A programmable matrix-robust plasmonic MetaRing biosensor for rapid SERS-based chemotherapeutic response profiling.

Rapid assessment of chemotherapeutic response is essential for precision oncology but remains hindered by tumor heterogeneity and complex biological matrices. Here, we develop MetaRing, a programmable coffee-ring-derived plasmonic biosensor fabricated through dual regulation of nanoparticle concentration and evaporation temperature. This strategy enables deterministic nanoassembly, generating hierarchical structures with dense and stable nanogaps and conferring exceptional matrix robustness in water, PBS, protein-rich buffers, and complex cell lysates. MetaRing enables rapid, label-free surface-enhanced Raman spectroscopy (SERS) profiling of paclitaxel (PTX) response using minimal biological material. Distinct PTX-sensitivity fingerprints are consistently identified across drug-resistant breast cancer cell lines, xenograft tumors, and patient-derived biopsy tissues. Metabolomic analysis reveals that these spectral signatures originate from metabolic reprogramming involving arginine and methionine-cysteine pathways, providing mechanistic insight into chemoresistance. Integration with a lightweight one-dimensional convolutional neural network enables accurate classification of PTX sensitivity within 10 min without labeling or culture expansion, achieving >92% accuracy in clinical cohorts. Collectively, MetaRing establishes a robust and scalable plasmonic platform for rapid phenotypic drug response profiling with strong translational potential.