Microfluidic Modeling of Cell?Cell Interactions in Malaria Pathogenesis

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�Cparasite 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（Plasmodium falciparum）感染人类后的临床结局仍具有高度不可预测性。要全面解析宿主细胞与疟原虫之间的复杂相互作用，亟需构建可同时捕获与致病机制相关的多种宿主-疟原虫互作的体外实验模型。本研究展示，先进微流控器件（microfluidic devices）可同时模拟以下三类过程：(a) 受感染红细胞对宿主细胞配体的黏附；(b) 在形状与尺寸模拟微小血管的毛细血管中，受感染红细胞随毛细血管管径变化所产生的流变学响应；(c) 巨噬细胞对感染红细胞的吞噬作用。所有实验均可在模拟体内生理流体环境的条件下开展，持续时长可达20小时。通过选取代表性实例，本研究展示了该使能技术如何以新颖的整合式方法，解析合成毛细血管内宿主细胞配体与被疟原虫感染的红细胞之间的相互作用。该微流控器件成本低廉、便于携带，且仅需微量样本体积，因此有望在各类研究实验室以及可获取新鲜患者样本的实地研究场景中得到广泛应用。