SUMMARY This administrative supplement for equipment is requesting funds for a Refeyn TwoMP Mass Photometer. Mass photometry is a revolutionary new technology that enables highly sensitive and accurate mass measurements of different types of biomolecules in solution without the need for labeling. This breakthrough technology derives molecular mass from light scattered by single molecules and can be used to examine sample homogeneity, assess oligomerization behavior, quantify biomolecular interactions, and measure the assembly or disassembly of large multicomponent complexes, which is not possible with ensemble methods. Hence, mass photometry provides a reliable and cost-effective means to rapidly screen biochemical conditions that are compatible with our desired macromolecules and eliminate conditions that prevent complex formation. The Refeyn TwoMP enables accurate quantification of single biomolecules across a wide mass range, from 30-kDa up to 5-MDa. Thus, the acquisition of the new mass photometer will directly benefit the project’s research plan by enhancing our ability to identify and optimize sample conditions for large protein machines (~1MDa) towards their 3D structure determination, which is within the original project scope. Currently, sample preparation presents a major bottleneck in structure analysis work due to its inherent unpredictability and time- consuming nature. Mass photometry provides an elegant and rational solution to this problem. Consequently, the TwoMP mass photometer is crucial for the successful completion of the specific aims of the parent application and to ensure that rapid progress is made continuously. The mass photometry technology is currently not available at Baylor College of Medicine, and the requested Refeyn TwoMP mass photometer will be the first in the greater Houston area. The TwoMP will provide a competitive advantage and will be available to other researchers at the college and its neighboring academic institutions, providing enhanced user access to this powerful new technology. The Tsai group will manage the new equipment that will be housed in dedicated laboratory space. To maintain the mass photometer in peak condition, the biochemistry department is committed to covering the annual maintenance of the TwoMP after the one-year installation warranty has expired.