Viscoelastic properties of suspended cells measured with shear flow deformation cytometry

Abstract

Numerous cell functions are accompanied by phenotypic changes in viscoelastic properties, and measuring them can help elucidate higher-level cellular functions in health and disease. We present a high-throughput, simple and low-cost microfluidic method for quantitatively measuring the elastic (storage) and viscous (loss) modulus of individual cells. Cells are suspended in a high-viscosity fluid and are pumped with high pressure through a 5.8 cm long and 200 μm wide microfluidic channel. The fluid shear stress induces large, near ellipsoidal cell deformations. In addition, the flow profile in the channel causes the cells to rotate in a tank-treading manner. From the cell deformation and tank treading frequency, we extract the frequency-dependent viscoelastic cell properties based on a theoretical framework developed by R. Roscoe that describes the deformation of a viscoelastic sphere in a viscous fluid under steady laminar flow. We confirm the accuracy of the method using atomic force microscopy-calibrated polyacrylamide beads and cells. Our measurements demonstrate that suspended cells exhibit power-law, soft glassy rheological behavior that is cell cycle-dependent and mediated by the physical interplay between the actin filament and intermediate filament networks.

Development of a microfluidic cell transfection device into gene-edited CAR T cell manufacturing workflow

“…This is in agreement with previous observation of increased cell stiffness under higher deformation frequency. 39 This hypothesis supports the finding that high strain rate in devices without gutters resulted in almost 100% delivery efficiency. We related this volume exchange driving force to the ratio of cell elasticity and viscosity using the Erickson's number.…”

“…The increase in the measured elastic modulus is consistent with a transition to a viscoelastic cytoplasm. 39 We noticed a sub-linear relation between the increase in stiffness and increase in strain rate. We also observed a linear change in cell relaxation rate with the compression rate (Fig.…”

Advances in mechanical biomarkers

“…Force application techniques actively deform the sample to probe its mechanical response. These include, among others, AFM, 15,51 nanoindenters, 52,53 acoustic, 54 magnetic 55,56 and optical tweezers (OTs), 57 optical stretchers, 58 deformation cytometry (DC) 59,60 and the biomembrane force probe (BFP) 61 . Instead, force sensing techniques specialize in detecting the forces exerted by cells.…”

“…Even more challenging is to find agreement in sample characterization across techniques of different nature, where force values are extracted from different mathematical approximations and the stress and deformation scales can be substantially different. While some works provide excellent agreement when viscoelastic parameters were compared across different mechanical techniques, 59 other studies reported differences of up to three orders of magnitude 70 . The study by Wu co‐workers specifically discussed how the mathematical models across techniques can notably change the values obtained on the sample.…”

Predicting cell stress and strain during extrusion bioprinting

“…Here, we show that this simple approach, while being correct in its order of magnitude, hides a good amount of the more complex features of intracellular stress. To illustrate this, we apply the theory of Roscoe [49] for a cell in linear shear flow, which accurately describes cell behavior in our numerical simulations (see section II C 4) and in microchannel experiments [69], provided that the cell does not flow in the channel center where the shear rate approaches zero. Inside a flowing cell, two qualitatively different kinds of stress arise.…”