TITLE: Development of a charge sensitive optical detection system for high-throughput study of small molecules SUMMARY Measuring the kinetics of small molecule binding to protein receptors and biochemical reactions of proteins, such as post-translational protein modifications, is a basic task in the understanding of diseases, discovering of diagnosis biomarkers, and screening of drugs. Various label-free techniques have been developed, but their sensitivity decreases with the molecular mass, which makes it challenging to detect small molecules and biochemical reactions. A charge sensitive optical detection (CSOD) system is proposed to address this unmet need. The technology is not only sensitive to small molecules, but also compatible with the standard microplate technology, which is particularly suitable for high-throughput applications. The working principle was established and validated with the support of NIH NCI IMAT (Innovative Molecular Analysis Technologies for cancer research) grants (R21 and R33) to the Arizona State University (ASU) team. In this SBIR direct phase II project, Biosensing Instrument Inc. (BI) will work with the ASU team to develop a commercially viable prototype system. We will continue collaborations with potential customers in biomedical research and pharmaceutical industries for testing samples relevant to their interest and validating the performance usability of the developing system. The success of the project will lead to a new high-throughput screening technology for measuring molecular interactions, particularly small molecule interactions with proteins, and post-translational modifications of proteins. These processes are highly important for biomarker discovery, disease diagnosis and drug screening.