Scaling up high-resolution X-ray nanoimaging

Seeing the intricate structures inside biological tissue in three dimensions is essential for understanding how cells are organized and how they function. But looking at those structures at the nanoscale is challenging. Conventional microscopy methods can provide high-resolution images, yet they often require samples to be cut into thin sections. X-ray imaging offers a different approach: It can penetrate relatively large samples and produce three-dimensional views without physically slicing those samples apart. At synchrotron facilities, highly focused and coherent X-ray beams can push this technique into the nanoscale.

One such technique is X-ray nano-holotomography, a form of three-dimensional phase-contrast imaging. Rather than simply measuring how much X-ray radiation passes through a sample, the technique also detects subtle phase shifts in the X-rays caused by the material. The technique is full-field, capturing the entire field of view in a single measurement rather than through sequential scanning, which makes it significantly faster than scanning-based methods. Images are collected at multiple distances from the sample, allowing researchers to recover information about the phase of the X-ray wave and reconstruct the sample’s three-dimensional refractive index. Hard X-rays, with their ability to penetrate materials and biological tissue, make the technique particularly useful for nondestructive nanoscale imaging. Modern synchrotron beamlines can achieve spatial resolutions below 50 nanometers, with data acquisition times of less than one hour.

However, achieving high resolution also makes the imaging process more sensitive to imperfections. The X-ray beam used for nano-holotomography is not perfectly uniform. Small errors in the position of the sample can also affect the measurements. These effects become particularly important when imaging features only tens of nanometers across. Traditionally, researchers address these problems in separate stages: First align the images, then retrieve the phase information, and finally reconstruct the three-dimensional object. While this approach works well for many experiments, errors introduced during one stage can carry into the next. 

Read more on the APS website

Image: A new joint nano-holotomography reconstruction technique, based on the bilinear Hessian method and multi-node, multi-GPU acceleration, enables processing of large 3D brain volumes (one slice is shown) and reveals synapses (orange), mitochondria (cyan), endoplasmic reticulum (pink), and chromatin (green) in a neuronal nucleus.

Optimizing Cryo EM Data Collection: New Study Provides Evidence Based Guidelines

A new publication presents a comprehensive analysis that strengthens the foundations of single particle cryogenic electron microscopy (cryo EM), one of the most powerful techniques currently available for visualizing biological structures at near atomic resolution. The research was conducted by a team of scientists from the SOLARIS National Synchrotron Radiation Centre, in collaboration with a representative of the Malopolska Centre of Biotechnology at the Jagiellonian University.

The research team systematically examined how key data‑collection parameters—such as electron dose, onset of radiation damage, pre‑exposure effects, and dose‑weighting strategies—impact the final quality of cryo‑EM reconstructions. Using ribosome particles from E. coli and human cells, the authors established practical recommendations that help researchers optimize imaging conditions and achieve higher‑resolution results, while also saving time and reducing the volume/size of data collected.

These findings offer an important reference point for the cryo‑EM community and support more efficient, reproducible, and reliable experimental workflows.

Read more on the SOLARIS website

Image: Graphical representation of the publication’s scope

Credit: SOLARIS

Lasing achieved with hard X-rays in a resonator

Novel “XFELO” laser system produces razor-sharp X-ray light

For the first time, researchers have amplified X-ray light multiple times in a resonator cavity, in a way highly similar to traditional lasers. With great success: the new technique delivers extremely energetic X-ray pulses for high-precision experiments. This development opens up entirely new possibilities for research in physics, chemistry, or biology. The system is called “XFELO”. Researchers from European XFEL, DESY and Hamburg University have published their findings in the latest edition of the journal Nature. 

The team of engineers and scientists have shown for the first time that a hard-X-ray cavity can provide net X-ray gain, with X-ray pulses being circulated between crystal mirrors and amplified in the process, much like happens with an optical laser. The result of the proof-of-concept at European XFEL is a particularly coherent, laser-like light of a quality that is unprecedented in the hard X-ray spectrum. Lasing inside a cavity had been challenging to achieve with short-wavelength X-rays for a variety of reasons, including – on a basic level – that the nature of the light makes it difficult to reflect the beam at large angles. The “XFELO” (short for: X-Ray Free-Electron Laser Oscillator) technique opens new perspectives for scientific investigations, from ultrafast chemical reactions to detailed analyses of the smallest biological structures.

Read more on the European XFEL website

Image: Illustration of the XFELO system: a hard X-ray pulse (red) is reflected by a set of diamond mirrors and oscillates through arrays of magnets, so called undulators. On each roundtrip the pulse meets a new electron bunch (blue), which emits X-rays while passing through the undulators on a slalom course.

Credit: European XFEL

X-raying auditory ossicles – a new technique reveals structures in record time

Scientists at the Paul Scherrer Institute PSI have refined an X-ray diffraction technique for detecting biological structures from nanometres to millimetres – reducing the time needed to make the measurement from around one day to about an hour. This opens up a wide range of possibilities for biomedical research – from analysing bone and tissue structures to supporting the development of new implants.

Biological materials are masterpieces created by nature. Bones, for example, are extremely hard, yet at the same time elastic enough to withstand lateral forces without breaking easily. This combination of properties results from their hierarchical structure as composite materials – they combine materials that have different structures on different scales. Human-made composite materials are similar in the way they are made up. In reinforced concrete, for example, the concrete component, consisting of cement and sand, can withstand high pressure, while a steel mesh provides high tensile strength and transverse stability. 

Until now, examining such biological materials in detail has required the use of several different instruments, such as electron microscopes or classic light microscopes. However, scientists at the PSI Center for Photon Science have now refined an X-ray diffraction technique that was developed at the institute ten years ago, allowing it to be used to characterise materials on scales from nanometres to millimetres simultaneously and much faster than before. A complete scan now only takes about an hour, instead of a whole day.

To demonstrate the efficiency of their method, the researchers used the Swiss Light Source SLS to reveal the alignment of collagen fibres in a human ossicle known as the incus, or anvil. Collagen fibres are thread-like protein structures that provide tensile strength and elasticity to bones. “In doing so, we have taken the leap from a scientific method to a practical technique,” says Christian Appel, postdoctoral researcher and first author of the study. The results have now been published in the journal Small Methods as its cover story. In future, this method could be valuable in areas such as the study of complex tissue, the analysis of bone diseases and the optimisation of implant designs.

Read more on the PSI website

Image: Scientists at PSI were able to observe the local collagen structures in an ossicle by scanning it with an X-ray beam. The different colours of the cylinders indicate how strongly the collagen bundles are spatially aligned in a section measuring 20 by 20 by 20 micrometres.

Credit: © Paul Scherrer Institute PSI/Christian Appel