盐差能驱动电化学发光传感平台的构建及其在卵巢癌肿瘤标志物检测中的研究

Development of a miniaturized and portable sensing platform for rapid, accurate and multiplexed point-of-care testing (POCT) is vital for disease diagnosis and monitoring. The project aims to develop a portable electrochemiluminescence (ECL) sensing platform powered by salinity gradient energy, and to develop a new strategy for POCT, combining reverse electrodialysis technique, bipolar electrode micro processing technique and signal amplification based on nano materials. Patches of organic/inorganic hybrid mesoporous silica membranes with ion-selectivity, large area and low cost can be used as salinity-gradient-driven power source to drive electrochemical reaction on bipolar electrode. Nano materials can be used to construct the ECL sensing interface on bipolar electrode with high conductivity, good anti-interference ability and biological compatibility. Multiplexed bipolar electrode arrays prepared by using micro processing technique can be used to simultaneously detect 3 tumour biomarkers of ovarian cancer in human serum by recording ECL images of all arrays. This project provides a practical, portable, miniaturized ECL sensing platform on bipolar electrode powered by salinity gradient energy, and 3 tumour biomarkers of ovarian cancer as models, which could make the early diagnosis of ovarian cancer more portable, miniature and multi-functional.

发展微型化、便携式传感平台用于快速、精准、多元化的床旁检测，对疾病诊断和监控均具有重要的应用价值。本项目拟结合反向电渗析技术、双极电极微加工技术、新型纳米材料增敏方法，开发便携式盐差能驱动电化学发光传感平台、发展床旁检测新方法。将具有离子选择性、大面积且价格低廉的有机/无机复合介孔二氧化硅膜材料串联构筑浓差能源转换电源。利用纳米材料构筑导电性能好、抗干扰能力强、生物相容性好的双极电极电化学发光传感界面。借助微加工技术构筑双极电极阵列检测系统，通过同时记录所有阵列的电化学发光成像，建立血清中三种卵巢癌肿瘤标志物多组分同时检测的方法。本项目旨在发展实用、便携式、微型化的盐差能驱动双极电极电化学发光传感平台，以血清中卵巢癌肿瘤标志物为分析模型，推动卵巢癌早期诊断技术向便携化、微型化、多组分同时检测方向发展。

项目开展了基于介孔二氧化硅薄膜（MSF）的电化学/电化学发光传感器的研究工作。MSF孔道高度有序且垂直于固体电极基底，具有尺寸、电荷和亲疏水等分子选择性以及高的选择渗透性。具体研究工作为i）氧化铟锡（ITO）电极表面具有羟基，可以与MSF形成O-Si-O化学键，得到高度稳定的MSF/ITO电极。基于MSF的电荷和尺寸选择性，构建了抗污染电化学传感器。ii）为了解决MSF与碳基电极之间弱的结合力，采用电化学活化或等离子体处理等方法对碳基电极进行预处理，在不引入粘合层的情况下，实现MSF在碳基电极上的稳定修饰并研究了其在复杂实际样品中直接分析的应用前景。iii）以石墨烯为导电粘合层，解决了ITO电极对有机小分子活性不强的问题，进一步开发了碳基电极上稳定生长MSF的新方法，构建了性能优异的MSF-石墨烯复合膜修饰电极传感平台，拓宽了MSF的检测对象。iv）制备表面带相反电荷的双极性二氧化硅纳米通道阵列，用于固定带电荷的电化学/电化学发光探针，进一步修饰抗原或抗体，构建高灵敏度、信号稳定的探针一体化免疫分析平台。项目执行期间共发表论文19篇，获得授权中国发明专利1项。