Wei Min, Research Statement


Live-cell imaging with alkyne-tagged small biomolecules by stimulated Raman Scattering. The introduction of GFP has revolutionized life sciences and biomedicine. At the same time, smaller biomolecules, such as nucleosides, amino acids, choline, fatty acids, metabolites and drugs, play indispensable roles inside cells, yet are too small to be tagged with fluorescent proteins. In fact, despite the extensive efforts, sensitive and specific visualization of these small biomolecules with subcellular resolution has proven to be highly challenging in living systems, because tagging them with fluorophores often destroys their biological activities. Here we report an alternative general strategy for monitoring a broad spectrum of small biomolecules in live cells and animals, by using stimulated Raman scattering (SRS) imaging of alkyne tags. We demonstrate this technique by visualizing de novo synthesis of DNA, RNA, proteins, phospholipids and triglycerides, even creating new vibrational colors for multi-chemical imaging, and also tracking drug delivery in living mouse tissue. This approach has the potential of becoming a general platform for the development of specific molecular labels, extending to small biomolecules the flexibility and power of selective live imaging