When Vic Armijo first began working on a prototype to solve one of structural biology’s most stubborn problems, he was staring down years of trial, error, and frozen samples gone wrong. Now, at EMBL Grenoble, that persistence has yielded two breakthrough instruments—EasyGrid and EasyGrid Control—that are transforming how scientists prepare and assess samples for cryo-electron microscopy. These systems, developed by Gergely Papp’s instrumentation team, automate the once finicky, manual process of vitrifying biological samples, ensuring consistent ice quality and drastically improving reproducibility in imaging proteins, viruses, and even whole cells.
Cryo-EM has long promised near-atomic views of life’s molecular machinery, ever since Jacques Dubochet’s pioneering work at EMBL helped earn him the 2017 Nobel Prize in Chemistry. But the technique’s potential has been bottlenecked by sample preparation: a delicate, human-dependent process where even a micron-thick layer of ice or a single ice crystal can ruin weeks of work. Until now, researchers had no reliable way to prescreen samples before loading them into million-euro microscopes—leading to wasted time, costly delays, and inconsistent results.
EasyGrid changes that. Using pressure waves to evenly spread liquid across a grid and an innovative ethane jet system for ultra-rapid vitrification, it produces uniformly thin, glass-like ice—critical for high-resolution imaging. Unlike conventional methods that rely on immersion in liquid ethane, the ethane jet cools samples up to ten times faster, preserving delicate internal structures even in the nuclei of whole cells. The system works across scales, handling everything from isolated proteins to cultured cells, and is compatible with cryo-EM, cryo-electron tomography, and X-ray nano-imaging. Meanwhile, EasyGrid Control automatically evaluates grid quality, using imaging and AI-driven analysis to flag only the best samples for microscopy.
"With EasyGrid and EasyGrid Control, the whole process line, from the loading of the grid to the screening, is done autonomously," says Armijo, mechatronics engineer and co-first author of the team’s Nature Methods paper. This end-to-end automation doesn’t just save time—it opens new doors for in situ structural biology, where scientists can now study macromolecules in their native cellular context with unprecedented clarity.
Already deployed at the EMBL Imaging Centre, the systems are poised to become new standards in structural biology labs worldwide. By removing human variability and streamlining quality control, EasyGrid and EasyGrid Control don’t just improve efficiency—they make high-resolution imaging more accessible, reliable, and scalable. As structural biology pushes toward ever more complex questions, tools like these ensure that the foundation—sample preparation—is finally solid enough to build on.