High-Throughput Crystal Screening

Typical methods for generation of polymorphs include sublimation, crystallization from different solvents, vapor diffusion, thermal treatment, melt crystallization, and rapid precipitation. High-throughput screening methods have been reported for polymorph screening.50... 

R. Hilfiker, J. Berghausen, F. Blatter, et at. Polymorphism - integrated approach from high-throughput screening to crystallization optimization, J. Therm. Anal. Calorim., 73, 429 440 (2003). 

Microbatch can be performed either manually or automatically (Chayen et ah, 1992). It is the simplest crystallization method and therefore can be easily performed in high-throughput trials. Current robots can dispense microbatch trials down to 1 nl volumes. Depending on the type of oils used to cover the trials, this technique can be harnessed for both screening and optimization experiments. 

A fully automated protein crystallography beamline at a third-generation synchrotron source can screen several hundred crystals daily. Automatic evaluation of the diffraction images to ascertain crystal quality is, therefore, a critical step for high-throughput data acquisition. Evaluation of each image requires software that mimics the traditional visual assessment of crystal quality. 

Cohen, A. E., McPhUlips, S. E., Song, J. and MiUer, M. D. (2005). Automation of high-throughput protein crystal screening at SSRL. Synchrotron Radiation News 18, 28-35. 

Zhang, Z., Sauter, N. K., van den Bedem, H., SneU, G. and Deacon, A. M. (2006). Automated diffraction image analysis and spot searching for high-throughput crystal screening. /. Appl. Crystallogr. 39,112-119. 

Walter, T. S., et al. (2005). A procedure for setting up high throughput nanolitre crystallization experiments. III. Crystalhzation workflow for initial screening. 

Hilfiker, R. Berghausen, J. Blatter, F. etal Polymorphism - Integrated Approach from High-Throughput Screening to Crystallization Optimization /. Therm. Anal. Calorim. 2003, 73, 429-140. 

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