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使用基于尺寸的高性能微流控芯片对具有多种生物标志物的肺癌患者循环肿瘤细胞进行分析。

Analysis of circulating tumor cells from lung cancer patients with multiple biomarkers using high-performance size-based microfluidic chip.

作者信息

Gao Wanlei, Yuan Haojun, Jing Fengxiang, Wu Shan, Zhou Hongbo, Mao Hongju, Jin Qinghui, Zhao Jianlong, Cong Hui, Jia Chunping

机构信息

State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China.

University of Chinese Academy of Sciences, Beijing 100039, China.

出版信息

Oncotarget. 2017 Feb 21;8(8):12917-12928. doi: 10.18632/oncotarget.14203.

Abstract

Circulating tumor cells (CTCs) have attracted pretty much attention from scientists because of their important relationship with the process of metastasis. Here, we developed a size-based microfluidic chip containing triangular pillar array and filter channel array for detecting single CTCs and CTC clusters independent of tumor-specific markers. The cell populations in chip were characterized by immune-fluorescent staining combining an epithelial marker and a mesenchymal marker. We largely decreased the whole time of detection process to nearly 1.5h with this microfluidic device. The CTCs were subsequently measured in 77 patients with lung cancer and 39 healthy persons. The microfluidic device allowed for the detection of CTCs with apparent high sensitivity and specificity (82.7% sensitivity and 100% specificity). Furthermore, the total CTC counts were found to be elevated in advanced patients with metastases when compared with those without (20.89±14.57 vs 8.428±5.858 cells/mL blood; P<0.01). Combined epithelial marker and mesenchymal marker analysis of CTCs could provide more information about metastasis in patients than only usage of epithelial marker. In conclusion, the development of the size-based microfluidic device for efficient capture of CTCs will enable detailed characterization of their biological properties and values in cancer diagnosis.

摘要

循环肿瘤细胞(CTCs)因其与转移过程的重要关系而备受科学家关注。在此,我们开发了一种基于尺寸的微流控芯片,其包含三角柱阵列和过滤通道阵列,用于检测单个CTCs和CTCs簇,且不依赖肿瘤特异性标志物。芯片中的细胞群体通过结合上皮标志物和间充质标志物的免疫荧光染色进行表征。使用这种微流控装置,我们将整个检测过程的时间大幅缩短至近1.5小时。随后对77例肺癌患者和39名健康人进行了CTCs检测。该微流控装置能够以明显较高的灵敏度和特异性检测CTCs(灵敏度为82.7%,特异性为100%)。此外,与无转移的晚期患者相比,有转移的晚期患者的CTCs总数升高(分别为20.89±14.57个/毫升血液和8.428±5.858个/毫升血液;P<0.01)。对CTCs进行上皮标志物和间充质标志物联合分析比仅使用上皮标志物能提供更多关于患者转移的信息。总之,开发用于高效捕获CTCs的基于尺寸的微流控装置将能够详细表征其生物学特性及其在癌症诊断中的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba7a/5355066/2849168d40be/oncotarget-08-12917-g001.jpg

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