HT-MMIP: Instrumentation for High Throughput Chiral Measurements

描述（由申请人提供）：大多数药物分子具有旋光性，并根据其手性表现出独特的性质。因此，化合物X可能是一种强效药物，而它的镜像可能是无活性的，甚至是有毒的。因此，制药行业正朝着开发手性纯药物的方向发展。手性分子的旋光性是用偏振光计测量的。现有的偏振光计用于一次测量一个样品，因此不是高通量筛选药物发现过程的一部分。本提案描述了一种高通量穆勒矩阵成像偏光计面向高通量筛选应用的发展。这项工作计划由智能光学系统、亚利桑那大学的Russell Chipman教授和布朗大学的Christopher Seto教授共同合作。在第一阶段，我们将设计和构建一个高通量偏振计，可以测量样品的光学旋转高通量格式从微孔的微量滴定板。该装置将通过手性文库进行校准和测试，以证明其灵敏度、吞吐量、光学分辨率、精度和其他特性。第一阶段工作的成功完成将导致第二阶段改进原型的开发和手性库的额外测试。第二阶段的工作还将进一步提高仪器的灵敏度，并将该装置集成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。该装置可用于药物发现，催化剂筛选，识别配体，生化研究，细胞相互作用研究以及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.