Development of a modular microfluidic platform for customisable in vitro neuroscience models

Central nervous system (CNS) disorders are the major public health problem in the developed world, leading to a huge societal and economic burden. These disorders are only set to increase given their long-term impact and the growing and ageing population. An increased understanding of the CNS under physiological and pathophysiological states is therefore essential to tackle the problem. However, many animal models have limited translational value, whilst traditional in vitro techniques fail to replicate the complex in vivo microenvironment. Conversely, microfluidic and organ-on-chip technologies can offer an opportunity to develop more physiologically relevant in vitro models of the CNS. These enable more precise cellular patterning and more complex network formation, ultimately providing enhanced experimental capabilities. Whilst microfluidic technology has been well established within neuroscience over the past two decades, there remains limited uptake outside labs with specialist microfabrication facilities required. Further, whilst there are some commercially available devices, there is limited customisable and reconfigurable options, restraining their potential. To increase the uptake and improve ease-of-use of the microfluidic technology, it must be readily accessible, without the need for additional complex equipment, and it must be user-friendly and reliable. A modular platform is therefore proposed, enabling user-defined device production with more flexibility to meet the needs of the individual. In this thesis a modular platform was developed consisting of multiple, individual microfluidic units that combine via a protrusion-intrusion interface on a pressure sensitive adhesive film. This allows components to be assembled in a user defined manner, enabling the creation of bespoke culture environments, making the technology customisable and appealing to novice users. Proof-of-concept experiments demonstrated functional connectivity between environmentally isolated hippocampal cultures across modules, alongside some example applications. This platform presents an opportunity to increase experimental capabilities in neuroscience, enabling the creation of bespoke circuits, and ultimately aid the development of novel therapies.