First electrons generated for revolutionary new tool in biological discovery

A team of scientists at Arizona State University’s Biodesign Institute has successfully achieved a milestone five years in the making — generating the first electrons from their highly innovative compact X-ray program.

The achievement is a major operational step as the ASU scientists race to complete the project's first phase, called a compact X-ray light source (CXLS).

“This is a kind of eureka moment, when we turn everything on, all of these complex systems, and we see those first electrons being generated,” said William Graves, an associate professor of physics at ASU and researcher at the Biodesign Center for Applied Structural Discovery. “We were very excited to get first electrons.”

Video by Steve Filmer

Once fully operational, the CXLS will make ultrashort pulses of X-rays to probe into the secrets of biology, medicine and advanced materials.

The first applications may include:

• Drug design and medicine research.
• Medical imaging research.
• Semiconductor quality control and research.
• Renewable energy research.

X-ray visionaries

For example, in biology, the CXLS acts like an ultrafast camera to see proteins and other building blocks of biology dynamically at work, analogous to how the very first X-rays yielded new views of our bodies.

“X-rays have been used for a hundred years to see what’s invisible, to see inside our bodies, but also to see molecular structure, to see how proteins are made,” Graves said.

But while conventional X-ray sources have been limited to taking static pictures, recent developments provide access to nature’s rapid dynamics. Indeed, a major goal of the finished CXLS device is to see reactions and relationships as they happen, said Graves, “taking high-speed movies of chemical reactions and molecules in action.”

Seeing molecules in action is often the first step in finding new biological targets for drug discovery.

As designed, the work of the device starts with packets of electrons generated by focusing extremely short ultraviolet laser pulses onto a copper surface. These electrons are accelerated to nearly the speed of light by a 1-meter-long linear accelerator and strong microwave-frequency electromagnetic fields with megawatt peak power. Next, they form a directed beam by passing a series of precision-aligned magnets. The resulting electron beam is blasted by an intense optical laser, which imparts an undulating motion on the electrons resulting in strong and predictable X-ray emission.

Once generated, the X-rays can then be used to reveal the atomic structures and functions of biomolecules and novel materials. They are images of how life works.

“We want to capture not just the static structure, but how it works,” Graves said. “What’s the function of the different molecules? Can we actually see the reaction taking place? We’d like to create a kind of stop-motion movie of the making and breaking of chemical bonds. And by doing that, we gain much more insight into how the chemistry and the molecules work,” he added. Graves says this could lead to new advanced understanding in several areas of scientific research.

“For instance, in how drugs are able to impact viruses. In developing new drugs, or looking at exotic materials that are so-called high temperature superconductors that could revolutionize energy production, because they don’t use any power to store the energy. And we don’t yet understand the physics of that,” he added.

The program would not have been possible without visionary philanthropists who wanted to spur new technologies to aid drug discovery and help alleviate human suffering and disease. In 2018, the program received a major boost with a generous $10 million contribution from Annette and Leo Beus to create the Beus Compact X-ray Free Electron Laser Lab. During the past few years, the program has generated much anticipation and excitement among scientists in the field and attracted scores of scientists to ASU.

Recently, condensed-matter and laser scientist Robert Kaindl was brought in as the first director of the CXFEL Science Program and an ASU faculty member in the Department of Physics. The lab opened in the ASU Biodesign C building in the fall of 2018, and since that time, deputy director and research scientist Mark Holl has spearheaded the design, engineering and construction of the complex equipment inside the lab.

About 100 researchers and students from ASU and other institutions are involved in these efforts, with both the design work and the construction of CXLS continuing at a rapid pace despite the ongoing COVID pandemic.

Flipping the switch

In the first phase of the project, the team is building the compact X-ray light source, or CXLS. Using an optical laser in the X-ray generation reduces the length of the electron undulator and the accelerator by many orders of magnitude. Reducing size and cost means that more universities and institutions could build similar sources, putting more minds to work looking at things like proteins.

The milestone for CXLS also represents a significant technical leap forward to ushering in the next phase of the ASU project, a future planned compact X-ray free electron laser (CXFEL). This will produce even more powerful X-rays with even shorter pulse durations to obverve the fundamental motions of electrons in molecules and materials and to capture biology in action with even greater fidelity.

The overarching goal of the program is to help scientists gain greater access to the emerging XFEL science to make new discoveries. Currently there are only about a handful of X-ray free-electron lasers around the world, because they are based on mile-long particle accelerators with associated billion-dollar construction costs. A single experiment can cost several hundreds of thousands of dollars to run.

But because they generate the most powerful and shortest pulses of X-rays in the world today, the X-ray beams of the big XFELs are used to find fundamental answers to some of the most important questions in biology, chemistry and physics. The revolutionary ASU CXFEL promises to dramatically shrink the costs and footprint from mile-long, billion-dollar underground bunkers of existing XFELs to garage-size, million-dollar startup labs — while enabling completely new science. Currently, such studies are limited and spread among the handful of large accelerator-based free-electron lasers around the world.

A further breakthrough will be needed for the transition from the innovative CXLS to the envisioned future CXFEL. In 2019, the National Science Foundation announced its support of the next-stage CXFEL project with a $4.7 million grant to fund a comprehensive design study of the new device.

Graves says this step will be a technology to create a nanopattern for the electrons, which would put them into a precise arrangement. The next steps in the application of CXLS and development of a CXFEL machine make these sources a centerpiece for future industry partnerships and scientific collaboration, as well as real-world opportunities for students to get experience in physics, biology and engineering.

Top photo: Associate Professor William Graves, master designer and builder of the new compact X-ray free electron laser, uses a model to talk about the device at the 2019 celebration of the Leo and Annette Beus donation to the Biodesign Institute for the Beus CXFEL Laboratory, in the Biodesign C building. The $10 million investment will help shape the future of research, medical imaging, cultural heritage, quantum information and energy. Photo by Charlie Leight/ASU News