Colloidal quantum dots-modified electrochemical sensor for high-sensitive extracellular vesicle detection

Small extracellular vesicles (sEVs), primarily referring to exosomes, have emerged as potent tools for investigating pathological mechanisms and facilitating precise diagnostics owing to their ability to transfer informative molecules between cells and their accessibility from diverse biological fluids. Despite the multitude of biomedical applications, achieving enhanced specificity and sensitivity in detecting trace sEV samples continues to pose a significant challenge. Considering the potential of electrochemical sensing in efficient molecular detection, this study proposes a viable strategy for specifically recognizing sEVs by targeting their membrane proteins. Additionally, it demonstrates sensitive and quantitative detection of sEVs based on the unique performance of PbS colloidal quantum dots (CQDs) nanomaterials. The results obtained from the analysis of differential pulse voltammetry demonstrate rapid and highly sensitive electrochemical responses. The good immobilization of target proteins on the chemically modified electrode is achieved through the synergistic effect of the charge–discharge mechanism and strong suspension bonds of PbS CQDs. The CD63 antibody-modified sensor can achieve highly sensitive detection of sEVs, providing a wide linear detection range (102 ∼ 108 particles mL−1) and a low detection limit (19 particles mL−1). The established method is ultimately employed to differentiate the sEVs originating from distinct tumor cells, thereby demonstrating its potential in membrane-biomarker-based diagnostics. Consequently, the presented electrochemical sensor demonstrates remarkable efficiency in quantifying EVs with exceptional specificity and sensitivity, thereby offering extensive prospects for applications in EV analysis and point-of-care tests.