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Journal of Biomolecular Screening
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Compound Transfer Efficiency from Polystyrene Surfaces: Application to Microarrayed Compound Screening

Xueheng Cheng

Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL

Bing Yan

Discovery Partners International, South San Francisco and San Diego, CA; Bristol-Myers Squibb Company, Wallingford, CT

Lan Gao

Hua Tang

Yihong Fan

Steven N. Anderson

Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL

Rhett Affleck

Discovery Partners International, South San Francisco and San Diego, CA

David J. Burns

Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL

In microarrayed compound screening (µARCS), compounds are spotted and dried onto a polystyrene sheet (ChemCard)ata high density and introduced into the assay by contacting with agarose gels that contain reagents for the assay. The authors have conducted studies to characterize the compound transfer process using 59 compounds of diverse properties. The amount of compounds remaining on the ChemCard was determined by liquid chromatography/mass spectrometry after incubation with agarose gels for predetermined time periods. The results showed good correlation with kinetics of compound transfer to phosphate-buffered saline (PBS) buffer, but only moderate correlation with equilibrium solubility of compounds in PBS buffer. These observations indicate that the major factor determining compound transfer efficiency is the kinetics of dissolution of compounds, rather than equilibrium solubility and diffusion of compounds in the gel. Compounds of lower ClogP showed a higher rate of transfer to agarose gels and vice versa. Other compound properties such as molecular weight, size, acid-base, and H-bonding properties did not significantly affect compound transfer. Importantly, the majority of the compounds studied show greater than 20% transfer after a 10-min incubation with agarose gels, providing sufficient amounts of compounds for screening purposes.

Key Words: microarrayed compound screening (µARCS) • compound transfer • dissolution • solubility • partition coefficient (ClogP) • hydrophobicity

Journal of Biomolecular Screening, Vol. 10, No. 4, 293-303 (2005)
DOI: 10.1177/1087057104272498
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