Live-Cell Super-Resolution Microscopy: Technological Progress, Hybrid Methodologies, and Applications in Omics
May 5, 2026 @ 09:00 – 10:00 CEST
Liangyi Chen, New Cornerstone Investigator, Institute of Molecular Medicine, National Biomedical Imaging Center, Peking University, China.
Host: Jan Ellenberg, SciLifeLab
Abstract
In this talk, I will present our decade-long efforts to advance state-of-the-art live-cell super-resolution microscopy. By introducing spatiotemporal Hessian regularization, we developed Hessian Structured Illumination Microscopy (Hessian-SIM), which substantially reduces phototoxicity and enables real-time, long-term imaging of dynamic structures such as mitochondrial cristae and insulin vesicle fusion pores in living cells. We next engineered a dual-modality fluorescence/label-free microscope for panoramic super-resolution imaging, facilitating the discovery of novel organelles. Our 4Pi-SIM and 3D multiplane SIM (3D-MP-SIM) techniques deliver ~100-nm isotropic resolution while achieving a tenfold increase in volumetric imaging speed for live cells.
Furthermore, we introduced a universal sparse deconvolution algorithm that overcomes the optical Rayleigh diffraction limit. When applied to structured illumination, it enables 60-nm resolution at 564 Hz for sustained live-cell imaging and enhances resolution in multiphoton and light-sheet microscopy in vivo. Finally, I will discuss our recent developments in a SIM-FLIM system and the integration of live-cell super-resolution SIM imaging with single-cell RNA sequencing to bridge nanoscale dynamics with transcriptomic profiles.


