Cell-free layer of red blood cells in a constricted microfluidic channel under steady and time-dependent flow conditions

Constricted blood vessels in the circulatory system can severely impact the spatiotemporal organization of red blood cells (RBCs) causing various physiological complications. In laboratory-on-a-chip applications, constrictions are commonly used for cell sorting and plasma separation based on the formation of a cell-free layer (CFL) at the channel boundary. However, such devices usually employ a steady flow, although time-dependent and pulsatile flow conditions enhance many microfluidic operations and possess significant relevance for in vitro studies under physiologically relevant flow conditions. In this study we examine the CFL dynamics in a constricted microchannel under steady and time-dependent flow. Therefore, we develop an image-processing routine that allows us to resolve the spatiotemporal evolution of the CFL under time-dependent driving of the flow with arbitrary waveform. First, we perform a characterization of the CFL and the cell-free area (CFA) before and after the constriction under steady flow conditions. Second, we employ our method to study the effect of the hematocrit and the parameters of the flow modulations on the CFL and CFA using a sinusoidal pressure profile. Our results highlight the dominant effects of the RBC concentration and the amplitude of the applied pressure signal predominantly on the CFA dynamics. Moreover, we observe a dampening of the CFA amplitude with increasing hematocrit or decreasing pressure amplitude, and a peculiar phase shift of the CFA oscillations pre- and postconstriction. Complementary numerical simulations reveal how the time-dependent CFA dynamics are coupled with the dynamically changing flow field at the constriction. Due to the increasing demand for investigations and applications under time-dependent flow conditions, our study provides crucial insight into the flow behavior of complex fluids in unsteady microscale flows.

Automated summary

Constricted blood vessels in the circulatory system can cause complications by affecting the organization of red blood cells. In this study, the dynamics of a cell-free layer (CFL) in a constricted microchannel under steady and time-dependent flow conditions were examined. A image-processing routine was developed to analyze the CFL evolution under various flow conditions. The results showed that the concentration of red blood cells and the amplitude of the pressure signal had dominant effects on the CFL dynamics.