Abstract:
Malaria caused by the wild type Plasmodium falciparum (WT) parasite remains the leading single-agent cause of mortality in children, particularly those from sub-Saharan Africa. The deformability of red blood cells (RBCs) refers to their ability to change shape via squeezing through capillaries. The P. falciparum glutamic rich acid protein (PfGARP) is a protein expressed on the exofacial surface of early-to-late-trophozoite-stage erythrocytes and is used to maintain their survival and continuous infection. △PfGARP cells are less virulent as a result of eliminating the PfGARP gene, which is suspected to help infected cells maintain a sustained deformability. Thus, △PfGARP RBCs are expected to lose their pathogenicity due to decreased deformability and become more susceptible to being trapped and eliminated by the spleen. This research engineers a microfluidic device with channels that mimic capillaries in the microvasculature, or the interendothelial slits in the spleen, where RBCs deform through. We demonstrate that our microfluidic design and set up have been accurately modified, (in terms of flow rate and composition of chemical components), and is ready to be used in tests evaluating the deformability of WT vs △PfGARP cells. By verifying the effect of knocking out PfGARP on the cells' deformability, the device will serve as a rapid, cost-effective tool for scientists testing anti-PfGARP drugs designed to eliminate the presence of the malaria parasite altogether.
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