A Three-Dimensional Arrayed Microfluidic Blood-Brain Barrier Model With Integrated Electrical Sensor Array.

Area of Science:

• Neuroscience
• Biotechnology
• Microfluidics

Background:

• The blood-brain barrier (BBB) restricts drug delivery to the brain, hindering neurological disorder treatment.
• Existing in vitro BBB models often fail to replicate in vivo conditions and functions accurately.

Purpose of the Study:

• To develop an advanced microfluidic BBB-on-a-chip model that better mimics in vivo BBB physiology.
• To enable more accurate prediction of drug permeability and toxicity for neurological therapeutics.

Main Methods:

• A co-culture microfluidic chip integrated with a multielectrode array was designed to mimic BBB interactions.
• The chip incorporated 16 BBB sites allowing for real-time transendothelial electrical resistance (TEER) measurements.
• In vivo level shear stress was applied to co-cultures of primary mouse endothelial cells and astrocytes.

Main Results:

• Co-culture and shear stress application resulted in tighter junctions and significantly reduced barrier permeability.
• Histamine drug testing demonstrated higher permeability in endothelial-only cultures compared to co-cultures.
• The developed BBB chip accurately reflected in vivo BBB characteristics.

Conclusions:

• The novel BBB-on-a-chip model provides a more physiologically relevant platform for studying the blood-brain barrier.
• This advanced model is expected to enhance the accuracy of drug screening and toxicity assessments for brain-targeted therapies.