PROJECT SUMMARY Mucociliary transport (MCT) of inhaled particles and bacteria is extremely important to maintain lung sterility. In trachea and bronchi, MCT is driven by breakage of mucus strands that emerge from submucosal glands through cilia beating. Discovery and development of better methods to investigate particle MCT has profound impacts on the study of lung disease pathogenesis and exploration of new therapeutic methods. Because of its importance, tremendous efforts have been made to access particle MCT, including inhalation of radioactive micro-disks in human/animal models, application of particles on airway epithelial cell cultures, and explanted trachea tissues. However, current methods fall short in recapitulating the biophysical/biochemical airway environment, including submucosal glands, and providing necessary resolution in studying MCT of natural inhaled-like particles. To address the unmet need, our overall objective is to develop a trachea-on-a-chip to study MCT of micro/nano-sized particles in precisely controlled airway environments. Our preliminary studies demonstrate the implementation of a microfluidic device with an explanted trachea to maintain airway physiology and function, named “trachea-on-a-chip”. In the proposed research, we aim to assess particle MCT on a non-submerged airway surface with trachea-on-a-chip (Aim 1), and control airway physical/chemical environment to impact particle MCT with trachea-on-a-chip (Aim 2). Upon completion of the proposed project, we expect three outcomes. First, we will deliver a novel trachea-on-a-chip technical platform to study airway particle MCT. Second, we will answer questions as to how the airway environment impacts the efficiency of MCT with trachea-on-a-chip. Third, the knowledge obtained in this project will be broadly applied to other lung diseases, which will be used for future R01 applications. In addition to research, the proposed project will further help the candidate to build a unique and vibrant research program on the cutting edge of engineering and medicine.