In vitro recording and stimulation performance of multi-electrode arrays passivated with plasma-enhanced atomic layer-deposited metal oxides

To achieve an intimate contact between neuronal cells and the electrode in non-invasive platforms intended for neurological research, in this study, we fabricated a raised-type Au multi-electrode array (MEA) by employing nanoscale-thick indium-tin oxide (ITO; 50 nm) as a track layer and plasma-enhanced atomic layer-deposited (PEALD) Al₂O₃ (30-60 nm) and HfO₂ (20 nm) as passivation layers. The PEALD Al₂O₃-passivated Au MEA was subsequently modified with electrodeposited AuPt nanoparticles (NPs) and IrO_x to demonstrate the passivation capability and chemical resistance of Al₂O₃ to Au-, Pt-, and IrO_x NP-containing electrolytes. Al₂O₃-passivated and IrO_x/AuPt-modified MEAs could resolve optogenetically activated spikes and spontaneous activities with a root-mean-square noise level of 2.8 ± 0.3 μV generated by the primarily cultured hippocampal neurons transfected with viral vectors. PEALD Al₂O₃ exhibited a poor resistance to the Ag leaching environment (concentrated nitric acid maintained at 70 °C); therefore, a nanoporous Au (NPG) structure could not be implemented on the Au MEA passivated with Al₂O₃. By depositing a 20 nm-thick HfO₂ over a 40 nm-thick Al₂O₃ layer, the NPG structure could be implemented on the Au MEA, confirming the chemical resistance of HfO₂ to the Ag leaching environment. The nontoxicity of Al₂O₃ and HfO₂ was confirmed by the successful primary culture of dissociated hippocampal neurons and electrophysiological studies performed using a hippocampal slice. Considering the advances in ALD technology and the vast number of metal oxides, these results extend the application of ALD metal oxides from water barriers for biomedical implants to passivation layers for in vitro MEAs.