MetaScat: Metasurface-Advanced Interferometric Scattering for Fluorescence-Free Single Extracellular Vesicle Analysis

Recent studies have confirmed that diagnostics based on liquid biopsy with single extracellular vesicle analysis reach sufficient clinical accuracy. The analysis at the single particle level is critical due to their clinically relevant heterogeneity. However, the current standard, fluorescence-based imaging platforms, cannot be scaled and require complex sample preparation.To provide a label-free and scalable alternative to fluorescence-based microscopy for single extracellular vesicle analysis in liquid biopsy, this project will lead to the development of a metasurface-based integrated imaging platform that controls the image-contrast via nanophotonic resonances (MetaScat). The hypothesis is that MetaScat will enable the label-free detection of tiny refractive index changes induced by the binding of specific antibodies to the membranes of extracellular vesicles and extract information about their single-particle biomarker distributions with a low-cost, compact imaging device. Interferometric scattering microscopy (iScat) could provide the required sensitivity. However, conventional iScat relies on high numerical aperture objectives, inherently cannot be scaled, and is restricted to a small field of view. To overcome these limitations and enable the combination of high sensitivity and throughput with low complexity, dielectric metasurfaces will here enable a nanophotonic equivalent of numerical aperture filtering while also providing homogeneous signal enhancement for each particle. The extensive expertise of my host, NanoLab at the University of Trento (UNITN), in the integration of silicon photonic platforms and computation, will be critical for this project. In collaboration with the clinical environment I currently work in, MetaScat is designed to meet the need for scaling and implementing easy-to-use, low-cost technology for single extracellular vesicle analysis in clinical laboratories and enable a wider use for early disease detection.