Metasurface-enhanced mid-infrared spectrochemical imaging of tissues

Label-free and nondestructive mid-infrared vibrational hyperspectral imaging is emerging as an important ex-vivo tissue analysis tool, providing spatially resolved biochemical information critical to understanding physiological and pathological processes. However, the chemically complex and spatially heterogeneous composition of tissue specimens and the inherently weak interaction of infrared light with biomolecules limit the analytical performance of infrared absorption spectroscopy. Here, we introduce an advanced mid-infrared spectrochemical tissue imaging modality using metasurfaces that support strong surface-localized electromagnetic fields to capture quantitative molecular maps of large-area murine brain-tissue sections. Our approach leverages polarization-multiplexed multi-resonance plasmonic metasurfaces to simultaneously detect many different functional biomolecules. The resulting surface-enhanced mid-infrared spectral imaging (SE-MIRSI) method eliminates the non-specific effects of bulk tissue morphology on the quantitative analysis of fingerprint spectra and improves the chemical selectivity. We show that the metasurface enhancement increases the retrieval of amide I and II absorption bands associated with secondary structures of proteins. Moreover, we demonstrate that plasmonic metasurfaces enhance the chemical contrast in infrared images and enable the detection of ultrathin tissue regions that are not otherwise visible to conventional mid-infrared spectral imaging. While we tested our approach on murine brain tissue sections, this chemical imaging method is well-suited for any tissue type, which significantly broadens the potential impacts of our method for both translational research and clinical histopathology.