Alterations in Red Blood Cell Deformability during Storage: A Microfluidic Approach

Abstract

Red blood cells (RBCs) undergo extensive deformation when travelling through the microcapillaries. Deformability, the combined result of properties of the membrane-cytoskeleton complex, the surface area-to-volume ratio, and the hemoglobin content, is a critical determinant of capillary blood flow. During blood bank storage and in many pathophysiological conditions, RBC morphology changes, which has been suggested to be associated with decreased deformability and removal of RBC. While various techniques provide information on the rheological properties of stored RBCs, their clinical significance is controversial. We developed a microfluidic approach for evaluating RBC deformability in a physiologically meaningful and clinically significant manner. Unlike other techniques, our method enables a high-throughput determination of changes in deformation capacity to provide statistically significant data, while providing morphological information at the single-cell level. Our data show that, under conditions that closely mimic capillary dimensions and flow, the capacity to deform and the capacity to relax are not affected during storage in the blood bank. Our data also show that altered cell morphology by itself does not necessarily affect deformability.

The mechanical properties of stored red blood cells measured by a convenient microfluidic approach combining with mathematic model

“…(3) The microfluidic devices could evaluate cells under flows that accurately mimic those in microcirculation. Cluitmans and colleagues 13 suggested that the storage did not alter the RBC deformability capacity during passage through the capillary system using a stenosis microfluidic. Zheng and colleagues 14 also found no significant changes of deformability, but a decrease in relaxation capacity after storage via applying 2.5 kPa to drive RBC flow in microchannels.…”

“…13,14 Among them, ektacytometry is a high-throughput method and reveals the mechanical properties of the RBC population via laser-diffraction patterns, while ignoring the heterogeneity or size differences within samples. 15 More recently, micropipette aspiration and optical tweezer techniques have been developed to give a single-cell test.…”

“…Huang and colleagues 8 have developed a simply microfluidic device with arrays of triangular pillars in parallel capillary channels to evaluate RBC deformability via the time required to pass through the gaps (from 3 to 4 lm). Cluitmans et al 13 and Zheng et al 14 designed microchannels to detect the RBCs deformability under flow. However, these microfluidic devices are based on high-speed cameras and complex microfluidic designs, which make them difficult to operate and restrict their application.…”

“…However, these microfluidic devices are based on high-speed cameras and complex microfluidic designs, which make them difficult to operate and restrict their application. 13,14 Recently, Zheng et al 17 and Alapan et al 18 developed simple microchannels to test the mechanical properties via the stretching of adherent RBCs under flow. However, the shear environment cannot simulate the shear stress in microcirculation factually, and the analyzed cell number is small.…”

A self-filling microfluidic device for noninvasive and time-resolved single red blood cell experiments

“…Singlecell analysis became increasingly important 3 and revealed that the RBC's unique deformability is the combined result of the elastic properties of the membrane-cytoskeleton complex, the surface area-to-volume ratio, and the viscosity determined by the hemoglobin content. 4 Especially, the vibratory motions of the RBC's plasma membrane, referred to as "flickering," 5 have been related to its biomechanical properties, which have been studied extensively in both single-cell experiments and theoretical work. [6][7][8][9][10] Moreover, the membrane fluctuations may also control adhesive phenomena, such as rouleau formation.…”