Red blood cells (RBCs) possess a unique capacity for undergoing cellular deformation to navigate across various human microcirculation vessels, enabling them to pass through capillaries that are smaller than their diameter and to carry out their role as gas carriers between blood and tissues. Since there is growing evidence that red blood cell deformability is impaired in some pathological conditions, measurement of RBC deformability has been the focus of numerous studies over the past decades. Nevertheless, reports on healthy and pathological RBCs are currently limited and, in many cases, are not expressed in terms of well-defined cell membrane parameters such as elasticity and viscosity. Hence, it is often difficult to integrate these results into the basic understanding of RBC behaviour, as well as into clinical applications. The aim of this review is to summarize currently available reports on RBC deformability and to highlight its association with various human diseases such as hereditary disorders (e.g., spherocytosis, elliptocytosis, ovalocytosis, and stomatocytosis), metabolic disorders (e.g., diabetes, hypercholesterolemia, obesity), adenosine triphosphate-induced membrane changes, oxidative stress, and paroxysmal nocturnal hemoglobinuria. Microfluidic techniques have been identified as the key to develop state-of-the-art dynamic experimental models for elucidating the significance of RBC membrane alterations in pathological conditions and the role that such alterations play in the microvasculature flow dynamics.

In this work, we report on a systematic fluidodynamic investigation of red blood cell (RBC) suspensions flowing in microcapillaries with diameters comparable to the cell size in vitro. By using high-speed video microscopy and image analysis, we provide the first simultaneous determination of both cell velocity and shape parameters related to RBC membrane deformability over an extended range of pressure drops, and the first quantitative comparison with theoretical results from the literature. Good agreement was found with the predicted axisymmetric shapes tending towards an apparent bullet-like asymptotic configuration at increasing cell velocity. A potential application of this work is in the design of flow-based devices to study the pathological conditions affecting cell deformability, thus allowing us to overcome the limits of classical static methods, such as micropipette aspiration, which are not suitable for handling a large number of cells.

In this work, a microfluidic system to investigate the flow behavior of red blood cells in a microcirculation-mimicking network of PDMS microchannels with thickness comparable to cell size is presented. We provide the first quantitative description of cell velocity and shape as a function of the applied pressure drop in such devices. Based on these results, a novel methodology to measure cell membrane viscoelastic properties in converging/diverging flow is developed, and the results are in good agreement with data from the literature. In particular, in the diverging channel the effect of RBC surface viscosity is dominant with respect to shear elasticity. Possible applications include measurements of cell deformability in pathological samples, where reliable methods are still lacking.

The high red blood cell (RBC) deformability is essential to optimal gas exchange between gas and tissues in microcirculation in vivo. This review is focused on the flow behavior of RBCs in microconfined geometries in vitro, such as circular section capillaries, rectangular channels and pores, where at least one transverse dimension is comparable to cell size. Experimental results on RBC velocity and shape are reviewed together with modeling predictions and numerical simulations. In spite of the progress made so far, the pathophysiological implications of altered RBC deformability are still to be fully elucidated, and more data from clinically-relevant experimental methods and modeling-based interpretation are needed. Future directions include the emerging application of microfluidics techniques to investigate RBC flow in complex geometries