Advancing Noninvasive Therapeutic Drug Monitoring via a 3D Microstructured Aptasensing Platform.

Therapeutic drug monitoring (TDM) typically involves inconvenient invasive blood sampling. Sweat has been identified as an alternative biofluid that offers a convenient, noninvasive solution for real-time monitoring, supporting the growing demand for personalized healthcare. To advance in noninvasive TDM, we have delivered a novel electrochemical aptamer-based (EAB) sensing platform for sweat analysis. The sensor was built on gold-coated 3D microstructured electrodes (MSEs), fabricated via polymeric replica using macroporous silicon (macro-pSi) molds. This novel platform showed strong potential to address major challenges in sweat sensing such as the accurate and precise detection of the low analyte concentrations present in sweat, enabled by boosting the signal output thanks to the increased surface area of MSEs when compared to planar electrodes, and compliance with comfortable long-term wear, ensured by the use of flexible poly-(dimethylsiloxane) (PDMS) for MSE fabrication. As a proof of concept, we demonstrated real-time quantification of vancomycin, a narrow therapeutic window antibiotic, in artificial sweat. The MSE EAB sensor achieved up to a 2-fold increase in current and a 3-fold enhancement in signal gain compared to planar electrodes, enabling rapid (<2 min), regenerable (up to 10 times without signal loss), and precise (%RSD < 5%) quantification of vancomycin across a concentration range of 1-50 μM. Moreover, kinetic analyses and cyclic voltammetry studies conducted before and after sensor regeneration and long-term storage confirmed that MSEs preserve more effectively the aptamer probes, minimizing their potential loss and demonstrating superior stability and sensing performance compared to planar electrodes. These attributes make the sensor ideal for real-time pharmacokinetic studies via sweat analysis, enabling precise monitoring to minimize vancomycin toxicity. This approach opens new possibilities for personalized healthcare and advances real-time TDM applications beyond traditional clinical settings.