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一种结合杂交链式反应扩增的适体响应型微针贴片传感器平台,用于检测皮肤间质液中的类固醇激素皮质醇。

An aptamer-responsive microneedle patch sensor platform combining with hybridization chain reaction amplification for detection of steroid hormone cortisol in skin interstitial fluid.

作者信息

Zhou Yan, He Lin, Zhang Min, Chen Mingjian, Wu Yuchen, Liu Lamei, Qi Lanlin, Zhang Bin, Yang Xiaohai, He Xiaoxiao, Wang Kemin

机构信息

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecule Engineering of Hunan Province, Hunan University, Changsha, 410082, China.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecule Engineering of Hunan Province, Hunan University, Changsha, 410082, China.

出版信息

Biosens Bioelectron. 2025 Feb 1;269:116935. doi: 10.1016/j.bios.2024.116935. Epub 2024 Nov 12.

DOI:10.1016/j.bios.2024.116935
PMID:39550776
Abstract

Fluctuations in cortisol levels from stressors are critical for the evaluation of endocrine function in body, and abnormal levels of cortisol may indicate serious health risks. Common strategies for cortisol detection are limited by the drawbacks of the intricate and time-consuming operations and the generation of body trauma. Herein, an aptamer-responsive microneedle patch sensor combining with hybridization chain reaction (HCR) amplification (Apt-HCR MN COR patch) was prepared for easy, accurate and minimally-invasive detection of cortisol in skin interstitial fluid (ISF). In this microneedle patch, swellable methacrylated hyaluronic acid (MeHA) was employed as the matrix for ISF extraction and probes loading. When cortisol bound its aptamer, the trigger DNA initiated the HCR in microneedle patch, producing a fluorescent signal proportional to the cortisol content. Under optimized conditions, in vitro and in vivo investigation confirmed the feasibility of the Apt-HCR MN COR patch for cortisol assay, and good biocompatibility was demonstrated. Benefiting from the aptamer recognition and HCR amplification, the Apt-HCR MN COR patch exhibited excellent selectivity and a detection limit (LOD = 0.048 μM) which could cover cortisol levels in ISF. As a proof of concept, after the established mouse model had shown a circadian rhythm of cortisol secretion, the patch was further used to track cortisol response in short duration of running fatigue exercise on this mouse model. It was demonstrated the detection results agreed well with those obtained by the classical enzyme-linked immunosorbent assay (ELISA). We believed that this strategy will inspire the development of MN sensors for cortisol-related disorders monitoring.

摘要

应激源引起的皮质醇水平波动对于评估体内内分泌功能至关重要,皮质醇水平异常可能预示着严重的健康风险。常见的皮质醇检测方法存在操作复杂、耗时以及会造成身体创伤等缺点。在此,我们制备了一种结合杂交链式反应(HCR)扩增的适体响应微针贴片传感器(Apt-HCR MN COR贴片),用于简便、准确且微创地检测皮肤间质液(ISF)中的皮质醇。在这种微针贴片中,可膨胀的甲基丙烯酸化透明质酸(MeHA)被用作ISF提取和探针加载的基质。当皮质醇与它的适体结合时,触发DNA在微针贴片中引发HCR,产生与皮质醇含量成正比的荧光信号。在优化条件下,体外和体内研究证实了Apt-HCR MN COR贴片用于皮质醇检测的可行性,并证明了其良好的生物相容性。受益于适体识别和HCR扩增,Apt-HCR MN COR贴片表现出优异的选择性和检测限(LOD = 0.048 μM),能够覆盖ISF中的皮质醇水平。作为概念验证,在建立的小鼠模型显示出皮质醇分泌的昼夜节律后,该贴片进一步用于追踪该小鼠模型在短时间跑步疲劳运动中的皮质醇反应。结果表明,检测结果与经典酶联免疫吸附测定(ELISA)获得的结果高度一致。我们相信,这种策略将推动用于监测与皮质醇相关疾病的微针传感器的发展。

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