Fiber laser based stimulated Raman photothermal microscopy towards a high-performance and user-friendly chemical imaging platform.

Abstract

Stimulated Raman scattering (SRS) microscopy is a highly sensitive chemical imaging technique. However, the SRS imaging performance hinges on two key factors: the reliance on low-noise but bulky solid-state laser sources and stringent sample requirements necessitated by high numerical aperture (NA) optics. Here, we present a fiber laser based stimulated Raman photothermal (SRP) microscope that addresses these limitations. While appreciating the portability and compactness of a noisy source, fiber laser SRP enables a two-order-of-magnitude improvement in signal to noise ratio over fiber laser SRS without balance detection. Furthermore, with the use of low NA, long working distance optics for signal collection, SRP expands the allowed sample space from millimeters to centimeters, which diversifies the sample formats to multi-well plates and thick tissues. The sensitivity and imaging depth are further amplified by using urea for both thermal enhancement and tissue clearance. Together, fiber laser SRP microscopy provides a robust, user-friendly platform for diverse applications.

Supplementary information: The online version contains supplementary material available at 10.1186/s43074-025-00196-1.