Simultaneous measurement of erythrocyte deformability and blood viscoelasticity using micropillars and co-flowing streams under pulsatile blood flows

Abstract

The biophysical properties of blood provide useful information on the variation in hematological disorders or diseases. In this study, a simultaneous measurement method of RBC (Red Blood Cell) deformability and blood viscoelasticity is proposed by evaluating hemodynamic variations through micropillars and coflowing streams under sinusoidal blood flow. A disposable microfluidic device is composed of two inlets and two outlets, two upper side channels, and two lower side channels connected to one bridge channel. First, to measure the RBC deformability, the left-lower side channel has a deformability assessment chamber (DAC) with narrow-sized micropillars. Second, to evaluate the blood viscoelasticity in co-flowing streams, a phosphate buffered saline solution is supplied at a constant flow rate. By closing or opening a pinch valve connected to the outlet of DAC, blood flows in forward or back-and-forth mode. A time-resolved micro-particle image velocimetry technique and a digital image processing technique are used to quantify the blood velocity and image intensity. Then, RBC deformability is evaluated by quantifying the blood volume passing through the DAC under forward flow, and quantifying the variations of blood velocity and image intensity in the DAC under back-and-forth flow. Using a discrete circuit model, blood viscoelasticity is obtained by evaluating variations of blood velocity and co-flowing streams. The effect of several factors (period, hematocrit, and base solution) on the performance is quantitatively evaluated. Based on the experimental results, the period of sinusoidal flow and hematocrit are fixed at 30 s and 50%, respectively. As a performance demonstration, the proposed method is employed to detect the homogeneous and heterogeneous blood composed of normal RBCs and hardened RBCs. These experimental results show that the RBC deformability is more effective to detect minor subpopulations of heterogeneous bloods, compared with blood viscoelasticity. Therefore, it leads to the conclusion that the proposed method has the ability to evaluate RBC deformability and blood viscoelasticity under sinusoidal blood flow, with sufficient accuracy and highthroughput. Published by AIP Publishing. [http://dx

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

“…Figure 3B-b showed variations of λ B with respect to T. The λ B tended to increase linearly for up to T = 360 s. However, the slope of λ B tended to decrease between T= 360 and T = 480 s. According to Equation (19), the λ B was linearly proportional to the period (i.e., λ B~T ). The experimental results showed appropriately consistent variations of λ B with respect to T. Using Equations (18) and (20), the blood viscosity (µ B ) and compliance (C B ) were obtained with respect to T. As shown in Figure 3B-c, µ B did not exhibit a linear dependency of T. It fluctuated at a shorter period. However, it remained constant at a longer period (T = 360, 480 s).…”

“…According to a previous study, blood viscosity remained constant with respect to the interface [18]. Because R WB and µ R µ B were independent of time, Equation (8) became a simple expression of Equation (9).…”

“…In other words, if β 0 and β 1 could be obtained from periodic variations of the interface (α B ) in the coflowing channel, µ B and C B as blood viscoelasticity could be evaluated from Equations (18) and (20), respectively.…”

“…To verify the contribution of the period (T) to the viscoelasticity of the blood sample (Equations [18] and [20]), the viscosity and compliance were evaluated by varying the period (T = 120, 240, 360, and 480 s). The blood sample (Hct = 50%) was prepared by adding normal RBCs into 1x PBS.…”

“…More recently, the author suggested a viscoelasticity measurement method under a sinusoidal blood flow rate (Q B (t)) (Q B (t) = Q α + Q β •sin (ωt), where Q α is the mean flow rate, Q β is the alternating flow rate, and ω is the angular frequency of syringe pump) [18]. While the blood sample is infused periodically, the viscoelasticity of the blood sample is obtained by monitoring the interface in coflowing streams and by calculating the pulsatility index (PI) (PI = 0.5 × (Q max -Q min )/Q ave , where Q max is the maximum flow rate, Q min is the minimum flow rate, and Q ave is the average flow rate).…”