The invention relates to a device and a method for the generation of molecular microarrays. The invention relates therefore to a universal approach for the generation of protein microarrays, DNA microarrays and RNA microarrays (in general nucleic acid microarrays), by production of an output molecule from a template molecule microarray via enzymatic or chemical processes and transfer of the output molecule onto the desired molecular microarray.

This disclosure provides methods and devices for the label-free detection of target molecules of interest. The principles of the disclosure are particularly applicable to the detection of biological molecules (e.g., DNA, RNA, and protein) using standard SiO.sub.2-based microarray technology.

A fluorous-modified composition, a fluorous nucleoside, nucleotide, or oligonucleotide microarray, a compositional detection process, a process of forming a fluorous nucleoside, nucleotide, or oligonucleotide microarray, and fluorous nucleoside, nucleotide, or oligonucleotide microarray processes are disclosed. The fluorous-modified composition includes a linker, a nucleoside, nucleotide, or oligonucleotide connected to the linker, and a fluorous domain connected to the linker. The fluorous-modified composition includes at least one terminal perfluoroalkyl group in the fluorous domain, a solid-phase attachment group connected to the linker, or a combination thereof. The compositional detection process includes using the fluorous microarray for compositional detection. The processes of forming a fluorous microarray include transfer blotting the fluorous-modified composition to form a fluorous microarray and the spotting of reaction mixtures containing a fluorous-modified nucleoside, nucleotide, or oligonucleotide. The fluorous microarray includes a fluorous-modified conductive surface and fluorous nucleoside, nucleotide, or oligonucleotides positioned on the fluorous-modified surface. The fluorous microarray process includes using information corresponding to a compositional detection process.

A catalytically active substance includes a copper (I) sulfide mineral particle, and an alkyne functionalized molecule bound to a surface of the copper (I) sulfide mineral particle. In an example method, a copper (I) sulfide mineral is reacted with an alkyne functionalized molecule to form a catalytically active substance. The catalytically active substance is reacted with an azide functionalized molecule to couple the catalytically active substance with the azide functionalized molecule.

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.

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.

The present disclosure relates to processes for inverting oligonucleotide probes in an in situ synthesized array. These processes can be used to reverse the orientation of probes with respect to the substrate from 3-bound to 5-bound. These processes can also be used to reduce or eliminate the presence of truncated probe sequences from an in situ synthesized array.

The invention relates to a method for producing polymers, in particular synthetic nucleic acid double strands of optional sequence, comprising the steps: (a) provision of a support having a surface area which contains a plurality of individual reaction areas, (b) location-resolved synthesis of nucleic acid fragments having in each case different base sequences in several of the individual reaction areas, and (c) detachment of the nucleic acid fragments from individual reaction areas.

Methods are provided for producing a molecular array comprising a plurality of molecules immobilized to a solid substrate at a density which allows individual immobilized molecules to be individually resolved, wherein each individual molecule in the array is spatially addressable and the identity of each molecule is known or determined prior to immobilization. The use of spatially addressable low density molecular arrays in single molecule detection and analysis techniques is also provided. Novel assays and methods are also provided.

Some embodiments described herein relate to a substrate with a surface comprising a silane or a silane derivative covalently attached to optionally substituted cycloalkene or optionally substituted heterocycloalkene for direct conjugation with a functionalized molecule of interest, such as a polymer, a hydrogel, an amino acid, a nucleoside, a nucleotide, a peptide, a polynucleotide, or a protein. In some embodiments, the silane or silane derivative contains optionally substituted norbornene or norbornene derivatives. Method for preparing a functionalized surface and the use in DNA sequencing and other diagnostic applications are also disclosed.