Advancing Parkinson's Disease Research Through Sensor-Integrated Organ-on-a-Chip Systems

Abstract

Parkinson's disease (PD) remains an incurable neurodegenerative disorder, with current treatments targeting symptoms rather than the underlying pathology. Emerging hypotheses suggest that the gut plays a pivotal role in the onset of PD. However, research is constrained by the limitations of animal models and simplified human in vitro systems. Organ-on-a-chip (OoC) platforms offer a promising solution by combining human-derived cells with tissue complexity. This doctoral thesis contributes to advancing PD research by developing and applying sensor-integrated OoC platforms and human-derived organoid models. Key advancements include the creation of a midbrain-on-a-chip platform integrating electrical, electrochemical, and optical sensors, enabling real-time monitoring of neuronal activity, oxygen consumption, and dopamine (DA) secretion. Early-stage PD phenotypes were modeled using midbrain-striatum assembloids, where DA sensors demonstrated disease-relevant physiological changes. The central part of this thesis was addressing the impact of cellular senescence, a key risk factor in PD. This impact on gut barrier integrity was investigated by developing and utilizing an impedance sensor integrated gut-on-a-chip system. An optical glucose sensor was further integrated into microfluidic platforms to provide insights into glucose consumption. The findings underscore the transformative potential of OoC platforms and sensor integration in PD research. These innovations enable deeper investigation into PD mechanisms and offer powerful tools for drug discovery and personalized medicine. The synergy of advanced sensor technologies with microphysiological systems sets the stage for breakthroughs in understanding neurodegenerative diseases and developing effective therapies.