Aptamer-Functionalized CuNPs for Label-Free and Highly-Sensitive Detection of Interleukin-6 Using a Light-Addressable Potentiometric Sensor

Interleukin-6 (IL-6) is a crucial biomarker for monitoring inflammatory responses and chronic diseases, including cancer. In this work, we present a novel label-free aptasensor that combines copper nanoparticles (CuNPs) with a light-addressable potentiometric sensor (LAPS) platform, enabling the highly-sensitive detection of IL-6. The presence of CuNPs significantly enhances electron transfer dynamics and potentiometric signal amplification, while IL-6-specific Aptamers offer high molecular recognition and binding affinity. The sensor transduces IL-6 binding events into detectable potential shifts, enabling quantitative analysis. The device exhibited exceptional selectivity in the presence of potential interfering substances, maintained high stability over multiple measurement cycles, and showed strong reproducibility. Under optimized parameters, the sensor achieved a wide linear detection range from 5 to 200 ng/mL, with a remarkably low detection limit of 2.1 pg/mL. Additionally, its successful performance in spiked human serum samples highlights its practicality and robustness for clinical diagnostic applications.