The microfluidic synthesis of structurally complex lipid nanoparticles
File(s)
Author(s)
Pilkington, Colin
Type
Thesis
Abstract
In nature, lipid assemblies exist in a wide range of complex configurations and phases. They impart colour, mediate intra-cellular communication, control cellular fusion and fission events, and allow organisms to adapt to changing environmental conditions. Researchers are understandably fascinated by how these complex structures are synthetically generated as nanoparticulate systems, for biophysical modelling purposes and for the design of novel materials, to be used in therapeutic delivery and biosensing. Existing generation methods lack requisite control however, restricting these assemblies to the simplest of morphologies (spherical, single compartmentalised capsules). When one considers the inextricable link between form and function this is a major impediment to advancing research. Microfluidic approaches have been adopted by many biophysicists, and great strides have been made in templating more complex lipid-based structures at the micrometre scale. Useful though they are, clinical and industrial applications often require particles to be sub-micron in size, necessitating the development of novel platforms and methodology. Drawing from synthetic polymer chemistry, biophysics, and microfluidics, the following work aims to present a number of approaches to address this, relying on continuous, hydrodynamic flow regimes and diffusion dominated mass-transport. Atypical nanoparticle structures were synthesised via microfluidics and characterised, including cubosomes and hexosomes, their coronas functionally enhanced, and their physical properties probed via several bespoke assays. We then exploit the same microfluidic platform, extending our understanding of lipid-assembly, to controllably synthesise multi-functional, compartmentalised vesicles at the nanoscale, successfully segregating two components of an enzymatic reaction within the same particle.
Version
Open Access
Date Issued
2023-12-09
Date Awarded
2024-06-01
Copyright Statement
Attribution-NonCommercial 4.0 International Licence (CC BY-NC)
License URL
Advisor
Seddon, John
Elani, Yuval
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)