基于无极QCM-D/LSPR双技术芯片的微流控系统及其对生物薄膜的多参数检测分析

The combination of two techniques is proposed, which have different principles, compatible structure, similar detection objects and measure precision. The nonpolar QCM-D/LSPR dual-technique chip is developed by integrating the LSPR sensing array into the QCM-D quartz chips, and the microfluidic bio-detection system is also studied with nanotechnology and MEMS technology. On the basis of studing the polar dual-technique chips, the major research is focus on the following aspects: the offchip electrode of the nonpolar dual-technique chip; the layout and design of noble metal nanoparticles; the design, fabrication and quantitative control modeling of the micropools and micropumps in the microfluidic system; the compatible process of the integrated system; the theory and method of the dual-technique detection; the merging, complement and correction algorithm of the testing data, etc. Through the testing and analysis of the specific and nonspecific interaction between protein molecules, the technical advantages in the biological detection of this system could be proved. In the case of the dual-technique synchronous real-time tesing toward the same membrane and bioreaction process using this system, it could not only obtain many parameters such as membrane thickness, bonding mass, viscoelasticity and sample concentration, but also improve the reliability and precision of the biological detection significantly. In summary, this research work could provide an effective technical means for the complex biological process detection and kenetics analysis.

将检测原理不同，结构相容，检测对象和检测精度相近的两种技术相结合，即将LSPR阵列集成到QCM-D的石英晶片上，研制成无极QCM-D/LSPR双技术芯片；并利用纳米技术与MEMS技术，研制出基于该芯片的生物微流控检测系统。在对有极双技术芯片研究的基础上，重点研究无极双技术芯片的片外电极和金属纳米阵列协调工作与布局问题，微流控系统中微测量池与微型泵的设计、制备与量化控制模型，系统集成兼容工艺，双技术检测理论和方法以及检测数据的融合、互补和校正算法等。通过对蛋白质分子的特异性与非特异性相互作用的检测分析，验证系统在生物检测中的技术优势。利用该系统对同一薄膜及生物作用过程进行双技术同步实时动态检测，不仅可获得薄膜的厚度、结合质量、粘弹性和被测样液浓度等众多参数信息，而且由于双技术间的互补与校正，还可显著提高生物检测的可靠性和精度；故该研究可以为复杂生物过程检测与动力学分析提供一种有效的技术手段。

将检测原理完全不同，结构相容，检测对象和检测精度相近的QCM-D和LSPR两种传感技术集成到同一石英晶片上， 分别研制成功了有极QCM-D/LSPR双技术芯片和无极QCM-D/LSPR双技术芯片，实现了双技术芯片同步检测，并完成了数据处理系统的程序设计与制作。采用MEMS与微电子等工艺技术研制做出了基于该芯片的生物微流控检测系统，大幅度提高了微流控系统样液输送的效率和样液流速的可控性。设计并制作了基于双技术芯片的微型测量池，使设计的光路（两透一反）、流场（密封）和电场（激励振荡）与测量池协调兼容，并为双技术检测提供了恒温环境，而且便于芯片的安装和拆卸。重点研究了无极双技术芯片的片外电极和金属纳米阵列协调工作与布局问题，微流控系统中微测量池与微型泵的设计、制备与量化控制模型，系统集成兼容工艺，双技术检测理论和方法以及检测数据的融合、互补和校正算法等。将上述生物芯片及系统应用于人免疫球蛋白以及刀豆球蛋白检测，不仅可获得薄膜的厚度、结合质量、粘弹性和被测样液浓度等众多参数信息，而且由于双技术间的互补与校正，还可显著提高生物检测的可靠性和精度。