Microfluidic Studies of Lung Injury, Infection, and Fibrosis
This presentation will describe microfluidic technologies and their application to in vitro cell culture systems that model lung diseases. Microchannel technologies will be described that produce life-like pulsatile flows for study of lung injury, enhancement of in vitro fertilization, and analysis of frequency-dependent cellular responses. The microchannel technologies include piezo-electric actuator arrays from Braille displays and self-switching microfluidic circuits that switch fluid flow on and off periodically on their own. An inflammatory chromatin biomaterial we call “microwebs” inspired by neutrophil extracellular trap (NET) will also be described. NETs are produced in the lung, urinary tract and other parts of the body when subjected to bacteria invasion. While NETs can be beneficial for fighting bacteria, an imbalance can lead to persistent infection in spite of excess NET production. We use microwebs with defined molecular composition and nanoscale structures to better understand what parameters might impact the effectiveness of NETs in fighting bacteria. For example, E. coli, including clinical isolates and resistant strains, are killed more efficiently by the last-resort antibiotic, colistin, when bound to microwebs. On the other hand, Pseudomonas aeruginosa can be quite persistent despite an excess of microwebs, particularly under conditions that mimic the lungs of cystic fibrosis patients. Finally, the presentation will describe use of aqueous two phase system (ATPS) droplets to bioprint miniature “scars” that represent an aspect of lung fibrosis that can accompany lung injuries.