CrystalDirect™: bridging the automation gap between crystallisation and X-ray data collection

by Annabelle Grimm

In a nutshell:

  • ŸEMBL HTX lab provides automated crystal harvesting and processing services though application of innovative technologies
  • Ÿthe technology serves as the basis for establishing a fully automated protein to structure crystallography pipeline
  • the approach provides new opportunities for structure-guided drug design through an automated pipeline for compound and fragment screening with macromolecular crystallography

The development of automated X-ray beamlines at synchrotron facilities, and the widespread use of crystallisation robots dramatically expanded the capabilities of crystallography beamlines and facilitated approaches in structure-guided drug design, such as the structural analysis of very challenging targets and the investigation of small molecule-protein interactions.

However, the preparation of the crystals for diffraction experiments still requires manual operations which are not only time consuming but can result in sample loss due to damage of crystals, and hence, represents a bottleneck in the workflow of crystallisation pipelines.

The CrystalDirect™ technology available at the EMBL High Throughput Crystallisation Laboratory (HTX lab) in Grenoble enables fully automated crystal harvesting, chemical delivery (soaking) and cryo-cooling, and therefore closes the automation gap between crystallisation and X-ray data collection. See a few impressions of CrystalDirect™ at work in the pictures below.

Picture credit: EMBL Grenoble.

The HTX lab operates its services in coordination with the European Synchrotron Radiation Facility (ESRF). The combination of the CrystalDirect™ technology and the Massively Automated Sample Selection Integrated Facility (MASSIF) at ESRF provide the opportunity to support fully automated protein to structure pipelines.

In the future two new types of access models will be available from the HTX lab:

  1. a fully automated, remote-controlled pipeline for macromolecular crystallography
  2. a fully automated pipeline for ligand and fragment screening

If you would like to obtain further information about the crystallisation services provided by EMBL, please contact us. You also have the chance to meet the inventors of the CrystalDirect™ technology in person at the 2016 PSDI conference from 13 to 15 November in Malmö.

Further reading:

Zander U, Hoffmann G, Cornaciu I, Marquette JP, Papp G, Landret C, Seroul G, Sinoir J, Röwer M, Felisaz F, Rodriguez-Puente S, Mariaule V, Murphy P, Mathieu M, Cipriani F, Márquez JA. (2016) Automated harvesting and processing of protein crystals through laser photoablation. Acta Crystallogr D Struct Biol 72(Pt 4):454-466. doi: 0.1107/s2059798316000954