  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.
