Probing Nanoscale Cellular Dynamics with Interferometric Scattering Microscopy

Abstract

Fluorescence microscopy has long been a cornerstone in the visualization of nanoscopic cellular structures, primarily due to its exceptional sensitivity. Nevertheless, achieving high-resolution fluorescence imaging in live cells presents significant challenges, particularly owing to the rapid dynamics of intracellular structures and limitations imposed by photobleaching and photon budget constraints. In this talk, I will introduce interferometric scattering (iSCAT) microscopy, an ultrasensitive, label-free imaging modality capable of directly visualizing cellular organelles and their dynamics with high spatial and temporal resolution. iSCAT microscopy effectively resolves a variety of cytosolic organelles, including mitochondria, the endoplasmic reticulum, and vesicles, by exploiting their distinct scattering signatures. Furthermore, I will describe a novel methodology for probing chromatin organization and dynamics in live-cell nuclei by analyzing dynamic iSCAT signals arising from local chromatin fluctuations. Lastly, I will discuss the integration of fluorescence microscopy with iSCAT imaging as a powerful strategy for investigating nanoscale cell biology, potentially opening new avenues for multi-modal, high-resolution cellular imaging.

Biography

Dr. Hsieh received his Ph.D. in 2011 from Caltech, where he studied nonlinear optics in nano-sized particles for bioimaging under Prof. Demetri Psaltis. He conducted much of his research as an exchange PhD student in the Optics Lab at EPFL in Switzerland. Afterward, he did postdoctoral work on interferometric scattering (iSCAT) microscopy and single-particle tracking with Prof. Vahid Sandoghdar at Max Planck Institute for the Science of Light in Erlangen, Germany. In 2012, he joined Academia Sinica in Taiwan as a PI and founded the Bio-Nano-Photonics Lab. His research interest is exploring nanoscale biological dynamics with advanced microscope techniques.