Electrochemical Sensors for Alpha-Fetoprotein Based Upon Poly(Lysine)-Titanium Dioxide-Black Phosphorus Composites

Alpha-fetoprotein (AFP) is a critical biomarker for hepatocellular carcinoma, yet reliable detection remained challenging due to the inherent limitations of conventional methods which are often labor‑intensive, time‑consuming, and required sophisticated instrumentation or expensive reagents. To address these issues, we report a robust and versatile sensing platform based on a poly(lysine)‑modified titanium dioxide‑black phosphorus (PLL‑TiO2‑BP) composite. The potential of the composite as a sensing interface material was evaluated by constructing an electrochemical immunosensor (EI) for AFP which exhibited a linear range of 0.01–1000 ng·mL−1 and a limit of detection (LOD) of 4.64 fg·mL−1, confirming the excellent electrochemical performance and platform suitability of the composites. Given the inherent drawbacks of antibodies, including high cost, limited stability, and operational complexity, an antibody‑free molecularly imprinted electrochemical sensor (MIECS) was fabricated based on the composites. Remarkably, the MIECS achieved a lower LOD of 0.383 fg·mL−1 and maintained the same broad linear range (0.01–1000 ng·mL−1) compared with EI. Meanwhile, the MIECS exhibited excellent repeatability, high specificity, and satisfactory performance in real serum sample analysis. With its significantly reduced cost, enhanced stability, and simplified operation, the MIECS based on PLL-TiO2-BP composites offers a highly attractive and scalable strategy for AFP detection.