Microfluidics for investigating vaso‐occlusions in sickle cell disease

Abstract

SCD stems from amutation in the beta globin gene. Upon deoxygenation, hemoglobin polymerizes and triggers RBC remodeling. This phenomenon is central to SCD pathogenesis as individuals suffering from the disease are plagued by painful vaso-occlusive crises episodes. These episodes are the result of a combination of processes including inflammation, thrombosis, and blood cell adhesion to the vascular wall which leads to blockages within the vasculature termed vaso-occlusions. Vaso-occlusive episodes deprive tissues of oxygen and are a major contributor to SCD-related complications; unfortunately, the complex mechanisms that contribute to vaso-occlusions are not well understood. Vaso-occlusions can occur in post-capillary venules; hence, the microvasculature is a prime target for SCD therapies. Traditional in vitro systems poorly recapitulate architectural and dynamic flow properties of in vivo systems. However, microfluidic devices can capture features of the native vasculature such as cellular composition, flow, geometry, and ECM presentation. This review, although not comprehensive, highlights microfluidic approaches that aim to improve our current understanding of the pathophysiological mechanisms surrounding SCD. Microfluidic platforms can aid in identifying factors that may contribute to disease severity and can serve as suitable test beds for novel treatment strategies which may improve patient outcomes.

Microfluidics contrasted to thrombelastography: perplexities in defining hypercoagulability

“…22,31 However, the utility of microfluidics to risk stratify patients for postoperative thrombotic complications remain largely unexplored. Other pathologic occlusion events in disease states such as sickle cell disease, 32 tumors, 33 and cardiovascular disease 34 have been tested in in vitro models, but have not been used clinically to risk stratify patients. Recent work with computational modeling paired with microfluidic devices suggest that flow is critical for determining the risk of vascular occlusion, particularly in arterial shear rates.…”

Microfluidics in Sickle Cell Disease Research: State of the Art and a Perspective Beyond the Flow Problem

“…Dissecting roles of RBC deformation, flow shear, distinct cell-cell interactions, adhesion activation, endothelial permeability/dysfunction, immune activation, and converging/diverging vascular bed geometry are essential to fully understand pathophysiology underlying VOC and beyond in SCD in order to develop mechanism-driven targeted therapeutics. Over the last decade, microfluidics have risen to this occasion to enable sickle cell researchers to fabricate and employ simple devices (Horton, 2017) that emulate microvascular dimensions and/or blood cell-endothelial interactions and facilitate in vitro experiments to study RBC sickling and VOC events.…”

“…This figure shows some examples of application of microfluidics in studying HbS polymerization, VOC, and enhanced adhesion of sickled RBCs. (A) This was the first device that demonstrated hypoxia induced sickling alone could obstruct microvascular network and demonstrated utility of microfluidics for the study of vaso-occlusion (Horton, 2017). (B) The authors utilized high throughput microfluidic single RBC analysis to quantify sickle hemoglobin polymerization in terms of RBC oxygen saturation (Du et al, 2015).…”

A microfluidic-informatics assay for quantitative physical occlusion measurement in sickle cell disease

“…13–15 It has been shown that SCD is caused by the abnormal hemoglobin polymerization of the RBC, 1,14 leading to a reduction in RBC deformability 13 as well as abnormality in RBC adhesion. 15 Microfluidic devices are a powerful tool for the analysis of factors such as red blood cell deformability and adhesiveness, 16–20 geometric variability in microcapillaries, 21–26 and changes in blood under different oxygen levels. 27–29…”