Department of Chemistry, KTH Royal Institute of Technology, Teknikringen 30, SE-114 28 Stockholm, Sweden.
UCAM-SENS, Universidad Católica San Antonio de Murcia, UCAM HiTech, Avda. Andres Hernandez Ros 1, 30107 Murcia, Spain.
ACS Sens. 2024 Jun 28;9(6):3115-3125. doi: 10.1021/acssensors.4c00337. Epub 2024 May 22.
Lactate is an important diagnostic and prognostic biomarker of several human pathological conditions, such as sepsis, malaria, and dengue fever. Unfortunately, due to the lack of reliable analytical decentralized platforms, the determination of lactate yet relies on discrete blood-based assays, which are invasive and inefficient and may cause tension and pain in the patient. Herein, we demonstrate the potential of a fully integrated microneedle (MN) sensing system for the minimally invasive transdermal detection of lactate in an interstitial fluid (ISF). The originality of this analytical technology relies on: (i) a strategy to provide a uniform coating of a doped polymer-based membrane as a diffusion-limiting layer on the MN structure, optimized to perform full-range lactate detection in the ISF (linear range of response: 0.25-35 mM, 30 s assay time, 8 h operation), (ii) double validation of ex vivo and in vivo results based on ISF and blood measurements in rats, (iii) monitoring of lactate level fluctuations under the administration of anesthesia to mimic bedside clinical scenarios, and (iv) in-house design and fabrication of a fully integrated and portable sensing device in the form of a wearable patch including a custom application and user-friendly interface in a smartphone for the rapid, routine, continuous, and real-time lactate monitoring. The main analytical merits of the lactate MN sensor include appropriate selectivity, reversibility, stability, and durability by using a two-electrode amperometric readout. The ex-vivo testing of the MN patch of preconditioned rat skin pieces and euthanized rats successfully demonstrated the accuracy in measuring lactate levels. The in vivo measurements suggested the existence of a positive correlation between ISF and blood lactate when a lag time of 10 min is considered (Pearson's coefficient = 0.85, mean difference = 0.08 mM). The developed MN-based platform offers distinct advantages over noncontinuous blood sampling in a wide range of contexts, especially where access to laboratory services is limited or blood sampling is not suitable. Implementation of the wearable patch in healthcare could envision personalized medicine in a variety of clinical settings.
乳酸是几种人类病理情况的重要诊断和预后生物标志物，例如败血症、疟疾和登革热。不幸的是，由于缺乏可靠的分析分散平台，乳酸的测定仍然依赖于离散的基于血液的检测，这些检测具有侵入性且效率低下，可能会给患者带来紧张和疼痛。在此，我们展示了一种完全集成的微针（MN）传感系统在间质液（ISF）中进行乳酸微创透皮检测的潜力。这种分析技术的新颖之处在于：（i）提供掺杂聚合物基膜的均匀涂层作为 MN 结构上的扩散限制层的策略，该策略经过优化可在 ISF 中进行全范围乳酸检测（响应线性范围：0.25-35 mM，30 s 检测时间，8 h 操作时间），（ii）基于 ISF 和大鼠血液测量对离体和体内结果进行双重验证，（iii）监测麻醉下乳酸水平波动以模拟床边临床情况，以及（iv）以可穿戴贴片的形式自行设计和制造完全集成和便携式传感设备，包括智能手机中的自定义应用程序和用户友好界面，用于快速、常规、连续和实时乳酸监测。乳酸 MN 传感器的主要分析优点包括使用两电极安培读数实现适当的选择性、可逆性、稳定性和耐用性。预处理大鼠皮肤片和安乐死大鼠的 MN 贴片的离体测试成功证明了测量乳酸水平的准确性。体内测量表明，当考虑 10 分钟的滞后时间时，ISF 和血液乳酸之间存在正相关关系（Pearson 系数= 0.85，平均差异= 0.08 mM）。与非连续血液采样相比，基于 MN 的平台在广泛的情况下具有明显优势，尤其是在获得实验室服务有限或不适合采血的情况下。可穿戴贴片在医疗保健中的实施可以在各种临床环境中设想个性化医疗。
