Fundamental Studies of the Drying of Complex Multiphase Aerosol Droplets

Aerosols consist of liquid droplets or solid particles dispersed within a gas phase (typically air). Such droplets and particles can range in size from nanometres to millimetres. Aerosols are widely used to treat asthma via inhalation of therapeutic drugs and, in principle, enable the treatment of systemic diseases and the delivery of vaccines. They also find widespread application in consumer and agrochemical products, are prevalent in the atmosphere as particulate matter (PM) affecting air quality and human health, and are vehicles for the transmission of respiratory pathogens such as SARS-CoV-2, the virus responsible for COVID-19, and the bacterium responsible for tuberculosis. In all cases, the dispersed phase is dynamic, changing rapidly in moisture content and particle/droplet size during transport in the atmosphere, and often interchanging phase. Further complexity arises in most real-world systems: the droplets/particles can be multiphase consisting, for example, of dispersed solid nanoparticles within a liquid host droplet. Understanding such complex multiphase systems is crucial for designing pharmaceutical formulations to deliver drugs to the lungs, controlling the drying kinetics and engineered final particle structure in industrial processes such as spray-drying, and rationalising the airborne survival of viruses and bacteria in exhaled respiratory aerosol. Despite the importance of this broad range of problems, there are very few relevant studies of the dynamic transformation of aerosol droplets containing dispersed nanoparticles.

We will integrate complementary expertise at the Universities of Bristol, Manchester and Sheffield to investigate the many physicochemical parameters that control the stability and structure of dried microparticles formed from solution aerosol droplets containing nanoparticles. The Bristol team has developed an array of state-of-the-art experimental methods to study the evaporation and drying of aerosol droplets in real time by monitoring their evolving size, composition, phase state and structure, while also capturing the final dried microparticles for post-mortem analysis. At Manchester, the team has extensive modelling capabilities to simulate the drying kinetics of evaporating aerosol droplets to account for changes in fluid viscosity, composition and temperature. The Sheffield team has developed synthetic routes to produce tailored polymer nanoparticles of varying size, shape, and surface chemistry in water, polar solvents or non-polar solvents, including the bio-inspired synthesis of several virus mimics. This combined expertise will enable us to examine a wide range of nanoparticles of selected size and character at known concentrations within host liquid droplets. Such nanoparticle-loaded droplets will be generated with reproducible size in a controlled environment of known temperature and gas phase composition, and their evaporation will be studied in real time (on timescales ranging from milliseconds to hours) through to the point of solidification. The structure of the final dried microparticles will be examined by scanning electron microscopy. These experiments will be compared with model predictions of evolving particle size and composition, and the structure and moisture stability of the microparticles will be evaluated. Ultimately, these observations will enable us to develop a framework for predicting how the various microphysical processes that occur during drying and the character of the nanoparticles within the host droplets affect the final microparticles.

Working closely with industrial partners with expertise in the pharmaceutical, consumer product and aerobiology sectors, we will establish robust physical principles for understanding the dynamics occurring in aerosols of complex composition and phase in domains extending from drug delivery to the lungs to spray-drying of commercial products to mechanisms of disease transmission.