Design of a multilayer lung chip with multigenerational alveolar ducts to investigate the inhaled particle deposition

Abstract

We present the development and application of a multilayer microfluidic lung chip designed to accurately replicate the human respiratory bronchi, providing an innovative platform for controlled particle deposition in the lung. By employing a quantitative control method of fluid velocity through the deformation of an elastic PDMS membrane, this platform mimics the passive breathing process in humans and allows for precise simulation of the respiration cycle. We utilized time-lapse photography of fluorescent particles in a water/glycerol solution to qualitatively observe fluid morphology in the channel, while a chip-aerosol exposure device combined with microscopy imaging was employed to visualise aerosol deposition. Both experimental and numerical simulation results showed that particle concentration decreased towards the distal generations of the lung, and that changes in breathing pattern significantly affected particle deposition trends. Furthermore, we found that increasing the residence time of particles in the channel facilitated deeper particle deposition, achievable by adjusting parameters such as breath-hold time, exhalation time, respiration cycle length, and tidal volume. The proposed microfluidic lung chip device has significant potential for future research in respiratory health and inhaled drug delivery, providing an efficient, cost-effective, and ethical alternative to traditional in vivo studies.