Liquid plug propagation in computer-controlled microfluidic airway-on-a-chip with semi-circular microchannels

Area of Science:

• Biomedical Engineering
• Pulmonary Physiology
• Microfluidics

Background:

• Distal airway fluid mechanics are critical in lung diseases.
• Previous models lacked the ability to stably generate and analyze liquid plugs.

Purpose of the Study:

• To develop and validate a lung-on-a-chip system for studying liquid plug dynamics in distal airways.
• To investigate the impact of surfactant, viscosity, and channel geometry on plug behavior and airway epithelial cell injury.

Main Methods:

• A two-inlet, one-outlet microfluidic device with computer-controlled fluidic switching was engineered.
• Leak-proof bonding and primary small airway epithelial cell culture were established.
• Surfactant-containing and viscous liquid plugs were generated and analyzed for speed, length, and pressure drop.
• Computational modeling supplemented experimental findings.
• Cell injury was assessed under varying channel geometries.

Main Results:

• The device reproducibly generated stable surfactant-containing liquid plugs, showing decreased pressure requirements.
• Increased fluid viscosity reduced plug propagation speed and increased pressure differentials.
• Computational modeling confirmed increased shear stress and pressure differentials with higher viscosity.
• Channel geometry influenced cell injury, with greater damage in the channel center.

Conclusions:

• The developed lung-on-a-chip system enables robust investigation of liquid plug dynamics relevant to distal airway diseases.
• Findings highlight the physiological significance of surfactant and mucus viscosity in obstructive lung conditions.
• Channel geometry plays a role in airway epithelial cell injury, mirroring in vivo conditions.