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

Abstract

Advances within in vitro biological system complexity have enabled new possibilities for the "Organs-on-a-Chip" field. Microphysiological systems (MPS) as such incorporate sophisticated biological constructs with custom biological sensors. For microelectromechanical systems (MEMS) sensors, the dielectric layer is critical for device performance, where silicon dioxide (SiO 2 ) represents an excellent candidate due to its biocompatibility and wide utility in MEMS devices. Yet, high temperatures traditionally preclude SiO 2 from incorporation in polymer-based BioMEMS. Electron-beam deposition of SiO 2 may provide a lowtemperature, dielectric serving as a nanoporous MPS growth substrate. Herein, we enable improved adherence of nanoporous SiO 2 to polycarbonate (PC) and 316L stainless steel (SS) via polydopamine (PDA)-mediated chemistry. The resulting stability of the combinatorial PDA−SiO 2 film was interrogated, along with the nature of the intrafilm interactions. A custom polymer−metal three-dimensional (3D) microelectrode array (3D MEA) is then reported utilizing PDA−SiO 2 insulation, for definition of novel dorsal root ganglion (DRG)/nociceptor and dorsal horn (DH) 3D neural constructs in excess of 6 months for the first time. Spontaneous/evoked compound action potentials (CAPs) are successfully reported. Finally, inhibitory drugs treatments showcase pharmacological responsiveness of the reported multipart biological activity. These results represent the initiation of a novel 3D MEA-integrated, 3D neural MPS for the long-term electrophysiological study.