The invention, depending on aspect and embodiment, relates to capture probe controls, and capture and signal probe configurations and combinations of configurations that can facilitate accurate and efficient multiplex analyte detection, especially in electrochemical detection schemes.

The present disclosure relates to novel macrocyclic compounds and libraries thereof containing heteroaryl moieties that are useful as research tools for drug discovery efforts. The present disclosure also relates to methods of preparing these compounds and libraries and methods of using these libraries, such as in high throughput screening. In particular, these libraries are useful for evaluation of bioactivity at existing and newly identified pharmacologically relevant targets, including G protein-coupled receptors, nuclear receptors, enzymes, ion channels, transporters, transcription factors, protein-protein interactions and nucleic acid-protein interactions. As such, these libraries can be applied to the search for new pharmaceutical agents for the treatment and prevention of a range of medical conditions.

The present disclosure relates to novel macrocyclic compounds and libraries thereof containing heteroaryl moieties that are useful as research tools for drug discovery efforts. The present disclosure also relates to methods of preparing these compounds and libraries and methods of using these libraries, such as in high throughput screening. In particular, these libraries are useful for evaluation of bioactivity at existing and newly identified pharmacologically relevant targets, including G protein-coupled receptors, nuclear receptors, enzymes, ion channels, transporters, transcription factors, protein-protein interactions and nucleic acid-protein interactions. As such, these libraries can be applied to the search for new pharmaceutical agents for the treatment and prevention of a range of medical conditions.

The present inventors have found that when screening for cyclic peptide compounds that can specifically bind to a target molecule, the use of a library including cyclic peptide compounds having a long side chain in the cyclic portion can improve the hit rate for cyclic peptide compounds that can specifically bind to the target molecule. Meanwhile, the present inventors have found that tryptophan and tyrosine residues, which have conventionally been used in oral low molecular-weight pharmaceuticals and are amino acid residues having an indole skeleton or a hydroxyphenyl group, are not suitable for peptides intended to attain high membrane permeability.

The present inventors have found that when screening for cyclic peptide compounds that can specifically bind to a target molecule, the use of a library including cyclic peptide compounds having a long side chain in the cyclic portion can improve the hit rate for cyclic peptide compounds that can specifically bind to the target molecule. Meanwhile, the present inventors have found that tryptophan and tyrosine residues, which have conventionally been used in oral low molecular-weight pharmaceuticals and are amino acid residues having an indole skeleton or a hydroxyphenyl group, are not suitable for peptides intended to attain high membrane permeability.

The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays and combinatorial chemistry. The invention provides for aqueous based emulsions containing uniquely labeled cells, enzymes, nucleic acids, etc., wherein the emulsions further comprise primers, labels, probes, and other reactants. An oil based carrier-fluid envelopes the emulsion library on a microfluidic device, such that a continuous channel provides for flow of the immiscible fluids, to accomplish pooling, coalescing, mixing, sorting, detection, etc., of the emulsion library.

The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays and combinatorial chemistry. The invention provides for aqueous based emulsions containing uniquely labeled cells, enzymes, nucleic acids, etc., wherein the emulsions further comprise primers, labels, probes, and other reactants. An oil based carrier-fluid envelopes the emulsion library on a microfluidic device, such that a continuous channel provides for flow of the immiscible fluids, to accomplish pooling, coalescing, mixing, sorting, detection, etc., of the emulsion library.

A method for co-compartmentalising a cyclic polypeptide with a polynucleotide encoding the cyclic polypeptide, comprising the steps of a) forming a compartment containing a polynucleotide encoding the cyclic polypeptide, b) expressing a polypeptide from the polynucleotide, and c) cyclising the polypeptide. Co-compartmentalised cyclic polypeptides and encoding polynucleotides. Libraries of co-compartmentalised cyclic polypeptide and encoding polynucleotide. Methods for screening libraries of co-compartmentalised cyclic polypeptide and encoding polynucleotide. Incorporation of non-canonical nucleic acids into such libraries.

A method for co-compartmentalising a cyclic polypeptide with a polynucleotide encoding the cyclic polypeptide, comprising the steps of a) forming a compartment containing a polynucleotide encoding the cyclic polypeptide, b) expressing a polypeptide from the polynucleotide, and c) cyclising the polypeptide. Co-compartmentalised cyclic polypeptides and encoding polynucleotides. Libraries of co-compartmentalised cyclic polypeptide and encoding polynucleotide. Methods for screening libraries of co-compartmentalised cyclic polypeptide and encoding polynucleotide. Incorporation of non-canonical nucleic acids into such libraries.

The invention generally relates to methods for quantifying an amount of enzyme molecules. Systems and methods of the invention are provided for measuring an amount of target by forming a plurality of fluid partitions, a subset of which include the target, performing an enzyme-catalyzed reaction in the subset, and detecting the number of partitions in the subset. The amount of target can be determined based on the detected number.