Interdisciplinary Research Centre on Biomaterials (CRIB), Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università degli Studi di Napoli "Federico II", Piazzale Tecchio 80, 80125 Naples, Italy.
Center for Advanced Biomaterials for Healthcare@CRIB, Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, 80125 Naples, Italy.
Lab Chip. 2020 Dec 15;20(24):4611-4622. doi: 10.1039/d0lc00911c.
Cell mechanical properties are powerful biomarkers for label-free phenotyping. To date, microfluidic approaches assay mechanical properties by measuring changes in cellular shape, applying extensional or shear flows or forcing cells to pass through constrictions. In general, such approaches use high-speed imaging or transit time measurements to evaluate cell deformation, while cell dynamics in-flow after stress imposition have not yet been considered. Here, we present a microfluidic approach to apply, over a wide range, tuneable compressive forces on suspended cells, which result in well distinct signatures of deformation-dependent dynamic motions. By properly conceiving microfluidic chip geometry and rheological fluid properties, we modulate applied single-cell forces, which result in different motion regimes (rolling, tumbling or tank-treating) depending on the investigated cell line. We decided to prove our approach by testing breast cell lines, with well-known mechanical properties. We measured a set of in-flow parameters (orientation angle, aspect ratio, cell deformation and cell diameter) as a backward analysis of cell mechanical response. By such an approach, we report that the highly invasive tumour cells (MDA-MB-231) are much more deformable (6-times higher) than healthy (MCF-10A) and low invasive ones (MCF-7). Thus, we demonstrate that a microfluidic design with tuneable rheological fluid properties and direct analysis of bright-field images can be suitable for the label-free mechanical phenotyping of various cell lines.
细胞力学特性是无标记表型分析的有力生物标志物。迄今为止，微流控方法通过测量细胞形状的变化、施加拉伸或剪切流或迫使细胞通过狭窄通道来测量力学特性。一般来说，这些方法使用高速成像或传输时间测量来评估细胞变形，而施加应力后细胞在流动中的动力学尚未被考虑。在这里，我们提出了一种微流控方法，可以在广泛的范围内对悬浮细胞施加可调的压缩力，从而产生与变形相关的动态运动的明显特征。通过合理构思微流控芯片几何形状和流变学流体特性，我们可以调节施加于单细胞的力，从而根据所研究的细胞系产生不同的运动状态（滚动、翻转或罐式处理）。我们决定通过测试具有已知力学特性的乳腺细胞系来验证我们的方法。我们测量了一组流动参数（取向角、纵横比、细胞变形和细胞直径），作为细胞力学响应的反向分析。通过这种方法，我们报告说高度侵袭性的肿瘤细胞（MDA-MB-231）比健康细胞（MCF-10A）和低侵袭性细胞（MCF-7）更具变形性（高 6 倍）。因此，我们证明了具有可调流变学流体特性和明场图像直接分析的微流控设计可以适用于各种细胞系的无标记力学表型分析。
