Automation of <i>In Vitro</i> Dose-Inhibition Assays Utilizing the Tecan Genesis and an Integrated Software Package to Support the Drug Discovery Process

Abstract

We have automated in vitro dose-inhibition assays to evaluate newly synthesized chemical entities and to rapidly produce and disseminate the results with minimal personnel. A variety of assay methods were automated using the Tecan Genesis Workstation to produce ten-point titration curves and generate reproducible K I values. Our integrated software package provides the unique ability to simultaneously inventory and schedule compounds into various in vitro assays. A worklist generator, in combination with a Gemini script automatically makes variable pre-dilutions of compounds, retrieves incubation plates from the Carousel using the RoMa Arm, performs serial dilutions of compounds within the final 96 well incubation plate using disposable tips, and adds essential assay reagents. Our “Expert System for Data Analysis” automatically retrieves data from a reader (e.g. TopCount, FLIPR or VIPR), analyzes the data based on a set of rules, and provides value added reports. An overview of the basic workflow and the integrated software for support of the drug discovery process is described. The ability of the Tecan Robot to produce dose-inhibition profiles is illustrated and validated by using a radioligand binding assay and a DMSO solubilized fluorescein dye method.