Fully Integrated 3D Microelectrode Arrays with Polydopamine-Mediated Silicon Dioxide Insulation for Electrophysiological Interrogation of a Novel 3D Human, Neural Microphysiological Construct
Charles M. Didier, David W. Fox, Kevin Pollard, Aliyah Baksh, Nisha Iyer, Alexander Bosak, Yuen Yee Li Sip, Julia Freitas Orrico, Avra Kundu, Randolph S. Ashton, Lei Zhai, Michael J. Moore, Swaminathan Rajaraman
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 low-temperature, 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.