Category: ESRF

Human Organ Atlas Hub co-chair wins the Lennart Nilsson Prize

Human Organ Atlas Hub co-chair wins the Lennart Nilsson Prize

ESRF user and Human Organ Atlas Hub co-chair Professor Maximilian  Ackermann, from the RWTH University Aachen, University Mainz and Helios University Clinics Wuppertal, has been awarded the Lennart Nilsson Prize 2025 by the Karolinska Institutet in Stockholm for his artistic images of human anatomy and pathology using notably the technique of Hierarchical Phase-Contrast Tomography (HiP-CT) at the ESRF, the European Synchrotron, Grenoble, France.

The Lennart Nilsson Prize, one of the world’s most prestigious awards in the field of scientific photography, recognises Ackermann’s achievements in the use of novel, unique high-resolution imaging techniques, and especially the use of Hierarchical Phase-Contrast Tomography (HiP-CT), developed at the ESRF, as well as his artistic view of the human anatomy and its pathological changes.

A pathologist at the University Hospital RWTH Aachen and Helios University Clinics Wuppertal and anatomist at the University Mainz, Ackermann is also co-chair of the Human Organ Atlas hub, where scientists and clinicians use HiP-CT technique at the European Synchrotron (ESRF) to provide valuable insights into human anatomy and diseases such as Covid-19, pulmonary fibrosis and cancer. A compendium of his artistic renderings of the human anatomy and numerous diseases can be found on the website PATHart.org.

The Human Organ Atlas Hub (HOAHub) is an international interdisciplinary scientific collaboration led by University College London (UCL) and the European Synchrotron (ESRF), with the University Medical Center Mainz, and the University Hospital RWTH Aachen. Funded by the Chan Zuckerberg Initiative, it aims to create a physical and virtual Hub that uses a novel technique developed at the ESRF, HiP-CT, to scan whole human organs with local cellular resolution, producing a “Human Organ Atlas in Health, Ageing and Disease“.

Read more on ESRF website

Image: The coloured scanning electron micrograph of a human lung with COVID19 infection shows numerous alveoli with inflammatory cells (yellow), hemorrhages (red) and hyaline membranes (blue).

 Credit: M. Ackermann

Nanoburgers with promising flaws

Nanoburgers with promising flaws

Publication in ACS Nano: DESY team finds surprising defects in tiny metal particles which could stimulate the development of more efficient catalysts

Catalysts are indispensable in many industries: they speed up chemical reactions, making them economically viable. They often consist of tiny particles, just a few nanometres across, to which molecules attach themselves, making it easier for them to form a bond with another reagent. The catalysts themselves are left unchanged. One class of nanocatalysts consists of the precious metals platinum and rhodium and is used, for example, in the purification of waste gases, in hydrogen production and in fuel cells.

The team led by DESY physicist Andreas Stierle has been studying such platinum-rhodium catalysts for quite some time. However, when they analysed the particles again using X-rays, they were surprised to find that some of the nanoparticles are not tiny, homogeneous lumps but consist of an upper and a lower half – like the two halves of a burger bun. Although the two halves are stuck together, the nature of this bond and how it affects the catalytic properties of the nanoparticles was unclear.

To work this out, Stierle’s team designed an experiment at the European Synchrotron Radiation Facility ESRF in Grenoble. ‘It produces an extremely narrow X-ray beam that can be used to study individual nanoparticles,’ explains Stierle. Specifically, the researchers used a method known as Bragg Coherent Diffraction Imaging (BCDI), in which the X-ray beam creates a special diffraction pattern as it passes through the nanoparticle, and this is recorded by a detector. ‘Special algorithms can then be used to reconstruct how the atoms are arranged in the crystal lattice and where they deviate from the regular structure – distortions, defects and dislocations in the crystal lattice,’ explains Ivan Vartanyants, who supervised the reconstructions.

What made their experiment different was that the measurements were performed while the nanocatalysts were active. The group directed a stream of carbon monoxide and oxygen to pass over the nanoparticles, on whose surface the gas was converted into CO2 – at temperatures of more than 400 degrees Celsius. ‘These experiments were extremely difficult; we had to keep the nanoparticles fixed to within ten nanometres so that the X-ray beam always illuminated the entire particle,’ explains first author Lydia Bachmann, who is studying this topic as part of her PhD. ‘To do this, we had to make sure that the conditions were absolutely steady.’

The outcome was unexpected: the experts discovered pronounced crystal defects where the upper and lower halves of the nanoburgers meet. The two boundary surfaces did not fit perfectly on top of each other; atoms were missing around the outer edges. These gaps cause all the atoms in the vicinity to shift, significantly distorting and displacing the crystal lattice.

What was truly remarkable was that these ‘flaws’ had an extremely positive effect on the catalytic properties of the nanoburgers. ‘The defects serve as unique absorption sites for molecules,’ explains co-author Thomas Keller. ‘Molecules such as oxygen adhere very well to them, which increases the effectiveness of the catalyst.’ In the future, these findings could help industry to develop more efficient and effective catalysts – through deliberate ‘defect engineering’ to create as many binding sites as possible on the nanoparticles, where molecules can be converted.

Read more on DESY website

Image: The Nano-Burger in action: The two ‘halves‘ of the platinum-rhodium catalyst interact with reagents in this simulation.

Credit: Science Communication Lab for DESY

A hidden form of rare earth element cerium identified in fossil fish bones under the sea

A hidden form of rare earth element cerium identified in fossil fish bones under the sea

Rare earth elements and yttrium (REY) are essential to modern technologies, yet we know little about how they concentrate at the Earth’s surface, particularly in marine sediments, which hold vast reserves.

REY are enriched in deep-sea mud by several billion times compared to seawater, and, from a fundamental perspective, determining the chemical forms of REY is critical to understanding one of the highest levels of metal partitioning on Earth. 

The sedimentary component hosting REY consists of biogenic and authigenic fluorapatite (FAp, Ca5(PO4)3F). When fish die, their bones and teeth accumulate on the seafloor, allowing biogenic FAp to adsorb REY from seawater and pore fluids over extensive periods, ranging from hundreds of thousands to millions of years, during the diagenesis process. Until now, scientists thought cerium just replaced calcium atoms in the bone structure. However, scientists led by the ESRF have found otherwise.

ESRF scientist Alain Manceau and his team, in the framework of his ERC Advanced Grant Deep-SEE, analysed several tens of fossil bones and teeth handpicked at 1.94 and 4.70 meters depth below the seafloor in a sediment core (16GC) collected in the Pacific Ocean’s Clarion-Clipperton Fracture Zone. They found that cerium actually forms a completely different local structure within the fish remains, separate from that of calcium. This structure is a new kind of cerium-phosphate compound precipitated in an amorphous phase at the surface of FAp nanocrystals.

The team used the techniques of X-ray fluorescence mapping, to see the location of cerium, and high-energy-resolution fluorescence-detected X-ray absorption spectroscopy (HERFD-XAS), to track how the cerium atoms bond to other atoms nearby, in the newly built ID24-DCM.

Read more on ESRF website

The role of methanol in large icy moons uncovered

The role of methanol in large icy moons uncovered

Scientists led by the ESRF find that the volatile compound methanol in icy moons gets trapped in hydrates at high pressure and low temperature. This finding is crucial for understanding evolution of subsurface oceans and interpreting data delivered by current and future space missions. The results are out in Earth and Planetary Science Letters.

Icy moons orbiting Jupiter and Saturn are some of the most intriguing bodies in our Solar System, as several of them are known to host liquid oceans beneath their frozen surfaces. Besides the Earth, these are the only places in the Universe, where the presence of liquid water has been confirmed. Subsurface oceans are the prime targets in search for extraterrestrial life and are central to several ongoing and upcoming space missions. Already launched ESA’s JUICE and NASA’s Europa Clipper missions will start exploration of Jupiter’s moons Europa, Ganymede and Callisto in less than a decade, while NASA’s rotorcraft Dragonfly will start its journey to Saturn’s moon Titan in 2028.

One of the most striking features of these icy moons is the size of their hydrospheres. For example, the largest moon Ganymede is believed to have ~1000 km deep hydrosphere, resulting in pressures at its base that are around 17 times higher than in the Earth’s ocean. Such high pressures can cause crystallization of the oceans at the bottoms. While many organic volatile compounds are expected to be present in the interior of icy moons, their fate at high pressures remains poorly understood.

Methanol, CH3OH, is a volatile of particular interest due to due to its expected abundance and debated role in ocean crystallization. Typically, it is considered as a powerful antifreeze agent that inhibits formation of ice and hydrates and contributes to long-term survival of the subsurface oceans. However, recent studies suggested that in chemically complex environments and in presence of promoters, small amounts of methanol can be incorporated in hydrate structures at low temperatures.

Now scientists led by the ESRF and in collaboration with the Laboratory of Planetology and Geosciences in Nantes (France), the University of Washington – Seattle (USA) and the University of Bayreuth (Germany) and have studied the fate of methanol in large icy moons. The team used high-pressure, low temperature, in situ single crystal X-ray diffraction on beamline ID15b.

“Our experiments show that, at high pressure, large amounts of methanol can be stored in hydrates that serve as a storage of methanol over geological timescales”, explains Anna Pakhomova, lead author and scientist at the ESRF.

Read more on ESRF website

Protein pH is key for improving texture in meat alternatives

Protein pH is key for improving texture in meat alternatives

Researchers have found that the pH of proteins significantly influences the texture of plant-based meat, in a multidisciplinary study where the ESRF has taken part. The results are out now in Food Hydrocolloids.

Consumption of meat, especially of red meat, represents a significant share of the global greenhouse emissions, in particular CO2, methane and nitrous oxide. Per kilo, beef generates 99.48 kilograms of carbon dioxide equivalent emissions, according to a Science publication from the University of Oxford.

Consequently, a plant-based diet is starting to take a prominent place in western countries. However, trying to mimic the desired textural properties typical of the hierarchical structure of fibers in animal meat has proven to be a challenge.

Today, manufacturers use high-moisture extrusion (HME) to recreate the right texture from plant proteins, such as soy or pea. During HME, proteins go under hydration, heat and shear, and this causes molecular changes that lead to anisotropic (directionally aligned) structures.

Recently, scientists have focused on alkalinization and acidification of water used during extrusion to control protein structure and texture, a process called protein pH-shifting.

Now a team led by the Wageningen University and in collaboration with food manufacturing company Unilever, TU Delft, the ESRF and ISIS, has investigated how pH-shifting during the HME of a soy protein concentrate affects the material’s structure across different scales, from nanometers to millimeters.

They used a multidisciplinary approach, which included Small Angle X-ray Scattering, carried out at the ESRF, and Small Angle Neutron Scattering at ISIS, to look into the nanoscale properties and magnetic resonance imaging and diffuse reflectance for the macroscale structure. “The multiscale nature of meat alternatives makes it necessary to use different methods, SAXS being one of the critical methods here”, explains John van Duynhoven, professor at Wageningen University,   senior scientist at Unilever and co-corresponding author of the publication.

At the ESRF’s ID02, they analysed how protein nano-aggregates change in size and structure depending on pH conditions during extrusion. They found that depending on pH levels, the aggregates further organize in particulate or fibrillar networks.

Read more on ESRF website

Clay emerges as a natural semiconductor

Clay emerges as a natural semiconductor

Vermiculite, a natural occurring clay mineral, can be a 2D wide band-gap semiconductor with unique electronic and magnetic properties, according to a study partially carried out at the ESRF and which is out now in the journal npj 2D Materials and Applications. The work at the ESRF focused on deciphering the structure of vermiculite, ensuring that it retained the features of semiconductors at the atomic level.

Vermiculite has long been used in insulation, construction, and environmental applications (like water purification and CO₂ capture); however, it had never been explored as a material for nanoelectronics or spintronics.

Now a team led by NTNU, in collaboration with the ESRF’s BM01, has successfully found that it can function as a 2D semiconductor. “Quantum technology is often associated with synthetic materials that have been developed in advanced, completely clean environments,” says Professor Jon Otto Fossum from NTNU’s Department of Physics. “We have found a naturally occurring clay material with sought-after properties for use in quantum technology,” he adds.

Scientists looked into exfoliating the material, because it has a layered structure and resembles that of graphite, which is used to make graphene. Until now, no one had explored it as a 2D material since it is very difficult to delaminate.

With help of in-situ diffraction experiments, the researchers established the way to reduce the material to a few atomic layers and discovered that its exfoliated form reveals semiconducting and antiferromagnetic properties. Nanosheets also have a high surface to volume ratio, which makes it interact more with light or electric fields. Due to their size, nanosheets can be integrated into thin films.

Dmitry Chernyshov, scientist in charge of BM01, explains the importance of this single-layered form: “The discovery of an antiferromagnetic ground state of vermiculite was only possible with its exfoliated form; it opens a route towards potential applications that would also require single nanosheets of this layered material”.

600 million tons of vermiculite

The exfoliation procedure was carried out at NTNU and optimized in three consecutive experiments at BM01, where synchrotron X-ray diffraction experiments solved the structural characterization of this clay and helped to establish a technology protocol in-situ to make its functional exfoliated form.

Unlike synthetic semiconductors, vermiculite is widely available, inexpensive and environmentally friendly, with global reserves estimated at 600 million tons. “Because of these features, it could help create sustainable, scalable materials for nanoelectronics and quantum technologies”, concludes Barabara Pacáková, the first author of the paper.

Read more on ESRF website

Scientists unveil the mechanism of light-sensing proteins that regulate internal clock

Scientists unveil the mechanism of light-sensing proteins that regulate internal clock

Scientists have unveiled the mechanism by which proteins that regulate the circadian rhythm, called cryptochromes, trigger light signaling. They used the TR-icOS instrument at the ESRF for spectroscopic characterization of the crystals. The results are out in Science Advances.

Cryptochromes are light-sensitive proteins found in all living things, including plants and animals. They help living things keep time with day and night by controlling internal clocks and responses to light. They are important for things like sleep cycles, plant growth, and possibly even sensing Earth’s magnetic field.

Until now, scientists knew that cryptochromes function by absorbing blue light, which triggers structural changes in the protein. This activates interactions with other cellular proteins, influencing gene expression and biological rhythms. However, the mechanism by which cryptochromes manifest this light-sensing ability remained unclear.

A team led by Manuel Maestre-Reyna at the National Taiwan University has now filmed a high-resolution, 3D molecular movie of a cryptochrome in action.

To achieve that, the team used time-resolved serial femtosecond crystallography (TR-SFX) at Spring-8 Angstrom Compact X-ray Free Electron Laser in Japan initially. They collected nineteen individual “frames” spanning from 10 nanoseconds to 233 milliseconds after illumination to put together the final movie.

TR-icOS completes the picture

They then used transient absorption spectroscopy (TAS) at the TR-icOS instrument at the ESRF. Maestre-Reyna explains the importance of these experiments at the ESRF: “The role of the ESRF, and in particular of TR-icOS, was crucial. Without in crystallo TAS experiments, that currently can only be performed at TR-icOS, the biological relevance of our results would be highly questionable. Furthermore, TRX can only detect structural changes, and is limited by the data quality in its ability to do so. In other words, chemical transformations that imply only very subtle structural changes, such as electron transfer, cannot be easily tracked by TRX. On the contrary, TAS can very easily detect such electronic reconfigurations, which change protein colour. Only by combining the two was it possible to fully understand the molecular mechanism of electron-transfer based signaling of cryptochromes”.

The experiments resulted in an ultra-slow motion, atomic resolution film that explains how the cryptochrome protein amplifies the subtle photochemical signal, which then snowballs into dramatic structural changes. The process is coordinated by the protein, with three molecular regions acting in unison to accomplish sensing.

Specifically, during the initial photochemical change, flavin adenine dinucleotide (FAD), a special light-gathering moiety within the protein, used the energy of blue light to capture an electron from the cryptochrome itself, inducing a highly unstable radical pair (RP) state. Early on, the protein attempts to stabilize this short-lived species by modulating its immediate environment. These local changes cascade over time, until, by about 100 milliseconds after RP formation, entire regions of the protein unfold like a ribbon, signaling that cryptochrome has sensed light.

Understanding sleep disorders

The results of this study provide a detailed description of the molecular basis of cryptochrome function, which can be relevant in research related to circadian rhythm, such as that focused on sleep disorders.

For example, recent studies have linked mutations in human cryptochrome 2 (CRY2) to Advanced Sleep Phase Disorder (ASPD). This disorder is characterized by disruption of the circadian rhythm, as patients fall asleep by 7 pm, but wake up at ~2 am, and it is not treatable with melatonin nor other effective therapeutics.

“Whilst our research is very fundamental, we hope that by delineating the structural principles of cryptochrome we can maybe lead to new drug design for the modulation of CRY2”, concludes Maestre-Reyna.

Read more on ESRF website

Industrial clients at ESRF fast-track drug discovery

Industrial clients at ESRF fast-track drug discovery

Researchers from the company Idorsia Pharmaceuticals Ltd have rapidly optimized a weak hit compound against SARS-CoV-2 to increase its potency by 1000-fold. They used artificial intelligence, computational chemistry, high throughput chemistry and structural biology at the ESRF. The results are out in Journal of Medicinal Chemistry and show the strong collaboration between the ESRF and industry.

It all started with a molecule that bound weakly to the SARS-CoV-2, the virus responsible for COVID-19. “About two year ago, we had identified this molecule, a diazepane scaffold, through artificial intelligence and computational screening and thought we would investigate further”, explains Julien Hazemann, first author of the publication and former researcher at Idorsia. The compound could potentially inhibit the virus’s main protease (Mpro)—a critical enzyme for viral replication.

In order to increase the efficiency of the molecule, so that it would bind to Mpro, the team from Idorsia used computational simulations, high-throughput chemistry and structural biology at the ESRF in collaboration with the company Expose GmbH. This approach, called hit-to-lead optimisation, has been used in antiviral drug discovery in the last ten years, but it is the first time that the techniques were integrated in such a tight and effective way in a global effort.  

First, the researchers employed computational docking and molecular dynamics simulations to predict how structural changes to the molecule might improve binding to Mpro.

Using high-throughput medicinal chemistry, they synthesized and tested a focused library of analogues. These steps led to a dramatic improvement of the original compound to a nearly 1,000-fold increase in potency.

However, predicting how a molecule behaves computationally was only one piece of the puzzle. Throughout the process, the researchers came to the ESRF’s macromolecular crystallography beamline ID23-1 to collect high-resolution X-ray diffraction data of the Mpro–inhibitor complexes. They were able to visualise how the inhibitor binds within the active site of the protease. “The ESRF has been crucial in this research, from the beginning, when we scanned the candidate compound, to the end, when we saw how the action takes place”, explains Daniel Ritz, senior director of biology at Idorsia.

One of the features of this study is the small number of compounds they needed, thanks to the highly targeted methodology the scientists used.

Read more on ESRF website

Catalyst Degradation Mechanisms in CO₂ Electrolysers

Catalyst Degradation Mechanisms in CO₂ Electrolysers

A new suite of operando X-ray techniques enables scientists to track the evolution of elemental and structural changes associated with catalyst and electrode degradation in carbon dioxide electrolysers in an unprecedented manner, all at once, thanks to a collaboration between Technical University of Denmark (DTU), the ESRF and the electrolyser company Twelve.

Converting carbon dioxide (CO₂) into valuable chemicals through electrolysis offers a promising way to make use of excess CO₂ emissions from industrial processes. Among the various technologies being explored, membrane–electrode assembly (MEA)-based systems stand out for their efficiency and scalability, making them strong candidates for future industrial applications to make artificial fuels or CO₂-to-CO conversion. However, MEAs’ long-term stability remains a key challenge, and the degradation mechanisms of catalysts and electrodes in MEAs are not yet understood.

So far, researchers have achieved CO production at current densities over 1 A/cm² and device stability lasting more than 3,000 hours. These advances are fueling commercial interest—but also highlight a new challenge: long-term testing under standard conditions is too slow to support fast development. “The performance of a CO₂ electrolysis can be determined in an hour, but 100s of hours are now needed for stability analysis.  The lack of a more efficient durability testing procedure is hampering our ability to most effectively use R&D resources”, says Brian Seger, professor at DTU and co-corresponding author of the publication. And first author Qiucheng Xu adds: “We need accelerated methods to mimic long-term operation and gain similar insights in a shorter timeframe.”

New characterization platform

The team from DTU, Twelve and the ESRF have now set up a new synchrotron X-ray characterization platform to track the time- and space-resolved evolution of ions and water movement, crystal structure, and catalyst variations in MEAs during accelerated testing. “This challenging problem must be tackled from various perspectives. We have developed a strong combination of operando X-ray techniques and chemical analyses, which can reveal the true complexity of the degradation mechanisms”, says Jakub Drnec, scientist in charge of beamline ID31, where the new suite of techniques take place, and co-corresponding author of the publication.

Specifically, they use Wide-Angle X-ray Scattering (WAXS), small-angle X-ray scattering (SAXS) and X-ray fluorescence (XRF) techniques on beamline ID31, all at once. The combined analysis of WAXS and SAXS enables the observation of the dynamic evolution of catalyst particle, allowing for differentiation between particle ripening and agglomeration. The inclusion of XRF facilitates monitoring of the cation distribution, which provides insight into whether cation concentration contributes to device operation and degradation.

The combination of these three techniques allows the researchers to more accurately isolate key physical phenomena, thereby bridging the gap between fundamental science and practical applications.

The team used gold and silver nanoparticle catalysts to test their new methodology. The results show that catalyst crystalline phase stability and nanoparticles-substrate adhesion strength are the key factors governing catalyst durability during CO₂ electrolysis.

Read more on ESRF website

Bioinspired controlled crystallisation: Towards sustainable artificial coral reefs

Bioinspired controlled crystallisation: Towards sustainable artificial coral reefs

Inspired by nature, scientists have replicated some aspects of the biomineralisation process used by marine organisms like corals, enabling them to control crystal phases in materials. This advancement could lead, among others, to artificial coral reefs that seamlessly integrate into marine environments without disrupting the ecosystem. Their results are out in Advanced Functional Materials.

Artificial coral reefs are often made of concrete or steel to provide stable structures for a marine habitat. However, they can also foster biofilm formation, promoting bacterial growth that may influence water chemistry.

Now a team led by Boaz Pokroy at Technion Israel Institute of Technology is working on artificial coral reefs that are as close to their natural counterparts as possible by reproducing the biomineralisation process typical of coral reefs and other marine organisms.

“For many years, we’ve extensively studied many marine organisms, such as the coralline alga Jania sp., sea urchins, starfish or brittle stars, and have unveiled the steps these organisms take to create a super hard skeleton through the process of biomineralisation”, explains Pokroy.

The natural process of biomineralisation starts as an amorphous phase before transforming into crystalline stable structures.

A key player in in this process is amorphous calcium carbonate (ACC), a precursor that can crystallise into different forms of calcium carbonate, including calcite, aragonite, and vaterite. The stability of ACC is influenced, among other factors, by impurities like magnesium, which affects the final crystal structure and properties. Traditionally, controlling this transformation required chemical additives and environmental adjustments.

Pokroy and his team used lasers to selectively transform ACC into different mineral phases. Laser power, scanning speed and the composition of the substrate are factors that affect the process of formation of distinct crystalline phases.

As the next step, the powders were analysed using synchrotron high-resolution powder X-ray diffraction (HR-PXRD) to identify the phases formed. “The experiments on beamline ID22 at the ESRF were crucial to characterise the different phases and track the impurities in the sample”, explains Hadar Shaked, scientist at Technion and first author of the publication. “With EBS providing higher flux, we were able to scan hundreds of samples in a very short time”, adds Pokroy.

Engineering bio-inspired materials

This method represents a significant advancement in bio-inspired material science, offering a way to engineer complex mineral structures with the same spatial accuracy seen in biological systems. “Whilst crystallisation from an amorphous phase was already possible through heating, it is the first time that we have full control of the process, which is key in engineering new structures as we wish”, says Shaked.

Dubbed ‘writing crystallography’, this approach opens exciting possibilities not only for artificial coral reefs but also for advanced additive manufacturing, semiconductors or single-layer patterning, where precise phase control is essential.

Read more on ESRF website

How an old drug could make a comeback against antibiotic resistance

How an old drug could make a comeback against antibiotic resistance

In the quest for solutions to modern antibiotic resistance, researchers at Goethe University Hospital in Frankfurt, together with their colleagues from European Synchrotron, the ESRF (Grenoble, France) and the EMBL Heidelberg are turning back to the past—and finding hope in an old, often-overlooked drug. Using X-ray nanofluorescence at the ESRF, they have uncovered how the rarely used antibiotic nitroxoline can fight back against drug-resistant bacteria. Their findings, published in Nature Communications, could spark renewed medical interest in the forgotten drug as a potential weapon against hard-to-treat infections.

Five years ago at Goethe University Hospital in Frankfurt, a patient in the intensive care unit was battling with a stubborn urinary tract infection. Despite multiple rounds of antibiotics, nothing seemed to make a difference. Then, as a last resort, doctors turned to an old drug from the 1960s—nitroxoline, typically reserved for uncomplicated urinary tract infections (UTIs). To their surprise, it worked.

Doctor and researcher Stephan Göttig was investigating this drug. “I realised that the potential of nitroxoline is huge towards multidrug-resistant Gram-negative bacteria, so we started studying its spectrum and mechanism”, he explains.

Targeting hospital pathogens

Nitroxoline is only used in a handful of countries today, after the rise of newer antibiotics and lack of clinical research. In Germany, where Göttig and the first author of the paper, Elisabetta Cacace were based (Cacace has now moved to ETH Zurich), it is an approved drug and it is still commonly prescribed for uncomplicated UTIs. However, it is not included in the WHO’s essential medicines list nor is it FDA approved in the US. “New pharmaceutical compounds are difficult to market, so it is useful to repurpose existing antibiotics”, explains Cacace.

Göttig and Cacace investigated more than a thousand isolates of different Gram-negative bacteria that nitroxoline could potentially fight against. Gram-negative bacteria have an outer membrane that can block many antibiotics and even some immune system components. They focused on Enterobacteriaceae, a group of bacteria that includes notorious hospital pathogens such as Klebsiella pneumoniae and Escherichia coli.

Read more on ESRF website

The Long Read: All in a spin

The Long Read: All in a spin

As 2025 marks the International Year of Quantum Technology, the ESRF contributes to the global exploration of quantum phenomena by delving into the mysteries of novel quantum magnets. These materials offer a fascinating window into the fundamental interactions of matter, yet their behaviour remains highly mysterious. To unravel them, ESRF users have had to push the boundaries of an X-ray technique. This article was first published in the March 2025 issue of the ESRFnews magazine, dedicated to quantum technology.

It is one of the most famous experiments in physics. Light illuminates a pair of slits in a wall, generating an array of bright and dark patches on a screen. The British physicist Thomas Young first performed the experiment at the turn of the 19th century to demonstrate that light can interfere with itself, behaving as a wave. Much later, quantum versions of the experiment would demonstrate something far more mysterious: that photons, electrons and other particles can exhibit wave-like interference patterns, but apparently only when no-one is watching. The experiment “has in it the heart of quantum mechanics”, wrote the American physicist and Nobel laureate Richard Feynman. “In reality, it contains the only mystery.”

Today, few scientists doubt the merits of quantum mechanics. It has proved itself through mind-boggling predictive power, not to mention a host of practical applications: semiconductor electronics, lasers, superconducting magnets, quantum cryptography and quantum computing, to name but a few. Yet it is still a subject ripe with puzzles, both in its basic interpretation and in its role in condensed matter, where each material can serve as a quantum playground.

One puzzle is the existence of peculiar types of magnetism, as studied by ESRF users such as Markus Grüninger from the University of Cologne in Germany. Unravelling these phenomena has led Grüninger and his colleagues to shift the boundaries of an X-ray technique – amazingly, in such a way as to recall Young’s famous experiment once again. “Our experiments rely on the excellent beam quality at the ESRF, the outstanding performance of the set-up at beamline ID20, and the fruitful collaboration with the beamline staff,” says Grüninger.

The technique in question is resonant inelastic X-ray scattering (RIXS). This begins with an X-ray photon knocking a tightly bound electron up to a higher atomic energy level. Almost instantaneously an electron from another high energy level relaxes into the resultant hole, releasing a new photon. By measuring the difference in energy between the incoming and outgoing photons, users can learn how the process has changed the solid in collective excitations of electron charge and spin – the latter being the basis of magnetism. The ESRF has helped develop RIXS since the 1990s, and currently offers it at two dedicated, world-leading beamlines: ID32 with soft X-rays, and ID20 with hard X-rays.

Hard X-ray photons can transfer a lot of momentum to a sample. In 2019, an international team led by Grüninger wanted to push ID20’s capabilities, and record an even greater range of momentum transfer than usual. Drawing on theory by Jeroen van den Brink at IFW Dresden in Germany, and making use of new ID20 instrumentation developed by beamline scientists Giulio Monaco (now at the University of Padova in Italy) and Marco Moretti (now at the Polytechnic University of Milan, also in Italy), the team studied the effect of large changes in momentum transfer on the intensity of the outgoing X-rays. Their sample was a crystal of an iridium oxide containing pairs or “dimers” of iridium ions. To their delight, the researchers found an interference pattern, demonstrating that the X-ray photons were exciting electrons at both iridium sites in the dimers at once – similar to light passing through Young’s double-slit, although in this case putting the dimer in an excited state

The experiment marked the beginning of RIXS interferometry, a technique that was predicted as far back as the mid 1990s. By demonstrating that the electrons in the iridium dimers experience a quantum, wave-like delocalization over a quasi-molecular dimer orbital, RIXS interferometry opened the door to the study of materials with novel magnetic properties, which physicists have been trying to understand for decades.

The most familiar type of magnetism – the sort that exists in a common fridge magnet – is ferromagnetism. In metals such as iron, it results from conduction electrons that are delocalized over an entire crystal, with spins able to align parallel to one another, producing a net magnetic moment. This is very different to one type of material with novel magnetism, the Mott insulator. Conduction in this type of material is forbidden due to strong electron repulsion, but it still has magnetism because its spins, while localized on individual ions, can interact with each other. Even more intriguing is the cluster Mott insulator, an emerging new class of material that exhibits what could be called a “local delocalization”. Here, electrons are fully delocalized over a dimer (or another small collection of ions), but they cannot propagate from one dimer to another. This results in local magnetic moments, residing not on individual ions but on quasi-molecular clusters. “In contrast to the usual electron spin, these cluster moments are something that we can tailor, by choosing the ionic species, cluster geometry, electron count, pressure and so on,” says Grüninger.

In 2022, Grüninger and colleagues used their new RIXS interferometry to unambiguously identify a cluster Mott insulator for the first time. The ID20 data could directly reveal the presence of three electron spins delocalized over an iridium dimer, creating a cluster magnetic moment [2] in a compound that is a candidate for a quantum spin liquid. The data also paved the way for a systematic exploration of more complex compounds, for example with trimers [3] or tetramers, rather than dimers. “Our results show that the trimers reside in an unexpected parameter regime that promises non-trivial magnetic moments,” says Grüninger. “They challenge previous views on trimer physics, highlighting the strength of RIXS interferometry.”

Cluster Mott insulators are exciting because of their potential as microscopic, fine-tuned magnets, as well as for their still-unexplored quantum properties. They also have potential to realize quantum “spin liquids”. First predicted by the US physicist and Nobel laureate Philip Anderson back in the 1970s, though experimentally elusive, spin liquids excel by the quantum-driven absence of magnetic order – even at temperatures close to absolute zero – that defines more conventional magnets. They are characterized by a quantum-entangled network of strongly fluctuating spins, driven by competing interactions that cannot be satisfied simultaneously. A simplified example of the situation is three spins on the vertices of a triangle: they may all want to align antiparallel to each other, but this is possible only for a pair of them, not all three simultaneously.   

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A highly stable and effective gold complex proves promising for anticancer treatment

A highly stable and effective gold complex proves promising for anticancer treatment

Chemists have discovered a highly stable gold complex in both model conditions and intracellular environment that triggers mitochondrial damages and hence could be used as an anticancer treatment. They came to the ESRF to characterize the complex on two beamlines. The results are out in Angewandte Chemie International Edition.

In ancient medicine, gold was used in Chinese medicine to treat various ailments. The Egyptians ingested gold for purification, while medieval alchemists sought its elixir for longevity. In the 20th century, gold compounds were developed to treat rheumatoid arthritis, marking transition into modern medicine.

 “The discovery of medicinal properties of platinum complexes has led to the development of novel anticancer metallodrugs with unique mechanisms of action, but toxic side effects and drug resistance from the body are pushing us to study other candidates, and in our case we focus on the design of ‘organogold’ complexes”, explains Hester Blommaert, researcher on beamline BM16 and first author of the publication.

The team, from the Sorbonne University, The Université Grenoble Alpes, the CNRS, the INSERM and the ESRF, has explored seven different gold compounds and used different synchrotron techniques at the ESRF to map how the gold compounds interact with cells. “This is a multidisciplinary team, including chemists, physicists, engineers and biologists”, says Jean-Louis Hazemann, group leader of the FAME-UHD BM16 beamline.

Toxic at low concentrations

“First, the team in Sorbonne University designed and synthesized the gold molecules and found that one of these compounds was very toxic towards cancer cells at low concentration, which is very promising”, explains Olivier Proux, scientist in charge of BM16.

At the ESRF, they used cryo-X-ray fluorescence microscopy on ID16A to pinpoint the precise intracellular location and quantity of gold in whole cells, without any sectioning and without the need for fluorescent dyes, and X-ray absorption spectroscopy on BM16 to gather information about the oxidation state and molecular transformations of gold within the cells. In particular, on BM16 they could solve spectra with a very high resolution for very low concentrations of gold, which is biologically relevant.

Sylvain Bohic, researcher at INSERM and part of the team, explains how the ESRF techniques allowed them to acquire their results: “We aimed to understand the compound’s mechanism of action at the subcellular level and assess its stability under biologically real-life conditions. While these compounds hold great potential against cancer, they cannot advance in drug development without a comprehensive understanding of their behavior within tumor cells, which is crucial for advancing novel chemotherapies. The application of these cutting-edge sensitive synchrotron techniques provided at ESRF is a critical first step toward achieving this goal”.

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A new 100 picosecond time-resolved technique images surface acoustic wave devices

A new 100 picosecond time-resolved technique images surface acoustic wave devices

Beamline ID01 can now study Surface Acoustic Waves (SAW) devices at operando conditions thanks to a new technique called stroboscopic full-field diffraction X-ray microscopy at the ESRF. Their results open the doors to more experiments with these systems and on electronic circuits and devices in general. They are published in Nature Communications.

A Surface Acoustic Wave (SAW) device is an electronic device that uses sound waves traveling along the surface of a material (usually a piezoelectric crystal) to process, filter or transmit signals. Their applications are wide, and include mobile phones, Wi-Fi, GPS, and 5G networks to filter and separate different frequency bands, touchscreens, sensors in the automotive and aviation industry, biosensors. They are also promising devices in nanoscale applications, such as quantum communication.

Because they are highly sensitive, durable, compact and cheap, there is a lot of ongoing research into understanding how to optimise their structure. This needs a deep understanding of energy conversion and loss mechanisms taking place in the device.

In SAW devices, electrical energy is converted into sound waves using interdigital transducers. These are tiny comb-shaped metal electrodes placed on a piezoelectric crystal. One set of electrodes is grounded, while the other receives an alternating voltage, causing the crystal’s surface to strain or deform. This vibration creates an acoustic wave that travels at several kilometers per second. These waves have extremely high frequencies (hundreds of MHz to GHz), far too fast for even the best high-speed cameras to capture.

However, now a team led by ESRF scientists has developed a technique called stroboscopic full-field diffraction x-ray microscopy on beamline ID01, which allows them to study the dynamic strain in SAW devices. “Today the spatial resolution at the ESRF’s ID01 is about 100nm and we have a time resolution in the storage ring of 100 picoseconds: this is practically the speed of sound . This means that we can image sound unblurred”, explains Tobias Schulli, scientist in charge of ID01 and co-corresponding author of the publication.

The experiments showed that there was an unexpected acoustic loss in a resonator device tested. It proved that propagating modes leak elastic energy away from the resonator. The high sensitivity of X-ray diffraction for changes in atomic distances by 1/100 000 together with the high time and spatial resolution available on ID01 represent the only available technique to detect and quantify such phenomena.

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Scientists find ways to reduce oil intake in deep fried foods

Scientists find ways to reduce oil intake in deep fried foods

A new 4D imaging system has tracked the process of frying foods at the ESRF, in a quest to make the products absorb less oil and therefore, healthier. Their insights show that it is especially after frying, during the cooling process, that food absorbs oil, and that the amount of oil absorbed depends on the porous structure created during frying. The results are out in Nature Communications.

Fried foods are staple especially in Western diets due to their distinct flavour and sensory characteristics. The frying process causes foods to develop unique textures related to their crispy outside and soft inside.

“People like fried products because of the texture and the taste, but they have been claimed to be an ultra-processed food that we should try to minimise in our diet”, explains Pieter Verboven of KU Leuven in Belgium, corresponding author of the publication. “Still, the final composition is more of a concern than the process itself”, he adds. Therefore, the KU Leuven research team are investigating ways to reduce oil content but preserve texture and taste.

When we fry food, we submerge it into hot oil that is more than 160 °C. This leads to very fast evaporation of water and creates internal pressure in the form of steam, which results in an expanding porous structure. “This process is extremely fast, in the order of seconds, and we don’t have the tools to see what happens in real-time, so we need to come to the ESRF to be able to track the process”, says Verboven.

A fryer on the beamline

The team came to ID19 to carry out high-speed 4D computed tomography on wheat flour dough, a common food material subjected to deep-frying. The experiments took place as the dough was frying in a custom oil fryer and afterwards, during the post-frying cooling, with the aim of investigating the structural deformation and pore formation, as well as oil uptake. “The experiment was extremely complex, as we needed to scan the sample submerged in oil very fast to track all the changes at the microstructural level”, explains Bratislav Lukic, researcher at the ESRF and co-author of the publication, “The fryer was also equipped with sensors and actuators to precisely control the process remotely. Thanks to high flux at high energy of the Extremely Brilliant Source, we were able to reach sub-second scanning times while maintaining microscopic spatial resolution, all that in a very large fryer, which is representative of the process.”

They visualised how the product expands due to steam during the frying process, which hinders the oil from getting inside. At the same time, the physico-chemical changes in starch and gluten structure determine the pore structure. The trick is to control this process well to create the desired texture with a crispy crust and fluffy interior. The team found that oil is absorbed mostly during the cooling of the fried dough and, in smaller percentage, during the frying process itself.

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The gut-brain connection in Alzheimer’s unveiled with X-rays

The gut-brain connection in Alzheimer’s unveiled with X-rays

Scientists led by the Institute of Nanotechnology in Italy, in collaboration with the ESRF, have discovered how X-ray micro- and nano- tomography can provide clues on the processes that link the gut neurons with those in the brain and may trigger Alzheimer’s. The results are out today in Science Advances.

Alzheimer’s disease, the most common type of dementia, is a neurodegenerative disorder characterized by brain alteration including synaptic loss, chronic inflammation and neuronal cell death.

In recent years, scientists have found evidence that the gut and the brain communicate through the neurons placed in both organs. Dysfunction in this axis has been linked to psychiatric and neurological disorders, including Alzheimer’s.

The gut microbiota, which refers to the microorganisms in the intestinal tract, plays a key role in human health and influences brain function, cognition and behaviour. “There are already many studies that support that changes in the gut composition can contribute to Alzheimer’s onset and progression”, explains Alessia Cedola, researcher from the Institute of Nanotechnology in Italy and corresponding author of the article.

In particular, dysbiosis, which is the process by which there is a loss of microbial diversity, induces the prevalence of dangerous bacteria producing toxic metabolites promoting inflammation, and, consequently, the breakage of the gut/brain barriers.

What happens exactly when gut dysbiosis occurs? “The main hypothesis is that changes trigger the escape of bad bacteria from the gut, entering the circulation, reaching the brain and triggering Alzheimer’s, but evidence is still poor”, adds Cedola.

Now scientists have discovered that nano- and micro X-ray phase-contrast tomography (XPCT) is a powerful tool to study structural and morphological alterations in the gut, without tissue manipulation. The team came to the ESRF to scan samples on beamline ID16A. “Thanks to this technique we can image soft biological tissues with excellent sensitivity in 3D, with minimal sample preparation and without contrast agents”, explains Peter Cloetens, scientist in charge of ID16A and co-author of the publication.

The data of the experiments, partially carried out at ANATOMIX at Soleil, showed the changes in cell abundance and organisation in the tissues, as well as structural alteration in different tissues of mice affected with Alzheimer’s. Specifically, it showed relevant alterations in the villi and crypts of the gut, cellular transformations in Paneth and goblet cells, along with the detection of telocytes, neurons, erythrocytes, and mucus secretion by goblet cells within the gut cavity. All these elements, when working correctly, maintain gut health, support digestion, and protect the intestinal lining from damage.

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Image: Nano-XPCT 3D rendering of the longitudinal view of one crypt of SAMR1 mouse. The epithelial layer of the crypt has been rendered in green. The Paneth cells are colored in yellow and the goblet cells in blue. Scale bars, 5 μm.

Credit: A. Cedola