Experimental Full-volume Airway Approximation for Assessing Breath-dependent Regional Aerosol Deposition

Modeling aerosol dynamics in the airways is challenging, and most modern personalized in vitro tools consider only a single inhalation maneuver through less than 10% of the total lung volume. Here, we present an in vitro modeling pipeline to produce a device that preserves patient-specific upper airways while approximating deeper airways, capable of achieving total lung volumes over 7 liters. The modular system, called TIDAL, includes tunable inhalation and exhalation breathing capabilities with resting flow rates up to 30 liters per minute. We show that the TIDAL system is easily coupled with industrially and clinically relevant devices for aerosol therapeutics. Using a vibrating mesh nebulizer, we report central-to-peripheral (C:P) aerosol deposition measurements aligned with both in vivo and in silico benchmarks. These findings underscore the effectiveness of the TIDAL model in predicting airway deposition dynamics for inhalable therapeutics.