Flow and diffusion in microfluidic environments bounded by fluid walls with applications in neuroscience

Thesis

Efforts towards the recapitulation of in-vivo systems in vitro remains a key goal of biological sciences. Microfluidic developments have the potential to revolutionise biology assays by providing better spatial and temporal control of cellular microenvironments. To this end, a wide range of microfluidic platforms have been proposed in literature to generate more biologically relevant and advanced cell-based models for drug discovery. However, less than 10% of microfluidics articles have authorship outside of core engineering or related disciplines, even fewer in pure biological sciences journals where traditional methods remain unchanged for decades. There are many reasons for this; some relevant ones to this thesis include the biocompatibility of the materials used to fabricate microfluidic platforms, poor ability to fabricate microenvironments on-demand and the inaccessibility of cells behind solid walls. Our group has led the development of a new microfluidics approach to overcome many existing limitations by forming microenvironments inside standard Petri dishes and confining them using ‘fluid walls’ (interfaces between immiscible liquids) rather than solid ones. This allows the microfluidic environments to be naturally biocompatible, easy to fabricate, integrated into traditional biology workflows, and cells are accessible everywhere simply by piercing through the bounding fluid interface. In addition, the method enables the microenvironments to be reshaped as fluid walls can be destroyed and rebuilt at will without harming the cultured cells.

The innovative fluid-walled technology also introduces an innovative engineering challenge: during flows, fluid walls shape is dependent on pressure and can morph in response to pressure changes. This thesis characterises properties of such morphing microenvironments to derive semi-analytical models predicting flows through them. The developed models are applied, with biology collaborators, to design, fabricate, and operate microfluidic environments to study neuronal interactions between different compartments of the human brain. As a whole, this work broadens the applications possible with microfluidics and provides an extended analytical basis to support wider adoption of the technology by providing accessible design and operational solutions to biologists.

Authors: Nebuloni, F

• DOI: 10.5287/ora-ye6pb2gd2
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: microfluidics; laplace pressure; interfacial tension; engineered cell cultures; multiphase systems; perfusion; neuronal circuits; neuroscience; passive flow
• Subjects: Biomedical engineering; Biology; Engineering