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Towards microfluidic-based depletion of stiff and fragile human red cells that accumulate during blood storage.

ABSTRACT: In this study, the effects of prolonged storage on several biophysical properties of red blood cells (RBCs) were investigated. Single cell deformability was used as an important criterion in determining subgroups of RBCs evolved during storage lesion. A deformability-based microfluidic cell sorting technology was applied, which demonstrates the ability to enrich and separate the less deformable subpopulations of stored blood. These less deformable RBC subpopulations were then associated with other important markers such as osmotic fragility indicating cell integrity as well as microparticle content. This work demonstrates a systematic methodology to both monitor and improve banked blood quality, thereby reducing risks related to blood transfusion.

SUBMITTER: Huang S

PROVIDER: S-EPMC4268274 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Towards microfluidic-based depletion of stiff and fragile human red cells that accumulate during blood storage.

Huang Sha S Hou Han Wei HW Kanias Tamir T Sertorio Jonas Tadeu JT Chen Huichao H Sinchar Derek D Gladwin Mark T MT Han Jongyoon J

Lab on a chip 20150101 2

In this study, the effects of prolonged storage on several biophysical properties of red blood cells (RBCs) were investigated. Single cell deformability was used as an important criterion in determining subgroups of RBCs evolved during storage lesion. A deformability-based microfluidic cell sorting technology was applied, which demonstrates the ability to enrich and separate the less deformable subpopulations of stored blood. These less deformable RBC subpopulations were then associated with oth ...[more]

PMID: 25406942

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Project description:Abnormal red blood cell (RBC) deformability contributes to hemolysis, thrombophilia, inflammation, and microvascular occlusion in various circulatory diseases. A quantitative and objective assessment of microvascular occlusion mediated by RBCs with abnormal deformability would provide valuable insights into disease pathogenesis and therapeutic strategies. To that end, we present a new functional microfluidic assay, OcclusionChip, which mimics two key architectural features of the capillary bed in the circulatory system. First, the embedded micropillar arrays within the microchannel form gradient microcapillaries, from 20 μm down to 4 μm, which mimic microcapillary networks. These precisely engineered microcapillaries retain RBCs with impaired deformability, such that stiffer RBCs occlude the wider upstream microcapillaries, while less stiff RBCs occlude the finer downstream microcapillaries. Second, the micropillar arrays are coupled with two side passageways, which mimic the arteriovenous anastomoses that act as shunts in the capillary bed. These side microfluidic anastomoses prevent microchannel blockage, and enable versatility and testing of clinical blood samples at near-physiologic hematocrit levels. Further, we define a new generalizable parameter, Occlusion Index (OI), which is an indicative index of RBC deformability and the associated microcapillary occlusion. We demonstrate the promise of OcclusionChip in diverse pathophysiological scenarios that result in impaired RBC deformability, including mercury toxin, storage lesion, end-stage renal disease, malaria, and sickle cell disease (SCD). Hydroxyurea therapy improves RBC deformability and increases fetal hemoglobin (HbF%) in some, but not all, treated patients with SCD. HbF% greater than 8.6% has been shown to improve clinical outcomes in SCD. We show that OI associates with HbF% in 16 subjects with SCD. Subjects with higher HbF levels (HbF > 8.6%) displayed significantly lower OI (0.88% ± 0.10%, N = 6) compared with those with lower HbF levels (HbF ≤ 8.6%) who displayed greater OI (3.18% ± 0.34%, N = 10, p < 0.001). Moreover, hypoxic OcclusionChip assay revealed a significant correlation between hypoxic OI and subject-specific sickle hemoglobin (HbS) level in SCD. OcclusionChip enables versatile in vitro assessment of microvascular occlusion mediated by RBCs in a wide range of clinical conditions. OI may serve as a new parameter to evaluate the efficacy of treatments improving RBC deformability, including hemoglobin modifying drugs, anti-sickling agents, and genetic therapies.

Dataset Information

Towards microfluidic-based depletion of stiff and fragile human red cells that accumulate during blood storage.

Publications

Towards microfluidic-based depletion of stiff and fragile human red cells that accumulate during blood storage.

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