Parallelizable Microfluidic Platform to Model and Assess In Vitro Cellular Barriers: Technology and Application to...

Area of Science:

• Biomedical Engineering
• Cell Biology
• Microfluidics

Background:

• Cellular barriers (endothelial and epithelial) are crucial for selective transport but are affected by inflammation and disease.
• In vitro modeling of cellular barriers aids in studying disease mechanisms and drug discovery.
• Current methods may lack the throughput or real-time monitoring capabilities for complex co-culture models.

Purpose of the Study:

• To develop a parallelizable microfluidic platform for co-culturing cellular barriers with 3D tumor spheroids.
• To integrate real-time barrier function monitoring into the microfluidic system.
• To demonstrate the platform's utility in studying tumor spheroid-cellular barrier interactions.

Main Methods:

• Fabrication of a microfluidic platform using microinjection molding, featuring ten independent cell culture chambers.
• Integration of electrodes for transepithelial/transendothelial electrical resistance (TEER) measurements using a FT-impedance system.
• Co-culture of HT29 tumor spheroids with MDCK cell barriers under continuous unidirectional flow.

Main Results:

• The microfluidic platform enabled parallelized, tubeless operation of ten distinct cultures.
• Real-time TEER measurements provided rapid assessment of cellular barrier integrity.
• Successful demonstration of HT29 tumor spheroid growth and interaction with MDCK cellular barriers.

Conclusions:

• The developed microfluidic platform offers a robust and efficient tool for in vitro modeling of cellular barriers and tumor spheroids.
• The integrated TEER measurement system allows for real-time monitoring of barrier function in complex co-culture models.
• This technology facilitates research into disease mechanisms, drug screening, and understanding tumor-host interactions.