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Designs are etched onto Silicon wafers and then cast designs into a flexible transparent material to create cell culture devices with miniature channels and features at a sub-cellular scale.
Neuronal axons aligned using microfludic channels
Human brain blood vessels grown in an 'organ on chip' system. Stroke like injury to one side causes vessels (red) to become leaky to a fluorescent dye (green).

Paul Holloway

Principal Investigator

My research utilises microfluidic technologies to precisely define the cellular micro-environment and enable new insights into neurovascular biology.

In the brain, endothelial cells, perivascular cells, glia and neurons are intimately coupled, enabling tight regulation of the blood brain barrier, responses to metabolic demands, and inflammatory status. This has lead to the consideration of these cellular elements as part of a functional unit termed the 'neurovascular unit'. Disruption of this system is evident in many human neurological disorders. However, investigating this system in humans and modelling the complex interactions in vitro is particularly challenging.

Recently, micro-fabrication techniques adopted from the semiconductor industry have allowed the production of miniaturised biological devices for complex, spatially-defined cell culture which can be used to mimic human organs.  In the Microfluidic Neurological Models Lab we are utilising ‘Organ on chip’ technologies to develop new, dynamic, heterotypic cellular model of the neurovascular unit to understand cell death mechanisms in stroke and cerebral small vessel disease.

Biography

Dr Holloway has a background incorporating both neurovascular biology and microfluidic engineering. His PhD at Imperial College London and Post-doctoral position at Louisiana State University focused on novel therapeutic approaches to modulate immune cell trafficking in the cerebral microcirculation following stroke. Initial investigations using minimalistic flow assays, to investigate human immune-brain cell interactions in vitro, led Dr Holloway to pursue training in microfluidic engineering approaches at Princeton University followed by a post-doctoral position at the Centre for Hybrid Biodevices, University of Southampton. In this position Dr Holloway helped develop compartmentalised microfluidic cell culture platforms for the preparation of defined neuronal circuits to shed light on axonal transport and disease propagation. He came to Oxford in 2017 joining the Buchan lab on a Royal Comission of 1851 Research Fellowship to develop an organ on chip model of the neurovascular unit. He is now leading the MNM lab and working with the Leducq Foundation Circadian Network to introduce circadian rhythums into microfluidic in vitro models of stroke and neurovascular function.