Sulfate-Directed Silver Dendrites with Enhanced Stability for Ultrasensitive SERS-Based Therapeutic Drug Monitoring

Silver-based surface-enhanced Raman spectroscopy (SERS) substrates offer exceptional signal enhancement but suffer from poor long-term stability due to oxidative degradation, limiting their utility for real-world applications. Here, we introduce sulfate-directed silver dendrites (s-AgDs) as oxidation-resistant SERS substrates with extended shelf life, reproducible signal performance, and sub-picomolar sensitivity. Sulfate ions promote anisotropic growth and form a surface-associated sulfate layer, resulting in dendritic morphologies with high hot-spot density and suppressed surface oxidation. The AgDs demonstrate robust SERS performance over seven months under ambient conditions. We demonstrate translational utility by detecting five clinically relevant drugs in aqueous and blood plasma matrices with minimal pretreatment and excellent reproducibility. These results establish s-AgDs as a stable, reproducible, and application-ready SERS platform for point-of-care therapeutic drug monitoring.