Blood Vessel-Inspired Surface-Emitting Microscopy for Label-Free Monitoring of Single Cell Dynamics

Cellular membrane dynamics play an important role when interacting with blood vessels and associated physiological processes. However, label-free mapping of cellular membrane dynamics on curved substrates remains challenging due to the strict light-coupling conditions required for exciting evanescent waves. Here, we report surface-emitting resonator interference microscopy (SERIM), which employs the evanescent wave naturally present in the near-field region of a whispering gallery mode (WGM) resonator to probe the subcellular membrane dynamics. The WGM resonator provides strong optical feedback for enhancing the light-matter interaction and offers a biomimetic curvature interface for investigating membrane dynamics. The interaction of the evanescent wave with the cell membrane caused significant scattering, forming a highly sensitive interference pattern. We found that the time-resolved interference patterns can be utilized to extract subcellular membrane dynamics with a high spatial resolution of 1 μm. We further employed the SERIM to investigate the spatial heterogeneity of membrane dynamics during migration, and also stimulus responses to temperature and drugs. In striking contrast to the conventional label-free methods, the easy excitation of the evanescent wave makes SERIM a versatile label-free strategy for studying cellular behavior on a curved surface. Our work holds promise for the sensitive detection of subtle biochemical and biophysical information during cell-substrate interaction.