A novel electrochemical biosensor based on aggregation-induced electrocatalytic enhancement for detection of M2-microglia derived exosomes.

The early diagnosis of cerebral infarction presents a profound clinical challenge in cerebrovascular disease management. Exosomes derived from M2-type microglia (M2 exosomes) are crucial mediators driving neural tissue repair, thus representing prognostic biomarkers with significant translational promise. Nevertheless, the accurate quantification of trace M2 exosomes is severely hindered by the complexity of biofluid matrices and extremely low abundance, highlighting an urgent demand for disruptive, ultrasensitive sensing paradigms. In this study, we developed a novel electrochemical biosensor utilizing gold-copper nanoclusters (AuCuNC) with aggregation-induced emission (AIE) properties to achieve enzyme-free, label-free, and highly sensitive analysis of M2 exosomes. A central innovation of this research is the conceptual introduction of the AIE mechanism into electrochemical enhancement. Consequently, the AIE-driven spatial conformation and electronic state transitions are directly converted into robust electrocatalytic signals, successfully circumventing the sensitivity limitations inherent to traditional electrochemical platforms. With proper reaction conditions, the developed biosensor exhibited high sensitivity in the range of 18 particles/mL to 1.8 × 107 particles/mL, along with a detection limit as low as 8 particles/mL. What's more, the biosensing strategy achieved detection of M2 exosomes with recoveries ranging from 99.8% to 101% in serum samples. This biosensor enables the dynamic tracking of M2 exosomes, providing a scientific investigation for the early diagnosis and personalized intervention of cerebral infarction.