A customizable microfluidic platform for medium-throughput modeling of neuromuscular circuits

Area of Science:

• Neuroscience
• Biomedical Engineering
• Stem Cell Biology

Background:

• Neuromuscular circuits (NMCs) are crucial for voluntary movement and modeling them is key for understanding diseases like muscular dystrophy and ALS.
• Existing microfluidic platforms face challenges with myotube detachment and limited experimental units, hindering disease modeling and drug discovery.

Purpose of the Study:

• To develop a scalable microfluidic platform for generating and analyzing functional neuromuscular circuits.
• To overcome limitations of current microfluidic systems for neuromuscular circuit research.

Main Methods:

• Developed a microfluidic platform (MFP) with over 100 experimental units.
• Incorporated a reactive polymer surface to prevent cell detachment and enable long-term co-culture.
• Utilized optogenetics and a novel rabies tracing assay to confirm functional NMCs.

Main Results:

• Achieved long-term co-culture of human motor neurons and induced pluripotent stem cell-derived myotubes within the MFP.
• Demonstrated the formation of functional neuromuscular circuits using optogenetics.
• Successfully applied a modified rabies tracing assay for efficient NMC identification.

Conclusions:

• The developed MFP supports medium-throughput applications for neuromuscular circuit research.
• This platform enables large-scale generation and quantification of functional NMCs.
• The platform is suitable for disease modeling and pharmacological drug targeting of neuromuscular disorders.