Breath-Based SERS Detection of Propofol Metabolites during Anesthesia Using Mesoporous Au Foam Chips

Propofol anesthesia is commonly guided by hemodynamic signs, infusion parameters, and electroencephalography-derived indices, yet noninvasive molecular approaches for distinguishing anesthesia-related states remain limited. Here, we developed a mesoporous Au foam-based surface-enhanced Raman spectroscopy (SERS) chip for breath analysis of propofol metabolites signatures and anesthesia-state discrimination. The Au foam was fabricated by selective dealloying of Au-Ag alloy films, producing an interconnected ligament-pore architecture with a pore size of 55 nm and ligament width of 24 nm, which showed broad optical extinction near 785 nm, and strong SERS activity with an enhancement factor of approximately 6.84 × 105, as well as spatially uniform mapping over 30 × 30 μm2, batch-to-batch reproducibility, humidity tolerance, 30-day storage stability, and resistance to breath-like gas flow. Using propofol, 4-hydroxypropofol, propofol glucuronide, and propofol sulfate as representative targets, molecule-specific SERS fingerprints and marker peaks were identified, enabling excellent discrimination of these structurally related molecules with classification accuracy above 85% with multivariate analysis. Quantitatively, all of these selected marker peaks showed linear responses over 2–75 ppb, with detection limits down to 0.663 ppb and spike recoveries above 90% in artificial breath matrix. Finally, breath SERS fingerprints collected from awake/pre-anesthesia, propofol anesthesia, and recovery states were analyzed by spectral scoring, PCA, supervised classification, and anesthesia-probability output, which achieved an overall state-discrimination accuracy of 86.7%, demonstrating the potential of mesoporous Au foam SERS chips for noninvasive molecular assessment of propofol anesthesia-related breath states. This work offered a compact optical strategy for molecularly informed assessment of propofol anesthesia-related breath signatures.