Transient modelling of impact driven needle-free injectors.

Needle-free jet injectors (NFJIs) are one of the alternatives to hypodermic needles for transdermal drug delivery. These devices use a high-velocity jet stream to puncture the skin and deposit drugs in subcutaneous tissue. NFJIs typically exhibit two phases of jet injection - namely - an initial peak-pressure phase (< 5 ms), followed by a constant jet speed injection phase (≳ 5 ms). In NFJIs, jet velocity and jet diameter are tailored to achieve the required penetration depth for a particular target tissue (e.g., intradermal, intramuscular, etc.). Jet diameter and jet velocity, together with the injectant volume, guide the design of the NFJI cartridge and thus the required driving pressure. For device manufacturers, it is important to rapidly and accurately estimate the cartridge pressure and jet velocities to ensure devices can achieve the correct operational conditions and reach the target tissue. And thus, we seek to understand how cartridge design and fluid properties affect the jet velocity and pressure profiles in this process. Starting with experimental plunger displacement data, transient numerical simulations were performed to study the jet velocity profile and stagnation pressure profile. We observe that fluid viscosity and cartridge-plunger friction are the two most important considerations in tailoring the cartridge geometry to achieve a given jet velocity. Using empirical correlations for the pressure loss for a given cartridge geometry, we extend the applicability of an existing mathematical approach to accurately predict the jet hydrodynamics. By studying a range of cartridge geometries such as asymmetric sigmoid contractions, we see that the power of actuation sources and nozzle geometry can be tailored to deliver drugs with different fluid viscosities to the intradermal region.

Computational study of fluid flow in tapered orifices for needle-free injectors.

Transdermal drug delivery using spring-powered jet injection has been studied for several decades and continues to be highly sought after due to the advent of targeted needle-free techniques, especially for viscous and complex fluids. As such, this paper reports results from numerical simulations to study the role of fluid rheology and cartridge geometry on characteristics such as jet exit velocity, total pressure drop and boundary layer thickness, since these all factor in to jet stability and collimation. The numerical approach involves incompressible steady flow with turbulence modelling based on the system Reynolds number at the orifice (Re = ρdovj/µ). The results are experimentally validated for a given geometry over a wide range of Reynolds numbers (101 < Re < 104), and our results indicate a sharp decrease in dimensionless pressure drop (Eu = 2∆P/ρvj2) for Re < 102) and gradually approaching the inviscid limit at Re ≥ 104. By extending the study to non-Newtonian fluids, whose rheological profile is approximated by the Carreau model, we also elucidated the effect of different rheological parameters. Lastly by studying a range of nozzle geometries such as conical, sigmoid taper and multi-tier tapers, we observe that fluid acceleration suppresses the boundary layer growth, which indicates there may be optimal geometries for creating jets to target specific tissue depths.

In-vitro studies of jet injections.

In this study, needle-free jet injection dynamics were studied using homogeneous gelatin as model substrates. Whilst keeping nozzle properties such as orifice diameter (do) and ampoule volume (V) constant, we demonstrate the effect of standoff (s), confinement around the gel, storage modulus (G') of model gel and liquid viscosity (µ) on the penetration depth of the jet injection. High-speed imaging was used to observe the liquid jet propagation and dispersion dynamics, whilst a load cell was implemented to measure the impact force for different standoff distance and viscosity of the liquid. The different parameters considered showed significant effects on penetration depth, with non-linear dependence on standoff being the key result, which may have implications for future injector designs. Moreover, the effect of confinement serves as a caution of using gelatin substrates as a proxy for human tissue.

Characterization of skin blebs from intradermal jet injection: Ex-vivo studies.

This paper presents results from an ex-vivo study of intradermal jet injections, which is an attractive method to achieve both needle-free and fractional dose delivery of vaccines. Due to the fact that fluid properties of many novel therapeutics and vaccines can vary significantly, a key parameter for our study is the fluid viscosity, whilst the main focus is on determining the best correlation between the delivered volume and geometrical dimensions of the fluid deposit. For this we use a combination of top-view (skin wheal), underside (below the dermis), and cross-section (true skin bleb) perspectives and find that the top-view alone, as done in clinical practice, is insufficient to estimate the volume deposited in the dermis. Overall, the best correlation is found between the injection volume and cross-sectional diameter, however there is significant variation amongst the different fluids. For mean injection volumes of 60 µL the mean bleb diameter is ≈8 mm, with mean aspect ratio h¯/d=0.38, indicating the blebs are mostly oblate. However, the shape varies with viscosity and the higher viscosity does not spread laterally to the same degree as lower viscosity fluids. In addition, our high-speed video observations of the injection process, reveal some interesting dynamics of the jet injection method, and we modeled the bleb growth with an exponential saturation.

Characterization of jet injection efficiency with mouse cadavers.

Needle-free drug delivery is highly sought after for reduction in sharps waste, prevention of needle-stick injuries, and potential for improved drug dispersion and uptake. Whilst there is a wealth of literature on the array of different delivery methods, jet injection is proposed as the sole candidate for delivery of viscous fluids, which is especially relevant with the advent of DNA-based vaccines. The focus of this study was therefore to assess the role of viscosity and jet configuration (i.e. stand-off relative to the skin) upon injection efficiency for a fixed spring-loaded system (Bioject ID Pen). We performed this assessment in the context of mouse cadavers and found that the dominant factor in determining success rates was the time from euthanasia, which was taken as a proxy for the stiffness of the underlying tissue. For overall injection efficiency, ANOVA tests indicated that stiffness was highly significant (P <  < 0.001), stand-off was moderately significant (P < 0.1), and viscosity was insignificant. In contrast, both viscosity and standoff were found to be significant (P < 0.01) when evaluating the percentage delivered intradermally. Using high-resolution micro-computed tomography (µ-CT), we also determined the depth and overall dispersion pattern immediately after injection.

Peering through the flames: imaging techniques for reacting aluminum powders.

Combusting metals burn at high temperatures and emit high-intensity radiation in the visible spectrum, which can oversaturate regular imaging sensors and obscure the field of view. Filtering the luminescence can result in limited information and hinder thorough combustion characterization. A method for "seeing through the flames" of a highly luminescent aluminum powder reaction is presented using copper vapor laser (CVL) illumination, synchronized with a high-speed camera. A statistical comparison of combusting aluminum particle agglomerates imaged using various filtration techniques shows the effectiveness of the high-speed camera with a CVL diagnostic approach. When ignited by an electrically induced plasma, aluminum particles are entrained as solid agglomerates that rotate about their centers of mass and are surrounded by emitted, burning gases. The average agglomerate diameter appears to be 160 µm when viewed with standard illumination and a high-speed camera. However, a significantly reduced diameter of 50 µm is recorded when imaged with CVL illumination coupled with a high-speed camera and a 511 nm notch filter. These results indicate alternative imaging techniques are required to resolve the complexities of metal particle combustion.

Experimental and numerical characterization of the water flow in spacer-filled channels of spiral-wound membranes.

Micro-scale flow distribution in spacer-filled flow channels of spiral-wound membrane modules was determined with a particle image velocimetry system (PIV), aiming to elucidate the flow behaviour in spacer-filled flow channels. Two-dimensional water velocity fields were measured in a flow cell (representing the feed spacer-filled flow channel of a spiral wound reverse osmosis membrane module without permeate production) at several planes throughout the channel height. At linear flow velocities (volumetric flow rate per cross-section of the flow channel considering the channel porosity, also described as crossflow velocities) used in practice (0.074 and 0.163 m·s(-1)) the recorded flow was laminar with only slight unsteadiness in the upper velocity limit. At higher linear flow velocity (0.3 m·s(-1)) the flow was observed to be unsteady and with recirculation zones. Measurements made at different locations in the flow cell exhibited very similar flow patterns within all feed spacer mesh elements, thus revealing the same hydrodynamic conditions along the length of the flow channel. Three-dimensional (3-D) computational fluid dynamics simulations were performed using the same geometries and flow parameters as the experiments, based on steady laminar flow assumption. The numerical results were in good agreement (0.85-0.95 Bray-Curtis similarity) with the measured flow fields at linear velocities of 0.074 and 0.163 m·s(-1), thus supporting the use of model-based studies in the optimization of feed spacer geometries and operational conditions of spiral wound membrane systems.

Generation of ultra-sound during tape peeling.

We investigate the generation of the screeching sound commonly heard during tape peeling using synchronised high-speed video and audio acquisition. We determine the peak frequencies in the audio spectrum and, in addition to a peak frequency at the upper end of the audible range (around 20 kHz), we find an unexpected strong sound with a high-frequency far above the audible range, typically around 50 kHz. Using the corresponding video data, the origins of the key frequencies are confirmed as being due to the substructure "fracture" bands, which we herein observe in both high-speed continuous peeling motions and in the slip phases for stick-slip peeling motions.

Dynamic air layer on textured superhydrophobic surfaces.

We provide an experimental demonstration that a novel macroscopic, dynamic continuous air layer or plastron can be sustained indefinitely on textured superhydrophobic surfaces in air-supersaturated water by a natural gas influx mechanism. This type of plastron is an intermediate state between Leidenfrost vapor layers on superheated surfaces and the equilibrium Cassie-Baxter wetting state on textured superhydrophobic surfaces. We show that such a plastron can be sustained on the surface of a centimeter-sized superhydrophobic sphere immersed in heated water and variations of its dynamic behavior with air saturation of the water can be regulated by rapid changes of the water temperature. The simple experimental setup allows for quantification of the air flux into the plastron and identification of the air transport model of the plastron growth. Both the observed growth dynamics of such plastrons and millimeter-sized air bubbles seeded on the hydrophilic surface under identical air-supersaturated solution conditions are consistent with the predictions of a well-mixed gas transport model.

Foam-film-stabilized liquid bridge networks in evaporative lithography and wet granular matter.

Evaporative lithography using latex particle templates is a novel approach for the self-assembly of suspension-dispersed nanoparticles into ordered microwire networks. The phenomenon that drives the self-assembly process is the propagation of a network of interconnected liquid bridges between the template particles and the underlying substrate. With the aid of video microscopy, we demonstrate that these liquid bridges are in fact the border zone between the underlying substrate and foam films vertical to the substrate, which are formed during the evaporation of the liquid from the suspension. The stability of the foam films and thus the liquid bridge network stability are due to the presence of a small amount of surfactant in the evaporating solution. We show that the same type of foam-film-stabilized liquid bridge network can also propagate in 3D clusters of spherical particles, which has important implications for the understanding of wet granular matter.

Ionic enhancement of silica surface nanowear in electrolyte solutions.

The nanoscale wear and friction of silica and silicon nitride surfaces in aqueous electrolyte solutions were investigated by using sharp atomic force microscope (AFM) cantilever tips coated with silicon nitride. Measurements were carried out in aqueous solutions of varying pH and in monovalent and divalent cation chloride and nitrate solutions. The silica surface was shown to wear strongly in solutions of high pH (≈11.0), as expected, but the presence of simple cations, such as Cs(+) and Ca(2+), was shown to dramatically effect the wear depth and friction force for the silica surface. In the case of monovalent cations, their hydration enthalpies correlated well with the wear and friction. The weakest hydrated cation of Cs(+) showed the most significant enhancement of wear and friction. In the case of divalent cations, a complex dependence on the type of cation was found, where the type of anion was also seen to play an important role. The CaCl(2) solution showed the anomalous enhancement of wear depth and friction force, although the solution of Ca(NO(3))(2) did not. The present results obtained with an AFM tip were also compared with previous nanotribology studies of silica surfaces in electrolyte solutions, and possible molecular mechanisms as to why cations enhance the wear and friction were also discussed.

Stabilization of Leidenfrost vapour layer by textured superhydrophobic surfaces.

In 1756, Leidenfrost observed that water drops skittered on a sufficiently hot skillet, owing to levitation by an evaporative vapour film. Such films are stable only when the hot surface is above a critical temperature, and are a central phenomenon in boiling. In this so-called Leidenfrost regime, the low thermal conductivity of the vapour layer inhibits heat transfer between the hot surface and the liquid. When the temperature of the cooling surface drops below the critical temperature, the vapour film collapses and the system enters a nucleate-boiling regime, which can result in vapour explosions that are particularly detrimental in certain contexts, such as in nuclear power plants. The presence of these vapour films can also reduce liquid-solid drag. Here we show how vapour film collapse can be completely suppressed at textured superhydrophobic surfaces. At a smooth hydrophobic surface, the vapour film still collapses on cooling, albeit at a reduced critical temperature, and the system switches explosively to nucleate boiling. In contrast, at textured, superhydrophobic surfaces, the vapour layer gradually relaxes until the surface is completely cooled, without exhibiting a nucleate-boiling phase. This result demonstrates that topological texture on superhydrophobic materials is critical in stabilizing the vapour layer and thus in controlling--by heat transfer--the liquid-gas phase transition at hot surfaces. This concept can potentially be applied to control other phase transitions, such as ice or frost formation, and to the design of low-drag surfaces at which the vapour phase is stabilized in the grooves of textures without heating.

Drag reduction by Leidenfrost vapor layers.

We demonstrate and quantify a highly effective drag reduction technique that exploits the Leidenfrost effect to create a continuous and robust lubricating vapor layer on the surface of a heated solid sphere moving in a liquid. Using high-speed video, we show that such vapor layers can reduce the hydrodynamic drag by over 85%. These results appear to approach the ultimate limit of drag reduction possible by different methods based on gas-layer lubrication and can stimulate the development of related energy saving technologies.