Photothermally Detected Stimulated Raman Microscopy towards 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 milli-molar level due to the 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 thereafter relaxation heats up the surrounding 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. Versatile applications of SRP microscopy on viral particles, cells, and tissues are demonstrated. SRP microscopy opens a new way to perform vibrational spectroscopic imaging with ultrahigh sensitivity. One-Sentence Summary We demonstrate a new spectroscopic imaging method that improves the signal intensity by >500-fold.