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 MEOs serve as a robust platform for non-enzymatic 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 A M-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 a synergy between M(II)/M(III) redox cycling, the generation of superoxide radicals at oxygen vacancies, and efficient electron transfer. The entropy-stabilized structure maintains 92% 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.