From hotspots to hotspaces: Cascaded photonic-plasmonic coupling for SERS-based deep profiling of whole small extracellular vesicles
Abstract
The spatial confinement of electromagnetic hotspots ( 106, a regime inaccessible to conventional surface-enhanced Raman scattering (SERS) platforms. In silico simulations and experiments reveal ~20-fold enhancements in signal intensity and spatial reach compared to conventional nanoarrays. As a proof of concept, we demonstrate ultrasensitive, label-free classification of extracellular vesicles, 80 to 200 nm in diameter, derived from patients with colorectal cancer with 99.8% accuracy, surpassing traditional SERS (<87.5%). More broadly, this cascaded excitation strategy shifts the emphasis from nanogap optimization to the engineering of spatially extended fields through hybrid light-focusing architectures, enabling advances in spectroscopy, biosensing, nanophotonics, and diagnostics.
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