Blood Biomarkers and Surface-Enhanced Raman Spectroscopy for Gout: A Comprehensive Review

Gout is a metabolic disorder of increasing global burden, driven by hyperuricemia and subsequent monosodium urate (MSU) crystal deposition. While early detection is critical for preventing irreversible joint damage, conventional diagnostic approaches, including synovial fluid microscopy and biochemical assays, remain invasive, labor-intensive, and often lack the sensitivity required for early-stage or asymptomatic disease. Surface-enhanced Raman spectroscopy (SERS) offers a transformative solution by enabling ultrasensitive molecular fingerprinting of urate, purine intermediates, and inflammatory mediators from microliter volumes of biofluids. This review highlights the diagnostic potential of recent advances in nanostructured substrates and machine-learning-integrated SERS systems, enabling rapid, minimally invasive point-of-care analysis. The integration of SERS-based biomarkers into routine clinical workflows could enable risk stratification, longitudinal disease monitoring, and personalized therapeutic interventions in gout management. The current landscape of blood-based SERS diagnostics is critically evaluated, with emphasis on persistent challenges related to matrix interference and signal reproducibility, and strategic directions are outlined to develop standardized, scalable platforms to reduce the global burden of gout.