An electrochemical biosensor for immobilization coupling and quantifying exosomes based on a UiO-66 metal−organic framework

Extracellular vesicles, particularly exosomes, have garnered attention as promising new cancer biomarkers in recent decades. Exosome membrane proteins act as a source of information about their parent cells and offer readily accessible targets. Here, we presented a sensitive electrochemical biosensor based on a Zr-based UiO-66 metal-organic framework for immobilization coupling, and quantifying lung-cancer-derived exosomes. In this design, the carcinoembryonic antigen (CEA) aptamer identified and bound the CEA protein on the exosome surface, and the UiO-66 was immobilized, coupling with the phosphate groups of exosomes. The biosensor demonstrated a higher sensitivity than most previously described approaches, with a wider linear range (10² to 5 × 10⁶ particles/μL) and a lower limit of detection (7 particles/μL). Moreover, the biosensor exhibited clinical potential by selectively binding CEA-specific exosomes across distinct lung cancer subtypes. Our proposed biosensor offers numerous application opportunities for early clinical diagnosis, along with the benefits of affordability, excellent sensitivity, and simple operation.