Recent advances in the complexity of in vitro biological systems have enabled new possibilities for "Organ-on-a-Chip" systems with greater physiological relevancy. Microphysiological Systems (MPS) represent one such advance which incorporates a sophisticated biological construct with a custom designed biological sensor. As the world grapples with grand challenges such as the Opioid Crisis, novel neural MPS offer a means to address both the safety and efficacy of alternative therapeutics, while potentially accelerating the bench-to-market timeframe for lifesaving addiction treatments. Investigations into custom microfabrication processes for such in vitro combinatorial biosensors are thus warranted. This Dissertation addresses the development of a 3D microelectrode array (MEA) biosensor, designed for integration with a custom peripheral-central nervous system, nociceptive circuit. For such Biological MicroElectroMechanical Systems (BioMEMS) sensors, the dielectric layer is crucial as an insulator and part of the cellular microenvironment. Nanoporous silicon dioxide (SiO2) represents an excellent material for this application, however, can be difficult to incorporate on polymer-based BioMEMS platforms. After development of the baseline 3D MEA platform that can integrate several sensing modalities on a single chip, the work presented in this Dissertation further establishes a novel polydopamine (PDA) mediated chemistry for nanoporous SiO2 / Polyethylene Glycol / Matrigel microenvironment definition. Dorsal Root Ganglion (DRG)/nociceptor and Dorsal Horn (DH) neural spheroids were then matured atop this 3D MEA platform, and spontaneous / evoked compound action potentials (CAPs) were successfully recorded during and at the 6-month timepoints. Lastly, inhibitory drug trials enabled confirmation of multi-part biological activity, indicative of the neural coculture that enables a novel 3D MEA-integrated neural 3D MPS, demonstrated for the first time to our knowledge, for long-term electrophysiological applications.
| Identifer | oai:union.ndltd.org:ucf.edu/oai:stars.library.ucf.edu:etd2020-2727 |
| Date | 15 December 2022 |
| Creators | Didier, Charles |
| Publisher | STARS |
| Source Sets | University of Central Florida |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Electronic Theses and Dissertations, 2020- |
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