Direct measurement of the impact of impaired erythrocyte deformability on microvascular network perfusion in a microfluidic device

Shevkoplyas, Sergey S.; Yoshida, Tatsuro; Gifford, Sean C.; Bitensky, Mark W.

doi:10.1039/b601554a

Cited by 107 publications

(147 citation statements)

References 25 publications

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“…2). Microfluidic models of vascular constriction have been explored to evaluate the behavior of natural and diseased RBCs (25) and synthetic mimics of RBCs (13). We designed a 3-μm tall channel with pores that were 3 μm wide and 50 μm long and repeated many times over the length of the device.…”

Section: Resultsmentioning

confidence: 99%

Using mechanobiological mimicry of red blood cells to extend circulation times of hydrogel microparticles

Merkel¹,

Jones

Herlihy³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

480

435

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It has long been hypothesized that elastic modulus governs the biodistribution and circulation times of particles and cells in blood; however, this notion has never been rigorously tested. We synthesized hydrogel microparticles with tunable elasticity in the physiological range, which resemble red blood cells in size and shape, and tested their behavior in vivo. Decreasing the modulus of these particles altered their biodistribution properties, allowing them to bypass several organs, such as the lung, that entrapped their more rigid counterparts, resulting in increasingly longer circulation times well past those of conventional microparticles. An 8-fold decrease in hydrogel modulus correlated to a greater than 30-fold increase in the elimination phase half-life for these particles. These results demonstrate a critical design parameter for hydrogel microparticles.biomimetic | deformability | drug carriers | long circulating | red blood cell mimic

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Section: Resultsmentioning

confidence: 99%

Using mechanobiological mimicry of red blood cells to extend circulation times of hydrogel microparticles

Merkel¹,

Jones

Herlihy³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

480

435

View full text Add to dashboard Cite

show abstract

“…A potentially promising, cost-effective, and high throughput method for measuring RBC deformability is microfluidics [35][36][37][38][39][40][41]. Deformability measurements using microfluidics uses minute amounts of a whole blood or RBC suspension flowing through a funnel-shaped microconstriction [42][43][44].…”

Section: Introductionmentioning

confidence: 99%

Microfluidic analysis of cellular deformability of normal and oxidatively damaged red blood cells

et al. 2013

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Microfluidic analysis of blood has potential clinical value for determining normal and abnormal erythrocyte deformability. To determine if a microfluidic device could reliably measure intra-and inter-personal variations of normal and oxidized human red blood cell (RBC), venous blood samples were collected from repeat donors over time. RBC deformability was defined by the cortical tension (pN/mm), as determined from the threshold pressure required to deform RBC through 2-2.5 lm funnel-shaped constrictions. Oxidized RBC were prepared by treatment with phenazine methosulphate (PMS; 50 mM). Analysis of the control and oxidized RBC demonstrated that the microfluidic device could clearly differentiate between normal and mildly oxidized (20.13 6 1.47 versus 27.51 6 3.64 pN/mm) RBC. In vivo murine studies further established that the PMS-mediated loss of deformability correlated with premature clearance. Deformability variation within an individual over three independent samplings (over 21 days) demonstrated minimal changes in the mean pN/mm. Moreover, inter-individual variation in mean control RBC deformability was similarly small (range: 19.37-21.40 pN/mm). In contrast, PMS-oxidized cells demonstrated a greater inter-individual range (range: 25.97-29.90 pN/mm) reflecting the differential oxidant sensitivity of an individual's RBC. Importantly, similar deformability profiles (mean and distribution width; 20.49 6 1.67 pN/mm) were obtained from whole blood via finger prick sampling. These studies demonstrated that a low cost microfluidic device could be used to reproducibly discriminate between normal and oxidized RBC. Advanced microfluidic devices could be of clinical value in analyzing populations for hemoglobinopathies or in evaluating donor RBC products post-storage to assess transfusion suitability. Am. J. Hematol. 88:682-689,

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“…Among them, viscosity would play a significant role as a fluidic resistance in steady blood flows. It depends on several factors, such as deformability, [1][2][3][4][5] aggregation, 6,7 plasma viscosity, 8 and haematocrit. 9 Furthermore, the viscosity of blood is altered depending on the chemical and biological functions of red blood cells (RBCs).…”

Section: Introductionmentioning

confidence: 99%

Blood viscoelasticity measurement using steady and transient flow controls of blood in a microfluidic analogue of Wheastone-bridge channel

Kang

Lee

2013

Biomicrofluidics

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Accurate measurement of blood viscoelasticity including viscosity and elasticity is essential in estimating blood flows in arteries, arterials, and capillaries and in investigating sub-lethal damage of RBCs. Furthermore, the blood viscoelasticity could be clinically used as key indices in monitoring patients with cardiovascular diseases. In this study, we propose a new method to simultaneously measure the viscosity and elasticity of blood by simply controlling the steady and transient blood flows in a microfluidic analogue of Wheastone-bridge channel, without fully integrated sensors and labelling operations. The microfluidic device is designed to have two inlets and outlets, two side channels, and one bridge channel connecting the two side channels. Blood and PBS solution are simultaneously delivered into the microfluidic device as test fluid and reference fluid, respectively. Using a fluidic-circuit model for the microfluidic device, the analytical formula is derived by applying the linear viscoelasticity model for rheological representation of blood. First, in the steady blood flow, the relationship between the viscosity of blood and that of PBS solution (l Blood /l PBS ) is obtained by monitoring the reverse flows in the bridge channel at a specific flow-rate rate (Q PBS SS /Q Blood L ). Next, in the transient blood flow, a sudden increase in the blood flow-rate induces the transient behaviors of the blood flow in the bridge channel. Here, the elasticity (or characteristic time) of blood can be quantitatively measured by analyzing the dynamic movement of blood in the bridge channel. The regression formulais selected based on the pressure difference (DP ¼ P A À P B ) at each junction (A, B) of both side channels. The characteristic time of blood (k Blood ) is measured by analyzing the area (A Blood ) filled with blood in the bridge channel by selecting an appropriate detection window in the microscopic images captured by a high-speed camera (frame rate ¼ 200 Hz, total measurement time ¼ 7 s). The elasticity of blood (G Blood ) is identified using the relationship between the characteristic time and the viscosity of blood. For practical demonstrations, the proposed method is successfully applied to evaluate the variations in viscosity and elasticity of various blood samples: (a) various hematocrits form 20% to 50%, (b) thermal-induced treatment (50 C for 30 min), (c) flow-induced shear stress (53 6 0.5 mL/h for 120 min), and (d) normal rat versus spontaneously hypertensive rat. Based on these experimental demonstrations, the proposed method can be effectively used to monitor variations in viscosity and elasticity of bloods, even with the absence of fully integrated sensors, tedious labeling and calibrations. V C 2013 AIP Publishing LLC.

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Direct measurement of the impact of impaired erythrocyte deformability on microvascular network perfusion in a microfluidic device

Cited by 107 publications

References 25 publications

Using mechanobiological mimicry of red blood cells to extend circulation times of hydrogel microparticles

Using mechanobiological mimicry of red blood cells to extend circulation times of hydrogel microparticles

Microfluidic analysis of cellular deformability of normal and oxidatively damaged red blood cells

Blood viscoelasticity measurement using steady and transient flow controls of blood in a microfluidic analogue of Wheastone-bridge channel

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