Eutectogel-Based Antifouling Interface: Addressing Sensitivity and Accuracy Challenges in Complex Serum

Nonspecific adsorption in complex biological matrices remains a major challenge for the clinical application of electrochemical biosensors. Although various antifouling strategies have been developed to resist nonspecific adsorption, their poor conductivity and inadequate stability create substantial challenges for sensor sensitivity and accuracy in complex serum samples. To address these issues, we present a multifunctional eutectogel with excellent antifouling capability, conductivity, and stability, enabling ultrasensitive and reliable electrochemical sensing in a complex serum. The eutectogel was synthesized using choline chloride/ethylene glycol as the solvent, carboxybetaine methacrylate (CBMA) and sulfobetaine methacrylate (SBMA) as monomers, and liquid metal nanoparticle-decorated reduced graphene oxide (LMNPs@rGO) as both the initiator and the conductive component. The resulting eutectogel exhibits excellent conductivity of 0.9546 S·m–1 along with superior antifouling performance. After incubation in undiluted serum for 2 h, the impedance change rate of the modified electrode was reduced by ∼4.68-fold compared to a BSA-modified electrode, and the antifouling performance remained stable even after continuous incubation for 72 h. Using carbohydrate antigen 19-9 as a model biomarker, the constructed sensor achieved a wide linear detection range (10 μU·mL–1 to 100 U·mL–1) and an ultralow detection limit (0.4554 μU·mL–1), which is 2–3 orders of magnitude lower than previously reported values. The proposed eutectogel-based sensor enables ultrasensitive and reliable detection of trace tumor biomarkers in complex serum, offering broad prospects for early cancer diagnosis, prognosis monitoring, and clinical application.