Nathan J. Quinlan

Investigations of gas and particle dynamics in first generation needle-free drug delivery devices

Abstract. Transdermal powdered drug delivery involves the propulsion of solid drug particles into the skin by means of high-speed gas-particle flow. The fluid dynamics of this technology have been investigated in devices consisting of a convergent-divergent nozzle located downstream of a bursting membrane, which serves both to initiate gas flow (functioning as the diaphragm of a shock tube) and to retain the drug particles before actuation. Pressure surveys of flow in devices with contoured nozzles of relatively low exit-to-throat area ratio and a conical nozzle of higher area ratio have indicated a starting process of approximately 200

Development of the meshless finite volume particle method with exact and efficient calculation of interparticle area

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Fluid Dynamics of Gas Exchange in High-Frequency Oscillatory Ventilation: In Vitro Investigations in Idealized and Anatomically Realistic Airway Bifurcation Models

s typical duration, followed by a quasi-steady supersonic flow. The velocity of drug particles exiting the contoured nozzles was measured at up to 1050 m/s, indicating that particle acceleration took place primarily in the quasi-steady flow. In the conical nozzle, which had larger exit area ratio, the quasi-steady nozzle flow was found to be overexpanded, resulting in a shock system within the nozzle. Particles were typically delivered by these nozzles at 400 m/s, suggesting that the starting process and the quasi-steady shock processed flow are both responsible for acceleration of the particle payload. The larger exit area of the conical nozzle tested enables drug delivery over a larger target disc, which may be advantageous.

Development of a novel bioreactor to apply shear stress and tensile strain simultaneously to cell monolayers

Abstract The Finite Volume Particle Method (FVPM) is a meshless method based on a definition of interparticle area which is closely analogous to cell face area in the classical finite volume method. In previous work, the interparticle area has been computed by numerical integration, which is a source of error and is extremely expensive. We show that if the particle weight or kernel function is defined as a discontinuous top-hat function, the particle interaction vectors may be evaluated exactly and efficiently. The new formulation reduces overall computational time by a factor between 6.4 and 8.2. In numerical experiments on a viscous flow with an analytical solution, the method converges under all conditions. Significantly, in contrast with standard FVPM and SPH, error depends on particle size but not on particle overlap (as long as the computational domain is completely covered by particles). The new method is shown to be superior to standard FVPM for shock tube flow and inviscid steady transonic flow. In benchmarking on a viscous multiphase flow application, FVPM with exact interparticle area is shown to be competitive with a mesh-based volume-of-fluid solver in terms of computational time required to resolve the structure of an interface.

Effect of Eddy Length Scale on Mechanical Loading of Blood Cells in Turbulent Flow

The objective of this work is to develop understanding of the local fluid dynamic mechanisms that underpin gas exchange in high-frequency oscillatory ventilation (HFOV). The flow field during HFOV was investigated experimentally using particle image velocimetry in idealized and realistic models of a single bifurcation. Results show that inspiratory and expiratory fluid streams coexist in the airway at flow reversal, and mixing between them is enhanced by secondary flow and by vortices associated with shear layers. Unsteady flow separation and recirculation occurs in both geometries. The magnitude of secondary flow is greater in the realistic model than in the idealized model, and the structure of secondary flow is quite different. However, other flow structures are qualitatively similar.

Fast exact evaluation of particle interaction vectors in the finite volume particle method

To date many bioreactor experiments have investigated the cellular response to isolated in vitro forces. However, in vivo, wall shear stress (WSS) and tensile hoop strain (THS) coexist. This article describes the techniques used to build and validate a novel vascular tissue bioreactor, which is capable of applying simultaneous wall shear stress and tensile stretch to multiple cellular substrates. The bioreactor design presented here combines a cone and plate rheometer with flexible substrates. Using such a combination, the bioreactor is capable of applying a large range of pulsatile wall shear stress (−30to+30dyn∕cm2) and tensile hoop strain (0%–12%). The WSS and THS applied to the cellular substrates were validated and calibrated. In particular, curves were produced that related the desired WSS to the bioreactor control parameters. The bioreactor was shown to be biocompatible and noncytotoxic and suitable for cellular mechanical loading studies in physiological condition, i.e., under simultaneous WSS and...

Application of 3D Smoothed Particle Hydrodynamics to a Shock Tube Flow: Effects and Control of Particle Distribution

Non-physiological turbulent blood flow is known to occur in and near implanted cardiovascular devices, but its effects on blood are poorly understood. The objective of this work is to investigate the effect of turbulent eddy length scale on blood cell damage, and in particular to test the hypothesis that only eddies similar in size to blood cells can cause damage. The microscale flow near a red blood cell (RBC) in an idealized turbulent eddy is modeled computationally using an immersed boundary method. The model is validated for the special case of a tank-treading RBC. In comparisons between turbulent flow fields, based on Kolmogorov theory, the model predicts that damage due to the smallest eddies is almost independent of the Kolmogorov length scale. The model predicts that within a given flow field, however, eddies of sub-cellular scale are less damaging than larger eddies. Eddy decay time and the turbulent energy spectral density are highlighted as important factors. The results suggest that Kolmogorov scale is not an adequate predictor of flow-induced blood trauma, and highlights the need for deeper understanding of the microscale structure of turbulent blood flow.

The characterisation and application of a pulsed neodymium YAG laser DGV system to a time-varying high-speed flow

The Finite Volume Particle Method (FVPM) is a mesh-free method which inherits many of the desirable properties of mesh-based finite volume methods. It relies on particle interaction vectors which are closely analogous to the intercell area vectors in the mesh-based finite volume method. To date, these vectors have been computed by numerical integration, which is not only a source of error but is also by far the most computationally expensive part of the algorithm. We show that by choosing an appropriate particle weight or kernel function, it is possible to evaluate the particle interaction vectors exactly and relatively quickly. The new formulation is validated for 2D viscous flow, and shown to enable modelling of freesurface flow.

High-Resolution Measurements of Velocity and Shear Stress in Leakage Jets From Bileaflet Mechanical Heart Valve Hinge Models

The effects of the initial particle distribution in Smoothe d Particle Hydrodynamics (SPH) are explored for standard and non-standard formulations. A Sod shock tube calculation is performed in three dimensions as a means of evaluating the ef fects of regular, non-aligned, and randomized initial distributions of particles. Resul ts from the classical formulation of SPH are compared to similar trials using a formulation tha t has been corrected for linear consistency, as well as a method that employs an adaptiv e particle distribution. When the initial particle distribution is not aligned with the d irection of the shock wave, or if particles are not uniformly spaced, the classical formulation of SPH y ields significant error. The integrity of the solution is restored by corrected methods, whi ch show similar results regardless of initial distribution. The three-dimensional s hock calculations are further improved with adaptive particle insertion and removal during the course of the simulation.

Application of the meshless finite volume particle method to flow-induced motion of a rigid body

Abstract Doppler Global Velocimetry (DGV) is a whole-field measurement technique which has attracted significant interest from the fluid-flow research community since its introduction in 1991. Practical implementations of the methodology have focused on two principal laser light sources: the argon ion laser, applied to steady state or slowly varying flows; and the pulsed neodymium YAG laser for the measurement of instantaneous velocity fields. However, the emphasis in the published literature has been very much on research using the argon laser. This paper reports the application of a Q-switched, injection-seeded neodymium YAG laser to the proven Oxford DGV system, and the use of this combination in a short duration unsteady high-speed flow. The pertinent characteristics of the apparatus are described, and the impact of these on the integrity of the resulting velocity measurements is presented. Adaptations to the commercial laser system that make it suitable for application to the measurement of transient high-speed flows are described. Finally, the application of this system to a short duration unsteady flow is described. This application is based on the flow found in a new type of transdermal drug delivery device, where particles of the drug material are projected at high speed through the skin. Whole-field velocities are recorded, and values as high as 800 m / s are evident.