Development of instrumentation for synchrotron X-ray and neutron beamlines

The Instrumentation Team at EMBL Grenoble has developed innovations to further advance the capabilities of EMBL technologies, such as X-ray crystallography.

X-ray crystallography involves shining intense X-ray beams at protein crystals to determine their structure. When the high-brilliance, third-generation synchrotron source at the ESRF opened in 1994, the entire operation of sample handling on crystallography beamlines was done manually.

Since the opening of the synchrotron source at the ESRF, the Instrumentation Team at EMBL Grenoble has worked closely with the ESRF Structural Biology Group to pioneer instruments and automate crystallography beamlines to increase the efficiency of structure determination processes, from sample preparation to data collection. Two of the most notable inventions are micro-diffractometer devices (called MD2 and MD3), which are goniometer devices that enable the automated and high-precision positioning of protein crystals in an X-ray beam, significantly increasing the efficient use of beamtime at synchrotrons.

With the support of EMBL's technology transfer partner, EMBLEM, micro-diffractometer devices -- MD2 and MD3 -- have been patented and, through partnering with scientific instrumentation manufacturer Arinax, commercialised to academia and industry. Ralf Siebrecht, Chief Executive Office of Arinax, underlined the importance of the trust and values shared with EMBL Grenoble: "At Arinax, we are aware of this symbiosis that works very well with EMBL." He also emphasised the special working environment at EMBL, which has enabled the Instrumentation Team to grow and support the needs of the technology development cycle: the emergence of a need from a scientist, the development of an innovation, use by the research community, and validation of the new technology.

Arinax has frequent discussions with EMBL about development projects based on feedback on device testing from other synchrotrons to fuel new innovations, such a MD2S, a follow-up to MD2. MD2S plays an important role in high-throughput crystallography, e.g. in ligand and compound screening for drug discovery. MD3, by contrast, provides new opportunities for conducting experiments to understand protein dynamics at biological temperatures.

"This device opens windows for cutting-edge research in structural biology. Today's protein micro-crystals would be impossible to align by simply doing it manually. The MD3 is doing this job automatically and with nanometre precision," said Siebrecht.

As of 2021, Arinax has installed micro-diffractometers in over 20 synchrotrons around the world (including in Europe, USA, Canada, Korea, China, Taiwan, and Australia). MD2S and MD3 micro-diffractometers cost around €450,000 and €600,000, respectively (depending on the options and services that customers choose), which is a sizable investment that synchrotron facilities are willing to pay to keep their services at the cutting edge.