How vision begins

Researchers at the Paul Scherrer Institute PSI have deciphered the molecular processes that first occur in the eye when light hits the retina. The processes – which take only a fraction of a trillionth of a second – are essential for human sight. The study has now been published in the scientific journal Nature.

It only involves a microscopic change of a protein in our retina, and this change occurs within an incredibly small time frame: it is the very first step in our light perception and ability to see. It is also the only light-dependent step. PSI researchers have established exactly what happens after the first trillionth of a second in the process of visual perception, with the help of the SwissFEL X-ray free-electron laser of the PSI.

At the heart of the action is our light receptor, the protein rhodopsin. In the human eye it is produced by sensory cells, the rod cells, which specialise in the perception of light. Fixed in the middle of the rhodopsin is a small kinked molecule: retinal, a derivative of vitamin A. When light hits the protein, retinal absorbs part of the energy. With lightning speed, it then changes its three-dimensional form so the switch in the eye is changed from “off” to “on”. This triggers a cascade of reactions whose overall effect is the perception of a flash of light.

Read more on the PSI website

Image: PSI researcher Valérie Panneels purifies the red protein rhodopsin in order to examine it later at the SwissFEL X-ray free-electron laser

Credit:  Scanderbeg Sauer Photography

Using light to switch drugs on and off

Scientists at the Paul Scherrer Institute PSI have used the Swiss X-ray free-electron laser SwissFEL and the Swiss Light Source SLS to make a film that could give a decisive boost to developing a new type of drug. They made the advance in the field of so-called photopharmacology, a discipline that develops active substances which can be specifically activated or deactivated with the help of light. The study is being published today in the journal Nature Communications.

Photopharmacology is a new field of medicine that is predicted to have a great future. It could help to treat diseases such as cancer even more effectively than before. Photopharmacological drugs are fitted with a molecular photoswitch. The substance is activated by a pulse of light, but only once it has reached the region of the body where it is meant to act. And after it has done its job, it can be switched off again by another pulse of light.

This could limit potential side effects and reduce the development of drug resistance – to antibiotics, for example.

Licht-switchable drugs

To make conventional drugs sensitive to light, a switch is built into them. In their study, the scientists led by the principal authors Maximilian Wranik and Jörg Standfuss used the active molecule combretastatin A-4, which is currently being tested in clinical trials as an anti-cancer drug. It binds to a protein called tubulin, which forms the microtubules that make up the basic structure of the cells in the body, and also drive cell division. Combretastatin A-4, or “CA4” for short, destabilises these microtubules, thereby curbing the uncontrolled division of cancer cells, i.e. it slows down the growth of tumours.

In the modified CA4 molecule, a bridge consisting of two nitrogen atoms is added, which makes it particularly photoactive. In the inactive state, the so-called azo bridge stretches the molecular components to which it is attached to form an elongated chain. The pulse of light bends the bond, bringing the ends of the chain closer together – like a muscle contracting to bend a joint. Crucially, in its elongated form, the molecule does not fit inside the binding pockets of the tubulin – depressions on the surface of the protein where the molecule can dock in order to exert its effect. However, when the molecule is bent, it fits perfectly – like a key in a lock. Molecules like this, which fit into corresponding binding pockets, are also called ligands.

Read more on the PSI website

Image: Jörg Standfuss (left) and Maximilian Wranik in front of the experimental station Alvra of the Swiss X-ray free-electron laser SwissFEL, where the photopharmacological studies were carried out. In the long term, the aim is to develop drugs that can be switched on and off by light.

Credit: Paul Scherrer Institute/Markus Fischer

Athos just got even better

An upgrade at the soft X-ray beamline of the free electron laser SwissFEL will open up new experimental capabilities. Using an external laser system to ‘seed’ the emission of X-ray photons, and thus imprint well-defined optical properties on the beam, the upgrade gives the Athos beamline unprecedented stability. With this, ultra-fast ‘attosecond’ timescales that probe the movements of electrons in chemical reactions become possible.

Free electron lasers (FELs) in the X-ray regime, such as the X-ray free electron laser SwissFEL, produce short pulses of brilliant light that give unique insights into the structure and dynamics of materials through so-called ‘molecular movies’. The Athos beamline of SwissFEL produces so-called ‘soft’ X-rays whose comparatively low photon energies are useful for studying the interactions between molecules.

A limitation for the Athos beamline, as for almost all FELs, is stability. The reason for this comes down to the process by which light is made: a process called self-amplified spontaneous emission (SASE). In a FEL, electrons, accelerated to close to the speed of the light, are wiggled by a series of magnets, called undulators. Once wiggling, they produce photons: at SwissFEL, in the form of X-rays. SASE describes the process by which these photons repeatedly interact with the electron beam and stimulate – or ‘seed’ – the emission of more photons in subsequent parts of the electron beam. The spontaneous emission of radiation in this way is a stochastic process. This means that the X-ray beam created is inherently unstable, characterised by variations in wavelength and pulse energy.

Thanks to funding from the European Research Council (ERC), a new upgrade of Athos tackles this fundamental challenge of X-ray FELs. The upgrade forms part of the HERO project, which in 2018 was awarded a prestigious Synergy grant of 14 million Euros and incorporates principal investigators from PSI, EPFL, ETHZ and Stockholm. Standing for ‘Hidden, Entangled and Resonating Orders’, the HERO project, which is coordinated by PSI, aims to uncover hidden quantum properties in materials that cannot be studied with existing methods. The HERO upgrade of the Athos beamline will enable such new insights.

“What is demonstrated here is the power of funding for blue-skies research that the ERC uniquely provides to associated countries,” states Gabriel Aeppli, head of the Photon Science Division at PSI, who is the coordinating principal investigator for the HERO project.

Bringing Athos in line

In a classroom, one particularly well-behaved child can serve as a role model for all the children. In a similar vein, at the Athos beamline, the upgrade uses an external laser to imprint its well-behaved properties on the FEL beam. Instead of relying on the stochastic, spontaneous emission of radiation, a ‘seed-laser’ interacts with the wiggling electron beam to amplify the emission of radiation. As this external, optical laser has a well-defined pulse and coherence properties, it can transfer these to the emitted X-rays.

There is a reason that an X-ray FEL has never before been externally seeded. “Although the principle of ‘seeding’ a FEL is not entirely new, seeding a FEL at an energy range as high as this is,” explains Alexandre Trisorio, head of the gun laser group, who developed the seed-laser system. “The trouble is that there are no external laser sources that operate in the right wavelength range”.

To get around this, the scientists – through some serious feats of electron bunch gymnastics and tricks of the light – are employing a technique known as echo-enabled high-harmonic generation (EEHG), whereby higher frequency resonances are created that seed the FEL. The full upgrade is a two phase project, the first of which has now been successfully completed.

Read more on the PSI website

Image: An X-ray FEL cannot be seeded with a simple optical laser: there is none that can deliver a short enough wavelength. So, more complicated techniques are required. In a dedicated room alongside the Athos beamline, an 11m optical bench will host two titanium sapphire seed laser systems. Martin Huppert fine tunes the first of these, installed in the first phase of the HERO upgrade.

Credit: Paul Scherrer Institute / Markus Fischer

New SwissFEL soft X-ray endstation welcomes first users

Maloja is go. On Wednesday, 23rd March 2022, first user experiments began at the Maloja endstation, which enables explorations into atomic, molecular and optical physics and chemical dynamics. These user experiments mark a double first, not only for Maloja but also for the second, soft X-ray beamline of the SwissFEL, Athos.

Following two years of tireless development, Maloja is beginning to yield its scientific fruits. Developed in parallel with soft X-ray beamline Athos, Maloja is the first endstation to be up and running, and takes advantage of advanced beam parameters, namely, very short pulses, two colour pulses and pump-probe experiments. A key feature of the Maloja endstation is its modular nature, enabling straightforward exchange of chambers and tailoring to individual experimental requirements.

“Because of its flexible design, a wide variety of investigations are possible at Maloja, such as time-resolved measurements of electronic structure changes, non-linear X-ray spectroscopy or research into gas-phase atoms or nanoparticles. I’m really excited to see the diverse science that future users will turn up with,” enthuses Kirsten Schnorr, lead scientist at the Maloja endstation.

Work began on the Maloja project in 2019, with the COVID pandemic striking a few months after first hardware deliveries. With staff working night shifts to create ‘time-dimensional social distancing’, in June 2020 first light entered the Maloja endstation. This heralded the beginning of commissioning experiments and a very close collaboration between the Maloja team and accelerator groups as, step-by-step, the teams developed not only the Maloja endstation, but also a whole new branch of the SwissFEL: Athos.

Read more on the PSI website

Image: Members of Nanostructures and Ultrafast X-ray Science Group, including Daniela Rupp and Mario Sauppe (3rd and 4th from L) together with the Maloja team and Christoph Bostedt (far R) during the beamtime

Credit: Alessandro Colombo

Opening the door to X-ray quantum optics

The possibility to generate coherent copies of X-ray pulses from FELs would facilitate a realm of X-ray techniques analogous to those currently available with optical laser light. Yet, this is a challenge due to the short wavelength of X-rays. Now, researchers have devised a new solution that ‘splits’ the electron bunch prior to generation of photons, producing two perfectly coherent copies of pulses.

X-ray free electron lasers (FELs) deliver ultra-bright, ultra-short and coherent X-ray pulses. Short pulses enable time-resolved studies of phenomena such as optical switching, whilst the short wavelength of X-rays, enables experiments with clear fingerprints of atomic species, which also resolve the distances between atoms in solids and liquids. In contrast, optical spectroscopies and microscopies primarily probe electrons shared across molecules, and provide neither images at the atomic scale nor allow unique identification of atomic constituents. Thus, X-ray FELs provide essential insights for fields ranging from pharmacology to electronic device engineering.

Yet, so far, part of the picture that is missing is the ability to do experiments with two – or more – coherent copies of beams. Splitting light is par for the course in optical spectroscopies. Phase-locked pulses – pulse pairs that have a fixed phase relation, split via mirrors, enable a host of interferometric and multidimensional spectroscopies. For X-ray light, the challenge comes with the advantage: the short wavelength. The wavelength – of the order of interatomic spacings – makes it extremely challenging to split the beam using mirrors, where even the smallest path length difference introduces phase jitter.

A perfect X-ray beam splitter

Now, researchers at the SwissFEL have come up with an ingenious solution. This takes a step back in the FEL and ‘splits’ the electron bunch in the accelerator, prior to the production of photons. Collaborators from both the electron and photon ends of SwissFEL have been a feature of this project, which uses a solution from the accelerator side to meet the photon requirements.

“What is really special is that from the beginning this has been a close interaction between quantum technologists and accelerator physicists. This is really facilitated by the interdisciplinarity of PSI, and its early recognition that the current, second quantum revolution will impact its core activity of building and operating large machines”, believes Simon Gerber, head of the Quantum Photon Science Group and corresponding author in the recent publication.

Read more on the PSI website

Image: Authors (L to R) Sven Reiche, Gabriel Aeppli and Simon Gerber standing outside the entrance to the SwissFEL

Credit: Paul Scherrer Institute / Mahir Dzambegovic

How to get chloride ions into the cell

For the first time, a molecular movie has captured in detail the process of an anion transported across the cell membrane by a light-fueled protein pump. Publishing in Science, the researchers utilized the unique synergy of a Free Electron Laser (SwissFEL) and synchrotron light source (SLS) offered by PSI to unravel the mystery of how light energy initiates the pumping process − and how nature made sure there is no anion leakage back outside.

Many bacteria and unicellular algae have light-driven pumps in their cell membranes: proteins that change shape when exposed to photons such that they can transport charged atoms in or out of the cell. Thanks to these pumps, their unicellular owners can adjust to the environment’s pH value or salinity.

One such bacteria is Nonlabens marinus, first discovered in 2012 in the Pacific Ocean. Among others, it possesses a rhodopsin protein in its cell membrane which transports chloride anions from outside the cell to its inside. Just like in the human eye, a retinal molecule bound to the protein isomerizes when exposed to light. This isomerization starts the pumping process. Researchers now gained detailed insight into how the chloride pump in Nonlabens marinus works.

The study was led by Przemyslaw Nogly, once a postdoc at PSI and now an Ambizione Fellow and Group Leader at ETH Zürich, in close collaboration with the ALVRA team at SwissFEL and the MX team at the SLS. It is one of the first studies to fully combine experimental capabilities at these large-scale research facilities, bridging the gap in time resolution to record a full molecular movie of a protein at work. Slower dynamics in the millisecond-range were investigated via time-resolved serial crystallography at SLS while faster, up to picosecond, events were captured at SwissFEL – then both sets of data were put together.

Read more the PSI website

Image: Photoactive chloride pumping through the cell membrane captured by time-resolved serial crystallography: Chloride ions (green spheres) are transported across the cell membrane by the NmHR chloride pump (pink).

Credit: Guillaume Gotthard, Sandra Mous

First light at Furka: The experiments can begin

It’s another milestone on the path to full operation of the X-ray free-electron laser SwissFEL with five experiment stations in all: “First light” at the experiment station Furka. It clears the way for experimental possibilities that are unique worldwide. Team leader Elia Razzoli explains what the Furka Group is planning to do.

Why is “first light” such an important occasion for your team?

Elia Razzoli: It means we’re in business. Or to be more specific: Now we can begin working on the first experiments.

The general public might imagine that you simply flip a switch, and then the light is there. But presumably it’s not that simple in your case . . .

No, it is a complex task. When we at SwissFEL talk about light, we do not mean visible light, but rather X-ray light with characteristics that are unique in the world. To generate that light, and for research to be able to use it, several teams at PSI have to work together. With the Furka experiment station we are, so to speak, at the end of the food chain. To generate the X-ray light of SwissFEL, electrons must be forced onto a sinuous track with the aid of magnets. In the process, they emit the X-ray light that we need to carry out the actual investigations. The magnets that redirect the electrons in this way are called undulators. And they are precisely what makes the whole thing so difficult, because they have to work exactly in sync; otherwise the X-ray light doesn’t have the quality that we need. The complexity of the system grows exponentially with the number and length of the undulators. That is why first light at Furka is already a masterful technical and organisational feat.

Read more on the PSI website

Image: Members of the team that achieved the milestone at the Furka station of SwissFEL: Eugenio Paris (left), Elia Razzoli, Cristian Svetina (right)

Credit: Paul Scherrer Institute/Mahir Dzambegovic

Microbes and viruses in the spotlight

The world of microbes and viruses is extremely old and extremely diverse. With the help of the large research facilities at PSI, researchers can look deep into this alien cosmos and above all explore the proteins of exotic beings.

Since they emerged as the first life on our planet around 3.5 billion years ago, they have shaped the earth like no other form of life: microorganisms. In this motley group there are such diverse representatives as bacteria, archaebacteria, algae, yeasts, amoebas or parasites like the malaria pathogen. But as diverse as microorganisms may be, they also do not include one biological form of existence: viruses. Because these are a borderline case between the animate and the inanimate. They do not have their own metabolism and therefore always need a host in order to awaken to life and multiply. The vast majority of microorganisms and viruses are harmless or very useful for humans, for example for digestion or to produce food, to purify wastewater or to form humus.

Read more about the ongoing research at Synchrotron Lichtquelle Schweiz (SLS) and SwissFEL on the PSI website

Image: Researchers are studying how a sodium pump works on a marine bacterium. The knowledge could lead to new insights in neurobiology. (Graphic: Christoph Frei)

In search of the lighting material of the future

At the Paul Scherrer Institute PSI, researchers have gained insights into a promising material for organic light-emitting diodes (OLEDs). The substance enables high light yields and would be inexpensive to produce on a large scale – that means it is practically made for use in large-area room lighting. Researchers have been searching for such materials for a long time. The newly generated understanding will facilitate the rapid and cost-efficient development of new lighting appliances in the future. The study appears today in the journal Nature Communications.

The compound is a yellowish solid. If you dissolve it in a liquid or place a thin layer of it on an electrode and then apply an electric current, it gives off an intense green glow. The reason: The molecules absorb the energy supplied to them and gradually emit it again in the form of light. This process is called electroluminescence. Light-emitting diodes are based on this principle.

Read more on the Swiss FEL and Swiss Light Source website

Image: Grigory Smolentsev in front of SwissFEL

Credit: Paul Scherrer Institute/Mahir Dzambegovic

Research and tinkering – SwissFEL in 2019

The newest large research facility at the Paul Scherrer Institute, SwissFEL, has been completed. Regular operation began in January 2019.

Henrik Lemke, head of the SwissFEL Bernina research group in the Photon Science Division, gives a first interm report.

Mr. Lemke, you have just published a technical article in which you report on the experience so far with SwissFEL. How would you sum it up?

With SwissFEL, we are entering new territory at PSI. It is one of only five comparable facilities on this scale worldwide. This means we still need to gain experience, because we are doing a lot of things for the first time. On January 1 this year we began regular operation. Research groups from other institutions have already been here, and they have successfully conducted experiments with us, just like PSI researchers themselves. These were already a big success. In parallel to this operation, we are also further optimising the facility and the experimental setup. This will enable us to join ranks with the comparable facilities and, in addition, develop particular methods into specialities of SwissFEL.

>Read more on the SwissFEL website

Image: Lemke at the experiment station Bernina of SwissFEL
Credit: Paul Scherrer Institute/Mahir Dzambegovic

Towards X-ray transient grating spectroscopy at SwissFEL

The high brilliance of new X-ray sources such as X-ray Free Electron Laser opens the way to non-linear spectroscopies.

These techniques can probe ultrafast matter dynamics that would otherwise be inaccessible. One of these techniques, Transient Grating, involves the creation of a transient excitation grating by crossing X-ray beams on the sample. Scientists at PSI have realized a demonstration of such crossing by using an innovative approach well suited for the hard X-ray regime. The results of their work at the Swiss Free Electron Laser have been published in the journal Optics Letters.
Non-linear optics is an important field of physics where the non-linear response of matter in extreme electromagnetic fields is studied and exploited for novel applications. It has been widely used for creating new laser wavelengths (Sum/Difference Frequency Generation – S/DFG) as well as for studying a variety of properties such as charge, spin, magnetic transfer as well as heat diffusion. A broad class of non-linear spectroscopy is Four Wave Mixing (FWM) where three laser beams are overlapped in space and time in a sample and a fourth beam with different wavelength and angle is detected, background free. This allows studying specific transitions and selectively excite the sample tuning the incoming beams’ wavelength while studying their dynamics by controlling the relative time delays between the laser pulses. Transient Grating (TG) spectroscopy is a special case of degenerate FWM where two of the incoming beams have the same wavelength and are crossed at the sample creating an interference pattern, or transient grating, which excites the sample as long as the field is present. When the TG impinges on the material, its index of refraction is locally perturbed and electrons exposed to the radiation are excited. These electrons then transfer their extra energy to the lattice and the heat is then dissipated by the system. A third beam, delayed with respect to the pump TG, probes the dynamics of this excitation.

>Read more on the SwissFEL at PSI website

Image: Layout depicting the experimental conditions at the Alvra experimental station. (Find all the details here)

SwissFEL makes protein structures visible

Successful pilot experiment on biomolecules at the newest large research facility of PSI

For the development of new medicinal agents, accurate knowledge of biological processes in the body is a prerequisite. Here proteins play a crucial role. At the Paul Scherrer Institute PSI, the X-ray free-electron laser SwissFEL has now, for the first time, directed its strong light onto protein crystals and made their structures visible. The special characteristics of the X-ray laser enable completely novel experiments in which scientists can watch how proteins move and change their shape. The new method, which in Switzerland is only possible at PSI, will in the future aid in the discovery of new drugs.

Less than two years after the X-ray free-electron laser SwissFEL started operations, PSI researchers, together with the Swiss company leadXpro, have successfully completed their first experiment using it to study biological molecules. With that, they have achieved another milestone before this new PSI large research facility becomes available for experiments, at the beginning of 2019, to all users from academia and industry. SwissFEL is one of only five facilities worldwide in which researchers can investigate biological processes in proteins or protein complexes with high-energy X-ray laser light.

>Read more on the SwissFEL website

Image: Michael Hennig (left) and Karol Nass at the experiment station in SwissFEL where their pilot experiment was conducted.
Credit: Paul Scherrer Institute/Mahir Dzambegovic

Movie directors with extra roles

Data storage devices based on novel materials are expected to make it possible to record information in a smaller space, at higher speed, and with greater energy efficiency than ever before.

Movies shot with the X-ray laser show what happens inside potential new storage media, as well as how the processes by which the material switches between two states can be optimised.
Henrik Lemke comes to work on his bicycle. Private cars are not allowed to drive to the SwissFEL building in the Würenlingen forest, and delivery vans and lorries need a permit. As a beamline scientist, the physicist is responsible for the experiment station named for Switzerland’s Bernina Pass. At the end of 2017, he led the first experiment at the Swiss free-electron X-ray laser, acting in effect as a movie director while SwissFEL was used, like a high-speed camera, to record how a material was selectively converted from a semiconducting to a conducting state – and back again. To this end the PSI team, together with a research group from the University of Rennes in France, studied a powder of nanocrystals made of titanium pentoxide. The sample was illuminated with infrared laser pulses that made the substance change its properties. Then X-ray pulses revealed how the crystal structure was deformed and enlarged – a cascade of dynamic processes that evidently depend on the size of the crystals.

Image: The directors: Henrik Lemke and Gerhard Ingold
Credit: Scanderbeg Sauer Photography

Biological light sensor filmed in action

Film shows one of the fastest processes in biology

Using X-ray laser technology, a team led by researchers of the Paul Scherrer Institute PSI has recorded one of the fastest processes in biology. In doing so, they produced a molecular movie that reveals how the light sensor retinal is activated in a protein molecule. Such reactions occur in numerous organisms that use the information or energy content of light – they enable certain bacteria to produce energy through photosynthesis, initiate the process of vision in humans and animals, and regulate adaptations to the circadian rhythm. The movie shows for the first time how a protein efficiently controls the reaction of the embedded light sensor. The images, now published in the journal Science, were captured at the free-electron X-ray laser LCLS at Stanford University in California. Further investigations are planned at SwissFEL, the new free-electron X-ray laser at PSI. Besides the scientists from Switzerland, researchers from Japan, the USA, Germany, Israel, and Sweden took part in this study.

>Read more on the SwissFEL at Paul Scherrer Institute website

Image: Jörg Standfuss at the injector with which protein crystals for the experiments at the Californian X-ray laser LCLS were tested. In the near future, this technology will also be available at PSI’s X-ray laser SwissFEL, for scientists from all over the world.
Credit: Paul Scherrer Institute/Mahir DzaAmbegovic

First Pilot Experiment at SwissFEL-Alvra

UV photo-induced charge transfer in OLED system

On the 17th of December 2017 SwissFEL saw its first pilot experiment in the Alvra experimental station of the SwissFEL ARAMIS beamline. A team of scientists from the University of Bremen, Krakow and PSI, led by Matthias Vogt (Univ. Bremen) and Chris Milne (PSI)in collaboration with J. Szlachetko, J. Czapla-Masztafiak, W. M. Kwiatek (Inst. of Nucl.Phys. PAN (Krakow), successfully did the first pilot experiment at SwissFEL-Alvra on UV photo-induced charge transfer in OLED system.

With ever-increasing demands on low-cost, low-power display technology, significant resources have been invested in identifying OLED materials that are based on Earth-abundant materials while maintaining high internal quantum efficiencies. The recent pilot experiment performed at SwissFEL’s Alvra experimental station aimed to use X-ray spectroscopy to investigate a promising OLED candidate based on copper and phosphorus. This molecule, synthesized by Dr. Matthias Vogt from the University of Bremen, is based on a physical phenomenon called thermally activated delayed fluorescence, which allows for extremely high energy efficiencies to be achieved. The experiment probed how the phosphorus atoms are involved in the fluorescence process as a complement to longer-timescale measurements on the copper atoms performed at the Swiss Light Source’s SuperXAS beamline by Dr. Grigory Smolentsev and collaborators. The SwissFEL measurements confirm that the phosphorus atoms are directly involved in the charge transfer process in the molecule, and lay the foundation for future investigations of the mechanisms behind the efficiency of the delayed fluorescence process.

>Read more on the SwissFEL website

Figure: please find here the full figure