Comment on “Three-Principal-Substrate SERS Profiling Enables Reliable Screening of Serum Biomarkers: A General Approach”

In their recent publication, Dong et al. ( Anal. Chem. 2026, 98, 9273; DOI: 10.1021/acs.analchem.5c08093 ) applied conventional band assignments to interpret serum SERS spectra. However, evidence from our group (Gobbato et al. Anal. Bioanal. Chem. 2025, 417, 6823; DOI: 10.1007/s00216-025-06192-5 ) shows that such spectra are dominated by purine metabolites (e.g., uric acid, hypoxanthine), with limited contribution from proteins or lipids. We argue that several assignments in the Dong et al. work may therefore be misleading, overstating biochemical specificity. Rigorous validation of band origins is essential to ensure a reliable interpretation of SERS-based diagnostics.