Advanced Bioelectronic and Microphysiological Systems for Functional Studies of Stem Cell-Derived Neural Models

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. Together, these platforms advance the field of neuroengineering by enabling scalable, non-invasive, and longitudinal interrogation of complex neural tissues, with implications for disease modelling, drug screening, and personalised medicine.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2025

Author dc:creator

• Haider, Belquis

Advisors dc:contributor.advisor

• Kaminski Schierle, Gabriele
• Malliaras, George

• Bioelectronics
• Electrophysiology
• Flexible electronics
• In vitro brain development
• In vitro neural systems
• Microelectrode arrays
• Microenvironment engineering
• Microfabrication
• Microphysiological systems
• Multimodal Electrophysiology Analysis
• Neuroengineering
• Organoids
• Tauopathy

Licence

• https://www.repository.cam.ac.uk/bitstreams/8d5d448b-c1b8-4d0f-8522-2044306efd1d/download
• http://purl.org/NET/rdflicense/allrightsreserved

Language dc:language

eng

Author Identifier

0009-0005-9440-0842

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/395448