P.C. Sousa

Extensional flow of blood analog solutions in microfluidic devices

In this study, we show the importance of extensional rheology, in addition to the shear rheology, in the choice of blood analog solutions intended to be used in vitro for mimicking the microcirculatory system. For this purpose, we compare the flow of a Newtonian fluid and two well-established viscoelastic blood analog polymer solutions through microfluidic channels containing both hyperbolic and abrupt contractions∕expansions. The hyperbolic shape was selected in order to impose a nearly constant strain rate at the centerline of the microchannels and achieve a quasihomogeneous and strong extensional flow often found in features of the human microcirculatory system such as stenoses. The two blood analog fluids used are aqueous solutions of a polyacrylamide (125 ppm w∕w) and of a xanthan gum (500 ppm w∕w), which were characterized rheologically in steady-shear flow using a rotational rheometer and in extension using a capillary breakup extensional rheometer (CaBER). Both blood analogs exhibit a shear-thinning behavior similar to that of whole human blood, but their relaxation times, obtained from CaBER experiments, are substantially different (by one order of magnitude). Visualizations of the flow patterns using streak photography, measurements of the velocity field using microparticle image velocimetry, and pressure-drop measurements were carried out experimentally for a wide range of flow rates. The experimental results were also compared with the numerical simulations of the flow of a Newtonian fluid and a generalized Newtonian fluid with shear-thinning behavior. Our results show that the flow patterns of the two blood analog solutions are considerably different, despite their similar shear rheology. Furthermore, we demonstrate that the elastic properties of the fluid have a major impact on the flow characteristics, with the polyacrylamide solution exhibiting a much stronger elastic character. As such, these properties must be taken into account in the choice or development of analog fluids that are adequate to replicate blood behavior at the microscale.

A review of hemorheology: Measuring techniques and recent advances

Significant progress has been made over the years on the topic of hemorheology, not only in terms of the development of more accurate and sophisticated techniques, but also in terms of understanding the phenomena associated with blood components, their interactions and impact upon blood properties. The rheological properties of blood are strongly dependent on the interactions and mechanical properties of red blood cells, and a variation of these properties can bring further insight into the human health state and can be an important parameter in clinical diagnosis. In this article, we provide both a reference for hemorheological research and a resource regarding the fundamental concepts in hemorheology. This review is aimed at those starting in the field of hemodynamics, where blood rheology plays a significant role, but also at those in search of the most up-to-date findings (both qualitative and quantitative) in hemorheological measurements and novel techniques used in this context, including technical advances under more extreme conditions such as in large amplitude oscillatory shear flow or under extensional flow, which impose large deformations comparable to those found in the microcirculatory system and in diseased vessels. Given the impressive rate of increase in the available knowledge on blood flow, this review is also intended to identify areas where current knowledge is still incomplete, and which have the potential for new, exciting and useful research. We also discuss the most important parameters that can lead to an alteration of blood rheology, and which as a consequence can have a significant impact on the normal physiological behavior of blood.

Shear viscosity and nonlinear behavior of whole blood under large amplitude oscillatory shear

We investigated experimentally the rheological behavior of whole human blood subjected to large amplitude oscillatory shear under strain control to assess its nonlinear viscoelastic response. In these rheological tests, the shear stress response presented higher harmonic contributions, revealing the nonlinear behavior of human blood that is associated with changes in its internal microstructure. For the rheological conditions investigated, intra-cycle strain-stiffening and intra-cycle shear-thinning behavior of the human blood samples were observed and quantified based on the Lissajous-Bowditch plots. The results demonstrated that the dissipative nature of whole blood is more intense than its elastic component. We also assessed the effect of adding EDTA anticoagulant on the shear viscosity of whole blood subjected to steady shear flow. We found that the use of anticoagulant in appropriate concentrations did not influence the shear viscosity and that blood samples without anticoagulant preserved their rheological characteristics approximately for up to 8 minutes before coagulation became significant.

Measurement of relaxation times in extensional flow of weakly viscoelastic polymer solutions

The characterization of the extensional rheology of polymeric solutions is important in several applications and industrial processes. Filament stretching and capillary breakup rheometers have been developed to characterize the extensional properties of polymeric solutions, mostly for high-viscosity fluids. However, for low concentration polymer solutions, the measurements are difficult using available devices, in terms of the minimum viscosity and relaxation times that can be measured accurately. In addition, when the slow retraction method is used, solvent evaporation can affect the measurements for volatile solvents. In this work, a new setup was tested for filament breakup experiments using the slow retraction method, high-speed imaging techniques, and an immiscible oil bath to reduce solvent evaporation and facilitate particle tracking in the thinning filament. Extensional relaxation times above around 100 μs were measured with the device for dilute and semi-dilute polymer solutions. Particle tracking velocimetry was also used to measure the velocity in the filament and the corresponding elongation rate, and to compare with the values obtained from the measured exponential decay of the filament diameter.

Purely elastic flow instabilities in microscale cross-slot devices

We present an experimental investigation of viscoelastic fluid flow in a cross-slot microgeometry under low Reynolds number flow conditions. By using several viscoelastic fluids, we investigate the effects of the microchannel bounding walls and the polymer solution concentration on the flow patterns. We demonstrate that for concentrated polymer solutions, the flow undergoes a bifurcation above a critical Weissenberg number (Wi) at which the flow becomes asymmetric but remains steady. The appearance of this elastic instability depends on the channel aspect ratio, defined as the ratio between the depth and the width of the channels. At high aspect ratios, when bounding wall effects are reduced, two types of elastic instabilities were observed, one in which the flow becomes asymmetric and steady, followed by a second instability at higher Wi, in which the flow becomes time-dependent. When the aspect ratio decreases, the bounding walls have a stabilizing effect, preventing the occurrence of steady asymmetric flow and postponing the transition to unsteady flow to higher Wi. For less concentrated solutions, the first elastic instability to steady asymmetric flow is absent and only the time-dependent flow instability is observed.

High performance microfluidic rectifiers for viscoelastic fluid flow

The flow of Newtonian and non-Newtonian fluids within microfluidic rectifiers with a hyperbolic shape was investigated to assess the effect of the bounding walls on the diodicity of the microfluidic device and achieve high flow anisotropy. Three microchannels were used, with different depths and the same geometrical configuration, which creates a strong extensional flow and generates high anisotropic flow resistance between the two flow directions. The Newtonian fluid, de-ionized water, was used as a reference fluid. The viscoelastic fluid used was an aqueous solution of polyethylene oxide (0.1% w/w) with high molecular weight. The flow patterns were visualized using streak photography and the velocity field was investigated using micro-particle image velocimetry. Moreover, pressure drop measurements were performed in order to compare the diodicity achieved in the microfluidic rectifiers. For the Newtonian fluid flow, the experimental results are compared with numerical predictions obtained using a finite-volume method and good agreement was found between both approaches. For the viscoelastic fluid, significant anisotropic flow resistance can be achieved. The effect of the bounding walls was analysed and found to be qualitatively similar for all microchannels. Nevertheless, in quantitative terms, the diodicity is enhanced when the wall effect is reduced, i.e. when the channels are deeper. A maximum diodicity above six was found for the deeper channel, a value well beyond those previously reported.

In vitro blood flow and cell-free layer in hyperbolic microchannels: Visualizations and measurements

Red blood cells (RBCs) in microchannels has tendency to undergo axial migration due to the parabolic velocity profile, which results in a high shear stress around wall that forces the RBC to move towards the centre induced by the tank treading motion of the RBC membrane. As a result there is a formation of a cell free layer (CFL) with extremely low concentration of cells. Based on this phenomenon, several works have proposed microfluidic designs to separate the suspending physiological fluid from whole in vitro blood. This study aims to characterize the CFL in hyperbolic-shaped microchannels to separate RBCs from plasma. For this purpose, we have investigated the effect of hyperbolic contractions on the CFL by using not only different Hencky strains but also varying the series of contractions. The results show that the hyperbolic contractions with a Hencky strain of 3 and higher, substantially increase the CFL downstream of the contraction region in contrast with the microchannels with a Hencky strain of 2, where the effect is insignificant. Although, the highest CFL thickness occur at microchannels with a Hencky strain of 3.6 and 4.2 the experiments have also shown that cells blockage are more likely to occur at this kind of microchannels. Hence, the most appropriate hyperbolic-shaped microchannels to separate RBCs from plasma is the one with a Hencky strain of 3.

Blood Flow Visualization and Measurements in Microfluidic Devices Fabricated by a Micromilling Technique

The authors acknowledge the financial support provided by PTDC/SAU-ENB/116929/2010 and EXPL/EMS-SIS/ 2215/2013 from FCT (Science and Technology Foundation), COMPETE, QREN and European Union (FEDER). DP acknowledge the PhD scholarship SFRH/BD/89077/2012, and P.C. Sousa acknowledges the fellowship SFRH/BPD/75258/ 2010, all attributed by FCT.

Rheological behavior of human blood in uniaxial extensional flow

We present an investigation of the rheological behavior of whole human blood under uniaxial extensional flow. For that purpose, capillary breakup experiments were carried out by combining the slow retraction method, high-speed imaging techniques, and an immiscible oil bath. The use of the oil bath was aimed at reducing liquid loss by evaporation and to reduce light refraction effects, thus allowing the visualization of the blood cells during the filament thinning. Extensional relaxation times were measured in whole blood samples collected from a total of 13 healthy adult volunteers from both genders, with hematocrit levels between 38.7% and 46.3%. For this range of red blood cell concentrations, the variation of the extensional relaxation time is small, with the average extensional relaxation times measured in air and in oil being 114 ± 30 and 259 ± 47 μs, respectively. An increase of the red blood cells concentration leads to an increase of the bulk viscosity of the sample, which delays the thinning of t...

Viscoelastic fluid flow through 3D square-square expansions

In this work we present an experimental study of the 3D laminar flow of Newtonian and Boger fluids through square‐square expansions with expansion ratios of 1:2.4, 1:4, 1:8 and 1:12. Visualizations of the flow patterns were performed using streak line photography and the velocity field of the flow was measured in detail using Particle Image Velocimetry (PIV). The experimental results obtained with the Newtonian fluid are compared with numerical predictions. The numerical code used is based on a Finite‐Volume method and an excellent agreement is found between experimental and numerical results. For all expansion ratios studied, a Moffatt corner vortex is observed downstream of the expansion and an increase in the flow inertia leads to an enhancement of the vortex size. On the other hand, the viscoelastic fluid flow also reveals the existence of a corner vortex downstream of the expansion, which decreases in size and strength when the Deborah number is increased. The vortices in square‐square expansion flow...