A computational framework for investigating bacteria transport in microvasculature.

Blood-borne bacteria disseminate in tissue through microvasculature or capillaries. Capillary size, presence of red blood cells (RBCs), and bacteria motility affect bacteria intracapillary transport, an important yet largely unexplored phenomenon. Computational description of the system comprising interactions between plasma, RBCs, and motile bacteria in 5-10 µm diameter capillaries pose several challenges. The Immersed Boundary Method (IBM) was used to resolve the capillary, deformed RBCs, and bacteria. The challenge of disparate coupled time scales of flow and bacteria motion are reconciled by a temporal multiscale simulation method. Bacterium-wall and bacterium-RBC collisions were detected using a hierarchical contact- detection algorithm. Motile bacteria showed a net outward radial velocity of 2.8 µm/s compared to -0.5 µm/s inward for non-motile bacteria; thus, exhibiting a greater propensity to escape the bolus flow region between RBCs and marginate for potential extravasation, suggesting motility enhances extravasation of bacteria from capillaries.

Kinematic and aerodynamic analysis of a bat performing a turning-ascending maneuver.

The flapping flight of many bat species is characterized by a high degree of maneuverability and provides fertile ground for biomimetic design. However, there has been little prior work toward understanding bat flight maneuvers, particularly using a coupled kinematic and aerodynamic framework. Here, wing kinematic data of a large insectivorous bat (Hipposideros armiger) in straight and turning flight is investigated. Fundamental to turning flight are asymmetries in the wing kinematics and consequently asymmetries in the aerodynamic forces. Forces were calculated from the wing kinematics using aerodynamic numerical simulations. Aspects of the wing kinematics in the turn that were distinguishable from straight flight were an increase in stroke plane deviation angle, nominal increase in flapping amplitude, and a decrease in the horizontal stroke plane angle of the wing inside the turn. While prior work on the mechanics of turning flight in animals has focused on classifying a turn as either banking or yawing, in the present work we show evidence of simultaneous and synergistic banking and yawing mechanisms. During the initiation of the turn, the bank angle was low, and elevated thrust by the outside wing generated a significant yaw rotational moment during both the upstroke and downstroke. Later in the turn, the bank angle increased to approximately 25 degrees tilting the net force vector toward the inside of the turn providing centripetal acceleration thereby turning the bat. Understanding the details of the turning mechanism-combined yaw and bank-provides useful design and control principles for biomimetic flapping MAVs.

Analysis of a 180-degree U-turn maneuver executed by a hipposiderid bat.

Bats possess wings comprised of a flexible membrane and a jointed skeletal structure allowing them to execute complex flight maneuvers such as rapid tight turns. The extent of a bat's tight turning capability can be explored by analyzing a 180-degree U-turn. Prior studies have investigated more subtle flight maneuvers, but the kinematic and aerodynamic mechanisms of a U-turn have not been characterized. In this work, we use 3D optical motion capture and aerodynamic simulations to investigate a U-turn maneuver executed by a great roundleaf bat (Hipposideros armiger: mass = 55 g, span = 51 cm). The bat was observed to decrease its flight velocity and gain approximately 20 cm of altitude entering the U-turn. By lowering its velocity from 2.0 m/s to 0.5 m/s, the centripetal force requirement to execute a tight turn was substantially reduced. Centripetal force was generated by tilting the lift force vector laterally through banking. During the initiation of the U-turn, the bank angle increased from 20 degrees to 40 degrees. During the initiation and persisting throughout the U-turn, the flap amplitude of the right wing (inside of the turn) increased relative to the left wing. In addition, the right wing moved more laterally closer to the centerline of the body during the end of the downstroke and the beginning of the upstroke compared to the left wing. Reorientation of the body into the turn happened prior to a change in the flight path of the bat. Once the bat entered the U-turn and the bank angle increased, the change in flight path of the bat began to change rapidly as the bat negotiated the apex of the turn. During this phase of the turn, the minimum radius of curvature of the bat was 5.5 cm. During the egress of the turn, the bat accelerated and expended stored potential energy by descending. The cycle averaged total power expenditure by the bat during the six wingbeat cycle U-turn maneuver was 0.51 W which was approximately 40% above the power expenditure calculated for a nominally straight flight by the same bat. Future work on the topic of bat maneuverability may investigate a broader array of maneuvering flights characterizing the commonalities and differences across flights. In addition, the interplay between aerodynamic moments and inertial moments are of interest in order to more robustly characterize maneuvering mechanisms.

Modeling iontophoretic drug delivery in a microfluidic device.

Iontophoresis employs low-intensity electrical voltage and continuous constant current to direct a charged drug into a tissue. Iontophoretic drug delivery has recently been used as a novel method for cancer treatment in vivo. There is an urgent need to precisely model the low-intensity electric fields in cell culture systems to optimize iontophoretic drug delivery to tumors. Here, we present an iontophoresis-on-chip (IOC) platform to precisely quantify carboplatin drug delivery and its corresponding anti-cancer efficacy under various voltages and currents. In this study, we use an in vitro heparin-based hydrogel microfluidic device to model the movement of a charged drug across an extracellular matrix (ECM) and in MDA-MB-231 triple-negative breast cancer (TNBC) cells. Transport of the drug through the hydrogel was modeled based on diffusion and electrophoresis of charged drug molecules in the direction of an oppositely charged electrode. The drug concentration in the tumor extracellular matrix was computed using finite element modeling of transient drug transport in the heparin-based hydrogel. The model predictions were then validated using the IOC platform by comparing the predicted concentration of a fluorescent cationic dye (Alexa Fluor 594®) to the actual concentration in the microfluidic device. Alexa Fluor 594® was used because it has a molecular weight close to paclitaxel, the gold standard drug for treating TNBC, and carboplatin. Our results demonstrated that a 50 mV DC electric field and a 3 mA electrical current significantly increased drug delivery and tumor cell death by 48.12% ± 14.33 and 39.13% ± 12.86, respectively (n = 3, p-value <0.05). The IOC platform and mathematical drug delivery model of iontophoresis are promising tools for precise delivery of chemotherapeutic drugs into solid tumors. Further improvements to the IOC platform can be made by adding a layer of epidermal cells to model the skin.

Determination of spatial fidelity required to accurately mimic the flight dynamics of a bat.

Bats possess unique flight capabilities enabled by their wing morphology. While the articulated bone structure and flexible membrane constituting the wing are known to play a critical role in aerodynamic performance, the relationship has never been robustly quantified. Characterization of the sensitivity between precise wing contour and aerodynamic performance is important when designing a biomimetic flight vehicle based on experimentally measured wing kinematics. 3D optical motion capture, a standard method for obtaining wing kinematic measurements, discretely samples the smooth surface of a bat wing during flight. If the constellation of tracked 3D points is too sparse, a loss of critical information occurs. Here, we have explored the relationship between the density of wing surface points and several aerodynamic metrics, specifically, wing surface area variation, aerodynamic loads, and power expenditure. Loads and power were calculated using an incompressible Navier-Stokes solver. Of the metrics examined, aerodynamic power was found to be most sensitive to the spatial fidelity of the wing-the normalized root mean squared difference (NRMSD) between the 10- and 238-point cases was 35%. Load calculations varied slightly less with a peak NRMSD of 24% between the highest and lowest fidelity cases. Lastly, the wing surface area was least sensitive to the spatial fidelity of the wing kinematics, with a maximum NRMSD surface area of 8%. Close similarity in aerodynamic behavior was observed when using either a 120- and 238-point surface representation, establishing a bound to the sensitivity between wing shape and aerodynamics. The results from the 10- and 22-point configurations demonstrate that sparse representation of a wing surface can lead to a loss of information. The characterization of kinematic complexity of the wings both informs how many degrees of freedom are important to measure and also informs how many degrees of freedom are required to robotically reproduce the flapping flight.

Canonical description of wing kinematics and dynamics for a straight flying insectivorous bat (Hipposideros pratti).

Bats, with highly articulated wings, are some of the most agile flyers in nature. A novel three-dimensional geometric decomposition framework is developed to reduce the complex kinematics of a bat wing into physical movements used to describe flapping flight: namely flapping, stroke plane deviation and pitching, together with cambering and flexion. The decomposition is combined with aerodynamic simulations to investigate the cumulative effect of each motion on force production, and their primary contribution to the unsteady vortex dynamics. For the nearly straight and level flight of Hipposideros pratti, results show that the flapping motion by itself induced a moderate drag and lift. Stroke plane deviation increased lift, and nullified the drag. With the inclusion of the pitching motion into the kinematics, lift production further increased by a factor of more than 2.5, and exhibited a positive net thrust by virtue of the favorable wing orientation during the upstroke. The primary contribution of cambering, which included a maximum chord line displacement of ≈40% standard mean chord, was the stabilization of the leading edge vortex during the downstroke. This increased mean lift by about 35% at the expense of net thrust. Flexion was perhaps the most complex motion with maximum displacements of 75% standard mean chord. This was instrumental in reducing the negative lift during the upstroke by preventing the formation of strong leading edge vortices. The aerodynamic effective angle of attack emerged as a heuristic parameter to describe lift and net thrust production across movements.

A computational investigation of lift generation and power expenditure of Pratt's roundleaf bat (Hipposideros pratti) in forward flight.

The aerodynamic mechanisms of bat flight have been studied using a numerical approach. Kinematic data acquired using a high resolution motion capture system was employed to simulate the unsteady air flow around a bat's wings. A flapping bat wing contains many degrees of freedom, which make 3D motion tracking challenging. In order to overcome this challenge, an optical motion capture system of 21 cameras was used to reduce wing self-occlusion. Over the course of a meter-long flight, 108 discrete marker points on the bat's wings (Pratt's roundleaf bat, Hipposideros pratti) were tracked. The time evolution of the surface of each wing was computationally reconstructed in 3D space. The resulting kinematic model was interfaced with an unsteady incompressible flow solver using the immersed boundary method (IBM) and large eddy simulation (LES). Verification and validation of the flow simulation were conducted to establish accuracy. The aerodynamic forces calculated from the simulation compared well to the forces theoretically needed to sustain the observed flight trajectory. The transient flow field generated by the simulation allowed for the direct calculation of lift, drag, and power output of the bat during flight. The mean lift coefficient was found to be 3.21, and the flap cycle averaged aerodynamic power output was 1.05 W. Throughout the flap cycle, the planform area of the wings varied up to 46% between the largest and smallest values. During the upstroke, wing rotation was found to mitigate negative lift thereby improving overall flight efficiency. The high resolution motion capture and flow simulation framework presented here has the potential to facilitate the understanding of complex bat flight aerodynamics for both straight and maneuvering flight modes.

Prediction of Thrombus Growth: Effect of Stenosis and Reynolds Number.

Shear stresses play a major role in platelet-substrate interactions and thrombus formation and growth in blood flow, where under both pathological and physiological conditions platelet adhesion and accumulation occur. In this study, a shear-dependent continuum model for platelet activation, adhesion and aggregation is presented. The model was first verified under three different shear conditions and at two heparin levels. Three-dimensional simulations were then carried out to evaluate the performance of the model for severely damaged (stripped) aortas with mild and severe stenosis degrees in laminar flow regime. For these cases, linear shear-dependent functions were developed for platelet-surface and platelet-platelet adhesion rates. It was confirmed that the platelet adhesion rate is not only a function of Reynolds number (or wall shear rate) but also the stenosis severity of the vessel. General correlations for adhesion rates of platelets as functions of stenosis and Reynolds number were obtained based on these cases. Finally using the new platelet adhesion rates, the model was applied to different experimental systems and shown to agree well with measured platelet deposition.

Modeling thrombus formation and growth.

The paper reviews the state-of-the-art in computational modeling of thrombus formation and growth and related phenomena including platelet margination, activation, adhesion, and embolization. Presently, there is a high degree of empiricism in the modeling of thrombus formation. Based on the experimentally observed physics, the review gives useful strategies for predicting thrombus formation and growth. These include determining blood components involved in atherosclerosis, effective blood viscosity, tissue properties, and methods proposed for boundary conditions. In addition to the guidelines, ongoing research on the effect of shear stress on platelet margination, activation and adhesion, and platelet-surface interactions are reviewed. Biotechnol. Bioeng. 2017;114: 2154-2172. © 2017 Wiley Periodicals, Inc.

Large eddy simulation for predicting turbulent heat transfer in gas turbines.

Blade cooling technology will play a critical role in the next generation of propulsion and power generation gas turbines. Accurate prediction of blade metal temperature can avoid the use of excessive compressed bypass air and allow higher turbine inlet temperature, increasing fuel efficiency and decreasing emissions. Large eddy simulation (LES) has been established to predict heat transfer coefficients with good accuracy under various non-canonical flows, but is still limited to relatively simple geometries and low Reynolds numbers. It is envisioned that the projected increase in computational power combined with a drop in price-to-performance ratio will make system-level simulations using LES in complex blade geometries at engine conditions accessible to the design process in the coming one to two decades. In making this possible, two key challenges are addressed in this paper: working with complex intricate blade geometries and simulating high-Reynolds-number (Re) flows. It is proposed to use the immersed boundary method (IBM) combined with LES wall functions. A ribbed duct at Re=20 000 is simulated using the IBM, and a two-pass ribbed duct is simulated at Re=100 000 with and without rotation (rotation number Ro=0.2) using LES with wall functions. The results validate that the IBM is a viable alternative to body-conforming grids and that LES with wall functions reproduces experimental results at a much lower computational cost.

Effects of elastic modulus change in helical tubes under the influence of dynamic changes in curvature and torsion.

The incidence of stent late restenosis is high (Zwart et al., 2010, "Coronary Stent Thrombosis in the Current Era: Challenges and Opportunities for Treatment," Curr. Treat. Options Cardiovasc. Med., 12(1), pp. 46-57) despite the extensive use of stents, and is most prevalent at the proximal and distal ends of the stent. Elastic modulus change in stented coronary arteries subject to the motion of the myocardium is not studied extensively. It is our objective to understand and reveal the mechanism by which changes in elastic modulus and geometry contribute to the generation of nonphysiological wall shear stress (WSS). Such adverse hemodynamic conditions could have an effect on the onset of restenosis. Three-dimensional (3D), spatiotemporally resolved computational fluid dynamics (CFD) simulations of pulsatile flow with moving wall boundaries and fluid structure interaction (FSI) were carried out for a helical artery with physiologically relevant flow parameters. To study the effect of coronary artery (CA) geometry change on stent elastic modulus mismatch, models where the curvature, torsion and both curvature and torsion change were examined. The elastic modulus is increased by a factor of two, five, and ten in the stented section for all three modes of motion. The changes in elastic modulus and arterial geometry cause critical variations in the local pressure and velocity gradients and secondary flow patterns. The pressure gradient change is 47%, with respect to the unstented baseline when the elastic modulus is increased to 10. The corresponding WSS change is 15.4%. We demonstrate that these changes are attributed to the production of vorticity (vorticity flux) caused by the wall movement and elastic modulus discontinuity. The changes in curvature dominate torsion changes in terms of the effects to local hemodynamics. The elastic modulus discontinuities along with the dynamic change in geometry affected the secondary flow patterns and vorticity flux, which in turn affects the WSS.

Investigation of the effects of dynamic change in curvature and torsion on pulsatile flow in a helical tube.

Cardiovascular diseases are the number one cause of death in the world, making the understanding of hemodynamics and the development of treatment options imperative. The effect of motion of the coronary artery due to the motion of the myocardium is not extensively studied. In this work, we focus our investigation on the localized hemodynamic effects of dynamic changes in curvature and torsion. It is our objective to understand and reveal the mechanism by which changes in curvature and torsion contribute towards the observed wall shear stress distribution. Such adverse hemodynamic conditions could have an effect on circumferential intimal thickening. Three-dimensional spatiotemporally resolved computational fluid dynamics (CFD) simulations of pulsatile flow with moving wall boundaries were carried out for a simplified coronary artery with physiologically relevant flow parameters. A model with stationary walls is used as the baseline control case. In order to study the effect of curvature and torsion variation on local hemodynamics, this baseline model is compared to models where the curvature, torsion, and both curvature and torsion change. The simulations provided detailed information regarding the secondary flow dynamics. The results suggest that changes in curvature and torsion cause critical changes in local hemodynamics, namely, altering the local pressure and velocity gradients and secondary flow patterns. The wall shear stress (WSS) varies by a maximum of 22% when the curvature changes, by 3% when the torsion changes, and by 26% when both the curvature and torsion change. The oscillatory shear stress (OSI) varies by a maximum of 24% when the curvature changes, by 4% when the torsion changes, and by 28% when both the curvature and torsion change. We demonstrate that these changes are attributed to the physical mechanism associating the secondary flow patterns to the production of vorticity (vorticity flux) due to the wall movement. The secondary flow patterns and augmented vorticity flux affect the wall shear stresses. As a result, this work reveals how changes in curvature and torsion act to modify the near wall hemodynamics of arteries.

Hydrodynamic effects of compliance mismatch in stented arteries.

Cardiovascular diseases are the number one cause of death in the world, making the understanding of hemodynamics and development of treatment options imperative. The most common modality for treatment of occlusive coronary artery diseases is the use of stents. Stent design profoundly influences the postprocedural hemodynamic and solid mechanical environment of the stented artery. However, despite their wide acceptance, the incidence of stent late restenosis is still high (Zwart et al., 2010, "Coronary Stent Thrombosis in the Current Era: Challenges and Opportunities for Treatment," Current Treatment Options in Cardiovascular Medicine, 12(1), pp. 46-57), and it is most prevailing at the proximal and distal ends of the stent. In this work, we focus our investigation on the localized hemodynamic effects of compliance mismatch due to the presence of a stent in an artery. The compliance mismatch in a stented artery is maximized at the proximal and distal ends of the stent. Hence, it is our objective to understand and reveal the mechanism by which changes in compliance contribute to the generation of nonphysiological wall shear stress (WSS). Such adverse hemodynamic conditions could have an effect on the onset of restenosis. Three-dimensional, spatiotemporally resolved computational fluid dynamics simulations of pulsatile flow with fluid-structure interaction were carried out for a simplified coronary artery with physiologically relevant flow parameters. A model with uniform elastic modulus is used as the baseline control case. In order to study the effect of compliance variation on local hemodynamics, this baseline model is compared with models where the elastic modulus was increased by two-, five-, and tenfold in the middle of the vessel. The simulations provided detailed information regarding the recirculation zone dynamics formed during flow reversals. The results suggest that discontinuities in compliance cause critical changes in local hemodynamics, namely, altering the local pressure and velocity gradients. The change in pressure gradient at the discontinuity was as high as 90%. The corresponding changes in WSS and oscillatory shear index calculated were 9% and 15%, respectively. We demonstrate that these changes are attributed to the physical mechanism associating the pressure gradient discontinuities to the production of vorticity (vorticity flux) due to the presence of the stent. The pressure gradient discontinuities and augmented vorticity flux are affecting the wall shear stresses. As a result, this work reveals how compliance variations act to modify the near wall hemodynamics of stented arteries.

Evaluation of microchamber geometries and surface conditions for electrokinetic driven mixing.

The paper presents numerical simulations and analysis of electrokinetic induced mixing in a microchamber in the presence of a fluctuating electric field. Two microchamber geometries are investigated; one plain and the other with strategically placed microbaffles. Both geometries are tested for two extreme surface conditions: a charged surface with induced electrokinesis and another with a neutral or passive surface. Through order of magnitude analysis and numerical experiments it is found that there is an optimal choice of nondimensional frequency and driving potential which leads to the best mixing characteristics. This is given by the relationship Re(eof)/f*< 5 and the condition that f*= O(1), where Re(eof) is the ratio of electrokinetic forces to viscous forces and f*is the nondimensional frequency. Optimal mixing is shown to occur at Re(eof) = 100 and f*= 30. In all cases, best mixing is found to occur when conditions are favorable for the establishment and sustenance of a rotational cell in the chamber driven by the fluctuating ac current. It is shown that the plain microchamber performs better under conditions of surface neutrality while microbaffles enhance mixing substantially in a charged microchamber. In the presence of a rotational cell, the characteristic time scale for mixing is reduced by 2-3 orders of magnitude compared to plain diffusion and is calculated to be between 5 and 10 s for aqueous buffers.