ZnO-Ag Hybrid SERS Platforms for Stress Biomarker Detection: From Mechanisms to Materials Engineering and Sensing Applications

Abstract

Abstract The increasing prevalence of physiological and psychological stress has created a growing demand for rapid, sensitive and non-invasive methods for detecting stress-related biomarkers. Surface-Enhanced Raman Scattering (SERS) has emerged as a highly promising analytical platform due to its exceptional sensitivity, molecular fingerprint specificity and capability for ultra-trace detection. Among the various SERS substrates explored, hybrid nanostructures composed of zinc oxide (ZnO) and silver (Ag) nanoparticles have attracted considerable attention because they integrate the strong localized surface plasmon resonance of Ag with the semiconducting properties, high surface area and chemical stability of ZnO. This synergistic interaction promotes both electromagnetic and charge-transfer enhancement mechanisms, significantly improving Raman signal amplification and detection sensitivity. This review provides a comprehensive overview of recent advances in ZnO-Ag nanocomposite SERS substrates and their emerging potential for stress biomarker detection. The fundamental principles of SERS enhancement are first discussed, followed by a critical evaluation of synthesis strategies, nanostructure engineering and interfacial design used to optimize plasmonic-semiconductor coupling. Particular emphasis is placed on the influence of morphology, particle size, defect engineering and surface functionalization on SERS performance. The applicability of ZnO-Ag hybrid platforms for detecting key stress-related biomarkers, including cortisol, catecholamines and oxidative stress indicators in biological fluids, is subsequently highlighted. Current challenges such as substrate reproducibility, signal stability and practical integration into portable sensing systems are also addressed. Finally, future perspectives are outlined toward the development of wearable and real-time SERS-based biosensing platforms for continuous stress monitoring. The integration of plasmonic-semiconductor nanostructures with advanced sensing technologies is expected to accelerate the development of next-generation diagnostic tools for precision health monitoring.