X-ray crystallography is the most successful method employed to gain an understanding of macromolecule structures at the atomic level. Obtaining the required crystals from a purified sample of a protein, nucleic acid or any macromolecular complex poses significant challenges since tedious experimental set-ups with poor success rates are involved. First, an initial crystallisation screen is carried out on the purified sample with a broad range of commercially available conditions. Then, in-house custom optimisation screens are prepared in order to reproduce and optimise any initial leads. With optimised crystals, it is later possible to acquire quality X-ray diffraction data and hence solve high-resolution structures.
Optimisation screens are usually prepared manually on traditional liquid handlers (i.e. a moving head with 8 tips where pipetting is controlled with a system liquid). The associated protocols are time consuming (10–20 minutes per screen). In addition, typical stock solutions contain reagents with low surface tension and/or high viscosity such as the high molecular weight polyethyleneglycols (PEGs). This often results in pipetting inaccuracy and cross-contamination.
This study shows the optimisation of crystals from three different protein samples at the Laboratory of Molecular Biology (LMB, Cambridge, UK) with a novel automated liquid handling technology developed by TTP Labtech called dragonfly.