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.

The invention features methods of making devices, or platens, having a high-density array of through-holes, as well as methods of cleaning and refurbishing the surfaces of the platens. The invention further features methods of making high-density arrays of chemical, biochemical, and biological compounds, having many advantages over conventional, lower-density arrays. The invention includes methods by which many physical, chemical or biological transformations can be implemented in serial or in parallel within each addressable through-hole of the devices. Additionally, the invention includes methods of analyzing the contents of the array, including assaying of physical properties of the samples.

A method of preparing a discrete polymer network array include mixing a plurality of nucleic acid polymer networks with a plurality of color-activated polymer networks to form a dispersion, applying the dispersion to an array of wells, the nucleic acid polymer networks selectively depositing into wells of the array of wells, and rinsing the array of wells to selectively remove the plurality of color-activated polymer networks.

This invention provides high unit density arrays of microparticles and methods of assembling such arrays. The microparticles in the arrays may be functionalized with chemical or biological entities specific to a given target analyte. The high unit density arrays of this invention are formed on chips which may be combined to form multichip arrays according to the methods described herein. The chips and/or multichip arrays of this invention are useful for chemical and biological assays.

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.

A kit and a method for enriching target nucleic acid sequences from a biological sample are disclosed. The method includes preparing, and contacting with the biological sample, a first RNA probe set and a second RNA probe set respectively targeting both of the two antiparallel strands of a duplex segment in each target nucleic acid sequence. Each RNA probe in the first RNA probe set and the second RNA probe set can be generated by chemical synthesis or by in vitro or in vivo transcription, and can be biotin-labelled to thereby allow capturing of the target nucleic acid sequences by magnetic beads labelled with streptavidin, or can be engineered to a microfluidic channel to facilitate the capturing. The method can be applied to capture double-stranded nucleic acid sequences or single-stranded nucleic acid sequences having duplex segments, and the nucleic acid sequences can include DNAs, RNAs, or DNA-RNA hybrid molecules.

The present invention provides methods, systems and kits for performing microwell analysis in sealed small volumes. The microwells of the invention are sealed through the pairing of microwell and bead geometry wherein the diameter of the beads is greater than the diameter of the bottom of the microwells. Loading the beads into the microwells seals samples within an analytical space between the bottom of a nested bead and the bottom of the subject microwell.

An electrode array including a substrate. The electrode array includes a first plurality of electrodes disposed above a first zone of the substrate, wherein the first plurality of electrodes has a first range of spacing. The electrode array further includes a second plurality of electrodes disposed above a second zone of the substrate, wherein the second plurality of electrodes has a second range of spacing that is less than the first range of spacing.

A method of manufacturing and using micro assembler systems are described. A method of manufacturing includes disposing a first plurality of electrodes above a first zone of the substrate, wherein the first plurality of electrodes has a first range of spacing. The method further includes disposing a second plurality of electrodes above a second zone of the substrate, wherein the second plurality of electrodes has a second range of spacing that is less than the first range of spacing. A method of using micro assembler systems includes disposing a mobile particle at least partially submersed in an assembly medium above a substrate, a first plurality of electrodes and a second plurality of electrodes. The method further includes conducting a field through individual electrodes of the first plurality of electrodes and the second plurality of electrodes to generate electrophoretic forces or dielectrophoretic forces on the mobile particle.

The present invention provides novel compositions, methods and apparatus for DNA sequencing that can be performed, e.g., in a two-electrode chamber. The present invention also provides a method for sequencing a nucleic acid comprising immobilizing a plurality of complexes comprising a target nucleic acid, a primer nucleic acid, and a polymerase onto a surface, contacting the surface with a plurality of charged particles comprising a nucleotide phosphate by applying an electric field, reversing the electric field to transport unbound charged particles away from the surface, and detecting the incorporation of a nucleotide phosphate into a single molecule of the primer nucleic acid.