Advances in high-throughput, automated techniques and instrumention for protein crystallization screening

In current structural biological researches, obtaining high quality protein crystals suitable for X-ray crystallography largely relies on high-throughput screening of hundreds to thousands of protein crystallization conditions. Recently, the rapid developments of automated liquid handling techniques and instrumentation provide effective and reliable solutions for protein crystallization and screening with high-throughput and low consumption. This article reviews the development of automated liquid handling techniques in protein crystallization area, including pipetting, syringe pump metering, synchronized nanoliter quantitative aspirate dispense, inkjet-printing, acoustic dispensing and microfluidics. Their advantages and disadvantages for protein crystallization are discussed. In addition, we also introduce several fully integrated crystallization workstations, which mostly based on pipetting and syringe pump techniques. These workstations integrate multiple functions including bar coding, plate handling, plate storage, environmental control and software management.