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.

The present invention relates to a patterned substrate comprising first regions having first dendrimer structures and second regions having second dendrimer structures on a surface of the substrate, as well as a to method for manufacturing a patterned substrate and the use of a patterned substrate for the chemical synthesis of a chemical synthesis product, as a characterizing platform and/or as a platform for cell treatment and/or cell cultivation.

De novo synthesized large libraries of nucleic acids are provided herein with low error rates. Further, devices for the manufacturing of high-quality building blocks, such as oligonucleotides, are described herein. Longer nucleic acids can be synthesized in parallel using microfluidic assemblies. Further, methods herein allow for the fast construction of large libraries of long, high-quality genes. Devices for the manufacturing of large libraries of long and high-quality nucleic acids are further described herein.

Various embodiments of the teachings relate to a system or method for sample preparation or analysis in biochemical or molecular biology procedures. The sample preparation can involve small volume processed in discrete portions or segments or slugs, herein referred to as discrete volumes. A molecular biology procedure can be nucleic acid analysis. Nucleic acid analysis can be an integrated DNA amplification/DNA sequencing procedure.

In an example method, a first functionalized layer is deposited over a resin layer including multi-depth depressions separated by interstitial regions, each depression including a deep portion and a shallow portion adjacent to the deep portion; a photoresist is deposited over the first functionalized layer; an ultraviolet light dosage is directed, through the resin layer, whereby a first photoresist portion generates an insoluble photoresist and a second photoresist portion becomes a soluble photoresist; the soluble photoresist is removed to expose a portion of the first functionalized layer; the portion of the first functionalized layer is removed to expose a portion of the resin layer; a second functionalized layer is deposited over the insoluble photoresist, and over the exposed portion of the resin layer; the insoluble photoresist is removed to expose the first functionalized layer; and the first functionalized layer or the second functionalized layer is removed from the interstitial regions.

A metal film is formed over a resin layer including a plurality of multi-depth depressions (MDP) separated by interstitial regions, each MDP including a deep portion and an adjacent shallow portion. A sacrificial layer is formed over the metal film. The sacrificial layer and metal film are sequentially dry etched to expose a resin layer surface at the shallow portion and interstitial regions. Resin layer portions are removed i) at the shallow portion to form a depression region having a surface directly adjacent to a surface at the deep portion and ii) at the interstitial regions to form new interstitial regions surrounding the deep portion and the depression region. First functionalized layer is deposited over the metal film, depression region, and new interstitial regions. The metal film is removed from the deep portion. Second functionalized layer is deposited over the surface at the deep portion. New interstitial regions are polished.

A method for forming discrete volumes of aqueous fluid may comprise flowing aqueous fluid into a first conduit from a supply of aqueous fluid and flowing into the first conduit a spacing liquid supplied from a second conduit, the spacing liquid being immiscible with the aqueous fluid. The flowing of the aqueous fluid and the spacing liquid into the first conduit forms discrete volumes of the aqueous fluid, with consecutive discrete volumes of the aqueous fluid separated by the spacing liquid. The method may further comprise transferring the discrete volumes of the aqueous fluid and spacing liquid from the first conduit to a third conduit for processing.

De novo synthesized large libraries of nucleic acids are provided herein with low error rates. Further, devices for the manufacturing of high-quality building blocks, such as oligonucleotides, are described herein. Longer nucleic acids can be synthesized in parallel using microfluidic assemblies. Further, methods herein allow for the fast construction of large libraries of long, high-quality genes. Devices for the manufacturing of large libraries of long and high-quality nucleic acids are further described herein.

A microfluidic synthesis platform includes a microfluidic chip holder that has a computer controlled heating element and cooling element therein. A microfluidic chip is mountable in the microfluidic chip holder. The microfluidic chip is formed by a hydrophobic substrate having patterned thereon a hydrophilic reaction site and a plurality of hydrophilic channels or pathways extending outward from the hydrophilic reaction site and terminating at respective loading sites on the substrate, wherein the hydrophilic channels or pathways are tapered with an increasing width in an inward direction toward the hydrophilic reaction site. A fixture is provided for holding a plurality of non-contact reagent dispensing devices above the microfluidic chip at locations corresponding to the loading sites of the plurality of hydrophilic channels or pathways, the fixture further holding a moveable collection tube disposed above the hydrophilic reaction site of the microfluidic chip for removing droplets containing reaction products.

A chemical synthesis platform based on a particularly simple chip is described herein, where reactions take place atop a hydrophobic substrate patterned with a circular hydrophilic liquid trap. The overall supporting hardware (heater, rotating carousel of reagent dispensers, etc.) can be packaged into a very compact format (about the size of a coffee cup). We demonstrate the consistent synthesis of [.sup.18F]fallypride with high yield, and show that protocols optimized using a high-throughput optimization platform we have developed can be readily translated to this device with no changes or reoptimization.