HT-MMIP: Instrumentation for High Throughput Chiral Measurements

描述(申请人提供)：大多数药物分子是光学活性的，并根据它们的手性表现出独特的性质。因此，化合物X可以是一种强效药物，它的镜像可能是不活跃的，甚至是有毒的。因此，制药行业正朝着手性纯药物的发展方向发展。用旋光仪测量了手性分子的旋光性。现有的旋光仪是一次测量一个样品，因此不是高通量筛选药物发现过程的一部分。本提案描述了用于高通量筛选应用的高通量Mueller矩阵成像偏振仪的开发。这项工作计划由智能光学系统公司、亚利桑那大学的拉塞尔·奇普曼教授和布朗大学的克里斯托弗·西托教授共同合作完成。在第一阶段，我们将设计和建造一台高通量偏振仪，它可以从微滴定板的微孔中以高通量格式测量样品的旋光度。该装置将用手性文库进行校准和测试，以展示其灵敏度、吞吐量、光学分辨率、准确度和其他特性。第一阶段工作的成功完成将导致在第二阶段开发改进的原型，并利用手性文库进行额外的测试。第二阶段的工作还将进一步提高仪器的灵敏度，并将该装置整合到高通量筛选实验室仪器中。该仪器的主要用户将是制药行业、生物技术行业、大学实验室和政府实验室的研究人员。该设备可用于药物发现、催化剂筛选、识别配体、生化研究、细胞相互作用研究和许多其他生命科学应用。

DESCRIPTION (provided by applicant): A majority of drug molecules are optically active and exhibit unique properties depending on their chirality. Thus, a compound X can be a potent drug, and its mirror image could be inactive, or even toxic. Therefore, the pharmaceutical industry is moving towards the development of chirally pure drugs. The optical activity of a chiral molecule is measured using a polarimeter. Existing polarimeters are used to measure one sample at a time, and therefore are not part of the high-throughput screening drug discovery process. This proposal describes the development of a high-throughput Mueller Matrix Imaging Polarimeter geared for high-throughput screening applications. This work is planned as a joint collaboration between Intelligent Optical Systems, Professor Russell Chipman of University of Arizona, and Professor Christopher Seto of Brown University. In Phase I, we will design and construct a high-throughput polarimeter that can measure optical rotation of samples in a high throughput format from the microwells of a microtiter plate. The proposed device will be calibrated and tested with chiral libraries to demonstrate its sensitivity, throughput, optical resolution, accuracy, and other features. The successful completion of the Phase I work will lead to the development of an improved prototype in Phase II and additional testing with chiral libraries. Phase II work will also look into further improving the sensitivity of the instrument, and integrating the unit into high throughput screening laboratory instrumentation. The primary users of this instrument will be researchers in pharmaceutical industries, biotech industries, university laboratories, and government laboratories. The device could be useful in drug discovery, catalyst screening, identifying ligands, biochemical studies, cellular interaction studies, and many other life science applications.