The Cipriani team develops instruments and methods for structural biology research and works with industry to make these available to scientists worldwide.
Previous and current research
The core activity of our team is developing instruments and methods for X-ray scattering experiments. The CrystalDirect™ harvesting station is extensively used at the Grenoble HTX lab. With storage capacity extended to several hundred samples, it is ideal for ligand-screening applications. Harvesting at 4°C will soon be possible with a new harvester currently under construction.
In order to shorten the time from crystal harvesting to data collection, and to reduce puck-handling effort, we propose to supply CrystalDirect plates directly to the beamlines. A proof of concept was made at the ESRF beamline ID30B with CrystalDirect-to-beam, a setup in which a CrystalDirect harvester is coupled to the FlexHCD sample changer and MD2S diffractometer (Figure 1). Here, crystals are harvested and directly mounted on the goniometer of the MD2S for data collection, to be processed one by one under user control or in a fully automated pipeline with a pre-defined processing plan. A specific MXPressR workflow was used to retrieve crystals from the harvester instead of the sample changer storage Dewar. An average sample turnover of six minutes was obtained. Data collections have also been operated at room temperature on harvested crystals, using an HC-lab humidity control device, and automated dehydration experiments were successfully performed.
The miniSPINE sample holders and pucks have been finalised, and will soon be commercialised. The MD3up diffractometer developed with Arinax was installed at the ESRF ID23-2 micro-focus beamline, where it is now regularly used for fast mesh and collect protocols. Furthermore, we have started the development of a new MD3up dedicated to solid support serial crystallography for the future ESRF EBS beamline ID29.
All these developments include contributions from the Márquez and McCarthy teams, and ESRF Structural Biology group. Supported by EMBLEM, most of our instruments are available to the scientific community worldwide.
Future projects and goals
A new ESRF EBS beamline will be equipped with a CrystalDirect™-to-Beam setup. In order to shorten crystal-centring times, we plan to use NewPin sample holders. Combined with the intensity of future beams, and the use of fast pixel detectors, the sample turnover time could be reduced to two minutes. We also hope to see miniSPINE become a new sample holder standard. Finally, the growing interest in Cryo-EM makes grid preparation and screening a real bottleneck. This is a new challenge we have started to consider with the Grenoble IBS platform and the Heidelberg Cryo-EM core facility.