Simple Assessment of Red Blood Cell Deformability Using Blood Pressure in Capillary Channels for Effective Detection of Subpopulations in Red Blood Cells

Assessment of red blood cell (RBC) deformability as a biomarker requires expensive equipment to induce and monitor deformation. In this study, we present a simple method for quantifying RBC deformability. We designed a microfluidic channel consisting of a micropillar channel and a coflowing channel connected in series. When blood (loading volume = 100 μL) was injected continuously into the device under constant pressure (1 bar), we monitored the boundary position of the blood and the reference flow in the coflowing channel. A decrease in the deformability of RBCs results in a growing pressure drop in the micropillar channel, which is mirrored by a decrease in blood pressure in the coflowing channel. Analysis of this temporal variation in blood pressure allowed us to define the clogging index (CI) as a new marker of RBC deformability. As a result of the analytical study and numerical simulation, we have demonstrated that the coflowing channel may serve as a pressure sensor that allows the measurement of blood pressure with accuracy. We have shown experimentally that a higher hematocrit level (i.e., more than 40%) does not have a substantial influence on CI. The CI tended to increase to a higher degree in glutaraldehyde-treated hardened RBCs. Furthermore, we were able to resolve the difference in deformability of RBCs between two different RBC density subfractions in human blood. In summary, our approach using CI provides reliable information on the deformability of RBCs, which is comparable to the readouts obtained by ektacytometry. We believe that our microfluidic device would be a useful tool for evaluating the deformability of RBCs, which does not require expensive instruments (e.g., high-speed camera) or time-consuming micro-PIV analysis.