Deformability measurement of red blood cells using a microfluidic channel array and an air cavity in a driving syringe with high throughput and precise detection of subpopulations

Abstract

Red blood cell (RBC) deformability has been considered a potential biomarker for monitoring pathological disorders. High throughput and detection of subpopulations in RBCs are essential in the measurement of RBC deformability. In this paper, we propose a new method to measure RBC deformability by evaluating temporal variations in the average velocity of blood flow and image intensity of successively clogged RBCs in the microfluidic channel array for specific time durations. In addition, to effectively detect differences in subpopulations of RBCs, an air compliance effect is employed by adding an air cavity into a disposable syringe. The syringe was equally filled with a blood sample (V(blood) = 0.3 mL, hematocrit = 50%) and air (V(air) = 0.3 mL). Owing to the air compliance effect, blood flow in the microfluidic device behaved transiently depending on the fluidic resistance in the microfluidic device. Based on the transient behaviors of blood flows, the deformability of RBCs is quantified by evaluating three representative parameters, namely, minimum value of the average velocity of blood flow, clogging index, and delivered blood volume. The proposed method was applied to measure the deformability of blood samples consisting of homogeneous RBCs fixed with four different concentrations of glutaraldehyde solution (0%-0.23%). The proposed method was also employed to evaluate the deformability of blood samples partially mixed with normal RBCs and hardened RBCs. Thereafter, the deformability of RBCs infected by human malaria parasite Plasmodium falciparum was measured. As a result, the three parameters significantly varied, depending on the degree of deformability. In addition, the deformability measurement of blood samples was successfully completed in a short time (∼10 min). Therefore, the proposed method has significant potential in deformability measurement of blood samples containing hematological diseases with high throughput and precise detection of subpopulations in RBCs.

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

“…These results show a consistency in trend with respect to hematocrit compared to the previous study. 21,28 These experimental results lead to the conclusion that the proposed method has the ability to measure the RBC deformability and blood viscoelasticity under sinusoidal blood flow with sufficient accuracy.…”

“…While the blood is delivered into micropillars under a constant flow rate, the deformability of RBCs is evaluated by analyzing the temporal variations of blood velocity or image intensity for a specific duration. 20,21 The previous method could provide high throughput and precise detection of minor differences in subpopulations. However, the previous method is applied to quantify the RBC deformability and blood viscosity, especially under a constant blood flow condition.…”

Haemocompatibility of iron oxide nanoparticles synthesized for theranostic applications: a high-sensitivity microfluidic tool

“…The abnormal RBCs rigidity has been already related to several diseases, pointing to the modification of the membrane structural components (e.g. skeletal filaments, transmembrane proteins and fatty acids) (Kang et al 2016;Zheng et al 2012) and cytoplasmatic content as the main reasons for this abnormal rigidity change (Rodrigues et al 2015). As a result, rigid RBCs can cause phenomena of clotting in the micro-circulatory vessels (namely, capillaries, arterioles and venules), leading to the blocking of the normal blood flow in microcirculation (Kang et al 2016), which in the worst scenarios can cause ischaemia in the tissues and/or lead to episodes of cerebrovascular accidents ).…”

“…skeletal filaments, transmembrane proteins and fatty acids) (Kang et al 2016;Zheng et al 2012) and cytoplasmatic content as the main reasons for this abnormal rigidity change (Rodrigues et al 2015). As a result, rigid RBCs can cause phenomena of clotting in the micro-circulatory vessels (namely, capillaries, arterioles and venules), leading to the blocking of the normal blood flow in microcirculation (Kang et al 2016), which in the worst scenarios can cause ischaemia in the tissues and/or lead to episodes of cerebrovascular accidents ). Hence, these blood cells have the potential to be used as natural biophysical markers (Kang et al 2016;Zheng et al 2012) without the costly labelling and sample handling that is common for most biochemical markers (Gossett et al 2012).…”

High-throughput and label-free parasitemia quantification and stage differentiation for malaria-infected red blood cells

“…It is well known that Plasmodium falciparum-infected red blood cells ( Pf -iRBCs) become increasingly rigid (less deformable) as they mature 15 , thus the deformability has the potential to be used as a mechanical biomarker to distinguish the healthy and the infected RBCs at various stages 16 . To date, various microfluidic-based methods have been developed to interrogate the cell deformability.…”