基于超浸润性微井电极阵列的尿液远程传感监测技术的研究

In this present proposal, a wireless point-of-care medical biosensing system has been proposed for the incontinence alarming of urine and especially the remote monitoring of the urinary biomarkers (i.e., amines, microRNA, urine glucose) and drug metabolites for some serious diseases such as cancers and diabetes. Here, the development of superwettable microwell arrays has been conducted with the patterned electrochemical working electrodes of ITO/gold/graphene and the biomimetic superhydrophobic surface by using the microelectrode fabrication technique and the lotus effect-inspired design strategy for the superhydrophobic interfaces. Some functional materials that are urine and / or biomarker sensitive have been prepared and modified onto the electrochemical electrodes of the microwell arrays including the mesoporous carbon, molecularly imprinted metal organic frameworks (MOF), mesoporous polymer materials, and other high-absorption target-sensitive materials. The resulting cheap, disposable, and high-throughput detectors of microelectrode-patterned microwell arrays should be inserted into the diapers to simultaneously probe the multiple disease biomarkers and drug contents or metabolites with the low levels in urine, based on the condensing and enrichment effect of the array microwells and the specific absorption of the mesoporous functional materials for the urinary targets. Moreover, the portable electrochemical devices are utilized to achieve the sensitive outputs of the response signals together with the signal amplifiers. Furthermore, some wireless transportation devices and signal monitoring equipments like network, WIFI, and cell phones are combined to facilitate the remote transportion of the electrochemical signals toward a wireless, wearable, and point-of-care biosensing system allowing for the high-throughput detections of multiple disease targets in urine. The as-developed medical sensing system can promise the applications for the incontinence management and the simultaneous medical monitoring of the disease progression and therapeutic drug effects for the disable people of the elderly, children, and serious disease patients in the hospitals, nursing homes, and families. The so obtained products of the proposal would help to release the burdens of hospital caregivers and familiy members in conducting the daily health care for the disability groups. The improvement of the life quality of patients and the recovery of diseases can also be expected. Therefore, this proposed project should be of great research significance to promise the practical and wide medical applications.

项目以生活不能自理人群的尿液警报以及癌症和糖尿病等重症标志物（如胺类、microRNA、尿糖）与药代物分析为目标，通过引入激光精加工和超疏水界面仿生制备技术，在微孔板上构筑具有“荷叶效应”和独特浸润性微井电极阵列，并经修饰介孔碳材料、金属有机骨架印迹膜、中空聚合物等目标物敏感的吸附材料，构造成可一次性使用、高通量的微井电极探头用以安插于尿布，借助超浸润性微井对目标物的浓缩富集效应及介孔材料的高吸附作用，联合检获尿液中多种低含量的疾病标志物与药代物，进而结合便携式电化学装置及网络、WIFI、手机等无线通讯设备，实现对响应信号的远程传输，构建一套可穿戴的Point-of-care尿液远程监测技术系统，用于医院、养老院、家庭等场所相关人群和重症患者的尿失禁管理以及疾病的进展监控与药效考察，对方便医护人员和家属日常监护失能人群、以及提高患者的生活质量与疾病治愈率，具有十分重要的研究意义和应用前景。

本项目以生活不能自理人群的尿液警报、癌症和糖尿病等重症大疾患标志物与药代物分析为目标，通过制备一系列新型纳米酶、光电催化剂、以及具有微纳通道结构的功能载体材料或复合物，并引入激光精加工、超疏水界面仿生、等离子表面处理等技术，在微孔板上构筑具有“荷叶效应”的超浸润性微井电极阵列或一次性电极探头，进而借助微井探头阵列对尿液或血液中目标物的富集效应，检获和监控多种低含量的疾病标志物 (例如，胺类、Hela细胞、ATP、MicroRNA、氨基酸、尿（血）糖、重金属离子、硫化氢、有机磷、组氨等) 与药代物（例如，多巴胺、左旋多巴、组胺酸等），进而结合便携式电化学装置及网络、WIFI、手机等无线通讯设备进行响应信号的远程传输，优选出一套可穿戴的医学无线远程监测技术系统，并初步应用于医院、养老院、家庭等场所失能人群的尿失禁管理和重症患者的病程进展监控与药效考察，对方便医护人员和家属日常监护失能人群、提高患者的生活质量与疾病治愈率，具有十分重要的研究意义和应用前景。项目执行期间，以负责人为第一或通讯作者，发表了标注本基金资助的SCI收录论文75篇（其中，高被引论文11篇，中科院分区SCI一区49篇，二区15篇, IF10.0以上6篇，IF8.0以上20篇），包括Anal. Chem.、 ACS Sensors、J. Mater. Chem. A、Green Chem.、Chem. Commun.、J. Hazard. Mater.、Chem. Eng. J.、 Biosens. Bioelectron.、Org. Lett.、Nanoscale、J. Org. Chem.、Sens. Actuat. B等国际权威期刊论文，项目负责人尚入选2017年度英国皇家化学会“Top1%高被引中国作者"榜，首位获山东省自然科学二等奖1项，首位获已授权国家发明专利19项；先后参加了第13届全国分析化学年会等国内外学术交流会议并做报告20余次；培养博士研究生5名，硕士研究生29名（已毕业19名），博士后5名（出站4名），青年骨干教师10余名。此外，负责人通过联合外来公司将项目研制的可穿戴式尿液无线远程监测器件，进一步拓展开发成一种智能化体温测试温度贴产品，并在抗击新冠肺炎疫情中，通过捐赠方式应用于山东、武汉、和深圳等多地疫情的隔离管控，获得了广泛的社会反响。