Ganden W X Kok, Emily Ortega, Michelle Z L Kee, Leon C Z Chan
Cortisol is a dynamic endocrine biomarker whose concentration varies with circadian timing, acute stressors, medication, sampling conditions and population characteristics. Saliva provides a non-invasive matrix for repeated measurement of the unbound hormone fraction and is compatible with decentralised point-of-care formats, but salivary cortisol should be interpreted as an adjunctive physiological measure rather than a standalone diagnostic test for psychiatric disorders. This review compares biological sampling matrices and critically evaluates lateral-flow immunoassays, electrochemical, surface-plasmon-resonance and quantum-dot-based cortisol sensors according to recognition chemistry, transduction mechanism, analytical range, sample matrix, validation level and translational readiness. Competitive lateral-flow assays offer rapid, low-cost and discrete measurements, whereas wearable electrochemical and microneedle platforms may support higher-frequency monitoring but face challenges in sample availability, biofouling, calibration drift and long-term stability. Across platforms, very low limits of detection do not by themselves establish suitability for salivary monitoring; physiologically relevant range coverage, authentic-saliva validation, comparison with reference methods and reproducibility are also required. Future progress will depend on standardised collection protocols, selective recognition chemistry, robust digital readout, circadian-aware interpretation and independent clinical validation.