Bioactive Gold Plasmonic Interfaces Meet Artificial Intelligence: Advancing Saliva-Based Surface-Enhanced Raman Spectroscopy Diagnostics.

Bioactive gold plasmonic nanostructures are enabling non-invasive saliva diagnostics by amplifying weak Raman signals and converting complex biofluid chemistry into information-rich spectral fingerprints. This Review examines saliva-based Raman and surface-enhanced Raman spectroscopy (SERS) integrated with artificial intelligence (AI) from a bioactive-materials perspective. Saliva is positioned as a cross-disease liquid biopsy relevant to oncological, infectious, inflammatory, metabolic, neurodegenerative, and pulmonary disorders. Particular emphasis is placed on how gold nanostructure geometry, substrate architecture, surface functionalization, antifouling strategies, affinity capture, and protein-corona formation govern molecular access to electromagnetic hot spots, spectral reproducibility, and computational reliability. Case studies spanning oncology, infectious, inflammatory, and pulmonary disorders illustrate how substrate engineering and dataset construction jointly determine diagnostic performance and clinical portability. Because human studies combining saliva, gold-enabled SERS, and AI remain limited, explicit inclusion criteria distinguish direct salivary evidence from contextual studies using related biospecimens. Clinically viable saliva-based SERS diagnostics require coordinated co-design of bioactive plasmonic interfaces and computational pipelines, together with standardized pre-analytics, reproducible substrates, rigorous patient-level validation, shared datasets, and independent multicenter evaluation.