Sphere‐on‐Tube Biomimetic Hierarchical Nanostructures Coupled with Engineered Surfaces for Enhanced Photoelectrochemical Biosensing of Cancer Cells Expressing Folate Receptors

Abstract The quantitative detection of cancer cells and the evaluation of folate receptor (FR) expression on cell membranes are of great significance for tumor‐related research. In this work, a photoelectrochemical (PEC) biosensing interface is proposed for detection of cancer cells based on the construction of nanostructured platforms coupled with surface engineering. A “sphere‐on‐tube” hierarchical nanostructure is fabricated by depositing biomimetic polydopamine nanospheres on TiO₂ nanotube arrays. Enhanced PEC responses are achieved with the formation of polyethylene glycol antifouling layers and the immobilization of folic acid as a recognition ligand. Based on the ligand–receptor interaction, the antifouling PEC biosensor exhibits a wide linear range for the detection of the breast cancer cell line MDA‐MB‐231 from 20 to 2.0 × 10⁶ cells mL⁻¹ with a low detection limit of 15 cells mL⁻¹ (S/N = 3). The expressing differentiation of FR on several cancer cells is well discriminated. The proposed PEC cytosensing method shows great potential in detection of cancer cells expressing folate receptors.