Mechanical differences of sickle cell trait (SCT) and normal red blood cells

Zheng, Yi; Cachia, Mark A.; Ge, Ji; Xu, Zhenghua; Wang, Chen; Sun, Yu

doi:10.1039/c5lc00543d

Cited by 25 publications

(21 citation statements)

References 56 publications

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“…Although soft‐lithography‐based systems have grown popular for their superior properties and a relatively rapid prototyping capability, fabrication of these microfluidic devices requires labor‐intensive processes and clean room facilities, which are limiting factors for high‐throughput clinical applications . Furthermore, oxygen tension control in soft‐lithographical microfluidic systems such as PDMS‐based devices has been achieved through the Fickian diffusion of gas molecules through the permeable channel walls from a source channel (filled with gas) to a sample channel, where biological sample is processed . This diffusion phenomenon is facilitated by creating multiple channels (source and sample) either in parallel or in stack configuration, requiring complex device design and implementation.…”

Section: Introductionmentioning

confidence: 99%

“…1,12,14,16,17,[19][20][21][22][23][24][25] The main advantages of microfluidic technologies involve fluid manipulation in microchannels with a plethora of physiological conditions such as flow, oxygen tension, and shear stress requiring only a miniscule volume of reagent and sample. 2,15,17,24,26 Furthermore, microfluidic systems provide a stable and closed-system microenvironment to observe biophysical characteristics at the single-cell level due to microscale geometries. 27 Most of the microfluidic devices in the literature have been fabricated via soft lithography by relying on PDMS, which is an optically transparent, gas-permeable, and biocompatible material.…”

mentioning

confidence: 99%

“…16,28 Furthermore, oxygen tension control in softlithographical microfluidic systems such as PDMS-based devices has been achieved through the Fickian diffusion of gas molecules through the permeable channel walls from a source channel (filled with gas) to a sample channel, where biological sample is processed. 1,2,12,23,24,26,29 This diffusion phenomenon is facilitated by creating multiple channels (source and sample) either in parallel or in stack configuration, requiring complex device design and implementation.…”

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confidence: 99%

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Hypoxia‐enhanced adhesion of red blood cells in microscale flow

et al. 2017

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Objectives The advancement of microfluidic technology has facilitated the simulation of physiological conditions of the microcirculation, such as oxygen tension, fluid flow, and shear stress in these devices. Here, we present a micro-gas exchanger integrated with microfluidics to study red blood cell (RBC) adhesion under hypoxic flow conditions mimicking post-capillary venules. Methods We simulated a range of physiological conditions and explored RBC adhesion to endothelial or sub-endothelial components (fibronectin, FN, or laminin, LN). Blood samples were injected into microchannels at normoxic or hypoxic physiological flow conditions. Quantitative evaluation of RBC adhesion was performed on 35 subjects with homozygous sickle cell disease (SCD). Results Significant heterogeneity in RBC adherence response to hypoxia was seen among SCD patients. RBCs from a hypoxia enhanced adhesion population showed a significantly greater increase in adhesion compared to RBCs from a hypoxia non-enhanced adhesion population, for both FN and LN. Conclusions The approach presented here enabled the control of oxygen tension in blood during microscale flow and the quantification of RBC adhesion in a cost-efficient and patient-specific manner. We identified a unique patient population in which RBCs showed enhanced adhesion in hypoxia in vitro. Clinical correlates suggest a more severe clinical phenotype in this subgroup.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Hypoxia‐enhanced adhesion of red blood cells in microscale flow

et al. 2017

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“…Formation of polymerized hemoglobin fibers disrupts cell morphology, decreases RBC deformability (increase in stiffness) and changes membrane adhesive properties [11][12][13][14] . Abnormal adhesion and decreased deformability of RBCs are the main causes of blood vessel occlusion (vaso-occlusion) in SCD 11,13,[15][16][17][18] . Vaso-occlusion is the hallmark of the disease and it has been associated with severe pain, crises, wide-spread organ damage, and early mortality 19,20 .…”

Section: Introductionmentioning

confidence: 99%

Dynamic deformability of sickle red blood cells in microphysiological flow

et al. 2016

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In sickle cell disease (SCD), hemoglobin molecules polymerize intracellularly and lead to a cascade of events resulting in decreased deformability and increased adhesion of red blood cells (RBCs). Decreased deformability and increased adhesion of sickle RBCs lead to blood vessel occlusion (vaso-occlusion) in SCD patients. Here, we present a microfluidic approach integrated with a cell dimensioning algorithm to analyze dynamic deformability of adhered RBC at the single-cell level in controlled microphysiological flow. We measured and compared dynamic deformability and adhesion of healthy hemoglobin A (HbA) and homozygous sickle hemoglobin (HbS) containing RBCs in blood samples obtained from 24 subjects. We introduce a new parameter to assess deformability of RBCs: the dynamic deformability index (DDI), which is defined as the time-dependent change of the cell's aspect ratio in response to fluid flow shear stress. Our results show that DDI of HbS-containing RBCs were significantly lower compared to that of HbA-containing RBCs. Moreover, we observed subpopulations of HbS containing RBCs in terms of their dynamic deformability characteristics: deformable and non-deformable RBCs. Then, we tested blood samples from SCD patients and analyzed RBC adhesion and deformability at physiological and above physiological flow shear stresses. We observed significantly greater number of adhered non-deformable sickle RBCs than deformable sickle RBCs at flow shear stresses well above the physiological range, suggesting an interplay between dynamic deformability and increased adhesion of RBCs in vaso-occlusive events.

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“…However, these microfluidic devices are based on high-speed cameras and complex microfluidic designs, which make them difficult to operate and restrict their application. 13,14 Recently, Zheng et al 17 and Alapan et al 18 developed simple microchannels to test the mechanical properties via the stretching of adherent RBCs under flow. However, the shear environment cannot simulate the shear stress in microcirculation factually, and the analyzed cell number is small.…”

Section: Introductionmentioning

confidence: 99%

The mechanical properties of stored red blood cells measured by a convenient microfluidic approach combining with mathematic model

et al. 2016

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The mechanical properties of red blood cells (RBCs) are critical to the rheological and hemodynamic behavior of blood. Although measurements of the mechanical properties of RBCs have been studied for many years, the existing methods, such as ektacytometry, micropipette aspiration, and microfluidic approaches, still have limitations. Mechanical changes to RBCs during storage play an important role in transfusions, and so need to be evaluated pre-transfusion, which demands a convenient and rapid detection method. We present a microfluidic approach that focuses on the mechanical properties of single cell under physiological shear flow and does not require any high-end equipment, like a high-speed camera. Using this method, the images of stretched RBCs under physical shear can be obtained. The subsequent analysis, combined with mathematic models, gives the deformability distribution, the morphology distribution, the normalized curvature, and the Young's modulus (E) of the stored RBCs. The deformability index and the morphology distribution show that the deformability of RBCs decreases significantly with storage time. The normalized curvature, which is defined as the curvature of the cell tail during stretching in flow, suggests that the surface charge of the stored RBCs decreases significantly. According to the mathematic model, which derives from the relation between shear stress and the adherent cells' extension ratio, the Young's moduli of the stored RBCs are also calculated and show significant increase with storage. Therefore, the present method is capable of representing the mechanical properties and can distinguish the mechanical changes of the RBCs during storage. The advantages of this method are the small sample needed, high-throughput, and easy-use, which make it promising for the quality monitoring of RBCs. V C 2016 AIP Publishing LLC.

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Mechanical differences of sickle cell trait (SCT) and normal red blood cells

Cited by 25 publications

References 56 publications

Hypoxia‐enhanced adhesion of red blood cells in microscale flow

Hypoxia‐enhanced adhesion of red blood cells in microscale flow

Dynamic deformability of sickle red blood cells in microphysiological flow

The mechanical properties of stored red blood cells measured by a convenient microfluidic approach combining with mathematic model

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