LAMP: Large-Area Molecular Mapping Platform

Abstract By providing unique chemical specificity and quantitative metabolic imaging, label-free stimulated Raman scattering (SRS) and coherent anti-Stokes Raman scattering (CARS) microscopy is now emerging as the next-generation clinical decision maker by providing molecular contrast of cancerous tissues. However, the field of view (FOV) of either SRS or CARS is limited to hundreds of microns so far, due to their nonlinear nature demanding a tight focal point and instantaneous high peak energy. Here, we adopt a 1 MHz femtosecond pulse laser to boost the CARS signal and highly sensitive fly-eye SiPM detectors for detection, and develop a large-area molecular mapping platform (LAMP) with an FOV of 3.5 × 3.5 cm2. LAMP combines CARS, second-harmonic generation (SHG), and two-photon excited fluorescence (TPEF), and achieves label-free multimodal imaging of intact bulk surgical tissue specimens. We performed large-area multimodal imaging of ovarian cancer tissues and obtained structural distributions of lipid accumulation, collagen fibers, and natural pigments that exhibit autofluorescence. LAMP holds great promise for real clinical applications, including chemical pathology and surgical guidance.