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能够快速测量分子混合物的手性的新传感器技术商业化。就像螺丝和钥匙一样，许多分子具有一定的手性，这在与生命系统相互作用时很重要。这个问题对药物研究至关重要，因为药物的一种形式可能会产生益处，而另一种形式可能会产生有害的副作用。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，对于现代药物发现和开发研究来说，进行这些测量的传统方法通常太慢，因为现代药物发现和开发研究每天要对数百甚至数千个样本进行高通量实验。该项目旨在通过利用最近推出的新仪器和商业化的试剂盒来消除这一瓶颈，该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。将这种改进的技术广泛提供给更多的研究和开发界，有可能以更低的成本精简药物开发工作，并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，从而为美国的健康和经济带来重大利益。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出来的，它将允许快速筛选各种不对称反应。这项史无前例的事业的重点是验证选定的传感器对药物相关化合物的影响，通过与传统技术（如手性高效液相色谱）的比较来确定光学分析的误差，评估潜在干扰物存在下的稳健性，并使用多孔板技术将传感器应用于不对称反应的分析。用户友好工具包的开发将包括测试用于创建预分配干燥传感器的不同方法，这些传感器可以重新组合而不会留下残留物，这些残留物可能会增加误差范围超过几个百分点，这对于高通量筛选应用通常是可以接受的。最终的结果将是一个方便的混合测量方案，能够快速分析数百种小规模不对称反应混合物。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.