A plate handler has been integrated with the Opera high throughput confocal screening system, permitting fully automated cell-based screening. Combining the Opera and the automated plate handler enables analysis of up to 80 plates in a fully automated, walk-away mode, managing plate densities from 96 to 2080-well format. Plate processing is controlled by Bernstein scheduling software, which provides real-time dynamic scheduling, permitting manual interruption and modification of the screen in progress. Optional bar code capabilities are provided in addition to date and time identification of individual plates. Data storage of the results in the Opera database permits run and plate oriented access to the screen output.