Multiplexed blood-brain barrier organ-on-chip

Area of Science:

• Biomedical Engineering
• Microfluidics
• Tissue Engineering

Background:

• Organ-on-chip (OOC) models are crucial for pharmaceutical and biomedical research.
• Existing OOC models often lack the capacity for parallel testing of multiple stimuli, limiting experimental throughput and reproducibility.

Purpose of the Study:

• To develop a multiplexed polydimethylsiloxane (PDMS) organ-on-chip device capable of simultaneously addressing eight parallel channels.
• To enable parallel testing of different experimental conditions and facilitate real-time cell culture monitoring.

Main Methods:

• Fabrication of a multiplexed PDMS chip with eight parallel channels and eight individual outlets using soft lithography.
• Assembly of a two-layer device with a transparent PDMS membrane featuring through-hole pores for visual inspection.
• Recapitulation of the blood-brain barrier model using human cerebral microvascular endothelial cells (hCMEC/D3) and human astrocytes.

Main Results:

• Successful culture of endothelial cells and astrocytes, confirmed by immunostaining for tight junction ZO-1, adherence junction VE-cadherin, and glial fibrillary acidic protein (GFAP).
• Demonstrated multiplexed permeability studies showing differential passage of FITC-dextran molecules (4 kDa and 20 kDa) across the cellular barrier.
• Validated the device's functionality in recapitulating a functional blood-brain barrier model.

Conclusions:

• The developed multiplexed organ-on-chip device significantly enhances experimental throughput and reproducibility.
• The device is suitable for parallel drug testing and serves as a valuable tool for studying barrier tissue functions.
• This technology holds promise for advancing pharmaceutical screening and personalized medicine applications.