Advances in electrochemical biosensor design for the detection of the stress biomarker cortisol

The monitoring of stress levels in humans has become increasingly relevant, given the recent incline of stress-related mental health disorders, lifestyle impacts, and chronic physiological diseases. Long-term exposure to stress can induce anxiety and depression, heart disease, and risky behaviors, such as drug and alcohol abuse. Biomarker molecules can be quantified in biological fluids to study human stress. Cortisol, specifically, is a hormone biomarker produced in the adrenal glands with biofluid concentrations that directly correlate to stress levels in humans. The rapid, real-time detection of cortisol is necessary for stress management and predicting the onset of psychological and physical ailments. Current methods, including mass spectrometry and immunoassays, are effective for sensitive cortisol quantification. However, these techniques provide only single measurements which pose challenges in the continuous monitoring of stress levels. Additionally, these analytical methods often require trained personnel to operate expensive instrumentation. Alternatively, low-cost electrochemical biosensors enable the real-time detection and continuous monitoring of cortisol levels while also providing adequate analytical figures of merit (e.g., sensitivity, selectivity, sensor response times, detection limits, and reproducibility) in a simple design platform. This review discusses the recent developments in electrochemical biosensor design for the detection of cortisol in human biofluids. Special emphasis is given to biosensor recognition elements, including antibodies, molecularly imprinted polymers (MIPs), and aptamers, as critical components of electrochemical biosensors for cortisol detection. Furthermore, the advantages and limiting factors of various electrochemical techniques and sensing in complex biofluid matrices are overviewed. Remarks on the current challenges and future perspectives regarding electrochemical biosensors for stress monitoring are provided, including matrix effects (pH dependence and biological interferences), wearability, and large-scale production.