A parallelized chain-synthesizing technique includes an array of wells, each well in the array providing a location where a specific arbitrary sequence for polymeric chains can be grown. An optical addressing system selectively delivers light to the wells to mediate or control reactions in the wells.

Methods for the automated template-free synthesis of user-defined sequence controlled biopolymers using microfluidic devices are described. The methods facilitate simultaneous synthesis of up to thousands of uniquely addressed biopolymers from the controlled movement and combination of regents as fluid droplets using microfluidic and EWOD-based systems. In some forms, biopolymers including nucleic acids, peptides, carbohydrates, and lipids are synthesized from step-wise assembly of building blocks based on a user-defined sequence of droplet movements. In some forms, the methods synthesize uniquely addressed nucleic acids of up to 1,000 nucleotides in length. Methods for adding, removing and changing barcodes on biopolymers are also provided. Biopolymers synthesized according to the methods, and libraries and databases thereof are also described. Modified biopolymers, including chemically modified nucleotides and biopolymers conjugated to other molecules are described.

Various aspects disclosed relate to a DNA synthesis substrate. the substrate includes a low temperature co-fired ceramic support. The substrate further includes a linker molecule functionalized to the low temperature co-fired ceramic support.

The invention relates to methods of generating templates for a nucleic acid sequencing reaction which comprise: providing at least one double-stranded nucleic acid molecule, wherein both strands of the double-stranded nucleic acid molecule are attached to a solid support at the 5 end, cleaving one or both strands of the double-stranded nucleic acid molecule, and subjecting the cleaved strand(s) to denaturing conditions to remove the portion of the cleaved strand(s) not attached to the solid support, thereby generating a partially or substantially single-stranded template for a nucleic acid sequencing reaction.

Screening assays and methods of performing such assays are provided. In certain examples, the assays and methods may be designed to determine whether or not two or more species can associate with each other. In some examples, the assays and methods may be used to determine if a known antigen binds to an unknown monoclonal antibody.

Provided is a method of synthesis comprising: (I) providing separate reaction sequences to TABs; (II) utilizing reaction vessels configured to react a separate combinatorial building block with a moiety on a surface of a TAB; and (III) operating one or more TAB sorters comprising a TAB reader, a sorting tree comprising valves or switches and sorting nodes, and a monitor configured to detect TAB location, wherein the operating comprises serially conducting: (a) reacting distinct combinatorial building blocks in the reaction chambers with surfaces of TABs distributed in the reaction chambers; (b) operating a controller to operate the TAB sorters to segregate the TABs to allocations appropriate for the next assigned reaction, the operating including recycling TABs with ambiguous identity back through the sorter; and (c) repeating steps (a) and (b) as needed to complete 30% or more of the assigned sequences.

A high-throughput combinatorial materials experimental apparatus for in-situ synthesis and real-time characterization includes a composition spread device to prepare continuous or discrete composition distribution as precursor of the high-throughput experimental samples library, a low temperature diffusion mixing device to thoroughly mix the composition spread in the thickness direction through diffusion at a relatively low temperature to form an amorphous precursor, and an integrated synthesis-characterization unit for heat treatment of the material library precursor in either a parallel or point-by-point scanning mode at different thermodynamic conditions for phase formation and to characterize features or properties of the materials of interest in an in-situ and real-time manner. The integrated synthesis-characterization unit includes a chamber maintained at desired vacuum and atmosphere, a micro-heating source, an excitation source, a signal collector, and a sample holder.

An example method includes reacting a first solution and a different, second solution on a flow cell by flowing the first solution over amplification sites on the flow cell and subsequently flowing the second solution over the amplification sites. The first solution includes target nucleic acids and a first reagent mixture that comprises nucleoside triphosphates and replication enzymes. The target nucleic acids in the first solution transport to and bind to the amplification sites at a transport rate. The first reagent mixture amplifies the target nucleic acids that are bound to the amplification sites to produce clonal populations of amplicons originating from corresponding target nucleic acids. The amplicons are produced at an amplification rate that exceeds the transport rate. The second solution includes a second reagent mixture and lacks the target nucleic acids. The second solution is to increase a number of the amplicons at the amplification sites.

The invention relates to methods of generating templates for a nucleic acid sequencing reaction which comprise: providing at least one double-stranded nucleic acid molecule, wherein both strands of the double-stranded nucleic acid molecule are attached to a solid support at the 5 end, cleaving one or both strands of the double-stranded nucleic acid molecule, and subjecting the cleaved strand(s) to denaturing conditions to remove the portion of the cleaved strand(s) not attached to the solid support, thereby generating a partially or substantially single-stranded template for a nucleic acid sequencing reaction.

The present invention relates to a method for combinatorial particle manipulation for producing high-density molecule arrays, and to the high-density molecule arrays obtained therefrom. In particular, the present invention relates to a method for producing high-density molecule arrays, in particular peptide or oligonucleotide arrays, by combinatorial patterning of particles, wherein the patterning is achieved by the selective and direct action of electromagnetic radiation.