High-throughput microfluidic characterization of erythrocyte shape and mechanical variability

Abstract

The motion of red blood cells (RBCs) in microchannels is important for microvascular blood flow and biomedical applications such as blood analysis in microfluidics. The current understanding of the complexity of RBC shapes and dynamics in microchannels is mainly based on several simulation studies, but there are a few systematic experimental investigations. Here, we present a combined study, which systematically characterizes RBC behavior for a wide range of flow rates and channel sizes. Even though simulations and experiments generally show good agreement, experimental observations demonstrate that there is no single well-defined RBC state for fixed flow conditions, but rather a broad distribution of states. This result can be attributed to the inherent variability in RBC mechanical properties, which is confirmed by a model that takes the variation in RBC shear elasticity into account. This represents a significant step toward a quantitative connection between RBC behavior in microfluidic devices and their mechanical properties, which is essential for a high-throughput characterization of diseased cells. STATEMENT OF SIGNIFICANCEThe ability to change shape is crucial for the proper functioning of red blood cells under harsh conditions in the microvasculature, since their shapes strongly affect the flow behavior of whole blood. Our results from simulations and systematic experiments reveal the shapes and dynamics of red blood cells for different flow conditions and channel dimensions, generally in good agreement. However, in the experiments, cells do not exhibit a single well-defined shape for fixed flow conditions. We show that this distribution of shapes can be attributed to the variability in mechanical properties of red blood cells.

Heterogeneity of Red Blood Cells: Causes and Consequences

“…So are their shapes, and, rather than discussing their "absolute shape, " it would be feasible to assign them a probability to be observed in one of the shape types. The first attempts to address RBC shapes in terms of probability density distribution are recently undertaken (Reichel et al, 2019). Each cell has its "static shape" that is preferred over the other ones if no force is applied to it.…”

“…There are also several preferred shape types caused by shear stress in flow. The probability to observe one of those depends on the shear rates and flow dynamics (Abkarian et al, 2008;Dupire et al, 2015;Lanotte et al, 2016;Kihm et al, 2018;Mauer et al, 2018;Reichel et al, 2019). The restoration of the initial shape of the cells as soon as the flow stops got the name of "shape memory" (Fischer, 2004;Cordasco and Bagchi, 2017).…”

Effect of Cytoplasmic Viscosity on Red Blood Cell Migration in Small Arteriole-level Confinements

“…al clearly revealed existence of more complicated multi-lobe shapes. Remarkably, there is a rich spectrum of shape states and motion that RBCs may undergo depending on the initial condition (Guckenberger et al, 2018), the ratio of convective forces to elastic restoring forces (denoted by the capillary number) (Sinha and Graham, 2015), and also the confinement level of the vessel (Reichel et al, 2018).…”