Disclosed herein are compositions, probes, devices, and processes useful for detecting specific reactions and binding interactions with biological molecules. In certain embodiments, methods of binding one or more biomolecules to a solid support are disclosed. Methods of generating site-specific sequences for one or more biomolecules from a solid support are also disclosed. Biological complexes generated by these methods are also disclosed.

High-fidelity, high-throughput nucleic acid sequencing enables healthcare practitioners and patients to gain insight into genetic variants and potential health risks. However, previous methods of nucleic acid sequencing often introduce sequencing errors (for example, mutations that arise during the preparation of a nucleic acid library, during amplification, or sequencing). Provided herein are methods and compositions for sequencing nucleic acids. Further provided are methods of identifying an error in a nucleic acid sequence.

High-fidelity, high-throughput nucleic acid sequencing enables healthcare practitioners and patients to gain insight into genetic variants and potential health risks. However, previous methods of nucleic acid sequencing often introduce sequencing errors (for example, mutations that arise during the preparation of a nucleic acid library, during amplification, or sequencing). Provided herein are methods and compositions for sequencing nucleic acids. Further provided are methods of identifying an error in a nucleic acid sequence.

Provided herein are methods for processing a plurality of nucleic acid molecules derived from a cell-free biological sample, comprising bringing said plurality of nucleic acid molecules or derivatives thereof in contact with a plurality of binding agents, to provide a first subset of said plurality of nucleic acid molecules coupled to said plurality of binding agents and a second subset of said plurality of nucleic acid molecules; separating said first subset of said plurality of nucleic acid molecules coupled to said plurality of binding agents from said second subset of said plurality of nucleic acid molecules; circularizing a nucleic acid molecule derived from said first subset of said plurality of nucleic acid molecules to obtain a circularized nucleic acid molecule; and identifying said circularized nucleic acid molecule or derivative thereof.

Provided herein are methods for processing a plurality of nucleic acid molecules derived from a cell-free biological sample, comprising bringing said plurality of nucleic acid molecules or derivatives thereof in contact with a plurality of binding agents, to provide a first subset of said plurality of nucleic acid molecules coupled to said plurality of binding agents and a second subset of said plurality of nucleic acid molecules; separating said first subset of said plurality of nucleic acid molecules coupled to said plurality of binding agents from said second subset of said plurality of nucleic acid molecules; circularizing a nucleic acid molecule derived from said first subset of said plurality of nucleic acid molecules to obtain a circularized nucleic acid molecule; and identifying said circularized nucleic acid molecule or derivative thereof.

A method of detecting materials in a mixture of materials may include providing materials, and providing oligonucleotides having different sequences than one another. Each of the oligonucleotides may be within, and may correspond to, a respective one of the materials. A mixture of at least two of the materials with one another may be obtained. The mixture may include the oligonucleotides corresponding to those materials. The method may include sequencing the oligonucleotides in the mixture; and detecting the materials corresponding to those oligonucleotides using the sequences of those oligonucleotides.

A method of detecting materials in a mixture of materials may include providing materials, and providing oligonucleotides having different sequences than one another. Each of the oligonucleotides may be within, and may correspond to, a respective one of the materials. A mixture of at least two of the materials with one another may be obtained. The mixture may include the oligonucleotides corresponding to those materials. The method may include sequencing the oligonucleotides in the mixture; and detecting the materials corresponding to those oligonucleotides using the sequences of those oligonucleotides.

A fluidic network for carrying out, in parallel, a plurality of analyses of biological samples is disclosed. The network has a flow cell array with a plurality of reaction chambers. The reaction chambers each have a first channel connection and a second channel connection. The first channel connections are connected to a first supply channel and the second channel connections are connected to a second supply channel. The first supply channel and the second channel connection are interconnected by a circulation line. At least one component is connected to the circulation line so that component test reagents can be introduced into the reaction chambers of the flow cell array.

A fluidic network for carrying out, in parallel, a plurality of analyses of biological samples is disclosed. The network has a flow cell array with a plurality of reaction chambers. The reaction chambers each have a first channel connection and a second channel connection. The first channel connections are connected to a first supply channel and the second channel connections are connected to a second supply channel. The first supply channel and the second channel connection are interconnected by a circulation line. At least one component is connected to the circulation line so that component test reagents can be introduced into the reaction chambers of the flow cell array.

A system may include a first conduit configured to form a first batch of discrete volumes of aqueous fluid separated by spacing liquid disposed between consecutive volumes of aqueous fluid, the spacing liquid being immiscible with the aqueous fluid volumes; a second conduit, fluidically coupled to the first conduit, the second conduit configured to statically hold the first batch of discrete volumes of aqueous fluid; and a third conduit configured to receive the first batch of discrete volumes of aqueous fluid from the second conduit. The third conduit can be configured to transfer the discrete volumes of aqueous fluid of the first batch for downstream processing.