Improving IC50 Results with Acoustic Droplet Ejection

IC50 analyses are typically sample, time, and labor intensive. They commonly require multiple dilution steps and consume significant amounts of sample compound. Aqueous intermediate dilutions of concentrated stock solutions can lead to rapid sample precipitation and the generation of false negatives (Spicer, T.; Fitzgerald, Y.; Burford, N.; Matson, S.; Chatterjee, M.; Gilchrist, M.; Myslik, J.; O'Connell, J. Pharmacological evaluation of different compound dilution and transfer paradigms on an enzyme assay in low volume 384-well format, Poster presented at Drug Discovery Technology, August 2005, Boston, MA). Hydrophobic compounds may stick to pipette tips or intermediate dilution vessels, reducing the concentration of the analyte in the dilution and also increasing the possibility of cross contamination. The requirement for multiple serial dilutions in common IC50 analyses causes significant accumulated error. Concentrations of dimethyl sulfoxide (DMSO), the typical solvent used to solubilize compound lib...