In-Plane Heterostructures Enable Deterministic and Repeated Biomolecular Sensing by Surface-Enhanced Raman Scattering

Abstract Applications of plasmonic nanopores for molecular sequencing remain limited by poorly controlled translocation dynamics and predominantly single-pass readout. Here, we propose an in-plane heterostructure architecture that integrates molecular transport, confinement, and surface-enhanced Raman scattering (SERS) readout to enable deterministic and repeated interrogation of individual biomolecules. Using all-atom molecular dynamics coupled with nanoplasmonic simulations, we show that the heterostructure can actively guide molecules into and through a localized sensing region while constraining their conformational and translational dynamics. Simulated SERS signatures discriminate single-stranded DNA sequences with resolution approaching the single-nucleobase scale and further suggest the feasibility of distinguishing polyglutamine tracts of different lengths. Importantly, the in-plane geometry allows molecules to be controllably transported back and forth across the sensing region, providing a route to repeated measurements of the same molecule rather than relying on stochastic single-pass translocation. These results suggest a strategy for improving the accuracy and reproducibility of nanopore-based biomolecular sensing.