A unified framework for sensitivity comparison across stimulated Raman, stimulated Raman photothermal, and mid-infrared photothermal microscopy

Label-free vibrational microscopy based on Raman scattering and mid-infrared (MIR) absorption has advanced biological imaging through the development of diverse high-sensitivity modalities. However, rigorous sensitivity comparisons across these techniques remain lacking. Here, we establish a unified theoretical framework for quantitatively comparing the shot-noise-limited sensitivities of stimulated Raman scattering (SRS), MIR photothermal (MIP), and stimulated Raman photothermal (SRP) microscopy. The framework is built on two quantities: an effective absorption coefficient, which places SRS on the same footing as linear absorption, and a photothermal (PT) factor, which isolates the contribution specific to PT readout. Using experimentally realistic parameters, we show that MIR absorption coefficients for representative polar vibrational modes are typically about two orders of magnitude larger than the effective absorption coefficients of SRS, even for strong off-resonant Raman bands. In MIP, however, this intrinsic advantage is partly offset by a small PT factor, limiting the net sensitivity gain over SRS to several-fold and, at most, about one order of magnitude. In SRP, by contrast, burst-pulse thermal accumulation substantially increases the PT factor. Under ideal shot-noise-limited conditions with matched per-pulse excitation-energy conditions in water, SRP is predicted to provide sensitivities several-fold higher than those of SRS and to approach those of MIP. This framework provides a common basis for sensitivity assessment across vibrational imaging modalities and clarifies how absorption strength, photothermal accumulation, and readout conditions determine the practical advantages of each modality.