Metasurface‐Enhanced Mid‐Infrared Spectrochemical Imaging of Tissues

Abstract

Label‐free and nondestructive mid‐infrared vibrational hyperspectral imaging is an essential 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, an advanced mid‐infrared spectrochemical tissue imaging modality is introduced using metasurfaces that support strong surface‐localized electromagnetic fields to capture quantitative molecular maps of large‐area murine brain tissue sections. The approach leverages polarization‐multiplexed multi‐resonance plasmonic metasurfaces to simultaneously detect various functional biomolecules. The surface‐enhanced mid‐infrared spectral imaging method eliminates the non‐specific effects of bulk tissue morphology on quantitative spectral analysis and improves chemical selectivity. This study shows that metasurface enhancement increases the retrieval of amide I and II bands associated with protein secondary structures. Moreover, it is demonstrated that plasmonic metasurfaces enhance the chemical contrast in infrared images and enable detection of ultrathin tissue regions that are not otherwise visible to conventional mid‐infrared spectral imaging. While this work uses murine brain tissue sections, the chemical imaging method is well‐suited for other tissue types, which broadens its potential impact for translational research and clinical histopathology.

Metasurfaces for Quantitative Biosciences of Molecules, Cells, and Tissues: Sensing and Diagnostics

“…The metasurfaces were previously designed to yield readout responses using optical spectral measurements, however, color camera-based imaging is now being developed to optimize costs and facilitate data analysis using existing products like plastic-tempered optical digital discs (DVDs) . Similarly, tuning the plasmon resonances of “ulu”-shaped metasurfaces to the vibrational levels of biomolecules present in biological tissues allows high contrast and quantitative monitoring of tissues without thickness-related artifacts . Whereas, metasurfaces yielding polarization-sensitive structural colors may enable fibrous tissue analysis.…”

“…76 Similarly, tuning the plasmon resonances of "ulu"-shaped metasurfaces to the vibrational levels of biomolecules present in biological tissues allows high contrast and quantitative monitoring of tissues without thickness-related artifacts. 68 Whereas, metasurfaces yielding polarization-sensitive structural colors may enable fibrous tissue analysis. We envision that metasurfaces could empower spatial omics approaches owing to their ability to achieve unprecedented subwavelength control of light in two-dimensional space.…”

“…Furthermore, plasmonic metasurfaces have emerged as label-free platforms for chemical composition analysis within the metasurface near field. Engineered “ulu”-shaped metasurfaces enhance mid-IR molecular spectral imaging, leading to high-quality absorbance mapping of murine brain tissue sections via hyperspectral imaging (Figure f) . Owing to multiple resonances supported by the meta-atom geometry at perpendicular polarizations of incident light, the metasurface can quantitatively assess the content of nucleic acids, proteins, lipids, and glycogen in tissues with subcellular resolution.…”

“…Engineered "ulu"-shaped metasurfaces enhance mid-IR molecular spectral imaging, leading to highquality absorbance mapping of murine brain tissue sections via hyperspectral imaging (Figure 4f). 68 Owing to multiple resonances supported by the meta-atom geometry at perpendicular polarizations of incident light, the metasurface can quantitatively assess the content of nucleic acids, proteins, lipids, and glycogen in tissues with subcellular resolution. Light confinement within the metasurface near field aids in the characterization of ultrathin tissue regions without experimental artifacts arising from tissue thickness variations.…”

Development of Meta‐Chemical Surface by Dip‐Pen Nanolithography for Precise Electrochemical Lead Sensing

“…We developed a meta‐chemical surface (MCS) using DPN, which is somewhat analogous to the widely used meta‐surface, [ 14 ] by patterning a surface with a mixture of poly‐methyl methacrylate (PMMA) and nitrilotris (methylene) tri‐phosphonic acid (NTPH), which was used as the ink composition. An MCS is defined as a periodically patterned meta‐surface [ 22–24 ] in which at least one of the patterned elements is in the nanoscale range. While the common meta‐surfaces enable a wide range of unique optical behaviors that are not commonly found in nature, [ 22 ] MCSs exhibit unique chemical properties that, though also present in the material's bulk form, are augmented when patterned.…”