Petar Liovic

Cavitation microstreaming and stress fields created by microbubbles

Cavitation microstreaming plays a role in the therapeutic action of microbubbles driven by ultrasound, such as the sonoporative and sonothrombolytic phenomena. Microscopic particle-image velocimetry experiments are presented. Results show that many different microstreaming patterns are possible around a microbubble when it is on a surface, albeit for microbubbles much larger than used in clinical practice. Each pattern is associated with a particular oscillation mode of the bubble, and changing between patterns is achieved by changing the sound frequency. Each microstreaming pattern also generates different shear stress and stretch/compression distributions in the vicinity of a bubble on a wall. Analysis of the micro-PIV results also shows that ultrasound-driven microstreaming flows around bubbles are feasible mechanisms for mixing therapeutic agents into the surrounding blood, as well as assisting sonoporative delivery of molecules across cell membranes. Patterns show significant variations around the bubble, suggesting sonoporation may be either enhanced or inhibited in different zones across a cellular surface. Thus, alternating the patterns may result in improved sonoporation and sonothrombolysis. The clear and reproducible delineation of microstreaming patterns based on driving frequency makes frequency-based pattern alternation a feasible alternative to the clinically less desirable practice of increasing sound pressure for equivalent sonoporative or sonothrombolytic effect. Surface divergence is proposed as a measure relevant to sonoporation.

Multi-physics treatment in the vicinity of arbitrarily deformable gas-liquid interfaces

A novel three-dimensional problem formulation is introduced for the simulation of turbulent interfacial multi-fluid flows. The strategy is built around the large eddy simulation (LES) concept, and can be employed for interfacial heat and mass transfer problems in which use can be made of either scalar transfer correlations, or exact mass/energy jump conditions. This multi-physics treatment capability at arbitrarily deformable interfaces translates into two main features: (i) a reconstructed distance function (RDF) is introduced to define a level-set interface-normal length scale, and (ii) an interfacial shear velocity is defined on the distance function support for further use in near-interface transport models. The solution algorithm uses VOF with piecewise planar interface reconstructions on a twice-as-fine mesh, and infers the convective mass fluxes from the interface solution to promote momentum conservation. The interfacial shear velocity defined on the distance function support is introduced to accommodate the asymptotic behaviour of turbulence approaching the interface in a proximity-dependent manner. Provided with highly accurate distance function data, the scheme generates near-interface damping functions that are second-order accurate and independent of interface orientation. The damping was found to be affected by errors introduced into shear velocity estimates by the high-frequency errors in the RDF scheme near the interface. The methodology has been applied for the simulation of a wave breaking scenario featuring multiple modes and interfacial length scales.

Efficient simulation of surface tension-dominated flows through enhanced interface geometry interrogation

In this paper, three improvements for modelling surface tension-dominated interfacial flows using interface tracking-based solution algorithms are presented. We have developed an improved approach to curvature estimation for incorporation into modern mesh-based surface tension models such as the Continuum Surface Force (CSF) and Sharp Surface Force (SSF) models. The scheme involves generating samples of curvature estimates from the multitude of height functions that can be generated from VOF representations of interfaces, and applying quality statistics based on interface orientation and smoothness to choose optimal candidates from the samples. In this manner, the orientation-dependence of past schemes for height function-based curvature estimation is ameliorated, the use of compact stencils for efficient computation can be maintained, and robustness is enhanced even in the presence of noticeable subgrid-scale disturbances in the interface representation. For surface tension-dominated flows, the explicit capillary timestep restriction is relaxed through timescale-separated slope limiting that identifies spurious modes in curvature evolution and omits them from contributing to surface force computations, thus promoting efficiency in simulation through the use of less timesteps. Efficiency in flow simulation is further promoted by incorporating awareness of interface location into multigrid preconditioning for Krylov subspace-based solution of elliptic problems. This use of interface-cognizance in solving problems such as the Helmholtz equation and the Poisson equation enables multigrid-like convergence in discontinuous-coefficient elliptic problems without the expense of constructing the Galerkin coarse-grid operator. The key improvements in the surface tension modelling and the numerical linear algebra are also applicable to level-set-based interfacial flow simulation.

Structural integrity of intramedullary rib fixation using a single bioresorbable screw

BACKGROUND Operative management of flail chest injury is receiving increasing interest. However, we have noticed in our own practice the difficulty in achieving reliable results with posterior rib fracture fixation. In this article, we analyze and model the physiologic forces acting on posterior rib fractures and assess the suitability of an intramedullary screw fixation technique in this site. METHODS Computerized finite element analysis (FEA) was used to model a typical sixth rib and analyze the physiologic forces that act on the rib in vivo. A fracture in the posterior aspect of the rib was incorporated into the model, and an intramedullary screw fixation concept was assessed, using both a bioabsorbable polymer screw and a stainless steel screw. The records of 120 consecutive patients with flail chest were reviewed, and 26 patients were identified as having multiple posterior rib fractures with displacement. These patients formed a clinical correlation group by which to assess the FEA model. RESULTS FEA modeling of the posterior rib fracture showed likely posterior displacement in response to physiologic forces. Review of the 26 patients with flail chest and displaced posterior fractures confirmed the direction of displacement. Modeling of an intramedullary screw fixation showed significant stresses in the bone/screw contact areas (stainless steel solution) and the prosthesis itself (bioabsorbable polymer solution) CONCLUSION This FEA model demonstrates that physiologic forces cause posterior displacement at posterior rib fracture sites. Fixation solutions to counteract these forces need to overcome significant stresses at both the bone/prosthesis contact regions and within the prosthetic material itself. LEVEL OF EVIDENCE Epidemiologic/therapeutic study, level V.

LES of Turbulent Bubble Formation and Break-Up Based on Interface Tracking

A 3D finite-difference method featuring piecewise planar volume tracking and explicit sub-grid scale modeling is used to simulate the violent, turbulent bubbling resulting from air venting into a water pool through a downcomer pipe. A moderate-sized mesh and domain decomposition-based parallelism were used for a O(105) − O(106)-timestep computation, in order to extract turbulence statistics representative of long-time simulation of fully-developed flow. Volume tracking is seen to be a robust basis for super-grid scale simulation of the bubble rise, fragmentation and coalescence phenomena; it captures the kinematics of interfaces that are adequately resolved on the grid, and preserves the existence of bubbles and liquid jets breaking up to grid-scale (1–2 cells) size. Interface deformations are seen to strongly correlate with the large-scale structures forming at the front in the gas phase. Enhanced energy decay according to the 8/3 power law seen in bubbly flow is generally attained, with also some tendency towards the Kolmogorov K41 slope. The bubbling is turbulent on the gas side, and the main sources of turbulence are bubble break-up and gas jetting from the downcomer tip.

A Newton-Krylov Solver for Remapping-Based Volume-of-Fluid Methods

A new conservative remapping method is presented here for generating multi-dimensional fluxes used for the time integration of hyperbolic equations through single-stage unsplit advection. A solution to the Lagrangian mesh location is generated that converges the volumes of all remapped flux definitions to the volumes of equivalent one-dimensional flux definitions at their corresponding cell faces. The method is most feasible within localized subdomains of an Eulerian solution domain. The main utility of the method is the generation of fluxes in the vicinity of discontinuities and sharp gradients that does not introduce physically spuriously extrema while locally conserving mass. In generating solutions to Lagrangian mesh location by solving a nonlinear equation system, the new remap requires the anchoring of the Lagrangian mesh—removal of degrees of freedom to make the problem definite. The method is based on characteristic tracing along trajectories assumed to be linear. This paper investigates the convergence and sensitivity of the Lagrangian mesh solver to mesh and timestep size, in assessing its merit for application in transient CFD codes. For single-stage unsplit advection volume-of-fluid methods, the new remap suppresses the introduction of undershoots, overshoots, and wisps. In combination with a conservative remapping phase, the new method for fixing the location of the Lagrangian mesh eliminates the need for heuristic redistribution or clipping procedures for spurious extrema removal.

Predictions for optimal mitigation of paracrine inhibitory signalling in haemopoietic stem cell cultures

IntroductionRecent studies in the literature have highlighted the critical role played by cell signalling in determining haemopoietic stem cell (HSC) fate within ex vivo culture systems. Stimulatory signals can enhance proliferation and promote differentiation, whilst inhibitory signals can significantly limit culture output.MethodsNumerical models of various mitigation strategies are presented and applied to determine effectiveness of these strategies toward mitigation of paracrine inhibitory signalling inherent in these culture systems. The strategies assessed include mixing, media-exchange, fed-batch and perfusion.ResultsThe models predict that significant spatial concentration gradients exist in typical cell cultures, with important consequences for subsequent cell expansion. Media exchange is shown to be the most effective mitigation strategy, but remains labour intensive and difficult to scale-up for large culture systems. The fed-batch strategy is only effective at very small Peclet number, and its effect is diminished as the cell culture volume grows. Conversely, mixing is effective at high Peclet number, and ineffective at low Peclet number. The models predict that cell expansion in fed-batch cultures becomes independent of increasing dilution rate, consistent with experimental results previously reported in the literature. In contrast, the models predict that increasing the flow rate in perfused cultures will lead to increased cell expansion, indicating the suitability of perfusion for use as an automated, tunable strategy. The effect of initial cell seeding density is also investigated, with the model showing that perfusion outperforms dilution for all densities considered.ConclusionsThe models predict that the impact of inhibitory signalling in HSC cultures can be mitigated against using media manipulation strategies, with the optimal strategy dependent upon the protein diffusion time-scale relative to the media manipulation time-scale. The key messages from this study can be applied to any complex cell culture scenario where cell-cell interactions and paracrine signalling networks impact upon cell fate and cell expansion.

Stress analysis of a centrally fractured rib fixated by an intramedullary screw

The stress on an intramedullary screw rib fixation device holding together a centrally fractured human rib under in vivo force loadings was studied using finite element analysis (FEA). Validation of the FEA modelling using pullout from porcine ribs proved FEA to be suitable for assessing the structural integrity of screw/bone systems such as rib fixated by a screw. In the human rib fixation investigation, it was found that intramedullary bioresorbable Bioretec screws can fixate centrally fractured human ribs under normal breathing conditions. However, under coughing conditions, simulation showed Bioretec fixating screws to bend substantially. High stresses in the screw are mainly the result of flexion induced by the force loading, and are restricted to thin regions on the outside of the screw shaft. Stiffer screws result in less locally intense stress concentrations in bone, indicating that bone failure in the bone/screw contact regions can be averted with improvements in screw stiffness.

Large-Eddy Simulation of Steep Water Waves

Large-Eddy Simulation is used for the investigation of the breaking of steep water waves on a beach of constant bed slope. The method is built within a multi-fluid flow solver, in which the free surface is tracked using a Volume-of-Fluid method featuring piecewise planar interface reconstructions on a twice-as-fine mesh. The Smagorinsky sub-grid scale model is used for explicit under-resolved turbulence closure, coupled with a new scheme for turbulence decay treatment on the air-side of massively deformable free surfaces. The simulations were conducted for shear Reynolds numbers Re G * ≈Re L * ≈400, based on the mean water depth. The Large-Eddy Simulation formulation in the interface tracking, single-fluid formulation is introduced for this purpose. The approach is demonstrated as a powerful tool for exploring large-scale, interfacial turbulent flows. The discussion focuses on coherent structures formation, the free surface flow effects at breaking, and form drag evolution with the surface.

Perceptive communicating capsules for fluid flow measurement and visualisation

A new approach to flow measurement and visualisation in fluid dynamics based on a group of perceptive communicating capsules has been developed. Experiments were carried out with fluid-mobilised and stationary capsules deployed in a fluid flow test rig (raceway pond). Each capsule contains a microcontroller, battery, infra-red and visible LEDs and other electronics. Using optical communications, capsules can record encounters with one another. From the resulting interaction patterns, fluid flow speed and path-frequency measurements were obtained. Additionally, the capsules have shown the capacity for distributed sensing, and their streaklines provide a valuable means of external visualisation.