Crystallization trials automating

The first semi-high-throughput automated system to dispense crystallization trials of less than 1 jl1 was designed in 1990 to deliver batch trials imder oil (Chayen et ah, 1990). The method was named microbatch to define a microscale batch experiment. It was designed to obtain maximum information on the molecule to be crystallized while using minimal amounts of sample. In order to prevent the evaporation of such small volumes, the trials are dispensed and incubated under low density (0.87 g/cm ) paraffin oil (Fig. 3.2). The crystallization drops remain under the oil since the aqueous drops are denser than the paraffin oil. 

A regularly formed crystal of reasonable size (typically >500 pm in each dimension) is required for X-ray diffraction. Samples of pure protein are screened against a matrix of buffers, additives, or precipitants for conditions under which they form crystals. This can require many thousands of trials and has benefited from increased automation over the past five years. Most large crystallographic laboratories now have robotics systems, and the most sophisticated also automate the visualization of the crystallization experiments, to monitor the appearance of crystalline material. Such developments [e.g., Ref. 1] are adding computer visualization and pattern recognition to the informatics requirements. 

An alternative means of conducting trials with a similar outcome to seeding, but without the need to handle crystals, is by dilution. An additional benefit of dilution methods is that they are more amenable to automation compared with seeding techniques (Chayen, 2005). The aim of dilution is to start the trial at nucleation conditions and after a given time... 

Wilson, J., Towards the automated evaluation of crystallisation trials. Acta Crystal-logr. 2002, D58, 1907-1914. 

To date robotic automation has been the dominant strategy both for miniaturizing standard crystallization protocols and for fostering high-throughput crystallization [11, 12]. This allows more trials to be conducted with a given sample volume. 

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