Syrrx's high-throughput image-scanning robot. Credit: AARON FELDMAN

Mapping the detailed atomic structure of a target protein is vital for identifying drug candidates that can bind with it. Elucidating protein structure by crystallography has for years been a laborious operation carried out by specialists, but automation is now beginning to bring the process up to the speeds demanded by high-throughput systems.

Automated crystallography systems for the general research market have been available for some time from specialists such as Tecan in Männedorf, Switzerland, and BSI Proteomics of Gaithersburg, Maryland. But dedicated drug-discovery companies are now forcing the pace, with the vast majority of commercial protein crystallography done by just two companies, Syrrx and Structural GenomiX, both based in San Diego.

Syrrx wants to automate every stage of protein-structure determination. It deploys a family of whimsically named robots, beginning with a high-throughput robot called Sonic Hedgehog that can purify about 100 proteins in five hours. The proteins are then crystallized by Agincourt, a robot named for English king Henry V's application of superior technology to overcome extreme odds. Agincourt crystallizes proteins from droplets of just 50 nanolitres, about a fortieth of the volume of previous systems. “Everything is miniaturized,” says business development director Ned David. “These droplets enable our whole approach to work in a way that is economically feasible. You can't do nano-drops without automation because you can't set your pipette for 50 nanolitres.”

To match the demands of Agincourt, Syrrx has two imaging-station robots called Fort Knox and Fort Bliss, each capable of scanning over a million images a day for suitable protein crystals. These are then taken to Syrrx's dedicated synchrotron beamline at the Advanced Light Source in Berkeley for X-ray diffraction. Data are collected by another robot called Robohutch, which David says can increase throughput at this stage tenfold.

There is still scope for further automation, particularly in the first stages of protein production. Syrrx is investigating how more mammalian proteins can be made in eukaryotic cell systems, rather than from genes cloned in bacteria.