功能图案化EQCM生物传感器用于乳腺癌微转移能力和标志物检测的研究

乳腺癌微转移严重威胁乳腺癌患者的生命安全，其机制尚未明了。肿瘤细胞的粘附能力，迁移能力及基质降解能力变化是肿瘤微转移机制研究中关键的科学问题。连续跟踪检测肿瘤细胞的这些变化是上述科学问题中关键的技术问题。本项目首先拟建立基于溶液中QCM芯片上多层膜的粘附特性检测的阻抗模型，然后在理论分析的基础上，搭建一种EQCM传感器系统，来连续跟踪检测肿瘤标志物(整合素：αVβ3)表达水平不同的乳腺癌细胞在游离、粘附（与贴壁）、铺展和衰退等不同生长阶段粘附能力的变化，研究标志物对细胞粘附能力的调控机制。进一步通过对EQCM传感器芯片表面薄膜的图形化设计和制作，来研究肿瘤标志物对乳腺癌细胞粘附类型与迁移能力的调控机制；以及通过制备纳米金标记的RGD肽修饰到表面薄膜图形化的EQCM传感器芯片上，来研究标志物和基质金属蛋白酶对胞外基质降解能力的影响，从而为乳腺癌转移的预后与临床治疗提供更全面的科学指导。

Breast cancer micrometastasis is a serious problem that threatens the lives of breast cancer patients. Its mechanism is far from clear. Tumor cell adhesion, migration and matrix degradation are key scientific problems in the study of tumor micrometastasis. Monitoring of cell adhesion, migration and matrix degradation abilities in real time have been identified as a key technical challenge in tumor micrometastasis studies. Firstly, A impedance model of QCM chip in relation to the viscoelasticity is established, with its multilayer adhesive film in the solution. Then, based on the theoretical analysis of the relationship between the change in frequency and that of the adhesive property, an EQCM piezoelectric electrochemical sensor system will be constructed to continuously track the changes of adhesion characteristics of different breast cancer cells with different tumor marker (integrin αVβ3) expression levels at different growth stages (free, adherent (adherence), spreading and recession) based on the theoretical analysis. The regulatory mechanism of breast cancer cells with different tumor marker expression levels on cell adhesion at different stages will be studied. Furthermore, the mechanism of tumor marker level on the adhesion type (homogeneous and heterogeneity adhesions) and migration ability of breast cancer cells will also be investigated by pattern designing and modifying the surface of the EQCM sensor chip. As well as the preparation and modification of the nanogold-labeled functionalized materials RGD peptide onto the surface-film patterned EQCM sensor chip to investigate the synergistic mechanism of matrix metalloproteinases involved in the degradation of extracellular matrix. The research will provide a more comprehensive scientific guidance for breast cancer metastasis prognosis and clinical treatment.