Nanomaterial-Enhanced Electrochemical Biosensor for Rifampicin Monitoring in Serum: Towards Precision Tuberculosis Therapy

Abstract

Tuberculosis (TB) treatment is hampered by the pharmacokinetic variability of the cornerstone drug, rifampicin (RIF). This can lead to sub-therapeutic dosing, treatment failure, and the subsequent emergence of drug resistance. Therapeutic drug monitoring (TDM) is essential but is often inaccessible in high-burden, resource-limited settings due to its reliance on slow, expensive, and lab-based techniques like HPLC, while point of care systems offer a rapid and low-cost alternative. To address this critical gap, we have developed a low-cost, rapid, and scalable electrochemical biosensor for point-of-care RIF monitoring. The sensor platform integrates a highly selective molecularly imprinted polymer (MIP) with a highly porous gold (HPG) nanomaterial on a disposable printed circuit board (PCB) electrode, costing approximately £0.09 per unit. The HPG layer significantly enhances the electroactive surface area and provides exceptional resistance to biofouling, a critical feature for clinical utility. This allows the sensor to operate directly in complex biological matrices, demonstrating robust performance in undiluted human serum. The sensor achieves a clinically relevant detection range of 8−24 μg mL−1 with a limit of detection (LOD) of 0.848 μg mL−1 and a limit of quantification (LOQ) of 1.31 μg mL−1. This work presents a significant step towards democratizing TDM, offering a practical tool to personalize TB therapy and combat drug resistance at the frontline of patient care.