April 10, 2019

10 ways SLAC’s X-ray laser has transformed science

10 ways SLAC’s X-ray laser has transformed science

In the decade since LCLS produced its first light, it has pushed boundaries in countless areas of discovery.
By Ali Sundermier

Structured Content

When scientists at the Department of Energy’s SLAC National Accelerator Laboratory took on the task of building the world’s very first X-ray laser capable of imaging matter at the atomic scale, they knew they were in for an uphill battle. The Linac Coherent Light Source (LCLS) was designed to generate X-ray pulses a billion times brighter than anything that had come before. It would be the first machine to produce high energy (or “hard”) X-ray laser pulses that would last for just femtoseconds, millionths of a billionth of a second.

If successful, LCLS would enable new science at ultrasmall, ultrafast scales. It would be a new tool, a “microscope” that could spy on the intricate movements of atoms and molecules, capturing their motion in freeze-frame “movies.” It would deepen our fundamental understanding of the building blocks of life and position scientists to make advancements in areas ranging from clean energy to next-generation computing and improved medicines.

In order to work, LCLS would need a tremendous leap in cutting-edge technologies, requiring scientists, engineers and technicians from around the world to pool their expertise and clear uncountable hurdles. Many thought it was a leap too far, requiring a precision that was simply not practical.

But the U.S. Department of Energy decided the scientific reward was great enough to take the risk, and invested almost half a billion dollars for the LCLS project. A team was formed that pulled together researchers from SLAC, Argonne, Lawrence Livermore, Los Alamos and Brookhaven national laboratories, along with the University of California, Los Angeles and many other institutions from around the world.

In April 2009, after more than a decade of painstaking effort, the lab made history when a tiny bunch of electrons completed a nearly speed-of-light journey through the kilometer-long accelerator to produce the very first burst of X-rays from an exquisitely aligned series of magnets: the first light from LCLS.

Since that moment, SLAC has been the birthplace of a host of scientific firsts. Here are 10 areas where LCLS has shined new light in the 10 years since it turned on.

1. Unpeeling atoms and molecules from the inside out

LCLS can produce X-ray pulses about 100 times more intense than all the sunlight hitting the Earth’s surface focused onto a thumbnail. These extreme pulses provide a revolutionary path forward for imaging man-made nanomachines and individual biological objects, such as proteins and other macromolecular complexes, at high resolution.

But that powerful beam also does a lot of damage, so a wholly new type of measurement had to be developed to take advantage of this new source of light. This method, called diffract-before-destroy, is one of the keys to LCLS’s success, allowing researchers to collect precise information from delicate samples in the instant before they’re blown apart.

Some of the first studies at LCLS took advantage of this unprecedented intensity. They showed that the brilliant laser light can strip electrons away from atoms from the inside out, creating “hollow atoms.” Many new aspects of the ionization of atoms were revealed for the first time, including the importance of transient phenomena, which informed the development of a more advanced theory of atomic physics.

Understanding this fundamental interaction of matter and light is essential for recreating the wild conditions needed to produce new states of matter, and for warding off damage in samples researchers are trying to image.

2. Recording molecular movies of chemistry in action

Ring-shaped molecules are a bedrock of biochemistry, such as the processes that lead to the formation of vitamin D, and lie at the heart of many pharmaceutical compounds and the synthesis of new types of materials. With LCLS, researchers were able to track, for the first time, the ultrafast movements of these molecules as they burst open and unfurled.

This video describes how the Linac Coherent Light Source, an X-ray free-electron laser at SLAC National Accelerator Laboratory, provided the first direct measurements of how a ring-shaped gas molecule unravels in the millionths of a billionth of a second after it is split open by light. The measurements were compiled in sequence to form the basis for computer animations showing molecular motion. (SLAC National Accelerator Laboratory)

The fact that the X-rays from LCLS arrive in a burst just a few femtoseconds long lets us generate a stop-motion “molecular movie” that reveals how the shape of the molecule changes throughout the reaction. Compared to other approaches, the extreme brightness and short pulse duration of LCLS provided measurements that were almost completely free of background noise, allowing clear interpretation of the molecular structures and the role of electrons in driving the reactions.

This ability to directly image the motion of atoms as they undergo a chemical reaction represents a step change in our capacity to link the structure of molecules with how they function and react, and it allows us to develop improved approaches to understanding and controlling complex material synthesis.

3. Watching molecules “breathe”

In a milestone for studying a class of chemical reactions relevant to novel solar cells and memory storage devices, scientists used LCLS to watch “molecular breathing” – waves of subtle in-and-out atomic motions – in real time and unprecedented detail.

These ripples of motion revealed how energy is exchanged between light and electrons. Researchers tracked how the energy led to tension and eventually motion of atoms in an iron-based molecule that’s a model for transforming light to electric energy, showing future potential for creating a switchable molecular memory device.

To see it “breathe,” the molecule was hit by a burst of laser light, immediately followed up with an X-ray pulse from LCLS to examine the changes that took place. The laser light excited an electron in the central iron atom of a molecule, which was then transferred to an outer wing of the molecule. When the electron returned to the iron atom 100 femtoseconds later, it flipped the magnetism of the iron. This caused the molecule to expand, setting off a breath-like oscillation through the entire structure.

4. Catching the birth of chemical bonds

The acceleration of chemical reactions, a process called “catalysis,” underpins a vast number of industrial processes, such as the production of fertilizer, but we lack a fundamental understanding of the chemical bond formation that underpins this and many other areas. LCLS’s laser pulses are so short that they can capture snapshots of reactions as they unfold, illuminating previously hidden steps at the atomic scale.

In one study, researchers watched in real time as a chemical bond formed between atoms on the surface of a catalyzing metal plate. They were able to follow, at the femtosecond timescale, subtle changes in the motions of carbon and oxygen atoms on a ruthenium surface when illuminated by laser light, and reveal the fleeting transition states that can lead to the formation of carbon dioxide.

Anders Nilsson, a professor at SLAC and at Stockholm University, explains how scientists used an X-ray laser to watch atoms form a tentative bond, and why that's important. (SLAC National Accelerator Laboratory)

Understanding chemical reactivity is also important for the development of solar energy conversion, where there is a need to develop new techniques for mapping subtle changes in the underlying photochemical processes. Femtosecond LCLS pulses and their ability to probe specific atoms in a complex molecule were used to resolve a long-standing uncertainty in a benchmark photochemical reaction. These techniques can be broadly applied in many areas of chemical sciences, and are a driving reason for the high repetition rate of LCLS-II.

5. Cracking the mysteries of photosynthesis

Despite its crucial role in creating and sustaining life on Earth, photosynthesis is still not fully understood. One of its best kept secrets is how photosystem II, a key protein complex in nature, harvests energy from sunlight and uses it to split water and produce the oxygen we breathe. A better understanding of how this process works could provide a blueprint for developing clean sources of renewable energy.

Until recently, it had only been possible to measure fragments of this process at extremely low temperatures. At LCLS, scientists can study and image steps of the process at its natural temperature, mapping both its structure and chemistry before the sample is destroyed. The ultrafast pulses of X-rays are used to produce two sets of data: X-ray crystallography data, a map of the molecular structure with atomic resolution, and spectroscopy data, a map of how electrons flow in the oxygen-evolving complex of photosystem II. This approach allowed the researchers to narrow down the proposed mechanisms put forward by the research community over the years.

The machinery responsible for photosynthesis – while commonplace and essential to life on Earth – is still not fully understood. One of its molecular mysteries involves how a protein complex, Photosystem II, harvests energy from light and uses it to split water into hydrogen and oxygen. This video explains how, in a previous paper, researchers were able to see two key steps in photosynthetic water splitting under conditions as it occurs in nature, a big step to decoding how the process works in detail. (SLAC National Accelerator Laboratory)

Most recently, they were able to track the position of the oxygen atoms and the heavier metal atoms in the molecule, capturing all four metastable states of the process as well as some fleeting steps in between, providing unprecedented insight into the mysteries of photosystem II.

6. Mapping drug targets in motion

To accelerate the design of more effective drugs with fewer side effects, researchers need to map how drugs dock with their protein targets in the cell with atomic resolution. The best way to do this is to crystallize the drug as it binds to a protein, but it’s sometimes difficult to grow crystals that are large enough for structural studies using conventional X-ray crystallography.

LCLS offers researchers a way to get data from much tinier crystals in ambient conditions, allowing faster, more accurate imaging of hard-to-study drug targets. LCLS has pioneered powerful new experimental methods – diffract-before-destroy and serial femtosecond crystallography – that have opened new areas of structural biology by enabling high-resolution, damage-free 3D structures of membrane proteins, metalloenzymes and small bio-crystals in near-native environments.

In an ongoing series of experiments, researchers are mapping the structure of G-protein coupled receptors that play a key role in controlling signaling in our cells, and which are targeted by a very large number of pharmaceutical drugs on the market.

Recent experiments in this series have revealed how a hypertension drug binds with a target (angiotensin-II) that helps regulate blood pressure, and provided key structural details for a cell signaling pathway in the human body (rhodopsin-arrestin) that regulates sensory and hormonal responses. Other experiments studied the atom-by-atom details of brain signaling to help underpin our understanding of neurological diseases and determined the structure of a larvicide to aid the battle against mosquito-borne illnesses such as Zika and dengue fever.

This video describes the function and 3-D structure of a protein complex that provides the ultrafast trigger for chemical messages sent between nerve cells in our brains. The details of this structure, brought to light in an experiment at SLAC’s Linac Coherent Light Source X-ray laser, provide a new understanding of the molecular machinery driving brain function. (SLAC National Accelerator Laboratory)

7. Uncovering the mechanics of biological machines

Every human is powered by a vast array of proteins and other biological machines that guide everything from how we see to how the body responds to viruses. For decades, biological function has been inferred from static maps of the 3D structure of crystallized molecules. But functioning biological systems are not static. To gain a deeper understanding, it’s important to study how the structures change over time, often as a result of external stimuli such as a change in environment.

With LCLS, researchers can now capture atomic-resolution snapshots of biological structures as they evolve over time. In one landmark experiment led by the National Institutes of Health, the dynamics of riboswitches, which are elements of messenger RNA central to genetic regulation, were mapped during a reaction initiated by the arrival of an external molecule. This resulted in a large change in the molecule’s shape, revealing at least four transient states and illustrating how the structure of the molecule is linked to the way signals are transmitted. More generally, these results opened up a new form of measurement for studying biochemically important interactions between bio-macromolecules and ligands.

Undulator Hall
hollow atoms
View of the The X-ray Pump Probe instrument at SLAC’s Linac Coherent Light Source.
Illustration of a transition state in a chemical reaction.
Image - This illustration shows a protein complex at work in brain signaling. Its structure, which contains joined protein complexes known as SNARE and synaptotagmin-1, is shown in the foreground. (SLAC National Accelerator Laboratory)