title: Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems.
abstract: We describe a microfabricated airway system integrated with computerized air-liquid two-phase microfluidics that enables on-chip engineering of human airway epithelia and precise reproduction of physiologic or pathologic liquid plug flows found in the respiratory system. Using this device, we demonstrate cellular-level lung injury under flow conditions that cause symptoms characteristic of a wide range of pulmonary diseases. Specifically, propagation and rupture of liquid plugs that simulate surfactant-deficient reopening of closed airways lead to significant injury of small airway epithelial cells by generating deleterious fluid mechanical stresses. We also show that the explosive pressure waves produced by plug rupture enable detection of the mechanical cellular injury as crackling sounds.
authors.affiliation: Department of Biomedical Engineering and Macromolecular Science, University of Michigan, Ann Arbor, MI 48109-2099, USA.
authors.forename: Dongeun
authors.initials: D
authors.lastname: Huh
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujioka
authors.forename: Yi-Chung
authors.initials: YC
authors.lastname: Tung
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Futai
authors.forename: Robert
authors.initials: R
authors.lastname: Paine
authors.forename: James B
authors.initials: JB
authors.lastname: Grotberg
authors.forename: Shuichi
authors.initials: S
authors.lastname: Takayama
mesh_terms: D000162:Acoustics / Q000295:instrumentation; D000388:Air; D001485:Basement Membrane / Q000502:physiology; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D004848:Epithelium / Q000293:injuries* / Q000503:physiopathology; D004867:Equipment Design; D006801:Humans; D008171:Lung Diseases / Q000209:etiology* / Q000503:physiopathology; D046210:Microfluidic Analytical Techniques; D044085:Microfluidics; D010477:Perfusion; D011663:Pulmonary Surfactants; D033081:Shear Strength; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000295:instrumentation
chemical_list: D011663:Pulmonary Surfactants