Neurospheres on Patterned PEDOT:PSS Microelectrode Arrays Enhance Electrophysiology Recordings

Microelectrode arrays (MEAs) are a versatile diagnostic tool to study neural networks. Culture of primary neurons on these platforms allows for extracellular recordings of action potentials. Despite many advances made in the technology to improve such recordings, the recording yield on MEAs remains sparse. Here, enhanced recording yield is shown induced by varying cell densities on poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)-coated MEAs. It is demonstrated that high cell densities (900 cells mm(-2)) of primary cortical cells increase the number of recording electrodes by 53.1% +/- 11.3%, compared with low cell densities (500 cells mm(-2)) with 6.3% +/- 1.4%. To further improve performance, 3D clusters known as neurospheres are cultured on the MEAs, significantly increasing single unit activity recordings. Extensive spike sorting is performed to analyze the unit activity recording multiple neurons with a single microelectrode. Finally, patterning of polyethylene glycol diacrylate through laser ablation is demonstrated, as a means to more precisely confine neurospheres on top of the electrodes. The possibility of recording single neurons with multiple neighboring electrodes is shown. Overall, a total recording yield of 21.4% is achieved, with more than 90% obtained from electrodes with neurospheres, maximizing the functionality of these planar MEAs as effective tools to study pharmacology-based effects on neural networks.