Oxygen vacancies-induced dual-interface modulation for TiO2/BiOI-based photoelectrochemical biosensor of urinary cancer markers.

Non-invasive urine-based cancer biomarker detection holds significant clinical value in cancer screening, treatment efficacy monitoring, recurrence warning, and auxiliary diagnosis. To address the issues of poor sensitivity and selectivity in photoelectrochemical (PEC) biosensing for the detection of cancer biomarkers in urine, oxygen vacancies (OVs)-induced dual-interface modulation strategy is proposed for constructing a TiO2/BiOI-based PEC sensor. The introduction of OVs not only induces the in-situ formation of bismuth nanoparticles at the solid-solid interface but also generates positive surface charge at the solid-liquid interface, which promotes the formation of the Z-scheme heterojunction and the modification with a negatively charged anti-fouling polymer layer (C-PEG), thereby effectively enhancing the photoelectric conversion efficiency and antifouling performance of the PEC sensor. Meanwhile, functionalization with aptamers further improves its selectivity. Leveraging the synergistic effects of the Z-scheme, anti-fouling polymer layers, and aptamers, the developed PEC sensor achieves highly sensitive and selective detection of alpha-fetoprotein (AFP), with a linear relationship in the range of 1.0 pg/mL∼150.0 ng/mL, and a detection limit of 0.3 pg/mL (LOD = 3s/k). In addition, the sensor successfully measures AFP levels in serum and urine samples from healthy individuals and hepatocellular carcinoma patients, and statistical analysis reveals a strong correlation between the serum and urinary AFP concentrations (r = 0.934, P < 0.001, n = 9). These findings indicate the preliminary feasibility of the proposed PEC sensor for non-invasive urine-based AFP detection, which may provide insights for future research.