Institute of Biomedical Engineering and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu, 300044, Taiwan.
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, 300044, Taiwan.
Adv Healthc Mater. 2023 Sep;12(24):e2300321. doi: 10.1002/adhm.202300321. Epub 2023 Apr 27.
Microneedle (MN) patches, which allow the extraction of skin interstitial fluid (ISF) without a pain sensation, are powerful tools for minimally invasive biofluid sampling. Herein, an MN-assisted paper-based sensing platform that enables rapid and painless biofluid analysis with ultrasensitive molecular recognition capacity is developed. First, a controllable-swelling MN patch is constructed through the engineering of a poly(ethylene glycol) diacrylate/methacrylated hyaluronic acid hydrogel; it combines rapid, sufficient extraction of ISF with excellent structural integrity. Notably, the analyte molecules in the needles can be recovered into a moist cellulose paper through spontaneous diffusion. More importantly, the paper can be functionalized with enzymatic colorimetric reagents or a plasmonic array, enabling a desired detection capacity-for example, the use of paper-based surface-enhanced Raman spectroscopy sensors leads to label-free, trace detection (sub-ppb level) of a diverse set of molecules (cefazolin, nicotine, paraquat, methylene blue). Finally, nicotine is selected as a model drug to evaluate the painless monitoring of three human volunteers. The changes in the nicotine levels can be tracked, with the levels varying significantly in response to the metabolism of drug in different volunteers. This as-designed minimally invasive sensing system should open up new opportunities for precision medicine, especially for personal healthcare monitoring.
微针 (MN) 贴片在无需疼痛感觉的情况下即可提取皮肤间质液 (ISF)，是微创生物流体采样的有力工具。在此，开发了一种 MN 辅助的基于纸的传感平台，该平台具有超灵敏的分子识别能力，可实现快速无痛的生物流体分析。首先，通过聚乙二醇二丙烯酸酯/甲基丙烯酰化透明质酸水凝胶的工程设计构建了一种可控溶胀的 MN 贴片；它结合了快速、充分的 ISF 提取和优异的结构完整性。值得注意的是，针中的分析物分子可以通过自发扩散回收到潮湿的纤维素纸上。更重要的是，纸可以用酶比色试剂或等离子体阵列进行功能化，从而实现所需的检测能力-例如，使用基于纸的表面增强拉曼光谱传感器可实现对各种分子（头孢唑林、尼古丁、百草枯、亚甲基蓝）的无标记、痕量检测（亚 ppb 级）。最后，选择尼古丁作为模型药物来评估三名志愿者的无痛监测。可以跟踪尼古丁水平的变化，并且不同志愿者的药物代谢会导致水平发生显著变化。这种设计的微创传感系统应该为精准医学开辟新的机会，特别是在个人医疗保健监测方面。
