Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 36-841, Cambridge, MA 02139, USA.
Lab Chip. 2011 Mar 21;11(6):1065-73. doi: 10.1039/c0lc00472c. Epub 2011 Feb 3.
Malaria resulting from Plasmodium falciparum infection is a major cause of human suffering and mortality. Red blood cell (RBC) deformability plays a major role in the pathogenesis of malaria. Here we introduce an automated microfabricated "deformability cytometer" that measures dynamic mechanical responses of 10(3) to 10(4) individual RBCs in a cell population. Fluorescence measurements of each RBC are simultaneously acquired, resulting in a population-based correlation between biochemical properties, such as cell surface markers, and dynamic mechanical deformability. This device is especially applicable to heterogeneous cell populations. We demonstrate its ability to mechanically characterize a small number of P. falciparum-infected (ring stage) RBCs in a large population of uninfected RBCs. Furthermore, we are able to infer quantitative mechanical properties of individual RBCs from the observed dynamic behavior through a dissipative particle dynamics (DPD) model. These methods collectively provide a systematic approach to characterize the biomechanical properties of cells in a high-throughput manner.
由恶性疟原虫感染引起的疟疾是人类痛苦和死亡的主要原因。红细胞(RBC)的变形性在疟疾的发病机制中起着重要作用。在这里,我们介绍了一种自动化的微加工“变形细胞仪”,它可以测量 10(3)到 10(4)个单个 RBC 在细胞群体中的动态力学响应。对每个 RBC 的荧光测量同时进行,从而在生化特性(如细胞表面标志物)和动态力学变形性之间产生基于群体的相关性。该设备特别适用于异质细胞群体。我们证明了它能够在大量未感染的 RBC 中对少量恶性疟原虫感染(环状阶段)的 RBC 进行力学表征。此外,我们能够通过耗散粒子动力学(DPD)模型从观察到的动态行为推断单个 RBC 的定量力学特性。这些方法共同为以高通量方式表征细胞的生物力学特性提供了一种系统的方法。