This microfluidic device produces a 3D model of the human neuromuscular junction using coculture chambers divided into three compartments. The first compartment receives myoblasts in collagen hydrogel, which form muscle bundles that wrap around pillars in the chamber. A second compartment receives individual neurospheres suspended in collagen hydrogel. Neurospheres are positioned with respect to muscle bundles to optimize neuromuscular junction formation. The third compartment resides between the muscle and neuronal compartments and serves as a buffer region for neuronal axons to navigate towards muscle cells, thus forming neuromuscular junctions.
This system can be comprised of normal muscle and neuronal components to study the biology of the normal neuromuscular junction, or it can contain motor neuron disease patient-derived neuronal components to model diseases such as ALS. Contraction of 3D muscle fibers can be induced using light and is measured by pillar deflection in the muscle compartment. The degree of pillar deflection is measurable and facilitates detection of neuromuscular defects and potential restoration of neuromuscular function by drug treatment. Multiple cultures can be prepared in parallel with high reproducibility for treatment with candidate drugs in a high-throughput manner.