Electrochemical Immunosensing of Interleukin-6 in Human Cerebrospinal Fluid and Human Serum as an Early Biomarker for Traumatic Brain Injury

In this work, we develop a label-free electrochemical immunosensor for the detection of interleukin-6 (IL-6) in human cerebrospinal fluid (CSF) and serum for diagnostic and therapeutic monitoring. The IL-6 immunosensor is fabricated from gold interdigitated electrode arrays (IDEAs) that are modified with IL-6 antibodies for direct antigen recognition and capture. A rigorous surface analysis of the sensor architecture was conducted to ensure high structural fidelity and performance. Electrochemical characterization was conducted by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), and sensing was performed using differential pulse voltammetry (DPV). The DPV peak current was used to quantify IL-6 in buffer, CSF, and serum in the range 1 pg mL^-1 < [IL-6] < 1 μg mL^-1. The IL-6 IDEA sensor achieved a limit of detection (LOD) of 1.63 pg mL^-1 in PBS, 2.34 pg mL^-1 in human CSF, and 11.83 pg mL^-1 in human serum. The sensor response is linear in the concentration range 10 pg mL^-1 < [IL-6] < 10 ng mL^-1, and the sensor is selective for IL-6 over other common cytokines, including IL-10 and TNF-α. EIS measurements showed that the resistance to charge transfer, R_CT, decreases upon IL-6 binding, an observation attributed to a structural change upon Ab-Ag binding that opens up the architecture so that the redox probe can more easily access the electrode surface. The IL-6 IDEA sensor can be used as a point-of-care diagnostic tool to deliver rapid results (∼3 min) in clinical settings for traumatic brain injury, and potentially address the unmet need for effective diagnostic and prognostic tools for other cytokine-related illnesses, such as sepsis and COVID-19 induced cytokine storms. Given the interdigitated electrode form factor, it is likely that the performance of the sensor can be further improved through redox cycling.