Interface-Enhanced Label-Free FeOOH-Mesoporous TiO2 Nanocomposite Biosensor for Highly Sensitive Quantitative Exosome Detection to Assist Cancer Screening

Exosome-based liquid biopsy has shown great promise in cancer diagnosis. Electrochemical biosensors, owing to their high efficiency, sensitivity, and operational simplicity, have become powerful tools for biological sample analysis. In this study, we developed a novel electrochemical biosensor based on FeOOH-mesoporous TiO 2 (FeOOH-mTiO 2 ) for label-free detection of exosomes in serum. Through a rationally engineered interface design, the biosensor addresses the critical challenge of simultaneously achieving high capture efficiency and high detection sensitivity. The composite material consists of a catalytic FeOOH core and a mesoporous TiO 2 shell. The high surface area of the mesoporous structure provides abundant active sites and enhances the selective interaction between TiO 2 and the phosphate groups on exosome membranes. Moreover, the formation of Ti–O–Fe interfacial bonds facilitate electron transfer and significantly improves the electrochemical response. The sensor achieves a detection limit of 2.04 particles/μL with a broad linear range of 10 2 –10 8 particles/μL, without the need for antibody-based capture or complex surface modifications. Clinical testing revealed that exosome levels in patients with hepatocellular carcinoma and colorectal cancer were 2.9 to 3.1-fold higher than those in healthy controls. This work advances exosome liquid biopsy technology through innovative material design and demonstrates strong potential for clinical cancer diagnosis and monitoring.