Nature-Inspired Metasurfaces for Next-Generation Imaging and Diagnostics

Although fibrotic diseases are associated with one-third of deaths worldwide, an incomplete understanding of their defining traits – including the role of tissue microstructure – hinders the development of effective diagnostic tools and treatments. The gold standard of tissue diagnostics encompasses biochemical staining techniques, such as Hematoxylin and Eosin (H&E), which selectively stains cell nuclei blue and the extracellular matrix red, and collagen-specific stains such as Picrosirius red, which enhance collagen birefringence and facilitate polarized light microscopy. These staining techniques fall short in several aspects. First, staining artefacts can skew tissue characterization by producing false positives or false negatives. Second, H&E staining provides morphological information on the tissue of interest but does not mark the tissue microstructure. Third, stains such as Picrosirius Red which selectively classify fibrous tissue properties, provide qualitative information about the presence of fibrous tissue structures but do not quantify their birefringence and orientation. Here, we leverage nature-derived structural color to introduce a new platform for tissue-microstructure imaging which overcomes the above-listed challenges and surpasses the performance of the current state of the art. We leverage the Morpho and Papilio Blumei butterfly wings and the Chalcothea Smaragdina beetle shell, as a novel imaging platform to elucidate the fibrous properties of biological tissue. Unstained and fixed murine breast cancer tissue sections are studied with high and low collagen content. By interfacing histological tissue sections with the studied nature-derived structural color system, we achieve selective structural coloration of the tissue based on its fibrous properties in a contact-free and label-free manner. Using Jones calculus and color theory, we define key figures of merit which quantify the anisotropic optical properties of the fibrous tissue for the tissue-structural color system and for the tissue on its own. The enhancement of the tissue optical anisotropy with the nature-derived metasurfaces will then be assessed, showcasing the potential of this technique in various diagnostic applications.