Microgravity effects on nonequilibrium melt processing of neodymium titanate: thermophysical properties, atomic structure, glass formation and crystallization.

The relationships between materials processing and structure can vary between terrestrial and reduced gravity environments. As one case study, we compare the nonequilibrium melt processing of a rare-earth titanate, nominally 83TiO2-17Nd2O3, and the structure of its glassy and crystalline products. Density and thermal expansion for the liquid, supercooled liquid, and glass are measured over 300-1850 °C using the Electrostatic Levitation Furnace (ELF) in microgravity, and two replicate density measurements were reproducible to within 0.4%. Cooling rates in ELF are 40-110 °C s-1 lower than those in a terrestrial aerodynamic levitator due to the absence of forced convection. X-ray/neutron total scattering and Raman spectroscopy indicate that glasses processed on Earth and in microgravity exhibit similar atomic structures, with only subtle differences that are consistent with compositional variations of ~2 mol. % Nd2O3. The glass atomic network contains a mixture of corner- and edge-sharing Ti-O polyhedra, and the fraction of edge-sharing arrangements decreases with increasing Nd2O3 content. X-ray tomography and electron microscopy of crystalline products reveal substantial differences in microstructure, grain size, and crystalline phases, which arise from differences in the melt processes.

In situ temperature measurements in sooting methane/air flames using synchrotron x-ray fluorescence of seeded krypton atoms.

Synchrotron x-ray fluorescence has been used to measure temperatures in optically dense gases where traditional methods would fail. These data provide a benchmark for stringent tests of computational fluid dynamics models for complex systems where physical and chemical processes are intimately linked. The experiments measured krypton number densities in a sooting, atmospheric pressure, nonpremixed coflow flame that is widely used in combustion research. The experiments not only form targets for the models, but the simulations also identify potential sources of uncertainties in the measurements, allowing for future improvements.

Time-resolved 3D imaging of two-phase fluid flow inside a steel fuel injector using synchrotron X-ray tomography.

The multiphase flow inside a diesel injection nozzle is imaged using synchrotron X-rays from the Advanced Photon Source at Argonne National Laboratory. Through acquisitions performed at several viewing angles and subsequent tomographic reconstruction, in-situ 3D visualization is achieved for the first time inside a steel injector at engine-like operating conditions. The morphology of the internal flow reveals strong flow separation and vapor-filled cavities (cavitation), the degree of which correlates with the nozzle's asymmetric inlet corner profile. Micron-scale surface features, which are artifacts of manufacturing, are shown to influence the morphology of the resulting liquid-gas interface. The data obtained at 0.1 ms time resolution exposes transient flow features and the flow development timescales are shown to be correlated with in-situ imaging of the fuel injector's hydraulically-actuated valve (needle). As more than 98.5% of the X-ray photon flux is attenuated within the steel injector body itself, we are posed with a unique challenge for imaging the flow within. Time-resolved imaging under these low-light conditions is achieved by exploiting both the refractive and absorptive properties of X-ray photons. The data-processing strategy converted these images with a signal-to-noise ratio of ~ 10 into a meaningful dataset for understanding internal flow and cavitation in a nozzle of diameter 200 µm enclosed within 1-2 millimeters of steel.

Drug distribution transients in solution and suspension-based pressurised metered dose inhaler sprays.

This paper presents in situ time-resolved drug mass fraction measurements in pressurised metered dose inhaler (PMDI) sprays, using a novel combination of synchrotron X-ray fluorescence and scattering. Equivalent suspension and solution formulations of ipratropium bromide in HFA-134a propellant were considered. Measurements were made both inside the expansion chamber behind the nozzle orifice, and in the first few millimeters of the spray where droplet and particle formation occur. We observed a consistent spike in drug mass fraction at the beginning of the spray when the first fluid exits the nozzle orifice. Approximately 20% of the total delivered dose exits the nozzle in the first 0.1 s of the spray. The drug mass fraction in the droplets immediately upon exiting the nozzle peaked at approximately 50% of the canister mass fraction, asymptoting to approximately 20% of the canister concentration. The effect is due to a change in the drug mass fraction inside the droplets, rather than changes in droplet size or distribution. The transient was found to originate inside the expansion chamber. We propose that this effect may be a major contributor to low delivery efficiency in PMDIs, and have important implications for oropharyngeal deposition and inhalation technique. This highlights the importance of expansion chamber and nozzle design on the structure of PMDI sprays, and indicates areas of focus that may lead to improvement in drug delivery outcomes.

High-speed, two-dimensional synchrotron white-beam x-ray radiography of spray breakup and atomization.

High-speed, two-dimensional synchrotron x-ray radiography and phase-contrast imaging are demonstrated in propulsion sprays. Measurements are performed at the 7-BM beamline at the Advanced Photon Source user facility at Argonne National Laboratory using a recently developed broadband x-ray white beam. This novel enhancement allows for high speed, high fidelity x-ray imaging for the community at large. Quantitative path-integrated liquid distributions and spatio-temporal dynamics of the sprays were imaged with a LuAG:Ce scintillator optically coupled to a high-speed CMOS camera. Images are collected with a microscope objective at frame rates of 20 kHz and with a macro lens at 120 kHz, achieving spatial resolutions of 12 µm and 65 µm, respectively. Imaging with and without potassium iodide (KI) as a contrast-enhancing agent is compared, and the effects of broadband attenuation and spatial beam characteristics are determined through modeling and experimental calibration. In addition, phase contrast is used to differentiate liquid streams with varying concentrations of KI. The experimental approach is applied to different spray conditions, including quantitative measurements of mass distribution during primary atomization and qualitative visualization of turbulent binary fluid mixing.

Revealing pMDI Spray Initial Conditions: Flashing, Atomisation and the Effect of Ethanol.

PURPOSE: Sprays from pressurised metered-dose inhalers are produced by a transient discharge of a multiphase mixture. Small length and short time scales have made the investigation of the governing processes difficult. Consequently, a deep understanding of the physical processes that govern atomisation and drug particle formation has been elusive. METHODS: X-ray phase contrast imaging and quantitative radiography were used to reveal the internal flow structure and measure the time-variant nozzle exit mass density of 50 µL metered sprays of HFA134a, with and without ethanol cosolvent. Internal flow patterns were imaged at a magnification of 194 pixels/mm and 7759 frames per second with 150 ps temporal resolution. Spray projected mass was measured with temporal resolution of 1 ms and spatial resolution 6 µm × 5 µm. RESULTS: The flow upstream of the nozzle comprised large volumes of vapour at all times throughout the injection. The inclusion of ethanol prevented bubble coalescence, altering the internal flow structure and discharge. Radiography measurements confirmed that the nozzle exit area is dominantly occupied by vapour, with a peak liquid volume fraction of 13%. CONCLUSION: Vapour generation in pMDIs occurs upstream of the sump, and the dominant volume component in the nozzle exit orifice is vapour at all times in the injection. The flow in ethanol-containing pMDIs has a bubbly structure resulting in a comparatively stable discharge, whereas the binary structure of propellant-only flows results in unsteady discharge and the production of unrespirable liquid masses.

Insights into Spray Development from Metered-Dose Inhalers Through Quantitative X-ray Radiography.

PURPOSE: Typical methods to study pMDI sprays employ particle sizing or visible light diagnostics, which suffer in regions of high spray density. X-ray techniques can be applied to pharmaceutical sprays to obtain information unattainable by conventional particle sizing and light-based techniques. METHODS: We present a technique for obtaining quantitative measurements of spray density in pMDI sprays. A monochromatic focused X-ray beam was used to perform quantitative radiography measurements in the near-nozzle region and plume of HFA-propelled sprays. RESULTS: Measurements were obtained with a temporal resolution of 0.184 ms and spatial resolution of 5 µm. Steady flow conditions were reached after around 30 ms for the formulations examined with the spray device used. Spray evolution was affected by the inclusion of ethanol in the formulation and unaffected by the inclusion of 0.1% drug by weight. Estimation of the nozzle exit density showed that vapour is likely to dominate the flow leaving the inhaler nozzle during steady flow. CONCLUSIONS: Quantitative measurements in pMDI sprays allow the determination of nozzle exit conditions that are difficult to obtain experimentally by other means. Measurements of these nozzle exit conditions can improve understanding of the atomization mechanisms responsible for pMDI spray droplet and particle formation.

Temporally and Spatially Resolved x-ray Fluorescence Measurements of in-situ Drug Concentration in Metered-Dose Inhaler Sprays.

PURPOSE: Drug concentration measurements in MDI sprays are typically performed using particle filtration or laser scattering. These techniques are ineffective in proximity to the nozzle, making it difficult to determine how factors such as nozzle design will affect the precipitation of co-solvent droplets in solution-based MDIs, and the final particle distribution. METHODS: In optical measurements, scattering from the constituents is difficult to separate. We present a novel technique to directly measure drug distribution. A focused x-ray beam was used to stimulate x-ray fluorescence from the bromine in a solution containing 85% HFA, 15% ethanol co-solvent, and 1 [Formula: see text] / [Formula: see text] IPBr. RESULTS: Instantaneous concentration measurements were obtained with 1 ms temporal resolution and 5 [Formula: see text] spatial resolution, providing information in a region that is inaccessible to many other diagnostics. The drug remains homogeneously mixed over time, but was found to be higher at the centerline than at the periphery. This may have implications for oropharyngeal deposition in vivo. CONCLUSIONS: Measurements in the dynamic, turbulent region of MDIs allow us to understand the physical links between formulation, inspiration, and geometry on final particle size and distribution. This will ultimately lead to a better understanding of how MDI design can be improved to enhance respirable fraction.

Quantitative time-averaged gas and liquid distributions using x-ray fluorescence and radiography in atomizing sprays.

A method for quantitative measurements of gas and liquid distributions is demonstrated using simultaneous x-ray fluorescence and radiography of both phases in an atomizing coaxial spray. Synchrotron radiation at 10.1 keV from the Advanced Photon Source at Argonne National Laboratory is used for x-ray fluorescence of argon gas and two tracer elements seeded into the liquid stream. Simultaneous time-resolved x-ray radiography combined with time-averaged dual-tracer fluorescence measurements enabled corrections for reabsorption of x-ray fluorescence photons for accurate, line-of-sight averaged measurements of the distribution of the gas and liquid phases originating from the atomizing nozzle.

Quantitative measurement of binary liquid distributions using multiple-tracer x-ray fluorescence and radiography.

The complex geometry and large index-of-refraction gradients that occur near the point of impingement of binary liquid jets present a challenging environment for optical interrogation. A simultaneous quadruple-tracer x-ray fluorescence and line-of-sight radiography technique is proposed as a means of distinguishing and quantifying individual liquid component distributions prior to, during, and after jet impact. Two different pairs of fluorescence tracers are seeded into each liquid stream to maximize their attenuation ratio for reabsorption correction and differentiation of the two fluids during mixing. This approach for instantaneous correction of x-ray fluorescence reabsorption is compared with a more time-intensive approach of using stereographic reconstruction of x-ray attenuation along multiple lines of sight. The proposed methodology addresses the need for a quantitative measurement technique capable of interrogating optically complex, near-field liquid distributions in many mixing systems of practical interest involving two or more liquid streams.

Measurements of spatial variations in response of ionization chambers.

Measurements of the spatial variations in the response of three ionization chamber (IC) designs were tested as a function of chamber bias voltage, incident X-ray flux and fill gas. Two components of spatial variation are seen. When the ionization chambers are near saturation, spatial variations exist that are tied to the chamber geometry. While the response of some chambers is relatively flat, others show significant variation across the IC. These variations appear to be inherent in the response of each IC at saturation. When the chamber is far from saturation, large spatial variations in response are present when N(2) is used as a fill gas, but not when ambient air is used as a fill gas. These appear to be tied to space charge effects.