Many revolutions in biology have been followed by breakthroughs in microscopy and chemistry.
Our research program is aimed to explore new frontiers of optical microscopy that may drive new revolutions in our understandings of life.
The resolution limit of optical microscopy is shattered by super-resolution fluorescence microscopy, awarded 2014 Nobel Prize in Chemistry. We explore new venues of STORM (STochastic Optical Reconstruction Microscopy) including resolution down to nanometer, time window lasting days and color channels up to thousands. These advances may lay stepping stones for collecting big data of biological systems spanning multiple scales of space, time and molecules.
In super-resolution fluorescene microscopy, there remains the intrinsic resolution limit set by fluorescent probes. We pursue ways to achieve diffraction-unlimited resolution of label-free optical microscopy such as Raman scattering. Since vibrational probes for Raman contrast is composed of a few atoms, the label-limited resolution can be vastly reduced. Our research will lay a stepping stone for achieving label-free, molecular-specific, molecular-resolution imaging tool.
SINGLE-CELL SYSTEMS BIOLOGY
In situ sequencing may revolutionize systems biology to access the spatial heterogeneity of gene expression. The current techniques in their infancy require new chemistry and microscopy tools for vastly improving the throughput. For instance, our light sheet microscope may enable faster and longer reading. We also develop a new combinatorial labeling chemistry for in situ genomics and proteomics. These methods will enable us to map the comprehensive molecular landscapes of a cell.