methods and systems are provided for small molecule analyte detection using digital signals, key encryption, and communications protocols. The methods provide detection of a large numbers of proteins, peptides, RNA molecules, and DNA molecules in a single optical or electrical detection assay within a large dynamic range.
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
G01N 33/58 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des substances marquées
Disclosed herein are methods and systems for detection and discrimination of optical signals from a densely packed substrate. These have broad applications for biomolecule detection near or below the diffraction limit of optical systems, including in improving the efficiency and accuracy of polynucleotide sequencing applications.
Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.
C07H 21/04 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p.ex. acides nucléiques avec le désoxyribosyle comme radical saccharide
C07H 19/207 - Radicaux purine avec le radical saccharide estérifié par des acides phosphoriques ou polyphosphoriques les acides phosphoriques ou polyphosphoriques étant estérifiés par un autre composé hydroxylique, p.ex. les dinucléotides de la flavine-adénine ou de la nicotinamide-adénine
C12Q 1/6876 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p.ex. amorces ou sondes
C09B 23/08 - Colorants méthiniques ou polyméthiniques, p.ex. du type cyanine caractérisés par la chaîne méthinique contenant un nombre impair de groupes CH plus de trois groupes CH, p.ex. polycarbocyanines
C09B 23/06 - Colorants méthiniques ou polyméthiniques, p.ex. du type cyanine caractérisés par la chaîne méthinique contenant un nombre impair de groupes CH trois groupes CH, p.ex. carbocyanines
C09B 69/00 - Colorants non prévus par un seul groupe de la présente sous-classe
The present disclosure provides compositions, methods and systems for sequencing a template nucleic acid using a polymerase based, nucleic acid binding reaction involving examination of the interaction between a polymerase and template nucleic acid in the presence of one or more unlabeled nucleotides. The methods rely, in part, on identifying a base of a template nucleic acid during nucleic acid synthesis by controlling the sequencing reaction conditions. Template nucleic acid bases may be identified during an examination step followed by an optional incorporation step.
Methods, compositions, and systems are provided that allow for reliable sequencing of the initial sequence region of a sequence of interest. The methods of the invention allow for more reliable barcoding of subpopulations of nucleic acids to be sequenced.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
Produits et services
Assays and reagents for scientific or research use; reagent kits for preparation or performance of single molecule assays for scientific or research use; buffers, enzymes, reagents, nucleotides, chemical preparations and/or biological compounds
Disclosed herein are blocked asymmetric hairpin adaptors that include a spacer that prevents extension by a strand-displacing polymerase. Such adaptors can be utilized for creating libraries of templates that can be processed into template concatemers and/or interrogated by various sequencing methods.
A sensor having a first electrode and a second electrode operably connected by a conduction channel, wherein a polymerase, primed template nucleic acid and nucleotide form a stabilized ternary complex that is immobilized in or on the conduction channel, whereby association and dissociation of the ternary complex is detected due to changes in electrical properties of the sensor. Identification of the nucleotide type that participates in the complex indicates the identity of the next template base in the template. Repeated cycles of extending the primer and detecting stabilized ternary complexes can allow determination of the sequence of nucleotides for the template.
Disclosed herein are methods and systems for detection and discrimination of optical signals from a densely packed substrate. These have broad applications for biomolecule detection near or below the diffraction limit of optical systems, including in improving the efficiency and accuracy of polynucleotide sequencing applications.
Disclosed herein are methods of detecting at least one target biomolecule in at least one single cell comprising lysing the single cell or cells and performing a cell identification assay and target identification assay. Also disclosed herein are methods for preparing a sample for undergoing single cell analysis, wherein the single cell analysis comprises performing a cell identification assay and a target identification assay.
G01N 33/58 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des substances marquées
C12Q 1/6876 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p.ex. amorces ou sondes
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
18.
DENSELY-PACKED ANALYTE LAYERS AND DETECTION METHODS
Disclosed herein are methods and systems for detection and discrimination of optical signals from a densely packed substrate. These methods and systems may have broad applications for biomolecule detection near or below the diffraction limit of optical systems, including in improving the efficiency and accuracy of polynucleotide sequencing applications.
The invention relates to methods and compositions for the detection and quantification of nucleotide sequence variants, such as genetic polymorphisms, with decreased error and increased sensitivity, including single molecule detection. Detection of genetic polymorphisms, including single nucleotide polymorphisms (SNPs), is highly useful for the study of physiology, disease, phylogeny and forensics. Current methods for the detection and identification of nucleic acid sequence variants, such as genetic polymorphisms, lack the sensitivity to accurately detect low incidence mutations, sequence variants or alleles. Detection techniques for highly multiplexed single molecule identification and quantification of analytes using optical systems are disclosed. Analytes include, but are not limited to, nucleic acid, such as DNA and RNA molecules, with and without modifications. Techniques described herein include use of specific and non-specific probes complementary to nucleic acids of interest for detailed characterization of nucleotide sequence variants and highly multiplexed single molecule identification and quantification.
The present disclosure provides methods, compositions, and systems for distributing polymerase compositions into array regions. In particular, the described methods, compositions, and systems utilize density differentials and/or additives to increase efficiency in the distribution of polymerase compositions to a surface as compared to methods utilizing only diffusion control.
Optical analytical devices and their methods of use are provided. The devices are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The devices include optical waveguides for illumination of the optical reactions. The devices further provide for the efficient coupling of optical excitation energy from the waveguides to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices of the invention are well suited for miniaturization and high throughput.
F21V 8/00 - Utilisation de guides de lumière, p.ex. dispositifs à fibres optiques, dans les dispositifs ou systèmes d'éclairage
G02B 6/024 - Fibres optiques avec revêtement avec des propriétés maintenant la polarisation
G01N 21/77 - Systèmes dans lesquels le matériau est soumis à une réaction chimique, le progrès ou le résultat de la réaction étant analysé en observant l'effet sur un réactif chimique
G02B 6/12 - OPTIQUE ÉLÉMENTS, SYSTÈMES OU APPAREILS OPTIQUES - Détails de structure de dispositions comprenant des guides de lumière et d'autres éléments optiques, p.ex. des moyens de couplage du type guide d'ondes optiques du genre à circuit intégré
G02F 1/365 - Optique non linéaire dans une structure de guide d'ondes optique
G02B 6/10 - OPTIQUE ÉLÉMENTS, SYSTÈMES OU APPAREILS OPTIQUES - Détails de structure de dispositions comprenant des guides de lumière et d'autres éléments optiques, p.ex. des moyens de couplage du type guide d'ondes optiques
G02B 6/122 - Elements optiques de base, p.ex. voies de guidage de la lumière
Methods, compositions, and systems for distributing nucleic acids into array regions are provided. The methods, compositions, and systems utilize nucleic acid condensing agents to increase efficiency of distribution of the nucleic acids into the array regions. Various methods for facilitating distribution of the nucleic acids to the array regions are provided.
Disclosed herein is a high throughput optical scanning device and methods of use. The optical scanning device and methods of use provided herein can allow high throughput scanning of a continuously moving object with a high resolution despite fluctuations in stage velocity. This can aid in high throughput scanning of a substrate, such as a biological chip comprising fluorophores. Also provided herein are improved optical relay systems and scanning optics.
G02B 27/64 - Systèmes pour donner des images utilisant des éléments optiques pour la stabilisation latérale et angulaire de l'image
G01D 5/347 - Moyens mécaniques pour le transfert de la grandeur de sortie d'un organe sensible; Moyens pour convertir la grandeur de sortie d'un organe sensible en une autre variable, lorsque la forme ou la nature de l'organe sensible n'imposent pas un moyen de conversion déterminé; Transducteurs non spécialement adaptés à une variable particulière utilisant des moyens optiques, c. à d. utilisant de la lumière infrarouge, visible ou ultraviolette avec atténuation ou obturation complète ou partielle des rayons lumineux les rayons lumineux étant détectés par des cellules photo-électriques en utilisant le déplacement d'échelles de codage
H04N 3/08 - TRANSMISSION D'IMAGES, p.ex. TÉLÉVISION - Détails des dispositifs de balayage des systèmes de télévision; Leur combinaison avec la production des tensions d'alimentation par des moyens optiques-mécaniques uniquement comportant un réflecteur mobile
H04N 23/60 - Commande des caméras ou des modules de caméras
Disclosed herein are methods and systems for detection and discrimination of optical signals from a densely packed substrate. There have broad applications for biomolecule detection near or below the diffraction limit of optical systems, including in improving the efficiency and accuracy or polynucleotide sequencing applications.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
05 - Produits pharmaceutiques, vétérinaires et hygièniques
Produits et services
(1) Assays and reagents for scientific or research use; reagent kits for preparation or performance of single molecule assays for scientific or research use; buffers, enzymes, reagents, nucleotides, chemical preparations and/or biological compounds for scientific or research use.
(2) Assays and reagents for medical and diagnostic use; reagent kits for medical and diagnostic use; buffers, enzymes, reagents, nucleotides, chemical preparations and/or biological compounds for medical and diagnostic use.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
05 - Produits pharmaceutiques, vétérinaires et hygièniques
09 - Appareils et instruments scientifiques et électriques
10 - Appareils et instruments médicaux
Produits et services
Assays and reagents for scientific or research use; reagent
kits for preparation or performance of ensemble or bulk
assays for scientific or research use; reagent kits
comprising components for single molecule assays for
scientific or research use. Assays and reagents for medical diagnosis. Laboratory instruments for scientific research, namely,
optical detectors for genetic sequencing and biochemical
analysis; analytical array chips; optical array chips for
genetic sequencing and biochemical analysis; downloadable
computer software for the analysis of biological data. Medical diagnostic instruments for clinical medical genetic
sequencing and biochemical analysis and for the analysis of
genes, molecules, DNA and RNA samples; medical analytical
array chips for clinical medical genetic sequencing and
biochemical analysis and for the analysis of genes,
molecules, DNA and RNA samples.
27.
SIZE SELECTION PURIFICATION USING A THERMOPLASTIC SILICA NANOMATERIAL
The present disclosure is directed to a method for purifying a sample containing nucleic acids to obtain isolated nucleic acids of a desired size range, either above a size cut-off, below a cut-off, or within a defined band of sizes, including: a) combining a nucleic acid-containing sample with a binding buffer to provide a binding mixture; b) contacting the binding mixture with a silica nanomembrane, wherein the silica nanomembrane adsorbs nucleic acids from the binding mixture within a desired size-range; and c) separating the bound nucleic acid from the remaining sample. Kits including a silica nanomembrane, a binding buffer and one or wash buffers are also provided herein.
C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN
B01J 20/10 - Compositions absorbantes ou adsorbantes solides ou compositions facilitant la filtration; Absorbants ou adsorbants pour la chromatographie; Procédés pour leur préparation, régénération ou réactivation contenant une substance inorganique contenant de la silice ou un silicate
28.
LABELED NUCLEOTIDE ANALOGS, REACTION MIXTURES, AND METHODS AND SYSTEMS FOR SEQUENCING
Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.
C09B 69/10 - Colorants polymères; Produits de réactions de colorants avec des monomères ou avec des composés macromoléculaires
C07H 19/10 - Radicaux pyrimidine avec le radical saccharide estérifié par des acides phosphoriques ou polyphosphoriques
C07H 19/207 - Radicaux purine avec le radical saccharide estérifié par des acides phosphoriques ou polyphosphoriques les acides phosphoriques ou polyphosphoriques étant estérifiés par un autre composé hydroxylique, p.ex. les dinucléotides de la flavine-adénine ou de la nicotinamide-adénine
Compositions, methods, and systems are provided for fluorescent polymerase enzyme substrates comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Fluorescent polymerase enzyme substrates of the invention have a protein shield between the fluorescent dye moieties and nucleotide moieties of the polymerase enzyme substrate. The polymerase enzyme substrates have a nucleotide component and a dye component, each attached to a protein. The attachments can be covalent. The protein can, for example, prevent the direct interaction of the fluorescent dye moiety with the enzyme when carrying out nucleotide synthesis, preventing photodamage to the enzyme. The polymerase enzyme substrates of the invention can have multiple dyes and multiple nucleotide moieties.
C07H 21/04 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p.ex. acides nucléiques avec le désoxyribosyle comme radical saccharide
C07K 14/36 - Peptides ayant plus de 20 amino-acides; Gastrines; Somatostatines; Mélanotropines; Leurs dérivés provenant de bactéries provenant de Streptomyces (G)
G01N 33/58 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des substances marquées
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
C09B 23/08 - Colorants méthiniques ou polyméthiniques, p.ex. du type cyanine caractérisés par la chaîne méthinique contenant un nombre impair de groupes CH plus de trois groupes CH, p.ex. polycarbocyanines
C09B 69/10 - Colorants polymères; Produits de réactions de colorants avec des monomères ou avec des composés macromoléculaires
30.
METHODS AND COMPOSITIONS FOR SEQUENCING DOUBLE STRANDED NUCLEIC ACIDS
A method for determining sequences from sense and antisense strands of a nucleic acid, including (a) providing a nucleic acid cluster attached to a solid support, wherein the nucleic acid cluster includes a sense strand and an antisense strand of a concatemer, the concatemer including multiple copies of a sequence unit, the sequence unit including a target sequence and a primer binding site; (b) hybridizing a primer to a primer binding site in the antisense strand; (c) extending the primer along the antisense strand to determine the sequence from at least a portion of the target sequence in the antisense strand; (d) hybridizing a second primer to a primer binding site in the sense strand; and (e) extending the second primer along the sense strand to determine the sequence from at least a portion of the target sequence in the sense strand.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
09 - Appareils et instruments scientifiques et électriques
Produits et services
Assays and reagents for scientific or research use; reagent
kits for preparation or performance of single molecule
assays for scientific or research use; reagent kits
comprising components for single molecule assays for
scientific or research use. Laboratory instruments for scientific research, namely,
optical detectors for genetic sequencing and biochemical
analysis; analytical array chips; optical array chips for
genetic sequencing and biochemical analysis; downloadable
computer software for the analysis of biological data.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
Produits et services
Assays and reagents for scientific or research use; Reagent kits for preparation or performance of single molecule assays for scientific or research use; buffers, enzymes, reagents, nucleotides, chemical preparations and/or biological compounds
A reagent cartridge including (a) a support having reservoirs; (b) a main channel within the support, the channel having first and second ends exiting the support; (c) a pump channel that connects to the main channel between the first and second ends; (d) a valve manifold in the support, including (i) a first passage at the first end of the main channel, (ii) a second passage at the second end of the main channel, (iii) a first master valve between the pump channel and the first end of the main channel, (iv) a second master valve between the pump channel and the second end of the main channel, and (v) reservoir valves for regulating flow from individual reservoirs to the main channel. The valves can be normally closed diaphragm valves formed by magnetic pistons attached to an elastomeric sheet that is sandwiched in the support.
Arrays of integrated analytical devices and their methods for production are provided. The arrays are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The devices allow the highly sensitive discrimination of optical signals using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices include an integrated diffractive beam shaping element that provides for the spatial separation of light emitted from the optical reactions.
G01N 21/78 - Systèmes dans lesquels le matériau est soumis à une réaction chimique, le progrès ou le résultat de la réaction étant analysé en observant l'effet sur un réactif chimique produisant un changement de couleur
G01N 21/77 - Systèmes dans lesquels le matériau est soumis à une réaction chimique, le progrès ou le résultat de la réaction étant analysé en observant l'effet sur un réactif chimique
G02B 6/132 - Circuits optiques intégrés caractérisés par le procédé de fabrication par le dépôt de couches minces
G02B 6/136 - Circuits optiques intégrés caractérisés par le procédé de fabrication par gravure
Methods, compositions, and systems are provided for characterization of modified nucleic acids. In certain preferred embodiments, single molecule sequencing methods are provided for identification of modified nucleotides within nucleic acid sequences. Modifications detectable by the methods provided herein include chemically modified bases, enzymatically modified bases, abasic sites, non-natural bases, secondary structures, and agents bound to a template nucleic acid.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
09 - Appareils et instruments scientifiques et électriques
Produits et services
(1) Assays and reagents for scientific or research use; reagent kits for preparation or performance of single molecule assays for scientific or research use; reagent kits comprising components for single molecule assays for scientific or research use.
(2) Laboratory instruments for scientific research, namely, optical detectors for genetic sequencing and biochemical analysis; analytical array chips; optical array chips for genetic sequencing and biochemical analysis; downloadable computer software for the analysis of biological data.
39.
SYSTEMS AND METHODS OF DETECTING DENSELY-PACKED ANALYTES
Disclosed herein are methods and systems for detection and discrimination of optical signals from a densely packed substrate. These may have broad applications for biomolecule detection near or below the diffraction limit of optical systems, including in improving the efficiency and accuracy of polynucleotide sequencing applications.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
05 - Produits pharmaceutiques, vétérinaires et hygièniques
09 - Appareils et instruments scientifiques et électriques
10 - Appareils et instruments médicaux
Produits et services
(1) Assays and reagents for scientific or research use; reagent kits for preparation or performance of ensemble or bulk assays for scientific or research use; reagent kits comprising components for single molecule assays for scientific or research use.
(2) Assays and reagents for medical diagnosis.
(3) Laboratory instruments for scientific research, namely, optical detectors for genetic sequencing and biochemical analysis; analytical array chips; optical array chips for genetic sequencing and biochemical analysis; downloadable computer software for the analysis of biological data.
(4) Medical diagnostic instruments for clinical medical genetic sequencing and biochemical analysis and for the analysis of genes, molecules, DNA and RNA samples; medical analytical array chips for clinical medical genetic sequencing and biochemical analysis and for the analysis of genes, molecules, DNA and RNA samples.
41.
DISTINGUISHING SEQUENCES BY DETECTING POLYMERASE DISSOCIATION
A method for determining the presence of an allele, including (a) binding a polymerase to a double stranded nucleic acid that includes a primer hybridized to a template, the template including a first allele of a locus; (b) adding a nucleotide to the primer via catalytic activity of the polymerase, thereby producing an extended nucleic acid; (c) dissociating the polymerase from the extended nucleic acid; (d) detecting dissociation of the polymerase from the extended nucleic acid; and (e) comparing the dissociation of the polymerase from the extended nucleic acid to dissociation of the polymerase from a second double stranded nucleic acid, the second double stranded nucleic acid including a primer hybridized to the same position of the locus as the primer of the extended nucleic acid.
Protected fluorescent reagent compounds and their methods of synthesis are provided. The compounds are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The compounds contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements.
C07H 19/10 - Radicaux pyrimidine avec le radical saccharide estérifié par des acides phosphoriques ou polyphosphoriques
C07F 9/6558 - Composés hétérocycliques, p.ex. contenant du phosphore comme hétéro-atome du cycle contenant au moins deux hétérocycles différents ou différemment substitués ni condensés entre eux ni condensés avec un carbocycle commun ou un système carbocyclique commun
C07F 9/6561 - Composés hétérocycliques, p.ex. contenant du phosphore comme hétéro-atome du cycle contenant des systèmes de plusieurs hétérocycles déterminants condensés entre eux ou condensés avec un carbocycle ou un système carbocyclique commun, avec ou sans autres hétérocycles non condensés
C09B 23/06 - Colorants méthiniques ou polyméthiniques, p.ex. du type cyanine caractérisés par la chaîne méthinique contenant un nombre impair de groupes CH trois groupes CH, p.ex. carbocyanines
C09B 23/08 - Colorants méthiniques ou polyméthiniques, p.ex. du type cyanine caractérisés par la chaîne méthinique contenant un nombre impair de groupes CH plus de trois groupes CH, p.ex. polycarbocyanines
C09B 69/10 - Colorants polymères; Produits de réactions de colorants avec des monomères ou avec des composés macromoléculaires
Provided herein include a method for modifying polymerase-nucleic acid complexes, including (a) providing a plurality of surface-immobilized polymerase-nucleic acid complexes in a vessel, wherein the nucleic acid includes a primed-template nucleic acid, wherein at least a subset of the surface-immobilized polymerase-nucleic acid complexes include ternary complexes further including nucleotides; and (b) washing the surface with an aqueous solution including a diol, sulfoxide or polyol, thereby removing the nucleotides from the vessel and retaining the surface-immobilized polymerase-nucleic acid complexes in the vessel.
Optics collection and detection systems are provided for measuring optical signals from an array of optical sources over time. Methods of using the optics collection and detection systems are also described.
B82Y 20/00 - Nano-optique, p.ex. optique quantique ou cristaux photoniques
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
G02B 6/122 - Elements optiques de base, p.ex. voies de guidage de la lumière
G01N 21/03 - Dispositions ou appareils pour faciliter la recherche optique - Détails de structure des cuvettes
G01N 21/75 - Systèmes dans lesquels le matériau est soumis à une réaction chimique, le progrès ou le résultat de la réaction étant analysé
G01N 21/77 - Systèmes dans lesquels le matériau est soumis à une réaction chimique, le progrès ou le résultat de la réaction étant analysé en observant l'effet sur un réactif chimique
C12Q 1/6825 - Détecteurs faisant intervenir la détection d’acides nucléiques
The present invention provides methods, compositions, and systems for distributing molecules and complexes into reaction sites. In particular, the methods, compositions, and systems of the present invention result in an active loading of molecules and complexes into reaction sites with improved efficiency over loading by passive diffusion methods alone.
A method of determining a nucleic acid sequence that includes steps of: (a) contacting a primed template nucleic acid with a series of mixtures for forming ternary complexes, wherein each of the mixtures includes a polymerase and nucleotide cognates for at least two different base types suspected of being present at the next template position of the template nucleic acid; (b) monitoring the next template position for ternary complexes formed by the series of mixtures, wherein a signal state indicates presence or absence of ternary complex formed at the next template position by each individual mixture, thereby determining a series of signal states that encodes a base call for the next template position; and (c) decoding the series of signal states to distinguish a correct base call for the next template position from an error in the base call.
Methods, compositions, and systems are provided for characterization of modified nucleic acids. In certain preferred embodiments, single molecule sequencing methods are provided for identification of modified nucleotides within nucleic acid sequences. Modifications detectable by the methods provided herein include chemically modified bases, enzymatically modified bases, abasic sites, non-natural bases, secondary structures, and agents bound to a template nucleic acid.
Optical analytical devices and their methods of use are provided. The devices are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The devices include integrated illumination elements and optical waveguides for illumination of the optical reactions. The devices further provide for the efficient coupling of optical excitation energy from the waveguides to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices of the invention are well suited for miniaturization and high throughput.
G01N 21/77 - Systèmes dans lesquels le matériau est soumis à une réaction chimique, le progrès ou le résultat de la réaction étant analysé en observant l'effet sur un réactif chimique
Provided herein are systems, devices, and methods for improved optical waveguide transmission and alignment in an analytical system. Waveguides in optical analytical systems can exhibit variable and increasing back reflection of single-wavelength illumination over time, thus limiting their effectiveness and reliability. The systems are also subject to optical interference under conditions that have been used to overcome the back reflection. Novel systems and approaches using broadband illumination light with multiple longitudinal modes have been developed to improve optical transmission and analysis in these systems. Novel systems and approaches for the alignment of a target waveguide device and an optical source are also disclosed.
G02B 6/12 - OPTIQUE ÉLÉMENTS, SYSTÈMES OU APPAREILS OPTIQUES - Détails de structure de dispositions comprenant des guides de lumière et d'autres éléments optiques, p.ex. des moyens de couplage du type guide d'ondes optiques du genre à circuit intégré
G02B 6/42 - Couplage de guides de lumière avec des éléments opto-électroniques
G02B 27/09 - Mise en forme du faisceau, p.ex. changement de la section transversale, non prévue ailleurs
G02B 6/122 - Elements optiques de base, p.ex. voies de guidage de la lumière
G01N 21/77 - Systèmes dans lesquels le matériau est soumis à une réaction chimique, le progrès ou le résultat de la réaction étant analysé en observant l'effet sur un réactif chimique
G01N 21/63 - Systèmes dans lesquels le matériau analysé est excité de façon à ce qu'il émette de la lumière ou qu'il produise un changement de la longueur d'onde de la lumière incidente excité optiquement
G01N 21/17 - Systèmes dans lesquels la lumière incidente est modifiée suivant les propriétés du matériau examiné
Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions, and/or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing. Such properties include increased resistance to photodamage, and can also include enhanced metal ion coordination, reduced exonuclease activity, reduced reaction rates at one or more steps of the polymerase kinetic cycle, decreased branching fraction, altered cofactor selectivity, increased yield, increased thermostability, increased accuracy, increased speed, increased readlength, and the like. Also provided are nucleic acids which encode the polymerases with the aforementioned phenotypes, as well as methods of using such polymerases to make a DNA or to sequence a DNA template.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
09 - Appareils et instruments scientifiques et électriques
Produits et services
Assays and reagents for scientific or research use; Reagent kits comprised of buffers, enzymes, reagents, nucleotides, chemical preparations and/or biological compounds for use in the preparation or performance of ensemble or bulk assays for scientific or research use; Reagent kits comprising components, namely, buffers, enzymes, reagents, nucleotides, chemical preparations and/or biological compounds, for single molecule assays for scientific or research use Laboratory instruments for scientific research, namely, optical detectors for genetic sequencing and biochemical analysis; analytical array chips for genetic sequencing and biochemical analysis; optical array chips for genetic sequencing and biochemical analysis
53.
FLOW CELLS AND METHODS FOR THEIR MANUFACTURE AND USE
A flow cell that includes (a) a gasket interposed between a first substrate and a second substrate, wherein the gasket, the first substrate and the second substrate are impermeable to aqueous liquid and liquid adhesive, wherein the gasket has a footprint on the first substrate that delineates a channel for containing the aqueous liquid; (b) a via in the gasket, the via containing a solidified liquid adhesive that bonds the first substrate to the second substrate, wherein the solidified liquid adhesive in the via is separated from the channel by the gasket; and (c) a channel port connecting the channel to the exterior of the flow cell, wherein the channel port is permeable to the aqueous liquid.
Provided herein are methods of purifying a sample containing nucleic acids to obtain isolated nucleic acids of a desired size range and methods of sequencing nucleic acids of a desired size range. The methods include a) combining a nucleic acid-containing sample with a precipitation buffer in a container to provide a precipitation mixture in which the precipitation buffer comprises water, a buffer, a salt, and polyvinyl pyrrolidinone (PVP) and/or Ficoll. The methods also include precipitating the nucleic acids in the precipitation mixture to provide a precipitated nucleic acid portion and a remaining sample portion. The precipitated nucleic acid portion predominantly comprises nucleic acid molecules above a selected size cutoff value and the remaining sample portion predominantly comprises nucleic acid molecules below the selected size cutoff value. The methods also include separating the precipitated nucleic acid portion from the remaining sample portion. Related compositions and kits are also provided herein.
Arrays of integrated analytical devices are provided. The arrays are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. In particular, the arrays provide increased efficiency of optical collection and decreased background signal as the lateral dimensions of the unit cell of devices within the array are decreased, for example as they are decreased to 2 μm, or even less.
G01N 35/00 - Analyse automatique non limitée à des procédés ou à des matériaux spécifiés dans un seul des groupes ; Manipulation de matériaux à cet effet
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
05 - Produits pharmaceutiques, vétérinaires et hygièniques
09 - Appareils et instruments scientifiques et électriques
10 - Appareils et instruments médicaux
Produits et services
Assays and reagents for scientific or research use; Reagent kits comprised of buffers, enzymes, reagents, nucleotides, chemical preparations and/or biological compounds for use in the preparation or performance of ensemble or bulk assays for scientific or research use; Reagent kits comprising components, namely, buffers, enzymes, reagents, nucleotides, chemical preparations and/or biological compounds for single molecule assays for scientific or research use Assays and reagents for medical diagnosis for medical use Laboratory instruments for scientific research, namely, optical detectors for genetic sequencing and biochemical analysis; analytical array chips; optical array chips for genetic sequencing and biochemical analysis; downloadable computer software for the analysis of biological data Medical diagnostic instruments for clinical medical genetic sequencing and biochemical analysis and for the analysis of genes, molecules, DNA and RNA samples; analytical array chips for clinical medical genetic sequencing and biochemical analysis and for the analysis of genes, molecules, DNA and RNA samples
The present invention provides methods and compositions for carrying out nucleic acid sequencing, particularly paired-end sequencing. The methods use concatemeric sequencing templates that can be produced by rolling circle amplification of asymmetric circular nucleic acids having a central double-stranded region comprising a target nucleic acid sequence that is connected at each end to form a circular construct.
The present invention provides methods and compositions for carrying out nucleic acid sequencing, particularly paired-end sequencing. The methods use concatemeric sequencing templates that can be produced by rolling circle amplification of asymmetric circular nucleic acids having a central double- stranded region comprising a target nucleic acid sequence that is connected at each end to form a circular construct.
Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.
C09B 69/10 - Colorants polymères; Produits de réactions de colorants avec des monomères ou avec des composés macromoléculaires
C07H 19/10 - Radicaux pyrimidine avec le radical saccharide estérifié par des acides phosphoriques ou polyphosphoriques
C07H 19/207 - Radicaux purine avec le radical saccharide estérifié par des acides phosphoriques ou polyphosphoriques les acides phosphoriques ou polyphosphoriques étant estérifiés par un autre composé hydroxylique, p.ex. les dinucléotides de la flavine-adénine ou de la nicotinamide-adénine
Disclosed herein are methods and systems for storing data and/or information on nucleic acid molecules, storing the nucleic acid molecules, and retrieving the data and/or information. These methods and systems have broad applications for data storage, including in improving the efficiency and accuracy of retrieving data.
A method for identifying a nucleotide in a primed template nucleic acid, including the steps of (a) providing a vessel having a primed template nucleic acid, polymerase and a nucleotide cognate of a first base type; (b) examining the vessel for a stabilized ternary complex including the polymerase and the nucleotide cognate of the first base type bound at a base position of the primed template nucleic acid; (c) delivering a nucleotide cognate of a second base type to the vessel, whereby the vessel retains the primed template nucleic acid and the polymerase from step (b); (d) examining the vessel for a stabilized ternary complex including the polymerase and the nucleotide cognate of the second base type bound at the base position of the primed template nucleic acid; and (e) identifying the type of nucleotide at the base position of the primed template nucleic acid.
The present invention provides methods, compositions, and systems for distributing molecules and complexes into reaction sites. In particular, the methods, compositions, and systems of the present invention result in loading of polymerase enzyme complexes into a predetermined number of reaction sites, including nanoscale wells.
Provided include methods, compositions, kits, and systems for replenishing a rolling circle amplification (RCA) reaction in a vessel. The RCA reaction can be initiated by contacting a nucleic acid template and a primer with a loading buffer comprising a DNA polymerase and polymerase extension agents including a divalent metal cation and a polyelectrolyte, followed by replenishing with an amplification buffer to continue the nucleic acid amplification through primer extension. The amplification buffer is different in composition from the loading buffer and does not comprise any DNA polymerase.
Provided includes methods, compositions and systems for single molecule seeding and amplification on a flow cell. In some embodiments, nucleic acids are isothermally seeded and amplified on a flow cell comprising multiple binding areas (e.g., pads), resulting in an ensemble of substantially the same amplified molecules on each of the binding areas.
Provided include methods, compositions, kits, and systems for replenishing a rolling circle amplification (RCA) reaction in a vessel. The RCA reaction can be initiated by contacting a nucleic acid template and a primer with a loading buffer comprising a DNA polymerase and polymerase extension agents including a divalent metal cation and a polyelectrolyte, followed by replenishing with an amplification buffer to continue the nucleic acid amplification through primer extension. The amplification buffer is different in composition from the loading buffer and does not comprise any DNA polymerase.
C12Q 1/6848 - Réactions d’amplification d’acides nucléiques caracterisées par les moyens d’empêcher la contamination ou d’augmenter la spécificité ou la sensibilité d’une réaction d’amplification
C12Q 1/6853 - Réactions d’amplification d’acides nucléiques utilisant des amorces ou des matrices modifiées
66.
ARRAYS OF INTEGRATED ANALYTICAL DEVICES WITH REDUCED-SCALE UNIT CELL
Arrays of integrated analytical devices are provided. The arrays are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. In particular, the arrays provide increased efficiency of optical collection and decreased background signal as the lateral dimensions of the unit cell of devices within the array are decreased, for example as they are decreased to 2 µm, or even less.
C12Q 1/6825 - Détecteurs faisant intervenir la détection d’acides nucléiques
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
B82Y 15/00 - Nanotechnologie pour l’interaction, la détection ou l'actionnement, p.ex. points quantiques comme marqueurs en dosages protéiques ou moteurs moléculaires
Provided includes methods, compositions and systems for single molecule seeding and amplification on a flow cell. In some embodiments, nucleic acids are isothermally seeded and amplified on a flow cell comprising multiple binding areas (e.g., pads), resulting in an ensemble of substantially the same amplified molecules on each of the binding areas.
Arrays of integrated analytical devices are provided. The arrays are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. In particular, the arrays provide increased efficiency of optical collection and decreased background signal as the lateral dimensions of the unit cell of devices within the array are decreased, for example as they are decreased to 2 µm, or even less.
C12Q 1/6825 - Détecteurs faisant intervenir la détection d’acides nucléiques
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
B82Y 15/00 - Nanotechnologie pour l’interaction, la détection ou l'actionnement, p.ex. points quantiques comme marqueurs en dosages protéiques ou moteurs moléculaires
A method for determining sequences from sense and antisense strands of a nucleic acid, including (a) providing a nucleic acid cluster attached to a solid support, wherein the nucleic acid cluster includes a sense strand and an antisense strand of a concatemer, the concatemer including multiple copies of a sequence unit, the sequence unit including a target sequence and a primer binding site; (b) hybridizing a primer to a primer binding site in the antisense strand; (c) extending the primer along the antisense strand to determine the sequence from at least a portion of the target sequence in the antisense strand; (d) hybridizing a second primer to a primer binding site in the sense strand; and (e) extending the second primer along the sense strand to determine the sequence from at least a portion of the target sequence in the sense strand.
Method of identifying a cognate nucleotide (i.e., the “next correct nucleotide”) for a primed template nucleic acid molecule. In some embodiments, an ordered or random array of primed target nucleic acids characterized by different cognate nucleotides can be evaluated using a single imaging step to identify different cognate nucleotides for a collection of different primed template nucleic acid molecules. An optional incorporation step can follow the identifying step. A polymerase different from the ones used in the binding and examination steps can be used to incorporate a nucleotide, such as a reversible terminator nucleotide, preliminary to identification of the next cognate nucleotide.
Disclosed herein include methods of specifying sites (e.g., sites for colony formation) on a surface (e.g., a planar surface) and generating a flow cell having the sites specified on a surface. Also disclosed are methods of performing sequencing (e.g., sequencing-by-synthesis and sequencing-by-binding) using the flow cell generated and processing (e.g., aligning, orienting, sorting, and assessing quality) images of the flow cell captured during sequencing.
Methods, compositions, kits and apparatuses that include a fluid, the fluid containing a ternary complex and Li+, wherein the ternary complex includes a primed template nucleic acid, a polymerase, and a nucleotide cognate for the next correct base for the primed template nucleic acid molecule. As an alternative or addition to Li+, the fluid can contain betaine or a metal ion that inhibits polymerase catalysis such as Ca2+. In addition to Li+, the fluid can contain polyethylenimine (PEI) with or without betaine.
Reaction mixtures are provided having at least a first nucleotide analog and a second nucleotide analog that produce signals in response to excitation illumination. The signals produced by the analogs have peaks at the same wavelengths, but have distinct signal intensities. The distinct intensities allow for identification of the analogs in nucleic acid sequencing. In some embodiments, FRET-labeled compounds are provided. In certain embodiments, FRET-labeled nucleotide analogs are used, for example, in DNA sequencing or RNA sequencing.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismes; Compositions à cet effet; Procédés pour préparer ces compositions faisant intervenir des acides nucléiques
C07H 19/207 - Radicaux purine avec le radical saccharide estérifié par des acides phosphoriques ou polyphosphoriques les acides phosphoriques ou polyphosphoriques étant estérifiés par un autre composé hydroxylique, p.ex. les dinucléotides de la flavine-adénine ou de la nicotinamide-adénine
G01N 33/542 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec formation d'un complexe immunologique en phase liquide avec inhibition stérique ou modification du signal, p.ex. extinction de fluorescence
G01N 33/58 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des substances marquées
C12Q 1/6818 - Tests d’hybridation caractérisés par les moyens de détection impliquant l’interaction de plusieurs marqueurs, p.ex. transfert d’énergie de résonance
74.
Recombinant polymerases for incorporation of protein shield nucleotide analogs
Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions, and/or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing or nucleic acid amplification. Such properties include enhanced performance with large nucleotide analogs, increased stability, increased readlength, and improved detection of modified bases, and can also include resistance to photodamage, enhanced metal ion coordination, reduced exonuclease activity, reduced reaction rates at one or more steps of the polymerase kinetic cycle, decreased branching fraction, altered cofactor selectivity, increased yield, increased accuracy, altered speed, increased cosolvent resistance, and the like. Also provided are nucleic acids which encode the polymerases with the aforementioned phenotypes, as well as methods of using such polymerases to make a DNA or to sequence a DNA template.
Provided herein are engineered DNA polymerases comprising modifications improving accuracy and processivity of the polymerase including modifications in the Motif A region, optionally, along with additional modifications in the palm and/or exonuclease domains of the polymerase. Also provided are nucleic acids encoding the engineered DNA polymerases comprising modifications in motif A of the polymerase, optionally, with additional modifications. Methods, vectors, kits, and compositions comprising the nucleic acids and compositions, methods and kits comprising the engineered polymerases are also provided.
Provided are nucleic acids encoding engineered polymerases comprising at least one modification in a motif A and/or at least one modification in a motif B of the polymerase and engineered polymerases encoded by the nucleic acids. Also provided are engineered DNA polymerases comprising a variant of SEQ ID NO:1, SEQ ID NO:2, or SEQ ID NO:3, the variant being at least 80% identical to SEQ ID NO:1, SEQ ID NO:2 or SEQ ID NO:3 and comprising an amino acid substitution at one or more positions selected from the group consisting of L408, Y409, P410, R484, A/L485, and I486. Methods, vectors, kits, and compositions comprising the nucleic acids and compositions, methods and kits comprising the engineered polymerases are also provided.
Disclosed herein include methods of specifying sites (e.g., sites for colony formation) on a surface (e.g., a planar surface) and generating a flow cell having the sites specified on a surface. Also disclosed are methods of performing sequencing (e.g., sequencing-by-synthesis and sequencing-by-binding) using the flow cell generated and processing (e.g., aligning, orienting, sorting, and assessing quality) images of the flow cell captured during sequencing.
B01J 19/00 - Procédés chimiques, physiques ou physico-chimiques en général; Appareils appropriés
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismes; Compositions à cet effet; Procédés pour préparer ces compositions faisant intervenir des acides nucléiques
Disclosed herein include methods of specifying sites (e.g., sites for colony formation) on a surface (e.g., a planar surface) and generating a flow cell having the sites specified on a surface. Also disclosed are methods of performing sequencing (e.g., sequencing-by-synthesis and sequencing-by-binding) using the flow cell generated and processing (e.g., aligning, orienting, sorting, and assessing quality) images of the flow cell captured during sequencing.
B01J 19/00 - Procédés chimiques, physiques ou physico-chimiques en général; Appareils appropriés
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismes; Compositions à cet effet; Procédés pour préparer ces compositions faisant intervenir des acides nucléiques
Methods are provided for detecting a single compound analyte immobilized to a solid substrate by serially contacting and removing different probes to the same analyte.
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
G01N 33/58 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des substances marquées
G01N 33/536 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec formation d'un complexe immunologique en phase liquide
C12Q 1/6825 - Détecteurs faisant intervenir la détection d’acides nucléiques
H03M 13/15 - Codes cycliques, c. à d. décalages cycliques de mots de code produisant d'autres mots de code, p.ex. codes définis par un générateur polynomial, codes de Bose-Chaudhuri-Hocquenghen [BCH]
G16B 25/00 - TIC spécialement adaptées à l’hybridation; TIC spécialement adaptées à l’expression de gènes ou de protéines
G16B 40/00 - TIC spécialement adaptées aux biostatistiques; TIC spécialement adaptées à l’apprentissage automatique ou à l’exploration de données liées à la bio-informatique, p.ex. extraction de connaissances ou détection de motifs
80.
Digital analysis of molecular analytes using electrical methods
Electrical detection methods are used to identify and further characterize single-molecule target analytes such as proteins and nucleic acids. A composition including a probe region and a tail region is contacted with a target analyte. The probe region specifically binds to the target analyte. The tail region is coupled to the probe region, and includes a nucleic acid template for polynucleotide synthesis. When conditions are such that polynucleotide synthesis occurs along the tail region, one hydrogen ion is released for every nucleotide that is incorporated into the tail region. A transistor such as an ISFET detects and measures changes in ion concentration, and these measurements can be used to identify the tail region and thus characterize the corresponding target analyte.
G01N 33/58 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des substances marquées
G01N 27/414 - Transistors à effet de champ sensibles aux ions ou chimiques, c. à d. ISFETS ou CHEMFETS
C12Q 1/6837 - Couplage enzymatique ou biochimique d’acides nucléiques à une phase solide utilisant des réseaux de sondes ou des puces à sondes
C12Q 1/6825 - Détecteurs faisant intervenir la détection d’acides nucléiques
C12Q 1/6804 - Analyse d’acides nucléiques utilisant des immunogènes
C40B 20/04 - Identification des éléments d'une bibliothèque au moyen d'une étiquette, d'un marqueur ou d'un autre identificateur lisible ou détectable, p.ex. procédés de décodage
81.
HIGH SPEED SCANNING SYSTEMS FOR SUPER RESOLUTION IMAGING
Disclosed herein is a high throughput optical scanning system to generate super resolution images and methods of use. The optical scanning device and methods of use provided herein can allow high throughput scanning of a continuously moving object with a high resolution despite fluctuations in stage velocity. This can aid in high throughput scanning of a substrate, such as a biological chip comprising fluorophores. Also provided herein are improved optical relay systems and scanning optics.
G06T 7/70 - Détermination de la position ou de l'orientation des objets ou des caméras
G06T 3/40 - Changement d'échelle d'une image entière ou d'une partie d'image
H04N 3/08 - TRANSMISSION D'IMAGES, p.ex. TÉLÉVISION - Détails des dispositifs de balayage des systèmes de télévision; Leur combinaison avec la production des tensions d'alimentation par des moyens optiques-mécaniques uniquement comportant un réflecteur mobile
Optical analytical devices and their methods of use are provided. The devices are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The devices include optical waveguides for illumination of the optical reactions. The devices further provide for the efficient coupling of optical excitation energy from the waveguides to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices of the invention are well suited for miniaturization and high throughput.
G02B 6/024 - Fibres optiques avec revêtement avec des propriétés maintenant la polarisation
F21V 8/00 - Utilisation de guides de lumière, p.ex. dispositifs à fibres optiques, dans les dispositifs ou systèmes d'éclairage
G01N 21/77 - Systèmes dans lesquels le matériau est soumis à une réaction chimique, le progrès ou le résultat de la réaction étant analysé en observant l'effet sur un réactif chimique
G02B 6/12 - OPTIQUE ÉLÉMENTS, SYSTÈMES OU APPAREILS OPTIQUES - Détails de structure de dispositions comprenant des guides de lumière et d'autres éléments optiques, p.ex. des moyens de couplage du type guide d'ondes optiques du genre à circuit intégré
G02F 1/365 - Optique non linéaire dans une structure de guide d'ondes optique
G02B 6/10 - OPTIQUE ÉLÉMENTS, SYSTÈMES OU APPAREILS OPTIQUES - Détails de structure de dispositions comprenant des guides de lumière et d'autres éléments optiques, p.ex. des moyens de couplage du type guide d'ondes optiques
G02B 6/122 - Elements optiques de base, p.ex. voies de guidage de la lumière
B82Y 15/00 - Nanotechnologie pour l’interaction, la détection ou l'actionnement, p.ex. points quantiques comme marqueurs en dosages protéiques ou moteurs moléculaires
B82Y 20/00 - Nano-optique, p.ex. optique quantique ou cristaux photoniques
G02B 23/24 - Instruments pour regarder l'intérieur de corps creux, p.ex. endoscopes à fibres
Sets of compounds bearing detectably different groups of labels are provided. Typically, different compounds bear different numbers of a single type of label and are thus distinguishable by the amplitude of signal produced by the label. The compounds are assembled from label components and protein cores to facilitate modular production of the compounds. In compounds containing two or more proteins, the proteins are typically covalently linked. Useful sets of compounds include sets of labeled nucleotide analogs, particularly dye-label nucleotide analogs that include tetravalent biotin-binding protein cores.
Methods, devices, and systems for performing intermittent detection during analytical reactions are provided. Such methods facilitate collection of reaction data from disparate reaction times. Further, such methods are useful for reducing photo-induced damage of one or more reactants in an illuminated analytical reaction at a given reaction time. In preferred embodiments, the reaction mixture is subjected to at least one illuminated and non-illuminated period and allowed to proceed such that the time in which the reaction mixture is illuminated is less than a photo-induced damage threshold period.
Provided are compositions, methods and systems for determining the sequence of a template nucleic acid using a polymerase-based, sequencing-by-binding procedure. An examination step involves monitoring the interaction between a polymerase and template nucleic acid in the presence of one or more nucleotides. Identity of the next correct nucleotide in the sequence is determined without incorporation of any nucleotide into the structure of the primer by formation of a phosphodiester bond. An optional incorporation step can be used after the examination step to extend the primer by one or more nucleotides, thereby incrementing the template nucleotides that can be examined in a subsequent examination step. The sequencing-by-binding procedure does not require the use of labeled nucleotides or polymerases, but optionally can employ these reagents.
G01N 33/50 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique
Disclosed herein, inter alia, are methods for modifying a nucleotide, for example including reacting a nucleotide having a 3′-O-oxime moiety such as
Disclosed herein, inter alia, are methods for modifying a nucleotide, for example including reacting a nucleotide having a 3′-O-oxime moiety such as
Disclosed herein, inter alia, are methods for modifying a nucleotide, for example including reacting a nucleotide having a 3′-O-oxime moiety such as
with a reagent having an —ONH2 moiety to produce a nucleotide having a 3′-O—NH2 moiety such as
Disclosed herein, inter alia, are methods for modifying a nucleotide, for example including reacting a nucleotide having a 3′-O-oxime moiety such as
with a reagent having an —ONH2 moiety to produce a nucleotide having a 3′-O—NH2 moiety such as
Disclosed herein, inter alia, are methods for modifying a nucleotide, for example including reacting a nucleotide having a 3′-O-oxime moiety such as
with a reagent having an —ONH2 moiety to produce a nucleotide having a 3′-O—NH2 moiety such as
wherein the reagent having the —ONH2 moiety further comprises alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, or (heteroalicyclyl)alkyl.
A method of characterizing a nucleic acid that includes steps of (a) contacting a primer-template nucleic acid hybrid with a polymerase and a mixture of nucleotides to produce an extended primer hybrid and to form a stabilized ternary complex including the extended primer hybrid, the polymerase and a nucleotide cognate of the next base in the template, wherein the mixture contains nucleotide cognates of four different base types, wherein the nucleotide cognate of the first base type has a reversible terminator, and wherein nucleotide cognates of the second, third and fourth base types are extendable; (b) detecting the stabilized ternary complex to distinguish the next base from other base types in the template; and (c) determining the presence of a base multiplet in the template nucleic acid, the base multiplet including the first base type followed by the next base.
A method for identifying a nucleic acid template that include (a) providing a plurality of primer-template hybrids, wherein a first hybrid of the plurality includes a first template hybridized to a first primer, and wherein a second hybrid of the plurality includes a second template hybridized to a second primer, the second primer having a ternary complex inhibitor moiety at the 3′ end; (b) delivering polymerases and nucleotides to the plurality, whereby the first hybrid binds a polymerase and nucleotide to form a stabilized ternary complex and whereby the second hybrid does not bind a polymerase and nucleotide to form a stabilized ternary complex; and (c) detecting the stabilized ternary complex to identify the first template.
Methods of producing substrates having selected active chemical regions by employing elements of the substrates in assisting the localization of active chemical groups in desired regions of the substrate. The methods may include optical, chemical and/or mechanical processes for the deposition, removal, activation and/or deactivation of chemical groups in selected regions of the substrate to provide selective active regions of the substrate.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
05 - Produits pharmaceutiques, vétérinaires et hygièniques
09 - Appareils et instruments scientifiques et électriques
10 - Appareils et instruments médicaux
Produits et services
Assays and reagents for scientific or research use; Reagent
kits for preparation or performance of single molecule
assays for scientific or research use; Reagent kits
comprising components for single molecule assays for
scientific or research use. Medical diagnostic assays and reagents. Laboratory instruments for scientific research, namely,
optical detectors for genetic sequencing and biochemical
analysis; analytical array chips; optical array chips for
genetic sequencing and biochemical analysis; downloadable
computer software for the analysis of biological data. Medical diagnostic instruments; analytical array chips.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
05 - Produits pharmaceutiques, vétérinaires et hygièniques
09 - Appareils et instruments scientifiques et électriques
10 - Appareils et instruments médicaux
Produits et services
Assays and reagents for use in biochemical analysis for
scientific or research use. Assays and reagents for medical diagnosis. Laboratory instruments for scientific research, namely
optical detectors for genetic sequencing and biochemical
analysis; downloadable computer software for the analysis of
biological data; analytical array chips; optical array chips
for genetic sequencing and biochemical analysis. Medical diagnostic instruments; medical analytical array
chips.
92.
SINGLE-MOLECULE NANOFET SEQUENCING SYSTEMS AND METHODS
Real time electronic sequencing devices, chips, and systems are described. Arrays of nanoFET devices are used to provide sequence information about a template nucleic acid in a polymerase-template complex bound to the nanoFET. The nanoFET devices typically have a source, a drain and a gate comprising a nanowire. A single polymerase enzyme complex comprising a polymerase enzyme complexed with the template nucleic acid is bound to the gate. The polymerase is bound to the gate non-covalently through a polymeric binding agent that has two strands, each strand interacting with the nanowire such that the polymerase is in a central location between the strands with the polymeric binding agent extending away from the polymerase complex along the nanowire in both directions.
B82Y 10/00 - Nanotechnologie pour le traitement, le stockage ou la transmission d’informations, p.ex. calcul quantique ou logique à un électron
B82Y 15/00 - Nanotechnologie pour l’interaction, la détection ou l'actionnement, p.ex. points quantiques comme marqueurs en dosages protéiques ou moteurs moléculaires
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
G01N 27/414 - Transistors à effet de champ sensibles aux ions ou chimiques, c. à d. ISFETS ou CHEMFETS
G11C 19/28 - Mémoires numériques dans lesquelles l'information est déplacée par échelons, p.ex. registres à décalage utilisant des éléments semi-conducteurs
H01L 29/06 - Corps semi-conducteurs caractérisés par les formes, les dimensions relatives, ou les dispositions des régions semi-conductrices
H01L 29/16 - Corps semi-conducteurs caractérisés par les matériaux dont ils sont constitués comprenant, mis à part les matériaux de dopage ou autres impuretés, seulement des éléments du groupe IV de la classification périodique, sous forme non combinée
93.
SIMULTANEOUS BACKGROUND REDUCTION AND COMPLEX STABILIZATION IN BINDING ASSAY WORKFLOWS
Method and apparatus to facilitate separation of solution-phase components surrounding an immobilized multicomponent complex while stabilizing association of the components within the complex. The technique can be used for reducing background signal arising from the presence of non-complexed components harboring detectable labels, thereby enhancing signal-to-background ratios and allowing enhanced detection of the multicomponent complex.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
05 - Produits pharmaceutiques, vétérinaires et hygièniques
09 - Appareils et instruments scientifiques et électriques
10 - Appareils et instruments médicaux
Produits et services
(1) Assays and reagents for scientific or research use; Reagent kits for preparation or performance of single molecule assays for scientific or research use; Reagent kits comprising components for single molecule assays for scientific or research use.
(2) Medical diagnostic assays and reagents.
(3) Laboratory instruments for scientific research, namely, optical detectors for genetic sequencing and biochemical analysis; analytical array chips; optical array chips for genetic sequencing and biochemical analysis; downloadable computer software for the analysis of biological data.
(4) Medical diagnostic instruments; analytical array chips.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
05 - Produits pharmaceutiques, vétérinaires et hygièniques
09 - Appareils et instruments scientifiques et électriques
10 - Appareils et instruments médicaux
Produits et services
Assays and reagents for scientific or research use; reagent kits for preparation or performance of single molecule assays for scientific or research use comprised of buffers, enzymes, reagents, nucleotides, chemical preparations and/or biological compounds; reagent kits comprising components in the nature of buffers, enzymes, reagents, nucleotides, chemical preparations and/or biological compounds that are used for single molecule assays for scientific or research use Assays and reagents for medical diagnosis for medical use laboratory instruments for scientific research, namely, optical detectors for genetic sequencing and biochemical analysis; analytical array chips for genetic sequencing and biochemical analysis; optical array chips for genetic sequencing and biochemical analysis; downloadable computer software for the analysis of biological data medical diagnostic instruments for clinical medical genetic sequencing and biochemical analysis and for the analysis of genes, molecules, DNA and RNA samples; analytical array chips for medical diagnostic purposes, excluding laboratory equipment array chips, for clinical medical genetic sequencing and biochemical analysis and for the analysis of genes, molecules, DNA and RNA samples
96.
TEMPERATURE CONTROL FOR ANALYSIS OF NUCLEIC ACIDS AND OTHER ANALYTES
Provided herein and methods and apparatuses for sequencing nucleic acids. For example, provided is an analytical detection apparatus, including (a) a stage configured to support a flow cell; (b) a detector configured to observe a detection channel of the flow cell when the flow cell is supported by the stage; (c) a plurality of fluid delivery channels, wherein each of the fluid delivery channels fluidically connects a reservoir to the detection channel of the flow cell; and (d) a first heater configured to heat the plurality of fluid delivery channels.
Compositions, methods, and systems are provided for fluorescent polymerase enzyme substrates comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Fluorescent polymerase enzyme substrates of the invention have a protein shield between the fluorescent dye moieties and nucleotide moieties of the polymerase enzyme substrate. The polymerase enzyme substrates have a nucleotide component and a dye component, each attached to a protein. The attachments can be covalent. The protein can, for example, prevent the direct interaction of the fluorescent dye moiety with the enzyme when carrying out nucleotide synthesis, preventing photodamage to the enzyme. The polymerase enzyme substrates of the invention can have multiple dyes and multiple nucleotide moieties.
C07H 21/04 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p.ex. acides nucléiques avec le désoxyribosyle comme radical saccharide
G01N 33/58 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des substances marquées
C07K 14/36 - Peptides ayant plus de 20 amino-acides; Gastrines; Somatostatines; Mélanotropines; Leurs dérivés provenant de bactéries provenant de Streptomyces (G)
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
C09B 23/08 - Colorants méthiniques ou polyméthiniques, p.ex. du type cyanine caractérisés par la chaîne méthinique contenant un nombre impair de groupes CH plus de trois groupes CH, p.ex. polycarbocyanines
C09B 69/10 - Colorants polymères; Produits de réactions de colorants avec des monomères ou avec des composés macromoléculaires
An analytical device including an optically opaque cladding, a sequencing layer including a substrate disposed below the cladding, and a waveguide assembly for receiving optical illumination and introducing illumination into the device. The illumination may be received from a top, a side edge, and a bottom of the device. The waveguide assembly may include a nanoscale aperture disposed in the substrate and extending through the cladding. The aperture defines a reaction cell for receiving a set of reactants. In various aspects, the device includes a sensor element and the illumination pathway is through the sensor element. Waveguides and illumination devices, such as plasmonic illumination devices, are also disclosed. Methods for forming and operating the devices are also disclosed.
B82Y 20/00 - Nano-optique, p.ex. optique quantique ou cristaux photoniques
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
G02B 6/122 - Elements optiques de base, p.ex. voies de guidage de la lumière
G01N 21/03 - Dispositions ou appareils pour faciliter la recherche optique - Détails de structure des cuvettes
G01N 21/75 - Systèmes dans lesquels le matériau est soumis à une réaction chimique, le progrès ou le résultat de la réaction étant analysé
G01N 21/77 - Systèmes dans lesquels le matériau est soumis à une réaction chimique, le progrès ou le résultat de la réaction étant analysé en observant l'effet sur un réactif chimique
C12Q 1/6825 - Détecteurs faisant intervenir la détection d’acides nucléiques
Method and composition for identifying cognate nucleotides in a Sequencing By Binding™ procedure, wherein one or more labeled nucleotides are detected in ternary complexes but never incorporated. Labeled nucleotides can be incorporable nucleotides that contact preformed blocked primed template nucleic acids. Alternatively, labeled nucleotides are labeled non-incorporable nucleotides. Labeled nucleotides, including labeled non-incorporable nucleotides, can be detected in ternary complexes in the same reaction mixture that incorporates a reversible terminator nucleotide to create a blocked primed template nucleic acid. Detection of ternary complexes can take place in the presence of a catalytic metal ion.
C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p.ex. pour test de réaction en chaîne par polymérase [PCR]
C07H 21/02 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p.ex. acides nucléiques avec le ribosyle comme radical saccharide
C07H 99/00 - Matière non prévue dans les autres groupes de la présente sous-classe
C07H 21/04 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p.ex. acides nucléiques avec le désoxyribosyle comme radical saccharide
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
A method for identifying target alleles, that includes steps of (a) forming a plurality of stabilized ternary complexes at a plurality of features on an array, wherein the stabilized ternary complexes each has a polymerase, a template nucleic acid having a target allele of a locus, a primer hybridized to the locus, and a next correct nucleotide having a cognate in the locus, wherein either (i) the primer is an allele-specific primer having a 3′ nucleotide that is a cognate nucleotide for the target allele, or (ii) the primer is a locus-specific primer and the next correct nucleotide hybridizes to the target allele; and (b) detecting stabilized ternary complexes at the features, thereby identifying the target alleles.
C12Q 1/6853 - Réactions d’amplification d’acides nucléiques utilisant des amorces ou des matrices modifiées
C12Q 1/6886 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p.ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique pour le cancer
C12Q 1/6827 - Tests d’hybridation pour la détection de mutation ou de polymorphisme
C12Q 1/686 - Réaction en chaine par polymérase [PCR]
C12Q 1/6883 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p.ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique
C12Q 1/6872 - Méthodes de séquençage faisant intervenir la spectrométrie de masse
