A microfluidic model for single-cell capillary obstruction by Plasmodium falciparum -infected erythrocytes

Abstract

Severe malaria by Plasmodium falciparum is a potentially fatal disease, frequently unresponsive to even the most aggressive treatments. Host organ failure is associated with acquired rigidity of infected red blood cells and capillary blockage. In vitro techniques have played an important role in modeling cell deformability. Although, historically they have either been applied to bulk cell populations or to measure single physical parameters of individual cells. In this article, we demonstrate the unique abilities and benefits of elastomeric microchannels to characterize complex behaviors of single cells, under flow, in multicellular capillary blockages. Channels of 8-, 6-, 4-, and 2-m widths were readily traversed by the 8 m-wide, highly elastic, uninfected red blood cells, as well as by infected cells in the early ring stages. Trophozoite stages failed to freely traverse 2-to 4-m channels; some that passed through the 4-m channels emerged from constricted space with deformations whose shape-recovery could be observed in real time. In 2-m channels, trophozoites mimicked ''pitting,'' a normal process in the body where spleen beds remove parasites without destroying the red cell. Schizont forms failed to traverse even 6-m channels and rapidly formed a capillary blockage. Interestingly, individual uninfected red blood cells readily squeezed through the blockages formed by immobile schizonts in a 6-m capillary. The last observation can explain the high parasitemia in a growing capillary blockage and the well known benefits of early blood transfusion in severe malaria.

Recent advances in microfluidic techniques for single-cell biophysical characterization

“…With the use of high-speed imaging or electrical impedance measurements, constriction-channel devices are capable of achieving a higher throughput than most other deformability measurement approaches. Due to these merits, constriction channels have been used to measure the deformability of RBCs, 22,23,[39][40][41][42][43][44] leukocytes 45 and cancer cells. 46,47 Due to the human capillary-like environment and the physiological relevance of RBC deformability, RBCs are mostly studied in the majority of existing constriction channel-based devices.…”

“…The first demonstration of microfluidic constriction channels for RBC deformability characterization was reported in 2003. 22 In this study, constriction channels with various diameters were used to study the deformability changes between healthy RBCs and malaria parasite-infected RBCs at different stages (early ring stage, early trophozoite, late trophozoite, and schizont). They found that the deformability of malaria-infected RBCs decreases as the parasite progresses from the early ring stage to a schizont, while healthy RBCs are exceptionally deformable and are even able to travel through the constriction channels blocked by infected RBCs.…”

Fluid dynamics topics in bloodstain pattern analysis: Comparative review and research opportunities

“…The same discipline of FD describes the motion of gases in extra-terrestrial space [28], the dynamics of atmospheres and oceans, and the motion of blood in capillaries thinner than a human hair [29]. To describe within a single framework events that span such a large range of time and length scales, FD relies on a three step analysis: first, the magnitude of all the forces acting on the fluid are evaluated, as in Table 2; then the relative magnitude of pairs of these forces is compared using scaling or dimensionless numbers, such as the ones listed in Table 2 Ratio of the drag force to the stagnation pressure force caused by the motion of the drop in air The culprit for slowing down the drop is the drag, the resistance force exerted by the air on the moving drop.…”

Automated Micropipette Aspiration of Single Cells

“…The study of RBCs at the cellular level has shown that the infection of RBCs can impair their rheological properties [11][12][13][14][15][16][17][18][19][20].…”