Utilization of the ORCA to Completely Automate Scintillation Proximity Assays

Abstract

A laboratory designed to carry out totally automated high throughput screening (HTS) assays was established recently at the Roche Research Center in Nutley, NJ. The system was designed by Sagian Inc. and uses an optimized robot for chemical analysis (ORCA) robotic arm to transport microplates from station to station. One of the first assays adapted for automation was a scintillation proximity assay (SPA), which screens for inhibitors of binding of a transcription factor to its target DNA. The SPA format was chosen because it is microplate based, and the required instrumentation is available in robot-friendly configurations. In addition to collecting inhibition data, we have compiled control data to assess the quality of results generated by a completely automated HTS system. Generation of usable data began approximately 1 month after the initial setup of the automated system. Results from automated and manual assays of the same compounds correlated well (r = 0.969), confirming the accuracy of the automated method. Over 25,000 compounds and mixtures have been tested in the automated SPA. Confirmatory assays revealed a false positive rate of -1.6%, possibly due to inadequate conditions during interim compound storage. Positive control data showed excellent within-plate and within-run reproducibility. The consistency and reproducibility of the data led to the elimination of duplicate determinations, doubling throughput to 2000 compounds/8 h.