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 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 invention relates to the preparation of a compound library comprising the following steps: i. Having available at least two different compounds each comprising at least a dioxaborolane or dioxaborinane ring. In said compounds: the boron of the dioxaborolane or dioxaborinane ring is directly linked to a carbon atom of a hydrocarbon radical; at least one carbon atom of the dioxaborolane or dioxaborinane ring is monosubstituted, the other carbon atoms of the dioxaborolane or dioxaborinane ring being non-substituted or monosubstituted; in at least two compounds, the hydrocarbon radicals linked to the boron are different; in at least two compounds, the substituents carried by at least one of the carbon atoms of the dioxaborolane or dioxaborinane rings are different and/or the size of the boronic ester ring is different; ii. Reacting the compounds of step (i.) and forming, by a boronic ester metathesis reaction, the library comprising at least four different compounds. The present invention also relates to a compound library.

In alternative embodiments, provided herein are transcription/translation (TX-TL) systems and methods of using them for use as rapid prototyping platforms for the synthesis, modification and identification of natural products (NPs), and natural product analogs (NPAs) and secondary metabolites, from biosynthetic gene cluster pipelines. In alternative embodiments, exemplary TX-TL systems as provided herein are used for the combinatorial biosynthesis of natural products (NPs), natural product analogs (NPAs) and secondary metabolites. In alternative embodiments, exemplary TX-TL systems as provided herein are used for the rapid prototyping of complex biosynthetic pathways as a way to rapidly assess combinatorial and biosynthetic designs before moving to cellular hosts. In alternative embodiments, these exemplary TX-TL systems are multiplexed for high-throughput (HT) automation and for prototyping engineered platforms for the synthesis or modification of natural products (NPs), and natural product analogs (NPAs) and secondary metabolites analogs.

In alternative embodiments, provided herein are transcription/translation (TX-TL) systems and methods of using them for use as rapid prototyping platforms for the synthesis, modification and identification of natural products (NPs), and natural product analogs (NPAs) and secondary metabolites, from biosynthetic gene cluster pipelines. In alternative embodiments, exemplary TX-TL systems as provided herein are used for the combinatorial biosynthesis of natural products (NPs), natural product analogs (NPAs) and secondary metabolites. In alternative embodiments, exemplary TX-TL systems as provided herein are used for the rapid prototyping of complex biosynthetic pathways as a way to rapidly assess combinatorial and biosynthetic designs before moving to cellular hosts. In alternative embodiments, these exemplary TX-TL systems are multiplexed for high-throughput (HT) automation and for prototyping engineered platforms for the synthesis or modification of natural products (NPs), and natural product analogs (NPAs) and secondary metabolites analogs.

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 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 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.