Myrand-Lapierre Marie-Eve, Deng Xiaoyan, Ang Richard R, Matthews Kerryn, Santoso Aline T, Ma Hongshen
Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, Canada V6T 1Z4.
Lab Chip. 2015 Jan 7;15(1):159-67. doi: 10.1039/c4lc01100g.
The extraordinary deformability of red blood cells gives them the ability to repeatedly transit through the microvasculature of the human body. The loss of this capability is part of the pathology of a wide range of diseases including malaria, hemoglobinopathies, and micronutrient deficiencies. We report on a technique for multiplexed measurements of the pressure required to deform individual red blood cell through micrometer-scale constrictions. This measurement is performed by first infusing single red blood cells into a parallel array of ~1.7 μm funnel-shaped constrictions. Next, a saw-tooth pressure waveform is applied across the constrictions to squeeze each cell through its constriction. The threshold deformation pressure is then determined by relating the pressure-time data with the video of the deformation process. Our key innovation is a self-compensating fluidic network that ensures identical pressures are applied to each cell regardless of its position, as well as the presence of cells in neighboring constrictions. These characteristics ensure the consistency of the measurement process and robustness against blockages of the constrictions by rigid cells and debris. We evaluate this technique using in vitro cultures of RBCs infected with P. falciparum, the parasite that causes malaria, to demonstrate the ability to profile the deformability signature of a heterogeneous sample.
红细胞非凡的可变形性使其能够反复通过人体的微血管系统。这种能力的丧失是包括疟疾、血红蛋白病和微量营养素缺乏症在内的多种疾病病理的一部分。我们报告了一种技术，用于对单个红细胞通过微米级收缩所需的压力进行多重测量。该测量首先通过将单个红细胞注入约1.7μm漏斗形收缩的平行阵列中来进行。接下来，在收缩处施加锯齿形压力波形，以挤压每个细胞通过其收缩处。然后通过将压力-时间数据与变形过程的视频相关联来确定阈值变形压力。我们的关键创新是一种自补偿流体网络，它确保无论细胞位置如何，以及相邻收缩处是否存在细胞，都能对每个细胞施加相同的压力。这些特性确保了测量过程的一致性以及对刚性细胞和碎片造成的收缩堵塞的鲁棒性。我们使用感染了导致疟疾的恶性疟原虫的红细胞体外培养物来评估这项技术，以证明对异质样本的可变形性特征进行分析的能力。
