Bridging two cultures: Minimalistic networks prepared by microfluidic arraying, and open access compartments for electrophysiology

Microfabrication protocols are described for two compartmentalized neuron culture platforms which extend beyond the capabilities of conventional systems. The first involves a differential flow microfluidic circuit for arraying single neurons, along with protocols for in chip biomaterial patterning and the selective treatment of somata or outgrowth compartments. These minimalistic neuronal networks are ideal for spatially resolved research using rare and precious neuronal subtypes as well as parallelization for screening biochemical libraries. The second, open-access, system solves the micro-to-macro interface challenge to enable the insertion of micromanipulators for electrophysiology studies or localized perturbation using a microinjector. This system is especially useful for the spatiotemporal investigation of mechanisms underlying disease, such as neurodegeneration and epileptic seizures. Design files along with soft lithography replication techniques are provided to facilitate the straightforward uptake of these platforms. Technology integration approaches are also presented for the alignment of arrayed neurons with individual microelectrodes for highly parallel electrophysiological and electrochemical measurements throughout nodes in the compartmentalized neuronal network.