use-capillary-aerosol-generator-continuous-production-controlled

Use of Capillary Aerosol Generator in Continuous Production of Controlled Aerosol for Non-Clinical Studies

The capillary aerosol generator (CAG) is operated with the principal of thermal liquid evaporation through heating of e-liquid in the initial phase, ...

Philip Morris Products S.A.

University of Twente

Inhalation of aerosols generated by electronic cigarettes leads to deposition of multiple chemical compounds in the human airways. In this work, an experimental method to determine regional deposition of multicomponent aerosols in an in vitro segmented, realistic human lung geometry was developed and applied to two aerosols, i.e. a monodisperse glycerol aerosol and a multicomponent aerosol. The method comprised the following steps: (1) lung cast model preparation, (2) aerosol generation and exposure, (3) extraction of deposited mass, (4) chemical quantification and (5) data processing. The method showed good agreement with literature data for the deposition efficiency when using a monodisperse glycerol aerosol, with a mass median aerodynamic diameter (MMAD) of 2.3 μm and a constant flow rate of 15 L/min. The highest deposition surface density rate was observed in the bifurcation segments, indicating inertial impaction deposition. The experimental method was also applied to the deposition of a nebulized multicomponent aerosol with a MMAD of 0.50 μm and a constant flow rate of 15 L/min. The deposited amounts of glycerol, propylene glycol and nicotine were quantified. The three analyzed compounds showed similar deposition patterns and fractions as for the monodisperse glycerol aerosol, indicating that the compounds most likely deposited as parts of the same droplets. The developed method can be used to determine regional deposition for multicomponent aerosols, provided that the compounds are of low volatility. The generated data can be used to validate aerosol deposition simulations and to gain insight in deposition of electronic cigarette aerosols in human airways.

Multicomponent aerosol particle deposition in a realistic cast of the human upper respiratory tract.

Direct physicochemical interactions between the major components of electronic cigarette liquids (e-liquids): glycerol (VG) and propylene glycol (PG), and lung surfactant (LS) were studied by determining the dynamic surface tension under a simulated breathing cycle using drop shape method. The studies were performed for a wide range of concentrations based on estimated doses of e-liquid aerosols (up to 2500 × the expected nominal concentrations) and for various VG/PG ratios. The results are discussed as relationships among mean surface tension, surface tension amplitude, and surface rheological properties (dilatational elasticity and viscosity) versus concentration and composition of e-liquid. The results showed that high local concentrations (>200 × higher than the estimated average dose after a single puffing session) may induce measurable changes in biophysical activity of LS; however, only ultra-high e-liquid concentrations inactivated the surfactant. Physiochemical characterization of e-liquids provide additional insights for the safety assessment of electronic nicotine delivery systems (ENDS).

Physicochemical studies of direct interactions between lung surfactant and components of electronic cigarettes liquid mixtures.

Chemical and physical characterization of transported evolving aerosols in an  system is complex. The challenges include appropriate sampling sensitivity, measurement capabilities, and performing online measurements of constituents in the flowing aerosol during exposure. We assessed the performance of single-photon ionization mass spectrometry in measuring aerosol properties within an  aerosol exposure system. The sampling efficiency of the instrument was studied under three protocols to capture the evolving aerosol process inside the exposure system, and it was evaluated using computational fluid dynamics modeling. The changes in the aerosol as dilution is applied show not only a reduction in concentration of the traced substances but also selective sampling due to evolution of the aerosol and (gas/liquid) phase partitioning of the substances forming the aerosol or a change in the aerosol properties. These effects have potentially a direct impact on the delivered dose, as aerosol deposition is dependent on particle size. Dilution affects the chemical concentration of the substances as well as the interconnected physical properties of the aerosol; therefore, the experimental design of  studies should not only report the dilution flow rates but also details of the applied dilution protocol. This adds a layer of complexity to the design and comparison of studies. We also discuss the potential and limitations of single-photon ionization mass spectrometry as a tool in  monitoring of aerosols.

Assessment of Single-Photon Ionization Mass Spectrometry for Online Monitoring of  Aerosol Exposure Experiments.

Understanding aerosol deposition in the human lung is of great significance in pulmonary toxicology and inhalation pharmacology. Adverse effects of inhaled environmental aerosols and pharmacological efficacy of inhaled therapeutics are dependent on aerosol properties as well as person-specific respiratory tract anatomy and physiology. Anatomical geometry and physiological function of human airways depend on age, gender, weight, fitness, health, and disease status. Tools for the generation of the population- and subject-specific virtual airway anatomical geometry based on anthropometric data and physiological vitals are invaluable in respiratory diagnostics, personalized pulmonary pharmacology, and model-based management of chronic respiratory diseases. Here we present a novel protocol and software framework for the generation of subject-specific airways based on anthropometric measurements of the subject's body, using the anatomical input, and the conventional spirometry, providing the functional (physiological) data. This model can be used for subject-specific simulations of respiration physiology, gas exchange, and aerosol inhalation and deposition.

Anthropometry-based generation of personalized and population-specific human airway models.

Accurately determining the delivered dose is critical to understanding biological response due to cell exposure to chemical constituents in aerosols. Deposition efficiency and uniformity of deposition was measured experimentally using monodisperse solid fluorescent particles with mass median aerodynamic diameters (MMAD) of 0.51, 1.1, 2.2 and 3.3 μm in the Vitrocell® AMES 48 air-liquid-interface (ALI) in vitro exposure system. Experimental results were compared with computational fluid dynamic, (CFD; using both Lagrangian and Eulerian approaches) predicted deposition efficiency and uniformity for a single row (N = 6) of petri dishes in the Vitrocell® AMES 48 system. The average experimentally measured deposition efficiency ranged from 0.007% to 0.43% for 0.51-3.3 μm MMAD particles, respectively. There was good agreement between average experimentally measured and the CFD predicted particle deposition efficiency, regardless of approach. Experimentally measured and CFD predicted average uniformity of deposition was greater than 45% of the mean for all particle diameters. During this work a new design was introduced by the manufacturer and evaluated using Lagragian CFD. Lagragian CFD predictions showed better uniformity of deposition, but reduced deposition efficiency with the new design. Deposition efficiency and variability in particle deposition across petri dishes for solid particles should be considered when designing exposure regimens using the Vitrocell® AMES 48 ALI in vitro exposure system.

Comparison of experimentally measured and computational fluid dynamic predicted deposition and deposition uniformity of monodisperse solid particles in the Vitrocell® AMES 48 air-liquid-interface in-vitro exposure system.

Article	Year
Multicomponent aerosol particle deposition in a realistic cast of the human upper respiratory tract. Inhalation toxicology\| PubMed ID: 28470142	2017
Physicochemical studies of direct interactions between lung surfactant and components of electronic cigarettes liquid mixtures. Inhalation toxicology\| PubMed ID: 29932004	2018
Assessment of Single-Photon Ionization Mass Spectrometry for Online Monitoring of Aerosol Exposure Experiments. Chemical research in toxicology\| PubMed ID: 31909610	2020
Anthropometry-based generation of personalized and population-specific human airway models. International journal for numerical methods in biomedical engineering\| PubMed ID: 32053266	2020
Comparison of experimentally measured and computational fluid dynamic predicted deposition and deposition uniformity of monodisperse solid particles in the Vitrocell® AMES 48 air-liquid-inte... Toxicology in vitro : an international journal published in association with BIBRA\| PubMed ID: 32330563	2020

Arkadiusz K. Kuczaj

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