Chang Ya-Nan, Liang Yuelan, Gu Weihong, Wang Jiayi, Qin Yanxia, Chen Kui, Li Juan, Bai Xue, Zhang Jiaxin, Xing Gengmei
CAS Key Laboratory for Biomedical Effects of Nanomaterial & Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, Beijing 100049, China.
School of Chemical Sciences, University of Chinese Academy of Sciences (UCAS), Beijing 100049, China.
ACS Omega. 2019 May 9;4(5):8318-8323. doi: 10.1021/acsomega.8b02249. eCollection 2019 May 31.
Increased deformability and softness endow tumor cells with highly invasive and metastatic capabilities. We exploited these characteristics to fabricate a high-throughput microfluidic device to measure cell deformability and separate cancer cells. Driven by hydrodynamic forces, the cells with better deformability passed through the chip faster, whereas stiffer cells passed through the device over a longer time period. The MDA-MB-231 and MCF-7 cell lines were used to evaluate the device because their metastatic potentials were known. We found that MDA-MB-231 cells, which were softer and exhibited stronger deformability, passed through the device more quickly. HeLa cells were also successfully separated into softer and stiffer subpopulations, whose distinct mechanical properties were confirmed by atomic force microscopy. We also measured the expression of metastasis-associated proteins (epidermal growth factor receptor and integrin β 1) and found that subpopulations with varied deformabilities had different expression levels. Our results suggested that this high-throughput microfluidic device could be used to screen and evaluate the curative effects of drug and cancer progression by simultaneously testing cell deformability and expression levels of metastasis-associated proteins in separated cell subpopulations.
增强的可变形性和柔软性赋予肿瘤细胞高度侵袭和转移能力。我们利用这些特性制造了一种高通量微流控装置，用于测量细胞可变形性并分离癌细胞。在流体动力的驱动下，可变形性更好的细胞更快地通过芯片，而较硬的细胞则需要更长时间才能通过该装置。MDA-MB-231和MCF-7细胞系被用于评估该装置，因为它们的转移潜能是已知的。我们发现，更柔软且表现出更强可变形性的MDA-MB-231细胞更快地通过了该装置。HeLa细胞也成功地被分离成较软和较硬的亚群，其不同的力学性质通过原子力显微镜得到了证实。我们还测量了转移相关蛋白（表皮生长因子受体和整合素β1）的表达，发现具有不同可变形性的亚群具有不同的表达水平。我们的结果表明，这种高通量微流控装置可用于通过同时检测分离的细胞亚群中的细胞可变形性和转移相关蛋白的表达水平来筛选和评估药物疗效及癌症进展。
