Microfluidics for drug discovery and healthcare

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I propose to create a paradigm shift in the way that drugs are tested early in the discovery process by building artificial cells that mimic human cells. My research proposes a way to build bespoke artificial cells from the bottom up that contain the major membrane-based cellular components and organelles. We can use these systems to study both active and passive transport of drugs at the same time. This has the potential to create an exciting new direction in our fight against disease and cause ground-breaking advances in the medicinal sciences of the future.New drugs take 10-15 years to be developed and cost around US $2.6 billion each. Even at the later stages of the discovery process, there is a high failure rate since drug candidates can have unexpected effects when tested in humans. Overall, only ~14% of drugs gain regulatory approval, and there is increasing concern that animal studies do not accurately predict drug behaviour in the human body. In broad terms, the current paradigm for scientific research concerned with the biology underpinning diseases and the development of new drugs to cure them follows conventional steps. Initially in vitro studies are used, where drug candidates are tested using cell-free and then cell-based assays. This is followed by in vivo studies in animals, and finally clinical trials in humans. Alongside, from a medical perspective doctors study these diseases as they progress in humans. Over the last five years my research group have performed the fundamental research to develop a unique new method to quantify how molecules enter cells by building custom-made human-mimetic artificial cell membranes on a chip. Here, I will add the remaining membrane-based cellular components to my artificial cells. We will use these systems to perform fundamental studies into the effect that different membrane components have on drug passive membrane permeability. These include lipid domain formation, and the effect of disease and sex on permeability. Then, we will insert human uptake and efflux membrane transport proteins to be able to quantify active transport. Thirdly, since each compartment in a cell is delineated by a membrane, we will mimic these inside our droplet interface bilayer (DIB)-based artificial cells using liposomes. Finally, we will develop detection methods that allow us to quantify the kinetics of drug transport accurately in each location of the compartmentalised artificial cells.