Design and evaluation of a breath-synchronized smart vibrating mesh nebulizer: from instrumentation to human pharmacokinetics.

Aerosol delivery systems play a critical role in the treatment of pulmonary diseases, yet conventional nebulizers suffer from inconsistent dosing, limited deposition efficiency, and significant fugitive aerosol emissions. This study presents the design and validation of a smart vibrating mesh nebulizer (BST-VMN), which integrates real-time acoustic signal analysis and a neural network-based classification algorithm to achieve precise breath-phase synchronization. The system features a custom acoustic sensing module and a lightweight neural classifier that detects inhalation phases from respiratory sounds with < 100 ms latency and 96.3% classification accuracy. Aerosol generation is triggered exclusively during inhalation, minimizing drug waste and environmental contamination. Comprehensive in vitro testing under simulated respiratory conditions-including COPD, ILD, and asthma-demonstrated a delivery efficiency of 95 ± 2%, significantly higher than that of conventional continuous nebulisation (38 ± 8%). While particle inertia and aerodynamic size jointly govern regional airway deposition, the system also enabled fine control of aerosol particle size via dual-frequency mesh actuation, reducing the mass median aerodynamic diameter (MMAD) from 3.82 μm to 1.85 μm while maintaining particle uniformity (GSD 1.63-2.05). In a randomized crossover pharmacokinetic study involving 24 healthy participants, BST-VMN achieved more than 2 × higher pulmonary drug deposition compared to the continuous mode (51.30 μg vs. 22.04 μg, P = 0.019). Environmental monitoring revealed a fourfold reduction in fugitive aerosol emissions (3.0 ± 2.3 μg/m3 vs. 11.9 ± 6.0 μg/m3, P < 0.0001), confirming improved occupational safety. These findings establish BST-VMN as a high-performance, precision aerosol delivery system that combines intelligent sensing, adaptive control, and tunable particle generation to enhance both therapeutic efficacy and environmental safety in clinical aerosol therapy.