Biomedical Applications of Stimulated Raman Scattering Microscopy

Abstract

Stimulated Raman scattering (SRS) microscopy emerged as a promising tool for label-free chemical sensitivity microscopy. SRS doesn’t have non-resonant four-wave mixing background that plagued coherent anti-Stokes Raman scattering and is capable of more sensitive quantitative chemical imaging at the speed of video rate. Despite the advantages of SRS, there are still challenges preventing SRS from becoming a major tool in biology and medicine. The thesis aims at solving these challenges and establish SRS as a major tool in biomedical research and clinical applications. The thesis first demonstrates the effort to reduce the cost of SRS with an all-fiber laser source and high-speed auto-balanced detector. Then, it shows several first of the kind applications of SRS: imaging neurotransmitters at frog neuromuscular junction, tracking disease progression in mouse models of amyotrophic lateral sclerosis (ALS), performing a drug test on ALS mice without sacrificing them, and clinical study of distribution of active ingredients of skin care product on live human in collaboration with Unilever. At last, it shows the development of a simultaneous two-color SRS setup by adding a fiber amplifier to conventional SRS setup, and efforts toward further improvement of the sensitivity of CRS by performing three-color time-resolved CARS. In summary, the thesis shows exciting new applications of SRS. It also presents key technological developments that leads to in vivo, high-speed, cost-effective, sensitive SRS imaging, which are crucial for broader applications of label-free chemical microscopy in the future.