Master's thesis in computational modelling of aerosol deposition in respiratory system

Delivering medications in and through the lungs of patients, in the form of inhaled aerosols, is a particularly challenging task as 260K years of natural selection made the lungs a very good filter for particles and droplets spanning several orders of magnitude in size [1]. The complexity comes from many different factors: the self-affine (fractal) structure of the lung airways; the multi-phase nature of the air flow transporting solid particle or liquid droplets; the highly non-linear behaviour of the multi-phase flow; the multi scale nature of turbulence developing in the extra-thoracic airways (mouth/nose, throat and trachea); the size of the aerosol particles spanning a large range, from mm to nm; the physical and chemical transformation taking place in and on the transported aerosol particles as they travel into the patient lungs. Mathematical modelling and numerical simulations proved to be good tools to help the design of novel drug products for inhalation. Their development poses interesting challenging to researchers interested in classical and statistical mechanics, bio-engineering and computational sciences [2]. Besides understanding and optimizing the design of new drug products, the possibility to create virtual patient lungs, aka lung digital twins, offers the interesting long-term perspective to replace long and expensive clinical trials with their in-silico counterpart. The same is true for toxicology and pharmacokinetic studies, if lung simulations could be extended to animal models (e.g. rodents of various kind such as mice, rats and guinea pigs) [3].

Through the thesis activity, students will contribute to develop computational models to simulate aerosol transport and deposition in human lungs through stochastic/statistical algorithms [4].

They will learn basic concepts in lung physics and physiology and in designing of therapeutic aerosols.

Students will be trained to work according to the standard computational physics/engineering best practices running their simulations in the top European supercomputing facilities.

[1] Breath Taking, M.J.Stephen, Grove Press (2021)

[2] The mechanics of inhaled pharmaceutical aerosols. W.H. Finlay, Academic Press (2001)

[3] G.H. Spasov et al. Modeling and simulation of the human respiratory system Part 1: Computational fluid dynamics simulations and whole lung models, Inhalation Magazine (December 2024 issue)

G.H. Spasov et al. Modeling and simulation of the human respiratory system Part 2: Inhaler design, in vitro experiments and imaging, Inhalation Magazine (April 2025 issue)

[4] Spasov, G.H.; Cottini, C.; Benassi, A. A Monte Carlo-Based 3D Whole Lung Model for Aerosol Deposition Studies: Implementation and Validation, Bioengineering (2025), 12, 1