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.