Photoelectrochemical Biosensor for Sensitive Detection of Soluble CD44 Based on the Facile Construction of a Poly(ethylene glycol)/Hyaluronic Acid Hybrid Antifouling Interface

The serum level of soluble CD44 is directly associated with several clinicopathological parameters of malignant diseases. There is a great need for the development of an easy and cost-effective detection method for soluble CD44 for both the diagnosis and the treatment of cancers. In this work, a simple photoelectrochemical (PEC) method for the sensitive detection of serum-soluble CD44 is proposed based on the construction of a hybrid antifouling coating on the TiO₂ substrate. Hyaluronic acid (HA) and poly(ethylene glycol) (PEG) are co-immobilized using a biomimetic one-step surface functionalization approach. The immobilized HA shows strong recognition abilities toward soluble CD44, and the synergistic antifouling effect achieved by the combination of PEG and HA improves the sensing specificity. Based on the inhibitory effect of CD44 recognition on the PEC signal of the TiO₂ substrate, a PEC biosensor is developed with a wide response range and a low detection limit. The development of antibody-free biosensors may promote the application of soluble CD44 as a biomarker for the diagnosis and treatment of malignant diseases.