Kinetics of cell sickling and morphological change have been recognized as important parameters that are correlated closely with altered blood rheology and vasoocclusion in microcirculation. A microfluidic transient hypoxia assay was developed to create repeated hypoxia-normoxia cycles for real time observation of repetitive sickling and unsickling of freely suspended red blood cells (RBCs) from sickle cell disease patients. Cell sickling behavior and kinetics were found to be influenced by its previous sickling-unsickling processes accumulatively, where those sickled RBCs that had a history of sickling in a previous hypoxia cycle would sickle again in subsequent hypoxia/sickling cycles and the collective sickling kinetics became progressively faster (with reduced delay time and higher sickled fraction versus deoxygenation time). Individual sickled RBCs would sickle into drastically different shapes randomly in subsequent hypoxia/sickling cycles, however, the collective shape distribution retained similar characteristics. These observations indicate a gradual worsening trend in sickling kinetics over repeated hypoxia cycles, as well as a relatively stable collective shape characteristics within a limited number of hypoxia-normoxia cycles.

中文翻译：

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在重复的脱氧和氧合循环中更快的镰状动力学和镰状细胞形状进化

镰状细胞的动力学和形态变化已被认为是与血液流变学改变和微循环血管闭塞密切相关的重要参数。开发了一种微流体瞬时缺氧测定，以创建重复的缺氧-常氧循环，以实时观察镰状细胞病患者自由悬浮的红细胞 (RBC) 的重复镰状和脱镰状。发现细胞镰状行为和动力学受其先前的镰状-脱镰过程累积的影响，其中那些在先前缺氧循环中有镰状化历史的镰状红细胞将在随后的缺氧/镰状循环中再次镰状化，并且集体镰状动力学逐渐变得渐进更快（与脱氧时间相比，延迟时间更短，镰刀形分数更高）。在随后的缺氧/镰状循环中，单个镰状红细胞会随机变成截然不同的形状，然而，集体形状分布保留了相似的特征。这些观察表明镰刀动力学在重复缺氧循环中逐渐恶化，以及在有限数量的缺氧-常氧循环内相对稳定的集体形状特征。