Mechanical response of red blood cells entering a constriction

Abstract

Most work on the dynamic response of red blood cells (RBCs) to hydrodynamic stress has focused on linear velocity profiles. Relatively little experimental work has examined how individual RBCs respond to pressure driven flow in more complex geometries, such as the flow at the entrance of a capillary. Here, we establish the mechanical behaviors of healthy RBCs undergoing a sudden increase in shear stress at the entrance of a narrow constriction. We pumped RBCs through a constriction in a microfluidic device and used high speed video to visualize and track the flow behavior of more than 4400 RBCs. We show that approximately 85% of RBCs undergo one of four distinct modes of motion: stretching, twisting, tumbling, or rolling. Intriguingly, a plurality of cells ($30%) exhibited twisting (rotation around the major axis parallel to the flow direction), a mechanical behavior that is not typically observed in linear velocity profiles. We present detailed statistical analyses on the dynamics of each motion and demonstrate that the behavior is highly sensitive to the location of the RBC within the channel. We further demonstrate that the observed tumbling, twisting, and rolling rotations can be rationalized qualitatively in terms of rigid body mechanics. The detailed experimental statistics presented here should serve as a useful resource for modeling of RBC behavior under physiologically important flow conditions. V C 2014 AIP Publishing LLC. [http://dx

Measuring Cell Viscoelastic Properties Using a Microfluidic Extensional Flow Device

“…However, our observations that cells only stretch near the stagnation point indicates that any shear velocity gradient effects due to the top and bottom walls contribute negligibly to cell deformation. This stands in contrast to the study described earlier in which four modes of deformation were observed (23), which featured significant, nonzero shear components in straight, narrow regions of the channel downstream of the extension-dominant converging section.…”

“…In a channel converging linearly from large (100 mm wide) to small (20 mm wide) widths over a downstream distance of 70 mm (height a constant 40 mm), four modes of deformation, stretching, twisting, tumbling, and rolling, were observed for cells at different cross-stream positions (23). The stretching mode occurred for red blood cells on the channel centerline where the velocity gradient was symmetric about the cell.…”

“…To address these issues, microfluidic tools have recently been explored as a strategy to measure cellular structural and mechanical properties with a rapidity that may be better suited to drug discovery and clinical application (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Although these approaches have indeed massively improved measurement throughput and reduced operator skill/bias issues relative to traditional measurements, the extraction of cell mechanical properties (e.g., elastic modulus) remains challenging, primarily due to complex viscous forces that severely complicate analysis of deformations.…”

Constriction Channel Based Single-Cell Mechanical Property Characterization

“…Initially, the constriction channel design was used to quantify the mechanical properties of RBCs [23,[27][28][29][30][31][32][33][34][35][36][37][38][39][40]. In 2003, Chiu et al, characterized complex behaviors of Plasmodium falciparum infected RBCs using the constriction channels with sizes at 8, 6, 4, and 2 µm in width [23] (see Figure 1a).…”

“…[47] Meanwhile, the microfluidic constriction channel is used to quantify the cellular entry and transition process through a micro channel with a cross-sectional area smaller than the dimensions of a single cell, enabling high-throughput single-cell mechanical property characterization [23][24][25][26] (see Table 1). This technique was first used to evaluate the mechanical properties of RBCs [23,[27][28][29][30][31][32][33][34][35][36][37][38][39][40], which was then expanded to study the deformability of WBCs [24,41,42] and tumor cells [25,[43][44][45]. Leveraging mechanical modeling of the cellular entry process into the constriction channel, the microfluidic constriction channel design can collect size-independent intrinsic biomechanical markers such as cortical tension or Young's modulus [35,[46][47][48].…”