Antia Meher, Herricks Thurston, Rathod Pradipsinh K
Department of Chemistry, University of Washington, Seattle, Washington, United States of America.
PLoS Pathog. 2007 Jul;3(7):e99. doi: 10.1371/journal.ppat.0030099.
The clinical outcomes of human infections by Plasmodium falciparum remain highly unpredictable. A complete understanding of the complex interactions between host cells and the parasite will require in vitro experimental models that simultaneously capture diverse host-parasite interactions relevant to pathogenesis. Here we show that advanced microfluidic devices concurrently model (a) adhesion of infected red blood cells to host cell ligands, (b) rheological responses to changing dimensions of capillaries with shapes and sizes similar to small blood vessels, and (c) phagocytosis of infected erythrocytes by macrophages. All of this is accomplished under physiologically relevant flow conditions for up to 20 h. Using select examples, we demonstrate how this enabling technology can be applied in novel, integrated ways to dissect interactions between host cell ligands and parasitized erythrocytes in synthetic capillaries. The devices are cheap and portable and require small sample volumes; thus, they have the potential to be widely used in research laboratories and at field sites with access to fresh patient samples.
恶性疟原虫感染人类的临床结果仍然极难预测。要全面了解宿主细胞与寄生虫之间的复杂相互作用，需要体外实验模型，该模型能够同时捕捉与发病机制相关的多种宿主 - 寄生虫相互作用。在此，我们展示了先进的微流控装置能够同时模拟：（a）受感染红细胞与宿主细胞配体的黏附；（b）对形状和大小与小血管相似的毛细血管尺寸变化的流变学反应；（c）巨噬细胞对受感染红细胞的吞噬作用。所有这些都在生理相关的流动条件下持续长达20小时完成。通过选取一些示例，我们展示了这项赋能技术如何能够以新颖、综合的方式应用于剖析合成毛细血管中宿主细胞配体与寄生红细胞之间的相互作用。这些装置价格低廉且便于携带，所需样本量小；因此，它们有潜力在研究实验室以及能够获取新鲜患者样本的现场广泛应用。
