Microwave-Assisted One-Pot Synthesis of Medium-Entropy Oxides for Dual-Mode Electrochemical and Colorimetric Analysis of Sweat Biomarkers

Enzyme-mimicking nanomaterials (nanozymes) promise robust alternatives to biological catalysts for continuous health monitoring, yet achieving sufficient catalytic activity remains challenging. Here, multimetallic medium-entropy oxide (MEO) nanoparticles incorporating five transition metals (Fe, Co, Mn, Ni, Cu) demonstrate exceptional dual-mode biosensing capabilities. A facile, one-pot microwave-assisted synthesis process yields nanoparticles (12 nm diameter, configurational entropy of 1.41 R) with abundant oxygen vacancies and mixed-valence states that serve as highly active catalytic centers. When integrated with graphene oxide, the MEO creates a robust platform for nonenzymatic electrochemical detection of the stress hormone cortisol, achieving a low limit of detection (LOD) of 1.9 nM and a high sensitivity of 46.5 ± 1.9 μA μM^-1 cm^-2. The material also exhibits powerful peroxidase-like activity, enabling dual-mode colorimetric sensing. This system provides a "signal-on" response for hydrogen peroxide (H₂O₂) detection with a LOD of 2.2 μM and a selective "signal-off" response for glutathione (GSH) quantification (LOD: 0.01 μM) through an inhibitory binding mechanism. Mechanistic studies establish that the versatile catalytic performance originates from the synergistic interplay between M(II)/M(III) redox cycling, superoxide radical generation at oxygen vacancies, and efficient electron transfer. The entropy-stabilized structure maintains 92% of its activity over 20 days without refrigeration. These findings establish multimetallic entropy engineering as a powerful strategy for creating stable, high-performance nanozymes suitable for wearable biosensors and point-of-care diagnostics.