Label-Free Electrochemical Interleukin-6 Sensor Exploiting rGO-Ti₃C₂T_<i>x</i> MXene Nanocomposites

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 Ti₃C₂T_<i>x</i> 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.