Arkadiusz K. Kuczaj

Homogeneous nucleation enables aerosol generation from supersaturated vapors. Despite extensive vapor-phase nucleation research, quantitative data on nucleation rates for specific substances and their mixtures remain limited. This study investigates the homogeneous nucleation of glycerol and propylene glycol using a laminar flow diffusion chamber at three saturator temperatures. Experimental nucleation rates were derived from the measured particle concentrations and normalized using computational fluid dynamics modeling based on the classical nucleation theory. Simulations were employed to resolve temperature and saturation ratio profiles, enabling accurate reconstruction of nucleation isotherms. Findings agree with prior diffusion cloud chamber studies and were further evaluated using Hale plot scaling. Results show that the nucleation of propylene glycol occurs at significantly lower supersaturation and smaller temperature gradients between the saturator and condenser compared to glycerol. Critical cluster sizes were determined both from the Kelvin equation and from the slopes of nucleation isotherms, revealing that glycerol forms smaller critical clusters (0.72–0.97 nm) than propylene glycol (1.3–1.5 nm). These findings align with previously reported results obtained using diffusion cloud chambers and confirm the influence of molecular structure on nucleation behavior. This study provides valuable insight into the fundamental nucleation mechanisms of polyhydroxylated compounds and supports the design and optimization of aerosol-forming processes in practical applications.

Introduction: For in vivo inhalation studies, aerosol dosimetry links aerosol exposure and deposited dose within the respiratory tract. Aerosol dosimetry programs like the Multiple Path Particle Deposition model utilize respiratory tract geometry, respiratory physiology, and aerosol properties to predict particle deposition within the respiratory tract. A challenge to wider use of these dosimetry programs for in vivo inhalation studies is the lack of species-specific or strain specific respiratory tract anatomy, and in some cases, strain specific respiratory physiology data. The objective of this work was to develop aerosol dosimetry predictions for the in vivo human disease models of chronic obstructive pulmonary disease (COPD; C57BL/6 mice) cardiovascular disease (CVD; ApoE-/- mice), and lung cancer (AJ mice) using the Multiple Path Particle Deposition dosimetry model. Methods: Microcomputed tomography derived tracheobronchial geometry data were combined with available pulmonary geometry data for C57BL/6, ApoE-/-, and AJ mice and incorporated into the Multiple Path Particle Deposition dosimetry model. Mouse strain specific respiratory physiology literature values were used as input into the Multiple Path Particle Deposition dosimetry model. Results: The resulting particle deposition predictions compared well with the very limited strain specific experimental particle deposition data. Since multiple tracheobronchial geometries and thus pulmonary anatomies were used for C57BL/6 and ApoE-/- mice, an estimate of intrastrain variability in predicted particle deposition was obtained. Discussion and Conclusions: The intrastrain variability in predicted particle deposition for C57BL/6 and ApoE-/- mice was always smaller in the tracheobronchial compared to pulmonary airways. The differences in reported respiratory physiology values for C57BL/6 mice resulted in greater intrastrain variability in predicted particle deposition than observed with the different tracheobronchial geometries and pulmonary anatomies. These mouse strain specific aerosol dosimetry predictions can provide insight into the delivered dose to specific respiratory tract regions that can be correlated with in vivo endpoints.

The capillary aerosol generator (CAG) is operated with the principal of thermal liquid evaporation through heating of e-liquid in the initial phase, followed by nucleation and condensation regulated through a mixture of airflow to generate aerosols, such as in an electronic cigarette (EC). The CAG is particularly useful in generating aerosols of large volumes in a continuous manner, for instances such as in vivo inhalation toxicology studies, where usage of ECs is not feasible. The thermal effects of generating aerosol from the CAG are similar in terms of temperature applied in an EC, thus allowing investigators to assess the vapors of e-liquids at scale and reproducibility. As the operation of the CAG allows users to control critical parameters such as the flow rate of e-liquid, heating temperatures and dilution air flows, it allows investigators to test various e-liquid formulations in a well-controlled device. Properties, such as aerosol particle size, are demonstrated to be regulated with the air flow rate with respect to the e-liquid flow and e-liquid composition. The CAG, however, is limited in assessing common EC-related issues, such as overheating of its elements. We seek to demonstrate that the CAG can generate aerosol that is reproducible and continuous, by assessing the chemical and physical aerosol characteristics with a chosen e-liquid formulation. The protocol describes the operating parameters of liquid flow rate, dilution air-flow rates and operating procedures needing to optimize the aerosol concentration and particle size required for an in vivo toxicology study. Presenting the representative results from the protocol and discussing the challenges and applications of working with a CAG, we demonstrate that CAG can be used in a reproducible fashion. The technology and protocol, that has been developed from prior work, serve as a foundation for future innovations for laboratory-controlled aerosol generation investigations.

Aerosol dosimetry estimates for mouse strains used as models for human disease are not available, primarily because of the lack of tracheobronchial airway morphometry data. By using micro‐CT scans of in‐situ prepared lung casts, tracheobronchial airway morphometry for four strains of mice were obtained: Balb/c, AJ, C57BL/6, and Apoe^−/−. The automated tracheobronchial airway morphometry algorithms for airway length and diameter were successfully verified against previously published manual and automated tracheobronchial airway morphometry data derived from two identical in‐situ Balb/c mouse lung casts. There was also excellent agreement in tracheobronchial airway length and diameter between the automated and manual airway data for the AJ, C57BL/6, and Apoe^−/− mice. Differences in branch angle measurements were partially due to the differences in definition between the automated algorithms and manual morphometry techniques. Unlike the manual airway morphometry techniques, the automated algorithms were able to provide a value for inclination to gravity for each airway. Inclusion of an inclination to gravity angle for each airway along with airway length, diameter, and branch angle make the current automated tracheobronchial airway data suitable for use in dosimetry programs that can provide dosimetry estimates for inhaled material. The significant differences in upper tracheobronchial airways between Balb/c mice and between C57BL/6 and Apoe^−/− mice highlight the need for mouse strain‐specific aerosol dosimetry estimates.