Gupta Rohit, Kalkal Ashish, Mandal Priya, Paital Diptiranjan, Brealey David, Tiwari Manish K
Nanoengineered Systems Laboratory, UCL Mechanical Engineering, University College London, London WC1E 7JE, U.K.
UCL Hawkes Institute, University College London, London W1W 7TS, U.K.
ACS Appl Mater Interfaces. 2025 Aug 6;17(31):44112-44122. doi: 10.1021/acsami.5c06701. Epub 2025 Jul 24.
This work introduces a novel, rapid, label-free, affinity-enabled electrochemical sensor for the detection of interleukin-6 (IL-6), a critical proinflammatory cytokine associated with severe conditions like sepsis and COVID-19. Unlike conventional approaches, this platform leverages an innovative biofunctional nanocomposite of TiCT MXene, tetraethylene pentaamine-functionalized reduced graphene oxide (TEPA-rGO), and Nafion, functionalized with anti-IL-6 antibodies, integrated into a carbon-based screen-printed three-electrode chip. The system achieves unprecedented sensitivity in IL-6 quantification, with a single-digit pg/mL detection limit and a broad range of 3-1000 pg/mL using ∼5 μL of serum. The sensor design is uniquely enhanced through the introduction of a genetic algorithm-based thin-layer diffusion model, which optimizes critical, previously unknown electrochemical transport parameters, including diffusion coefficient, rate constant, charge transfer coefficient, and electrochemically active surface area. This approach represents a significant advancement in biosensor modeling and performance tuning. The sensor demonstrates exceptional selectivity (signal-to-noise ratio ∼ 6.9) against relevant interferents (e.g., sepsis-related antigens, small molecules, electroactive compounds), retains operational stability for a month, and offers a sample-to-answer time of ∼15 min (i.e., up to 12 times faster than traditional ELISA), while maintaining comparable sensitivity. Detailed morphological, topographical, and chemical analyses validate the structural and functional integrity of the TEPA-rGO/MXene/Nafion nanocomposite. By combining cutting-edge nanomaterials with advanced computational modeling, this IL-6 sensor sets a new benchmark for rapid, precise cytokine detection, offering transformative potential for early disease diagnosis and prognosis.
这项工作介绍了一种新型、快速、无标记、基于亲和作用的电化学传感器，用于检测白细胞介素-6（IL-6），这是一种与败血症和新冠肺炎等严重病症相关的关键促炎细胞因子。与传统方法不同，该平台利用了一种创新的生物功能纳米复合材料，它由TiCT MXene、四乙烯五胺功能化的还原氧化石墨烯（TEPA-rGO）和用抗IL-6抗体功能化的Nafion组成，并集成到基于碳的丝网印刷三电极芯片中。该系统在IL-6定量方面实现了前所未有的灵敏度，使用约5μL血清时，检测限为个位数pg/mL，检测范围宽达3 - 1000 pg/mL。通过引入基于遗传算法的薄层扩散模型，独特地增强了传感器设计，该模型优化了关键的、以前未知的电化学传输参数，包括扩散系数、速率常数、电荷转移系数和电化学活性表面积。这种方法代表了生物传感器建模和性能调整方面的重大进展。该传感器对相关干扰物（如败血症相关抗原、小分子、电活性化合物）表现出卓越的选择性（信噪比约为6.9），保持一个月的操作稳定性，提供约15分钟的样本到答案时间（即比传统酶联免疫吸附测定法快多达十二倍），同时保持相当的灵敏度。详细的形态、形貌和化学分析验证了TEPA-rGO/MXene/Nafion纳米复合材料的结构和功能完整性。通过将前沿纳米材料与先进的计算建模相结合，这种IL-6传感器为快速、精确的细胞因子检测树立了新标杆，为疾病早期诊断和预后提供了变革性潜力。
