{"id":{"repo_id":"cambridge","oai_identifier":"oai:www.repository.cam.ac.uk:1810/395448"},"canonical_url":"https://search.dev.ndltd.org/etd/cambridge/oai:www.repository.cam.ac.uk:1810/395448","repository":{"repo_id":"cambridge","name":"Cambridge University","base_url":"https://api.repository.cam.ac.uk/server/oai/request"},"display":{"title":"Advanced Bioelectronic and Microphysiological Systems for Functional Studies of Stem Cell-Derived Neural Models","abstract":"This thesis presents an integrated bioelectronic and computational framework for functional interrogation of stem cell-derived neural models. Motivated by the staggering failure rate (exceeding 90%) of neurological drug candidates in clinical trials, the work addresses limitations in preclinical modelling by combining advanced microfabrication, flexible electronics, and human-relevant in vitro systems. The research spans: • 2D compartmentalised cultures for studying tauopathy in Alzheimer’s disease using microphysiological and bioelectronic systems; • Air-liquid interface cerebral organoids (ALI-COs), interfaced with Neuroweb, a porous, ultra-flexible microelectrode array enabling chronic electrophysiology; • NeuroMaps, a modular MATLAB-based GUI for multimodal electrophysiological analysis, integrating spike sorting, spectral decomposition, and network mapping across longitudinal measurements. Key findings include: • Material and substrate-related effects on 2D stem-cell-derived neuronal growth. • Tau-induced hyperexcitability and synaptic disruption in iNeuron-astrocyte co-cultures. • Axonal swelling and lysosomal clustering in microfluidic chips following tau exposure. • Stable long-term recordings from ALI-COs, revealing maturation-linked shifts in firing rate, synchrony, and phase-amplitude coupling. • Neuroweb enabled the detection of cross-species differences in signalling using air-liquid interface cerebral organoids and changes in oscillatory activity possibly linked to metabolic recycling. • The development of a full GUI framework for electrophysiological analysis, providing morphological and electrophysiological context to analysis. 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The research spans: • 2D compartmentalised cultures for studying tauopathy in Alzheimer’s disease using microphysiological and bioelectronic systems; • Air-liquid interface cerebral organoids (ALI-COs), interfaced with Neuroweb, a porous, ultra-flexible microelectrode array enabling chronic electrophysiology; • NeuroMaps, a modular MATLAB-based GUI for multimodal electrophysiological analysis, integrating spike sorting, spectral decomposition, and network mapping across longitudinal measurements. Key findings include: • Material and substrate-related effects on 2D stem-cell-derived neuronal growth. • Tau-induced hyperexcitability and synaptic disruption in iNeuron-astrocyte co-cultures. • Axonal swelling and lysosomal clustering in microfluidic chips following tau exposure. • Stable long-term recordings from ALI-COs, revealing maturation-linked shifts in firing rate, synchrony, and phase-amplitude coupling. • Neuroweb enabled the detection of cross-species differences in signalling using air-liquid interface cerebral organoids and changes in oscillatory activity possibly linked to metabolic recycling. • The development of a full GUI framework for electrophysiological analysis, providing morphological and electrophysiological context to analysis. 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Key findings include: • Material and substrate-related effects on 2D stem-cell-derived neuronal growth. • Tau-induced hyperexcitability and synaptic disruption in iNeuron-astrocyte co-cultures. • Axonal swelling and lysosomal clustering in microfluidic chips following tau exposure. • Stable long-term recordings from ALI-COs, revealing maturation-linked shifts in firing rate, synchrony, and phase-amplitude coupling. • Neuroweb enabled the detection of cross-species differences in signalling using air-liquid interface cerebral organoids and changes in oscillatory activity possibly linked to metabolic recycling. • The development of a full GUI framework for electrophysiological analysis, providing morphological and electrophysiological context to analysis. 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