Elongation index as a sensitive measure of cell deformation in high-throughput microfluidic systems

Abstract

AO_SCPLOWBSTRACTC_SCPLOWOne 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 vs. 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 m, 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 "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 3,500 Pa, while the standard DI output was unable to distinguish between these two groups of cells. The successful suppression of the offset artefacts with a narrower data distribution was shown for the EI output of MCF-7 cells. SO_SCPLOWTATEMENTC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWOFC_SCPLOW SO_SCPLOWIGNIFICANCEC_SCPLOWThis study establishes a new measure of high-throughput microfluidic deformability cytometry, referred to as "elongation index", that is not subject to cell offset artefacts and can sensibly and reliably detect disease-induced changes in mechanical properties of living cells.