2:00 pm to 3:00 pm
Seeing through light: unveiling new biological structures by manipulating and resolving light in the sub-diffraction regime
Light reveals and hides. While bioimaging uncovers rich structural and chemical information of cells and tissues, the spatial resolution set by the diffraction limit of approximately 200 nanometers hampers optical interrogation of sub-diffraction ultrastructures. In this talk, I will present approaches that enhance the footprint of light by engineered plasmonic nanoantennas, and achieve sub-diffraction resolution by single-molecule super-resolution imaging. For manipulating light in the sub-diffraction regime, I will demonstrate a class of noble-metal-based nanostructures, which “appear” several times larger than their physical dimensions. Owing to the interaction between oscillatory surface electrons and light, these nanostructures serve as highly tunable light antennas for contrast imaging and photothermal therapy. To achieve sub-diffraction resolution, I will demonstrate a light-sheet single-molecule super-resolution microscope. Through a prism-coupled mechanism, the novel imaging system provides high signal-to-noise ratio by illuminating the biological sample with a thin-plane optical illumination at arbitrary depths. Combined with localization-based super-resolution imaging techniques and cloud-based high-performance computing, the system revealed 50-nanometer chromosome domains marked by the heterochromatin protein HP1α in the nuclei of human embryonic stem cells, and the concatenation of T-cell receptor protein islands across the diffraction limit during immune activation in the mouse lymph nodes. These engineering approaches open doorways to investigate the previously hidden ultrastructures pertaining to development, function, and disorders, while maintaining a global perspective with physiological, pathological, and biochemical environments native to the cells.
Short Bio: Dr. Hu develops novel techniques to manipulate and resolve light in the region near or below the diffraction limit of light. His research is at the interface between engineering approaches, including designing a class of highly tunable light antennas and light-sheet single-molecule super-resolution microscopy, and imaging-driven biomedical studies, including investigating the nanometer-scale nuclear and membrane structures pertaining to embryonic development and adaptive immunity. Dr. Hu received his Ph.D. in Bioengineering from Rice University as a Department of Energy Computational Science Graduate Fellow (2011), and B.S. in Electrical Engineering from the University of Houston (summa cum laude, 2006). He is currently a postdoctoral fellow from the California Institute for Generative Medicine at the Salk Institute for Biological Studies.