Engineered Microneedles for Interstitial Fluid Cell-Free DNA Capture and Sensing Using Iontophoretic Dual-Extraction Wearable Patch
Engineered Microneedles for Interstitial Fluid Cell-Free DNA Capture and Sensing Using Iontophoretic Dual-Extraction Wearable Patch
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DOI：
10.1002/adfm.202000591
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发表时间：
2020-04-20
影响因子：
19
通讯作者：
Kong, Jilie
中科院分区：
文献类型：
--
作者：
Yang, Bin;Fang, Xueen;Kong, Jilie
间质液（ISF）作为一种新兴的生物标志物来源，对疾病诊断具有重要意义。微针（MN）提供了用于从ISF提取所需分子的微创方法。然而，现有的MN受到其捕获效率和灵敏度的限制，这阻碍了早期疾病诊断。本文提出了一种工程化的可穿戴表皮系统，其具有反向离子电渗和MN的组合，用于快速捕获和感测EB病毒无细胞DNA（鼻咽癌的重要生物标志物）。由于反向离子电渗和MN证明的双重提取效应，工程化可穿戴平台在10分钟内成功地从ISF中分离出游离DNA靶标，阈值为5拷贝/μ L，最大捕获效率为95.4%。捕获的游离DNA也直接用于重组酶聚合酶扩增电化学微流体生物传感器，其检测限为1.1拷贝/μ L（或单个拷贝）。免疫缺陷小鼠模型的实验数据证明了可穿戴系统的可行性和实用性。总的来说，所开发的方法为无细胞DNA相关癌症筛查和预后的ISF微创采样开辟了一条创新途径。
Interstitial fluid (ISF), as an emerging source of biomarkers, is unmistakably significant for disease diagnosis. Microneedles (MNs) provide a minimally invasive approach for extracting the desired molecules from ISF. However, existing MNs are limited by their capture efficiency and sensitivity, which impedes early disease diagnosis. Herein, an engineered wearable epidermal system is presented with a combination of reverse iontophoresis and MNs for rapid capture and sensing of Epstein-Barr virus cell-free DNA (an important biomarker of nasopharyngeal carcinoma). Owing to a dual-extraction effect demonstrated by reverse iontophoresis and MNs, the engineered wearable platform successfully isolates the cell-free DNA target from ISF within 10 min, with a threshold of 5 copies per mu L and a maximum capture efficiency of 95.4%. The captured cell-free DNA is also directly used in a recombinase polymerase amplification electrochemical microfluidic biosensor with a detection limit of 1.1 copies per mu L (or a single copy). The experimental data from immunodeficient mouse models rationalizes the feasibility and practicality of the wearable system. Collectively, the developed method opens an innovative route for minimally invasive sampling of ISF for cell-free DNA-related cancer screening and prognosis.