A dual interpenetrating conductive hydrogel based 3D immunointerface for ultrasensitive electrochemical CEA detection

Early and precise diagnosis of cancer is crucial for improving patient survival rates. However, achieving ultrasensitive detection of trace-level tumor markers remains a significant challenge. In this study, we developed a novel electrochemical immunosensor for the highly sensitive detection of carcinoembryonic antigen (CEA) by employing a synergistic enhancement strategy that integrates a three-dimensional (3D) conductive interpenetrating network sensing interface with layered signal-amplifying nanoprobes. The sensing interface was constructed as a dual-interpenetrating conductive network hydrogel based on polydopamine (PDA) and a metal-organic framework (MOF) Ni₃(HITP)₂. This design not only provides excellent electrical conductivity but, owing to its 3D porous architecture and uniformly distributed gold nanoparticles (AuNPs), also offers abundant, high-activity immobilization sites for antibodies, thereby establishing an efficient 3D immunocapture interface. For signal amplification, we designed and synthesized NiCoCu-LDH@Fc nanoprobes. By leveraging the unique layered structure of double hydroxides, these probes enable high-density loading of the ferrocene signal tag, ensuring that each antigen-antibody binding event introduces thousands of electroactive molecules and triggers efficient cascade signal amplification. The sensor demonstrates a detection limit as low as 0.1067 pg/mL, along with good selectivity, reproducibility, and stability. It also shows promising clinical applicability in real serum sample detection. This work presents an innovative material design strategy and an efficient immunosensor for ultrasensitive tumor marker detection, demonstrating significant potential for early cancer diagnosis.