应用于肺癌转移研究的一种微流控捕捉芯片的设计与制作

发布时间：2018-10-07 17:23

【摘要】：研究背景及意义:肺癌是全球最常见的恶性肿瘤,具有极高的致死率和发病率。肺癌患者往往在诊断时就已出现远处转移,因而错失了最佳的治疗时机。肺癌的转移是患者致死的主要因素,因此,探究转移机制,揭示关键路径,对癌症治疗有重要的意义。然而,由于传统实验手段的限制,对于癌症转移的研究一直难以深入。随着微流控芯片技术的发展,越来越多的学者将其与生物学技术相结合,实现了高通量、高灵敏度、多因素分析、真实模拟体内环境的实验要求,极大地促进了癌症研究的发展。研究工作:1.针对肺癌的转移开展了全面而深入的调研,一方面明确了转移机制的研究进展,确定肺癌细胞的上皮间质转化(epithelial-mesenchymal transition,EMT)为目前研究的热点和重点;另一方面,整理和归纳当前的实验方法,明确了集成化的微流控芯片技术将是未来发展的方向。因此,本文选择微流控芯片技术来研究肺癌转移的关键环节——EMT。2.根据调研结果,本文利用微流控技术设计和制作了一种基于抗原抗体结合原理的微流控细胞捕捉芯片。该芯片的制作依托肿瘤微环境社会学研究实验室,利用光刻工艺分别制备抗体通道SPR-220模板和细胞通道SU-8模板。在此基础上,浇注液态聚二甲基硅氧烷(polydimethylsiloxane,PDMS),然后固化脱膜与修饰好抗体的载玻片封接成微流控细胞捕捉芯片。研究结论:1.设计和制作了一种针对肺癌EMT检测的微流控捕捉芯片,用于肺癌患者样本的分析。该芯片有望为临床的检测提供支持,并进一步应用于癌细胞与微环境相互影响的机制研究。2.优化了微流控芯片的制作流程,确定了前期加工失败的原因,为后续肺癌EMT的体外分析创造了实验条件。
[Abstract]:Background and significance: lung cancer is the most common malignant tumor in the world with high mortality and morbidity. Lung cancer patients often have distant metastasis at the time of diagnosis, thus missing the best treatment opportunity. Metastasis of lung cancer is the main cause of death. Therefore, it is important to explore the mechanism of metastasis and reveal the key pathway for cancer treatment. However, due to the limitations of traditional experimental means, the study of cancer metastasis has been difficult to deepen. With the development of microfluidic chip technology, more and more scholars combine it with biological technology to achieve high throughput, high sensitivity, multi-factor analysis, real simulation of the internal environment experimental requirements. It greatly promoted the development of cancer research. Research work: 1. A comprehensive and in-depth investigation was carried out on the metastasis of lung cancer. On the one hand, the research progress of metastasis mechanism was clarified, and the epithelial mesenchymal transformation (epithelial-mesenchymal transition,EMT) of lung cancer cells was identified as the hot spot and focus of current research; on the other hand, The current experimental methods are summarized and the integrated microfluidic chip technology will be the future development direction. Therefore, this paper chooses microfluidic chip technology to study the key link of lung cancer metastasis-EMT. 2. Based on the investigation results, a microfluidic cell capture chip based on antigen-antibody binding principle was designed and fabricated using microfluidic technology. The fabrication of the chip relies on the laboratory of sociology of tumor microenvironment. The antibody channel SPR-220 template and the cell channel SU-8 template are prepared by photolithography. On this basis, liquid poly (dimethylsiloxane) (polydimethylsiloxane,PDMS) was poured, and then solidified and demembranized with modified antibody slides sealed to form a microfluidic cell capture chip. Conclusion: 1. A microfluidic capture chip for EMT detection of lung cancer was designed and fabricated for the analysis of lung cancer patients. The chip is expected to provide support for clinical detection and be further applied to study the mechanism of the interaction between cancer cells and microenvironment. The fabrication process of microfluidic chip was optimized, and the reasons for the failure were determined, which created the experimental conditions for the in vitro analysis of lung cancer EMT.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TN492;R734.2

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