Signal-amplified ECL biosensor for exosomes: Integrating Zr-MOF/Au nanoclusters with catalytic hairpin assembly

Exosomes, as extracellular vesicles, represent ideal biomarkers for liquid biopsy, enabling non-invasive, sensitive, and dynamic disease monitoring. Detection or profiling of exosomes are essential for advancing exosome-based cancer diagnostics or prognostic prediction. Here, we developed an enhanced electrochemiluminescence (ECL) biosensing platform that combines magnetic enrichment with catalytic hairpin assembly (CHA), an enzyme-free DNA amplification circuit triggered by the complementary sequences of CD63 aptamer (Apt), to achieve sensitive exosome detection. The enhanced ECL signal relies on a nanocomposite of a zirconium-based metal-organic framework (Zr-MOF) and water soluble gold nanoclusters (AuNCs), denoted as Zr-MOF/AuNCs. The platform exhibits a wide linear range (6.12 × 10² - 6.12 × 10⁷ particles/mL) and a low detection limit (187.4 particles/mL) for tumor-derived exosomes. Spike-recovery assays in complex serum matrices and high specificity confirm its robustness and clinical potential. By combining magnetic preconcentration, signal amplification via Zr-MOF and CHA, and Apt-mediated recognition, this work establishes a new paradigm for non-invasive cancer diagnostics.