COMPOSITIONS AND METHODS FOR REPRESENTATIONAL SELECTION OF NUCLEIC ACIDS FROM COMPLEX MIXTURES USING HYBRIDIZATION

The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion ...

Oligonucleotide synthesizer

An apparatus for high-throughput combinatorial syntheses of organic molecules including a reaction vessel for containing a combinatorial-chemistry synthetic reaction, a liquid dispenser for dispensing the liquid, a liquid aspirator and an adjustment mechanism. The reaction vessel includes an ingress aperture allowing a liquid to enter into an interior of the vessel and an egress aperture for aspirating the liquid from the vessel. The liquid dispenser dispenses liquid through the ingress aperture. The liquid aspirator aspirates liquid through the egress aperture and includes a rotor for carrying the vessel and orbiting the vessel about an axis of rotation. The rotor is oriented generally in a horizontal plane and includes an adjustment mechanism for adjusting the angle of the vessel relative to the horizontal plane in response to the centrifugal force generated by orbiting the vessel about the axis of rotation. A method of combinatorial synthesis of organic molecules is also disclosed.

Encoding and decoding of array sensors utilizing nanocrystals

Described herein are assays and components for encoding and decoding microspheres. Each assay or component described utilizes at least one nanocrystal.

MANIPULATION OF DROPLETS ON HYDROPHILIC OR VARIEGATED-HYDROPHILIC SURFACES

Provided herein is a droplet actuator including (a) first and second substrates separated by a droplet-operations gap, the first and second substrates including respective hydrophobic surfaces that face the droplet-operations gap; (b) a plurality of electrodes coupled to at least one of the first substrate and the second substrate, the electrodes arranged along the droplet-operations gap to control movement of a droplet along the hydrophobic surfaces within the droplet-operations gap; and (c) a hydrophilic or variegated-hydrophilic surface exposed to the droplet-operations gap, the hydrophilic or variegated-hydrophilic surface being positioned to contact the droplet when the droplet is at a select position within the droplet-operations gap.

Array compositions for improved signal detection

The invention relates methods of improving signal detection from an array and methods for background subtraction in an array. The invention provides for novel array compositions including arrays with wells with different shapes, or surfaces coated with reflective or selectively absorptive coatings. In addition, the array include a signal transducer element.

Optical sensors with reflective materials

Provided is an optical sensor including a support and a detection layer, wherein the detection layer includes:(a) a luminescent material wherein the luminescence intensity of the luminescent material varies as the amount of an analyte varies;(b) a reflective material having a highly efficient reflectance of the wavelengths of excitation and of emission of the luminescent material; and(c) a polymeric binder to support and hold together the luminescent material and the reflective material. Such an optical sensor can be advantageously used in the detection of gaseous, ionic, and nonionic analytes in highly scattering samples. Also provided are methods for the manufacture of such optical sensors.

COMPOSITIONS AND METHODS FOR REPRESENTATIONAL SELECTION OF NUCLEIC ACIDS FROM COMPLEX MIXTURES USING HYBRIDIZATION

The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion of one or more nucleic acids within the complex mixture. A method of selecting a representational sample of genomic sequences from a complete genome also is provided. The invention further provides a nucleic acid population that includes a representational sample having a complexity of less than 10% but more than 0.001% of a complex mixture, the representational sample comprising a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of sequences in a predetermined portion of a sequence collectively present in one or more nucleic acids within the complex mixture.

GEL PATTERNED SURFACES

Provided is an array including a solid support having a surface, the surface having a plurality of wells, the wells containing a gel material, the wells being separated from each other by interstitial regions on the surface, the interstitial regions segregating the gel material in each of the wells from the gel material in other wells of the plurality; and a library of target nucleic acids in the gel material, wherein the gel material in each of the wells comprises a single species of the target nucleic acids of the library. Methods for making and using the array are also provided. 1. An array , comprisinga solid support comprising a surface, the surface comprising a plurality of wells, the wells containing a gel material, the wells being separated from each other by interstitial regions on the surface, the interstitial regions segregating the gel material in each of the wells from the gel material in other wells of the plurality; anda library of target nucleic acids in the gel material, wherein the gel material in each of the wells comprises a single species of the target nucleic acids of the library and wherein the target nucleic acids are covalently attached to the gel material.2. The array of claim 1 , wherein the volume of each of the wells is at most 1000 μm.3. The array of claim 1 , wherein the plurality of wells form an array having a repeating pattern.4. The array of claim 3 , wherein the wells in the pattern have a pitch of no more than 5 micrometers.5. The array of claim 1 , wherein the gel material comprises a hydrogel.6. An array claim 1 , comprisinga solid support comprising a surface, the surface comprising a plurality of wells, the wells containing a gel material, the wells being separated from each other by interstitial regions on the surface, the interstitial regions segregating the gel material in each of the wells from the gel material in other wells of the plurality; anda library of target nucleic acids in the gel material, wherein the gel ...

Compositions and methods for representational selection of nucleic acids from complex mixtures using hybridization

The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion ...

Compositions and methods for representational selection of nucleic acids from complex mixtures using hybridization

The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion ...

Oligonucleotide synthesizer

An apparatus for high-throughput combinatorial synthesis of organic molecules including a reaction vessel for containing a combinatorial chemistry synthetic reaction, a liquid dispenser for dispensing the liquid, a liquid aspirator and an adjustment mechanism. The reaction vessel includes an ingress aperture allowing a liquid to enter into an interior of the vessel and an egress aperture for aspirating the liquid from the vessel. The liquid dispenser dispenses liquid through the ingress aperture. The liquid aspirator aspirates liquid through the egress aperture and includes a rotor for carrying the vessel and orbiting the vessel about an axis of rotation. The rotor is oriented generally in a horizontal plane and includes an adjustment mechanism for adjusting the angle of the vessel relative to the horizontal plane in response to the centrifugal force generated by orbiting the vessel about the axis or rotation. A method of combinatorial synthesis of organic molecules is also disclosed.

Compositions and methods for representational selection of nucleic acids from complex mixtures using hybridization

The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion ...

COMPOSITIONS AND METHODS FOR REPRESENTATIONAL SELECTION OF NUCLEIC ACIDS FROM COMPLEX MIXTURES USING HYBRIDIZATION

The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion ...

Compositions and methods for stabilizing surface bound probes

The present invention provides a method for detecting a target analyte by providing a substrate having attached polynucleotides and a stabilization polymer layer; removing the stabilization polymer layer; contacting the substrate with a target analyte; and detecting the target analyte.

Encoding and decoding of array sensors utilizing nanocrystals

Described herein are assays and components for encoding and decoding microspheres. Each assay or component described utilizes at least one nanocrystal.

COMPOSITIONS AND METHODS FOR REPRESENTATIONAL SELECTION OF NUCLEIC ACIDS FROM COMPLEX MIXTURES USING HYBRIDIZATION

The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion of one or more nucleic acids within the complex mixture. A method of selecting a representational sample of genomic sequences from a complete genome also is provided. The invention further provides a nucleic acid population that includes a representational sample having a complexity of less than 10% but more than 0.001% of a complex mixture, the representational sample comprising a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of sequences in a predetermined portion of a sequence collectively present in one or more nucleic acids within the complex mixture. 1. A method of selecting a representational sample of nucleic acid sequences from a complex mixture , comprising:(a) contacting a complex mixture of nucleic acids with a population of solid support-attached capture probes under conditions sufficient for hybridization of said nucleic acids with said capture probes,wherein said ...

GEL PATTERNED SURFACES

An example method includes contacting a substrate coated with a sol-gel material with a stamp that includes a plurality of protruding features. While contacting the coated sol-gel material with the stamp, the example method further includes curing the coated sol-gel material so as to form a patterned sol-gel layer that includes a plurality of wells. The stamp is separated from the patterned sol-gel layer. 128-. (canceled)29. A method comprising:contacting a substrate coated with a sol-gel material with a stamp that includes a plurality of protruding features;while contacting the coated sol-gel material with the stamp, curing the coated sol-gel material so as to form a patterned sol-gel layer that comprises a plurality of wells; andseparating the stamp from the patterned sol-gel layer.30. The method of claim 29 , further comprising forming the coated substrate by coating the substrate with the sol-gel material claim 29 , wherein the coating is performed by spin-coating claim 29 , dipping claim 29 , or spray-coating.31. The method of claim 29 , wherein the curing the coated sol-gel material is performed by exposing the coated sol-gel material to light.32. The method of claim 29 , wherein the curing the coated sol-gel material is performed by exposing the coated sol-gel material to heat.33. The method of claim 29 , further comprising claim 29 , after separating the stamp from the patterned sol-gel layer claim 29 , sintering the patterned sol-gel layer.34. The method of claim 29 , further comprising depositing a gel material in the wells claim 29 , wherein the gel material is adapted to promote capture and/or amplification of target nucleic acids.35. The method of claim 34 , where depositing the gel material in the wells comprises:coating the gel material on the patterned sol-gel layer such that the gel material enters the wells and coats interstitial regions between the wells; andpolishing the patterned sol-gel layer so as to remove the gel material from the ...

COMPOSITIONS AND METHODS FOR REPRESENTATIONAL SELECTION OF NUCLEIC ACIDS FROM COMPLEX MIXTURE

The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion of one or more nucleic acids within the complex mixture. A method of selecting a representational sample of genomic sequences from a complete genome also is provided. The invention further provides a nucleic acid population that includes a representational sample having a complexity of less than 10% but more than 0.001% of a complex mixture, the representational sample comprising a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of sequences in a predetermined portion of a sequence collectively present in one or more nucleic acids within the complex mixture. 1. A method of selecting a representational sample of nucleic acid sequences from a complex mixture , comprising:(a) contacting a complex mixture of nucleic acids with a population of solid support-attached capture probes under conditions sufficient for hybridization of said nucleic acids with said capture probes,wherein said ...

GEL PATTERNED SURFACES

Provided is an array including a solid support having a surface, the surface having a plurality of wells, the wells containing a gel material, the wells being separated from each other by interstitial regions on the surface, the interstitial regions segregating the gel material in each of the wells from the gel material in other wells of the plurality; and a library of target nucleic acids in the gel material, wherein the gel material in each of the wells comprises a single species of the target nucleic acids of the library. Methods for making and using the array are also provided. 128.-. (canceled)29. A method comprising:coating at least a portion of the support with a gel material, the solid support comprising a planar surface interrupted by a plurality of concave features bordered by one or more interstitial regions on the planar surface, wherein the portion comprises at least some of the concave features and at least some of the interstitial regions; andpolishing the gel material from the at least some of the interstitial regions while maintaining the gel material in the at least some of the concave features, including on bottom surfaces of the at least some of the concave features.30. The method of claim 29 , wherein the support comprises a solid support.31. The method of claim 30 , wherein the solid support comprises glass claim 30 , silicon claim 30 , or a plastic material claim 30 , or a combination thereof.32. The method of claim 29 , wherein coating comprises contacting the solid support with a preformed gel material.33. The method of claim 29 , wherein coating comprises contacting the solid support with a liquid that subsequently forms the gel material.34. The method of claim 29 , wherein the gel comprises poly(N-(5-azidoacetamidylpentyl)acrylamide-co-acrylamide) that non-covalently associates with the at least some of the concave features.35. The method of claim 34 , wherein the concave features comprise a non-silanized surface.36. The method of claim 29 ...

Nanopore sequencers

Example nanopore sequencers include a cis well, a trans well, and a nanopore fluidically connecting the cis and trans wells. In one example sequencer, a modified electrolyte (including an electrolyte and a cation complexing agent) is present in the cis well, or the trans well, or in the cis and the trans wells. In another example sequencer, a gel state polyelectrolyte is present in the cis well, or the trans well, or in the cis and the trans wells.

COMPOSITIONS AND METHODS FOR REPRESENTATIONAL SELECTION OF NUCLEIC ACIDS FROM COMPLEX MIXTURE

The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion of one or more nucleic acids within the complex mixture. A method of selecting a representational sample of genomic sequences from a complete genome also is provided. The invention further provides a nucleic acid population that includes a representational sample having a complexity of less than 10% but more than 0.001% of a complex mixture, the representational sample comprising a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of sequences in a predetermined portion of a sequence collectively present in one or more nucleic acids within the complex mixture. 1(a) contacting a complex mixture of nucleic acids with a population of solid support-attached capture probes under conditions sufficient for hybridization of said nucleic acids with said capture probes,wherein said capture probes are complementary to nucleic acids comprising a predetermined portion of the sequence ...

POLYMER SHEETS FOR SEQUENCING APPLICATIONS

Embodiments of the present application relate to patterned polymer sheets and processes to prepare the same for sequencing applications. In particular, flexible micro- and nano-patterned polymer sheets are prepared and used as a template surface in sequencing reaction and new polish-free methods of forming isolated hydrogel plugs in nanowells are described. 1. A process for preparing a polymer sheet for sequencing applications , comprising:providing a substrate with a surface;depositing a layer of a polymer composition onto the surface of the substrate, wherein the polymer composition comprises functional groups for grafting oligonucleotides;forming the polymer composition into a polymer sheet on the surface; andremoving said polymer sheet from the surface of the substrate.2. The process of claim 1 , wherein the polymer composition comprises a hydrogel.3. The process of or claim 1 , wherein the polymer composition comprises poly(N-(5-azidoacetamidylpentyl) acrylamide-co-acrylamide) (PAZAM).4. The process of any one of to claim 1 , wherein the forming of the polymer sheet comprises dehydrating the polymer composition.5. The process of claim 4 , wherein the dehydrating is performed at an elevated temperature.6. The process of claim 5 , wherein the dehydrating occurs at about 60° C.7. The process of any one of to claim 5 , wherein the surface of the substrate comprises micro-scale or nano-scale patterns.8. The process of claim 7 , wherein the micro-scale or nano-scale patterns comprise channels claim 7 , trenches claim 7 , posts claim 7 , wells claim 7 , or combinations thereof.9. The process of or claim 7 , wherein an imprint of the micro-scale or nano-scale patterns of the patterned surface is transferred to the polymer sheet to form a patterned polymer sheet.10. A process for preparing a substrate surface for sequencing applications claim 7 , comprising:providing a polymer sheet comprising a first plurality of functional groups;contacting said polymer sheet with a ...

SUBSTRATES COMPRISING NANO-PATTERNING SURFACES AND METHODS OF PREPARING THEREOF

Substrates comprising a functionalizable layer, a polymer layer comprising a plurality of micro-scale or nano-scale patterns, or combinations thereof, and a backing layer and the preparation thereof by using room-temperature UV nano-embossing processes are disclosed. The substrates can be prepared by a roll-to-roll continuous process. The substrates can be used as flow cells, nanofluidic or microfluidic devices for biological molecules analysis. 1. A substrate comprising:a functionalizable layer comprising one or more functional groups;a polymer layer comprising a plurality of micro-scale or nano-scale patterns, or combinations thereof; anda backing layer; wherein the micro-scale or nano-scale patterns of the polymer layer comprises channels, trenches, wells, posts, or combinations thereof.2. (canceled)3. The substrate of claim 1 , wherein the functionalizable layer is disposed between the backing layer and the polymer layer claim 1 , and wherein at least a portion of the micro-scale or nano-scale patterns of the polymer layer perforate the polymer layer to expose the underlying functionalizable layer.4. (canceled)5. The substrate of claim 3 , wherein the functionalizable layer comprises a plurality of micro-scale or nano-scale patterns claim 3 , or combinations thereof claim 3 , and at least a portion of the micro-scale or nano-scale patterns of the polymer and functionalizable layers perforate the polymer and functionalizable layers to expose the underlying backing layer.6. The substrate of claim 1 , wherein the polymer layer is disposed between the backing layer and the functionalizable layer claim 1 , and wherein the functionalizable layer comprises a plurality of micro-scale or nano-scale patterns claim 1 , or combinations thereof claim 1 , wherein at least a portion of the micro-scale or nano-scale patterns of the functional layer perforate the functionalizable layer to expose the underlying polymer layer.7. (canceled)8. The substrate of claim 6 , wherein at ...

Compositions and methods for representational selection of nucleic acids from complex mixtures using hybridization

The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion of one or more nucleic acids within the complex mixture. A method of selecting a representational sample of genomic sequences from a complete genome also is provided. The invention further provides a nucleic acid population that includes a representational sample having a complexity of less than 10% but more than 0.001% of a complex mixture, the representational sample comprising a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of sequences in a predetermined portion of a sequence collectively present in one or more nucleic acids within the complex mixture.

SUBSTRATES COMPRISING NANO-PATTERNING SURFACES AND METHODS OF PREPARING THEREOF

Substrates comprising a functionalizable layer, a polymer layer comprising a plurality of micro-scale or nano-scale patterns, or combinations thereof, and a backing layer and the preparation thereof by using room-temperature UV nano-embossing processes are disclosed. The substrates can be prepared by a roll-to-roll continuous process. The substrates can be used as flow cells, nanofluidic or microfluidic devices for biological molecules analysis. 1. A substrate comprising:a functionalizable layer comprising one or more functional groups;a polymer layer comprising a plurality of micro-scale or nano-scale patterns, or combinations thereof; anda backing layer.2. The substrate of claim 1 , wherein the micro-scale or nano-scale patterns of the polymer layer comprises channels claim 1 , trenches claim 1 , wells claim 1 , posts claim 1 , or combinations thereof.3. The substrate of or claim 1 , wherein the functionalizable layer is disposed between the backing layer and the polymer layer.4. The substrate of claim 3 , wherein at least a portion of the micro-scale or nano-scale patterns of the polymer layer perforate the polymer layer to expose the underlying functionalizable layer.5. The substrate of claim 4 , wherein the functionalizable layer comprises a plurality of micro-scale or nano-scale patterns claim 4 , or combinations thereof claim 4 , and at least a portion of the micro-scale or nano-scale patterns of the polymer and functionalizable layers perforate the polymer and functionalizable layers to expose the underlying backing layer.6. The substrate of or claim 4 , wherein the polymer layer is disposed between the backing layer and the functionalizable layer.7. The substrate of claim 6 , wherein the functionalizable layer comprises a plurality of micro-scale or nano-scale patterns claim 6 , or combinations thereof claim 6 , wherein at least a portion of the micro-scale or nano-scale patterns of the functional layer perforate the functionalizable layer to expose the ...

SUBSTRATES COMPRISING NANO-PATTERNING SURFACES AND METHODS OF PREPARING THEREOF

Substrates comprising a functionalizable layer, a polymer layer comprising a plurality of micro-scale or nano-scale patterns, or combinations thereof, and a backing layer and the preparation thereof by using room-temperature UV nano-embossing processes are disclosed. The substrates can be prepared by a roll-to-roll continuous process. The substrates can be used as flow cells, nanofluidic or microfluidic devices for biological molecules analysis. 1. A process of preparing a substrate , comprising:contacting a template having a plurality of micro-scale or nano-scale patterns with a surface of a substrate comprising a photocurable polymer layer disposed thereon;applying pressure to the template or substrate to transfer the plurality of micro-scale or nano-scale patterns to the photocurable polymer layer, wherein the contacting and applying are performed at room temperature;irradiating the photocurable polymer with UV light to cure the photocurable polymer to form a UV cured polymer layer; andseparating the template from substrate;wherein the substrate comprises a functionalizable layer in contact with the photocurable polymer layer, wherein the functionalizable layer comprises a functionalizable hydrogel or a functionalizable polymer, and wherein the functionalizable hydrogel or functionalizable polymer comprises one or more functional groups capable of attaching to biomolecules.2. The process of claim 1 , wherein at least a portion of the micro-scale or nano-scale patterns of the template are transferred to the functionalizable layer.3. The process of claim 1 , further comprising applying a sealing layer to the substrate after removing the template to substantially seal the UV cured polymer layer and the functionalizable layer.4. The process of claim 1 , wherein at least a portion of the micro-scale or nano-scale patterns are posts having an average diameter or an average height of less than about 500 nm.5. The process of claim 1 , wherein the functionalizable ...

COMPOSITIONS AND METHODS FOR REPRESENTATIONAL SELECTION OF NUCLEIC ACIDS FROM COMPLEX MIXTURES USING HYBRIDIZATION

The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion of one or more nucleic acids within the complex mixture. A method of selecting a representational sample of genomic sequences from a complete genome also is provided. The invention further provides a nucleic acid population that includes a representational sample having a complexity of less than 10% but more than 0.001% of a complex mixture, the representational sample comprising a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of sequences in a predetermined portion of a sequence collectively present in one or more nucleic acids within the complex mixture. 1. A method of selecting a representational sample of nucleic acid sequences from a complex mixture , comprising:(a) contacting a complex mixture of nucleic acids with a population of solid support-attached capture probes under conditions sufficient for hybridization of said nucleic acids with said capture probes,wherein said ...

Compositions and methods for representational selection of nucleic acids from complex mixtures using hybridization

The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion of one or more nucleic acids within the complex mixture. A method of selecting a representational sample of genomic sequences from a complete genome also is provided. The invention further provides a nucleic acid population that includes a representational sample having a complexity of less than 10% but more than 0.001% of a complex mixture, the representational sample comprising a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of sequences in a predetermined portion of a sequence collectively present in one or more nucleic acids within the complex mixture.

Substrates comprising nano-patterning surfaces and methods of preparing thereof

Substrates comprising a functionalizable layer, a polymer layer comprising a plurality of micro-scale or nano-scale patterns, or combinations thereof, and a backing layer and the preparation thereof by using room-temperature UV nano-embossing processes are disclosed. The substrates can be prepared by a roll-to-roll continuous process. The substrates can be used as flow cells, nanofluidic or microfluidic devices for biological molecules analysis.

Imaging fiber optic array sensors, apparatus, and methods for concurrently detecting multiple analytes of interest in a fluid sample

The present invention provides a unique fiber optic sensor which is able to conduct multiple assays and analysis concurrently using a plurality of different dyes immobilized at individual spatial positions on the surface of the sensor. The present invention also provides apparatus for making precise optical determinations and measurements for multiple analytes of interest concurrently and provides methods of detection for multiple analytes of interest which can be correlated with specific parameters or other ligands for specific applications and purposes.

Fiber optic array sensors, apparatus, and methods for concurrently visualizing and chemically detecting multiple analytes of interest in a fluid sample

The present invention provides a unique fiber optic sensor which is able to provide a viewing zone for visual examination of a sample and its surrounding environment; and is able to conduct multiple assays concurrently using a plurality of different dyes immobilized at individual spatial positions within a dye sensing zone on the surface of the sensor. The present invention also provides apparatus for making precise optical determinations and measurements for multiple analytes of interest concurrently and provides methods of detection for multiple analytes of interest which can be correlated with specific parameters or other ligands for specific applications and purposes.

Method of making imaging fiber optic sensors to concurrently detect multiple analytes of interest in a fluid sample

The present invention provides a unique fiber optic sensor which is able to conduct multiple assays and analyses concurrently using a plurality of different dyes immobilized at individual spatial positions on the surface of the sensor. The present invention also provides apparatus for making precise optical determinations and measurements for multiple analytes of interest concurrently and provides methods of detection for multiple analytes of interest which can be correlated with specific parameters or other ligands for specific applications and purposes.

Substrates comprising nano-patterning surfaces and methods of preparing thereof

Substrates comprising a functionalizable layer, a polymer layer comprising a plurality of micro-scale or nano-scale patterns, or combinations thereof, and a backing layer and the preparation thereof by using room-temperature UV nano-embossing processes are disclosed. The substrates can be prepared by a roll-to-roll continuous process. The substrates can be used as flow cells, nanofluidic or microfluidic devices for biological molecules analysis.

Substrates comprising nano-patterning surfaces and methods of preparing thereof

Substrates comprising a functionalizable layer, a polymer layer comprising a plurality of micro-scale or nano-scale patterns, or combinations thereof, and a backing layer and the preparation thereof by using room-temperature UV nano-embossing processes are disclosed. The substrates can be prepared by a roll-to-roll continuous process. The substrates can be used as flow cells, nanofluidic or microfluidic devices for biological molecules analysis.

Substrates comprising nano-patterning surfaces and methods of preparing thereof

Substrates comprising a functionalizable layer, a polymer layer comprising a plurality of micro-scale or nano-scale patterns, or combinations thereof, and a backing layer and the preparation thereof by using room-temperature UV nano-embossing processes are disclosed. The substrates can be prepared by a roll-to-roll continuous process. The substrates can be used as flow cells, nanofluidic or microfluidic devices for biological molecules analysis.

Encoding and decoding of array sensors utilizing nanocrystals

Described herein are assays and components for encoding and decoding microspheres. Each assay or component described utilizes at least one nanocrystal.

Fiber optic array sensors, apparatus, and methods for concurrently visualizing and chemically detecting multiple analytes of interest in a fluid sample

The present invention provides a unique fiber optic sensor which is able to provide a viewing zone (S14, S18-S24, S39-S46, S51-S58, S63-S70, S75-S82, S89-S96, S100-S106) for visual examination of a sample and its surrounding environment; and is able to conduct multiple assays concurrently using a plurality of different dyes (250, 252, 254, 256) immobilized at individual spatial positions within a dye sensing zone (260A-260D) on the surface of the sensor. The present invention also provides apparatus for making precise optical determinations and measurements for multiple analytes of interest concurrently and provides methods of detection for multiple analytes of interest which can be correlated with specific parameters or other ligands for specific applications and purposes.

Manipulation of droplets on hydrophilic or variegated-hydrophilic surfaces

Provided herein is a droplet actuator including (a) first and second substrates separated by a droplet- operations gap, the first and second substrates including respective hydrophobic surfaces that face the droplet-operations gap; (b) a plurality of electrodes coupled to at least one of the first substrate and the second substrate, the electrodes arranged along the droplet-operations gap to control movement of a droplet along the hydrophobic surfaces within the droplet-operations gap; and (c) a hydrophilic or variegated-hydrophilic surface exposed to the droplet-operations gap, the hydrophilic or variegated- hydrophilic surface being positioned to contact the droplet when the droplet is at a select position within the droplet-operations gap.

gel patterned surface

【課題】表面に複数のウェルがあり、ウェルがゲル材料を含有し、ウェルが表面上の間隙領域によって分けられ、間隙領域が各ウェルのゲル材料を他のウェルのゲル材料から隔離する、固体支持体と、各ウェルのゲル材料がライブラリーの単一種の標的核酸を含む、ライブラリーとを含むアレイの作製方法を提供する。【解決手段】ゾル‐ゲル材料で被覆された基板を、複数の隆起型フィーチャーを含むスタンプと接触させ、被覆したゾル‐ゲル材料をスタンプと接触させながら、前記被覆したゾル‐ゲル材料を硬化させて、間隙領域によって分離された複数のウェルを含むパターン化ゾル‐ゲル層を形成し、該パターン化ゾル‐ゲル層から前記スタンプを分離し、ゲル材料を前記ウェルに蒸着させ、ここで、前記間隙領域はゲル材料を欠いており、その後、プライマー核酸を前記ゲル材料に付着させる、ことを含む、方法である。【選択図】図１

Nanopore sequencers

Example nanopore sequencers include a cis well, a trans well, and a nanopore fluidically connecting the cis and trans wells. In one example sequencer, a modified electrolyte (including an electrolyte and a cation complexing agent) is present in the cis well, or the trans well, or in the cis and the trans wells. In another example sequencer, a gel state polyelectrolyte is present in the cis well, or the trans well, or in the cis and the trans wells.

Nanopore sequencers

Nanopore sequencers

Example nanopore sequencers include a cis well, a trans well, and a nanopore fluidically connecting the cis and trans wells. In one example sequencer, a modified electrolyte (including an electrolyte and a cation complexing agent) is present in the cis well, or the trans well, or in the cis and the trans wells. In another example sequencer, a gel state polyelectrolyte is present in the cis well, or the trans well, or in the cis and the trans wells.

Method for gel patterned surfaces

Un método para obtener una matriz de ácido nucleico, que comprende: revestir con un material de gel al menos una porción de un soporte sólido que comprende una superficie plana interrumpida por una o más características cóncavas bordeadas por una o más regiones intersticiales en la superficie plana, en donde la porción comprende al menos una de las características cóncavas y al menos una de las regiones intersticiales, y en donde el material de gel se confirmará a la forma de las características cóncavas; pulir la superficie plana para eliminar el material de gel de al menos una región intersticial y mantener el material de gel en el al menos una característica cóncava; en donde el método además comprende una etapa de silanización para permitir la unión subsiguiente del material de gel al sustrato a través el silano. en donde el material de gel además está unido a los ácidos nucleicos para obtener la matriz de ácido nucleico. A method for obtaining a nucleic acid matrix, comprising: coating with a gel material at least a portion of a solid support comprising a flat surface interrupted by one or more concave features bordered by one or more interstitial regions in the flat surface , wherein the portion comprises at least one of the concave features and at least one of the interstitial regions, and wherein the gel material will conform to the shape of the concave features; polishing the flat surface to remove gel material from at least one interstitial region and retain the gel material in the at least one concave feature; wherein the method further comprises a silanization step to allow subsequent attachment of the gel material to the substrate through the silane. wherein the gel material is further bound to nucleic acids to obtain the nucleic acid matrix.

Nanopore sequencers

Encoding and decoding of array sensors utilizing nanocrystals

Described herein are assays and components for encoding and decoding microspheres. Each assay or component described utilizes at least one nanocrystal.

Polymer sheets for sequencing applications

Embodiments of the present application relate to patterned polymer sheets and processes to prepare the same for sequencing applications. In particular, flexible micro- and nano-patterned polymer sheets are prepared and used as a template surface in sequencing reaction and new polish-free methods of forming isolated hydrogel plugs in nanowells are described.

Optical sensors with reflective materials and methods for producing such optical sensors

Provided is an optical sensor including a support and a detection layer, wherein the detection layer includes: (a) a luminescent material wherein the luminescence intensity of the luminescent material varies as the amount of an analyte varies; (b) a reflective material having a highly efficient reflectance of the wavelengths of excitation and of emission of the luminescent material; and (c) a polymeric binder to support and hold together the luminescent material and the reflective material. Such an optical sensor can be advantageously used in the detection of gaseous, ionic, and nonionic analytes in highly scattering samples. Also provided are methods for the manufacture of such optical sensors.

Gel pattern surfaces

Substrates comprising nano-patterning surfaces and methods of preparing thereof

Substrates comprising a functionalizable layer, a polymer layer comprising a plurality of micro-scale or nano-scale patterns, or combinations thereof, and a backing layer and the preparation thereof by using room-temperature UV nano-embossing processes are disclosed. The substrates can be prepared by a roll-to-roll continuous process. The substrates can be used as flow cells, nanofluidic or microfluidic devices for biological molecules analysis.

Encoding and decoding of array sensors utilizing nanocrystals

Described herein are assays and components for encoding and decoding microspheres. Each assay or component described utilizes at least one nanocrystal.

Gel patterned surface

【課題】各ウェルのゲル材料がライブラリーの単一種の標的核酸を含む、ライブラリーとを含むアレイ、アレイの作製方法及び使用方法を提供する。【解決手段】表面を含む固体支持体であって、表面が複数のウェルを含み、ウェルが、ウェル内で非共有結合的に保持されるゲル材料を含有し、ウェルが表面上の間隙領域によって互いに分けられ、間隙領域が、各ウェルのゲル材料を、他の複数のウェルのゲル材料から隔離する、固体支持体と、ゲル材料中の標的核酸のライブラリーであって、各ウェルのゲル材料が、固体支持体の他のウェルにおける標的核酸の種と比較される、ライブラリーの異なる種の標的核酸を含む、ライブラリーとを含む、アレイとする。【選択図】図１

Compositions and methods for representational selection of nucleic acids fro complex mixtures using hybridization

The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion of one or more nucleic acids within the complex mixture. A method of selecting a representational sample of genomic sequences from a complete genome also is provided. The invention further provides a nucleic acid population that includes a representational sample having a complexity of less than 10% but more than 0.001% of a complex mixture, the representational sample comprising a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of sequences in a predetermined portion of a sequence collectively present in one or more nucleic acids within the complex mixture.

Faseroptischer matrixsensor und methode zum gleichzeitigen sichtbarmachen und chemischen nachweis mehrerer analyte in einer flüssigkeit

Nanopore sequencers

Example nanopore sequencers include a cis well, a trans well, and a nanopore fluidically connecting the cis and trans wells. In one example sequencer, a modified electrolyte (including an electrolyte and a cation complexing agent) is present in the cis well, or the trans well, or in the cis and the trans wells. In another example sequencer, a gel state polyelectrolyte is present in the cis well, or the trans well, or in the cis and the trans wells.

Codierung und decodierung von sensor-arrays mittels nanokristalle

Nanopore sequencing method

Compositions and methods for representational selection of nucleic acids from complex mixtures using hybridization

The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion of one or more nucleic acids within the complex mixture. A method of selecting a representational sample of genomic sequences from a complete genome also is provided. The invention further provides a nucleic acid population that includes a representational sample having a complexity of less than 10% but more than 0.001% of a complex mixture, the representational sample comprising a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of sequences in a predetermined portion of a sequence collectively present in one or more nucleic acids within the complex mixture.

Gel patterned surfaces

Provided is an array including a solid support having a surface, the surface having a plurality of wells, the wells containing a gel material, the wells being separated from each other by interstitial regions on the surface, the interstitial regions segregating the gel material in each of the wells from the gel material in other wells of the plurality; and a library of target nucleic acids in the gel material, wherein the gel material in each of the wells comprises a single species of the target nucleic acids of the library. Methods for making and using the array are also provided.