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.