PROJECT SUMMARY Experimental techniques that enable quantitative interrogation of the interactions between different biological molecules are critical to biomedical research. Such techniques provide important data to understand the molecular basis of diverse diseases, develop new mechanistic models, discover new drugs and therapies, and guide other experiments. Surface plasmon resonance (SPR) has emerged as a trusted, robust, and versatile method to explore the thermodynamics and kinetics of molecular binding events. For twenty years, SPR instrumentation has been an important and integral part of the Biophysics Core on the University of Colorado Anschutz Medical Campus (CU-AMC) and has been used to support a wide variety of NIH-funded projects. However, after two decades the equipment has become unreliable, costly to maintain, obsolete, and will soon no longer be repairable. We propose to purchase a new SPR instrument to replace our current instrument, ensuring SPR continues as a critical part of our campus’ research infrastructure. The instrument will be housed in an established, well-managed, and funded Biophysics Core facility that will allow it to be maintained and to be coupled with expertise. This instrument will be used by researchers from multiple basic science and clinical departments and will be a key part of training the next generation of biophysicists and biochemists. Furthermore, compared to the old instrument, the new instrument’s enhanced capabilities will allow for experiments to be conducted with much less material, with a greater variety of molecules, and in a higher-throughput way with greater sensitivity. Acquisition of this new instrument will have an immediate and lasting impact on NIH-funded research in areas as diverse as infectious diseases, virology, cancer, RNA splicing, cellular protein localization, gene regulation, immunology, and drug design. The benefits to these (and other) research areas include time and material savings, faster data collection, greater sensitivity, ability to collect data under more diverse conditions, better small molecule binding detection, and enhanced training opportunities.