A simple microfluidic device for the deformability assessment of blood cells in a continuous flow

Abstract

Blood flow presents several interesting phenomena in microcirculation that can be used to develop microfluidic devices capable to promote blood cells separation and analysis in continuous flow. In the last decade there have been numerous microfluidic studies focused on the deformation of red blood cells (RBCs) flowing through geometries mimicking microvessels. In contrast, studies focusing on the deformation of white blood cells (WBCs) are scarce despite this phenomenon often happens in the microcirculation. In this work, we present a novel integrative microfluidic device able to perform continuous separation of a desired amount of blood cells, without clogging or jamming, and at the same time, capable to assess the deformation index (DI) of both WBCs and RBCs. To determine the DI of both WBCs and RBCs, a hyperbolic converging microchannel was used, as well as a suitable image analysis technique to measure the DIs of these blood cells along the regions of interest. The results show that the WBCs have a much lower deformability than RBCs when subjected to the same in vitro flow conditions, which is directly related to their cytoskeleton and nucleus contents. The proposed strategy can be easily transformed into a simple and inexpensive diagnostic microfluidic system to simultaneously separate and assess blood cells deformability.

Measuring Cell Viscoelastic Properties Using a Microfluidic Extensional Flow Device

“…S3). Our definition of cell strain is equivalent to the Taylor deformation parameter (28) historically used to define droplet deformation (29)(30)(31) and adapted to quantify red blood cell deformations (20,24,32). The cell strain measurement was taken at the time point at which the cell was closest to the stagnation point.…”

“…To address these issues, microfluidic tools have recently been explored as a strategy to measure cellular structural and mechanical properties with a rapidity that may be better suited to drug discovery and clinical application (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Although these approaches have indeed massively improved measurement throughput and reduced operator skill/bias issues relative to traditional measurements, the extraction of cell mechanical properties (e.g., elastic modulus) remains challenging, primarily due to complex viscous forces that severely complicate analysis of deformations.…”

In vitro particulate analogue fluids for experimental studies of rheological and hemorheological behavior of glucose-rich RBC suspensions

“…Several studies have been performed both in vivo 11,13,14 and in vitro 2,9,[15][16][17][18] to better understand the CFL formation, which influences its thickness and the advantages and disadvantages of the presence of this layer in the human microcirculatory system 6 and in microchannels. 8,16,19 It is also important to refer that in real blood, there is a migration of white blood cells from the core towards the wall region of the vessels, a phenomenon called margination, 20,21 but this issue is outside the scope of this work. Additionally, it is also known that CFL is influenced by the presence of several pathological disorders that also change the rheological properties of whole blood 22,23 as is the case of diabetic disorders.…”

Generation of micro-sized PDMS particles by a flow focusing technique for biomicrofluidics applications

“…1,2 It is widely used to fabricate microfluidic devices to perform blood cells separation [3][4][5][6] and deformability analysis, 7,8 to culture endothelial cells, [9][10][11] and to investigate several flow phenomena happening in microvessels. [12][13][14] In the last years, the production of monodisperse particles with this inert elastomer has stimulated great interest of researchers because of their potential applications, especially in biomedicine.…”