基于纳米功能材料的循环肿瘤细胞转移研究

Detection of circulating tumor cells (CTCs) in peripheral blood of cancer patients is a newly-developed method for facile, fast, repeatable and non-invasive cancer diagnosis and becomes a research focus in Oncology. Researches nowadays mainly focusing on capture of CTCs faces a considerable challenge about cell separation and collection from the substrates, which limits seriously the downstream biological and biochemical analysis on CTCs. To address such challenge, our project utilize biocompatible and biodegradable nanomaterial to form 3D nanostructures with modifiable surface and controllable morphology, and, on the basis of microfluidic technology, integrate microvalve structures to fabricate a capture and recovery system of CTCs, greatly improving the capture sensitivity and purity while realizing the effective release at the same time. Furthermore, we aim to establish and optimize a multi-means joint identification method to recognize the isolated CTCs. According to the immuno-staining, fluorescence in situ hybridization (FISH), genetic analysis and subsequent biochemical identification of membrane protein, an effective platform can be achieved for the in vitro diagnosis of tumor itself, the rapid assessment of drug response, the monitoring of tumor recurrence and metastasis, the mechanism research and so on.

外周血循环肿瘤细胞（CTCs）检测作为一种易获得、创伤小、可重复和非入侵的新型肿瘤诊断途径，受到国内外研究机构的广泛关注。目前 CTCs 技术无法有效完成CTCs的释放与收集，严重限制了CTCs的后续生化分析。本项目计划利用具有良好生物兼容性的可降解纳米材料，在衬底材料上形成尺寸与形状可控表面可修饰的三维纳米结构，并在此基础上利用微流控技术集成泵阀结构，制备循环肿瘤细胞微流捕获与释放系统，在大幅度提高循环肿瘤细胞捕获灵敏度与分离纯度的同时实现细胞从芯片中的有效释放；建立并优化多手段联合循环肿瘤细胞鉴定识别检测方法，针对收集到的CTCs完成细胞荧光免疫、细胞荧光原位杂交、基因分析和后续细胞表面膜蛋白的生化鉴定分析等步骤，为肿瘤体外诊断，药效快速评估，肿瘤复发与转移的监测以及机制研究等方面提供更加有效的实现平台。

本项目利用具有良好生物兼容性的可降解纳米材料，在衬底材料上形成尺寸与形状可控表面可修饰的三维纳米结构，并在此基础上利用微流控技术集成结构，制备循环肿瘤细胞微流捕获与释放系统，在大幅度提高循环肿瘤细胞捕获灵敏度与分离纯度的同时实现细胞从芯片中的有效释放；建立并优化多手段联合循环肿瘤细胞鉴定识别检测方法，针对收集到的CTCs完成细胞荧光免疫、细胞荧光原位杂交、基因分析和后续细胞表面膜蛋白的生化鉴定分析等步骤，为肿瘤体外诊断，药效快速评估，肿瘤复发与转移的监测以及机制研究等方面提供更加有效的实现平台。