Haji-Hashemi Hedieh, Bahadorikhalili Saeed, Prieto-Simón Beatriz
Institute of Chemical Research of Catalonia, The Barcelona Institute of Science and Technology, Av. Països Catalans, 16, Tarragona 43007, Spain.
Department of Electronic Engineering, Universitat Rovira i Virgili, Tarragona 43007, Spain.
ACS Omega. 2025 Aug 6;10(32):35689-35697. doi: 10.1021/acsomega.5c02245. eCollection 2025 Aug 19.
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.
治疗药物监测（TDM）通常需要进行不便的侵入性血液采样。汗液已被确定为一种替代生物流体，它为实时监测提供了一种方便、非侵入性的解决方案，满足了对个性化医疗日益增长的需求。为了推进非侵入性TDM，我们开发了一种基于电化学适体的新型传感平台用于汗液分析。该传感器构建在镀金的3D微结构电极（MSE）上，通过使用大孔硅（macro-pSi）模具的聚合物复制法制造。这个新型平台在解决汗液传感的主要挑战方面显示出强大潜力，例如准确精确地检测汗液中存在的低分析物浓度，这得益于与平面电极相比MSE表面积增加从而提高了信号输出，以及通过使用柔性聚二甲基硅氧烷（PDMS）制造MSE确保了舒适的长期佩戴。作为概念验证，我们展示了对万古霉素（一种治疗窗窄的抗生素）在人工汗液中的实时定量。与平面电极相比，MSE EAB传感器的电流增加了2倍，信号增益提高了3倍，能够在1-50μM的浓度范围内快速（<2分钟）、可再生（高达10次且无信号损失）且精确（%RSD<5%）地定量万古霉素。此外，在传感器再生和长期储存前后进行的动力学分析和循环伏安法研究证实，MSE能更有效地保留适体探针，将其潜在损失降至最低，并与平面电极相比显示出卓越的稳定性和传感性能。这些特性使该传感器非常适合通过汗液分析进行实时药代动力学研究，能够精确监测以将万古霉素毒性降至最低。这种方法为个性化医疗开辟了新的可能性，并推动了实时TDM应用超越传统临床环境。
