Non-invasive electrochemical detection of cortisol in artificial sweat using molecularly imprinted polymer

Cortisol or its medicinal form hydrocortisone (HCT) in accessible biofluids is widely used as a biomarker of stress and stress-related disorders, including Cushing syndrome, chronic fatigue syndrome, post-traumatic stress disorders, and fibromyalgia. Here, we report a simple nanomaterial-free electrochemical sensing strategy for selective cortisol detection based on a molecularly imprinted polymer (MIP) formed directly on indium tin oxide (ITO). The resulting sensor exhibited a wide linear dynamic range (100 pg/mL to 160 ng/mL) in artificial sweat, covering clinically relevant cortisol concentrations. Detection limits of 2.2 pg/mL and 8.2 ng/mL in phosphate-buffered saline (PBS) and artificial sweat respectively, were achieved. Sensor's selectivity was validated against structurally related steroid hormones (cortisone, progesterone, estradiol, and testosterone) and other interferents of comparable molecular weight. The sensor also demonstrated strong initial operational stability and reusability over at least nine rebinding/regeneration cycles with minimal performance drift (RSD <5%). Thus, despite the exclusion of signal amplifying nanomaterial in the sensor preparation, an analytical platform with high performance was achieved through intelligent molecular design. This approach is readily transferrable to other electrode architectures that support more flexible and wearable cortisol monitoring in non-invasive biofluids for clinical and well-being applications.