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Bright lights, big science

September 17, 2019

Revolutionary laser instrument CXFEL receives $4.7 million boost from the National Science Foundation

Deep within the subterranean confines of Building C — the latest addition to the Biodesign Institute at Arizona State University — a pathbreaking machine is quietly taking shape. Designed to unlock some of nature’s tiniest and most fleeting mysteries, the Compact X-ray Free Electron Laser (CXFEL) is the only instrument of its kind in the world.

The device is the brainchild of physicist William Graves, a passionate authority on massive, intricate machines for leading-edge science. For the past 30 years he has worked on the design and construction of particle accelerators. The CXFEL represents ASU’s bold attempt to dramatically reduce the size of such instruments, making them suitable for universities and medical institutions.

The CXFEL, a very special type of laser, will help scientists explore far-flung realms in molecular biology, medical imaging, exploration geology, material science, astrophysics, renewable energy, quantum computing and even art history with spectacular clarity.

Today, the National Science Foundation (NSF) announced it is supporting the project with a $4.7 million grant to advance the audacious undertaking, funding a comprehensive design study of the new device.

“What we're building here is called an XFEL, which stands for X-ray free electron laser,” said Graves, a researcher in the Biodesign Center for Applied Structural Discovery and associate professor of physics at ASU. “The electrons aren't free in the sense that they cost nothing. They're fairly expensive electrons, but they're free in the sense they are not bound to atoms, which means they are free to lase at any wavelength we choose.”  

Such lasing occurs when electrons emit coherent light, where all the light waves are in phase with each other. The pulses of laser light produced by XFELs are about a billion times as bright as conventional X-rays and can be produced in lightning-fast bursts lasting on the order of femtoseconds or less. (A femtosecond is a millionth of a billionth of a second.)

Video by ASU

Intrepid innovation

In recent years, ASU has earned a reputation for daring and futuristic research. It has just been awarded the title of most innovative university for the fifth straight year by U.S. News and World Report. The CXFEL is a prime example of this uncompromising spirit of scientific inquiry.

“The CXFEL is not just a first for ASU’s Biodesign Institute, but potentially the first instrument of its kind in the world,” according to Joshua LaBaer, executive director of the Biodesign Institute and director of the Biodesign Virginia G. Piper Center for Personalized Diagnostics.

“This instrument truly represents a sea change in many diverse fields of research," LaBaer said. "My own area of proteomics or protein research is but one such domain, where the CXFEL will offer powerful insights into the detailed structure of these molecules, which are vital for virtually all biological processes and major players in disease.

“But what really excites me is the CXFEL’s unique capacity to examine what biology has been doing at speedy timescales that have remained hidden from science until now, from the behavior of viruses and other pathogens to protein binding events occurring at the atomic scale. We will now be able to produce high-resolution movies of these dynamical processes, and that’s really just the beginning of the new scientific frontiers open to us. Molecular science, medical imaging science and materials science will never be the same.” 

first X-ray

Hand Mit Ringen: Wilhelm Conrad Röntgen, German professor of physics, discovered "a new kind of ray" — later known as the X-ray — in November 1895 and recorded the first X-ray images on photographic plates during the following weeks. This blurry image is a print from one of the first X-rays of a human being ever produced and is said to depict the hand and wedding ring of Röntgen’s wife, Bertha.

An intimate view of nature

It turns out that such brilliant X-rays dispersed in femtosecond flashes can act like a high-def camera on steroids, revealing previously unseen phenomena, including the elusive dynamics of proteins, which have profound implications in the study of multiple diseases and the design of more effective drugs. 

Conventional XFELs however, come with a big catch: the price tag. “They cost $1 billion or more each. There are now five in the world — about one per continent,” Graves said. These complex and gargantuan machines, like the Linac Coherent Light Source at Stanford University, are a mile or more in length. The Stanford instrument sits on a massive 426-acre plot at its home in California. “It takes hundreds of people and $100 million a year to operate and run one of these things.”

This is where the C in ASU’s CXFEL comes in. The Compact X-ray Free-electron Laser under construction at Biodesign accomplishes most of the same scientific feats as the large XFELs in a laboratory-sized instrument 100 times less expensive to build and operate. In fact, as Graves notes, the CXFEL complements the huge XFELs as a more precise tool, while the big ones have more powerful beams. Graves compares the CXFEL to a scalpel instead of a hammer.

Big science peers into the tiniest worlds

The grant is part of the NSF’s Big Ideas initiative, specifically its midscale research infrastructure program, designed to fund “everything from major observatories to nationwide sensor networks to smaller experiments,” and will complement work already underway by Graves’ ASU colleagues, including Petra Fromme, the Paul V. Galvin Professor of Molecular Sciences and director of the Biodesign Center for Applied Structural Discovery, and John Spence, the Richard Snell Professor of Physics at ASU. Fromme and Spence have pioneered ultrafast X-ray science at the big XFELs under another NSF grant known as BioXFEL, applying the technology to the study of biological phenomena.

“Petra and John saw what I was working on at MIT and brought me here to implement this project,” Graves said. “ASU said, ‘We want to do that,’ and here we are doing it. We've made great strides and are turning on the prototype Compact X-ray Light Source in early 2020."

XFELs represent a truly revolutionary advance for many kinds of scientific research and have been particularly fruitful in unlocking atomic-scale dynamics of proteins and other biomolecules — a domain in which Fromme and Spence have both made major contributions. Having such a device on campus is a dream come true for such researchers and something that would have been unthinkable a short time ago, when scientists around the world had to hustle for precious beam time for their experiments at a handful of large facilities like SLAC National Accelerator Lab at Stanford University.

With a generous $10 million contribution from Annette and Leo Beus to create the Beus Compact X-ray Free Electron Laser Lab, Graves’ exhilarating vision has become a reality. Since the grand opening of Biodesign C in the fall of 2018, Mark Holl, deputy director of CXFEL, has led construction of the equipment in state-of the-art labs expressly designed to accommodate the new CXFEL.

XFEL 101

How do XFEL devices produce their ultrafast, brilliant X-rays? It starts with the riverlike flow of the famous free electrons. In the large machines, the electrons are accelerated to near light speed through vast tunnels like the 2-mile tube at SLAC. During the course of their flight, the electrons are fed into an undulator — a series of powerful magnets of alternating polarity. As the electrons jiggle up and down under the magnetic field, they emit intense X-rays.

One of the key innovations that allows the new device to be radically reduced in size is the replacement of the undulator magnets. In the compact X-ray light source or CXLS — the initial phase of the project — the job of jiggling the electrons and inducing them to emit X-ray light is accomplished with an infrared laser, which reduces the size of the undulator by about 10,000 times and the size of the accelerator by 100 times.

A further breakthrough is required for the transition from CXLS to CXFEL, which involves taking disorganized bunches of electrons and converting them into a precise arrangement or nanopattern.

“They're just a blob of about a billion electrons, and we need to sort them into very small bins. These bins are each about the size of an atom,” Graves said. “And through the sorting technique that we do using electron diffraction, we're able to greatly increase the power and the coherence of the X-rays that are emitted.”

All-seeing eye on nature: The CXFEL, a very special type of laser, will help scientists explore far-flung realms in molecular biology, medical imaging, exploration geology, material science, astrophysics, renewable energy, quantum computing and even art history with spectacular clarity.

An ambitious timetable

The new NSF Big Ideas grant carries the project forward through four areas of investigation. The first involves detailed simulation in design, physics and engineering of the instrument. The remaining three areas are focused on applications of the new device for advanced science. 

“These awards represent the first in NSF’s agency-wide effort to support the midrange infrastructure that will be invaluable to strengthening the U.S. scientific research enterprise,” said Jim Ulvestad, National Science Foundation chief officer for research facilities. “The funded projects include an impressive collection of new design efforts and advanced instrumentation. These projects fill gaps and provide unique research capabilities for the U.S that will engage many early-career scientists and engineers in the pursuit of groundbreaking discoveries.” 

The first application is in attosecond physics, which examines how molecules connect with each other and the dynamics of chemical reactions and catalysis. Attosecond dynamics are the fastest processes in nature and also have important implications for industry.

Another area is in quantum materials, a new frontier involving very subtle effects in materials at the quantum level that cause them to display unique characteristics and behavior. Such research could eventually lead to the development of superconductivity at room temperature, which could have a profound effect on energy use and contribute to the development of quantum computing. The CXFEL is a precise probe for such investigations.

The third and the most important area for ASU research is Fromme’s realm of expertise, known as time-resolved biochemistry. This involves the subtle interplay between biological and chemical processes.

“Perhaps the best example of this is photosynthesis,” Graves said. “We don't quite understand yet how that works. How does a plant absorb a photon from the sun and then transfer that energy into electric and chemical energy? We have some idea of the steps, but we've never been able to map them out. They happen at femtosecond and sub-femtosecond levels. And we think that with this probe, we'll be able to finally successfully unravel that.”

In addition to the power of the CXFEL for uncovering new science, the compact dimensions will allow the technology to go where it is needed, at universities, institutions and hospitals. One application of the CXFEL, for example, is for phase contrast medical imaging, capable of examining soft tissues in the body, including malignancies, with unprecedented resolution. ASU is currently in collaboration with Mayo Clinic to study and apply phase contrast imaging for next-generation diagnosis of disease.

Functional dynamics – visualizing molecules in action

Nov. 6-8, 2019
Arizona State University, Tempe campus

The Biodesign Institute at Arizona State University and the publications Nature, Nature Chemistry, Nature Communications, Nature Methods and Nature Physics are pleased to present the gathering of leading researchers from around the world who will explore pioneering efforts to observe molecules in action, including XFEL technology.

The National Science Foundation is an independent federal agency that supports fundamental research and education across all fields of science and engineering. In fiscal year 2019, its budget is $8.1 billion. NSF funds reach all 50 states through grants to nearly 2,000 colleges, universities and other institutions. Each year, NSF receives more than 50,000 competitive proposals for funding and makes about 12,000 new funding awards.

Top photo: Bill Graves is a researcher in the Biodesign Center for Applied Structural Discovery and an associate professor of physics at ASU.  

Richard Harth

Science writer , Biodesign Institute at ASU


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Diversifying healthy aging

Age is the biggest risk factor for developing Alzheimer's disease.
Alzheimer's affects about 2/3 of women and 1/3 of men.
September 17, 2019

New ASU center for healthy aging partners with Banner Alzheimer's Institute to host conference for Hispanic community

Roughly 5.8 million Americans are currently living with Alzheimer’s disease, and by 2050, that number is expected to increase to roughly 14 million. Over that time, the population with the largest projected increase in instances of the disease are Hispanic Americans, underscoring the need to address taboos and misconceptions and spread knowledge and resources within that community.

Last week, the Banner Alzheimer’s Institute and Arizona State University’s recently established Center for Innovation in Healthy and Resilient Aging partnered to host the first-ever Hispanics and Alzheimer’s Disease Conference at the Banner Estrella Medical Center in Phoenix.

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David Coon

“While the Center for Innovation in Healthy and Resilient Aging is not focused solely on Alzheimer’s disease, it is dedicated to improving the quality of life of older adults through education, prevention, care and research,” said David Coon, director of the center, which is housed in ASU’s Edson College of Nursing and Health Innovation. “We’re happy and excited to partner with Banner to reach out to the Hispanic community, who have been underserved in this area.”

Aside from increasing awareness, the other main goal of the conference was to educate the community about the importance of participating in clinical trials.

“At Banner, we have noticed there is a dire need to diversify our clinical trials,” said Daniel Viramontes Apodaca, clinical research coordinator with the Banner Alzheimer’s Institute. “So this initiative is part of our year of diversity, where we’re putting an emphasis on diversity in Alzheimer’s awareness.”

At the conference, Alzheimer's experts from Banner Health, ASU and the greater Phoenix area led simultaneous panels and discussions in both Spanish and English for a crowd of about 120 community members, many of whom were caregivers themselves.

Edward Quinones, a 72-year-old Vietnam veteran, attended the conference Friday at the behest of his daughter, in hopes of learning more about caregiving resources and clinical trials. Quinones’ wife has been diagnosed with dementia, and he is in the process of being diagnosed himself.

“I don’t think there’s enough talk about it (in the Hispanic community),” Quinones said. “My understanding was always that it was just a part of getting older, just a part of life.”

That was one of many misconceptions addressed in a panel discussion titled “Fact or Fiction: The Truth about Alzheimer’s Disease,” led in Spanish by Claudia Fernandez of Hospice of the Valley and in English by Heather Mulder, outreach program senior manager at Banner Alzheimer’s Institute.

Other myths busted by the panel:

  • Forgetting what you ate for lunch is a normal part of aging: This is false because normal aging results in lapses in long-term memory while Alzheimer’s damages the hippocampus, the part of the brain responsible for short-term memory.
  • Men are affected more by Alzheimer’s: This is false because roughly two-thirds of women are affected by the disease while only about one-third of men are. The assumption used to be that this was because women lived longer, but recent findings indicate it may have something to do with how hormonal changes women experience during menopause affect their brains.
  • Supplements help boost memory: This is false because supplements are not regulated by the FDA in the same way pharmaceutical drugs are, so there is no hard research to prove they boost memory. One of the best ways to boost memory is through mental exercise, such as games and hobbies, but the best mental exercise is to learn something new.

The discussion also covered the 10 warning signs of Alzheimer’s, risk factors, lifestyle factors and hope for the future.

Risk factors are something people have no control over, such as genetics and age, with age being the greatest risk factor for Alzheimer’s. At the age of 65, chances of developing the disease are about 1 in 8. Those chances double every five years, reaching nearly 50-50 by the age of 85. By the age of 95, however, the risk begins to drop off.

Lifestyle factors are something we do have control over, such as diet and health. Hispanics have a much higher rate — about two times higher — of developing Alzheimer’s than other populations because of higher incidences of diseases that affect the heart among the community. The good news is that following a healthy lifestyle plan to avoid such diseases drops the risk for Alzheimer’s considerably.

While about 80% of clinical trials are delayed or fail because of a lack of participants, much of the hope for the future lies in what doctors and scientists have been able to discover through that kind of research, highlighting the great need in that area.

“Your life does not end because you’ve been diagnosed with Alzheimer’s,” said Berta Carbajal, a research specialist at the Edson College and co-founder of the Promotores HOPE (Helping Other Promotores Excel) Network who led a discussion about caregiver concerns. “But culturally, it’s like we shut off, we go into denial. That’s why we want to be able to open up these doors of communication and talk about those fears and educate people about the resources and research opportunities available to them.”

Top photo: Attendees at the Banner Alzheimer's Insititute Hispanics and Alzheimer’s Disease Conference on Friday hold up paddles to indicate whether they think a statement about Alzheimer's disease is fact or fiction. Photo by Deanna Dent/ASU Now