Automation of protein crystallization trials: use of a robot to deliver reagents to a novel multi-chamber vapor diffusion plate.

We report here the automation of search procedures to rapidly screen a large number of reagents and incubation conditions that lead to the formation of protein crystals. The system consists of a Biomek 1000 Automated Laboratory Workstation from Beckman Instruments under the control of a custom user-interface program developed by Cryschem. A plate composed of twenty-four vapor diffusion chambers, each with its own reservoir well and protein drop holder was designed by Cryschem to fit the Biomek table. The Cryschem software manages a large data base of incubation conditions and generates instructions for the workstation to dispense the protein, buffers, detergents, cofactors and other reagents used to promote the formation of protein crystals. The plate is manually positioned on the Biomek table and then under program control additions are automatically made to each chamber as follows: Precipitating solution is added to each reservoir well and the protein solution along with the precipitating solution and various other reagents are added to each drop holder. The plate is removed from the table and a mylar tape is applied to simultaneously seal all the chambers. The plates are placed at a controlled temperature and periodically examined for crystal formation.