Small molecule absorption by PDMS in the context of drug response bioassays

Abstract

The polymer polydimethylsiloxane (PDMS) is widely used to build microfluidic devices compatible with cell culture. Whilst convenient in manufacture, PDMS has the disadvantage that it can absorb small molecules such as drugs. In microfluidic devices like “Organs-on-Chip”, designed to examine cell behavior and test the effects of drugs, this might impact drug bioavailability. Here we developed an assay to compare the absorption of a test set of four cardiac drugs by PDMS based on measuring the residual non-absorbed compound by High Pressure Liquid Chromatography (HPLC). We showed that absorption was variable and time dependent and not determined exclusively by hydrophobicity as claimed previously. We demonstrated that two commercially available lipophilic coatings and the presence of cells affected absorption. The use of lipophilic coatings may be useful in preventing small molecule absorption by PDMS.

Graphical abstract

Highlights

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  Binding of different compounds to PDMS varies greatly.

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  Previous reported correlations of absorption and LogP values could not be repeated.

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  Topological polar surface area possibly related to compound absorption.

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  A lipid based coating partially obviates compound absorption.

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  Presence of cultured cells affects free drug concentration, but less than substrate.