A method is provided for detecting a hybridisation indication indicative of an amount of hybridisation between a set of probe biomolecules provided at a reaction site and a set of sample biomolecules. The method includes supplying the set of sample biomolecules to the reaction site comprising the set of probe biomolecules. The reaction site is heated to cause dissociation of probe/sample-biomolecule-pairs previously hybridized when the set of sample biomolecules were provided to the reaction site. The hybridisation indication is generated based on detecting the dissociation of the probe/sample-biomolecule pairs caused by heating the reaction site.
The present invention relates to methods for the high fidelity synthesis of oligonucleotides and polynucleotides on a solid surface. In particular, the invention relates to methods of synthesising oligonucleotides, polynucleotides, and doublestranded polynucleotides/nucleic acids, such as DNA and XNA, wherein the process comprises thermally controlled deprotection steps at the 5′-OH of previously coupled nucleosides or nucleotides at selected sites on the surface of the substrate.
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 1/00 - Procédés de préparation des dérivés du sucre
C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN
C12Q 1/6811 - Méthodes de sélection pour la production ou l’élaboration d’oligonucléotides spécifiques cibles ou de molécules de liaison
4.
REACTION DURATION CONTROL FOR REACTION PERFORMED ON BIOMOLECULE SAMPLES
A reaction duration is controlled for a reaction performed on biomolecule samples on an apparatus comprising temperature control circuitry to independently control temperature for respective reaction sites. A higher temperature is applied to a first subset of reaction sites and a lower temperature is applied to a second subset of reaction sites. The reaction is started at a first time and ended at a second time when the reaction duration has elapsed since the first time. The reaction duration is selected depending on an analysis of dependence of an error rate on the reaction duration, the error rate comprising a rate of errors caused by an unreacted fraction of biomolecule samples at the first subset of reaction sites that remain unreacted at the second time and a reacted fraction of biomolecule samples at the second subset of reaction sites that have already reacted at the second time.
09 - Appareils et instruments scientifiques et électriques
40 - Traitement de matériaux; recyclage, purification de l'air et traitement de l'eau
Produits et services
Scientific apparatus, laboratory instruments, parts and fittings therefor; apparatus for synthesis of nucleic acids and kits, cartridges and components for use therewith; computer software for use in controlling the operation of scientific apparatus and laboratory instruments. Custom manufacture for others of nucleic acids for use in medicine, research and science; consultancy services connected with the aforesaid.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
09 - Appareils et instruments scientifiques et électriques
35 - Publicité; Affaires commerciales
37 - Services de construction; extraction minière; installation et réparation
40 - Traitement de matériaux; recyclage, purification de l'air et traitement de l'eau
41 - Éducation, divertissements, activités sportives et culturelles
42 - Services scientifiques, technologiques et industriels, recherche et conception
Produits et services
Chemicals for use in science and industry; reagents for use
in DNA synthesis; buffers solutions for use in the
analytical chemistry or for scientific purposes; chemical
preparations for use as solvents; highly-purified water;
phosphoramidites. Scientific apparatus, laboratory instruments, parts and
fittings therefor; apparatus for synthesis of nucleic acids
and kits, cartridges and components for use therewith;
computer software for use in controlling the operation of
scientific apparatus and laboratory instruments. Online retail services connected with the sale of chemicals
for use in science and industry, reagents for use in DNA
synthesis, buffers, solvents, highly-purified water,
phosphoramidites, scientific apparatus, laboratory
instruments, parts and fittings therefor, apparatus for
synthesis of nucleic acids, kits, cartridges and components
for use therewith, computer software for use in controlling
the operation of scientific apparatus and laboratory
instruments. Installation, repair, servicing and maintenance of
scientific apparatus and laboratory instruments. Custom manufacture for others of nucleic acids for use in
medicine, research and science; consultancy services
connected with the aforesaid. Education, tuition and training; organising seminars,
webinars, conferences and workshops; all the aforesaid
concerning scientific apparatus, laboratory instruments and
in vitro synthesis of nucleic acids. Scientific research and design services, all connected with
the selection, design, manufacture and characterisation of
synthetic nucleic acids; software as a service (SaaS), and
platform as a service (PaaS), relating to the selection,
design, manufacture and characterisation of synthetic
nucleic acids.
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
09 - Appareils et instruments scientifiques et électriques
35 - Publicité; Affaires commerciales
37 - Services de construction; extraction minière; installation et réparation
40 - Traitement de matériaux; recyclage, purification de l'air et traitement de l'eau
41 - Éducation, divertissements, activités sportives et culturelles
42 - Services scientifiques, technologiques et industriels, recherche et conception
Produits et services
Chemicals for use in science and industry; reagents for use in DNA synthesis; buffers for use in analytic chemistry; aromatic solvents for industrial and commercial use; highly-purified water for industrial purposes; phosphoramidites for use in science Scientific apparatus for DNA synthesis, laboratory instruments for DNA synthesis not for medical purposes, and parts and fittings therefor; apparatus for synthesis of nucleic acids for laboratory use and kits comprising solid phase extraction cartridges for purification of DNA for laboratory use; downloadable computer software for use in controlling the operation of scientific apparatus and laboratory instruments Online retail store services featuring chemicals for use in science and industry, reagents for use in DNA synthesis, buffers, solvents, highly-purified water, phosphoramidites, scientific apparatus, laboratory instruments, parts and fittings therefor, apparatus for synthesis of nucleic acids, kits, cartridges and components for use therewith, and computer software for use in controlling the operation of scientific apparatus and laboratory instruments Installation, repair and maintenance of DNA synthesizers Custom manufacture for others of nucleic acids for use in medicine, research and science; consultancy services connected with the aforesaid Education in the nature of seminars, conferences, workshops, training and providing non-downloadable webinars in the field of scientific apparatus and laboratory instruments for synthesis of DNA, and in vitro synthesis of nucleic acids Scientific research in the field of selection, manufacture and characterization of synthetic nucleic acids; Software as a service (SaaS) featuring software for use in the selection, design, manufacture and characterization of synthetic nucleic acids; platform as a service (PaaS) featuring software for use in the selection, design, manufacture and characterization of synthetic nucleic acids
01 - Produits chimiques destinés à l'industrie, aux sciences ainsi qu'à l'agriculture
09 - Appareils et instruments scientifiques et électriques
40 - Traitement de matériaux; recyclage, purification de l'air et traitement de l'eau
42 - Services scientifiques, technologiques et industriels, recherche et conception
Produits et services
Reagents for use in DNA synthesis; buffers; solvents; highly-purified water; phosphoramidites. Apparatus for synthesis of nucleic acids and kits, cartridges and components for use therewith; computer software for use in controlling the operation of scientific apparatus and laboratory instruments for synthesising acids. Custom manufacture for others of nucleic acids for use in medicine, research and science; consultancy services connected with the aforesaid. Scientific research and design services, all connected with the selection, design, manufacture and characterisation of synthetic nucleic acids; Software as a service (SaaS), and Platform as a service (PaaS), relating to the selection, design, manufacture and characterisation of synthetic nucleic acids.
9.
Accessing data storage provided using double-stranded nucleic acid molecules
Data storage is provided using double-stranded nucleic acid molecules provided on a thermal control device comprising a plurality of sites and temperature control circuitry to independently control a temperature of each of the plurality of sites. The temperature control circuitry, controls the site temperatures to provide a different temperature at a target site compared to other sites of the plurality of sites. The different temperatures at the target site and the other sites provide a greater probability of a read or write operation acting on the target site compared to the other sites. The temperature-based addressing helps to increase physical storage density.
A method for identifying a group of single-stranded oligonucleotides for self-assembly into a double-stranded polynucleotide, the group comprising a plurality of overlapping complementary oligonucleotides, wherein each overlap between complementary oligonucleotides is selected to have a melting temperature (Tm) that differs from the melting temperatures of all other overlapping complementary oligonucleotides in the group.
Data storage is provided using double-stranded nucleic acid molecules (70) provided on a thermal control device (52) comprising a plurality of sites (54) and temperature control circuitry (56) to independently control a temperature of each of the plurality of sites. The temperature control circuitry (56), controls the site temperatures to provide a different temperature at a target site compared to other sites of the plurality of sites. The different temperatures at the target site and the other sites provide a greater probability of a read or write operation acting on the target site compared to the other sites. The temperature-based addressing helps to increase physical storage density.
The present invention relates to methods for the high fidelity synthesis of oligonucleotides and polynucleotides on a solid surface. In particular, the invention relates to methods of synthesising oligonucleotides, polynucleotides, and doublestranded polynucleotides/nucleic acids, such as DNA and XNA, wherein the process comprises thermally controlled deprotection steps at the 5'-OH of previously coupled nucleosides or nucleotides at selected sites on the surface of the substrate.
C07H 1/00 - Procédés de préparation des dérivés du sucre
C07H 19/073 - Radicaux pyrimidine avec un désoxy-2 ribosyle comme radical saccharide
C07H 21/00 - 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
C07H 23/00 - Composés contenant du bore, du silicium ou un métal, p. ex. chélates ou vitamine B12
C40B 10/00 - Évolution moléculaire dirigée des macromolécules, p. ex. ARN, ADN ou protéines
13.
ERROR DETECTION DURING HYBRIDISATION OF TARGET DOUBLE-STRANDED NUCLEIC ACID
FEEE comprise at least one erroneous hybridised fragment, and discarding at least part of the erroneous fragment to exclude it from a subsequent further hybridisation step. By detecting and removing erroneous fragments throughout a staged and controlled hybridisation process, erroneous fragments are prevented from diluting the pool of error-free fragments at each hybridisation step, to improve yield.
The present invention relates to chemical linkers and protecting groups, compounds and compositions containing the chemical linkers or protecting groups, and intermediates and processes that can be used to prepare them. The chemical linkers and protecting groups are based on pyrrolidine and piperidine activating groups, which undergo intramolecular cyclisation upon heating with release of carbon dioxide, thereby releasing the organic compound from a substrate. In particular, those chemical linkers and protecting groups are useful in the solid phase synthesis of oligonucleotides according to the following representative schemes.
C07D 207/09 - Radicaux substitués par des atomes d'azote ne faisant pas partie d'un radical nitro
C07D 211/26 - Composés hétérocycliques contenant des cycles pyridiques hydrogénés, non condensés avec d'autres cycles avec uniquement des atomes d'hydrogène et de carbone liés directement à l'atome d'azote du cycle ne comportant pas de liaison double entre chaînons cycliques ou entre chaînons cycliques et chaînons non cycliques avec des radicaux hydrocarbonés ou des radicaux hydrocarbonés substitués, liés directement aux atomes de carbone du cycle avec des radicaux hydrocarbonés substitués liés aux atomes de carbone du cycle avec des radicaux hydrocarbonés, substitués par des atomes d'azote
C07H 1/00 - Procédés de préparation des dérivés du sucre
C07H 19/073 - Radicaux pyrimidine avec un désoxy-2 ribosyle comme radical saccharide
C07H 19/173 - Radicaux purine avec un désoxy-2 ribosyle comme radical saccharide
C07H 21/00 - 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
C07H 23/00 - Composés contenant du bore, du silicium ou un métal, p. ex. chélates ou vitamine B12
15.
METHOD FOR PRODUCING DOUBLE STRANDED POLYNUCLEOTIDES BASED ON OLIGONUCLEOTIDES WITH SELECTED AND DIFFERENT MELTING TEMPERATURES
A method for identifying a group of single-stranded oligonucleotides for self-assembly into a double-stranded polynucleotide, the group comprising a plurality of overlapping complementary oligonucleotides, wherein each overlap between complementary oligonucleotides is selected to have a melting temperature (Tm) that differs from the melting temperatures of all other overlapping complementary oligonucleotides in the group.
A temperature control device (2) comprises a number of active thermal sites (6) disposed at respective locations on a substrate (10), each comprising a heating element (13) for applying a variable amount of heat to a corresponding site of a medium and a thermal insulation layer (16) disposed between the heating element and the substrate. At least one passive thermal region (8) is disposed between the active thermal sites (6) on the substrate (10), each passive thermal region (8) comprising a thermal conduction layer (18) for conducting heat from a corresponding portion of the medium to the substrate (10). The thermal conduction layer (18) has a lower thermal resistance in a direction perpendicular to a plane of the substrate (10) than the thermal insulation layer (16). This enables precise control over both heating and cooling of individual sites in a flowing fluid, for example.
A technique for measuring the resistance of a resistive element (4) in the presence of a series diode (10) is provided. By supplying three different currents I1, l2, l3 and measuring corresponding voltages V1, V2, V3 across the resistive element (4) and diode (10), the voltages can be combined to at least partially eliminate an error in the measured resistance of the resistive element (4) caused by a voltage drop across the diode (10). A technique for current control in an array of resistive elements (60) is also described in which a column of resistive elements (60) is provided with two or more current sources (70, 72) switched so that while one current source (70) is providing current to the column line (66) corresponding to a selected resistive element (60), another current source (72) has its amount of current adjusted.
G01R 1/20 - Modifications des éléments électriques fondamentaux en vue de leur utilisation dans des appareils de mesures électriquesCombinaisons structurelles de ces éléments avec ces appareils
G01K 17/16 - Indication directe du produit de l'écoulement par la différence de température en utilisant des moyens électriques pour les deux mesures
A controller for a thermo-electric cooler is disclosed. The controller comprises a current source for providing current for driving the thermo-electric cooler and a plurality of voltage supply connections for providing a plurality of different voltages for driving current controlled by the current source through the thermo-electric cooler. Voltage selection circuitry is provided for selecting a voltage from the plurality of different voltages, when connected, and for applying the voltage selected to the thermo-electric cooler. When selecting the voltage from the plurality of different voltages, the voltage selection circuitry is configured to select the voltage that, when compared to the other voltages of the plurality of voltages, minimises a potential difference across the current source.
F25B 21/00 - Machines, installations ou systèmes utilisant des effets électriques ou magnétiques
F25B 21/02 - Machines, installations ou systèmes utilisant des effets électriques ou magnétiques utilisant l'effet PeltierMachines, installations ou systèmes utilisant des effets électriques ou magnétiques utilisant l'effet Nernst-Ettinghausen
19.
Method of selectively masking one or more sites on a surface and a method of synthesising an array of molecules
A method of creating a mask on a surface of a substrate is disclosed. The substrate comprises a plurality of spaced heating elements on or proximal to the surface. The method comprises applying a layer of masking material to the surface and employing the heating elements to apply energy to a phase change in the masking material at the selected sites such that it adheres to the surface or can be displaced from the surface to mask or unmask the selected sites respectively. A method of synthesising an array of molecules, an apparatus for selectively masking one or more sites on a surface and a semi-conductor chip that uses micro-heaters to modulate a masking layer on areas of the chip surface.
B01J 19/00 - Procédés chimiques, physiques ou physico-chimiques en généralAppareils appropriés
C40B 50/18 - Synthèse en phase solide, c.-à-d. dans laquelle au moins un bloc servant à créer la bibliothèque est lié à un support solide au cours de la création de la bibliothèqueProcédés particuliers de clivage à partir du support solide utilisant un procédé particulier d'ancrage au support solide
C40B 60/14 - Appareils spécialement adaptés à une utilisation en chimie combinatoire ou avec des bibliothèques pour créer des bibliothèques
20.
A METHOD OF SELECTIVELY MASKING ONE OR MORE SITES ON A SURFACE AND A METHOD OF SYNTHESISING AN ARRAY OF MOLECULES
A method of creating a mask on a surface of a substrate is disclosed. The substrate comprises a plurality of spaced heating elements on or proximal to the surface. The method comprises applying a layer of masking material to the surface and employing the heating elements to apply energy to the masking material at selected sites, whereby the applied energy brings about a phase change in the masking material at the selected sites such that it adheres to the surface or can be displaced from the surface to mask or unmask the selected sites respectively. A method of synthesising an array of molecules, an apparatus for selectively masking one or more sites on a surface and a semiconductor chip that uses micro-heaters to modulate a masking layer on areas of the chip surface.
B01J 19/00 - Procédés chimiques, physiques ou physico-chimiques en généralAppareils appropriés
C40B 50/18 - Synthèse en phase solide, c.-à-d. dans laquelle au moins un bloc servant à créer la bibliothèque est lié à un support solide au cours de la création de la bibliothèqueProcédés particuliers de clivage à partir du support solide utilisant un procédé particulier d'ancrage au support solide
C40B 60/14 - Appareils spécialement adaptés à une utilisation en chimie combinatoire ou avec des bibliothèques pour créer des bibliothèques
The present invention relates to methods for the high fidelity synthesis of oligonucleotides and polynucleotides on a solid surface. In particular, the invention relates to methods of synthesising oligonucleotides, polynucleotides, and doublestranded polynucleotides/nucleic acids, such as DNA and XNA, wherein the process comprises thermally controlled deprotection steps at the 5'-OH of previously coupled nucleosides or nucleotides at selected sites on the surface of the substrate.
C07H 1/00 - Procédés de préparation des dérivés du sucre
C07H 19/073 - Radicaux pyrimidine avec un désoxy-2 ribosyle comme radical saccharide
C07H 21/00 - 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
C07H 23/00 - Composés contenant du bore, du silicium ou un métal, p. ex. chélates ou vitamine B12
C40B 10/00 - Évolution moléculaire dirigée des macromolécules, p. ex. ARN, ADN ou protéines
A temperature control device (2) comprises a number of active thermal sites (6) disposed at respective locations on a substrate (10), each comprising a heating element (13) for applying a variable amount of heat to a corresponding site of a medium and a thermal insulation layer (16) disposed between the heating element and the substrate. At least one passive thermal region (8) is disposed between the active thermal sites (6) on the substrate (10), each passive thermal region (8) comprising a thermal conduction layer (18) for conducting heat from a corresponding portion of the medium to the substrate (10). The thermal conduction layer (18) has a lower thermal resistance in a direction perpendicular to a plane of the substrate (10) than the thermal insulation layer (16). This enables precise control over both heating and cooling of individual sites in a flowing fluid, for example.
A series of hybridisations is performed for forming a target double-stranded nucleic acid from initial fragments, where each further hybridisation step hybridises the direct products of a pair of earlier hybridisation steps. For at least one further hybridisation step HF, both of the corresponding pair of earlier hybridisation steps HE comprise an error-detecting type of hybridisation step, which includes an error detecting operation to detect whether the hybridised fragments formed in the error-detecting type of hybridisation step HE comprise at least one erroneous hybridised fragment, and discarding at least part of the erroneous fragment to exclude it from a subsequent further hybridisation step. By detecting and removing erroneous fragments throughout a staged and controlled hybridisation process, erroneous fragments are prevented from diluting the pool of error-free fragments at each hybridisation step, to improve yield.
Data storage is provided using double-stranded nucleic acid molecules (70) provided on a thermal control device (52) comprising a plurality of sites (54) and temperature control circuitry (56) to independently control a temperature of each of the plurality of sites. The temperature control circuitry (56), controls the site temperatures to provide a different temperature at a target site compared to other sites of the plurality of sites. The different temperatures at the target site and the other sites provide a greater probability of a read or write operation acting on the target site compared to the other sites. The temperature-based addressing helps to increase physical storage density.
