A microparticle blood analogue suspension matching blood rheology.

The handling of blood in vitro is demanding because of ethical, economical and safety issues. Although several Newtonian and non-Newtonian blood analogues are found in the literature, few studies have used particles to mimic red blood cells (RBCs) and built an analogue with similar rheological properties of blood. This work reports the development of a blood analogue suspension composed of polydimethylsiloxane (PDMS) microparticles with an average diameter of ∼7 µm. High throughput production of PDMS particles is possible using a multi-stage membrane emulsification process; up to ∼6 mL of microparticles are manufactured in 3 hours. PDMS particles at a concentration of around 21% (w/w) at 20 °C present steady, oscillatory and extensional rheologies very similar to those of blood under physiological conditions (37 °C and ∼41% hematocrit), making them a good candidate whole blood analogue. Also, flow studies were performed in microchannels with contraction to study the cell-free layer (CFL) formation and particle deformation, achieving good qualitative results. Using the procedure developed, it is possible to obtain blood analogue fluids with a shelf life of at least 6 months.

Cell adhesion in microchannel multiple constrictions - Evidence of mass transport limitations.

Biofilm growth (fouling) in microdevices is a critical concern in several industrial, engineering and health applications, particularly in novel high-performance microdevices often designed with complex geometries, narrow regions and multiple headers. Unfortunately, on these devices, the regions with local high wall shear stresses (WSS) also show high local fouling rates. Several explanations have been put forward by the scientific community, including the effect of cell transport by Brownian motion on the adhesion rate. In this work, for the first time, both WSS and convection and Brownian diffusion effects on cell adhesion were evaluated along a microchannel with intercalate constriction and expansion zones designed to mimic the hydrodynamics of the human body and biomedical devices. Convection and Brownian diffusion effects were numerically studied using a steady-state convective-diffusion model (convection, diffusion and sedimentation). According to the numerical results, the convection and Brownian diffusion effects on cell adhesion are effectively more significant in regions with high WSS. Furthermore, a good agreement was observed between experimental and predicted local Sherwood numbers, particularly at the entrance and within the multiple constrictions. However, further mechanisms should be considered to accurately predict cell adhesion in the expansion zones. The described numerical approach can be used as a way to identify possible clogging zones in microchannels, and defining solutions, even before the construction of the prototype.

Fabrication and Hydrodynamic Characterization of a Microfluidic Device for Cell Adhesion Tests in Polymeric Surfaces.

A fabrication method is developed to produce a microfluidic device to test cell adhesion to polymeric materials. The process is able to produce channels with walls of any spin coatable polymer. The method is a modification of the existing poly-dimethylsiloxane soft lithography method and, therefore, it is compatible with sealing methods and equipment of most microfluidic laboratories. The molds are produced by xurography, simplifying the fabrication in laboratories without sophisticated equipment for photolithography. The fabrication method is tested by determining the effective differences in bacterial adhesion in five different materials. These materials have different surface hydrophobicities and charges. The major drawback of the method is the location of the region of interest in a lowered surface. It is demonstrated by bacterial adhesion experiments that this drawback has a negligible effect on adhesion. The flow in the device was characterized by computational fluid dynamics and it was shown that shear stress in the region of interest can be calculated by numerical methods and by an analytical equation for rectangular channels. The device is therefore validated for adhesion tests.

Numerical study on the hemodynamics of patient-specific carotid bifurcation using a new mesh approach.

The definition of a suitable mesh to simulate blood flow in the human carotid bifurcation has been investigated. In this research, a novel mesh generation method is proposed: hexahedral cells at the center of the vessel and a fine grid of tetrahedral cells near the artery wall, in order to correctly simulate the large blood velocity gradients associated with specific locations. The selected numerical examples to show the pertinence of the novel generation method are supported by carotid ultrasound image data of a patient-specific case. Doppler systolic blood velocities measured during ultrasound examination are compared with simulated velocities using 4 different combinations of hexahedral and tetrahedral meshes and different fluid dynamic simulators. The Lin's test was applied to show the concordance of the results. Wall shear stress-based descriptors and localized normalized helicity descriptor emphasize the performance of the new method. Another feature is the reduced computation time required by the developed methodology. With the accurate combined mesh, different flow rate partitions, between the internal carotid artery and external carotid artery, were studied. The overall effect of the partitions is mainly in the blood flow patterns and in the hot-spot modulation of atherosclerosis-susceptible regions, rather than in their distribution along the bifurcation.

Link between deviations from Murray's Law and occurrence of low wall shear stress regions in the left coronary artery.

Murray developed two laws for the geometry of bifurcations in the circulatory system. Based on the principle of energy minimization, Murray found restrictions for the relation between the diameters and also between the angles of the branches. It is known that bifurcations are prone to the development of atherosclerosis, in regions associated to low wall shear stresses (WSS) and high oscillatory shear index (OSI). These indicators (size of low WSS regions, size of high OSI regions and size of high helicity regions) were evaluated in this work. All of them were normalized by the size of the outflow branches. The relation between Murray's laws and the size of low WSS regions was analysed in detail. It was found that the main factor leading to large regions of low WSS is the so called expansion ratio, a relation between the cross section areas of the outflow branches and the cross section area of the main branch. Large regions of low WSS appear for high expansion ratios. Furthermore, the size of low WSS regions is independent of the ratio between the diameters of the outflow branches. Since the expansion ratio in bifurcations following Murray's law is kept in a small range (1 and 1.25), all of them have regions of low WSS with similar size. However, the expansion ratio is not small enough to completely prevent regions with low WSS values and, therefore, Murray's law does not lead to atherosclerosis minimization. A study on the effect of the angulation of the bifurcation suggests that the Murray's law for the angles does not minimize the size of low WSS regions.

Numerical study of wall shear stress-based descriptors in the human left coronary artery.

The present work is about the application of wall shear stress descriptors - time averaged wall shear stress (TAWSS), oscillating shear index (OSI) and relative residence time (RRT) - to the study of blood flow in the left coronary artery (LCA). These descriptors aid the prediction of disturbed flow conditions in the vessels and play a significant role in the detection of potential zones of atherosclerosis development. Hemodynamic descriptors data were obtained, numerically, through ANSYS® software, for the LCA of a patient-specific geometry and for a 3D idealized model. Comparing both cases, the results are coherent, in terms of location and magnitude. Low TAWSS, high OSI and high RRT values are observed in the bifurcation - potential zone of atherosclerosis appearance. The dissimilarities observed in the TAWSS values, considering blood as a Newtonian or non-Newtonian fluid, releases the importance of the correct blood rheologic caracterization. Moreover, for a higher Reynolds number, the TAWSS values decrease in the bifurcation and along the LAD branch, increasing the probability of plaques deposition. Furthermore, for a stenotic LCA model, very low TAWSS and high RRT values in front and behind the stenosis are observed, indicating the probable extension, in the flow direction, of the lesion.