Assistant Professor of Chemistry
Columbia University
Fluorescence microscopy is currently the most popular contrast mechanism employed in optical imaging. However, fluorescence imaging faces fundamental limitations for studying the vast number of small bio-molecules such as metabolites (e.g., amino acids), second messengers, neurotransmitters and drugs, because the relatively bulky fluorescent tags often destroy or significantly alter the biological activities of small biomolecules. Therefore, how to probe these vital species inside cells represents a grand challenge. The Min laboratory aims to develop a novel and general strategy that would enable an unprecedented ability to map out the distribution and to follow the dynamics of small bio-molecules in living systems. Dr. Min’s work aims to label these small molecules with bio orthogonal tags such as alkyne (CC) or stable isotopes including deuterium and 13C, and then image the labeled species in cells by stimulated Raman scattering (SRS) microscopy, a nonlinear vibrational microscopy originally developed by Freudiger, Min and Xie as a label-free technique (Folick, Min et al. 2011, Freudiger, Min et al. 2011, Wang, Min et al. 2011). Such a strategic coupling of bioorthogonal tags with nonlinear vibrational microscopy, which is named bio orthogonal nonlinear Raman imaging, could do for small biomolecules what fluorescence imaging has done for larger species, extending the regime of light microscopy beyond the common fluorescence and label-free approaches. A broad range of exciting applications have been demonstrated to be possible (most are for the first time), such as imaging protein synthesis, protein degradation, DNA replication, RNA turnover, drug distribution, choline metabolism and glucose uptake in living cells, tissues and animals (Gatzogiannis, Chen et al. 2012, Chen, Paley et al. 2014, Wang, Friedman et al. 2014, Wei, Hu et al. 2014, Hu, Chen et al. 2015). New biological insights are emerging.