靶向肺癌循环肿瘤细胞的单分子检测技术研究

Lung cancer poses a serious hazard to human health with the highest mortality rate in China, and its early diagnosis and treatment have remained great challenge. Recently, the circulating tumor cells have emerged as the promising biomarkers for early diagnosis of lung cancers. However, the amount of lung cancer-related circulating tumor cells is extremely low in patient’s blood samples, making them difficult to be quantitatively analyzed with high accuracy. We propose to develop a new method for accurate detection of lung cancer-related circulating tumor cells at single-cell and even single-molecule level. We will combine new capturing and enrichment method with microfluidic-based single-molecule detection technique for sensitive detection of intracellular nucleic acid and protein biomarkers in circulating tumor cells. We will further explore the application of this new technology in early clinical diagnosis of lung cancers, the evaluation of prognosis and the discovery of new anti-cancer drugs.

肺癌是我国致死率最高的癌症，严重危害人类健康，目前肺癌的早诊早治面临巨大的挑战。循环肿瘤细胞作为一种新型生物标志物在肺癌症早期诊断中受到越来越广泛关注。然而，肺癌循环肿瘤细胞在患者血液中含量极低，如何对其进行精准定量分析是一个悬而未决的难题。本项目拟发展高效特异肺癌循环肿瘤细胞的捕获富集方法，开发基于微流控的单分子检测技术，在单细胞和单分子水平上对肺癌循环肿瘤细胞及细胞内核酸和蛋白标志物进行超灵敏定量分析，以期实现临床肺癌早期诊断，并进一步应用于治疗预后评估及药敏性检测。

本项目通过组合不同抗体包被的磁珠，发展了一种高效富集NSCLC循环肿瘤细胞（CTC）的新技术，进一步将单分子荧光技术和微流控技术相整合建立了单个CTC的分析平台。该平台能有效减少样品消耗量、缩短样品分析时间，提高检测灵敏度。我们进一步利用该平台动态监测肿瘤细胞内相关生物标志物的变化，有助于疾病进程的实时监测。本项目实施过程中，我们在国际杂志Coordination Chemistry Review、TRAC-Trends in Analytical Chemistry、ACS Nano、Nano Letters、Biosensors and Bioelectronics、Chemical Science和Analytical Chemistry等发表高水平SCI论文157篇，累积影响因子达到1281.253，授权国家发明专利27项，获科研奖励1项。