Department of Electrical and Computer Engineering, Faculty of Engineering, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada.
Department of Bioengineering, McGill University, 815 Sherbrooke St. W, Montreal, Quebec, H3A 0C3, Canada.
Adv Sci (Weinh). 2024 Nov;11(41):e2309027. doi: 10.1002/advs.202309027. Epub 2024 Sep 9.
Current methods for therapeutic drug monitoring (TDM) have a long turnaround time as they involve collecting patients' blood samples followed by transferring the samples to medical laboratories where sample processing and analysis are performed. To enable real-time and minimally invasive TDM, a microneedle (MN) biosensor to monitor the levels of two important antibiotics, vancomycin (VAN) and gentamicin (GEN) is developed. The MN biosensor is composed of a hydrogel MN (HMN), and an aptamer-functionalized flexible (Flex) electrode, named HMN-Flex. The HMN extracts dermal interstitial fluid (ISF) and transfers it to the Flex electrode where sensing of the target antibiotics happens. The HMN-Flex performance is validated ex vivo using skin models as well as in vivo in live rat animal models. Data is leveraged from the HMN-Flex system to construct pharmacokinetic profiles for VAN and GEN and compare these profiles with conventional blood-based measurements. Additionally, to track pH and monitor patient's response during antibiotic treatment, an HMN is developed that employs a colorimetric method to detect changes in the pH, named HMN-pH assay, whose performance has been validated both in vitro and in vivo. Further, multiplexed antibiotic and pH detection is achieved by simultaneously employing the HMN-pH and HMN-Flex on live animals.
目前的治疗药物监测（TDM）方法需要很长的周转时间，因为它们涉及采集患者的血液样本，然后将样本转移到医学实验室进行样本处理和分析。为了实现实时和微创的 TDM，开发了一种用于监测两种重要抗生素万古霉素（VAN）和庆大霉素（GEN）水平的微针（MN）生物传感器。MN 生物传感器由水凝胶 MN（HMN）和适配体功能化的柔性（Flex）电极组成，称为 HMN-Flex。HMN 提取真皮间质液（ISF）并将其转移到 Flex 电极，在那里发生目标抗生素的传感。使用皮肤模型和活体大鼠动物模型对 HMN-Flex 进行了体外验证，并对其进行了验证。从 HMN-Flex 系统中获取数据，构建 VAN 和 GEN 的药代动力学曲线，并将这些曲线与传统的基于血液的测量方法进行比较。此外，为了跟踪 pH 值并监测抗生素治疗期间患者的反应，开发了一种使用比色法检测 pH 值变化的 HMN，称为 HMN-pH 测定，其性能已在体外和体内得到验证。此外，通过在活体动物上同时使用 HMN-pH 和 HMN-Flex，实现了多重抗生素和 pH 值检测。
