Advances in Electrochemical Nanobiosensors for Noninvasive Stress Biomarker Detection

Cortisol is a key stress-related hormone whose accurate monitoring is essential for assessing physiological responses. Traditional detection methods are invasive and impractical for continuous use. This mini-review highlights recent advances in electrochemical biosensors, particularly immunosensors, aptasensors, and molecularly imprinted polymers for non-invasive cortisol detection in blood, saliva, interstitial fluid, and sweat. While saliva correlates strongly with serum free cortisol and is widely used in psychoneuroendocrinology, its reliance on active user compliance makes it unsuitable for continuous monitoring. In contrast, interstitial fluid and sweat offer routes for minimally invasive or fully non-invasive, on-body sampling, with sweat emerging as particularly promising due to its accessibility and correlation with serum analysis, paving the way for future personalized health applications. In this mini-review, we provide a concise overview of electrochemical biosensors for cortisol in blood, saliva, and interstitial fluid, and place particular emphasis on wearable sweat-based platforms, using the former matrices mainly as reference points for performance comparison and physiological validation.