Electrical Impedance Characterization of Erythrocyte Response to Cyclic Hypoxia in Sickle Cell Disease
Electrical Impedance Characterization of Erythrocyte Response to Cyclic Hypoxia in Sickle Cell Disease
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DOI：
10.1021/acssensors.9b00263
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发表时间：
2019-07-01
期刊：
影响因子：
8.9
通讯作者：
Du, E.
中科院分区：
文献类型：
--
作者：
Liu, Jia;Qiang, Yuhao;Du, E.
细胞镰状硬化是指细胞内缺氧镰状血红蛋白（HbS）聚合导致细胞变形、硬化，从而导致血液流变学异常和血管阻塞。目前检测这一过程的方法主要依赖于细胞形态学的光学显微镜和细胞变形性和血液流变学的测量。由于细胞的电阻抗是细胞结构和生物物理特性变化的敏感指标，因此它可以成为表征异常血液流变学的有希望的标记物，并且比光学更方便地集成到护理点设备中。在这项工作中，开发了一种基于微流体的电阻抗传感器，用于表征镰状血中细胞镰状-非镰状的动态过程。该传感器能够测量镰状细胞悬浮液中由于循环缺氧诱导的细胞内HbS聚合和解聚而产生的连续变化。细胞形态变化的同时显微成像显示了基于电阻抗的细胞镰状和非镰状过程测量的可靠性和可重复性。电阻抗测量与患者血液学参数（如HbS和胎儿血红蛋白水平）有很强的相关性。电阻抗测量与片上缺氧控制相结合，为快速评估镰状细胞病患者细胞镰状和非镰状的动态过程提供了一种很有前景的方法。
Cell sickling is the process in which intracellular polymerization of deoxygenated sickle hemoglobin (HbS) leads to distorted, rigid cells, resulting in abnormal blood rheology and painful vaso-occlusion. Current methods for detection of this process mainly rely on optical microscopy of cellular morphology and measurements of cell deformability and blood rheology. As electrical impedance of cells is a sensitive indicator of changes in cellular structure and biophysical characteristics, it can be a promising marker for characterization of abnormal blood rheology and a means more convenient than optics to be integrated into point-of-care devices. In this work, a microfluidics-based electrical impedance sensor has been developed for characterizing the dynamic cell sickling-unsickling processes in sickle blood. The sensor is capable of measuring the continuous variation in the sickle cell suspension due to cyclic hypoxia-induced intracellular HbS polymerization and depolymerization. Simultaneous microscopic imaging of cell morphological change shows the reliability and repeatability of the electrical impedance-based measurements of cell sickling and unsickling processes. Strong correlation is found between the electrical impedance measurement and patients' hematological parameters such as levels of HbS and fetal hemoglobin. The combination of electrical impedance measurement and on-chip hypoxia control provides a promising method for rapid assessment of the dynamic processes of cell sickling and unsickling in patients with sickle cell disease.