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

JP Shelby, J White, K Ganesan… - Proceedings of the …, 2003 - National Acad Sciences
JP Shelby, J White, K Ganesan, PK Rathod, DT Chiu
Proceedings of the National Academy of Sciences, 2003National Acad Sciences
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 …
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-μm widths were readily traversed by the 8 μm-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-μm channels; some that passed through the 4-μm channels emerged from constricted space with deformations whose shape-recovery could be observed in real time. In 2-μm 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-μm 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-μm 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.
National Acad Sciences