Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, Ministry of Education; Shandong Key Laboratory of Biochemical Analysis; Key Laboratory of Analytical Chemistry for Life Science in Universities of Shandong; College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, PR China.
Anal Chem. 2024 Sep 3;96(35):14108-14115. doi: 10.1021/acs.analchem.4c01412. Epub 2024 Aug 21.
In electrochemical analysis, developing biosensors that can resist the nonspecific adsorption of interfering biomolecules in human serum remains a huge challenge, which depends on the design of efficient antifouling materials. Herein, 3-aminopropyldimethylamine oxide (APDMAO) biomimetic zwitterions were prepared as antifouling interfaces. Among them, the unique positive and negative charges (N-O) of APDMAO promoted its hydrogen bonding with water molecules, forming a firm hydration barrier that endowed it with strong and stable antifouling performance. Meanwhile, its inherent amino groups could copolymerize with the biomimetic adhesive dopamine to form a thin layer of quinone intermediates, providing conditions for the subsequent binding of aptamers and signal probes. Importantly, the biomimetic APDMAO with functional groups and one-step oxidation characteristics solved the challenges of zwitterionic synthesis and modification, as well as improved biocompatibility of the sensing interface, thereby expanding the application potential of zwitterions as antifouling materials in sensing analysis. Thiol-containing alpha-fetoprotein (AFP) aptamers modified with methylene blue (MB) were coupled under controllable potential, greatly reducing the incubation time, which promoted the productization application of biosensors. In addition, the ratio sensing strategy using MB as internal standard factors and concanavalin-silver nanoparticles (ConA-Ag NPs) as signal probes was introduced to reduce background and instrument interferences, thus improving detection accuracy. On this basis, the proposed antifouling electrochemical biosensor achieved sensitive and accurate AFP detection over a wide dynamic range (10 fg/mL-10 ng/mL), with a low detection limit of 3.41 fg/mL (3σ/). This work provides positive insights into the development of zwitterionic antifouling materials and clinical detection of liver cancer markers in human serum.
在电化学分析中，开发能够抵抗人血清中干扰生物分子非特异性吸附的生物传感器仍然是一个巨大的挑战，这取决于高效抗污材料的设计。在此，制备了 3-氨丙基二甲基氧化胺（APDMAO）仿生两性离子作为抗污界面。其中，APDMAO 独特的正、负电荷（N-O）促进了其与水分子的氢键结合，形成坚固的水化屏障，赋予其强大而稳定的抗污性能。同时，其固有氨基可以与仿生粘合剂多巴胺共聚，形成一层醌中间产物，为随后适配体和信号探针的结合提供条件。重要的是，具有官能团和一步氧化特性的仿生 APDMAO 解决了两性离子的合成和修饰的挑战，以及提高了传感界面的生物相容性，从而扩大了两性离子作为抗污材料在传感分析中的应用潜力。含巯基的甲胎蛋白（AFP）适配体经亚甲基蓝（MB）修饰后在可控电位下偶联，大大缩短了孵育时间，促进了生物传感器的产品化应用。此外，还引入了使用 MB 作为内标因子和伴刀豆球蛋白-Ag 纳米颗粒（ConA-Ag NPs）作为信号探针的比率传感策略，以减少背景和仪器干扰，从而提高检测精度。在此基础上，所提出的抗污电化学生物传感器实现了在宽动态范围内（10 fg/mL-10 ng/mL）对 AFP 的灵敏和准确检测，检测限低至 3.41 fg/mL（3σ/）。这项工作为两性离子抗污材料的发展和人血清中肝癌标志物的临床检测提供了积极的思路。
