Abstract: Provided herein are methods and devices for characterizing a biomolecule parameter by a nanopore-containing membrane, and also methods for making devices that can be used in the methods and devices provided herein. The nanopore membrane is a multilayer stack of conducting layers and dielectric layers, wherein an embedded conducting layer or conducting layer gates provides well-controlled and measurable electric fields in and around the nanopore through which the biomolecule translocates. In an aspect, the conducting layer is graphene.

Abstract: A microarray is designed capture one or more molecules of interest at each of a plurality of sites on a substrate. The sites comprise base pads, such as polymer base pads, that promote the attachment of the molecules at the sites. The microarray may be made by one or more patterning techniques to create a layout of base pads in a desired pattern. Further, the microarrays may include features to encourage clonality at the sites.

Abstract: Provided herein are methods and devices for characterizing a biomolecule parameter by a nanopore-containing membrane, and also methods for making devices that can be used in the methods and devices provided herein. The nanopore membrane is a multilayer stack of conducting layers and dielectric layers, wherein an embedded conducting layer or conducting layer gates provides well-controlled and measurable electric fields in and around the nanopore through which the biomolecule translocates. In an aspect, the conducting layer is graphene.

Abstract: A method of making a flowcell includes bonding a first surface of an organic solid support to a surface of a first inorganic solid support via a first bonding layer, wherein the organic solid support includes a plurality of elongated cutouts. The method further includes bonding a surface of a second inorganic solid support to a second surface of the organic solid support via a second bonding layer, so as to form the flowcell. The formed flowcell includes a plurality of channels defined by the surface of the first inorganic solid support, the surface of the second inorganic solid support, and walls of the elongated cutouts.

Abstract: A method includes forming a patterned substrate including a plurality of base pads, using a nano-imprint lithography process. A capture substance is attached to each of the plurality of base pads, optionally through a linker, the capture substance being adapted to promote capture of a target molecule.

Abstract: Presented are methods and compositions for spatial detection and analysis of nucleic acids in a tissue sample. The methods can enable the characterization of transcriptomes and/or genomic variations in tissues while preserving spatial information about the tissue.

Abstract: 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.

Abstract: A fluidic device including an inorganic solid support attached to an organic solid support by a bonding layer, wherein the inorganic solid support has a rigid structure and wherein the bonding layer includes a material that absorbs radiation at a wavelength that is transmitted by the inorganic solid support or the organic solid support; and a channel formed by the inorganic solid support and the organic solid support, wherein the bonding layer that attaches the inorganic solid support to the organic solid support provides a seal against liquid flow. Methods for making fluidic devices, such as this, are also provided.

Abstract: Structured substrate including (a) a plurality of nanoparticles distributed on a solid support, (b) a gel material forming a layer in association with the plurality of nanoparticles, and (c) a library of target nucleic acids in the gel material.

Abstract: A method including (a) providing an amplification reagent including an array of sites, and a solution having different target nucleic acids; and (b) reacting the amplification reagent to produce amplification sites each having a clonal population of amplicons from a target nucleic acid from the solution. The reacting can include simultaneously transporting the nucleic acids to the sites at an average transport rate, and amplifying the nucleic acids that transport to the sites at an average amplification rate, wherein the average amplification rate exceeds the average transport rate. The reacting can include producing a first amplicon from a nucleic acid that transports to each of the sites, and producing subsequent amplicons from the nucleic acid or from the first amplicon, wherein the average rate at which the subsequent amplicons are generated exceeds the average rate at which the first amplicon is generated.

Abstract: A method including (a) providing an amplification reagent including an array of sites, and a solution having different target nucleic acids; and (b) reacting the amplification reagent to produce amplification sites each having a clonal population of amplicons from a target nucleic acid from the solution. The reacting can include simultaneously transporting the nucleic acids to the sites at an average transport rate, and amplifying the nucleic acids that transport to the sites at an average amplification rate, wherein the average amplification rate exceeds the average transport rate. The reacting can include producing a first amplicon from a nucleic acid that transports to each of the sites, and producing subsequent amplicons from the nucleic acid or from the first amplicon, wherein the average rate at which the subsequent amplicons are generated exceeds the average rate at which the first amplicon is generated.

Abstract: A microarray is designed capture one or more molecules of interest at each of a plurality of sites on a substrate. The sites comprise base pads, such as polymer base pads, that promote the attachment of the molecules at the sites. The microarray may be made by one or more patterning techniques to create a layout of base pads in a desired pattern. Further, the microarrays may include features to encourage clonality at the sites.

Abstract: A microarray is designed capture one or more molecules of interest at each of a plurality of sites on a substrate. The sites comprise base pads, such as polymer base pads, that promote the attachment of the molecules at the sites. The microarray may be made by one or more patterning techniques to create a layout of base pads in a desired pattern. Further, the microarrays may include features to encourage clonality at the sites.

Abstract: Provided are methods and systems for characterizing a biomolecular parameter of a polynucleotide. A polynucleotide of interest from a sample comprising a heterogeneous mixture of polynucleotides is concentrated and provided to a first fluid compartment of a solid-state nanopore. An electric potential is established across the solid-state nanopore to force the polynucleotide of interest from a first fluid compartment to a second fluid compartment via the nanopore. A passage parameter output is monitored during passage of the polynucleotide of interest through the nanopore, wherein the passage parameter output depends on the biomolecular parameter status of the polynucleotide of interest. In this manner, the methods and systems are compatible with a wide range of applications, including epigenetic modifications to DNA indicative of a disease state such as cancer, in an integrated, reliable and low cost system.

Abstract: 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.

Abstract: 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.

Abstract: A method including (a) providing an amplification reagent including an array of sites, and a solution having different target nucleic acids; and (b) reacting the amplification reagent to produce amplification sites each having a clonal population of amplicons from a target nucleic acid from the solution. The reacting can include simultaneously transporting the nucleic acids to the sites at an average transport rate, and amplifying the nucleic acids that transport to the sites at an average amplification rate, wherein the average amplification rate exceeds the average transport rate. The reacting can include producing a first amplicon from a nucleic acid that transports to each of the sites, and producing subsequent amplicons from the nucleic acid or from the first amplicon, wherein the average rate at which the subsequent amplicons are generated exceeds the average rate at which the first amplicon is generated.

Abstract: A fluidic device including an inorganic solid support attached to an organic solid support by a bonding layer, wherein the inorganic solid support has a rigid structure and wherein the bonding layer includes a material that absorbs radiation at a wavelength that is transmitted by the inorganic solid support or the organic solid support; and a channel formed by the inorganic solid support and the organic solid support, wherein the bonding layer that attaches the inorganic solid support to the organic solid support provides a seal against liquid flow. Methods for making fluidic devices, such as this, are also provided.

Abstract: A method including (a) providing an amplification reagent including an array of sites, and a solution having different target nucleic acids; and (b) reacting the amplification reagent to produce amplification sites each having a clonal population of amplicons from a target nucleic acid from the solution. The reacting can include simultaneously transporting the nucleic acids to the sites at an average transport rate, and amplifying the nucleic acids that transport to the sites at an average amplification rate, wherein the average amplification rate exceeds the average transport rate. The reacting can include producing a first amplicon from a nucleic acid that transports to each of the sites, and producing subsequent amplicons from the nucleic acid or from the first amplicon, wherein the average rate at which the subsequent amplicons are generated exceeds the average rate at which the first amplicon is generated.

Abstract: A method including (a) providing an amplification reagent including an array of sites, and a solution having different target nucleic acids; and (b) reacting the amplification reagent to produce amplification sites each having a clonal population of amplicons from a target nucleic acid from the solution. The reacting can include simultaneously transporting the nucleic acids to the sites at an average transport rate, and amplifying the nucleic acids that transport to the sites at an average amplification rate, wherein the average amplification rate exceeds the average transport rate. The reacting can include producing a first amplicon from a nucleic acid that transports to each of the sites, and producing subsequent amplicons from the nucleic acid or from the first amplicon, wherein the average rate at which the subsequent amplicons are generated exceeds the average rate at which the first amplicon is generated.