A method of characterizing candidate agents including steps of (a) providing a library of candidate agents attached to nucleic acid tags; (b) contacting the library with a solid support to attach the candidate agents to the solid support, whereby an array of candidate agents is formed; (c) contacting the array with a screening agent, wherein one or more candidate agents in the array react with the screening agent; (d) detecting the array to determine that at least one candidate agent in the array reacts with the screening agent; (e) sequencing the nucleic acid tag to determine the tag sequences attached to candidate agents in the array; and (f) identifying the at least one candidate agent in the array that reacts with the screening agent based on the tag sequence that is attached to the at least one candidate agent.

Provided are methods for non-enzymatically synthesizing nucleic acids. The methods include submerging a first portion of the outer surface of a cylinder in a non-enzymatic nucleic acid synthesis reaction mixture. The reaction mixture has a pH of 4 or less and includes an organizing matrix reagent and monophosphate nucleotides. The methods further include rotating the cylinder about its axis of radial symmetry so that the first portion of the outer surface of the cylinder is no longer submerged in the reaction mixture, thereby providing a thin film of the reaction mixture on the first portion of the outer surface of the cylinder. The methods further include heating and drying the thin film to form phosphodiester bonds between the monophosphate nucleotides of the thin film. Also provided are devices that find use, e.g., in practicing the methods of the present disclosure.

Methods, systems, compositions, and devices for the manufacturing of high-quality building blocks, such as polynucleotides, are described herein. Processes described herein provide for efficient washing of residual reagents, solvents, or byproducts from previous synthetic steps to allow for the generation of polynucleotides with low error rates. Processes described herein also provide for reduction in deletion rates during chemical nucleic acid synthesis. Further, methods and devices described herein allow for the rapid construction and assembly of large libraries of highly accurate polynucleotides.

A method for DNA synthesis using protected nucleosides is disclosed. The nucleosides may be nucleoside triphosphates or nucleoside phosphoramidites with nucleobases attached to electrochemically-cleavable linkers. Removal of a protecting group by application of a voltage in solution triggers a cyclization reaction that cleaves the electrochemically-cleavable linkers. The electrochemically-cleavable linkers may include an amide linkage and an amide that forms a lactam or an ester linkage and a protected alcohol that forms a lactone when the protecting group is removed. The voltage used to cleave the electrochemically-cleavable linkers may be generated by activation of individual electrodes on a microelectrode array. The microelectrode array can be a substrate for solid-phase synthesis of oligonucleotides. Activation of specific electrodes removes the protecting groups at those electrodes and thus enables spatially-controlled extension of the oligonucleotides. Protected nucleosides linked to protecting groups by electrochemically-cleavable linkers are also disclosed.

An example flow cell includes a patterned substrate having an active region and a bonding region that at least partially surrounds the active region. The active region includes first depressions defined in a layer of the patterned substrate, surface chemistry positioned in the first depressions, and first interstitial regions surrounding the first depressions. The bonding region includes second depressions defined in the layer and second interstitial regions surrounding the second depressions. An adhesive is positioned over the second depressions and over the second interstitial regions. A cover is attached to the adhesive such that a flow channel is defined between a portion of the cover and the active region.

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.

Methods of transferring bio-molecular components of individual cells in a biological sample to a solid porous substate, as well as methods of examining or detecting one or more bio-molecular components of individual cells in a biological sample. The method transferring including contacting the biological sample to a first side of the porous solid substrate having a plurality of interstices or pores extending contiguously from the first side to a second side, transferring and affixing the bio-molecular components of the biological sample to the interstices or pores of the solid substrate, and the method of examining or detecting includes detecting one or more of the bio-molecular components of the biological sample transferred to the solid porous substrate.

Methods, systems, compositions, and devices for the manufacturing of high-quality building blocks, such as polynucleotides, are described herein. Processes described herein provide for efficient washing of residual reagents, solvents, or byproducts from previous synthetic steps to allow for the generation of polynucleotides with low error rates. Processes described herein also provide for reduction in deletion rates during chemical nucleic acid synthesis. Further, methods and devices described herein allow for the rapid construction and assembly of large libraries of highly accurate polynucleotides.

The invention relates to a method for microarray transformation, wherein, by using a cavity chip with transformation matrix, a template array can be copied onto a planar support, and the information or spatial arrangement is changed in the process, so that a transformed second array forms. The invention further relates to a device for carrying out such a method.

The present disclosure provides methods of transferring bio-molecular components of individual cells in a biological sample to a solid porous substate. The method including contacting the biological sample to a first side of the porous solid substrate having a plurality of interstices or pores extending contiguously from the first side to a second side, transferring and affixing the bio-molecular components of the biological sample to the interstices or pores of the solid substrate. The present disclosure further provides methods of examining or detecting one or more bio-molecular components of individual cells in a biological sample. The method includes transferring one or more bio-molecular components of individual cells in a biological sample to a solid porous substate, and detecting one or more of the bio-molecular components of the biological sample.