Abstract
A totally integrated serial dilution assay plate preparation system that fully uses the high precision nanoliter dispensing capabilities of acoustic liquid handlers has been developed and implemented. The application uses a hybrid of a serial dilution method and a direct dilution method, achieving a wide concentration range for the dilution series, while avoiding additive errors inherent to traditional serial dilution methods. The method allows assay miniaturization, which greatly reduces reagent and consumable costs to the customers. The system is in production at AstraZeneca and has generated high-quality assay ready plates for high-throughput screening and secondary screening since 2005. Further development in recent years has expanded the flexibility of the assay ready plate creation process to meet varied screening requirements. We will discuss the requirements for assay ready plates for concentration response testing and describe the novel plate creation method in detail with the rigorous validation procedures. Along with method validation data, some real-life screening results will be presented to compare an experiment conducted on compounds prepared using the novel hybrid method and those prepared using a more traditional serial dilution method, which endorses the application of the novel method.
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