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.

Methods and compositions are disclosed relating to the localization of nucleic acids to arrays such as silane-free arrays, and of sequencing the nucleic acids localized thereby.

An apparatus and system for contacting a mobile elongate solid phase, e.g. a ribbon with a flowing fluid phase, and a method for using the same in, for example solid phase synthesis. A particular apparatus comprises (i) a conduit which is of circular or non-circular transverse cross section and which defines a lumen to contain both the flowing fluid phase and the mobile elongate solid phase; (ii) fluid phase ports in communication with the lumen to allow the fluid phase to enter the lumen, flow through it and exit it; and (iii) solid phase ports in communication with the lumen to allow the mobile solid phase to enter the lumen, move through it and exit it, the apparatus being adapted to prevent fluid egress from its interior through the solid phase ports.

Provided are methods for biological sample processing and analysis. A method can comprise providing a substrate configured to rotate. The substrate can comprise an array having immobilized thereto a biological analyte. A solution comprising a plurality of probes may be directed, via centrifugal force, across the substrate during rotation of the substrate, to couple at least one of the plurality of probes with the biological analyte. A detector can be configured to detect a signal from the at least one probe coupled to the biological analyte, thereby analyzing the biological analyte.

Provided are methods for biological sample processing and analysis. A method can comprise providing a substrate configured to rotate. The substrate can comprise an array having immobilized thereto a biological analyte. A solution comprising a plurality of probes may be directed, via centrifugal force, across the substrate during rotation of the substrate, to couple at least one of the plurality of probes with the biological analyte. A detector can be configured to detect a signal from the at least one probe coupled to the biological analyte, thereby analyzing the biological analyte.

A machine-readable medium and methods of reading and writing same are disclosed. The machine-readable medium comprises a substrate having an array of addressable locations thereon, each addressable location adapted to be physically associated with a collection of non-polymeric molecules. The molecules in each collection are selected from a set of unambiguously identifiable molecules, each molecule uniquely associated with a predetermined position in a numerical value, wherein the presence of the molecule in the collection indicates a predetermined digit at the associated position and the absence of said molecule in the collection indicates a zero at said associated position.

Substrates for solid-phase synthesis are reused by freeing synthesized polymers without removing the linkers that hold the polymers to the substrate. The linkers may be made of oligonucleotides or polypeptides. In an implementation, the polymers are released by cleavage of the linkers and then the truncated linkers are regenerated by adding back the portion that was removed. In an implementation, molecular bonds between the linkers and the polymers are cleaved releasing the polymers while leaving the linkers available for reuse without regeneration. In an implementation, single-stranded oligonucleotide linkers are hybridized to complementary strands that hold the polymers to the substrate with double-stranded oligonucleotide complexes. The double-stranded oligonucleotide complexes are denatured releasing the polymers while leaving the original linkers attached to the substrate. The polymers that are synthesized with these techniques may be the same or different type of molecules than the linkers.

Method for manufacturing microarrays and verifying the quality of said microarrays, wherein the method comprises: a) providing at least one reagent, b) loading said at least one reagent in a dispensing print head, in a predetermined arrangement, c) in a first print pass, generating instructions for the print head and moving said print head with respect to a substrate to print said at least one reagent on the substrate to obtain microarrays, d) obtaining an image of the printed microarrays by means of a camera, e) processing the obtained images of the printed microarrays, to calculate parameters indicative for the quality of the printed microarrays, f) comparing, at the end of the first print pass, the calculated parameters for the printed microarrays with predetermined criteria for the microarrays, to identify possible printing defects, g) comparing, for the printed microarrays, the identified printing defects of step f), h) using the outcome of the comparison of step g) to select a corrective action to improve the quality of the microarrays, prior to the printing of a subsequent print pass.

Provided herein are biomolecular hybridization devices comprising a substrate with a permanently and covalently attached surface of functional groups and an adsorbed monolayer of unmodified, single-stranded oligonucleotides all of which are 10 to about 24 bases in length as a saturated film of constrained oligonucleotides on the surface via direct non-covalent phosphate-surface adsorptive contact of substantially all phosphate groups of each oligonucleotide. The constrained oligonucleotides are effective to dissociably hybridize to a complementary single-stranded nucleic acid with asymmetric, non-helical base pairing and without oligonucleotide dissociation from the surface of the device. Also, provided are methods for hybridizing solution-state target nucleic acids to probe nucleic acids and for identifying a nucleotide sequence to which a nucleotide-binding protein binds using the biomolecular hybridization devices.

Disclosed herein are methods for forming one or more nanoparticles. The methods include depositing a solution comprising a block copolymer and a metal salt into one or more square pyramidal nanoholes formed in a substrate, and annealing the substrate to provide a single nanoparticle in each of the one or more square pyramidal nanoholes.