The invention provides an amphiphilic coating for the direct and rapid synthesis of an array of peptides and small molecular compounds on a planar surface of a solid support, comprising a hydrophilic chemical structure and a lipophilic group, wherein said peptides and small molecular compounds differ from spot to spot from each other in the chemical structure, characterized in that said amphiphilic coating possesses low wettability to polar aprotic solvents used in the array synthesis; said amphiphilic coating possessing low wettability is designed that it can be converted to a coating possessing high wettability by hydrolysis of the lipophilic group; and said amphiphilic coating comprises an amino group for the reaction with an electrophilic reagent. The invention further provides a solid support comprising said amphiphilic coating and a method for method for the direct and rapid synthesis of an array of peptides and small molecular compounds on a planar surface of a solid support, wherein said planar surface of a solid support comprises said amphiphilic coating. Said method includes the enhancing of the wettability of a glass surface to organic solvents to realize automated on-demand biomolecular array synthesis comprising both, peptides and small molecular compounds. The amphiphilic surface can be switched to a hydrophilic surface, resulting in high density arrays suitable for protein- and cell-based screening.

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.

Selectively controllable cleavable linkers include electrochemically-cleavable linkers, photolabile linkers, thermolabile linkers, chemically-labile linkers, and enzymatically-cleavable linkers. Selective cleavage of individual linkers may be controlled by changing local conditions. Local conditions may be changed by activating electrodes in proximity to the linkers, exposing the linkers to light, heating the linkers, or applying chemicals. Selective cleaving of enzymatically-cleavable linkers may be controlled by designing the sequences of different sets of the individual linkers to respond to different enzymes. Cleavable linkers may be used to attach polymers to a solid substrate. Selective cleavage of the linkers enables release of specific polymers from the solid substrate. Cleavable linkers may also be used to attach protecting groups to the ends of growing polymers. The protecting groups may be selectively removed by cleavage of the linkers to enable growth of specific polymers.

Provided in some aspects are methods for light-controlled in situ surface patterning of an array. Compositions such as nucleic acid arrays produced by the methods are also disclosed.

Disclosed herein is an apparatus comprising: a probe carrier comprising: a first substrate comprising a first plurality of through holes in the first substrate, a transparent window attached to the first substrate and across an opening of each of the first plurality of through holes, wherein the transparent window closes the opening; and probes attached to one or more locations on the transparent window, wherein interaction between the probes and an analyte generates a signal; a second substrate comprising a second plurality of through holes in the second substrate, wherein the second plurality of through holes are configured as a plurality of collimators; a sensor comprising a plurality of pixels configured to detect the signal.

Methods for designing scaffolded RNA nanostructures of desired shape are described. In some forms, the methods design nucleic acid “staple” sequences that hybridize to a user-defined RNA scaffold and fold it into the desired shape based on A-form helical nucleic acid geometry. In some forms, the methods implement asymmetry in nucleotide positions across two helices of an edge to account for A-form nucleic acid geometry. In preferred forms, crossover asymmetry is implemented in the staples. In other forms, crossover asymmetry is implemented in the RNA scaffold. In other forms, the methods do not introduce crossover asymmetry. Scaffolded RNA nanostructures produced according to the methods including messenger RNAs, replicating RNAs, functional RNAs and other RNA species within the scaffold, staples, or both scaffold and staples are provided. Modified nanostructures including chemically modified nucleotides are also described.

Selectively controllable cleavable linkers include electrochemically-cleavable linkers, photolabile linkers, thermolabile linkers, chemically-labile linkers, and enzymatically-cleavable linkers. Selective cleavage of individual linkers may be controlled by changing local conditions. Local conditions may be changed by activating electrodes in proximity to the linkers, exposing the linkers to light, heating the linkers, or applying chemicals. Selective cleaving of enzymatically-cleavable linkers may be controlled by designing the sequences of different sets of the individual linkers to respond to different enzymes. Cleavable linkers may be used to attach polymers to a solid substrate. Selective cleavage of the linkers enables release of specific polymers from the solid substrate. Cleavable linkers may also be used to attach protecting groups to the ends of growing polymers. The protecting groups may be selectively removed by cleavage of the linkers to enable growth of specific polymers.

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.

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.

Disclosed herein is an apparatus comprising: a probe carrier comprising: a first substrate comprising a first plurality of through holes in the first substrate, a transparent window attached to the first substrate and across an opening of each of the first plurality of through holes, wherein the transparent window closes the opening; and probes attached to one or more locations on the transparent window, wherein interaction between the probes and an analyte generates a signal; a second substrate comprising a second plurality of through holes in the second substrate, wherein the second plurality of through holes are configured as a plurality of collimators; a sensor comprising a plurality of pixels configured to detect the signal.