High surface area coatings are applied to solid substrates to increase the surface area available for solid-phase synthesis of polymers. The high surface area coatings use three-dimensional space to provide more area for functional groups to bind polymers than an untreated solid substrate. The polymers may be oligonucleotides, polypeptides, or another type of polymer. The solid substrate is a rigid supportive layer made from a material such as glass, a silicon material, a metal material, and plastic. The coating may be thin films, hydrogels, microparticles. The coating may be made from a metal oxide, a high- dielectric, a low- dielectric, an etched metal, a carbon material, or an organic polymer. The functional groups may be hydroxyl groups, amine groups, thiolate groups, alkenes, n-alkenes, alkalines, N-Hydroxysuccinimide (NHS)-activated esters, polyaniline, aminosilane groups, silanized oxides, oligothiophenes, and diazonium compounds. Techniques for applying coatings to solid substrates and attaching functional groups are also disclosed.

Disclosed herein is a substrate which includes a functional group protected with a photolabile group covalently attached to the substrate and a film of solvent thereof covering the substrate, where the thickness of the film is less than about 100 m. Also disclosed herein are methods of preparing such substrates. Further disclosed are methods of synthesizing polymers, methods of synthesizing arrays of polymers and methods of removing photolabile protecting groups. These methods all employ covering the substrate with a thin film of solvent where the thickness of the film is less than 100 m.

Disclosed herein are formulations, substrates, and arrays. In certain embodiments, substrates and arrays comprise a porous layer for synthesis and attachment of polymers or biomolecules. Also disclosed herein are methods for manufacturing and using the formulations, substrates, and arrays, including porous arrays. Also disclosed herein are formulations and methods for one-step coupling, e.g., for synthesis of peptides in an N->C orientation. In some embodiments, disclosed herein are formulations and methods for high efficiency coupling of biomolecules to a substrate.

A method for producing a nucleic acid array which includes: a step of forming a resist film using a positive resist composition containing a photo acid generator for generating an acid as a result of being exposed to light on a solid phase which has a molecule immobilized thereon and having functional groups protected by an acid-decomposable protective group; a step of exposing a desired position of the resist film to light; a step of developing the resist film which has been subjected to development using a developing liquid; and a step of bringing the solid phase including the resist film which has been subjected to development into contact with a nucleotide derivative having an acid-decomposable protective group is provided.

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.

Disclosed herein are formulations, substrates, and arrays for the synthesis of PNA chains and PNA-DNA chimera on microarrays. In some embodiments, the formulations include a photo-protective compound that shields any PNA monomers, PNA polymers, or PNA-DNA chimera already attached to a microarray from radiation exposure during the synthesis of the PNA or PNA-DNA chains. In some embodiments, substrates and arrays comprise a porous or a planar layer for synthesis and attachment of PNA or DNA monomers, or PNA or PNA-DNA polymers. In some embodiments, disclosed herein are formulations and methods for high efficiency coupling of PNA monomers or PNA polymers to a microarray substrate.

Silanation compositions containing a mixture of two or more silanation reagents, where at least one silanation reagent includes a functional group capable of supporting polymer synthesis and at least one silanation reagent includes no functional group capable of supporting polymer synthesis are useful in modulating the active site density and hydrolytic stability of a surface. These compositions are particularly useful in silanating a surface prior to preparation of a polymer array and provide for increased hybridization results.

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.

Provided herein are methods, chemical library and simulation system for performing in situ patterned chemistry. Methods, systems and assays comprising the use of the synthesized chemical libraries, which increase explored protein space in a knowledge-based manner, are also provided for characterizing antibody-target interactions including: identifying target proteins of antibodies, characterizing antibody-binding regions in target proteins, identifying linear and structural epitopes in target proteins, and determining the propensity of antibody binding to target proteins.

The present disclosure provides methods, device, and system for wafer processing. The wafer processing apparatus uses lid dispenser to disperse at least one reagent to the surface of the wafer. Further, the wafer is positioned on top of a rotatable vacuum chuck configured to spread at least one reagent over the surface of the wafer via a centrifugal force or surface tension, thereby permitting the at least one reagent to react with an additional reagent. Further, when dispensing the at least one reagent, a separation gap between the lid dispenser and the wafer is at a predetermined distance, for example, from 50 m to 2 mm.