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

这个SBIR第一阶段项目寻求将新的传感器技术商业化，使其能够快速测量分子混合物的左旋手。就像螺丝和钥匙一样，许多分子都有一定的利手，这在与生命系统相互作用时可能是很重要的。这个问题对制药研究至关重要，药物的一种形式可能会带来益处，而相反的形式可能会产生有害的副作用。因此，在现代药学研究中，测量分子混合物的手性是非常重要的。然而，对于每天对数百甚至数千个样品进行高通量实验的现代药物发现和开发研究来说，进行这些测量的传统方法往往太慢了。该项目旨在消除这一瓶颈，利用最近推出的一种新仪器，并将已在学术实验室中展示的试剂盒商业化，以实现一种更快、更简单的方法来测量分子混合物的手性。将这种改进后的技术广泛提供给更多的研究和开发社区，有可能以更低的成本简化药物开发工作，并最大限度地减少废物产生，预计这将提高利润率，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实质性好处。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，将允许快速筛选各种不对称反应。这一史无前例的事业的重点是针对药物相关化合物验证选定的传感器，通过与手性高效液相色谱等传统技术进行比较来确定光学分析的误差，评估潜在干扰物存在时的稳定性，并使用多孔板技术将传感器应用于不对称反应的分析。开发用户友好的试剂盒将包括测试不同的方法来创建预先分配的干式传感器，这些传感器可以在不留下可能使误差幅度增加到几个百分点以上的残留物的情况下进行重组，这对于高通量筛查应用通常是可以接受的。最终结果将是一个方便的混合测量方案，能够快速分析数百个小规模的不对称反应混合物。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.