Project Summary In this proposal, a group of accomplished molecular scientists at the University of Texas Southwestern Medical Center requests funds for a mass photometry device. Specifically, the request is for the OneMP model of mass photometer manufactured by Refeyn Ltd. Mass photometry (MP) is a relatively new method that is very attractive to our user base. It uses the scattering of light as macromolecules adhere to at a water/glass interface (i.e. on a standard cover slip) to measure their respective molecular masses. It does this by recombining the scattered light with light reflected from the interface. The resulting images are processed to reveal the contrast in them as a function of time; the contrast can in turn be related directly to the molecular mass of the adherence event that gave rise to it. MP yields remarkably accurate molecular mass distributions, and it does so without labeling, immobilization, or interaction with a matrix. MP uses very small amounts of material, consuming only tens of picograms per experiment. It is also very fast, as an optimized experiment can be performed in 15 min or less. UTSW has a vigorous program of molecular research, and the MP fills a need for many of our scientists. Some will incorporate the MP into a workflow that will greatly amplify speed and efficiency with which they can produce structural data. For some of these researchers, the low sample consumption and accurate mass-distribution quantification of the method will open avenues of characterization heretofore unavailable to them. Others will use it to examine questions that can be probed only at very low sample concentration, for example thermodynamic characterization of very tight binding. Still others will utilize the technology as a fast and robust complement to other methods, enhancing scientific rigor. The OneMP will be overseen by the already existing Macromolecular Biophysics Resource, a successful core lab at UTSW with an excellent track record of incorporating and mastering new biophysical equipment. The commitment of UTSW to the success of the instrument is strong, and the overall benefit of its procurement is that it will strongly enhance the scientific, innovation, and educational missions of the University.