PROJECT SUMMARY: The Scripps Research Molecular Screening Center (SRMSC) is requesting funds for the purchase of two microplate readers as a replacement for its current uHTS Perkin Elmer Viewlux which has reached end of life. The ViewLux has been the gold standard for high-speed microplate imaging; ideally suited for simultaneous plate-well imaging analysis where speed, reliability and high quality data is required. The integrated Viewlux reader on our HTS screening platform has served our needs admirably since its initial installment in 2005. However, after ~15-years of service, reliability has become a critical issue compounded by Perkin Elmer’s end of production (2017) and service support exacerbated by the discontinued manufacture of all parts/components. As of date, there is not a current reader on the market that equals the speed of the Viewlux, which is especially problematic with respect to ever increasing need to perform low light luminescence and BRET readouts. Not surprisingly, many comprehensive HTS screening centers (both Pharma & academic) must now rely on multiple readers to meet HTS automation throughput needs while maintaining high quality and reliable data. High Throughput Screening (HTS) has become an indispensable tool for probe development and drug discovery and the Scripps Research Molecular Screening Center (SRMSC) has been in the forefront in serving NIH investigators at Scripps and other academic institutes. Since establishing operations in 2005, we have screened over 300 targets to generate more than 100 million data points for our collaborators at Scripps and at other institutions. Over 122 scientific papers and numerous presentations demonstrate our ability to produce excellent research-driven data. Our screening results have led to the development of over 77 bioactive molecular probes as novel drug targets for biomedical studies that have successfully advanced as INDs for clinical trial testing and eventually NDA/FDA drugs. The tandem multi-modal plate readers will replace the aged ViewLux; allowing SRMSC to fulfill its current HTS screening obligations and continue to serve the NIH community at large with its comprehensive HTS drug discovery capabilities.