HT-MMIP: Instrumentation for High Throughput Chiral Measurements

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.