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Spray drying is a technique that can be used to stabilize biopharmaceuticals, such as vaccines, within dry particles. Compared to liquid pharmaceutical products, dry powder has the potential to reduce costs associated with refrigerated storage and transportation. In this study, spray drying was investigated for processing an adjuvanted tuberculosis subunit vaccine, formulated as an oil-in-water nanoemulsion, into a dry powder composed of microparticles. Applying in-silico approaches to the development of formulation and processing conditions, successful encapsulation of the adjuvanted vaccine within amorphous microparticles was achieved in only one iteration, with high retention (>90%) of both the antigen and adjuvant system. Moisture-controlled stability studies on the powder were conducted over 26 months at temperatures up to 40 °C. Results showed that the powder was physically stable after 26 months of storage for all tested temperatures. Adjuvant system integrity was maintained at temperatures up to 25 °C after 26 months and after one month of storage at 40 °C. The spray-dried product demonstrated improved antigen thermostability when stored above refrigerated temperatures as compared to the liquid product. These results demonstrate the feasibility of spray drying as a method of encapsulating and stabilizing an adjuvanted vaccine.

We describe a new instrument and method for measuring compressed bulk density of respirable pharmaceutical powders under low compression pressure: the modulated compression tester. The instrument modulates compression and decompression steps, allowing scrutiny of the overall compression response of samples. Compared to established methods for the determination of density and related parameters for pharmaceutical powders, this instrument has the capability of measuring smaller samples. The relative humidity can also be controlled in the instrument (3 % to 95 % RH), allowing assessment of the effect of moisture on compression response. We have used the instrument to determine the compressed bulk density of Trehalose, Leucine, Trileucine, and Mannitol powders of varying crystalline and amorphous compositions and particle size and size distribution, demonstrating that the new modulated compression tester is suitable for low pressure (< 1200 kPa) density measurement of respirable powders (< 10 μm) and expensive active pharmaceutical ingredients available in limited quantities (typical sample mass requirement of < 100 mg). In addition, the modulation feature of the instrument allows the analysis of the transition from plastic to semi-elastic compression response. The outputs and features of this instrument are useful for formulation development, quality control measurements, discerning between different or similar powders due to differences in the compression response, and optimizing powder compression parameters for pharmaceutical applications.

Fluxgate magnetometers are important tools for geophysics and space physics, providing high-precision magnetic field measurements. Fluxgate magnetometer noise performance is typically limited by a ferromagnetic element that is periodically forced into magnetic saturation to modulate, or gate, the local magnetic field. The parameters that control the intrinsic magnetic noise of the ferromagnetic element remain poorly understood. Much of the basic research into producing low-noise fluxgate sensors was completed in the 1960s for military purposes and was never publicly released. Many modern fluxgates depend on legacy Infinetics S1000 ring cores that have been out of production since 1996 and for which there is no published manufacturing process. We present a manufacturing approach that can consistently produce fluxgate ring cores with a noise of ∼6–11 pT per square root hertz – comparable to many of the legacy Infinetics ring cores used worldwide today. As a result, we demonstrate that we have developed the capacity to produce the low-noise ring cores essential for high-quality, science-grade fluxgate instrumentation. This work has also revealed potential avenues for further improving performance, and further research into low-noise magnetic materials and fluxgate magnetometer sensors is underway.

Protection against primarily respiratory infectious diseases, such as tuberculosis (TB), can likely be enhanced through mucosal immunization induced by direct delivery of vaccines to the nose or lungs. A thermostable inhalable dry powder vaccine offers further advantages, such as independence from the cold chain. In this study, we investigate the formulation for a stable, inhalable dry powder version of ID93 + GLA-SE, an adjuvanted subunit TB vaccine candidate, containing recombinant fusion protein ID93 and glucopyranosyl lipid A (GLA) in a squalene emulsion (SE) as an adjuvant system, via spray drying. The addition of leucine (20% w/w), pullulan (10%, 20% w/w), and trileucine (3%, 6% w/w) as dispersibility enhancers was investigated with trehalose as a stabilizing agent. Particle morphology and solid state, nanoemulsion droplet size, squalene and GLA content, ID93 presence, and aerosol performance were assessed for each formulation. The results showed that the addition of leucine improved aerosol performance, but increased aggregation of the emulsion droplets was demonstrated on reconstitution. Addition of pullulan preserved emulsion droplet size; however, the antigen could not be detected after reconstitution. The trehalose-trileucine excipient formulations successfully stabilized the adjuvant system, with evidence indicating retention of the antigen, in an inhalable dry powder format suitable for lung delivery.

The Experimental Albertan satellite #1 (Ex-Alta 1) was a three-unit cube satellite (CubeSat) developed at the University of Alberta (UAlberta). As the first ‘made in Alberta’ spacecraft, the Ex-Alta 1 CubeSat was the Canadian contribution to the international QB50 CubeSat constellation mission ( www.qb50.eu ). Ex-Alta 1’s mission incorporated four science objectives, two technical objectives, and one educational outreach objective. These are reviewed in the context of the Ex-Alta 1 mission design, as well as future CubeSat constellation missions that may follow demonstration missions such as Ex-Alta 1 and the experiences of the QB50 project. In support of its objectives, Ex-Alta 1 flew the multi-needle Langmuir probe (m-NLP) QB50 standardized payload, a UAlberta developed miniaturized digital fluxgate magnetometer (DFGM) mounted on a two-element articulated deployable boom, a radiation dosimeter from Teledyne, and an open source onboard computer (OBC) developed at UAlberta. Ex-Alta 1 was released by a NanoRacks deployer from the International Space Station on May 26, 2017, and commanded and controlled from a ground-station developed and operated at UAlberta. Ex-Alta 1 operated continuously throughout its mission until it burned up in the atmosphere on November 14, 2018. The last two-way contact occurred on that day at 07:49:29 UTC, when the spacecraft reported an onboard temperature of 47 °C in eclipse at an altitude of 152 km and which marked the effective end of the mission. This paper provides an overview of the Ex-Alta 1 mission, its development, the spacecraft and mission design, and reports preliminary results from the payload focusing on the DFGM instrument. We also report briefly on related education and outreach activities, including the development and delivery of curriculum-targeted and CubeSat focused classroom sessions inspired by the Ex-Alta 1 mission to school pupils in Alberta.

The simultaneous evaporation and condensation of multiple volatile components from multicomponent aerosol droplets leads to changes in droplet size, composition and temperature. Measurements and models that capture and predict these dynamic aerosol processes are key to understanding aerosol microphysics in a broad range of contexts. We report measurements of the evaporation kinetics of droplets (initially ∼25 μm radius) formed from mixtures of ethanol and water levitated within a electrodynamic balance over timescales spanning 500 ms to 6 s. Measurements of evaporation into a gas phase of varied relative humidity and temperature are shown to compare well with predictions from a numerical model. We show that water condensation from the gas phase can occur concurrently with ethanol evaporation from aqueous-ethanol droplets. Indeed, water can condense so rapidly during the evaporation of a pure ethanol droplet in a humid environment, driven by the evaporative cooling the droplet experiences, that the droplet becomes pure water within 0.4 s.

A proof-of-concept hybrid magnetometer is presented, which simultaneously operates as both a fluxgate and a search coil, allowing it to sense the magnetic field from DC to 2 kHz using a single sensor. Historically, such measurements would normally require two dedicated instruments, and each would typically require deployment on its own dedicated boom as the instruments mutually interfere. A racetrack fluxgate core combined with a long solenoidal sense winding is shown to be moderately effective as a search coil magnetometer, and the search coil effect can be captured without introducing significant hardware complexity beyond what is already present in a typical fluxgate instrument. Several methods of optimising the search coil action of the hybrid instrument are compared with the best method providing sensitivity and noise performance between comparably sized traditional air-core and solid-core search coil instruments. This hybrid sensor topology should miniaturise to platforms such as CubeSats for which multiple boom-mounted instruments are generally impractical, so a single hybrid instrument providing modest, but scientifically useful, sensitivity from DC to kHz frequencies would be beneficial.

The Publisher regrets having introduced the following errors into the article when performing proof corrections.

Purpose: Evaporation and particle formation from multi-solvent microdroplets containing solid excipients pertaining to spray-drying of therapeutic agents intended for lung delivery were studied. Various water and ethanol co-solvent systems containing a variety of actives and excipients (beclomethasone, budesonide, leucine, and trehalose) were considered. Methods: Numerical methods were used to predict the droplet evaporation rates and internal solute transfers, and their results verified and compared with results from two separate experimental setups. In particular, an electrodynamic balance was used to measure the evaporation rates of multicomponent droplets and a monodisperse droplet chain setup collected dried microparticles for further analytical investigations and ultramicroscopy. Results: The numerical results are used to explain the different particle morphologies dried from solutions at different co-solvent compositions. The obtained numerical data clearly show that the two parameters controlling the general morphology of a dried particle, namely the Péclet number and the degree of saturation, can change with time in a multi-solvent droplet. This fact complicates product development for such systems. However, this additional complexity vanishes at what we define as the iso-compositional point, which occurs when the solvent ratios and other composition-dependent properties of the droplet remain constant during evaporation, similar to the azeotrope of such systems during distillation. Conclusions: Numerical and experimental analysis of multi-solvent systems indicate that spray-drying near the iso-compositional ratio simplifies the design and process development of such systems.

Fluxgate magnetometers are important tools for geophysics and space physics providing high precision magnetic field measurements. Fluxgate magnetometer noise performance is typically limited by a ferromagnetic element that is periodically forced into magnetic saturation to modulate, or gate, the local magnetic field. The parameters that control the intrinsic magnetic noise of the ferromagnetic element remain poorly understood. Much of the basic research into producing low-noise fluxgate sensors was completed in the 1960s for military purposes and was never publicly released. Many modern fluxgates depend on legacy Infinetics S1000 ring-cores that have been out of production since 1996 and for which there is no published manufacturing process. We present a manufacturing approach that can consistently produce fluxgate ring-cores with a noise of ∼6–11 pT per square root Hertz – comparable to many of the legacy Infinetics ring-cores used worldwide today. As a result, we demonstrate that we have developed the capacity to produce the low-noise ring-cores essential for high-quality, science-grade fluxgate instrumentation. This work has also revealed potential avenues for further improving performance, and further research into low-noise magnetic materials and fluxgate magnetometer sensors is underway.

A new shadowgraphic imaging method and an associated instrument for analyzing the physical stability of pharmaceutical suspensions are introduced in this paper. The new suspension tester consists mainly of a high-resolution camera that takes sequential shadowgraphic images of emulsions or suspensions and a 2D collimated LED for simultaneous whole-sample illumination in bright field. A built-in ultrasonic bath provides controlled initial agitation to the samples of interest. Sequential images acquired by the experimental setup were used to derive normalized transmission profiles from which an instability index was developed for quantitative stability comparison between samples. Instrument performance was verified by measuring the stability of a series of oil-in-water emulsions prepared with surfactant mixtures of different ratios. The new instrument correctly determined the required hydrophilic-lipophilic balance for sunflower oil to be 7.0. The stability of a pressurized suspension of spray dried lipid (DSPC) particles was monitored for 5 days after propellant filling. Although stable for the first 24 h, the lipid suspension was found to decrease in stability from day 1 to day 4. Morphological and spectroscopic analysis revealed that the suspended DSPC particles had reformed into large thin sheets of lipid, thereby causing the gradual stability decrease during the aging study. The effects of initial agitation on the stability of suspensions were demonstrated by agitating a suspension of micronized fluticasone propionate in propellant using a wrist action shaker and an ultrasonic bath respectively. A significant improvement of suspension stability was achieved by replacing the wrist action shaker method with ultrasonic agitation. Simultaneous illumination of the complete suspension, a high image acquisition rate, and controlled initial agitation are features that make this new suspension tester a suitable and more reliable instrument for investigating the stability of pressurized pharmaceutical suspensions.

A new macro-Raman system equipped with a motorized translational sample stage and low-frequency shift capabilities was developed for bulk composition and homogeneity analysis of multi-component pharmaceutical powders. Different sampling methods including single spot and scanning measurement were compared. It was found that increasing sample volumes significantly improved the precision of quantitative composition analysis, especially for poorly mixed powders. The multi-pass cavity of the macro-Raman system increased effective sample volumes by 20 times from the sample volume defined by the collection optics, i.e., from 0.02μL to about 0.4μL. A stochastic model simulating the random sampling process of polydisperse microparticles was used to predict the sampling errors for a specific sample volume. Comparison of fluticasone propionate mass fractions of the commercial products Flixotide® 250 and Seretide® 500 simulated for different sampling volumes with experimentally measured compositions verified that the effective sample volume of a single point macro-Raman measurement in the multi-pass cavity of this instrument was between 0.3μL and 0.5μL. The macro-Raman system was also successfully used for blend uniformity analysis. It was concluded that demixing occurred in the binary mixture of l-leucine and d-mannitol from the observation that the sampling errors indicated by the standard deviations of measured leucine mass fractions increased during mixing, and the standard deviation values were all larger than the theoretical lower limit determined by the simulation. Since sample volume was shown to have a significant impact on measured homogeneity characteristics, it was concluded that powder homogeneity analysis results, i.e., the mean of individual test results and absolute and relative standard deviations, must be presented together with the effective sample volumes of the applied testing techniques for any measurement of powder homogeneity to be fully meaningful.

Excellent results from a reentry campaign developed in 2014 in Ecuador have proven the benefits of implementing new drilling technologies for reentry drilling. In this campaign, rotary steerable systems (RSS) were drivers for directional control, and logging-while-drilling tools acquired critical information while drilling. Together these tools open up possibilities for giving new life to aging oil fields and to produce from unexploited drainage zones by enabling reentry drilling. Drilling the reentry wells in Ecuador involve using the 9.625-in. casing to open an 8.5-in. window and drilling to the geological objectives in just one hole section. For this purpose, the combination of a point-the-bit RSS system, a multi depth laterolog resistivity tool with high-resolution images, and a sourceless tool that delivers density, porosity, spectroscopy, and sigma provided 100% of directional control while acquiring comprehensive formation evaluation information in real time. Because of the casing configuration in most of the wells in Ecuador, the most commonly used reentry option is to make the window in the 9.625-in. casing and drill the 8.5-in. hole section from the Tena formation (claystone) and Napo formation (several intercalations of claystone, limestone, unstable shales, and pay zones of sandstone). This particular configuration of formation layers is a challenge for directional control and for running wireline logs. The use of the bottomhole assembly (BHA) with the RSS and tools described above enables successfully drilling the reentries in just one 8.5-in. run, reaching the geological targets with 100% directional control, in spite of the complexity of the well trajectory, and avoiding risks such as packoff, geometrical sticking, and differential sticking. The smoother well profile obtained by use of the point-the-bit RSS and verified through the LWD measurements guaranteed the successful run of the 7-in. liner in all of the reentries drilled in the campaign. Reentry wells provide operators with the opportunity to have new production at less than half the cost of a completely new well and in less than half of the total execution time. Building on this reentry campaign, continued reentry drilling will be improved with implementation of the new generation of hybrid RSS (push - and point-the-bit RSS), which will enable drilling engineers to plan trajectories to deliver greater dogleg severities (DLS). This will, in turn, enable developing deeper reentries, further reducing cost and execution time.

Difficulty in making low noise magnetic measurements is a significant challenge to the use of cube-satellite (CubeSat) platforms for scientific constellation class missions to study the magnetosphere. Sufficient resolution is required to resolve three-dimensional spatiotemporal structures of the magnetic field variations accompanying both waves and current systems of the nonuniform plasmas controlling dynamic magnetosphere-ionosphere coupling. This paper describes the design, validation, and test of a flight-ready, miniature, low-mass, low-power, and low-magnetic noise boom-mounted fluxgate magnetometer for CubeSat applications. The miniature instrument achieves a magnetic noise floor of 150–200 pT/√Hz at 1 Hz, consumes 400 mW of power, has a mass of 121 g (sensor and boom), stows on the hull, and deploys on a 60 cm boom from a three-unit CubeSat reducing the noise from the onboard reaction wheel to less than 1.5 nT at the sensor. The instrument's capabilities will be demonstrated and validated in space in late 2016 following the launch of the University of Alberta Ex-Alta 1 CubeSat, part of the QB50 constellation mission. We illustrate the potential scientific returns and utility of using a CubeSats carrying such fluxgate magnetometers to constitute a magnetospheric constellation using example data from the low-Earth orbit European Space Agency Swarm mission. Swarm data reveal significant changes in the spatiotemporal characteristics of the magnetic fields in the coupled magnetosphere-ionosphere system, even when the spacecraft are separated by only approximately 10 s along track and approximately 1.4° in longitude.

A new method for making superhydrophobic (SH) paper based on spraying a nanocomposite film is developed. Furthermore, manipulating the wetting characteristics of SH paper has been demonstrated through a new method, i.e. printing solid grey patterns of different intensities with simple printing technology (home or office grade ink-jet and laser printers). It has been found that for a range of ink intensities (0-85%), water drop mobility can be changed at a different rate (almost independently) from repellency. The repellency of water decreases minimally up to 85% ink intensity with a sharp decrease up to 100% ink intensity. Drop mobility remains constant up to 30% ink intensity with a steady decrease up to 100% ink intensity. It was observed that using ink-jet or laser printing would yield different results for the change of mobility or repellency with higher amounts of ink/toner used. Being able to achieve almost independent control of water drop mobility over water drop repellency on SH paper would allow inexpensive lab-on-paper devices to be used for sampling, mixing and transport of liquids.

Digital microfluidics depends on efficient movement of individual drops for a variety of tasks, e.g. reagent delivery, mixing, sampling, etc. Superhydrophobic (SH) coatings generally show high repellency and low adhesion for a variety of liquids. Therefore, SH coatings can provide for an efficient drop delivery and hence low energy requirements for a fluidic chip. However, wide application of such coatings is hampered by fragile nature of such coatings to date. A new SH coating is developed that addresses the fragility challenge of such coatings. It is based on application of nanoparticles to fluoropolymers. The mechanical stability, wear resistance and durability under prolonged liquid exposure of this new coating is discussed. It is shown that the new SH coating can maintain high contact angles, low contact angle hysteresis needed for drop mobility under adverse conditions/application of digital microfluidic devices. The developed SH coating can also be sprayed onto various surfaces, including glass used in traditional lab-on-chip (LOC) devices, or even paper for enabling novel Lap-on-paper (LOP) devices.Copyright © 2011 by ASME