Redox-Active Molecularly Imprinted Polymer: Synergistic Integration of Recognition and Signal Transduction for Sweat Cortisol Sensing

Cortisol is an important biomarker in response to psychological stress. Detecting its content in biological samples is crucial for gaining insights into individual stress and personalized healthcare. The limitations of traditional techniques for cortisol detection make them unsuitable for rapid and real-time analysis, thereby motivating the development of alternative sensing strategies. Herein, we report a molecularly imprinted polymer (MIP) electrochemical sensor based on laser-induced graphene (LIG), fabricated via a one-step electropolymerization that integrates a Cu²⁺-l-histidine metal complex as intrinsic redox probes and 3,4-ethylenedioxythiophene (EDOT) as a conductive scaffold. The morphology, structure, electrochemical performance, and adsorption kinetics of the MIP film were systematically characterized. This MIP/LIG has a wide linear range of 0.05 to 100 μM, covering its physiological concentration range, with a detection limit as low as 5.6 nM, which is far below the lowest cortisol level in human sweat. Furthermore, it shows good selectivity for structurally similar steroid hormones and common sweat metabolites. Its excellent reproducibility, renewability, and long-term stability make it suitable for the detection of cortisol in both artificial and real human sweat, and the results are consistent with the physiological circadian rhythm changes. Importantly, this work first proposes the redox-active MIP using metal complexes, providing a new strategy for the development of electrochemical sensors for nonelectroactive substances.