ARTICLES ALSO ON IT ANGEORDETEN LOCATED MOLECULES AND MANUFACTURING PROCESSES FOR IT

MICROARRAY SYNTHESIS INSTRUMENT AND METHOD

During the light illumination period of a monomer addition cycle in synthesizing an DNA microarray, undesirable reflections of illumination light from various interfaces that the illumination light passes through near the synthesis surface of the substrate may reduce the light dark contrast, and negatively affect the precision and resolution of the microarray synthesis. The present invention provides an flow cell that reduces the undesired reflections by constructing certain flow cell structures with materials that have similar refractive indexes as that of the solution that is in the oligomer synthesis chamber during the illumination period and/or constructing certain flow cell structures or covering the structures with a layer of a material that has a high extinction coefficient.

Articles Having Localized Molecules Disposed Thereon and Methods of Producing Same

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.

MICROARRAY SYNTHESIS INSTRUMENT AND METHOD

During the light illumination period of a monomer addition cycle in synthesizing an DNA microarray, undesirable reflections of illumination light from various interfaces that the illumination light passes through near the synthesis surface of the substrate may reduce the light dark contrast, and negatively affect the precision and resolution of the microarray synthesis. The present invention provides an flow cell that reduces the undesired reflections by constructing certain flow cell structures with materials that have similar refractive indexes as that of the solution that is in the oligomer synthesis chamber during the illumination period and/or constructing certain flow cell structures or covering the structures with a layer of a material that has a high extinction coefficient.

Self-encoding sensor with microspheres

A microsphere-based analytic chemistry system is disclosed in which self-encoding microspheres having distinct characteristic optical response signatures to specific target analytes may be mixed together while the ability is retained to identify the sensor type and location of each sensor in a random dispersion of large numbers of such sensors in a sensor array using an optically interrogatable encoding scheme. An optical fiber bundle sensor is also disclosed in which individual microsphere sensors are disposed in microwells at a distal end of the fiber bundle and are optically coupled to discrete fibers or groups of fibers within the bundle. The identities of the individual sensors in the array are self-encoded by exposing the array to a reference analyte while illuminating the array with excitation light energy. A single sensor array may carry thousands of discrete sensing elements whose combined signal provides for substantial improvements in sensor detection limits, response times and ...

DECODING OF MATRIX SENSORS WITH MICROSPHERES

Articles having localized molecules disposed thereon and methods of producing same

Self-encoding sensor with microspheres

SELF-ENCODING SENSOR WITH MICROSPHERES

A microsphere-based analytic chemistry system is disclosed in which self- encoding microspheres having distinct characteristic optical response signatures to specific target analytes may be mixed together while the ability is retained to identify the sensor type and location of each sensor in a random dispersion of large numbers of such sensors in a sensor array using an optically interrogatable encoding scheme. An optical fiber bundle sensor is also disclosed in which individual microsphere sensors are disposed in microwells at a distal end of the fiber bundle and are optically coupled to discrete fibers or groups of fibers within the bundle. The identities of the individual sensors in the array are self-encoded by exposing the array to a reference analyte while illuminating the array with excitation light energy. A single sensor array may carry thousands of discrete sensing elements whose combined signal provides for substantial improvements in sensor detection limits, response times ...

ARTICLES HAVING LOCALIZED MOLECULES DISPOSED THEREON AND METHODS OF PRODUCING SAME

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.

SELF-ENCODING SENSOR WITH MICROSPHERES

L'invention concerne un système de chimie analytique à microsphères dans lequel des microsphères d'auto-codage, présentant différentes signatures de réponse optique caractéristiques en fonction de cibles spécifiques, peuvent être mélangées tout en permettant d'identifier le type de capteur et l'emplacement de chaque capteur dans la dispersion aléatoire d'un grand nombre de capteurs dans un réseau de capteurs, grâce à un système de codage à interrogation optique. L'invention concerne également un capteur à faisceau de fibres optiques dans lequel des capteurs à microsphères individuels sont placés dans des micropuits à une extrémité distale du faisceau de fibres optiques et sont optiquement couplés à des fibres discrètes ou à des groupes de fibres discrètes du faisceau. L'identité des capteurs individuels du réseau est auto-codée par exposition du réseau à un analyte de référence tout en l'éclairant à l'aide d'énergie d'excitation lumineuse. Un seul réseau de capteurs peut comporter des milliers ...

DECODING OF ARRAY SENSORS WITH MICROSPHERES

The invention relates to compositions and methods for decoding microsphere array sensors.

Manufacturing a flowcell with a planar waveguide

Provided in one example is a method of manufacturing a flowcell that includes: forming a core layer, the core layer disposed between a substrate and a nanowell layer, the nanowell layer having nanowells to receive a sample, the core layer having a higher refractive index than the substrate and the nanowell layer; and forming a grating to couple light to the core layer.

"SELF - ENCODING SENSOR WITH MICROSPHERES "

A microsphere-based analytic chemistry system is disclosed in which self-encoding microspheres having distinct characteristic optical response signatures to specific target analytes may be mixed together while the ability is retained to identify the sensor type and location of each sensor in a random dispersion of large numbers of such sensors in a sensor array using an optically interrogatable encoding scheme. An optical fiber bundle sensor is also disclosed in which individual microsphere sensors are disposed in microwells at a distal end of the fiber bundle and are optically coupled to discrete fibers or groups of fibers within the bundle. The identities of the individual sensors in the array are self-encoded by exposing the array to a reference analyte while illuminating the array with excitation light energy. A single sensor array may carry thousands of discrete sensing elements whose combined signal provides for substantial improvements in sensor detection limits, response times and ...

MICROARRAY SYNTHESIS INSTRUMENT AND METHOD

Manufacturing a flowcell with a planar waveguide

Provided in one example is a method of manufacturing a flowcell that includes: forming a core layer, the core layer disposed between a substrate and a nanowell layer, the nanowell layer having nanowells to receive a sample, the core layer having a higher refractive index than the substrate and the nanowell layer; and forming a grating to couple light to the core layer.

Decoding of array sensors with microspheres

ARTICLES HAVING LOCALIZED MOLECULES DISPOSED THEREON AND METHODS OF PRODUCING SAME

Synthesis of arrays of oligonucleotides and other chain molecules

Synthesis of arrays of chain molecules, such as oligonucleotides, in large quantities can be carried out utilizing projection onto an active substrate of a magnified image of a light emitting object array having selectable regions of light and dark areas forming a pattern. Projection optics formed entirely of mirrors are used to receive the light emitted from the object array and image the pattern of the array onto the active surface of the substrate. The mirrors in the projection optics include a first, concave mirror, a second, convex mirror, a third, concave mirror, and a fourth, convex mirror, each receiving the beam of light in turn, with the light reflected from the fourth mirror being imaged onto the active surface of the substrate with an image area greater than that of the original light emitting array.

DECODING OF ARRAY SENSORS WITH MICROSPHERES

The invention relates to compositions and methods for decoding microsphere array sensors.

MANUFACTURING A FLOWCELL WITH A PLANAR WAVEGUIDE

Provided in one example is a method of manufacturing a flowcell that includes: forming a core layer, the core layer disposed between a substrate and a nanowell layer, the nanowell layer having nanowells to receive a sample, the core layer having a higher refractive index than the substrate and the nanowell layer; and forming a grating to couple light to the core layer.

MANUFACTURING A FLOWCELL WITH A PLANAR WAVEGUIDE

Articles having localized molecules disposed thereon and methods of producing same

Microarray synthesis instrument and method

MICROARRAY SYNTHESIS INSTRUMENT AND METHOD

During the light illumination period of a monomer addition cycle in synthesizing an DNA microarray, undesirable reflections of illumination light from various interfaces that the illumination light passes through near the synthesis surface of the substrate may reduce the light dark contrast, and negatively affect the precision and resolution of the microarray synthesis. The present invention provides an flow cell that reduces the undesired reflections by constructing certain flow cell structures with materials that have similar refractive indexes as that of the solution that is in the oligomer synthesis chamber during the illumination period and/or constructing certain flow cell structures or covering the structures with a layer of a material that has a high extinction coefficient.

ARTICLES HAVING LOCALIZED MOLECULES DISPOSED THEREON AND METHODS OF PRODUCING SAME

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.

Articles having localized molecules disposed thereon and methods of producing same

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.

CONTROLLED ALTERATION OF PORES USING FLUID FLOW AND FABRICATION OF ARTICLES THEREBY

The invention relates to microscopic structures and methods of making and using the structures. A method of forming a microscopic structure of a material includes obtaining a solution (310) containing the material, establishing a flowing stream of the solution (310) in a capillary (104), wherein the capillary (104) has an inner dimension that is smaller than about 300 micrometers, and maintaining the stream until a layer is built up along an inner wall of the capillary (104) from material deposited from the flowing stream, thereby forming a microscopic structure.

ARTICLES HAVING LOCALIZED MOLECULES DISPOSED THEREON AND METHODS OF PRODUCING SAME

DECODING OF ARRAY SENSORS WITH MICROSPHERES

The invention relates to compositions and methods for decoding microsphere array sensors.

DECODING OF ARRAY SENSORS WITH MICROSPHERES

The invention relates to compositions and methods for decoding microsphere array sensors.

SYNTHESIS OF ARRAYS OF OLIGONUCLEOTIDES AND OTHER CHAIN MOLECULES

Synthesis of arrays of chain molecules, such as oligonucleotides, in large quantities can be carried out utilizing projection onto an active substrate of a magnified image of a light emitting object array having selectable regions of light and dark areas forming a pattern. Projection optics formed entirely of mirrors are used to receive the light emitted from the object array and image the pattern of the array onto the active surface of the substrate. The mirrors in the projection optics include a first, concave mirror, a second, convex mirror, a third, concave mirror, and a fourth, convex mirror, each receiving the beam of light in turn, with the light reflected from the fourth mirror being imaged onto the active surface of the substrate with an image area greater than that of the original light emitting array.

DEKODIERUNG VON MATRIXSENSOREN MIT MIKROKUGELN

MICROARRAY SYNTHESIS INSTRUMENT AND METHOD

During the light illumination period of a monomer addition cycle in synthesizing an DNA microarray, undesirable reflections of illumination light from various interfaces that the illumination light passes through near the synthesis surface of the substrate may reduce the light dark contrast, and negatively affect the precision and resolution of the microarray synthesis. The present invention provides an flow cell that reduces the undesired reflections by constructing certain flow cell structures with materials that have similar refractive indexes as that of the solution that is in the oligomer synthesis chamber during the illumination period and/or constructing certain flow cell structures or covering the structures with a layer of a material that has a high extinction coefficient.

Self-encoding sensor with microspheres

A microsphere-based analytic chemistry system is disclosed in which self-encoding microspheres having distinct characteristic optical response signatures to specific target analytes may be mixed together while the ability is retained to identify the sensor type and location of each sensor in a random dispersion of large numbers of such sensors in a sensor array using an optically interrogatable encoding scheme. An optical fiber bundle sensor is also disclosed in which individual microsphere sensors are disposed in microwells at a distal end of the fiber bundle and are optically coupled to discrete fibers or groups of fibers within the bundle. The identities of the individual sensors in the array are self-encoded by exposing the array to a reference analyte while illuminating the array with excitation light energy. A single sensor array may carry thousands of discrete sensing elements whose combined signal provides for substantial improvements in sensor detection limits, response times and ...

Articles having localized molecules disposed thereon and methods of producing same

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.

Self-encoding sensor with microspheres

A microsphere-based analytic chemistry system is disclosed in which self-encoding microspheres having distinct characteristic optical response signatures to specific target analytes may be mixed together while the ability is retained to identify the sensor type and location of each sensor in a random dispersion of large numbers of such sensors in a sensor array using an optically interrogatable encoding scheme. An optical fiber bundle sensor is also disclosed in which individual microsphere sensors are disposed in microwells at a distal end of the fiber bundle and are optically coupled to discrete fibers or groups of fibers within the bundle. The identities of the individual sensors in the array are self-encoded by exposing the array to a reference analyte while illuminating the array with excitation light energy. A single sensor array may carry thousands of discrete sensing elements whose combined signal provides for substantial improvements in sensor detection limits, response times and ...

FLUID PROCESSING COMPRISING REGULATION BY SURFACE TENSION CONTROLLED VALVE

A fluid processing method, adapted to produce different oligomers in a plurality of respective reaction sites is claimed. The described fluid processing device comprises a first manifold for delivering reactants to the plurality of reaction sites, a second manifold for removing waste from and, optionally, delivering wash fluid to the plurality of reaction sites. Surface tension controlled valves can be disposed in fluid communication with the first manifold, the second manifold or both. They can selectively allow reactants and/or fluids into the reaction sites. The valves can be configured by light activation, e.g. by directing electromagnetic radiation towards them whereby reflecting of the radiation can be controlled by a plurality of mirrors. Electrowetting, optoelectrowetting, thermo capillary effects represent examples of triggering liquid movement. A method of synthesizing oligonucleotides is also disclosed.

Articles having localized molecules disposed thereon and methods of producing and using same

Sequencing methods and compositions, substrates, devices and systems are provided. Methods include synthesizing a nascent nucleic acid sequence that is greater than 100 bases in length and sequencing the nucleic acids by detecting synthesis. Compositions and substrates that include polymerization complexes for the methods are included.

Articles having localized molecules disposed thereon and methods of producing same

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.

System and method for addressable light-directed microarray printing

Systems and methods are described for synthesizing probe arrays of polymers. In one such system, a network server processes customer orders to provide data indicative of at least one probe array sequence desired by the customer to be included in a synthesized probe array. A probe array design and control computer executes a probe array design application that processes the probe and array configuration data to provide probe array design data that is then processed by a manufacturing control application to provide gating data. A probe array manufacturing apparatus selectively switches optical transfer elements between substantially light-passing and substantially light-not-passing states in response to the gating data. Light from those optical transfer elements in the light-passing states strikes one or more biological probe array substrates, thereby enabling selective addition of monomers, such as nucleotides, amino acids or saccharides, to the substrate.

ARTICLES HAVING LOCALIZED MOLECULES DISPOSED THEREON AND METHODS OF PRODUCING SAME

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.

Articles having localized molecules disposed thereon and methods of producing same

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.

CONTROLLED ALTERATION OF PORES USING FLUID FLOW AND FABRICATION OF ARTICLES THEREBY

The invention relates to microscopic structures and methods of making and using the structures. A method of forming a microscopic structure of a material includes obtaining a solution (310) containing the material, establishing a flowing stream of the solution (310) in a capillary (104), wherein the capillary (104) has an inner dimension that is smaller than about 300 micrometers, and maintaining the stream until a layer is built up along an inner wall of the capillary (104) from material deposited from the flowing stream, thereby forming a microscopic structure.

SELF-ENCODING SENSOR WITH MICROSPHERES

L'invention concerne un système de chimie analytique à microsphères dans lequel des microsphères d'auto-codage, présentant différentes signatures de réponse optique caractéristiques en fonction de cibles spécifiques, peuvent être mélangées tout en permettant d'identifier le type de capteur et l'emplacement de chaque capteur dans la dispersion aléatoire d'un grand nombre de capteurs dans un réseau de capteurs, grâce à un système de codage à interrogation optique. L'invention concerne également un capteur à faisceau de fibres optiques dans lequel des capteurs à microsphères individuels sont placés dans des micropuits à une extrémité distale du faisceau de fibres optiques et sont optiquement couplés à des fibres discrètes ou à des groupes de fibres discrètes du faisceau. L'identité des capteurs individuels du réseau est auto-codée par exposition du réseau à un analyte de référence tout en l'éclairant à l'aide d'énergie d'excitation lumineuse. Un seul réseau de capteurs peut comporter des milliers ...

Articles having localized molecules disposed thereon and methods of producing same

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.

SYNTHESIS OF ARRAYS OF OLIGONUCLEOTIDES AND OTHER CHAIN MOLECULES

Synthesis of arrays of chain molecules, such as oligonucleotides, in large quantities can be carried out utilizing projection onto an active substrate of a magnified image of a light emitting object array having selectable regions of light and dark areas forming a pattern. Projection optics formed entirely of mirrors are used to receive the light emitted from the object array and image the pattern of the array onto the active surface of the substrate. The mirrors in the projection optics include a first, concave mirror, a second, convex mirror, a third, concave mirror, and a fourth, convex mirror, each receiving the beam of light in turn, with the light reflected from the fourth mirror being imaged onto the active surface of the substrate with an image area greater than that of the original light emitting array.

Self-encoding sensor with microspheres

A microsphere-based analytic chemistry system is disclosed in which self-encoding microspheres having distinct characteristic optical response signatures to specific target analytes may be mixed together while the ability is retained to identify the sensor type and location of each sensor in a random dispersion of large numbers of such sensors in a sensor array using an optically interrogatable encoding scheme. An optical fiber bundle sensor is also disclosed in which individual microsphere sensors are disposed in microwells at a distal end of the fiber bundle and are optically coupled to discrete fibers or groups of fibers within the bundle. The identities of the individual sensors in the array are self-encoded by exposing the array to a reference analyte while illuminating the array with excitation light energy. A single sensor array may carry thousands of discrete sensing elements whose combined signal provides for substantial improvements in sensor detection limits, response times and ...

Affinity Reagent and Catalyst Discovery Through Fiber-Optic Array Scanning Technology

Devices, systems and methods for affinity reagent and catalyst discovery employing a library on a bead HTS platform, each bead comprising affixed non-natural polymers of a distinct bioactive monomer with sequence pre-defined branching and folding in tertiary structures, and fiber-optic array scanning technology. 120-. (canceled)28. A compound prepared by deprotecting the monomer of .29. A polymer prepared from the monomer of .30. A bead for high-throughput drug screening having affixed thereto the polymer of .31. A fiber optic scanner mounted with a slide bearing the bead of .32. A library of beads for high-throughput drug screening claim 29 , each bead having affixed thereto the polymer of .380. A bead for high-throughput drug screening having affixed thereto the polymer of claim .390. A fiber optic scanner mounted with a slide bearing the bead of claim .400. A library of beads for high-throughput drug screening claim 29 , each bead having affixed thereto the polymer of claim . This application is a continuation of PCT/US15/50306, filed Sep. 16, 2015, which claims priority to Ser. No. 62/050,922; filed Sep. 16, 2014.This invention was made with government support under contract number N66001-14-C-4059 awarded by the Space and Naval Warfare Systems Command Systems Center Pacific. The government has certain rights in this inventionRapid and cost effective ways of screening large compound collections for biological, physical or chemical properties still remain a challenge in many industries. Pharmaceutical companies have developed high through screening operations which can screen up to 2 million compounds in a matter of months, but these operations require high end automation, compound storage and retrieval system and several FTEs to run and maintain.Based on a fiber-optic array scanning technology (FAST) developed by SRI for screening for circulating tumor cells (CTCs), we conceived of using the same platform to screen compounds either covalently attached or ...

MICROARRAY SYNTHESIS INSTRUMENT AND METHOD

During the light illumination period of a monomer addition cycle in synthesizing an DNA microarray, undesirable reflections of illumination light from various interfaces that the illumination light passes through near the synthesis surface of the substrate may reduce the light dark contrast, and negatively affect the precision and resolution of the microarray synthesis. The present invention provides an flow cell that reduces the undesired reflections by constructing certain flow cell structures with materials that have similar refractive indexes as that of the solution that is in the oligomer synthesis chamber during the illumination period and/or constructing certain flow cell structures or covering the structures with a layer of a material that has a high extinction coefficient.

Microarray synthesis instrument and method

During the light illumination period of a monomer addition cycle in synthesizing an DNA microarray, undesirable reflections of illumination light from various interfaces that the illumination light passes through near the synthesis surface of the substrate may reduce the light-dark contrast, and negatively affect the precision and resolution of the microarray synthesis. The present invention provides an flow cell that reduces the undesired reflections by constructing certain flow cell structures with materials that have similar refractive indexes as that of the solution that is in the oligomer synthesis chamber during the illumination period and/or constructing certain flow cell structures or covering the structures with a layer of a material that has a high extinction coefficient.

Articles Having Localized Molecules Disposed Thereon and Methods of Producing Same

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.

Microarray synthesis instrument and method

During the light illumination period of a monomer addition cycle in synthesizing an DNA microarray, undesirable reflections of illumination light from various interfaces that the illumination light passes through near the synthesis surface of the substrate may reduce the light-dark contrast, and negatively affect the precision and resolution of the microarray synthesis. The present invention provides an flow cell that reduces the undesired reflections by constructing certain flow cell structures with materials that have similar refractive indexes as that of the solution that is in the oligomer synthesis chamber during the illumination period and/or constructing certain flow cell structures or covering the structures with a layer of a material that has a high extinction coefficient.

Self-encoding sensor with microspheres

Disclosed herein are compositions and methods for combining the output obtained from redundant sensor elements in a sensor array.

Microarray synthesis instrument and method

During the light illumination period of a monomer addition cycle in synthesizing an DNA microarray, undesirable reflections of illumination light from various interfaces that the illumination light passes through near the synthesis surface of the substrate may reduce the light-dark contrast, and negatively affect the precision and resolution of the microarray synthesis. The present invention provides an flow cell that reduces the undesired reflections by constructing certain flow cell structures with materials that have similar refractive indexes as that of the solution that is in the oligomer synthesis chamber during the illumination period and/or constructing certain flow cell structures or covering the structures with a layer of a material that has a high extinction coefficient.

Articles having localized molecules disposed thereon and methods of producing same

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.

ARTICLES HAVING LOCALIZED MOLECULES DISPOSED THEREON AND METHODS OF PRODUCING SAME

Articles having localized molecules disposed thereon and methods of producing same

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.

DECODING OF ARRAY SENSORS WITH MICROSPHERES

Self-encoding sensor with microspheres

Disclosed herein are compositions and methods for combining the output obtained from redundant sensor elements in a sensor array.

SELF-ENCODING SENSOR WITH MICROSPHERES

Disclosed herein are compositions and methods for combining the output obtained from redundant sensor elements in a sensor array.

Articles having localized molecules disposed thereon and methods of producing same

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.

Fluid processing device comprising surface tension controlled valve

A fluid processing device adapted to produce different oligomers in a plurality of respective reaction sites and methods of using the same are provided. The fluid processing device can comprise a first manifold for delivering reactants to the plurality of reaction sites, and a second manifold for removing waste from, and optionally delivering wash fluid to, the plurality of reaction sites. Surface tension controlled valves can be disposed in fluid communication with the first manifold, the second manifold, or both, and can selectively allow reactants and/or fluids into the reaction sites. A method of making oligonucleotides is also provided.

Articles having localized molecules disposed thereon and methods of producing same

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.

Synthesis of arrays of oligonucleotides and other chain molecules

Synthesis of arrays of chain molecules, such as oligonucleotides, in large quantities can be carried out utilizing projection onto an active substrate of a magnified image of a light emitting object array having selectable regions of light and dark areas forming a pattern. Projection optics formed entirely of mirrors are used to receive the light emitted from the object array and image the pattern of the array onto the active surface of the substrate. The mirrors in the projection optics include a first, concave mirror, a second, convex mirror, a third, concave mirror, and a fourth, convex mirror, each receiving the beam of light in turn, with the light reflected from the fourth mirror being imaged onto the active surface of the substrate with an image area greater than that of the original light emitting array.

SELF-ENCODING SENSOR WITH MICROSPHERES

A microsphere-based analytic chemistry system is disclosed in which self-encoding microspheres having distinct characteristic optical response signatures to specific target analytes may be mixed together while the ability is retained to identify the sensor type and location of each sensor in a random dispersion of large numbers of such sensors in a sensor array using an optically interrogatable encoding scheme. An optical fiber bundle sensor is also disclosed in which individual microsphere sensors are disposed in microwells at a distal end of the fiber bundle and are optically coupled to discrete fibers or groups of fibers within the bundle. The identities of the individual sensors in the array are self-encoded by exposing the array to a reference analyte while illuminating the array with excitation light energy. A single sensor array may carry thousands of discrete sensing elements whose combined signal provides for substantial improvements in sensor detection limits, response times and ...

Encoded molecular sieve particle-based sensors

A molecular sieve particle-based analytic chemistry system is disclosed in which populations of encoded molecular sieve particles carrying different chemical functionalities are distributed into wells etched in an optical fiber bundle. The chemical functionalities are encoded on separate shaped molecular sieve particles using luminescent dyes and/or molecular sieve particle shapes and thus, a single sensor array may carry thousands of chemistries. Such encoded molecular sieve particles can provide at least a five-fold enhancement in tunable parameters for increasing the encoding possibilities of high throughput screening assays relative to the present dye-modified polymeric microsphere standard.

Surface Tension Controlled Valves

The present teachings relate to surface tension controlled valves used for handling biological fluids. The valves controlled by optically actuating an electrowetting circuit.

Microarray synthesis instrument and method

During the light illumination period of a monomer addition cycle in synthesizing an DNA microarray, undesirable reflections of illumination light from various interfaces that the illumination light passes through near the synthesis surface of the substrate may reduce the light-dark contrast, and negatively affect the precision and resolution of the microarray synthesis. The present invention provides an flow cell that reduces the undesired reflections by constructing certain flow cell structures with materials that have similar refractive indexes as that of the solution that is in the oligomer synthesis chamber during the illumination period and/or constructing certain flow cell structures or covering the structures with a layer of a material that has a high extinction coefficient.

Articles having localized molecules disposed thereon and methods of producing same

The invention discloses the articles having localized molecules disposed thereon and the methods of producing same. 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.

Fluid processing device for oligonucleotide synthesis and analysis

The present teachings provide a fluid processing device adapted to produce different oligomers in a plurality of respective reaction sites. The fluid processing device can comprise a first manifold for delivering reactants to the plurality of reaction sites, and a second manifold for removing waste from, and optionally delivering wash fluid to, the plurality of reaction sites. Surface tension control valves can be disposed in fluid communication with the first manifold and can selectively allow reactants and/or fluids into the reaction sites. A method of making oligonucleotides is also provided.

AFFINITY REAGENT AND CATALYST DISCOVERY THOUGH FIBER-OPTIC ARRAY SCANNING TECHNOLOGY

SURFACE TENSION CONTROLLED VALVES

The present teachings relate to surface tension controlled valves used for handling biological fluids. The valves controlled by optically actuating an electro-wetting circuit.

Fluid Processing Device for Oligonucleotide Synthesis and Analysis

The present teachings provide a fluid processing device adapted to produce different oligomers in a plurality of respective reaction sites. The fluid processing device can comprise a first manifold for delivering reactants to the plurality of reaction sites, and a second manifold for removing waste from, and optionally delivering wash fluid to, the plurality of reaction sites. Surface tension control valves can be disposed in fluid communication with the first manifold and can selectively allow reactants and/or fluids into the reaction sites. A method of making oligonucleotides is also provided.

SELF-ENCODING SENSOR WITH MICROSPHERES

Disclosed herein are compositions and methods for combining the output obtained from redundant sensor elements in a sensor array.

Encoded molecular sieve particle-based sensors

A molecular sieve particle-based analytic chemistry system is disclosed in which populations of encoded molecular sieve particles carrying different chemical functionalities are distributed into wells etched in an optical fiber bundle. The chemical functionalities are encoded on separate shaped molecular sieve particles using luminescent dyes and/or molecular sieve particle shapes and thus, a single sensor array may carry thousands of chemistries. Such encoded molecular sieve particles can provide at least a five-fold enhancement in tunable parameters for increasing the encoding possibilities of high throughput screening assays relative to the present dye-modified polymeric microsphere standard.

Controlled alteration of pores using fluid flow and fabrication of articles thereby

The invention relates to microscopic structures and methods of making and using the structures. A method of forming a microscopic structure of a material includes obtaining a solution (310) containing the material, establishing a flowing stream of the solution (310) in a capillary (104), wherein the capillary (104) has an inner dimension that is smaller than about 300 micrometers, and maintaining the stream until a layer is built up along an inner wall of the capillary (104) from material deposited from the flowing stream, thereby forming a microscopic structure.

Articles having localized molecules disposed thereon and methods of producing same

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.

Self-encoding sensor with microspheres

A microsphere-based analytic chemistry system is disclosed in which self-encoding microspheres having distinct characteristic optical response signatures to specific target analytes may be mixed together while the ability is retained to identify the sensor type and location of each sensor in a random dispersion of large numbers of such sensors in a sensor array using an optically interrogatable encoding scheme. An optical fiber bundle sensor is also disclosed in which individual microsphere sensors are disposed in microwells at a distal end of the fiber bundle and are optically coupled to discrete fibers or groups of fibers within the bundle. The identities of the individual sensors in the array are self-encoded by exposing the array to a reference analyte while illuminating the array with excitation light energy. A single sensor array may carry thousands of discrete sensing elements whose combined signal provides for substantial improvements in sensor detection limits, response times and ...

Articles having localized molecules disposed thereon and methods of producing and using same

Sequencing methods and compositions, substrates, devices and systems are provided. Methods include synthesizing a nascent nucleic acid sequence that is greater than 100 bases in length and sequencing the nucleic acids by detecting synthesis. Compositions and substrates that include polymerization complexes for the methods are included.

Self-encoding sensor with microspheres

Disclosed herein are compositions and methods for combining the output obtained from redundant sensor elements in a sensor array.

System and method for addressable light-directed microarray printing

Systems and methods are described for synthesizing probe arrays of polymers. In one such system, a network server processes customer orders to provide data indicative of at least one probe array sequence desired by the customer to be included in a synthesized probe array. A probe array design and control computer executes a probe array design application that processes the probe and array configuration data to provide probe array design data that is then processed by a manufacturing control application to provide gating data. A probe array manufacturing apparatus selectively switches optical transfer elements between substantially light-passing and substantially light-not-passing states in response to the gating data. Light from those optical transfer elements in the light-passing states strikes one or more biological probe array substrates, thereby enabling selective addition of monomers, such as nucleotides, amino acids or saccharides, to the substrate.

ARTICLES HAVING LOCALIZED MOLECULES DISPOSED THEREON AND METHODS OF PRODUCING SAME

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. 113-. (canceled)14. A substrate comprising:a plurality of nanoscale wells disposed through an opaque layer, each well having a bottom surface formed from a transparent layer underlying the opaque layer; wherein the wells comprise a coupling group bound to the bottom surface and located in an observation region; and wherein density of the coupling group on the bottom surface of the wells is 100 times or more greater than density of the coupling group on the opaque layer's surface.15. The substrate of claim 14 , wherein the transparent layer comprises SiO.16. The substrate of claim 14 , wherein the opaque layer comprises a metal or metal oxide.17. The substrate of claim 14 , wherein the opaque layer comprises aluminum.18. The substrate of claim 17 , wherein the transparent layer comprises SiO.19. The substrate of claim 14 , wherein the opaque layer is passivated with a compound comprising one or more phosphonic acid groups.20. The substrate of claim 14 , wherein density of the coupling group on the bottom surface of the wells is 1000 times or more greater than density of the coupling group on the opaque layer's surface.21. The substrate of claim 14 , wherein the coupling group comprises one or more functional chemical moieties selected from the group consisting of an amine group claim 14 , a carboxyl group claim 14 , a hydroxyl group claim 14 , and a sulfhydryl group.22. The substrate of claim 14 , wherein the coupling group comprises biotin.23. The substrate of claim 14 , wherein the coupling group comprises avidin claim 14 , ...

SURFACE TENSION CONTROLLED VALVES

The present teachings relate to surface tension controlled valves used for handling biological fluids. The valves controlled by optically actuating an electro-wetting circuit.

Affinity Reagent and Catalyst Discovery Though Fiber-Optic Array Scanning Technology

Devices, systems and methods for affinity reagent and catalyst discovery employing a library on a bead HTS platform, each bead comprising affixed non-natural polymers of a distinct bioactive monomer with sequence pre-defined branching and folding in tertiary structures, and fiber-optic array scanning technology.

Microarray synthesis instrument and method

During the light illumination period of a monomer addition cycle in synthesizing an DNA microarray, undesirable reflections of illumination light from various interfaces that the illumination light passes through near the synthesis surface of the substrate may reduce the light-dark contrast, and negatively affect the precision and resolution of the microarray synthesis. The present invention provides an flow cell that reduces the undesired reflections by constructing certain flow cell structures with materials that have similar refractive indexes as that of the solution that is in the oligomer synthesis chamber during the illumination period and/or constructing certain flow cell structures or covering the structures with a layer of a material that has a high extinction coefficient.

Self-encoding sensor with microspheres

A microsphere-based analytic chemistry system is disclosed in which self-encoding microspheres having distinct characteristic optical response signatures to specific target analytes may be mixed together while the ability is retained to identify the sensor type and location of each sensor in a random dispersion of large numbers of such sensors in a sensor array using an optically interrogatable encoding scheme. An optical fiber bundle sensor is also disclosed in which individual microsphere sensors are disposed in microwells at a distal end of the fiber bundle and are optically coupled to discrete fibers or groups of fibers within the bundle. The identities of the individual sensors in the array are self-encoded by exposing the array to a reference analyte while illuminating the array with excitation light energy. A single sensor array may carry thousands of discrete sensing elements whose combined signal provides for substantial improvements in sensor detection limits, response times and ...

ARTICLES HAVING LOCALIZED MOLECULES DISPOSED THEREON AND METHODS OF PRODUCING SAME

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. 113-. (canceled)14. A method of preferentially localizing desired molecules within optical confinements disposed upon a substrate , comprising:depositing the desired molecules over the surface of the substrate; andselectively removing the desired molecules from the surface of the substrate that is not within the optical confinements.15. The method of claim 14 , wherein the substrate comprises an opaque layer on a transparent layer claim 14 , and wherein the optical confinements comprise nanoscale wells disposed through the opaque layer and exposing part of the transparent layer.16. The method of claim 15 , wherein the transparent layer comprises SiO.17. The method of claim 15 , wherein the opaque layer comprises a metal or metal oxide.18. The method of claim 15 , wherein the opaque layer comprises aluminum and the transparent layer comprises SiO.19. The method of claim 14 , wherein the optical confinements comprise zero mode waveguides.20. The method of claim 14 , wherein selectively removing the desired molecules from the surface of the substrate that is not within the optical confinements comprises contacting the substrate with a deactivation component coupled to an exclusionary component claim 14 , which exclusionary component is at least partially excluded from entering into the optical confinements.21. The method of claim 20 , wherein the deactivation component comprises an enzyme.22. The method of claim 21 , wherein the enzyme is selected from the group consisting of a protease claim 21 , a nuclease claim 21 , and a ...

Articles having localized molecules disposed thereon and methods of producing same

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.

SURFACE TENSION CONTROLLED VALVES

The present teachings relate to surface tension controlled valves used for handling biological fluids. The valves controlled by optically actuating an electro-wetting circuit.

Articles having localized molecules disposed thereon and methods of producing same

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.

Fluid processing device for oligonucleotide synthesis and analysis

The present teachings provide a fluid processing device adapted to produce different oligomers in a plurality of respective reaction sites. The fluid processing device can comprise a first manifold for delivering reactants to the plurality of reaction sites, and a second manifold for removing waste from, and optionally delivering wash fluid to, the plurality of reaction sites. Surface tension control valves can be disposed in fluid communication with the first manifold and can selectively allow reactants and/or fluids into the reaction sites. A method of making oligonucleotides is also provided.

Microarray synthesis instrument and method

During the light illumination period of a monomer addition cycle in synthesizing an DNA microarray, undesirable reflections of illumination light from various interfaces that the illumination light passes through near the synthesis surface of the substrate may reduce the light-dark contrast, and negatively affect the precision and resolution of the microarray synthesis. The present invention provides an flow cell that reduces the undesired reflections by constructing certain flow cell structures with materials that have similar refractive indexes as that of the solution that is in the oligomer synthesis chamber during the illumination period and/or constructing certain flow cell structures or covering the structures with a layer of a material that has a high extinction coefficient.

METHODS FOR PATTERNING HYDROGELS INTO MULTI-WELL PLATES

The inventive subject matter provides methods for reproducibly fabricating hydrogel-based organ and tumor models inside multi-well plates. A hydrogel precursor, which can include cells, is instilled into a well. A pillar is inserted into the well to contact the hydrogel precursor with a surface that can be shaped or textured to provide a desired surface configuration or contour, for example that of a desired organoid or tumor feature. The hydrogel precursor is polymerized and the pillar removed. A second hydrogel precursor, which can contain a different cell type, is then instilled into the well and a second pillar, which can have a different configuration or texture, inserted. Subsequent polymerization generates a second hydrogel portion within the well. Polymerization can be carried out by photopolymerization. Different wells can be aligned with different, individually controlled light sources or a single, collimated light source.

SELF-ENCODING SENSOR WITH MICROSPHERES

Surface tension controlled valves

The present teachings relate to surface tension controlled valves used for handling biological fluids. The valves controlled by optically actuating an electro-wetting circuit.

Controlled alteration of pores using fluid flow and fabrication of articles thereby

The invention relates to microscopic structures and methods of making and using the structures. A method of forming a microscopic structure of a material includes obtaining a solution (310) containing the material, establishing a flowing stream of the solution (310) in a capillary (104), wherein the capillary (104) has an inner dimension that is smaller than about 300 micrometers, and maintaining the stream until a layer is built up along an inner wall of the capillary (104) from material deposited from the flowing stream, thereby forming a microscopic structure.

Synthesis of arrays of oligonucleotides and other chain molecules

Synthesis of arrays of chain molecules, such as oligonucleotides, in large quantities can be carried out utilizing projection onto an active substrate of a magnified image of a light emitting object array having selectable regions of light and dark areas forming a pattern. Projection optics formed entirely of mirrors are used to receive the light emitted from the object array and image the pattern of the array onto the active surface of the substrate. The mirrors in the projection optics include a first, concave mirror, a second, convex mirror, a third, concave mirror, and a fourth, convex mirror, each receiving the beam of light in turn, with the light reflected from the fourth mirror being imaged onto the active surface of the substrate with an image area greater than that of the original light emitting array.

Articles having localized molecules disposed thereon and methods of producing same

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.

Encoded microcarriers, assay system using them and method for performing an assay

The present invention relates to an encoded microcarrier comprising a readable code attached to it for identification, said encoded microcarrier comprising a body having at least a detection surface to detect a chemical and/or biological reaction, the microcarrier further comprising at least a spacing element projecting from the body and shaped to ensure that, when the encoded microcarrier is laid on a flat plane with the detection surface facing said flat plane, a gap exists between said flat plane and the detection surface. The invention also relates to an assay device designed to use a plurality of said encoded microcarriers to perform assays. The invention relates finally to a method for monitoring a chemical or biological reaction.

Optical system and method for reading encoded microbeads

A method and apparatus for reading a microbead having a code thereon is provided wherein the code is projected on and read from a Fourier plane. The microbead may be 1-1000 microns (um) or smaller in feature size. The code is projected on the Fourier plane by scattering input light off the microbead. The scattered light from the microbead is directed through an optical arrangement having a transform lens for projecting the code on the Fourier plane, and read on the Fourier plane using a charge coupled device (CCD) or other similar device. The code may include periodic layers of material having different refractivities or phase, including index of refraction differences; periodic spatial modulations having a different phase or amplitude; a periodic binary phase change used to code information in the Fourier plane; a photonic crystal used to encode the information on the microbead, wherein a pattern of holes causes interference between incident and scattered light to form spatial and spectral patterns in the far field that are unique to the pattern of holes; or may be formed in the microbead using a single photoactive inner region, a series of longitudinal holes, different fluorescence regions, or concentric rings of material in a preform.

JOINT PRODUCTION METHOD AND DEVICE FOR AZIRIDINE, PIPERAZINE AND TRIETHYLENEDIAMINE

Disclosed are a joint production method and device for aziridine, piperazine and triethylenediamine. The method comprises: reaction 1, preparing piperazine and triethylenediamine by taking ethanol amine as a raw material under the existence of a cyclamine catalyst; reaction 2, preparing aziridine by taking the ethanol amine as the raw material under the existence of a catalyst B; and taking heat released in the reaction 1 as a heat source of heat absorption in the reaction 2. The device comprises a reactor 1 for carrying out the reaction 1 and the heat exchange between reaction materials of the reaction 1 and the raw material of the reaction 2 and a reactor 2 for carrying out the reaction 2. According to the present invention, the same raw material, namely the ethanol amine is adopted, aziridine, piperazine and triethylenediamine can be produced in a joint manner, the heat released in the reaction 1 is used for preheating materials in the reaction 2, so that heat coupling between the reactions is implemented, energy conservation is facilitated and competitiveness of the device is improved. 1. A joint production method for aziridine , piperazine and triethylenediamine , characterized in that , the method comprises:reaction 1, preparing piperazine and triethylenediamine by taking ethanol amine as a raw material in the presence of a cyclamine catalyst; andreaction 2, preparing aziridine by taking the ethanol amine as a raw material in the presence of a catalyst B;{'sub': a', 'b', 'c', 'd', 'e', 'f, 'wherein the catalyst B is TiPBXYO, wherein: X is an alkaline earth metal, Y is an alkaline metal, 0 is an oxygen element; a, b, c, d, e, and f are the mole ratios of each element atom, and a=1, b=0.02˜0.2, c=0.002˜0.02, d=0.01˜0.1, e=0.001˜0.01, and f is dependent on a, b, c, d, and e;'}the heat released in the reaction 1 is used as a heat source for the reaction 2.2. The joint production method for aziridine claim 1 , piperazine and triethylenediamine of claim 1 , ...

OPTICAL CONTROLLING OF A CHEMICAL REACTION

The present invention relates to a device () and a method for optically controlling a chemical reaction in a reaction chamber () comprising a reagent fluid (). In a preferred embodiment, the chemical reaction comprises a nucleic acid sequencing on a wiregrid. Based on strong optical confinement of excitation light () and of cleavage light (), the sequencing reaction can be read-out. Stepwise sequencing is achieved by using nucleotides with optically cleavable blocking moieties. After read-out the built in nucleotide is deblocked by cleavage light through the same substrate. This ensures that only bound nucleotides will be unblocked. In order to avoid overheating by cleavage light, the reagent fluid is circulated along the surface of the substrate (). 1. A device for optically controlling a chemical reaction in a reaction chamber comprising a reagent fluid , said device comprising:a substrate for binding at least one molecule on a first surface of the substrate, wherein said first surface is a wall of the reaction chamber;an optical arrangement configured to direct cleavage light to the substrate to optically induce a photochemical cleavage reaction;a circulation arrangement for circulating the reagent fluid in the reaction chamber, wherein the substrate is configured as a wiregrid.2. The device according to claim 1 ,wherein the reagent fluid is circulated along the first surface of the substrate.3. The device according to claim 1 ,wherein the circulation arrangement comprises a pumping element for actively pumping reagent fluid and/or a cooling element for cooling reagent fluid.4. The device according to claim 1 ,wherein the circulation arrangement comprises at least one pneumatically driven actuator.5. The device according to claim 1 ,wherein the circulation arrangement is adapted to synchronize the circulation of the reagent fluid with the irradiation of cleavage light.6. The device according to claim 1 ,wherein the chemical reaction comprises a nucleic acid ...

Manufacturing a flowcell with a planar waveguide

Provided in one example is a method of manufacturing a flowcell that includes: forming a core layer, the core layer disposed between a substrate and a nanowell layer, the nanowell layer having nanowells to receive a sample, the core layer having a higher refractive index than the substrate and the nanowell layer; and forming a grating to couple light to the core layer.

MICROARRAY SYNTHESIS AND ASSEMBLY OF GENE-LENGTH POLYNUCLEOTIDES

There is disclosed a process for in vitro synthesis and assembly of long, gene-length polynucleotides based upon assembly of multiple shorter oligonucleotides synthesized in situ on a microarray platform. Specifically, there is disclosed a process for in situ synthesis of oligonucleotide fragments on a solid phase microarray platform and subsequent, “on device” assembly of larger polynucleotides composed of a plurality of shorter oligonucleotide fragments. 1. (canceled)2. A method for producing a polynucleotide comprising a target sequence , the method comprising: [ is identical to an overlapping sequence region of another double-stranded oligonucleotide in the plurality of double-stranded oligonucleotides; and', 'comprises a Type II restriction endonuclease cleavage site; and, '(i) an internal sequence identical to a portion of the target sequence, wherein the internal sequence, at one or both ends, comprises an overlapping sequence region that, '(ii) one or more flanking sequences, wherein each flanking sequence comprises a Type II restriction endonuclease recognition site corresponding to the Type II restriction endonuclease cleavage site of the internal sequence;, '(a) providing a plurality of double-stranded oligonucleotides, each double-stranded oligonucleotide comprising(b) digesting the plurality of double-stranded oligonucleotides with a Type II restriction endonuclease that recognizes the Type II restriction endonuclease recognition site; and(c) ligating the digested oligonucleotides to produce the polynucleotide comprising the target sequence.3. The method of claim 2 , wherein each double-stranded oligonucleotide in (a) comprises a flanking sequence at each end.4. The method of claim 2 , wherein the plurality of double-stranded oligonucleotides are digested in (b) with a Type IIS restriction endonuclease.5. The method of claim 2 , wherein the Type IIS restriction endonuclease includes at least one of MylI claim 2 , BspMI claim 2 , BsaXI claim 2 , BsrI ...

Biopolymer synthesis system and method

The present invention provides improved automated systems and methods for synthesis of biopolymers including DNA and RNA. The automated systems and methods represent a number of improvements over existing systems for multiplex synthesis of biopolymers in a combinatorial fashion.

MICROFLUIDIC DEVICES AND METHODS OF USE IN THE FORMATION AND CONTROL OF NANOREACTORS

The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays and combinatorial chemistry. The invention provides for aqueous based emulsions containing uniquely labeled cells, enzymes, nucleic acids, etc., wherein the emulsions further comprise primers, labels, probes, and other reactants. An oil based carrier-fluid envelopes the emulsion library on a microfluidic device, such that a continuous channel provides for flow of the immiscible fluids, to accomplish pooling, coalescing, mixing, sorting, detection, etc., of the emulsion library. 230. The method of claim , wherein the aqueous droplets are surrounded by the immiscible carrier fluid.330. The method of claim , wherein the immiscible carrier fluid is injected from a direction substantially perpendicular to the channel.430. The method of claim , wherein the aqueous droplets have the same composition.530. The method of claim , wherein the aqueous droplets have different compositions.630. The method of claim , wherein the immiscible carrier fluid is an oil.7. The method of claim 6 , wherein the oil comprises a surfactant.8. The method of claim 7 , wherein the surfactant is a fluorosurfactant.930. The method of claim claim 7 , wherein the immiscible carrier fluid is a fluorinated oil.1030. The method of claim claim 7 , wherein the immiscible carrier fluid is injected using a syringe or pump.1130. The method of claim claim 7 , wherein the immiscible carrier fluid is injected using positive or negative pressure source.1230. The method of claim claim 7 , wherein the product of the PCR reaction detected in the one or more aqueous droplets comprises a plurality of fluorescent reporter molecules.13. The method of claim 12 , wherein the fluorescent reporter molecules are separated by a polymerase from quencher molecules during the PCR reaction.1430. The method of claim claim 12 , wherein the nucleic acid is an antibiotic resistant gene.1530. The ...

JOINT PRODUCTION METHOD AND DEVICE FOR AZIRIDINE, PIPERAZINE AND TRIETHYLENEDIAMINE

Disclosed are a joint production method and device for aziridine, piperazine and triethylenediamine. The method comprises: reaction 1, preparing piperazine and triethylenediamine by taking ethanol amine as a raw material under the existence of a cyclamine catalyst; reaction 2, preparing aziridine by taking the ethanol amine as the raw material under the existence of a catalyst B; and taking heat released in the reaction 1 as a heat source of heat absorption in the reaction 2. The device comprises a reactor for carrying out the reaction 1 and the heat exchange between reaction materials of the reaction 1 and the raw material of the reaction 2 and a reactor for carrying out the reaction 2. According to the present invention, the same raw material, namely the ethanol amine is adopted, aziridine, piperazine and triethylenediamine can be produced in a joint manner, the heat released in the reaction 1 is used for preheating materials in the reaction 2, so that heat coupling between the reactions is implemented, energy conservation is facilitated and competitiveness of the device is improved. 15-. (canceled)6. A device for production of aziridine , piperazine and triethylenediamine , the device comprising:a first reactor, for carrying out a first reaction and for heat exchange between reaction materials of the first reaction and raw materials of a second reaction;a second reactor, for carrying out the second reaction; anda combination separation unit, comprising a flash unit, an aziridine separation unit, and a polyamine separation unit connected successively, wherein the flash unit is configured for separating nitrogen, the aziridine separation unit is configured for separating aziridine, and the polyamine separation unit is configured for separating piperazine and triethylenediamine.7. The device of claim 6 , wherein the flash unit is a flash tower having a theoretical plate number of 1 to 3 claim 6 , and is configured for operation at a temperature in a range of 0° C. ...

Process and apparatus for sequential synthesis of biological polymers

A method and apparatus for nucleic acid synthesis. The method employs a device including at least one deprotection unit to carry out a step of deprotection, at least one coupling unit to carry out a step of coupling, at least one oxidation/thiolation unit to carry out a step of oxidation orthiolation, at least one capping unit to carry out a step of capping, and at least one washing unit to carry out a step of washing. A plurality of reaction vessels for nucleic acid synthesis are moved to the units in accord with a synthesis scheme for a desired nucleic acid sequence and at least two reaction vessels are simultaneously acted upon at several of the units in series.

PLATFORM FOR DISCOVERY AND ANALYSIS OF THERAPEUTIC AGENTS

A method of characterizing candidate agents including steps of (a) providing a library of candidate agents attached to nucleic acid tags; (b) contacting the library with a solid support to attach the candidate agents to the solid support, whereby an array of candidate agents is formed; (c) contacting the array with a screening agent, wherein one or more candidate agents in the array react with the screening agent; (d) detecting the array to determine that at least one candidate agent in the array reacts with the screening agent; (e) sequencing the nucleic acid tag to determine the tag sequences attached to candidate agents in the array; and (f) identifying the at least one candidate agent in the array that reacts with the screening agent based on the tag sequence that is attached to the at least one candidate agent. 1. A method of characterizing candidate agents , comprising(a) providing a library of candidate agents, wherein each candidate agent is attached to a nucleic acid tag haying a tag sequence;(b) conflicting the library of candidate agents with a solid support to attach the candidate agents to the solid support, whereby an array of candidate agents is formed comprising individual features on the solid support that each attach to an individual candidate agent from the library;(c) contacting the array of candidate agents with a screening agent, wherein one or more candidate agents in the array react with the screening agent;(d) detecting the array during or after the contacting of the array with the screening agent, thereby determining that at least one candidate agent in the array reacts with the screening agent;(e) sequencing the nucleic acid tags on the array to determine the tag sequence that is attached to each of the candidate agents; and(f) identifying the at least one candidate agent in the array that reacts with the screening agent based on the tag sequence that is attached to the at least one candidate agent.2. The method of claim 1 , wherein the ...

Sample Plate Systems and Methods

A sample plate comprising a sample well is disclosed. The sample well can comprise one or more bead retaining chambers. Also provided herein is a method of using the sample plate and kits comprising the sample plate. 1. An Immunoassay sample plate comprising a circular sample well having a circular arrangement of probes , wherein the probes are defined by reagent beads.2. The Immunoassay sample plate as claimed in claim 1 , wherein said probes comprise a nucleic acid claim 1 , antibody claim 1 , antibody fragment claim 1 , protein claim 1 , peptide claim 1 , aptamer claim 1 , chemical compound or oligonucleotide.3. The Immunoassay sample plate as claimed in claim 2 , wherein each said probe is attached to a respective one of said beads.4. The Immunoassay sample plate as claimed in claim 3 , wherein said bead comprises a microparticle claim 3 , particle or microsphere.5. The Immunoassay sample plate as claimed in claim 3 , wherein each bead has a diameter in the range 0.5-1.0 mm.6. The Immunoassay sample plate as claimed in claim 1 , wherein the sample well comprises a central fluid receiving area.7. The Immunoassay sample plate as claimed in claim 6 , wherein the central fluid receiving area is in fluid communication with each of the probes of the sample well.8. The Immunoassay sample plate as claimed in claim 6 , wherein each of the probes is located radially outward of and fluidly exposed to the central fluid receiving area.9. The Immunoassay sample plate as claimed in claim 1 , further comprising concentric circles of probes.10. The Immunoassay sample plate as claimed in claim 1 , wherein said sample well comprises a base portion claim 1 , wherein said base portion comprises a plurality of recesses claim 1 , wherein a bead is located in each recess claim 1 , each recess having a circular cross-section and comprising a tapered section.11. The Immunoassay sample plate as claimed in claim 10 , wherein said beads are retained or secured within said recesses by an ...

PLATFORM FOR DISCOVERY AND ANALYSIS OF THERAPEUTIC AGENTS

A method of characterizing candidate agents including steps of (a) providing a library of candidate agents attached to nucleic acid tags; (b) contacting the library with a solid support to attach the candidate agents to the solid support, whereby an array of candidate agents is formed; (c) contacting the array with a screening agent, wherein one or more candidate agents in the array react with the screening agent; (d) detecting the array to determine that at least one candidate agent in the array reacts with the screening agent; (e) sequencing the nucleic acid tag to determine the tag sequences attached to candidate agents in the array; and (f) identifying the at least one candidate agent in the array that reacts with the screening agent based on the tag sequence that is attached to the at least one candidate agent. 1. A method of characterizing candidate agents , comprising(a) providing a library of candidate agents, wherein each candidate agent is attached to a nucleic acid tag having a tag sequence;(b) contacting the library of candidate agents with a solid support to attach the candidate agents to the solid support, whereby an array of candidate agents is formed comprising individual features on the solid support that each attach to an individual candidate agent from the library;(c) contacting the array of candidate agents with a screening agent, wherein one or more candidate agents in the array react with the screening agent;(d) detecting the array during or after the contacting of the array with the screening agent, thereby determining that at least one candidate agent in the array reacts with the screening agent;(e) sequencing the nucleic acid tags on the array to determine the tag sequence that is attached to each of the candidate agents; and(f) identifying the at least one candidate agent in the array that reacts with the screening agent based on the tag sequence that is attached to the at least one candidate agent.2. The method of claim 1 , wherein the ...

PROCESS FOR THE MANUFACTURE OF FLUORINATED OLEFINS

A method for producing 1,1,1,2-tetrafluoropropene and/or 1,1,1,2,3-pentafluoropropene using a single set of four unit operations, the unit operations being (1) hydrogenation of a starting material comprising hexafluoropropene and optionally recycled 1,1,1,2,3-pentafluoropropene; (2) separation of the desired intermediate hydrofluoroalkane, such as 1,1,1,2,3,3-hexafluoropropane and/or 1,1,1,2,3-pentafluoropropane; (3) dehydrofluorination of the intermediate hydrofluoroalkane to produce the desired 1,1,1,2-tetrafluoropropene and/or 1,1,1,2,3-pentafluoropropene, followed by another separation to isolate the desired product and, optionally, recycle of the 1,1,1,2,3-pentafluoropropene. 1. A method for producing at least one fluorinated olefin comprising: {'br': None, 'sub': n', '3−n', 'a', 'b', 'z', 'm', '2−m, 'sup': 1', '2, '(CXY)(CRR)CX═CHX\u2003\u2003(I)'}, 'a. hydrogenating a starting material stream comprising at least one alkene according to Formula (I) {'br': None, 'sub': n', '3−n', 'a', 'b', 'z', 'm+1', '2−m, 'sup': 1', '2, '(CXY)(CRR)CHXCHX\u2003\u2003(II)'}, 'by contacting said starting material with a reducing agent to produce an intermediate product stream comprising at least one alkane according to Formula (II)where:each X is independently Cl, F, I or Br, provided that at least two Xs are F;each Y is independently H, Cl, F, I or Br;{'sup': '1', 'each Ris independently H, Cl, F, I, Br or unsubstituted or halogen substituted methyl or ethyl radical;'}{'sub': '2', 'each Ris independently H, Cl, F, I, Br or unsubstituted or halogen substituted methyl or ethyl radical;'}n is 1, 2 or 3;a and b are each 0, 1 or 2, provided that a+b=2;m is 0, 1 or 2; andz is 0, 1, 2 or 3;b. optionally, separating said intermediate product stream into a plurality of stream, said plurality of intermediate product streams comprising two or more stream selected from the group consisting of a first stream rich in at least a first alkane according to Formula II, a seconds stream rich in ...

Sample Plate Systems and Methods

A sample plate comprising a sample well is disclosed. The sample well can comprise one or more bead retaining chambers. Also provided herein is a method of using the sample plate and kits comprising the sample plate. 1. A kit comprising:a sample plate comprising one or more sample wells, each sample well comprising a base portion, wherein the base portion comprises one or more pockets, recesses or bores; anda corresponding one or more reagent beads for insertion into each one of the respective pockets, recesses or bores of the sample plate, wherein the one or more reagent beads are composed of glass, andwherein the one or more pockets, recesses or bores are each arranged to retain and secure a single, respective reagent bead by an interference or friction fit to substantially fluid-tightly seal the pocket, recess or bore.2. The kit of claim 1 , wherein the base portion of each sample well comprises a plurality of pockets claim 1 , recesses or bores.3. The kit of claim 2 , wherein the plurality of pockets claim 2 , recesses or bores are arranged circumferentially in one or more concentric circles around a central portion of the sample well.4. The kit of claim 1 , wherein the reagent beads are spherical.5. The kit of claim 1 , wherein the reagent beads are non-spherical.6. The kit of claim 1 , wherein a reagent bead is inserted into each of the pockets claim 1 , recesses or bores of the sample plate.7. A kit comprising:a sample plate comprising one or more sample wells, each sample well comprising a base portion, wherein the base portion comprises a plurality of pockets, recesses or bores arranged circumferentially in one or more concentric circles around a central fluid receiving area such that each pocket, recess or bore is located radially outward of and fluidly exposed to the central fluid receiving area; anda corresponding one or more reagent beads for insertion into each one of the respective pockets, recesses or bores of the sample plate, wherein the one or ...

TARGET ANALYTE SENSORS UTILIZING MICROSPHERES

A microsphere-based analytic chemistry system and method for making the same is disclosed in which microspheres or particles carrying bioactive agents may be combined randomly or in ordered fashion and dispersed on a substrate to form an array while maintaining the ability to identify the location of bioactive agents and particles within the array using an optically interrogatable, optical signature encoding scheme. A wide variety of modified substrates may be employed which provide either discrete or non-discrete sites for accommodating the microspheres in either random or patterned distributions. The substrates may be constructed from a variety of materials to form either two-dimensional or three-dimensional configurations. In a preferred embodiment, a modified fiber optic bundle or array is employed as a substrate to produce a high density array. The disclosed system and method have utility for detecting target analytes and screening large libraries of bioactive agents. 1. A composition comprising:a) a substrate with a surface comprising discrete sites; andb) a population of microspheres distributed on said sites.218-. (canceled)19. A method of determining the presence of a target analyte in a sample comprising: i) a substrate with a surface comprising discrete sites; and', 1) a bioactive agent; and', '2) an optical signature capable of identifying said bioactive agent;, 'ii) a population of microspheres comprising at least a first and a second subpopulation each comprising, 'wherein said microspheres are distributed on said surface such that said discrete sites contain microspheres; and, 'a) contacting said sample with a composition comprisingb) determining the presence or absence of said target analyte.2023-. (canceled) This application is a continuation-in-part of copending U.S. application Ser. No. 08/818,199, filed Mar. 14, 1997.The use of optical fibers and optical fiber strands in combination with light absorbing dyes for chemical analytical determinations ...

CONNECTION PIPE, TITANIUM SPONGE PRODUCING APPARATUS COMPRISING THE CONNECTION PIPE, TITANIUM SPONGE PRODUCING METHOD USING THE APPARATUS, AND TITANIUM SPONGE PRODUCED BY THE METHOD

A connection pipe for coupling at least one reaction vessel used in producing titanium sponge with at least one recovering vessel for condensing and recovering magnesium and magnesium chloride separated from the titanium sponge in the reaction vessel; wherein the connection pipe is configured as a dual wall structure constituted of an inner pipe and an outer pipe, and comprises at least one heating unit provided between the inner pipe and the outer pipe, two or more sets of lead terminals located through the outer pipe to provide electrical connection to a power terminal in the outside of the connection pipe, insulators for sealing the lead terminals, lead wires for electrically coupling the heating unit with the lead terminals, and a stress absorbed portion provided on the outer pipe; wherein the stress absorbed portion is provided between the lead terminals thereby preventing short circuit and meltdown of the lead wires. 1. A connection pipe for coupling at least one reaction vessel used in producing titanium sponge with at least one recovering vessel for condensing and recovering magnesium and magnesium chloride separated from the titanium sponge in the reaction vessel;wherein the connection pipe is configured as a dual wall structure constituted of an inner pipe and an outer pipe, and comprises at least one heating unit provided between the inner pipe and the outer pipe, two or more sets of lead terminals located through the outer pipe to provide an electrical connection to power terminal in the outside of the connection pipe, insulators for sealing the lead terminals, lead wires for electrically coupling the heater unit with the lead terminals, and a stress absorbed portion provided on the outer pipe;wherein the stress absorbed portion is provided between the lead terminals.2. The connection pipe according to claim 1 , wherein two or more heating units are provided between the inner pipe and the outer pipe.3. The connection pipe according to claim 1 , wherein a ...

MICROARRAY SYNTHESIS AND ASSEMBLY OF GENE-LENGTH POLYNUCLEOTIDES

There is disclosed a process for in vitro synthesis and assembly of long, gene-length polynucleotides based upon assembly of multiple shorter oligonucleotides synthesized in situ on a microarray platform. Specifically, there is disclosed a process for in situ synthesis of oligonucleotide fragments on a solid phase microarray platform and subsequent, “on device” assembly of larger polynucleotides composed of a plurality of shorter oligonucleotide fragments. 1. (canceled)2. A method for producing a polynucleotide comprising a target sequence , the method comprising: [ is identical to an overlapping sequence region of another double-stranded oligonucleotide in the plurality of double-stranded oligonucleotides; and', 'comprises a Type II restriction endonuclease cleavage site; and, '(i) an internal sequence identical to a portion of the target sequence, wherein the internal sequence, at one or both ends, comprises an overlapping sequence region that, '(ii) one or more flanking sequences, wherein each flanking sequence comprises a Type II restriction endonuclease recognition site corresponding to a Type II restriction endonuclease cleavage site of the internal sequence;, '(a) providing a plurality of double-stranded oligonucleotides, each double-stranded oligonucleotide comprising(b) digesting the plurality of double-stranded oligonucleotides with a Type II restriction endonuclease that recognizes the Type II restriction endonuclease recognition site; and(c) ligating the digested oligonucleotides to produce the polynucleotide comprising the target sequence.3. The method of claim 2 , wherein each double-stranded oligonucleotide in (a) comprises a flanking sequence at each end.4. The method of claim 2 , wherein the plurality of double-stranded oligonucleotides are digested in (b) with a Type IIS restriction endonuclease.51. The method of claim 4 , wherein the Type IIS restriction endonuclease includes at least one of MylI claim 4 , BspMI claim 4 , BsaXI claim 4 , BsrI ...

Microfluidic Devices, Solid Supports for Reagents and Related Methods

A microfluidic device includes a plurality of reaction wells; and a plurality of solid supports, and each of the solid supports has a reagent attached thereto. The reagent is attached to the solid support via a labile reagent/support bond such that the reagent is configured to be cleaved from the support via a cleaving operation.

Color-Encoding and In-Situ Interrogation of Matrix-Coupled Chemical Compounds

A method and apparatus for the physico-chemical encoding of a collection of beaded resin (“beads”) to determine the chemical identity of bead-anchored compounds by in-situ interrogation of individual beads. The present invention provides method and apparatus to implement color-coding strategies in applications and including the ultrahigh-throughput screening of bead-based combinatorial compounds libraries as well as multiplexed diagnostic and environmental testing and other biochemical assays.

SYSTEM AND METHOD FOR EFFICIENTLY USING EXCESS ELECTRICAL ENERGY

A plant having a first device for the preparation of ethyne by partial oxidation of at least one hydrocarbon, generating a first ethyne-containing product gas stream, having a second device for the electrothermal preparation of ethyne, generating a second ethyne-containing product gas stream, and having a separating device for separating ethyne from a gas stream, to which both the first and the second product gas streams are fed, can make efficient use of excess electrical energy by operating the device for the electrothermal preparation of ethyne with excess electrical energy. 114-. (canceled)15. A plant for the efficient utilization of excess electrical energy , comprising:a) a first device for the preparation of ethyne by partial oxidation of at least one hydrocarbon, generating a first ethyne-containing product gas stream;b) a second device for the electrothermal preparation of ethyne, generating a second ethyne-containing product gas stream; andc) a separating device for separating ethyne from a gas stream, to which both the first and the second product gas streams are fed.16. The plant of claim 15 , further comprising a control device which matches the generation of ethyne in the first device and in the second device to one another claim 15 , thereby maintaining the total amount of ethyne separated in the separating device within a specified range.17. The plant of claim 15 , wherein the first device for the preparation of ethyne by partial oxidation comprises at least one burner fed with a mixture of oxygen and at least one hydrocarbon.18. The plant of claim 15 , wherein the second device for the electrothermal preparation of ethyne comprises at least one arc reactor.19. The plant of claim 15 , wherein the first and the second device for the preparation of ethyne each comprise a device for the rapid cooling of product gas stream claim 15 , and the gas streams obtained after these devices for rapid cooling are fed to the separating device for the removal of ...

TARGET ANALYTE SENSORS UTILIZING MICROSPHERES

A microsphere-based analytic chemistry system and method for making the same is disclosed in which microspheres or particles carrying bioactive agents may be combined randomly or in ordered fashion and dispersed on a substrate to form an array while maintaining the ability to identify the location of bioactive agents and particles within the array using an optically interrogatable, optical signature encoding scheme. A wide variety of modified substrates may be employed which provide either discrete or non-discrete sites for accommodating the microspheres in either random or patterned distributions. The substrates may be constructed from a variety of materials to form either two-dimensional or three-dimensional configurations. In a preferred embodiment, a modified fiber optic bundle or array is employed as a substrate to produce a high density array. The disclosed system and method have utility for detecting target analytes and screening large libraries of bioactive agents. 1. A composition comprising:a) a substrate with a surface comprising discrete sites wherein said substrate is not a fiber optic bundle; andb) a population of microspheres comprising first and second subpopulations, wherein said first subpopulation comprises a first bioactive agent and a first encoding parameter capable of identifying said first bioactive agent and said second subpopulation comprises a second bioactive agent and a second encoding parameter capable of identifying said second bioactive agent, wherein said first and second bioactive agents are different, and wherein said microspheres are present in a random pattern on said substrate such that said sites contain not more than one microsphere.223-. (canceled)24. The composition according to claim 1 , wherein said sites comprise wells.25. The composition according to claim 1 , wherein said substrate is selected from the group consisting of glass and plastic.26. The composition according to claim 1 , wherein said sites comprise chemically ...

ARRAY OF MICROMOLDED STRUCTURES FOR SORTING ADHERENT CELLS

An apparatus for collecting or culturing cells or cell colonies includes: a common substrate formed from a flexible resilient polymeric material and having a plurality of wells formed therein; and a plurality of rigid cell carriers releasably connected to said common substrate, with said carriers arranged in the form of an array, and with each of the carriers resiliently received in one of the wells. A method of collecting or culturing cells or cell colonies with such an apparatus is carried out by depositing a liquid media carrying cells on the apparatus so that said cells settle on or adhere to said the carriers; and then (c) releasing at least one selected carrier having said cells thereon by gradual application of release energy to each carrier from the cavity in which it is received (e.g., by pushing with a probe). 1. An apparatus for collecting or culturing cells or cell colonies , said apparatus comprising:a substrate formed from an elastomer and having a first surface and an opposed second surface and a plurality of wells formed in the first surface in the form of an array, anda plurality of rigid cell carriers each carrier disposed in one of said wells, the carriers configured to release from said substrate upon mechanical distortion of said substrate.2. The apparatus of claim 1 , wherein said carriers are transparent or semitransparent.3. The apparatus of wherein:said wells in said substrate are separated by walls, said walls have an average width of at least 2 micrometers, up to 1000 micrometers;and said walls have an average height of at least 2 micrometers, up to 1000 micrometers;said wells in said substrate have floors, and said floors have an average thickness of from 2 to 500 micrometers;said substrate has a top surface and said carriers have a top surface, and said carrier top surfaces are positioned at or below said substrate top surface;said carriers have heights of at least 2 micrometers, up to 500 micrometers; and said carriers have maximum ...

PLASMA POLYMERISATION APPARATUS

Plasma polymerisation apparatus is disclosed including a reaction zone and at least one gas inlet for supplying at least one monomer in a gaseous form to the reaction zone, a first electrode and a second electrode spaced apart and configured to generate an electric field in the reaction zone to form plasma polymer nanoparticulate material from the at least one monomer, a plurality of collectors configured to collect plasma-polymer nanoparticulate material formed in the reaction zone, the plurality of collectors being located adjacent the second electrode, and a cooling device located adjacent the second electrode and configured to cool the plurality of collectors. Also disclosed is plasma polymerisation apparatus that includes a confinement grid extending between a first electrode and a second electrode of the apparatus. 1. Plasma polymerisation apparatus comprising:a reaction zone;at least one gas inlet for supplying at least one monomer in a gaseous form to the reaction zone;a first electrode and a second electrode spaced apart and configured to generate an electric field in the reaction zone to form plasma polymer nanoparticulate material from the at least one monomer;a plurality of collectors configured to collect plasma-polymer nanoparticulate material formed in the reaction zone, the plurality of collectors being located adjacent the second electrode; anda cooling device located adjacent the second electrode and configured to cool the plurality of collectors.2. The apparatus of claim 1 , wherein the cooling device is located between the plurality of collectors and the second electrode.3. The apparatus of or claim 1 , wherein the cooling device comprises one or more thermoelectric semiconductor devices.4. The apparatus of claim 3 , wherein the cooling device comprises one or more Peltier devices.5. The apparatus of any one of the preceding claims claim 3 , wherein the cooling device is coupled to a rear surface of the plurality of collectors.6. The apparatus of ...

MICROARRAY HAVING A BASE CLEAVABLE LINKER

There is disclosed a microarray having base cleavable linkers and a process of making the microarray. The microarray has a solid surface with known locations, each having reactive hydroxyl groups. The density of the known locations is greater than approximately 100 locations per square centimeter. Optionally, oligomers are synthesized in situ onto the cleavable linkers and subsequently cleaved using a cleaving base. Optionally, the oligomers are cleaved and recovered as a pool of oligomers. 2. The compound of claim 1 , where the one or more oligonucleotides is selected from the group consisting of DNA claim 1 , RNA and combinations thereof.3. The compound of claim 1 , where the one or more oligonucleotides are synthesized in situ by a method selected from the group consisting of (a) printing reagents via ink jet or other printing technology and using regular phosphoramidite chemistry claim 1 , (b) maskless photo-generated acid controlled synthesis and using regular phosphoramidite chemistry claim 1 , (c) mask-directed parallel synthesis using photo-cleavage of photolabile protecting groups claim 1 , and (d) maskless parallel synthesis using photo-cleavage of photolabile protecting groups and digital photolithography.4. The compound of claim 1 , where the cleaving base is selected from the group consisting of ammonium hydroxide claim 1 , electrochemically generated base claim 1 , sodium hydroxide claim 1 , potassium hydroxide claim 1 , methylamine claim 1 , and ethylamine and combinations thereof.5. The compound of claim 1 , where the Compound is synthesized with a sulfonate amidite.6. The compound of claim 5 , where the sulfonyl amidite moiety is 2-[2-(4 claim 5 ,4′-dimethoxytrityloxy)ethylsulfonyl)ethyl-(2-cyanoethyl)-(N claim 5 ,N-dii-sopropyl)-phosphoramidite.7. The compound of claim 1 , where a porous reaction layer is attached to the known locations to provides the one or more of the plurality of hydroxyl reactive groups in the plurality of known locations.8. ...

ARRAY OF MICROMOLDED STRUCTURES FOR SORTING ADHERENT CELLS

An apparatus for collecting or culturing cells or cell colonies includes: a common substrate formed from a flexible resilient polymeric material and having a plurality of wells formed therein; and a plurality of rigid cell carriers releasably connected to said common substrate, with said carriers arranged in the form of an array, and with each of the carriers resiliently received in one of the wells. A method of collecting or culturing cells or cell colonies with such an apparatus is carried out by depositing a liquid media carrying cells on the apparatus so that said cells settle on or adhere to said the carriers; and then (c) releasing at least one selected carrier having said cells thereon by gradual application of release energy to each carrier from the cavity in which it is received (e.g., by pushing with a probe). 1. A probe for use in releasing a carrier from a microarray with the aid of a microscope objective , comprising:an elongate body portion having a proximal end and a distal end;a tip portion formed on or connected to said body portion distal end and configured for releasing a carrier from a microarray; anda retainer formed on or connected to said body portion proximal end and configured for engaging said microscope objective in a configuration in which said tip portion is positioned at or adjacent the focal point of said microscope objective.2. The probe of claim 2 , further comprising a drive assembly interconnecting said probe and said retainer portion.3. The probe of claim 2 , further comprising a transparent mount connected to said retainer and configured to overly the lens of said objective claim 2 , with said probe connected to said mount. This application is a divisional application of U.S. application Ser. No. 13/513,310 filed Jun. 1, 2012, which is a continuation-in-part application of PCT Application No. PCT/US2011/025018, filed Feb. 16, 2011, which in turn claims the benefit of US Provisional Applications No. 61/375,596, filed Aug. 20, 2010 ...

OLEFIN POLYMERIZATION APPARATUS AND OLEFIN POLYMERIZATION PROCESS

Provided in the present invention are an olefin polymerization apparatus and an olefin polymerization process. The following operations and effects can be realized by the apparatus or method provided in the present invention: the gas material discharged from the polymerization reactor is condensed, after the gas-liquid separation, the resulting gas portion is recycled to the reactor to form a circulation loop; the condensate can be selectively introduced to the polymerization reactor, in order to achieve the free switch between the homopolymerization reaction and the copolymerization reaction or between different copolymerization reactions, and at the same time the condensate can absorb the heat generated by the reaction. By using the apparatus and method provided in the present invention, polyolefin products having excellent mechanical properties and processability can be prepared as needed. 1. An olefin polymerization apparatus , comprising:a polymerization reactor for olefin homopolymerization and/or copolymerization reaction;a condensation unit for condensing a gas material discharged from the polymerization reactor;a gas-liquid separation unit for carrying out gas-liquid separation on the material from the condensation unit to generate a gas and a condensate;storage tanks for receiving the condensate discharged from the gas-liquid separation unit; anda control unit,wherein,the gas from the gas-liquid separation unit is introduced into the polymerization reactor, andthe condensate from the storage tanks is selectively introduced into the polymerization reactor under the action of the control unit to achieve the switch between the olefin homopolymerization and copolymerization in the polymerization reactor.2. The apparatus according to claim 1 , characterized in that claim 1 , the numbers of the storage tanks are 2 or more claim 1 , preferably 2 to 4 claim 1 , and the storage tanks are respectively used for storing the condensate containing different comonomers.3 ...

Microarray Having a Base Cleavable Linker

There is disclosed a microarray having base cleavable linkers and a process of making the microarray. The microarray has a solid surface with known locations, each having reactive hydroxyl groups. The density of the known locations is greater than approximately 100 locations per square centimeter. Optionally, oligomers are synthesized in situ onto the cleavable linkers and subsequently cleaved using a cleaving base. Optionally, the oligomers are cleaved and recovered as a pool of oligomers. 2. The compound of claim 1 , where the nucleotide base group is selected from the group consisting of adenine claim 1 , guanine claim 1 , cytosine claim 1 , uracil and thymine.3. The compound of claim 1 , where the acid labile protecting group is selected from the group consisting of dimethoxytrityl claim 1 , t-butyloxycarbonyl and benzyloxycarbonyl.4. The compound of claim 1 , where the Spacer is selected from the group consisting of DNA claim 1 , RNA claim 1 , polyethylene glycol claim 1 , and polypeptides claim 1 , and combinations thereof.5. The compound of claim 4 , where the Spacer is between a one-mer and a thirty five-mer.6. The compound of claim 1 , where the Spacer is selected from the group consisting of 10-T (deoxythymidine) and 15-T (deoxythymidine).7. The compound of claim 6 , where deoxyadenosine claim 6 , deoxyguanosine claim 6 , deoxycytidine claim 6 , deoxyuridine claim 6 , adenosine claim 6 , guanosine claim 6 , cytidine claim 6 , uridine and thymidine can be used instead of deoxythymidine.8. The compound of claim 1 , where the Spacer is selected from the group consisting of (CH—CH—O)—X claim 1 , and [X—(CH—CH—O)]—Y.9. The compound of claim 1 , where the plurality of hydroxyl reactive groups are present on a porous reaction layer.10. The compound of claim 9 , where the porous reaction layer comprises sucrose.11. The compound of claim 1 , further comprising where at the first location the acid labile protecting group is removed and a protected monomer is bound ...

SYSTEM AND METHOD FOR POLYMERIZATION

Techniques are provided for polymerization. A polymerization method may include polymerizing a monomer in a polymerization reactor to produce a slurry comprising polyolefin particles and a diluent, flowing the slurry out of the polymerization reactor through an outlet of the polymerization reactor, receiving the slurry from the outlet into a slurry handling system, conveying a first mixture from the slurry handling system to a diluent and monomer recovery system, and injecting steam into the first mixture downstream of the slurry handling system using a steam injection system. 130.-. (canceled)31. A system , comprising:a loop slurry polymerization reactor configured to polymerize a monomer into polyolefin particles;a slurry handling system configured to receive a slurry comprising the polyolefin particles suspended in a liquid diluent from the polymerization reactor and to provide the slurry to a diluent and monomer recovery system downstream of the slurry handling system; anda steam injection system configured to inject steam into the slurry such that the steam interacts with the slurry downstream of the loop slurry polymerization reactor to substantially prevent further polymerization of the monomer.32. The system of claim 31 , wherein the steam injection system comprises a steam control valve and a mass flow meter to control the amount of steam injected into the slurry claim 31 , and wherein the mass flow meter is an inertial flow meter claim 31 , a Coriolis meter claim 31 , a thermodynamic meter claim 31 , or a combination thereof.33. The system of claim 31 , comprising a feed system configured to provide a catalyst to the loop slurry polymerization reactor claim 31 , such that the slurry comprises the catalyst claim 31 , and wherein the catalyst is a chromium-based catalyst claim 31 , a Ziegler-Natta catalyst claim 31 , a metallocene catalyst claim 31 , a vanadium-based catalyst claim 31 , a nickel-based catalyst claim 31 , or a combination thereof.34. The ...

Ultrahigh throughput microinjection device

Many applications in cell biology, genetic engineering, cell-based therapeutics, and drug discovery require precise and safe methods for introducing membrane-impermeable molecules into cells. This can be implemented satisfactorily by microinjection. However, disadvantages of traditional manual microinjection include high degree of operator skill, low throughput and labor-intensiveness. Many studies have focused on developing automated and high-throughput systems for microinjection to address these limitations. However, none have provided sufficient throughput for applications such as ex vivo cell therapy, where manipulation of many cells is helpful.

MICROREACTOR SYSTEM

A microreactor system that can mix fluids at precise timing has two inlets into which fluids are introduced and merges, in a channel, a first fluid introduced from a first inlet and a second fluid introduced from a second inlet, a first pump that sends the first fluid toward the inlets, and a second pump that sends the second fluid toward the inlets, a first fluid detector that detects an arrival of the first fluid at the first inlet, and a second fluid detector that detects an arrival of the second fluid at the second inlet. 1. A microreactor system comprising:a microreactor that has two inlets into which fluids are introduced and a channel merging the fluids, and mixes, in the channel, a first fluid introduced from a first inlet of the inlets and a second fluid introduced from a second inlet of the inlets;a first pump that sends the first fluid toward the inlets;a second pump that sends the second fluid toward the inlets;a first fluid detector that detects an arrival of the first fluid at the first inlet; anda second fluid detector that detects an arrival of the second fluid at the second inlet,wherein the first pump, after starting a transfer of the first fluid toward the first inlet, stops the transfer by detection by the first fluid detector,the second pump, after starting a transfer of the second fluid toward the second inlet, stops the transfer by detection by the second fluid detector,each of the first pump and the second pump resumes the transfer after the transfer of the first fluid is stopped and after the transfer of the second fluid is stopped, andthe first fluid of which transfer has been temporarily stopped and the second fluid of which transfer has been temporarily stopped are introduced into the microreactor and mixed.2. A microreactor system comprising:a microreactor that has two inlets into which fluids are introduced and a channel merging the fluids, and mixes, in the channel, a first fluid introduced from a first inlet of the inlets and a second ...

PROCESS FOR THE MANUFACTURE OF FLUORINATED OLEFINS

A method for producing 1,1,1,2-tetrafluoropropene and/or 1,1,1,2,3-pentafluoropropene using a single set of four unit operations, the unit operations being (1) hydrogenation of a starting material comprising hexafluoropropene and optionally recycled 1,1,1,2,3-pentafluoropropene; (2) separation of the desired intermediate hydrofluoroalkane, such as 1,1,1,2,3,3-hexafluoropropane and/or 1,1,1,2,3-pentafluoropropane; (3) dehydrofluorination of the intermediate hydrofluoroalkane to produce the desired 1,1,1,2-tetrafluoropropene and/or 1,1,1,2,3-pentafluoropropene, followed by another separation to isolate the desired product and, optionally, recycle of the 1,1,1,2,3-pentafluoropropene. 1. A method for producing at least one fluorinated olefin comprising: {'br': None, 'sub': n', '3−n', 'a', 'b', 'z', 'm', '2−m, 'sup': 1', '2, '(CXY)(CRR)CX═CHX\u2003\u2003(I)'}, 'a. hydrogenating a starting material stream comprising at least one alkene according to Formula (I) {'br': None, 'sub': n', '3−n)(CR', 'a', 'b', 'z', 'm+1', '2−m, 'sup': 1', '2, '(CXYR)CHXCHX\u2003\u2003(II)'}, 'by contacting said starting material with a reducing agent to produce an intermediate product stream comprising at least one alkane according to Formula (II)where:each X is independently Cl, F, I or Br, provided that at least two Xs are F;each Y is independently H, Cl, F, I or Br;{'sup': '1', 'each Ris independently H, Cl, F, I, Br or unsubstitued or halogen substituted methyl or ethyl radical;'}{'sub': '2', 'each Ris independently H, Cl, F, I, Br or unsubstitued or halogen substituted methyl or ethyl radical;'}n is 1, 2 or 3;a and b are each 0, 1 or 2, provided that a+b=2;m is 0, 1 or 2; andz is 0, 1, 2 or 3;b. optionally, separating said intermediate product stream into a plurality of stream, said plurality of intermediate product streams comprising two or more stream selected from the group consisting of a first stream rich in at least a first alkane according to Formula II, a seconds stream rich in at ...

METAL-NANOPARTICLE-ARRAYS AND PRODUCTION OF METAL-NANOPARTICLE-ARRAYS

In metal-nanoparticle arrays and methods of producing metal-nanoparticle arrays, the metal-nanoparticle size and the interparticle distance between the metal nanoparticles can be adjusted. In the method of producing metal-nanoparticle arrays, a colloidal dispersion of microspheres is deposited on a substrate as a densely packed monolayer via convective assembly, after which the deposited monolayer is coated with at least one thinly deposited metal-nanoparticle layer by a physical deposition process, and after which the microspheres deposited on the substrate as a monolayer and coated with at least one metal-nanoparticle layer are removed by thermal decomposition. 11. Method of producing metal-nanoparticle arrays () , wherein{'b': 2', '4', '3, 'a colloidal dispersion of microspheres () is deposited on a substrate () as a densely packed monolayer () via convective assembly,'}{'b': 3', '5', '6, 'after which the deposited monolayer () is coated with at least one thinly deposited metal-nanoparticle layer () by means of a physical deposition process (), and'}{'b': 2', '4', '3', '5', '7, 'after which the microspheres () deposited on the substrate () as a monolayer () and coated with at least one metal-nanoparticle layer () are removed by thermal decomposition ().'}21. Method of producing metal-nanoparticle arrays () , wherein{'b': 2', '5', '6, 'microspheres () are coated with at least one thinly deposited metal-nanoparticle layer () by means of a physical deposition process (),'}{'b': 2', '5, 'after which the microspheres () coated with at least one metal-nanoparticle layer () are dispersed colloidally,'}{'b': 2', '5', '4', '3, 'after which the colloidal dispersion of microspheres () coated with a metal-nanoparticle layer () is deposited on a substrate () as a densely packed monolayer () by convective assembly, and'}{'b': 2', '5', '4', '3', '7, 'after which the microspheres () coated with at least one metal-nanoparticle layer () and deposited on the substrate () as a ...

METHOD AND APPARATUS FOR RECOVERY OF RADIOACTIVE NUCLIDES FROM SPENT RESIN MATERIALS

A process for the recovery of a radioisotope from a waste resin of a nuclear power plant comprises the steps of: a) treating a waste resin loaded with at least one radioisotope with an organic acid or alkaline compound to release the at least one radioisotope and to obtain a process solution containing the at least one radioisotope; b) separating the at least one radioisotope from the process solution through a reaction specific to the radioisotope so as to obtain a treated process solution depleted of the at least one radioisotope, wherein said depleted process solution comprises the organic acid or alkaline compound and optionally a non-reacted radioisotope; c) reacting the organic acid or alkaline compound in the depleted process solution from step b) by thermal and/or photochemical oxidation to form gaseous reaction products; and d) reloading the waste resin with the reacted process solution from step c) to bind the non-reacted radioisotope on the waste resin. Further, an apparatus is provided to carry out the above method. 1. A method for the recovery of a radioactive isotope from a spent waste resin of a nuclear power plant , wherein the waste resin is an ion exchange resin selected from the group consisting of cationic and anionic exchange resins , mixed bed ion-exchange resins , and mixtures thereof , and wherein the spent waste is loaded with at least one radioisotope , the method comprising the steps of:a) treating a waste resin loaded with at least one radioisotope with an organic acid or an alkaline compound to release the at least one radioisotope from the spent waste resin and to obtain a process solution containing the at least one radioisotope;b) separating the at least one radioisotope from the process solution through a reaction specific to the radioisotope so as to obtain a process solution depleted of the at least one radioisotope, wherein said reaction specific to the radioisotope is selected from the group of a physical reaction, an ...

MANIPULATION OF MICROPARTICLES IN MICROFLUIDIC SYSTEMS

An array of transportable particle sets is used in a microfluidic device for performing chemical reactions in the microfluidic device. The microfluidic device comprises a main channel and intersecting side channels, the main channel and side channels forming a plurality of intersections. The array of particle sets is disposed in the main channel, and the side channels are coupled to reagents. As the particle sets are transported through the intersections of the main channel and the side channels, reagents are flowed through the side channels into contact with each array member (or selected array members), thereby providing a plurality of chemical reactions in the microfluidic system. 1. A method of modifying flow in a microchannel , the method comprising:flowing a first particle set into a microchannel;performing a first assay in the microchannel;moving the particle set within the microchannel, or flowing a second particle set into the microchannel, thereby altering the hydrodynamic resistance in the microchannel; and,performing a second assay in the microchannel.2. The method of claim 1 , the method further comprising altering the surface charge on the first particle set claim 1 , thereby modifying the zeta potential of the first particle.3. The method of claim 1 , the method further comprising altering the surface charge on the first particle set claim 1 , thereby modifying the zeta potential of the first particle claim 1 , wherein the zeta potential is altered in response to the results of the first or second assay in the microchannel.4. The method of claim 1 , the method further comprising altering the surface charge on the first particle set claim 1 , thereby modifying the zeta potential of the first particle claim 1 , wherein the zeta potential is altered in response to the results of the first or second assay in the microchannel claim 1 , wherein the results of the first or second assay are detected using a system comprising a microprocessor and the ...

MICROFLUIDIC DEVICES AND METHODS OF USE IN THE FORMATION AND CONTROL OF NANOREACTORS

The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays and combinatorial chemistry. The invention provides for aqueous based emulsions containing uniquely labeled cells, enzymes, nucleic acids, etc., wherein the emulsions further comprise primers, labels, probes, and other reactants. An oil based carrier-fluid envelopes the emulsion library on a microfluidic device, such that a continuous channel provides for flow of the immiscible fluids, to accomplish pooling, coalescing, mixing, sorting, detection, etc., of the emulsion library. 1. A method for preparing nucleic acids for sequencing , the method comprising:providing a solution comprising primers, microbeads, and nucleic acid templates;emulsifying the solution to generate droplets comprising one microbead and one nucleic acid template;amplifying the nucleic acids with the primers to generate bead-bound amplified nucleic acids;breaking the droplets to release the bead-bound amplified nucleic acids;enriching the bead-bound amplified nucleic acids from microbeads that are not bound to amplified nucleic acids; anddepositing the bead-bound amplified nucleic acids onto a solid support for sequencing.2. The method of claim 1 , wherein the nucleic acid templates comprise DNA or RNA.3. The method of claim 1 , wherein the nucleic acid templates comprise a whole genome.4. The method of claim 1 , wherein the nucleic acid templates comprise an adaptor.5. The method of claim 1 , further comprising shearing the nucleic acid templates into reads of less than 1 kb.6. The method of claim 1 , wherein the primers comprise a selectable gene.7. The method of claim 1 , wherein the primers each comprise a unique identifier.8. The method of claim 7 , wherein the unique identifier is incorporated into the bead-bound amplified nucleic acids during amplification.9. The method of claim 1 , wherein the microbeads comprise a polymer.10. The method of claim 1 , ...

REVERSING BIAS IN POLYMER SYNTHESIS ELECTRODE ARRAY

Polymers synthesized by solid-phase synthesis are selectively released from a solid support by reversing the bias of spatially addressable electrodes. Change in the current and voltage direction at one or more of the spatially addressable electrodes changes the ionic environment which triggers cleavage of linkers that leads to release of the attached polymers. The spatially addressable electrodes may be implemented as CMOS inverters embedded in an integrated circuit (IC). The IC may contain an array of many thousands of spatially addressable electrodes. Control circuity may independently reverse the bias on any of the individual electrodes in the array. This provides fine-grained control of which polymers are released from the solid support. Examples of polymers that may be synthesized on this type of array include oligonucleotides and peptides. 1. A method for selectively releasing polymers from a solid support comprising an array of spatially addressable electrodes , the method comprising:synthesizing the polymers on the solid support; andreversing voltage and current on all or part of the array of spatially addressable electrodes, wherein the polymers separate from the solid support only at locations on the solid support corresponding to spatially addressable electrodes where voltage and current are reversed.2. The method of claim 1 , wherein the polymers comprise oligonucleotides and the synthesizing uses the phosphoramidite method or enzymatic nucleotide synthesis.3. The method of claim 1 , further comprising selecting the part of the spatially addressable electrodes based on sequences of the polymers or lengths of the polymers.4. The method of claim 1 , further comprising:returning the voltage and current of the part of the array of spatially addressable electrodes to an original voltage and current; andinitiating synthesis of additional polymers on the locations on the solid support corresponding to the spatially addressable electrodes where the voltage and ...

Olefin polymerization apparatus and olefin polymerization process

Планшет для образцов

Группа изобретений относится к области медицины, а именно к лабораторной диагностике. Планшет для образцов содержит одну или более лунок, имеющих основание и одно или более гнезд, выполненных в основании и имеющих сужающееся углубление, причем в процессе использования планшета гранула или микросфера реагента, по существу, фиксируется за счет плотного контакта внутри сужающегося углубления таким образом, что ее нижняя часть, лежащая ниже линии плотного контакта, не вступает в контакт с жидкостью, диспенсированной в одну или более лунок. Группа изобретений относится также к наборам для проведения диагностического тестирования, автоматизированному устройству и способу диспенсирования гранул или микросфер реагента в лунки указанного планшета, устройству для анализа жидкости на наличие одного или более интересующих аналитов, а также к способу изготовления указанного планшета для образцов. Группа изобретений обеспечивает надежную фиксацию гранул реагента в требуемом положении, а также позволяет уменьшить количество жидкости, требуемое для проведения анализа. 13 н. и 18 з.п. ф-лы, 18 ил. РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 476 889 (13) C2 (51) МПК G01N 33/543 (2006.01) B01L 3/00 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2010114864/15, 15.04.2010 (24) Дата начала отсчета срока действия патента: 15.04.2010 (72) Автор(ы): БАНС Эдриан (GB), ФУЗЕЛЬЕ Эндрю (GG) (73) Патентообладатель(и): ДИНЕКС ТЕКНОЛОДЖИЗ, ИНК. (US) R U Приоритет(ы): (30) Конвенционный приоритет: 29.07.2009 GB 0913258.0 07.10.2009 GB 0917555.5 13.04.2010 GB 1006087.9 2 4 7 6 8 8 9 (43) Дата публикации заявки: 20.10.2011 Бюл. № 29 (45) Опубликовано: 27.02.2013 Бюл. № 6 2 4 7 6 8 8 9 R U Адрес для переписки: 191186, Санкт-Петербург, а/я 230, "АРСПАТЕНТ", пат.пов. С.В.Новоселовой C 2 C 2 (56) Список документов, цитированных в отчете о поиске: US 2009/0069200 А1, 12.03.2009. SU 1530242 А1, 23.12.1989. WO 03/036263 А2, 01.05.2003. RU 2262939 ...

Microfluidic devices and methods of use in the formation and control of nanoreactors

The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays and combinatorial chemistry. Such methods can include labeling a library of compounds by emulsifying aqueous solutions of the compounds and aqueous solutions of unique liquid labels on a microfluidic device, which includes a plurality of electrically addressable, channel bearing fluidic modules integrally arranged on a microfabricated substrate such that a continuous channel is provided for flow of immiscible fluids, whereby each compound is labeled with a unique liquid label, pooling the labeled emulsions, coalescing the labeled emulsions with emulsions containing a specific cell or enzyme, thereby forming a nanoreactor, screening the nanoreactors for a desirable reaction between the contents of the nanoreactor, and decoding the liquid label, thereby identifying a single compound from a library of compounds.

Biochips with surfaces coated with polysaccharide-based hydrogels

The present invention provides a substrate having a polymerized, polysaccharide-based hydrogel attached to the surface. The hydrogel can be derivatized with binding functionalities that bind analytes from a sample. The invention further provides methods of using the device and gels that are capable of selectively binding one or more analytes from a sample.

Method of research for creating and testing novel catalysts, reactions and polymers

A method and system for researching and developing and/or optimizing new catalysts and products in a combinatorial manner is disclosed. The method begins with starting components or a ligand library and provides methods of creating catalyst or product libraries, which are then tested in a reaction of interest. The system uses methods of robotic handling for moving libraries from station to station. The method and apparatus are especially useful for synthesizing, screening, and characterizing combinatorial catalyst libraries, but also offer significant advantages over conventional experimental methods as well.

System for creating and testing novel catalysts, reactions and polymers

A method and system for researching and developing and/or optimizing new catalysts and products in a combinatorial manner is disclosed. The method begins with starting components or a ligand library and provides methods of creating catalyst or product libraries, which are then tested in a reaction of interest. The system uses methods of robotic handling for moving libraries from station to station. The method and apparatus are especially useful for synthesizing, screening, and characterizing combinatorial catalyst libraries, but also offer significant advantages over conventional experimental methods as well.

Apparatus and method of research for creating and testing novel catalysts, reactions and polymers

A method and system for researching and developing and/or optimizing new catalysts and products in a combinatorial manner is disclosed. The method begins with starting components or a ligand library and provides methods of creating catalyst or product libraries, which are then tested in a reaction of interest. The system uses methods of robotic handling for moving libraries from station to station. The method and apparatus are especially useful for synthesizing, screening, and characterizing combinatorial catalyst libraries, but also offer significant advantages over conventional experimental methods as well.

Microfluidic device for analyzing nucleic acids and/or proteins, methods of preparation and uses thereof

The invention relates to a microfluidic device for nucleic acid and/or protein analysis, wherein said device comprises a capillary on the inner surface of which is attached an array of at least two reagents. Also encompassed by the invention is such a capillary. In addition, the invention concerns methods for attaching at least two reagents on the inner surface of a capillary, as well as methods using a microfluidic device and enabling a multiplex analysis of nucleic acids and/or proteins to be performed.

Olefin polymerization apparatus and olefin polymerization process

Provided in the present invention are an olefin polymerization apparatus and an olefin polymerization process. The following operations and effects can be realized by the apparatus or method provided in the present invention: the gas material discharged from the polymerization reactor is condensed, after the gas-liquid separation, the resulting gas portion is recycled to the reactor to form a circulation loop; the condensate can be selectively introduced to the polymerization reactor, in order to achieve the free switch between the homopolymerization reaction and the copolymerization reaction or between different copolymerization reactions, and at the same time the condensate can absorb the heat generated by the reaction. By using the apparatus and method provided in the present invention, polyolefin products having excellent mechanical properties and processability can be prepared as needed.

Method and apparatus for very large scale immobilised polymer synthesis

Polymeric beads for oligonucleotide synthesis

The present invention provides solid support media for use in oligomer synthesis, methods of producing the media, and methods of using the media. In some embodiments, the processes of the invention comprise (a) providing an organic phase comprising an olefin monomer, a cross-linker, a functionalizing reagent and an initiator; and (b) contacting the organic phase with an aqueous phase under conditions of time and temperature effective to form the polymeric bead.

Matrices with memories in automated drug discovery and units therefor

Automated drug discovery protocols, or partially automated protocols, in which matrices-with-memories serve as the platform on which all manipulations are performed or serve as the repository of information that is transferred to other memories as the synthesized compounds are processed and screened. Also provided are automated drug discovery units for use in the protocols. The units provide a means for seamless data tracking and include instrumentation and vials with memories for information transfer to other memories in a unit. The units, which are provided herein, include some or all of the following: an automated or manual sorter, microreactors and microvessels, which contain memories, an automated or semi-automated synthesizer, a microreactor washer/dryer, a manual or automated cleaver for removing compounds from the matrix-with-memory microreactors, and associated software. The memories may be any of any type, including electromagnetically encodable memories and optical memories, or combinations thereof. The memories may be pre-encoded or may be encodable during, after or before processing. Also provided are manual and automated methods for sorting matrices with memories.

Magnetic bead-based arrays

The present invention relates to magnetic particle separators using micromachined magnetic arrays (52) deposited on to a substrate (50).

Method of operating a fluidic device and a fluidic device for use in the method

A method comprises introducing a fluid carrying mobile elements, such as particles (24), into a fluidic device. Simultaneously a mobile element receiving fluid and one or more further fluids are also introduced into the fluidic device. The fluids are passed through a chamber (12) in respective, parallel fluid streams (32, 34, 36, 38, 40). The fluid streams are arranged such that each fluid stream contacts at least another one of the fluid streams in the chamber (12). The dimensions of the chamber are such that the fluid streams undergo laminar flow and remain generally distinct from one another. A force is applied to the mobile elements (24) which causes the mobile elements to leave the fluid stream (32) of the mobile element carrying fluid, pass through the fluid stream(s) (34, 36, 38) of the further fluid(s) and enter into the fluid stream (40) of the mobile element receiving fluid. As the mobile elements pass through the fluid streams reactions can take place between species bound to the mobile elements and species carried in the fluid streams.

METHOD AND APPARATUS USING AN ELECTRIC FIELD FOR IMPROVED BIOLOGICAL TESTS

Optimization of gene expression analysis using immobilized capture probes

Disclosed are methods of multiplexed analysis of oligonucleotides in a sample, including: methods of probe and target “engineering”, as well as methods of assay signal analysis relating to the modulation of the probe-target affinity constant, K by a variety of factors including the elastic properties of target strands and layers of immobilized (“grafted”) probes; and assay methodologies relating to: the tuning of assay signal intensities including dynamic range compression and on-chip signal amplification; the combination of hybridization-mediated and elongation-mediated detection for the quantitative determination of abundance of messages displaying a high degree of sequence similarity, including, for example, the simultaneous determination of the relative expression levels, and identification of the specific class of, untranslated AU-rich subsequences located near the 3′ terminus of mRNA; and a new method of subtractive differential gene expression analysis which requires only a single color label.

Optimization of gene expression analysis using immobilized capture probes

Disclosed are methods of multiplexed analysis of oligonucleotides in a sample, including a method of preventing a significant reduction in duplexes detectable in a hybridization assay involving (i) selecting probe lengths for sets of oligonucleotide probes, wherein probes include different subsequences such that at least one subsequence is complementary to a subsequence in a cognate target; wherein probes for longer cognate targets are longer in length than probes for shorter cognate targets, (ii) selecting, for each set of probes, a density of oligonucleotides probes attached per unit area on a solid phase carrier which is below a limit at which the significant reduction in detectable duplexes is predicated to take place, (iii) producing the probes and affixing them to different solid phase carriers at the selected density, and (iv) annealing targets to the probes, wherein signal intensities of probes and targets of different lengths are about the same.

Microdevice containing photorecognizable coding patterns and methods of using and producing the same

This invention relates generally to the field of moiety or molecule analysis, isolation, detection and manipulation and library synthesis. In particular, the invention provides a microdevice, which microdevice comprises: a) a substrate; and b) a photorecognizable coding pattern on the substrate. Preferably, the microdevice does not comprise an anodized metal surface layer. Methods and kits for isolating, detecting and manipulating moieties, and synthesizing libraries using the microdevices are also provided. The invention further provides two-dimensional optical encoders and uses thereof.

Microdevices having a preferential axis of magnetization and uses thereof

This invention relates generally to the field of moiety or molecule isolation, detection and manipulation and library synthesis. In particular, the invention provides a microdevice, which microdevice comprises: a) a magnetizable substance; and b) a photorecognizable coding pattern, wherein said microdevice has a preferential axis of magnetization. Systems and methods for isolating, detecting and manipulating moieties and synthesizing libraries using the microdevices are also provided.

Microfluidic device and method with trapping of sample in cavities having lids that can be opened or closed

System and method for providing a sample preparing arrangement ( 10 ) submergible in a liquid medium that includes a carrier structure ( 11 ) having at least one cavity ( 12 ) therein and that is in communication with an arrangement ( 13 ) for controllable generation of a magnetic field through influence of a control signal. The sample preparing arrangement includes a magnetic covering structure ( 14 ) for covering and/or uncovering the cavity in operative interaction with the magnetic field.

Microfluidic device and method with trapping of sample in cavities having lids that can be opened or closed

Method and arrangement ( 10, 20 ) for preparing samples ( 15, 27 ) submergible in a liquid medium. The arrangement includes a carrier structure ( 11 ). The carrier includes a device ( 13, 23 ) for controllable generation of a magnetic field through influence of a control signal to attract at least part of the at least first and second type of samples ( 15, 27 ) towards specific locations on the carrier when connected to a first control signal and to repel at least one of the first or second type of samples when connected to a second control signal.

Method and system for the detection of cardiac risk factors

A system for the rapid characterization of multi-cardiovascular risk factor analyte fluids, in one embodiment, includes a light source, a sensor array, and a detector. The sensor array is formed from a supporting member, in which a plurality of cavities may be formed. A series of chemically sensitive particles, in one embodiment, are positioned within the cavities. The particles may produce a signal when a receptor, coupled to the particle, interacts with the cardiovascular risk factor analyte and the particle-analyte complex is visualized using a visualization reagent. Using pattern recognition techniques, the analytes within a multi-analyte fluid may be characterized. In an embodiment, each cavity of the plurality of cavities is designed to capture and contain a specific size particle. Flexible projections may be positioned over each of the cavities to provide retention of the particles in the cavities.

Microfluidic device and method with trapping of sample in cavities having lids that can be opened or closed

Method and arrangement ( 10, 20 ) for preparing samples ( 15, 27 ) submergible in a liquid medium. The arrangement includes a carrier structure ( 11 ). The carrier includes a device ( 13, 23 ) for controllable generation of a magnetic field through influence of a control signal to attract at least part of the at least first and second type of samples ( 15, 27 ) towards specific locations on the carrier when connected to a first control signal and to repel at least one of the first or second type of samples when connected to a second control signal.

Microfluidic device and method with trapping of sample in cavities having lids that can be opened or closed

System and method for providing a sample preparing arrangement ( 10 ) submergible in a liquid medium that includes a carrier structure ( 11 ) having at least one cavity ( 12 ) therein and that is in communication with an arrangement ( 13 ) for controllable generation of a magnetic field through influence of a control signal. The sample preparing arrangement includes a magnetic covering structure ( 14 ) for covering and/or uncovering the cavity in operative interaction with the magnetic field.

Magnetic bead-based arrays

The present invention relates to magnetic particle separators using micromachined magnetic arrays and more particularly, to magnetic particle separators or manipulators using controlled magnetization on micromachined magnetic arrays for the separation of cells and other biological materials. The present invention also pertains to using such devices for the separation and analysis of biological materials for immunoassays, DNA sequencing, protein analysis, and biochemical detection applications. The present invention can also be viewed as a novel method for fabricating fully integrated permanent magnet components within any microelectromechanical system (“MEMS”) structures. The present invention also provides a magnetic particle separation and manipulation system for rapid separation and accurate manipulation of magnetic particles in two-dimensional electromagnetic arrays, which utilize high throughput biological analyses. A disposable cartridge can be produced in low cost using a low cost substrate such as plastic or other polymer, glass, or metal. Magnetic flux is generated by conventional or micromachined electromagnets a platform system consisting of magnetic flux sources, magnetic flux guidance, and a microprocessor control interface. By controlling direction of electric currents into inductors on the platform system, arbitrary magnetic poles can be generated on Permalloy structures of the cartridge to separate and manipulate magnetic particles. The magnetic particle separator and manipulator in the present invention can be easily combined with automated detection systems such as a fluorescent monitoring system.

Magnetic bead-based arrays

The present invention relates to magnetic particle separators using micromachined magnetic arrays and more particularly, to magnetic particle separators or manipulators using controlled magnetization on micromachined magnetic arrays for the separation of cells and other biological materials. The present invention also pertains to using such devices for the separation and analysis of biological materials for immunoassays, DNA sequencing, protein analysis, and biochemical detection applications. The present invention can also be viewed as a novel method for fabricating fully integrated permanent magnet components within any microelectromechanical system (“MEMS”) structures. The present invention also provides a magnetic particle separation and manipulation system for rapid separation and accurate manipulation of magnetic particles in two-dimensional electromagnetic arrays, which utilize high throughput biological analyses. A disposable cartridge can be produced in low cost using a low cost substrate such as plastic or other polymer, glass, or metal. Magnetic flux is generated by conventional or micromachined electromagnets a platform system consisting of magnetic flux sources, magnetic flux guidance, and a microprocessor control interface. By controlling direction of electric currents into inductors on the platform system, arbitrary magnetic poles can be generated on Permalloy structures of the cartridge to separate and manipulate magnetic particles. The magnetic particle separator and manipulator in the present invention can be easily combined with automated detection systems such as a fluorescent monitoring system.

Systems and methods for localizing and analyzing samples on a bio-sensor chip

Chips that include one or more particle manipulation mechanisms, or force transduction elements, provided at specific locations to manipulate and localize particles proximal the substrate surface. In one embodiment, individually addressable magnetic control mechanisms such as electric coils are provided at specific locations to create a magnetic field to attract magnetic particles, such a magnetic or magnetizable beads, to those specific locations. In another embodiment, electrostatic control mechanisms such as electrodes are provided to attract and manipulate electrically charged micro-particles. A location may include a crater or well formed in the substrate, or it may include an element on the surface of the substrate. In some embodiments, one or more sensors are located proximal specific locations, e.g., specific craters, so as to analyze specific conditions at each location. In other embodiments, multiple locations share one or more sensors.

Array using microspheres

A microarray containing microspheres is provided. A substrate defines an arrayed pattern of test sites, and one or more microspheres are retained in proximity to each test site by an attachment point disposed on the test site. Each microsphere retained at a particular test site has a common ligand on its surface, which binds a particular analyte. Preferably, different ligands are used at each of the test sites, allowing for the detection of multiple analytes. A method of fabricating a microarray according to the present invention is also provided.

Methods and apparatus for DNA sequencing

Microfuidic device and method with trapping of sample in carities having lids that can be opened or closed

The present invention relates to a sample preparing arrangement (10) submergible in a liquid medium, comprising a carrier structure (11), at least one cavity (12) in said carrier, in communication with said cavity an arrangement (13) for controllable generation of a magnetic filed through influence of a control signal. The sample preparing arrangement comprises a magnetic covering structure (4) for covering/uncovering said cavity in operative interaction with said magnetic field.

Composite beads comprising magnetizable substance and electro-conductive substance

This invention relates generally to the field of moiety or molecule isolation, detection and manipulation and library synthesis. In particular, the invention provides a bead, which bead comprises: a) a magnetizable substance; and b) an electrically conductive substance or an optical labeling substance. Methods and kits for isolating, detecting and manipulating moieties and synthesizing libraries using the beads are also provided.

Systems and methods for localizing and analyzing samples on a bio-sensor chip

Chips that include one or more particle manipulation mechanisms, or force transduction elements, provided at specific locations to manipulate and localize particles proximal the substrate surface. In one embodiment, individually addressable magnetic control mechanisms such as electric coils are provided at specific locations to create a magnetic field to attract magnetic particles, such a magnetic or magnetizable beads, to those specific locations. In another embodiment, electrostatic control mechanisms such as electrodes are provided to attract and manipulate electrically charged micro-particles. A location may include a crater or well formed in the substrate, or it may include an element on the surface of the substrate. In some embodiments, one or more sensors are located proximal specific locations, e.g. specific craters, so as to analyze specific conditions at each location. In other embodiments, multiple locations share one or more sensors.

Manipulation of microparticles in microfluidic systems

Arrays of flowable or fixed particle sets are used in microfluidic systems for performing assays and modifying hydrodynamic flow. Also provided are assays utilizing flowable or fixed particle sets within a microfluidic system, as well as kits, apparatus and integrated systems comprising arrays and array members.

Sample preparing arrangement and a method relating to such an arrangement

The present invention relates to an arrangement (10, 20) for preparing samples (15, 27), submergible in a liquid medium. The arrangement comprises a section provided with a device (13, 23) for controllable generation of a magnetic field through influence of a control signal, said magnetic field being generated to trap at least part of said samples (15, 27).

Sample preparing arrangement and a method relating to such an arrangement

The present invention relates to an arrangement ( 10, 20 ) for preparing samples ( 15, 27 ), submergible in a liquid medium. The arrangement comprises a section provided with a device ( 13, 23 ) for controllable generation of a magnetic field through influence of a control signal, said magnetic field being generated to trap at least part of said samples ( 15, 27 ).

Sample preparing arrangement and a method relating to such an arrangement

The present invention relates to an arrangement ( 10, 20 ) for preparing samples ( 15, 27 ), submergible in a liquid medium. The arrangement comprises a section provided with a device ( 13, 23 ) for controllable generation of a magnetic field through influence of a control signal, said magnetic field being generated to trap at least part of said samples ( 15, 27 ).

Encoded particle having a grating with variations in the refractive index

Microparticles 8 includes an optical substrate 10 having at least one diffraction grating 12 disposed therein. The grating 12 having a plurality of colocated pitches Λ which represent a unique identification digital code that is detected when illuminated by incident light 24 . The incident light 24 may be directed transversely from the side of the substrate 10 with a narrow band (single wavelength) or multiple wavelength source, in which case the code is represented by a spatial distribution of light or a wavelength spectrum, respectively. The code may be digital binary or may be other numerical bases. The micro-particles 8 can provide a large number of unique codes, e.g., greater than 67 million codes, and can withstand harsh environments. The micro-particles 8 are functionalized by coating them with a material/substance of interest, which are then used to perform multiplexed experiments involving chemical processes, e.g., DNA testing and combinatorial chemistry.

Fine particle array analysis system, fine particle array kit, and chemical analysis method

Sequencing by incorporation

Nucleotides and nucleotide analogs are used in various sequencing by incorporation/sequencing by synthesis methods. Nucleotide analogs comprising 3'-blocking groups are used to provide reversible chain-termination for sequencing by synthesis. Typical blocking groups include phosphate groups and carbamate groups. Fluorescent nucleotides are used to perform sequencing by synthesis with detection by incorporation of the fluorescently labeled nucleotide, optionally followed by photobleaching and intercalating dyes are used to detect addition of a non-labeled nucleotide in sequencing by synthesis with detection by intercalation. Mircrofluidic devices, including particle arrays, are used in the sequencing methods.

Sequencing by incorporation

Nucleotides and nucleotide analogs are used in various sequencing by incorporation/sequencing by synthesis methods. Nucleotide analogs comprising 3′-blocking groups are used to provide reversible chain-termination for sequencing by synthesis. Typical blocking groups include phosphate groups and carbamate groups. Fluorescent nucleotides are used to perform sequencing by synthesis with detection by incorporation of the fluorescently labeled nucleotide, optionally followed by photobleaching and intercalating dyes are used to detect addition of a non-labeled nucleotide in sequencing by synthesis with detection by intercalation. Microfluidic devices, including particle arrays, are used in the sequencing methods.

Signal detection methods and apparatus

A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.

Nucleotides and analogs having photoremoveable protecting groups

A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protective groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.

Method for comparing copy number of nucleic acid sequences

The present invention provides methods for comparing and identifying differences in nucleic acid sequences using a plurality of sequence specific recognition reagents (i.e., probes comprising a nucleic acid complementary to a nucleic acid sequence in collections to be compared) bound to a solid surface.

Products for detecting nucleic acids

The present invention provides methods and apparatus for sequencing, fingerprinting and mapping biological macromolecules, typically biological polymers. The methods make use of a plurality of sequence specific recognition reagents which can also be used for classification of biological samples, and to characterize their sources.

Photolithographic and other means for manufacturing arrays

The present invention provides methods and apparatus for sequencing, fingerprinting and mapping biological macromolecules, typically biological polymers. The methods make use of a plurality of sequence specific recognition reagents which can also be used for classification of biological samples, and to characterize their sources.

Very large scale immobilized polymer synthesis

A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.

Apparatus for forming polynucleotides or polypeptides

A method for synthesizing oligonucleotides on a solid substrate. The method provides for the irradiation of a first predefined region of the substrate without irradiation of a second predefined region of the substrate. The irradiation step removes a protecting group therefrom. The substrate is contacted with a first nucleotide to couple the nucleotide to the substrate in the first predefined region. By repeating these steps, an array of diverse oligonucleotides is formed on the substrate.

Products for detecting nucleic acids

The present invention provides methods and apparatus for sequencing, fingerprinting and mapping biological macromolecules, typically biological polymers. The methods make use of a plurality of sequence specific recognition reagents which can also be used for classification of biological samples, and to characterize their sources.

Very large scale immobilized polymer synthesis

A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protecting groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.

Method of comparing nucleic acid sequences

The present invention provides methods for comparing and identifying differences in nucleic acid sequences using a plurality of sequence specific recognition reagents (i.e., probes comprising a nucleic acid complementary to a nucleic acid sequence in collections to be compared) bound to a solid surface.

Polypeptide arrays

The present invention provides methods and apparatus for sequencing, fingerprinting and mapping biological macromolecules, typically biological polymers. The methods make use of a plurality of sequence specific recognition reagents which can also be used for classification of biological samples, and to characterize their sources.

Apparatus comprising polymers

A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protecting groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.

Methods for polymer synthesis

A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.

Nucleic acid reading and analysis system

A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group; is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.

Polymer arrays

A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protective groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.

Apparatus for polymer synthesis

A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.

Very large scale immobilized polymer synthesis

A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.

Nucleic acid reading and analysis system

A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.

Methods of synthesizing a plurality of different polymers on a surface of a substrate

A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.