Fully Integrated 3D Microelectrode Arrays with Polydopamine-Mediated Silicon Dioxide Insulation for Electrophysiological Interrogation of a Novel 3D Human, Neural Microphysiological Construct

Advances within in vitro biological system complexityhave enablednew possibilities for the "Organs-on-a-Chip" field.Microphysiological systems (MPS) as such incorporate sophisticatedbiological constructs with custom biological sensors. For microelectromechanicalsystems (MEMS) sensors, the dielectric layer is critical for deviceperformance, where silicon dioxide (SiO2) represents anexcellent candidate due to its biocompatibility and wide utility inMEMS devices. Yet, high temperatures traditionally preclude SiO2 from incorporation in polymer-based BioMEMS. Electron-beamdeposition of SiO2 may provide a low-temperature, dielectricserving as a nanoporous MPS growth substrate. Herein, we enable improvedadherence of nanoporous SiO2 to polycarbonate (PC) and316L stainless steel (SS) via polydopamine (PDA)-mediated chemistry.The resulting stability of the combinatorial PDA-SiO2 film was interrogated, along with the nature of the intrafilm interactions.A custom polymer-metal three-dimensional (3D) microelectrodearray (3D MEA) is then reported utilizing PDA-SiO2 insulation, for definition of novel dorsal root ganglion (DRG)/nociceptorand dorsal horn (DH) 3D neural constructs in excess of 6 months forthe first time. Spontaneous/evoked compound action potentials (CAPs)are successfully reported. Finally, inhibitory drugs treatments showcasepharmacological responsiveness of the reported multipart biologicalactivity. These results represent the initiation of a novel 3D MEA-integrated,3D neural MPS for the long-term electrophysiological study.