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Elongation Index as a Sensitive Measure of Cell Deformation In High-Throughput Microfluidic Systems
Biophysical Journal ( IF 3.4 ) Pub Date : 2020-08-01 , DOI: 10.1016/j.bpj.2020.06.027
Scott J Hymel 1 , Hongzhi Lan 2 , Damir B Khismatullin 1
Affiliation  

One of the promising approaches for high-throughput screening of cell mechanotype is microfluidic deformability cytometry (mDC), in which the apparent deformation index (DI) of the cells stretched by extensional flow at the stagnation point of a cross-slot microchannel is measured. The DI is subject to substantial measurement errors due to cell offset from the flow centerline and velocity fluctuations in inlet channels, leading to artificial widening of DI versus cell size plots. Here, we simulated an mDC experiment using a custom computational algorithm for viscoelastic cell migration. Cell motion and deformation in a cross-slot channel was modeled for fixed or randomized values of cellular mechanical properties (diameter, shear elasticity, cortical tension) and initial cell placement, with or without sinusoidal fluctuations between the inlet velocities. Our numerical simulation indicates that mDC loses sensitivity to changes in shear elasticity when the offset distance exceeds 5 μm, and just 1% velocity fluctuation causes an 11.7% drop in the DI. The obtained relationships between the cell diameter, shear elasticity, and offset distance were used to establish a new measure of cell deformation, referred to as the "elongation index" (EI). In the randomized study, the EI scatter plots were visibly separated for the low- and high-elasticity populations of cells, with a mean of 300 and 3500 Pa, whereas the standard DI output was unable to distinguish between these two groups of cells. The successful suppression of the offset artifacts with a narrower data distribution was shown for the EI output of MCF-7 cells.

中文翻译:

伸长指数作为高通量微流体系统中细胞变形的敏感量度

细胞机械型高通量筛选的一种有前途的方法是微流体变形性细胞术 (mDC),其中测量在跨槽微通道的停滞点处由拉伸流拉伸的细胞的表观变形指数 (DI)。由于细胞偏离流动中心线和入口通道中的速度波动,DI 会受到大量测量误差的影响,导致 DI 与细胞尺寸图的人为加宽。在这里,我们使用用于粘弹性细胞迁移的自定义计算算法模拟了 mDC 实验。交叉槽通道中的细胞运动和变形被建模为固定或随机的细胞机械特性值(直径、剪切弹性、皮质张力)和初始细胞放置,入口速度之间有或没有正弦波动。我们的数值模拟表明,当偏移距离超过 5 μm 时,mDC 失去对剪切弹性变化的敏感性,仅 1% 的速度波动就会导致 DI 下降 11.7%。获得的细胞直径、剪切弹性和偏移距离之间的关系用于建立细胞变形的新度量,称为“伸长指数”(EI)。在随机研究中,低弹性和高弹性细胞群的 EI 散点图明显分开,平均值为 300 和 3500 Pa,而标准 DI 输出无法区分这两组细胞。对于 MCF-7 细胞的 EI 输出,显示成功抑制了具有较窄数据分布的偏移伪影。我们的数值模拟表明,当偏移距离超过 5 μm 时,mDC 失去对剪切弹性变化的敏感性,并且仅 1% 的速度波动会导致 DI 下降 11.7%。获得的细胞直径、剪切弹性和偏移距离之间的关系用于建立细胞变形的新度量,称为“伸长指数”(EI)。在随机研究中,低弹性和高弹性细胞群的 EI 散点图明显分开,平均值为 300 和 3500 Pa,而标准 DI 输出无法区分这两组细胞。对于 MCF-7 细胞的 EI 输出,显示成功抑制了具有较窄数据分布的偏移伪影。我们的数值模拟表明,当偏移距离超过 5 μm 时,mDC 失去对剪切弹性变化的敏感性,并且仅 1% 的速度波动会导致 DI 下降 11.7%。获得的细胞直径、剪切弹性和偏移距离之间的关系用于建立细胞变形的新度量,称为“伸长指数”(EI)。在随机研究中,低弹性和高弹性细胞群的 EI 散点图明显分开,平均值为 300 和 3500 Pa,而标准 DI 输出无法区分这两组细胞。对于 MCF-7 细胞的 EI 输出,显示成功抑制了具有较窄数据分布的偏移伪影。
更新日期:2020-08-01
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