It is crucial to construct antifouling electrochemical biosensors with long-term stability and high sensitivity for the detection of biomarkers in complex biological environments to prevent the unspecific adsorption of proteins and other biomolecules. Herein, a glassy carbon electrode electropolymerization with polyaniline (PANI/GCE) was further modified with a copolymerization (PSN) of zwitterionic sulfobetaine methacrylate (SBMA) and hydrophobic N-isopropyl acrylamide (NIPAM) by simple hydrophobic interaction to construct an antifouling biosensor. PSN forms a stable self-assembled monolayer on the PANI/GCE surface and exhibits good antifouling performance in serum due to the advantages of hydrophobic anchoring and the antifouling performance of zwitterionic polymers. Ascribe to the large specific surface area and excellent conductivity, the present biosensor can detect CA125 in undiluted samples in the range of 0.01–1000 U mL⁻¹ with a limit of detection of 2.7 mU mL⁻¹ (3σ/k). Both with good biocompatibility and biological stability, PSN modified sensing surface realizes a long-term antifouling for 15 days in a buffer solution. The present work provides a simple strategy for the direct analysis of CA125 in human serum without a complicated construction of biosensors, indicating the potential application in clinical diagnosis.

构建具有长期稳定性和高灵敏度的防污电化学生物传感器对于检测复杂生物环境中的生物标志物以防止蛋白质和其他生物分子的非特异性吸附至关重要。在此，通过两性离子磺基甜菜碱甲基丙烯酸酯(SBMA) 和疏水性 N-异丙基酯的共聚 (PSN) 进一步改性聚苯胺 (PANI/GCE) 的玻碳电极电聚合丙烯酰胺（NIPAM）通过简单的疏水相互作用构建防污生物传感器。由于疏水锚定的优点和两性离子聚合物的防污性能，PSN在PANI/GCE表面形成稳定的自组装单分子层，在血清中表现出良好的防污性能。由于大的比表面积和优异的电导率，本生物传感器可以检测未稀释样品中 CA125，范围为 0.01–1000 U mL^-1，检测限为 2.7 mU mL^-1(3σ/k)。PSN修饰的传感表面兼具良好的生物相容性和生物稳定性，可在缓冲溶液中实现15天的长效防污。本工作为直接分析人血清中的 CA125 提供了一种简单的策略，无需复杂的生物传感器构建，表明其在临床诊断中的潜在应用。