Automatic implementation of precise grid screens: the four-corners method.

Crystallization trials can be designed as a systematic gradient of the concentration of key reagents and/or pH centered on the original conditions. While the concept of the grid screen is simple, its implementation is tedious and difficult by hand. A procedure has been developed for preparing crystallization grid screens that is both efficient and achieves high accuracy because it relies on a limited number of solutions that are carefully prepared by hand. The ;four-corners' approach to designing grid screens uses the minimum and maximum concentrations of the components being varied in the grid screen as the sole stock solutions. For an N-dimensional grid only 2(N) corner solutions require detailed preparation, making the screens efficient. Furthermore, by keeping the concentrations as tight as possible to the grid, the potential impact of pipette errors is minimized, creating a highly precise screen.