Investigations into characterising and measuring bio-membrane permeability have been ongoing
for over a century. Driven by both industry and academia, a variety of in vivo, in vitro, and in
silico techniques have been developed and employed to understand the mechanisms and thermodynamics
of drug and agrochemical transport in living systems. Unfortunately, many of the
techniques suffer from a lack of high-throughput implementation or suffer physical restrictions
such as bulk diffusion limitations. Moreover, it is apparent that membrane permeability data
is lacking, particularly with respect to the agricultural industry and non-mammalian biological
sciences.
With the invention of the droplet interface bilayer (DIB) a decade ago, there have been
several breakthroughs in membrane technologies for electro-physiology, membrane protein reconstitution,
and membrane permeability assay methods. In this thesis, I have studied DIBs
as a possible candidate for a rapid and high-throughput membrane permeability assay that can
be used to measure rates for speci c agrochemicals in varying lipid systems in situ.
The rst output of this research includes device engineering, design and fabrication techniques
of novel micro
uidic chips for improved DIB formation, droplet rendering, and manipulation.
More speci cally, on demand and high through-put DIB manufacture has been achieved
for the rst time, the results of which has been published in the peer reviewed journal, Lab
on a Chip. Furthermore, to prove that the application of DIBs are not categorically limited
to a small subset of lipid types, it has been proven that DIBs can be formed with a variety
of lipids, including some plant lipid extracts. For the rst time, DIB model membranes have
been formed to mimic soy, Arabidopsis, tobacco, and oat plasma membranes. A successful
permeability assay was performed with these DIBs, and the results were published in the peer
reviewed journal, Biomicro
uidics.
A serious challenge of measuring membrane permeability in DIBs is the limitation of bulk
diffusion, which often leads to underestimates in intrinsic membrane permeability rates. To
further the understanding of this limitation, the
uid dynamics of coupled advection-diffusion in
stirred droplets has been investigated experimentally and computationally. As a result, a novel
micro
uidic device has been developed to induce shear stress along the membrane to disrupt
the effects of the bulk
uid stagnation in the permeability assay, which allows for more accurate
measurements of the intrinsic membrane permeability. To the best of my knowledge, this is the
most accurate technique available, and is a breakthrough tool for future applications, such as
supplying permeability data to systems transport models. The results of the intrinsic membrane
permeability of various lipid types have been published in the journal, Nature Scienti c Reports.
Furthermore, the physical properties of DIBs have been investigated including surface energy
driven morphology, formation dynamics, and bilayer surface tension measurements. For the
rst time, the effect of membrane curvature in DIBs has been thoroughly scrutinized, and new
insights into DIB behaviour have been established.