Research

Felix Thorsten Sheffield

Novel techniques for high throughput membrane permeability assays in the agrochemical industry

Felix Thorsten Sheffield - MRes

Abstract

The biological activity of an agrochemical depends upon multiple molecular interactions including that between the agrochemical and its target protein. The interaction of an agrochemical with cellular membranes is however also fundamentally important, as numerous membranes from different tissue and even species types lie between an applied agrochemical and its target. Each membrane potentially acts as a barrier to transport or a sink for storing the agrochemical, thereby preventing it from reaching its intended target. Surprisingly there is a significant lack of understanding of the engineering rules that dictate and control agrochemical translocation in plants. This results from two technology voids. The first of these is the effect of the ‘unstirred water layer’ (UWL), a significant barrier to the performance and applicability of engineered membrane permeability measurements including the commonly used PAMPA assay. The second is the ability to form biologically relevant model plant membranes for in-vitro studies and in-situ agrochemical concentrations. We aim to directly address both bottlenecks by developing a novel technology platform, the “Rheo-Droplet Interface Bilayer” (Rheo-DIB) which will for the first time, remove the effect of the so-called ‘unstirred water layer’ (UWL) via the implementation of spinning disks to induce mixing. By capitalising on this innovation in the physical sciences and implementing high-throughput configurations of the Rheo-DIB we will develop a novel passive permeability assay that will redefine the state-of-the art in drug-membrane interactions. This system, which has no other competing technique will be used to measure the passive membrane translocation of a series of agrochemicals and establish engineering rules that will facilitate rational agrochemical design.