Chiral Plasmonic Nanocavity of Gold Helical Nanorods-on-Film for Enhanced Enantioselective Raman Metabolites Sensing.

Enantiomeric discrimination of chiral metabolites is crucial for disease diagnosis and drug screening. Herein, a chiral plasmonic cavity configuration was constructed by coupling helical Au nanorod (AuNRs) with an Au film (AuF) for enantioselective surface-enhanced Raman scattering (SERS) recognition. The optimized chiral AuNRs/AuF cavity substrate creates strong localized hotspots with defined handedness, leading to significantly boosted Raman signals with an enhancement factor of 1.2 × 108 and amplified chiral discrepancy. Quantitatively, the substrate achieves a chiral discrimination ability of 74.0%, and a detection limit of 10-8 M for L-phenylalanine. The combined experimental and theoretical results demonstrate that the superior enantioselectivity originates from the cooperative effect between chiral plasmonic field localization and stereospecific molecular interaction. As a proof of concept, the proposed chiral AuNRs/AuF substrates realized real-time quantitative detection of a chiral drug metabolite in human sweat, allowing dynamic monitoring of an individual's metabolic profile. This work provides a novel strategy for developing advanced biosensing chips suitable for sensitive detection of disease-related chiral molecules, with great potential in diagnosis, prognosis, and personalized medicine.