DOI: https://doi.org/10.29363/nanoge.eimc.2021.004
Publication date: 5th July 2021
Biologically active chemistry is mostly concerned with the design of compounds able to translocate biological membranes; complex organelles of interwoven lipids, sugars and proteins. Historically, much work has focused on simple diffusion across the lipid matrix as a major transport route. Current in vitro assays to delineate a small molecules structural dependency on different transport routes have been limited, where typically the model interface is oversimplified. Droplet interface bilayers (DIBs) are formed at the contact of two lipid monolayer coated water in oil droplets and have shown vast potential within biomimetic synthetic biology. DIB technology is highly applicable within microfluidics and bespoke chip design, in particular as a chassis for the study of permeant translocation across biomimetic membranes. Up till now, permeation studies within DIBs have mostly utilised fluorescent microscopy, thus limiting the application of DIB technology in divergent physicochemical space typical of small molecule drug discovery. Here, we address this technological bottleneck by presenting a novel, label free approach enabled by custom chip design principles. Our method is highly implementable in multiple applications and can perform in situ measurement with a data interval as low as 0.02 s. Our platform has enabled us to undertake structure - function relationship studies across compositionally varied bilayers unlocking the complementarity of DIB technology to current widely used assays.
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