A novel electrochemical biosensor based on TiO 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 (TiONTAs) for the sensitive detection of exosomes in complex biological samples. This innovative biosensor takes advantage of the excellent electrochemical properties of TiONTAs and their specific interactions with the phosphate groups of exosomes. The transport of ions and electrons within the exosome-captured TiO 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 × 10 to 1 × 10 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 TiONTAs 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.