Harnessing complex light-matter interactions for point-of-care nano-optical biosensing

Recent advancements in nanoscale physics have resulted in a paradigm shift towards point-of-care (POC) complex healthcare diagnostics, enabling real-time biomolecular detection. These innovations are based on manipulating complex light–matter interactions at the nanoscale, where photons couple with plasmons, excitons, phonons, and resonant cavities to transduce biomolecular events into quantifiable optical signals. This review presents a physics-oriented overview and quantitative comparison of POC nano-optical biosensors based on the dominant fundamental light–matter interaction mechanism at the nanoscale. It includes surface plasmon resonance (localized, imaging, and long-range), interferometric methods (plasmon-assisted, dual-beam, and frequency-domain reflectometry), fluorescence and colorimetric assays, along with resonator-enabled architectures including whispering gallery modes, photonic crystals, Raman scattering, and optical coherence tomography. Emerging modalities, including photothermal, chemiluminescence, and nonlinear optical biosensors, are highlighted due to their wide and dynamic detection range, spanning from the micromolar to the challenging attomolar range. Besides, it details the advancements, device-miniaturization strategies, integration with advanced nanomaterials and microfluidics, and persistent challenges such as stability, non-specificity, and signal interference alongside proposed solutions. Finally, it presents future directions, including multi-modal sensing, wearable platforms, and AI-assisted predictive modelling, pointing towards next-generation of physics-enabled POC biosensors that can deliver accessible, accurate, and personalised healthcare.