UV-DIB: label-free permeability determination using droplet interface bilayers
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Accepted version
Supporting information
Author(s)
Type
Journal Article
Abstract
Simple diffusion of molecular entities through a phospholipid bilayer, is a phenomenon of great importance to the pharmaceutical and agricultural industries. Current model lipid systems to probe this typically only employ fluorescence as a readout, thus limiting the range of assessable chemical matter that can be studied. We report a new technology platform, the UV-DIB, which facilitates label free measurement of small molecule translocation rates. This is based upon the coupling of droplet interface bilayer technology with implemented fiber optics to facilitate analysis via ultraviolet spectroscopy, in custom designed PMMA wells. To improve on current DIB technology, the platform was designed to be reusable, with a high sampling rate and a limit of UV detection in the low μM regime. We demonstrate the use of our system to quantify passive diffusion in a reproducible and rapid manner where the system was validated by investigating multiple permeants of varying physicochemical properties across a range of lipid interfaces, each demonstrating differing kinetics. Our system permits the interrogation of structural dependence on the permeation rate of a given compound. We present this ability from two structural perspectives, that of the membrane, and the permeant. We observed a reduction in permeability between pure DOPC and DPhPC interfaces, concurring with literature and demonstrating our ability to study the effects of lipid composition on permeability. In relation to the effects of permeant structure, our device facilitated the rank ordering of various compounds from the xanthine class of compounds, where the structure of each permeant differed by a single group alteration. We found that DIBs were stable up to 5% DMSO, a molecule often used to aid solubilisation of pharmaceutical and agrochemical compounds. The ability of our device to rank-order compounds with such minor structural differences provides a level of precision that is rarely seen in current, industrially applied technologies.
Date Issued
2022-03-07
Date Acceptance
2022-01-07
ISSN
1473-0189
Publisher
Royal Society of Chemistry
Start Page
972
End Page
985
Journal / Book Title
Lab on a Chip: miniaturisation for chemistry, physics, biology, materials science and bioengineering
Volume
22
Issue
5
Copyright Statement
© The Royal Society of Chemistry 2022.
Sponsor
Engineering & Physical Science Research Council (E
Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Identifier
https://pubs.rsc.org/en/content/articlelanding/2022/LC/D1LC01155C
Grant Number
EP/R511547/1
EP/J017566/1
EP/V048244/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Technology
Biochemical Research Methods
Chemistry, Multidisciplinary
Chemistry, Analytical
Nanoscience & Nanotechnology
Instruments & Instrumentation
Biochemistry & Molecular Biology
Chemistry
Science & Technology - Other Topics
MEMBRANE PERMEATION ASSAY
FATTY-ACID-COMPOSITION
UNSTIRRED WATER LAYER
LIPID-COMPOSITION
SMALL MOLECULES
ABSORPTION
MODEL
METABOLISM
PREDICTION
DIVERSITY
Diffusion
Kinetics
Lipid Bilayers
Permeability
Phospholipids
Lipid Bilayers
Phospholipids
Diffusion
Kinetics
Permeability
Analytical Chemistry
03 Chemical Sciences
09 Engineering
Publication Status
Published
Date Publish Online
2022-02-02