Microfluidic-Based Technique for Measuring RBC Aggregation and Blood Viscosity in a Continuous and Simultaneous Fashion

Abstract

Hemorheological properties such as viscosity, deformability, and aggregation have been employed to monitor or screen patients with cardiovascular diseases. To effectively evaluate blood circulating within an in vitro closed circuit, it is important to quantify its hemorheological properties consistently and accurately. A simple method for measuring red blood cell (RBC) aggregation and blood viscosity is proposed for analyzing blood flow in a microfluidic device, especially in a continuous and simultaneous fashion. To measure RBC aggregation, blood flows through three channels: the left wide channel, the narrow channel and the right wide channel sequentially. After quantifying the image intensity of RBCs aggregated in the left channel (<IRA>) and the RBCs disaggregated in the right channel (<IRD>), the RBC aggregation index (AIPM) is obtained by dividing <IRA> by <IRD>. Simultaneously, based on a modified parallel flow method, blood viscosity is obtained by detecting the interface between two fluids in the right wide channel. RBC aggregation and blood viscosity were first evaluated under constant and pulsatile blood flows. AIPM varies significantly with respect to blood flow rate (for both its amplitude and period) and the concentration of the dextran solution used. According to our quantitative comparison between the proposed aggregation index (AIPM) and the conventional aggregation index (AICM), it is found that AIPM provides consistent results. Finally, the suggested method is employed to obtain the RBC aggregation and blood viscosity of blood circulating within an in vitro fluidic circuit. The experimental results lead to the conclusion that the proposed method can be successfully used to measure RBC aggregation and blood viscosity, especially in a continuous and simultaneous fashion.

Microfluidic-Based Biosensor for Sequential Measurement of Blood Pressure and RBC Aggregation Over Continuously Varying Blood Flows

“…As illustrated in Figure 6(A-b), two indices (i.e., AI CONV [54] and AI ESR [52,55,57]) as previous methods were employed to evaluate the variations of S EAI with the concentration of dextran solution. Figure 6(A-a) showed variations of AI CONV and AI ESR with respect to C dextran .…”

“…Because a microfluidic-based technique can provide several advantages such as small volume requirement, disposable device, and short measurement time, RBCs aggregation of blood has been quantified under microfluidic platform [48,49,50]. After a microfluidic channel is filled with blood, blood flows or stops by sequentially operating external devices such as a syringe pump [51,52], pinch valve [47], and vacuum pump [49]. When blood flows decrease to extremely lower shear rates, RBCs tend to aggregate over time.…”

“…When blood flows decrease to extremely lower shear rates, RBCs tend to aggregate over time. Several measurement quantifies such as photometric intensity [49,50], electric conductivity [53,54], optical tweezer [16], and microscopic image intensity [18,52,55,56,57] have been adopted to obtain a syllectogram (i.e., quantity versus time) [54]. Thereafter, the RBCs aggregation index is calculated from syllectogram.…”

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

“…The inset of Figure A4 (A-c) showed the interfacial location of blood flow (α B ) in a microscopic image captured at the focal plane (Z f = 0). The blood viscosity (µ B ) was obtained by inserting α B into the viscosity formula as reported in previous studies [32,33]. As α B and µ B remained constant with respect to Z f , the relocation of the object plane did not contribute to varying the blood viscosity.…”

“…Second, various devices such as a microelectromechanical system (MEMS)-based microfluidic device, a 3D-printed microfluidic device [13,24], and a paper-based device [25] have been suggested for inducing blood flow in a specifically constrained direction. Third, quantification techniques such as advancing meniscus (i.e., variations of a blood column over time) [15,22,26,27], the falling time of a metal sphere in a tube [28], electric impedances (i.e., resistance, capacitance) [29,30], droplet length [31], digital flow compartment with a microfluidic channel array [11,12], interface detection in co-flowing streams [32,33], and reversal flow switching in a Wheatstone bridge analog of a fluidic circuit [14] have been suggested to measure blood viscosity.…”