JCP-DCP Future Chemical Physics Award: Functional Chemical Imaging at the Single-Molecule Level

Advances in optical spectroscopy and microscopy have revolutionized our understanding of fundamental molecular functions, especially in biological systems at the subcellular levels. In this talk, I will present our recent efforts in developing next-generation bond-selective spectro-microscopy for retrieving functional chemical information in live cells and neurons, and at the ultimate single molecule level. I will first briefly discuss the coupling of the stimulated Raman scattering (SRS) imaging, a nonlinear Raman imaging modality, with newly developed biorthogonal chemical strategies for quantitative subcellular analysis of protein aggregates in neurodegenerative diseases and for intracellular local environmental sensing through alkyne- hydrogen–deuterium exchange (Alkyne-HDX). I will then focus on a mid-infrared near-infrared double-resonance imaging technique, BonFIRE, for bond-selective fluorescence imaging with single-molecule sensitivity. BonFIRE has proven to be effective for wide-field super-multiplex imaging, vibrational lifetime imaging for sensing heterogeneous cellular interactions and environment, and for revealing the inherent heterogeneity of vibrational decays with 2D analysis.