A novel electrochemical biosensor based on TiO₂ nanotube array films for highly sensitive detection of exosomes

Exosomes have emerged as a powerful biomarker for early cancer diagnosis, however, accurately detecting cancer-derived exosomes in biofluids remains a crucial challenge. In this study, we present a novel label-free electrochemical biosensor utilizing titanium dioxide nanotube array films (TiO₂NTAs) for the sensitive detection of exosomes in complex biological samples. This innovative biosensor takes advantage of the excellent electrochemical properties of TiO₂NTAs and their specific interactions with the phosphate groups of exosomes. The transport of ions and electrons within the exosome-captured TiO₂ nanotubes is hindered, leading to a significant alteration in the electrochemical response signal and enabling highly sensitive detection of exosomes. Consequently, the biosensor demonstrates a wide linear detection range from 5 × 10¹ to 1 × 10⁷ particles/μL with a limit of detection of 12.7 particles/μL and 12.6 particles/μL for the exosomes derived from hepatocellular carcinoma and colon cancer cells, respectively. Furthermore, the TiO₂NTAs biosensor can successfully distinguish the signal of extracellular vesicles in real human serum samples between 20 hepatocellular carcinoma, 20 colon cancer and 20 healthy persons (p < 0.0001). This method had a promising potential in biochemical analysis and clinical cancer diagnosis.