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

Abstract

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.

Quantitative Monitoring of Dynamic Blood Flows Using Coflowing Laminar Streams in a Sensorless Approach

“…However, it tended to decrease after t = t 6 . According to previous experimental results obtained with the micro-PIV technique [41], hematocrit had a strong influence on blood velocity obtained with micro-PIV. In this study, it was impossible to obtain information on the hematocrit of blood flow over time.…”

“…French et al demonstrated that the flow rate of suspension blood (RBCs in 1× PBS, hematocrit [Hct] = 10-20%) could be quantified with the micro-PIV technique [40]. The blood flow rate obtained with micro-PIV is varied significantly depending on the hematocrit [41]. For example, when aggregation-enhanced blood is circulated in an in vitro loop, the hematocrit of blood is varied continuously over time [30].…”

Sequential quantification of blood and diluent using red cell sedimentation-based separation and pressure-induced work in a microfluidic channel

“…This study was primarily aimed at minimizing the blood volume suctioned in the driving syringe. In previous studies, RBC sedimentation has been tested under different conditions, including suction blood volume (40–200 μL, 41 0.2 mL, 17,33 0.3 mL, 45 0.6 mL, 35 1 mL, 16,32,36 and 4–10 mL 56,62 ), and test reservoir (straight tube, 21,28 disposable syringe, 36 polycarbonate cartridge, 41 conical tube 17,33 ). A considerable blood volume (∼1 mL) was injected into the blood syringe to monitor RBC sedimentation in a driving syringe pump.…”

Editorial for the Special Issue on Micro/Nano Devices for Blood Analysis, Volume II

“…Then, blood viscosity was determined using a parallel co-flowing method with a correction factor. The author was able to measure blood viscosity and the RBCs' sedimentation rates consistently for samples with hematocrit 30%, 40% and 50% [7].…”

“…Kang [7] presented a microfluidic-based biosensor for the measurement of blood viscosity and red blood cells' (RBCs') sedimentation rates. The author used two aircompressed syringes to deliver blood samples and a reference fluid into a T-shaped microfluidic channel and measured the average velocity of the fluids using micro-particle image velocimetry and digital image processing.…”