Mid-Infrared Photothermal Mesoscopy with Millimeter Field of View and Sub-micron Spatial Resolution

By optically sensing mid-infrared absorption through a visible probe beam, mid-infrared photothermal (MIP) microscopy has emerged as a powerful tool for chemical imaging with micromolar sensitivity and submicron spatial resolution. The adoption of spatially multiplexed camera-based widefield detection further enhanced the imaging speed. However, current widefield MIP systems suffer from a small field of view (FOV)-typically tens of square micrometers, which constrains their utility in large-area tissue imaging applications. Here, we report a laser-scan MIP mesoscope that achieves millimeter-scale FOV while preserving submicron resolution. By leveraging an all-reflective laser scanning architecture, low-magnification and medium numerical-aperture objectives, and a defocused signal collection scheme, our MIP mesoscope achieves a 1.2 × 1.2 mm² FOV, 650 nm lateral resolution, and microsecond-scale pixel dwell time. In vivo chemical imaging of whole Caenorhabditis elegans and high-throughput detection of beta-amyloids in both mouse and human brain tissues associated with Alzheimer's disease are demonstrated.