Development of a general method for designing microvascular networks using distribution of wall shear stress

In the present study, theoretical formulations for calculation of optimal bifurcation angle and relationship between the diameters of mother and daughter vessels using the power law model for non-Newtonian fluids are developed. The method is based on the distribution of wall shear stress in the mother and daughter vessels. Also, the effect of distribution of wall shear stress on the minimization of energy loss and flow resistance is considered. It is shown that constant wall shear stress in the mother and daughter vessels provides the minimum flow resistance and energy loss of biological flows. Moreover, the effects of different wall shear stresses in the mother and daughter branches, different lengths of daughter branches in the asymmetric bifurcations and non-Newtonian effect of biological fluid flows on the bifurcation angle and the relationship between the diameters of mother and daughter branches are considered. Using numerical simulations for non-Newtonian models such as power law and Carreau models, the effects of optimal bifurcation angle on the pressure drop and flow resistance of blood flow in the symmetric bifurcation are investigated. Numerical simulations show that optimal bifurcation angle decreases the pressure drop and flow resistance especially for bifurcations at large Reynolds number.     

Wall shear stress in backward-facing step flow of a red blood cell suspension.

An experimental investigation of the wall shear stress distribution downstream of a backward-facing step is carried out. The wall shear stress distribution was determined by measuring the deformation of a gel layer, attached to the wall downstream of the step. Speckle pattern interferometry was applied to measure the deformation of the gel layer. The measured deformation, combined with the properties of the gel layer, served as an input for a finite element solid mechanics computation to determine the stress distribution in the gel layer. The wall shear stress, required to generate the measured deformation of the gel layer, was determined from these computations. A Newtonian buffer solution and a non-Newtonian red blood cell suspension were used as measuring fluids. The deformation of the gel layer was determined for a Newtonian buffer solution to evaluate the method and to obtain the properties of the gel layer. Subsequently, the wall shear stress distribution for the non-Newtonian red blood cell suspension was determined for three different flow rates. The inelastic non-Newtonian Carreau-Yasuda model served as constitutive model for the red blood cell suspension. Using this model, the velocity and wall shear stress distribution were computed by means of a finite element fluid mechanics computation. From the comparison between the numerical and the experimental results, it can be concluded that wall shear stresses, induced by the red blood cell suspension, can be modeled accurately by employing a Carreau-Yasuda model.     

CFD simulation of non-Newtonian fluid flow in anaerobic digesters

A general mathematical model that predicts the flow fields in a mixed-flow anaerobic digester was developed. In this model, the liquid manure was assumed to be a non-Newtonian fluid, and the flow governed by the continuity, momentum, and k-epsilon standard turbulence equations, and non-Newtonian power law model. The commercial computational fluid dynamics (CFD) software, Fluent, was applied to simulate the flow fields of lab-scale, scale-up, and pilot-scale anaerobic digesters. The simulation results were validated against the experimental data from literature. The flow patterns were qualitatively compared for Newtonian and non-Newtonian fluids flow in a lab-scale digester. Numerical simulations were performed to predict the flow fields in scale-up and pilot-scale anaerobic digesters with different water pump power inputs and different total solid concentration (TS) in the liquid manure. The optimal power inputs were determined for the pilot-scale anaerobic digester. Some measures for reducing dead and low velocity zones were proposed based upon the CFD simulation results.     

Numerical study of the impact of non-Newtonian blood behavior on flow over a two-dimensional backward facing step

Endothelial cell (EC) responsiveness to shear stress is essential for vasoregulation and plays a role in atherogenesis. Although blood is a non-Newtonian fluid, EC flow studies in vitro are typically performed using Newtonian fluids. The goal of the present study was to determine the impact of non-Newtonian behavior on the flow field within a model flow chamber capable of producing flow disturbance and whose dimensions permit Reynolds and Womersley numbers comparable to those present in vivo. We performed two-dimensional computational fluid dynamic simulations of steady and pulsatile laminar flow of Newtonian and non-Newtonian fluids over a backward facing step. In the non-Newtonian simulations, the fluid was modeled as a shear-thinning Carreau fluid. Steady flow results demonstrate that for Re in the range 50-400, the flow recirculation zone downstream of the step is 22-63% larger for the Newtonian fluid than for the non-Newtonian fluid, while spatial gradients of shear stress are larger for the non-Newtonian fluid. In pulsatile flow, the temporal gradients of shear stress within the flow recirculation zone are significantly larger for the Newtonian fluid than for the non-Newtonian fluid. These findings raise the possibility that in regions of flow disturbance, EC mechanotransduction pathways stimulated by Newtonian and non-Newtonian fluids may be different.     

The flow of power law fluids in elastic networks and porous media

The flow of power law fluids, which include shear thinning and shear thickening as well as Newtonian as a special case, in networks of interconnected elastic tubes is investigated using a residual-based pore scale network modeling method with the employment of newly derived formulae. Two relations describing the mechanical interaction between the local pressure and local cross-sectional area in distensible tubes of elastic nature are considered in the derivation of these formulae. The model can be used to describe shear dependent flows of mainly viscous nature. The behavior of the proposed model is vindicated by several tests in a number of special and limiting cases where the results can be verified quantitatively or qualitatively. The model, which is the first of its kind, incorporates more than one major nonlinearity corresponding to the fluid rheology and conduit mechanical properties, that is non-Newtonian effects and tube distensibility. The formulation, implementation, and performance indicate that the model enjoys certain advantages over the existing models such as being exact within the restricting assumptions on which the model is based, easy implementation, low computational costs, reliability, and smooth convergence. The proposed model can, therefore, be used as an alternative to the existing Newtonian distensible models; moreover, it stretches the capabilities of the existing modeling approaches to reach non-Newtonian rheologies.     

In vivo mimicking model for solid tumor towards hydromechanics of tissue deformation and creation of necrosis

The present work addresses transvascular and interstitial fluid transport inside a solid tumor surrounded by normal tissue (close to an in vivo mimicking setup). In general, biological tissues behave like a soft porous material and show mechanical behavior towards the fluid motion through the interstitial space. In general, forces like viscous drag that are associated with the fluid flow may compress the tissue material. On the macroscopic level, we try to model the motion of fluids and macromolecules through the interstitial space of solid tumor and the normal tissue layer. The transvascular fluid transport is assumed to be governed by modified Starling’s law. The poroelastohydrodynamics (interstitial hydrodynamics and the deformation of tissue material) inside the tumor and normal tissue regions is modeled using linearized biphasic mixture theory. Correspondingly, the velocity distribution of fluid is coupled to the displacement field of the solid phase (mainly cellular phase and extracellular matrix) in both the normal and tumor tissue regions. The corresponding velocity field is used within the transport reaction equation for fluids and macromolecules through interstitial space to get the overall solute (e.g., nutrients, drug, and other macromolecules) distribution. This study justifies that the presence of the normal tissue layer plays a significant role in delaying/assisting necrosis inside the tumor tissue. It is observed that the exchange process of fluids and macromolecules across the interface of the tumor and normal tissue affects the effectiveness factor corresponding to the tumor tissue.     

Flow-induced deformation from pressurized cavities in absorbing porous tissues

The behaviour of a cavity during an injection of fluid into biological tissue is considered. High cavity pressure drives fluid into the neighbouring tissue where it is absorbed by capillaries and lymphatics. The tissue is modelled as a nonlinear deformable porous medium with the injected fluid absorbed by the tissue at a rate proportional to the local pressure. A model with a spherical cavity in an infinite medium is used to find the pressure and displacement of the tissue as a function of time and radial distance. Analytical and numerical solutions for a step change in cavity pressure show that the flow induces a radial compression in the medium together with an annular expansion, the net result being an overall expansion of the medium. Thus any flow induced deformation of the material will aid in the absorption of fluid.     

Non-Newtonian rheology of leukemic blood and plasma: are n and k parameters of power law model diagnostic?

When discussing the rheological properties of normal and leukemic blood it must be considered that blood is a suspension of cells in aqueous solution which is also known as plasma. Whole blood viscosity and plasma viscosity were determined by Rheometer LS30 which allows measuring whole blood and plasma viscosity in the middle and low shear rate ranges. The measurements of the viscosity showed that whole blood and plasma behave as non-Newtonian power law fluid. The values of n (non-Newtonian index) and k (consistency index) of power law fluid were calculated for both leukemic blood and plasma samples. The importance of this phenomenon for the micro-circulation is discussed.     

Pressure losses in non-Newtonian flow through rigid wall tapered tubes

Pressure drop and pressure gradient were measured in steady Newtonian and non-Newtonian flow through tapered tubes having angles of taper, alpha, between 0.5 degree and 1.25 degrees. Aqueous solutions of polyacrylamide, characterized as power law fluids, were used for the non-Newtonian flow measurements. These solutions had power law parameters similar in magnitude to those of blood. The pressure drop-flow rate data compared well with the predictions of a semi-empirical flow model over a large range of flow rates (Re alpha up to 10 for Newtonian flow and 5.7 for non-Newtonian flow). The pressure gradient increased with distance, z, into the taper as the radius decreased. The linear relationship between pressure gradient and z, derived by Oka (Biorheology, 10, 207-212, 1973) was found to be valid only when alpha z was small. For the tapered tubes examined here, agreement was confined to the region near the inlet. If higher order terms in alpha z were taken into account the agreement was extended further into the taper. However, under higher flow conditions, when the inertial losses are not negligible, the semi-empirical model provides much better estimates of pressure gradient.     

Flush mounted hot film anemometer measurement of wall shear stress distal to a tri-leaflet valve for Newtonian and non-Newtonian blood analog fluids

Wall shear stress has been measured by flush-mounted hot film anemometry distal to an Ionescu-Shiley tri-leaflet valve under pulsatile flow conditions. Both Newtonian (aqueous glycerol) and non-Newtonian (aqueous polyacrylamide) blood analog fluids were investigated. Significant differences in the axial distribution of wall shear stress between the two fluids are apparent in flows having nearly identical Reynolds numbers. The Newtonian fluid exhibits a (peak) wall shear rate which is maximized near the valve seat (30 mm) and then decays to a fully developed flow value (by 106 mm). In contrast, the shear rate of the non-Newtonian fluid at 30 mm is less than half that of the Newtonian fluid and at 106 mm is more than twice that of the Newtonian fluid. It is suggested that non-Newtonian rheology influences valve flow patterns either through alterations in valve opening associated with low shear separation zones behind valve leaflets, or because of variations in the rate of jet spreading. More detailed studies are required to clarify the mechanisms. The Newtonian wall shear stresses for this valve are low. The highest value observed anywhere in the aortic chamber was 2.85 N/m2 at a peak Reynolds number of 3694.     

Non-Newtonian Blood Flow in Left Coronary Arteries with Varying Stenosis: A Comparative Study

This paper presents Computational fluid dynamic (CFD) analysis of blood flow in three different 3-D models of left coronary artery (LCA). A comparative study of flow parameters (pressure distribution, velocity distribution and wall shear stress) in each of the models is done for a non-Newtonian (Carreau) as well as the Newtonian nature of blood viscosity over a complete cardiac cycle. The difference between these two types of behavior of blood is studied for both transient and steady states of flow. Additionally, flow parameters are compared for steady and transient boundary conditions considering blood as non-Newtonian fluid. The study shows that the highest wall shear stress (WSS), velocity and pressure are found in artery having stenosis in all the three branches of LCA. The use of Newtonian blood model is a good approximation for steady as well as transient blood flow boundary conditions if shear rate is above 100 s-1. However, the assumption of steady blood flow results in underestimating the values of flow parameters such as wall shear stress, pressure and velocity.     

The influence of the non-Newtonian properties of blood on the flow in large arteries: steady flow in a carotid bifurcation model.

Laser Doppler anemometry experiments and finite element simulations of steady flow in a three dimensional model of the carotid bifurcation were performed to investigate the influence of non-Newtonian properties of blood on the velocity distribution. The axial velocity distribution was measured for two fluids: a non-Newtonian blood analog fluid and a Newtonian reference fluid. Striking differences between the measured flow fields were found. The axial velocity field of the non-Newtonian fluid was flattened, had lower velocity gradients at the divider wall, and higher velocity gradients at the non-divider wall. The flow separation, as found with the Newtonian fluid, was absent. In the computations, the shear thinning behavior of the analog blood fluid was incorporated through the Carreau-Yasuda model. The viscoelastic properties of the fluid were not included. A comparison between the experimental and numerical results showed good agreement, both for the Newtonian and the non-Newtonian fluid. Since only shear thinning was included, this seems to be the dominant non-Newtonian property of the blood analog fluid under steady flow conditions.     

Follicular fluid rheology and the duration of the ovulatory process

The fluid dynamics of ovulation were investigated to understand the mechanical role of follicular fluid in oocyte release. A set of equations describing the flow of fluid from an evacuating follicle was derived from basic principles. These equations demonstrate that, subject to assumptions about the available pressure differential and the source of the expulsive force, the size and shape of the ovulatory orifice have the largest influences on the rate of fluid loss, although the viscosity of the fluid is also an important variable. A thorough rheological examination of pig, bovine and human follicular fluids, performed using a cone-plate viscometer, demonstrated that these fluids have complex, non-Newtonian characteristics. The fluids also undergo time-dependent and spontaneous changes in viscosity at constant shear rates; some fluids were subject to coagulation-like events. Viscosity characteristics were unrelated to broad parameters of follicle development. The models used representative viscosity values to demonstrate that variations in the rate and duration of follicle evacuation, as observed by ultrasonography, could be explained largely by variations in fluid viscosity and the characteristics of the ovulatory orifice.     

A Mathematical Model of Spatial Self-Organization in a Mechanically Active Cellular Medium

A general continual model of a medium composed of mechanically active cells is proposed. The medium is considered to be formed by three phases: cells, extracellular fluid, and an additional phase that is responsible for active interaction forces between cells and, for instance, may correspond to a system of protrusions that provide the development of active contractile forces. The deformation of the medium, which is identified with the deformation of the cell phase, consists of two components: elastic deformation of individual cells and cell rearrangements. The elastic deformation is associated with stresses in the cell phase. The spherical component of the stress tensor describes the nonlinear resistance of the cellular medium, which leads to the impossibility of its excessive compression. The constitutive equation for pressure in the cell phase is taken in the form of a nonlinear dependence on the volume cell density. The rearrangement of cells is considered as a flow controlled by stresses in the cell phase, active stresses, and fluid pressure. The tensor of active stresses is assumed to be spherical and nonlocally dependent on the cell density. Assuming that the process of biological tissue deformation is slow, we obtained a reduced model that neglects the elastic deformation of cells, compared to the inelastic deformation. A linear stability analysis of a spatially uniform steady-state solution was performed. The hydrostatic pressure of fluid is present among the parameters that are responsible for the loss of stability of the steady-state solution: an increase in it has a destabilizing effect owing to the action of the component of the interphase interaction force that is determined by the fluid pressure. The model we obtained can be used to describe the process of cavity formation in an initially homogeneous cell spheroid. The role of local and nonlocal mechanisms of active stress generation in the formation of cavity is investigated.     

Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network

Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor’s surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy’s law for tissue, and simplified Navier–Stokes equation for blood flow through capillaries) are used for simulating interstitial and intravascular flows and Starling’s law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model.     

Comments on the communication: on the calculation of shear rate and apparent viscosity in airlift and bubble column bioreactors

The determination of the shear rate in bubble column and airlift bioreactors is an important question from both the perspective of cell damage and the correlation of hydrodynamic parameters in non-Newtonian fluids in these contractors. In the context of correlating hydrodynamic parameters in non-Newtonian fluids, a common approach involves assuming that there exists an average shear rate in the column that is proportional to the superficial gas velocity. This average shear rate is then used to evaluate an effective viscosity of the non-Newtonian fluid that is subsequently used to quantify the fluid's rheological behavior in correlation. Contrary to a recent communication, this report illustrates that this approach, which has mainly been applied to bubble columns, can also be applied to external loop airlift contractors, replacing the superficial gas velocity by the superficial gas velocity by the superficial gas velocity supplied to the riser of the contractor. This extension is based upon consideration of the relevant characteristic velocity in the active zone (i.e., the riser section) of the reactor.     

Investigations into the rheological characteristics of bovine amniotic fluid

The rheological characteristics of bovine amniotic fluid have been studied at different shear rates. The viscosity of bovine amniotic fluid at 20°C was found to increase with time at a constant low shear rate during the measurement. Additionally, the viscosity was observed to decrease with increasing shear rate, indicating that a shear thinning behaviour of the fluid was occurring. The log-log plot of shear stress versus shear rate yielded a straight line, consistent with non-Newtonian behaviour of the fluid and characteristic of pseudoplastic liquids. The data of shear stress versus shear rate could be represented by a power law model. The treatment of amniotic fluid with cetylpyridinium chloride (CPC) resulted in the precipitation of a mixture of components, including complex sulphated polysaccharides and extracellular proteoglycans, with the viscosity of the resulting liquid similar to that of water at 20°C. In addition, the viscosity of the CPC-pretreated fluid did not increase with time at constant shear rate and remained constant with the increase in shear rate. The apparent increase in viscosity with time and the shear thinning behaviour of the amniotic fluid can thus be attributed to pseudoplastic liquid behaviour associated with the presence of structurally complex polysaccharides and extracellular proteoglycans. The implications of this fluid viscosity behaviour are discussed in terms of their impact on the operation of packed or expanded (fluidized) chromatographic bed systems when amniotic fluid biofeed-stocks are used as a source of commercially important proteins.     

Mass transfer in blood oxygenators using blood analogue fluids

Mass transfer correlations for hollow fiber blood oxygenators have been determined experimentally using Newtonian and non-Newtonian blood analogue fluids. The Newtonian fluids consisted of deionized water and glycerol/water mixtures. The non-Newtonian fluids were prepared by adding small amounts of xanthan gum to the Newtonian blood analogue fluids. The rheological behavior of the non-Newtonian blood analogue fluids was modeled using the power law. The diffusion of oxygen into and out of the Newtonian and non-Newtonian blood analogue fluids has been studied. The liquid stream flowed outside and across bundles of woven hollow fibers, while the gas stream flowed inside the fibers.