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30-Mar-2026
In transmission electron microscopy (TEM), a beam of electrons is passed through a thin sample to obtain extremely high-resolution images. To produce samples suitable for TEM imaging, a focused ion beam (FIB) is used to shave material away from the sample until only a thin layer is left, in a process called “milling”. Brenner, Plitzko, and Klumpe recently developed a novel technique for shaping focused ion beams into an “ion knife”, supported by funding from the Instruct-ERIC R&D pilot scheme to Klumpe.
The ion beam used in FIB milling methods is typically generated using plasma or liquid metal ion sources, most commonly gallium. The use of ion beams for sample thinning has been common in the fields of semiconductors and material science for many years and has more recently been adopted in structural biology. However, no one has explored whether the ion beam could be shaped to potentially improve the process. This is what the team set out to do in their study.
Taking inspiration from the field of light-sheet microscopy, Brenner, Plitzko, and Klumpe used the stigmator of an FIB instrument to approximate the effect of a cylindrical lens, producing an elongated ion beam resembling a knife edge. They also showed that the dimensions of the ion knife can be manipulated by adjusting the stigmator strength and they developed techniques to allow users to characterize the beam profile of the ion knife in a streamlined way to facilitate sample thinning. The team concluded their study by using the ion knife to prepare thinned samples from frozen-hydrated cells and thicker tissue samples for cryo-electron tomography, a technique where TEM is used to reconstruct 3D volumes.
Due to the wider profile of the ion knife compared with a conventional, converged ion beam spot, larger areas can be removed from a sample at a time, allowing for faster milling and potentially a higher sample-preparation throughput. The ion knife, with its narrow shape, could also reduce loss of sample material during serial lift-out procedures, in which many thinned sections are produced from a single sample. Together, these results highlight the potential of the ion knife as a simple strategy to improve the efficiency of FIB-based sample preparation for cryo-electron tomography.
Figure 1 – Example of a sample (a) before and (b-c) after production of a thin section using an ion knife. (a-b) shows the sample from the front, (c) shows an image from above. Sample material has been shaved away using a shaped focused ion beam to produce a thin section of sample, giving a trench-like appearance.
"The excellent infrastructure provided by Instruct-ERIC enabled us to develop prototypes for the next generation of ion knives. It represents a highly valuable resource for technological developments that are otherwise difficult to fund, yet are essential for advancing complex sample preparation workflows in cryo-electron tomography." says Sven Klumpe.
This study demonstrates that a shaped ion beam can perform similar to conventional non-shaped beams and has the potential to speed up preparation of samples for transmission electron microscopy and support high-throughput methodologies.
Johann Brenner and Jürgen M. Plitzko are based at the Max Planck Institute of Biochemistry in Martinsried, Germany. Sven Klumpe is based at the Vienna BioCenter and affiliated with the Institute of Molecular Biology and the Research Institute of Molecular Pathology, in Austria.
Instruct-ERIC runs several schemes providing researchers with the opportunity to focus on R&D. The Instruct-ERIC R&D pilot award is aimed at early career researchers and provides funding to support small pilot R&D projects that focus on technology or software development within integrated structural biology. Instruct ERIC also offers access to electron microscopy and associated sample preparation at several of its facilities.
You can read the full paper here - “Exploring shaped focused ion beams for lamella preparation”.
