Sorption and release of small molecules in PDMS and COC for Organs on chip.

Accurate risk assessment in drug development is crucial, as conventional in vitro and in vivo models often fail to predict human-specific responses. Organs on chips offer a promising alternative, but widespread use of polydimethylsiloxane introduces challenges due to its sorption of small lipophilic molecules, distorting pharmacokinetic and pharmacodynamic data. Cyclic olefin copolymer, a chemically stable alternative with minimal sorption, has emerged as a potential solution. This study investigates the sorption behavior of seven pharmaceutically active compounds in microfluidic devices and washout of these compounds, using high-performance liquid chromatography-mass spectrometry to evaluate recovery of compounds. Lipophilic molecules exhibited substantial sorption in polydimethylsiloxane and lower retention in cyclic olefin copolymer. Imipramine (logP = 4.80) decreased from 100 µM to 0.0384 µM for polydimethylsiloxane and 31.5 µM for cyclic olefin copolymer after 24 h incubation. Sorption was governed by multiple factors - lipophilicity and rotatable bond count were critical for both materials, hydrogen bond acceptors and molecular weight played a larger role in cyclic olefin copolymer, whereas topological polar surface area was critical for polydimethylsiloxane. Washout studies revealed that polydimethylsiloxane retains lipophilic compounds through bulk absorption, causing slow release, while cyclic olefin copolymer facilitated easier desorption. The cumulative sum of the first 5 h washout of loperamide (logP = 5.13) is 37.8% for polydimethylsiloxane and 71.5% for cyclic olefin copolymer. These findings highlight the importance of material selection and molecular properties in minimizing sorption and ensuring reliable experimental outcomes especially in microfluidic systems with distinctly different surface to volume ratios to other models.