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.
In this study, a self-powered biosensor based on an enzymatic biofuel cell was proposed for the first time for the ultrasensitive detection of soluble CD44 protein. The as-prepared biosensor was composed of the co-exist aptamer and glucose oxidase bioanode and bilirubin oxidase modified biocathode. Initially, the electron transfer from bioanode to biocathode was hindered due to the presence of the aptamer with high insulation, generating a low open-circuit voltage (E OCV ). Once the target CD44 protein was present, it was recognized and captured by the aptamer at the bioanode, thus the interaction between the target CD44 protein and the immobilized aptamer caused the structural change at the surface of the electrode, which facilitated the transfer of electrons. The E OCV showed a good linear relationship with the logarithm of the CD44 protein concentrations in the range of 0.5–1000 ng mL −1 and the detection limit was 0.052 ng mL −1 (S/N = 3). The sensing platform showed excellent anti-interference performance and outstanding stability that maintained over 97% of original E OCV after 15 days. In addition, the relative standard deviation (1.40–1.96%) and recovery (100.23–101.31%) obtained from detecting CD44 protein in real-life blood samples without special pre-treatment indicated that the constructed biosensor had great potential for early cancer diagnosis.