Phasics SID4-sC8 QPM Camera System - Nikon Ti2-E Inverted Microscope and Imaging Platform Combined - Project Summary/Abstract Quantitative measurement of cellular physical properties has become a powerful approach for uncovering fundamental principles of cell physiology. At UC San Diego, a core group of investigators—including our lab and major users of this proposal, Drs. Terry Hwa, Gürol Süel, and Suckjoon Jun—have made pioneering contributions to single-cell physiology by integrating physical and quantitative methods in microbial and mammalian systems. These efforts have revealed how cytoplasmic density influences gene expression and stress responses, how ion dynamics drive bacterial spore germination, and how dry mass accumulation links to cell size control and division cycles. The Quantitative Phase Microscope (QPM) is a uniquely powerful tool that enables label-free, high-resolution measurement of dry mass in live cells—a core physical quantity foundational to quantitative single-cell physiology. Yet, access to such live-cell measurement tools remains limited, creating a bottleneck for research that seeks to integrate physical measurement with mechanistic understanding of cell function. To address this need, we propose to acquire a Phasics QPM system integrated with a Nikon epifluorescence microscope and a live-cell incubation platform. This system employs quadriwave lateral shearing interferometry to capture single-shot phase maps with high spatial sensitivity, enabling dynamic, label-free imaging of cellular morphology and biophysical properties such as refractive index and dry mass. It is the only commercially available system capable of reliably performing these measurements in both bacterial and mammalian cells, making it exceptionally versatile and user-friendly for interdisciplinary research. The instrument will support a wide range of NIH-funded research at UC San Diego, including studies of bacterial stress adaptation, cytoplasmic homeostasis, stem cell characterization, and developmental dynamics in chondrocytes. Major users span departments including Physics, Cellular and Molecular Medicine, and Molecular Biology, and share a commitment to quantitative, mechanistic understanding of cellular systems. The QPM system will be housed in the Nikon Imaging Center (NIC), which provides established infrastructure for training, scheduling, data support, and long-term maintenance. NIC staff will manage user access and assist with protocol development and data interpretation to ensure broad impact. We will actively promote the instrument through seminars, demonstrations, and collaborative outreach. As awareness grows, we anticipate increasing demand across disciplines. By enabling routine measurement of physical properties in live cells— including dry mass, refractive index, and density—this system will empower biomedical research that integrates physical principles with molecular mechanisms, and help establish UC San Diego as a hub for physics-informed life science.
