Elongation Index as a Sensitive Measure of Cell Deformation in High-Throughput Microfluidic Systems.

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.

Cell trapping in Y-junction microchannels: A numerical study of the bifurcation angle effect in inertial microfluidics.

The majority of microfluidic technologies for cell sorting and isolation involve bifurcating (e.g., Y- or T-shaped junction) microchannels to trap the cells of a specific type. However, the microfluidic trapping efficiency remains low, independently of whether the cells are separated by a passive or an active sorting method. Using a custom computational algorithm, we studied the migration of separated deformable cells in a Y-junction microchannel, with a bifurcation angle ranging from 30° to 180°. Single or two cells of initially spherical shape were considered under flow conditions corresponding to inertial microfluidics. Through the numerical simulation, we identified the effects of cell size, cytoplasmic viscoelasticity, cortical tension, flow rate, and bifurcation angle on the critical separation distance for cell trapping. The results of this study show that the trapping and isolation of blood cells, and circulating tumor cells in a Y-junction microchannel was most efficient and least dependent on the flow rate at the bifurcation angle of 120°. At this angle, the trapping efficiency for white blood cells and circulating tumor cells increased, respectively, by 46% and 43%, in comparison with the trapping efficiency at 60°. The efficiency to isolate invasive tumor cells from noninvasive ones increased by 32%. This numerical study provides important design criteria to optimize microfluidic technology for deformability-based cell sorting and isolation.