Sickle cell disease biochip: a functional red blood cell adhesion assay for monitoring sickle cell disease.
Sickle cell disease biochip: a functional red blood cell adhesion assay for monitoring sickle cell disease.
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DOI：
10.1016/j.trsl.2016.03.008
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Gurkan UA
中科院分区：
文献类型：
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作者：
Alapan Y;Kim C;Adhikari A;Gray KE;Gurkan-Cavusoglu E;Little JA;Gurkan UA
镰状细胞病 (SCD) 困扰着全世界数百万人，并具有相当高的发病率和死亡率。慢性和急性血管闭塞是 SCD 的临床标志，可导致疼痛危象、广泛的器官损伤和早期活动。尽管 SCD 的分子基础在 60 多年前就已被确定，但临床上尚无可行测量的疾病严重程度的分子或生物物理标记。细胞对血管内皮的异常粘附是血管闭塞的根源。然而，目前尚未在临床上评估细胞粘附。在这里，我们提出了一种临床适用的微流体装置（SCD生物芯片），它允许在封闭且无需预处理的系统中对红细胞（RBC）与内皮相关蛋白固定微通道的粘附进行连续定量评估。利用 SCD 生物芯片，我们分析了 100 多名受试者的血液样本，并显示了测量的红细胞与内皮相关蛋白（纤连蛋白和层粘连蛋白）的粘附与个体红细胞特征（包括血红蛋白含量、胎儿血红蛋白浓度、血浆乳酸脱氢酶水平和网织红细胞计数）之间的关联。 SCD生物芯片是一种功能性粘附测定，反映红细胞粘附的定量评估，可用于基线、危机期间、相对于各种长期并发症以及治疗干预前后。
Sickle cell disease (SCD) afflicts millions of people worldwide and is associated with considerable morbidity and mortality. Chronic and acute vaso-occlusion are the clinical hallmarks of SCD and can result in pain crisis, widespread organ damage, and early movtality. Even though the molecular underpinnings of SCD were identified more than 60 years ago, there are no molecular or biophysical markers of disease severity that are feasibly measured in the clinic. Abnormal cellular adhesion to vascular endothelium is at the root of vaso-occlusion. However, cellular adhesion is not currently evaluated clinically. Here, we present a clinically applicable microfluidic device (SCD biochip) that allows serial quantitative evaluation of red blood cell (RBC) adhesion to endothelium-associated protein-immobilized microchannels, in a closed and preprocessing-free system. With the SCD biochip, we have analyzed blood samples from more than 100 subjects and have shown associations between the measured RBC adhesion to endothelium-associated proteins (fibronectin and laminin) and individual RBC characteristics, including hemoglobin content, fetal hemoglobin concentration, plasma lactate dehydrogenase level, and reticulocyte count. The SCD biochip is a functional adhesion assay, reflecting quantitative evaluation of RBC adhesion, which could be used at baseline, during crises, relative to various long-term complications, and before and after therapeutic interventions.