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

Aggregation of red blood cells (RBCs) varies substantially depending on changes of several factors such as hematocrit, membrane deformability, and plasma proteins. Among these factors, hematocrit has a strong influence on the aggregation of RBCs. Thus, while measuring RBCs aggregation, it is necessary to monitor hematocrit or, additionally, the effect of hematocrit (i.e., blood viscosity or pressure). In this study, the sequential measurement method of pressure and RBC aggregation is proposed by quantifying blood flow (i.e., velocity and image intensity) through a microfluidic device, in which an air-compressed syringe (ACS) is used to control the sample injection. The microfluidic device used is composed of two channels (pressure channel (PC), and blood channel (BC)), an inlet, and an outlet. A single ACS (i.e., air suction = 0.4 mL, blood suction = 0.4 mL, and air compression = 0.3 mL) is employed to supply blood into the microfluidic channel. At an initial time (t < 10 s), the pressure index (PI) is evaluated by analyzing the intensity of microscopy images of blood samples collected inside PC. During blood delivery with ACS, shear rates of blood flows vary continuously over time. After a certain amount of time has elapsed (t > 30 s), two RBC aggregation indices (i.e., S(EAI): without information on shear rate, and erythrocyte aggregation index (EAI): with information on shear rate) are quantified by analyzing the image intensity and velocity field of blood flow in BC. According to experimental results, PI depends significantly on the characteristics of the blood samples (i.e., hematocrit or base solutions) and can be used effectively as an alternative to blood viscosity. In addition, S(EAI) and EAI also depend significantly on the degree of RBC aggregation. In conclusion, on the basis of three indices (two RBC aggregation indices and pressure index), the proposed method is capable of measuring RBCs aggregation consistently using a microfluidic device.