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bioRxiv · 10.1101/2025.11.03.686410

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

Tang, R.·Yin, J.·Weinberg, B.·Lin, H.·Lu, J.·Gate, D.·Klementieva, O.·Cheng, J.-X.
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Abstract

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 x 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 Alzheimers disease are demonstrated.

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Tang, R., Yin, J., Weinberg, B., Lin, H., Lu, J., Gate, D., Klementieva, O., Cheng, J.-X.. 2025-11-05. Mid-Infrared Photothermal Mesoscopy with Millimeter Field of View and Sub-micron Spatial Resolution. https://doi.org/10.1101/2025.11.03.686410

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