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

SBIR第一阶段项目旨在将新的传感器技术商业化，从而能够快速测量分子混合物的手性。 就像螺丝钉和钥匙一样，许多分子都具有一定的手性，这在与生命系统相互作用时非常重要。 这个问题对药物研究至关重要，药物的一种形式可能会带来好处，而相反的形式可能会导致有害的副作用。 因此，测量分子混合物的手性在现代药物研究中是至关重要的。 然而，进行这些测量的常规方法对于现代药物发现和开发研究来说通常太慢，在现代药物发现和开发研究中，每天对数百甚至数千个样品进行高通量实验。 该项目旨在通过利用最近推出的新仪器和商业化试剂盒来消除这一瓶颈，这些试剂盒已在学术实验室中展示，以实现更快，更简单的方法来测量分子混合物的手性。 向更大的研究和开发界广泛提供这种改进的技术，有可能简化药物开发工作，降低成本，最大限度地减少废物的产生，预计这将增加利润率，并在研究、开发和制造方面创造新的就业机会，给美国的健康和经济带来巨大利益。 该项目的创新包括一系列光学传感器，这些传感器是在参与实验室十年的基础研究中开发的，它将允许快速筛选各种不对称反应。这一前所未有的企业的重点是验证选定的传感器对药物相关的化合物，通过与传统技术，如手性HPLC比较，确定光学测定的误差，以评估在潜在的干扰物存在下的鲁棒性，并应用传感器在分析中的不对称反应使用多孔板技术。开发一个用户友好的套件将包括测试不同的方法，用于创建预分配的干燥传感器，可以重建而不会留下残留物，这可能会增加误差幅度超过百分之几，这是通常可接受的高通量筛选应用。最终成果将是一个方便的混合和测量协议，使数百个小规模的不对称反应mixture.This奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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.