Hydrogel-based sensing interface with valence transition and antifouling strategies for ultrasensitive detection of neuron-specific enolase

The improvement of detection sensitivity and accuracy have been the focus on the development of biosensing analysis. In this work, a dual-function sensing interface with valence transition and antifouling strategies was designed to realize this target. On the one hand, the transition of Cu⁺/Cu²⁺ was utilized to catalyze the generation of more SO₄^•-, thus improving the electrochemiluminescence (ECL) signal of the sensor. On the other hand, polyacrylamide (PAM) hydrogel was selected as antifouling component to hinder the non-specific binding between interfering biomolecules and sensing surface. In addition, MXene nanosheets (MXene NSs) were introduced as the conductive framework and substrate. Therefore, Cu₂O-MXene NSs@PAM hydrogel was prepared as the dual-function coating for signal amplification and interface antifouling. It is worth mentioning that KHRFNKDC was designed as the short peptide ligand to specifically bind to the Fc fragment of antibodies, thus avoiding the occupation of the binding sites between antigens and antibodies, which could shorten the construction time and improve service life of the sensor. Based on this, the detection sensitivity and accuracy of the constructed ECL sensor were greatly improved, showing a wide linear range of 10 fg/mL ∼ 100 ng/mL and a low detection limit of 3.67 fg/mL (S/N = 3), which provided a feasible way for clinical detection of neuron-specific enolase in complex serum medium.