SBIR Phase I: A chemical assay kit for the high-throughput screening of chiral amine enantiomeric excess

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This SBIR Phase I project seeks to commercialize new sensor technologies that enable the rapid measurement of the handedness of molecular mixtures. Like screws and keys, many molecules possess a certain handedness that can be important when interacting with living systems. This issue is vital to pharmaceutical research, where one handed form of a drug may result in benefits while the opposite form may cause harmful side effects. Consequently, measuring the handedness of molecular mixtures is of paramount importance in modern pharmaceutical research. However, conventional approaches to making these measurements are often too slow for modern pharmaceutical discovery and development research where high-throughput experiments on hundreds or even thousands of samples per day are performed. This project aims to remove this bottleneck by leveraging a recently introduced new instrument and commercializing reagent kits that have been shown in academic laboratories to achieve a much faster and simpler method for measuring the handedness of molecular mixtures. Making this improved technology widely available to the greater research and development community has the potential to streamline drug development efforts at reduced cost and minimized waste production, which is expected to increase profit margins and create new jobs in research, development and manufacturing, resulting in substantial benefit to the health and economy of the United States. The innovation of this project comprises a series of optical sensors, developed during a decade of fundamental research in the participating laboratories, which will allow rapid eescreening of a variety of asymmetric reactions. The focus of this unprecedented enterprise is to validate selected sensors against pharmaceutically relevant compounds, determine the error of the optical assays by comparison with traditional techniques such as chiral HPLC, to evaluate the robustness in the presence of potential interferants, and to apply a sensor in the analysis of an asymmetric reaction using multi-well plate technology. The development of a user-friendly kit will include the testing of different methods for the creation of pre-dispensed dried sensors that can be reconstituted without leaving behind residues that might increase the error margin beyond a few percent which is generally acceptable for high-throughput screening applications. The final outcome will be a convenient mix-and-measure protocol that enables rapid analysis of hundreds of small-scale asymmetric reaction mixtures.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.