Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation and progressive joint damage. Early detection and biomarker‐based monitoring are crucial for effective clinical management. Among several potential biomarkers, the soluble receptor for advanced glycation end products (sRAGE) has emerged as a promising inverse indicator of RA severity. In this study, we present a label‐free, non‐Faradaic electrochemical impedance spectroscopy biosensor for sRAGE detection. The developed sensor incorporates gold‐modified electrodes functionalized with dithiobis(succinimidyl propionate) (DSP) and RAGE‐specific antibodies. Optimal performance was achieved using a concentration of 1 µg/mL antibody and 2 mM DSP, yielding a linear dose–response with a detection limit of 17.76 pg/mL across a dynamic range from 1000 to 6274 pg/mL. The proposed platform demonstrated excellent analytical precision and spike‐recovery accuracy, confirming its reproducibility. Additionally, the sensor was evaluated for interference by C‑reactive protein, demonstrating that sRAGE could be specifically detected even in the presence of this potential interferent. Furthermore, COMSOL Multiphysics simulations modeled electric field distribution, current density, and biolayer perturbation under varying total dissolved solids and electrical conductivity, demonstrating alignment between simulated field gradients and experimental impedance shifts. These findings support a mechanistic understanding of the sensor's behaviour and buffer optimization for clinical matrices. The platform shows strong potential for point‐of‐care sRAGE monitoring in RA and other inflammatory conditions, offering a rapid, cost‐effective diagnostic tool with translational relevance.
Mathew et al. (Sun,) studied this question.