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水平集方法在微流控装置中正常细胞和癌细胞变形性模拟中的应用。

Application of level-set method in simulation of normal and cancer cells deformability within a microfluidic device.

作者信息

Mirzaaghaian Arman, Ramiar Abas, Ranjbar Ali Akbar, Warkiani Majid Ebrahimi

机构信息

Department of Mechanical Engineering, Babol Noshirvani University of Technology, Babol 47148, Iran.

Department of Mechanical Engineering, Babol Noshirvani University of Technology, Babol 47148, Iran.

出版信息

J Biomech. 2020 Nov 9;112:110066. doi: 10.1016/j.jbiomech.2020.110066. Epub 2020 Sep 28.

Abstract

Application of microfluidic systems for the study of cellular behaviors has been a flourishing area of research in the past decade. In the process of probing cell biomechanics the passage of a cell through a narrow microchannel or a small pore has attracted much attention during the recent years. And the study of cellular deformability and transportability using these systems with enhanced resolution and accuracy has opened a new paradigm for high-throughput characterization of both healthy and diseased cell populations.Here we use the level-set method to explore the relationship between the transit time and mechanical properties of normal white blood cells (WBCs) and breast cancer epithelial cells (MCF7) under different microenvironmental parameters (i.e., pressure difference, cell size, effective cell surface tension, constriction size and taper angle) in a 2-D computational domain by considering the cell as a viscous drop. The novel biomechanical relations are obtained for each cell type by the Response Surface Method (RSM), relating microenvironmental parameters to the dimensionless entry time of the normal and cancer cells. Our results revealed that MCF7 cells show asignificantly different behavior (a bifurcating behavior when the pressure difference of inlet/outlet increases) in regards to the dimensionless entry time as a function of microchannel taper angle in comparison with the WBC. These results suggest that the microenvironmental parameters have a significant effect on the transportability of the cells and different cells have different behaviors in response to a specific microenvironmental parameter. Finally, it can be claimed that this method can be also utilized to distinguish between benign and cancerous cells or even to probe tumor heterogeneity toward high throughput cell cytometry.

摘要

在过去十年中,微流控系统在细胞行为研究中的应用一直是一个蓬勃发展的研究领域。在探索细胞生物力学的过程中,近年来细胞通过狭窄微通道或小孔的过程引起了广泛关注。利用这些具有更高分辨率和精度的系统来研究细胞的可变形性和可运输性,为健康和患病细胞群体的高通量表征开辟了新的范例。在这里,我们使用水平集方法,通过将细胞视为粘性液滴,在二维计算域中研究不同微环境参数(即压差、细胞大小、有效细胞表面张力、收缩尺寸和锥角)下正常白细胞(WBC)和乳腺癌上皮细胞(MCF7)的通过时间与力学性能之间的关系。通过响应面法(RSM)为每种细胞类型获得了新的生物力学关系,将微环境参数与正常细胞和癌细胞的无量纲进入时间联系起来。我们的结果表明,与白细胞相比,MCF7细胞在无量纲进入时间方面表现出显著不同的行为(当进出口压差增加时出现分叉行为),这是微通道锥角的函数。这些结果表明,微环境参数对细胞的可运输性有显著影响,不同细胞对特定微环境参数的反应不同。最后,可以声称这种方法还可用于区分良性和癌细胞,甚至用于探索肿瘤异质性以实现高通量细胞计数。

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