A Silicon Micromesh Biosensing Platform for Blood-Brain Barrier Inflammaging-on-Chip Models of Neurodegeneration and Drug Discovery

Ageing is the greatest risk factor for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and vascular dementia. Increasing evidence highlights the blood-brain barrier (BBB) and the broader neurovascular unit as key regulators of brain health during ageing. In particular, vascular inflammaging, characterized by chronic inflammation, endothelial dysfunction, impaired barrier integrity, and altered neurovascular signaling, is increasingly recognized as a major driver of neurodegeneration. However, the mechanisms linking BBB ageing to neuronal decline remain poorly understood, largely due to the lack of human-relevant models capable of dynamically monitoring neurovascular dysfunction over time.

This PhD project aims to develop a Blood-Brain Barrier Inflammaging-on-Chip platform by integrating advanced human stem cell-derived neurovascular models with imec's silicon micromesh bioimpedance sensing technology. The platform will enable real-time, label-free, and non-invasive monitoring of BBB integrity, inflammatory responses, cellular crosstalk, and age-associated neurovascular dysfunction, providing new insights into how vascular ageing contributes to BBB breakdown and neurodegenerative disease progression.

The research will establish progressively more complex BBB models using hiPSC-derived brain microvascular endothelial cells, initially as endothelial monocultures and subsequently as multicellular neurovascular unit models including hiPSC-derived pericytes and astrocytes. These models will be benchmarked against primary human brain endothelial cells, pericytes, and astrocytes to assess physiological relevance and translational potential. Using integrated bioimpedance sensing, the project will investigate key hallmarks of vascular inflammaging, including endothelial senescence, chronic inflammation, barrier dysfunction, altered permeability, oxidative stress, extracellular matrix remodeling, and disrupted neurovascular communication.

Working at the interface of stem cell biology, neuroscience, vascular biology, biosensing, and organ-on-chip engineering, the successful candidate will gain expertise in hiPSC culture and differentiation, BBB model development, neurovascular unit engineering, and advanced microphysiological systems. Training will include molecular and cellular characterization techniques such as immunocytochemistry, confocal microscopy, live-cell imaging, qPCR, ELISA, western blotting, permeability assays, and quantitative biomarker analysis. The candidate will also gain exposure to microfabrication, microfluidics, semiconductor-enabled biosensing technologies, computational modelling, machine learning, and AI-assisted data analytics.

A major objective of the project is to establish a human-relevant platform for neurodegenerative disease modelling and drug discovery. By recreating ageing-associated BBB dysfunction in vitro, the system will enable mechanistic studies of neurovascular ageing, identification of predictive biomarkers, and longitudinal evaluation of therapies aimed at restoring BBB function, reducing neuroinflammation, and slowing neurodegenerative disease progression.

The candidate will join a multidisciplinary team spanning bioengineering, microelectronics, biosensing, and neurobiology, while benefiting from imec's world-class research infrastructure. This PhD offers a unique opportunity to develop a highly sought-after interdisciplinary skillset while contributing to next-generation technologies that advance neurodegeneration research, therapeutic discovery, and precision medicine.