Interleukin-6 (IL-6) is an important cytokine involved in immune responses and maintaining body homeostasis. Elevated IL-6 levels, exceeding ∼ 40 pg/mL in bodily fluids, are associated with inflammation and diseases such as COVID-19, cardiovascular disorders, and Alzheimer’s, necessitating real-time health monitoring for personalized healthcare. In this study, we developed a highly sensitive and selective IL-6 sensing platform by depositing a poly(o-phenylenediamine) (P(o-PD))-based molecularly imprinted polymer (MIP) onto an oxygen-functionalized screen-printed carbon electrode with gold nanoparticles, 3-aminopropyltriethoxysilane (APTES), and glutaraldehyde (GA). While APTES enhanced the peak current due to redox probe adsorption, GA reduced it due to non-conductive aldehyde groups. This functionalized surface improved hydrophilicity due to the presence of amino and carbonyl groups. We identified that a 120-minute NaCl treatment effectively removed IL-6 templates, ensuring the successful embedding of IL-6 in the P(o-PD) matrix. We calculated an imprinting factor of 11.2, indicating the effective imprinting of IL-6 by P(o-PD) and the presence of IL-6 specific binding sites within the MIP, resulting in a robust current response to IL-6. After optimizing the MIP deposition through five cycles, we detected IL-6 concentrations ranging from 2 to 400 pg/mL, with a sensitivity of 3.48 μA/log(pg/mL) and a limit of detection of 1.74 pg/mL. When tested in real human serum, the sensor encountered challenges due to P(o-PD) matrix adsorbing other active molecules. Despite this challenge, our platform demonstrates high selectivity and long-term stability in IL-6 detection. These qualities position our sensor well-suited for point-of-care diagnostics, emphasizing its potential as a reliable tool for real-world applications.
