随着精准医学概念的提出，循环肿瘤细胞（CTC）检测因其具有微创、获取便利、可动态监控病情等优点日益成为肿瘤邻域的研究热点。我们前期研制的第一代NanoVelcro芯片可高效捕获CTC；第二代PLGA芯片实现了CTC的分子检测；然而，他们无法同时进行CTC计数、分子检测和体外培养。本课题拟研发的ThermoRelease系统以热敏材料PIPAAm为基底，通过微流控、温控循环等优化实现37℃特异捕获CTC，4℃快速释放CTC并达到90%以上良好的细胞活性；进一步利用CTC计数预测肺腺癌的预后、复发和转移；通过比较CTC与原发肿瘤的基因差异，分析体外培养的CTC功能与基因改变之间的关系，深入探明肺腺癌侵袭转移的机制；通过ARMS PCR和NGS等技术动态分析CTC多基因改变与药物疗效的相关性，阐明肺腺癌靶向药物的耐药机制。该课题的顺利实施将为肺腺癌的精准治疗提供更加可靠的检测手段。

Along with the proposal of precision medicine, circulating cancer cell (CTC) detection is increasingly becoming a hot field in cancer research, for its minimal invasiveness, convenient specimen obtaining and dynamic disease monitoring. Based on our previous studies, two generations of CTC chips have been developed to meet different clinical need: the first-gen NanoVelcro chip recruited CTC efficiently and the second-gen PLGA chip achieved the molecular analysis of CTC. However, both of them failed to accomplish CTC enumeration, molecular analysis and in vitro cultivation synchronously. ThermoRelease system established in this project introduced a thermo-sensitive material PIPAAm, which could specifically capture CTCs under 37℃ and then rapidly release them under 4℃ with super viability. We will further finely adjust some parameters, such as microfluid, temperature-controlled cycle and so on, to optimize our system in order to attain accurate CTC number from patients. According to above CTC numbers, we will set cut-off value to predict the prognosis, recurrence and metastasis for lung adenocarcinoma. Then, by comparing the gene differentiation between CTC and primary tumor and analyzing the relationship between gene changes and functions in in vitro cultures CTCs, we will explore the molecule mechanism of lung adenocarcinoma invasion and metastasis. ARMS PCR and NGS technologies were used to dynamically detect multi-gene change and to evaluate the link of these changes with therapeutic effect. Our study aims to illuminate the molecular mechanism of drug-resistance in lung adenocarcinoma and to provide a more reliable detection method for the precision treatment of lung adenocarcinoma.