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PMID: 18006663 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 104 ·No. 48 ·2007-11-27 ·Pages 18886-91

Huh D, Fujioka H, Tung YC, Futai N, Paine R, Grotberg JB, Takayama S

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.

MeSH Terms
Acoustics/instrumentation Air Basement Membrane/physiology Cell Differentiation Cell Division Cell Survival Cells, Cultured/physiology Epithelial Cells/physiology Epithelium/injuries,physiopathology Equipment Design Humans Lung Diseases/etiology,physiopathology Microfluidic Analytical Techniques Microfluidics Perfusion Pulmonary Surfactants Shear Strength Stress, Mechanical Tissue Engineering/instrumentation
Chemicals
Pulmonary Surfactants
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Huh Dongeun
Department of Biomedical Engineering and Macromolecular Science, University of Michigan, Ann Arbor, MI 48109-2099, USA.
Fujioka Hideki
Tung Yi-Chung
Futai Nobuyuki
Paine Robert
Grotberg James B
Takayama Shuichi
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0610868104
Published
2007-11-27
Epub
2007-00-15
Pages
18886-91
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2141877
Subset
IM
Grants
NHLBI NIH HHS · R01 HL084370 · United States
NHLBI NIH HHS · HL084370-01 · United States
External Links
PubMed source DOI: 10.1073/pnas.0610868104 PMC Full Text View journal details
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