Stimulated Raman photothermal microscopy toward ultrasensitive chemical imaging.

Stimulated Raman scattering (SRS) microscopy has shown enormous potential in revealing molecular structures, dynamics, and couplings in complex systems. However, the sensitivity of SRS is fundamentally limited to the millimolar level due to shot noise and the small modulation depth. To overcome this barrier, we revisit SRS from the perspective of energy deposition. The SRS process pumps molecules to their vibrationally excited states. The subsequent relaxation heats up the surroundings and induces refractive index changes. By probing the refractive index changes with a laser beam, we introduce stimulated Raman photothermal (SRP) microscopy, where a >500-fold boost of modulation depth is achieved. The versatile applications of SRP microscopy on viral particles, cells, and tissues are demonstrated. SRP microscopy opens a way to perform vibrational spectroscopic imaging with ultrahigh sensitivity.