集成电化学方法的宽频自适应差分石英晶体微天平的研制及其在肿瘤标志物检测中的应用

In this study, the electrochemistry-integrated broadband adaptive differential quartz crystal microbalance would be developed. The broadband adaptive response capacity would be introduced to address the demand of electrode modification, biological molecules recognition and biochemical cycling amplification reaction; and the time-resolved differential measurement technique would be introduced to address the demand of the universal measurement of various bioanalytes, to which the analysis sensitivity would be expected to be improved. The electrochemical technique would be integrated into this system together with the time-resolving technique to enable the QCM system to be capable to carry out both the steady-state and the transient electrochemical methods. Compared with the traditional QCM units, the system in this study would be more universally adaptive to the contemporary detection of bioanalytes of various types and of different properties accompanying the superiority of improving the sensitivity from pM to fM, and can be utilized in the detection of tumor markers, broading the application space of QCM technique. Thus, the universal QCM bioanalysis platform with independent intellectual property rights can be established.

本项目拟设计开发集成电化学方法的宽频自适应差分石英晶体微天平系统，针对电极修饰、生物分子识别与生物化学循环放大反应等应用的需求，引入宽频自适应响应系统；针对多种性质的生物分子的广泛检测的需求，将时间分辨的差分测量技术引入到仪器系统设计中，提高测量的精确度；集成电化学测量技术，结合时间分辨测量技术，构建同时适用于稳态电化学方法和暂态电化学方法的电化学-石英晶体微天平联用体系。该系统与传统QCM仪器相比，预计更广泛适用于电化学与石英晶体微天平同时检测的不同种类、不同性质的生物待测分子的分析并将灵敏度从pM级提高到fM级，可应用于肿瘤标志物的检测，拓展了其应用研究领域，并具备较高的检测灵敏度和特异性，从而形成自主知识产权的集成电化学方法的宽频自适应差分石英晶体微天平分析平台。

本项目研发了一种能够在较宽频率范围内具有自适应功能、频率测量准确快速、能够同时测量液体的粘弹性系数和耗散因子、能够同电化学系统联用并且具有恒温控制功能的QCM系统。将研制的联用系统应用于肿瘤标志物的分析检测，通过生物条形码纳米粒子等对芯片进行修饰，提高芯片检测的灵敏度；结合工具酶循环放大、滚环复制及链替代等分析放大方法，实现了肿瘤标志物的高灵敏快速检测。发表影响因子5.0以上SCI收录论文4篇，获山东省自然科学二等奖。培养硕士研究生7名，培养博士研究生5名。主办或承办国内学术会议3次，参加国内国际学术会议11次。