Sub-Nyquist time-domain surface-enhanced Raman mapping

Abstract: Surface-enhanced Raman scattering (SERS) combines analyte-specificity and single-molecule sensitivity, but its potential is limited by slow readout where sophisticated nanosensors are analysed in a serial fashion, one particle at a time. We introduce SERS lock-in sampling to resolve the decades-old trade-off between spectral resolution and widefield imaging. By leveraging the inherent sparsity of Raman spectra, we demonstrate that a simple digital lock-in scheme allows high-quality chemical imaging far beyond the Nyquist-Shannon limit. Our approach integrates an in-situ temporal reference to transform mechanical jitter into an exploitable feature, enabling near-random sampling. We validate SERS lock-in sampling through the multiplexed and simultaneous imaging of thousands of individual SERS-encoded sensors, achieving an orders-of-magnitude throughput-increase over the state-of-the-art. Furthermore, we demonstrate volumetric 3D chemical imaging in biomedically relevant matrices. This robust, computationally simple strategy transforms SERS from a point-observation tool to an imaging modality for clinical diagnostics and real-time chemical observations.