HTS Library Plate Rejuvenation Using a DMSO-Rich Atmosphere.

Dry DMSO can rapidly pull water vapor out of the air due to its hygroscopic nature. This is a well-documented problem within drug discovery, particularly within high-throughput screening (HTS). This hydration is caused by atmospheric moisture being absorbed each time a compound library is used. This effect becomes increasingly pronounced when a compound library is used routinely. The result of this hydration is a change to both the total volume of solution and the concentration of sample still in solution. This can result in a large amount of variability in the measured biological activity of a sample depending on the library usage. In this paper, we show the detrimental effects the hydration of sample libraries has on the reproducibility of biological data and present a novel way to remove it from HTS library plates. Our approach involves creating a DMSO-rich environment, created by placing anhydrous DMSO in compound storage pods purged with nitrogen, and incubating library plates in this environment for up to 3 days. Quantification via evaporative light scattering detection (ELSD) showed that removing water greatly increased the molarity of solutions, with a greater effect being seen for compounds with poor solubility. We also demonstrated how this approach can restore the inhibitory activity of stock solutions of compounds (pIC

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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.