A physiometer for simultaneous measurement of whole blood viscosity and its determinants: hematocrit and red blood cell deformability

Kim, Byung Jun; Lee, Ye Sung; Zhbanov, A. I.; Yang, Sung

doi:10.1039/c8an02135j

Cited by 40 publications

(33 citation statements)

References 55 publications

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“…The previous methods for measuring blood viscosity are conveniently divided into three categories (i.e., driving sources, devices, and quantification techniques). First, extrinsic driving sources such as SPs [20], pressure sources, and hand-held pipettes [13] have been suggested for delivering a blood sample into a specific device. Additionally, intrinsic driving sources such as capillary force (or surface tension) [21,22] and gravity force [23] have been applied to supply blood samples into a device.…”

Section: Introductionmentioning

confidence: 99%

Microfluidic-Based Biosensor for Blood Viscosity and Erythrocyte Sedimentation Rate Using Disposable Fluid Delivery System

Kang

2020

Micromachines

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To quantify the variation of red blood cells (RBCs) or plasma proteins in blood samples effectively, it is necessary to measure blood viscosity and erythrocyte sedimentation rate (ESR) simultaneously. Conventional microfluidic measurement methods require two syringe pumps to control flow rates of both fluids. In this study, instead of two syringe pumps, two air-compressed syringes (ACSs) are newly adopted for delivering blood samples and reference fluid into a T-shaped microfluidic channel. Under fluid delivery with two ACS, the flow rate of each fluid is not specified over time. To obtain velocity fields of reference fluid consistently, RBCs suspended in 40% glycerin solution (hematocrit = 7%) as the reference fluid is newly selected for avoiding RBCs sedimentation in ACS. A calibration curve is obtained by evaluating the relationship between averaged velocity obtained with micro-particle image velocimetry (μPIV) and flow rate of a syringe pump with respect to blood samples and reference fluid. By installing the ACSs horizontally, ESR is obtained by monitoring the image intensity of the blood sample. The averaged velocities of the blood sample and reference fluid (<UB>, <UR>) and the interfacial location in both fluids (αB) are obtained with μPIV and digital image processing, respectively. Blood viscosity is then measured by using a parallel co-flowing method with a correction factor. The ESR is quantified as two indices (tESR, IESR) from image intensity of blood sample (<IB>) over time. As a demonstration, the proposed method is employed to quantify contributions of hematocrit (Hct = 30%, 40%, and 50%), base solution (1× phosphate-buffered saline [PBS], plasma, and dextran solution), and hardened RBCs to blood viscosity and ESR, respectively. Experimental Results of the present method were comparable with those of the previous method. In conclusion, the proposed method has the ability to measure blood viscosity and ESR consistently, under fluid delivery of two ACSs.

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Section: Introductionmentioning

confidence: 99%

Microfluidic-Based Biosensor for Blood Viscosity and Erythrocyte Sedimentation Rate Using Disposable Fluid Delivery System

Kang

2020

Micromachines

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“…Finally, the method was employed to quantify the contribution of hardened RBCs to the viscoelasticity of blood samples. According to previous studies [27,28], normal RBCs were hardened chemically with GA solution. The degree in rigidity increased gradually by varying concentrations of the GA solution.…”

Section: Quantification Of the Contribution Of Hardened Rbcs To Bloodmentioning

confidence: 99%

Blood Viscoelasticity Measurement Using Interface Variations in Coflowing Streams under Pulsatile Blood Flows

Kang

2020

Micromachines

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Blood flows in microcirculation are determined by the mechanical properties of blood samples, which have been used to screen the status or progress of diseases. To achieve this, it is necessary to measure the viscoelasticity of blood samples under a pulsatile blood condition. In this study, viscoelasticity measurement is demonstrated by quantifying interface variations in coflowing streams. To demonstrate the present method, a T-shaped microfluidic device is designed to have two inlets (a, b), one outlet (a), two guiding channels (blood sample channel, reference fluid channel), and one coflowing channel. Two syringe pumps are employed to infuse a blood sample at a sinusoidal flow rate. The reference fluid is supplied at a constant flow rate. Using a discrete fluidic circuit model, a first-order linear differential equation for the interface is derived by including two approximate factors (F1 = 1.094, F2 = 1.1087). The viscosity and compliance are derived analytically as viscoelasticity. The experimental results showed that compliance is influenced substantially by the period. The hematocrit and diluent contributed to the varying viscosity and compliance. The viscoelasticity varied substantially for red blood cells fixed with higher concentrations of glutaraldehyde solution. The experimental results showed that the present method has the ability to monitor the viscoelasticity of blood samples under a sinusoidal flow-rate pattern.

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“…Although these viscometers provide accurate and reliable results, they require large sample volumes, long processing times, and technical expertise, limiting their utility, where rapid viscosity measurements with low sample volumes may be necessary. To overcome these limitations, a number of microfluidic‐based techniques for blood rheology assessment have been introduced 38‐45 . Majority of these methods are equipped with complex instrumentation techniques, such as vibrational noise spectrum, 46 cantilever deflection, 47 or electrical resistance measurement 48 .…”

Section: Introductionmentioning

confidence: 99%

“…To overcome these limitations, a number of microfluidic-based techniques for blood rheology assessment have been introduced. [38][39][40][41][42][43][44][45] Majority of these methods are equipped with complex instrumentation techniques, such as vibrational noise spectrum, 46 cantilever deflection, 47 or electrical resistance measurement. 48 Other microfluidic models based on conventional lithographic techniques have recently been implemented to measure blood viscosity in both normoxic and hypoxic conditions.…”

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confidence: 99%

Whole blood viscosity and red blood cell adhesion: Potential biomarkers for targeted and curative therapies in sickle cell disease

et al. 2020

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Sickle cell disease (SCD) is a recessive genetic blood disorder exhibiting abnormal blood rheology. Polymerization of sickle hemoglobin, due to a point mutation in the β-globin gene of hemoglobin, results in aberrantly adhesive and stiff red blood cells (RBCs). Hemolysis, abnormal RBC adhesion, and abnormal blood rheology together impair endothelial health in people with SCD, which leads to cumulative systemic complications. Here, we describe a microfluidic assay combined with a micro particle image velocimetry technique for the integrated in vitro assessment of whole blood viscosity (WBV) and RBC adhesion. We examined WBV and RBC adhesion to laminin (LN) in microscale flow in whole blood samples from 53 individuals with no hemoglobinopathies (HbAA, N = 10), hemoglobin SC disease (HbSC, N = 14), or homozygous SCD (HbSS, N = 29) with mean WBV of 4.50 cP, 4.08 cP, and 3.73 cP, respectively. We found that WBV correlated with RBC count and hematocrit in subjects with HbSC or HbSS. There was a significant inverse association between WBV and RBC adhesion under both normoxic and physiologically hypoxic (SpO 2 of 83%) tests, in which lower WBV associated with higher RBC adhesion to LN in subjects with HbSS. Low WBV has been found by others to associate with endothelial activation. Altered WBV and abnormal RBC adhesion may synergistically contribute to the endothelial damage and cumulative pathophysiology of SCD. These findings suggest that WBV and RBC adhesion may serve as clinically relevant biomarkers and endpoints in assessing emerging targeted and curative therapies in SCD. 1 | INTRODUCTION Sickle cell disease (SCD) is one of the most common inherited diseases in the world. 1,2 It is caused by a single-point mutation in the β-globin gene of hemoglobin. Sickle hemoglobin (HbS) polymerizes into long and stiff chains within the red blood cell (RBC) under low-oxygen conditions. 3,4 As a result, HbS-containing RBCs (sickle RBCs) become abnormally stiff and adherent (impairing microcirculatory blood flow), and fragile (resulting in hemolysis). Microvascular occlusion causes episodic and unpredictable vaso-occlusive events (VOE), pain, and Erdem Kucukal and Yuncheng Man contributed equally to this study.

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A physiometer for simultaneous measurement of whole blood viscosity and its determinants: hematocrit and red blood cell deformability

Abstract: In this study, a microfluidic-based physiometer capable of measuring the whole blood viscosity, hematocrit, and red blood cell (RBC) deformability on a chip is introduced.

Cited by 40 publications

References 55 publications

Microfluidic-Based Biosensor for Blood Viscosity and Erythrocyte Sedimentation Rate Using Disposable Fluid Delivery System

Microfluidic-Based Biosensor for Blood Viscosity and Erythrocyte Sedimentation Rate Using Disposable Fluid Delivery System

Blood Viscoelasticity Measurement Using Interface Variations in Coflowing Streams under Pulsatile Blood Flows

Whole blood viscosity and red blood cell adhesion: Potential biomarkers for targeted and curative therapies in sickle cell disease

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