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

Abstract

Suspensions of healthy and pathological red blood cells (RBC) flowing in microfluidic devices are frequently used to perform in vitro blood experiments for a better understanding of human microcirculation hemodynamic phenomena. This work reports the development of particulate viscoelastic analogue fluids able to mimic the rheological and hemorheological behavior of pathological RBC suspensions flowing in microfluidic systems. The pathological RBCs were obtained by an incubation of healthy RBCs at a high concentration of glucose, representing the pathological stage of hyperglycaemia in diabetic complications, and analyses of their deformability and aggregation were carried out. Overall, the developed in vitro analogue fluids were composed of a suspension of semi-rigid microbeads in a carrier viscoelastic fluid made of dextran 40 and xanthan gum. All suspensions of healthy and pathological RBCs, as well as their particulate analogue fluids, were extensively characterized in steady shear flow, as well as in small and large amplitude oscillatory shear flow. In addition, the well-known cell-free layer (CFL) phenomenon occurring in microchannels was investigated in detail to provide comparisons between healthy and pathological in vitro RBC suspensions and their corresponding analogue fluids at different volume concentrations (5% and 20%). The experimental results have shown a similar rheological behavior between the samples containing a suspension of pathological RBCs and the proposed analogue fluids. Moreover, this work shows that the particulate in vitro analogue fluids used have the ability to mimic well the CFL phenomenon occurring downstream of a microchannel contraction for pathological RBC suspensions. The proposed particulate fluids provide a more realistic behavior of the flow properties of suspended RBCs when compared with existing non-particulate blood analogues, and consequently, they are advantageous for detailed investigations of microcirculation.

In vitro blood flow visualizations and cell-free layer (CFL) measurements in a microchannel network

“…Additionally, by increasing the Hct there is a decrease in the thickness of all existing CFLs. This latter phenomenon is in accordance with the previous results observed in both in vivo and in vitro experiments [20,39,[47][48][49].…”

“…These microscale hemodynamic phenomena play an important role in blood mass transport mechanisms [3,11]. The CFL thickness depends of several factors such as cell concentration, deformability, vessel diameter, cell aggregation, flow rate, presence of microbubbles and geometry of the microchannels [12][13][14][15][16][17][18][19][20]. For instance, by increasing the concentration of RBCs, i.e., increasing the hematocrit (Hct), there is a decrease of CFL thickness [17,21].The bifurcations are geometries extremely common in both microvessels and microfluidic devices and it is important to improve our current understanding regarding the influence of the bifurcations and confluences on the blood flow behavior at a microscale level.…”

Flexible PDMS microparticles to mimic RBCs in blood particulate analogue fluids

“…. Due to these merits, during the last decade, several research works have measured the effects of the extensional flow in these kind of microchannels using blood analogue fluids and in vitro blood containing different kinds of blood cells [10,13,31,[44][45][46][47] .…”

“…Stiffness and deformability are particle characteristics that have gained increasing interest, for example, the reversible deformability found in vivo for the red blood cells (RBCs) plays an important role in blood rheology for vessels with diameters smaller than 300 μm, where the effective viscosity gets reduced due to RBCs migration to the vessel centre, resulting in the formation of a cell-free layer close to the vessels or microdevices walls [25][26][27][28][29] . These blood phenomena drive the development of particulate blood analogue fluids with similar properties and flow behaviour [19,30,31] . One of the main challenges in the development of these particulate fluids is the production of particles with the required mechanical properties.…”

“…In this way Pinho et al [31] and Calejo et al [30] have developed particulate blood analogues with rigid particles able to show the cell-free layer (CFL) formation downstream of a microchannel contraction and the reproduction of the viscosity curve of rigid RBCs suspensions. However, both studies have suggested that the only way to closely mimic some microscale blood-flow phenomena is by using deformable microparticles.…”