ITS short, intense pulses of x rays
will reveal for the first time the structure and dynamic behavior
of many proteins and viruses at atomic resolution and in three
dimensions. It will unlock the secrets of high-energy-density plasmas,
which are of interest to the nation’s Stockpile Stewardship
Program. And it will create the hot, dense matter believed to exist
in the center of large planets.
It’s the Linac Coherent Light Source (LCLS), the world’s
first large-scale x-ray laser, being designed for installation
at the Stanford Linear Accelerator Center (SLAC). “The immense
power of its short-pulse, laserlike x rays will create a revolution
in science,” says Alan Wootton, chief scientist for Livermore’s
Physics and Advanced Technologies Directorate.
The heart of the LCLS is a free-electron laser that produces beams
of coherent, high-energy x rays. Coherence—the phenomenon
of all photons in a beam acting together in perfect lockstep—makes
laser light far brighter than ordinary light. Think of a 10-watt
night light; then compare its brightness with that from a 10-watt
laser—a beam so bright it can cut metal. Because x-ray photons
at the LCLS will be coherent, the resulting beam of light will
be as much as 10 billion times brighter than any other x-ray light
source available today.
The LCLS, and a cousin planned in Germany, will improve on so-called
third-generation light sources. The third-generation sources are
circular, stadium-size synchrotrons, and they produce streams of
incoherent x-ray photons. Because their pulses are long compared
to the motion of electrons around an atom, synchrotron light sources
cannot begin to explore the dynamic motion of molecules. The light
from the fourth-generation LCLS will last for quadrillionths of
a second, allowing its beam to capture such dynamic behavior.
The goal of the new fourth-generation
light source is to image single molecules. Shown here are
(left) the lethal-factor protein of an anthrax spore
and (above in title image) a simulation of its diffraction
determining the static structure of proteins and molecules will
be easier and faster with the LCLS. Today, proteins and other
macromolecules must be crystallized before their structure can
be probed with synchrotron radiation. But not all proteins can
be crystallized, and the crystallization process is long and involved.
With the LCLS, a single powerful pulse will image one molecule
with no prior crystallization required.
Livermore is part of a SLAC-led consortium to plan, design, and
build the LCLS. Other partners include the University of California
at Los Angeles (UCLA) and Los Alamos, Brookhaven, and Argonne national
Livermore’s primary responsibility, under physicist Richard
Bionta, is to design and fabricate the optics that will transport
the x-ray beam to experimental chambers and to measure, or diagnose,
the beam’s condition. The extreme brilliance and ultrashort
duration of the beam’s pulses will give the beam a peak power
of as much as 10 gigawatts. These features make designing optics
a challenge because, says Bionta, “The energy of the beam
can melt many materials in a single pulse.”
physicist Henry Chapman and other Livermore scientists are planning
the first experiments at the LCLS and that are needed for various
“At the LCLS, we’ll use lens-less imaging to determine
the three-dimensional arrangement of atoms in a molecule,” Chapman
says. “We’ll detect x rays scattered by a sample
when the beam hits it and then examine the diffraction pattern.” Radiation
from the powerful beam will destroy each sample, but the beam’s
ultrashort pulse will generate diffraction data before that happens. “Every
molecule has a unique diffraction pattern,” says Chapman, “and
that pattern depends on the molecule’s structure.”
at the LCLS will reveal protein structure, which determines protein
function. Hence, the LCLS is expected to profoundly benefit
structural biology and medical research. It could eventually help
scientists solve the proteome—the entire system of proteins
in the human genome.
Linac Coherent Light Source will use the linear accelerator
(linac) at the Stanford Linear Accelerator Center to create
very bright, ultrashort pulses of laser radiation.
A Single Straight Shot
the LCLS becomes operational, sometime in 2008, the free-electron
laser’s photoinjector will shoot electrons down part of the
SLAC linear accelerator, or linac. The photoinjector will produce
tiny bunches of electrons that travel in a narrow, bright beam
at almost the speed of light. After the electrons enter the kilometer-long
linac, compressors along the accelerator path reduce the length
of each bunch by a factor of 30, which increases their peak current.
Their energies may be pushed as high as 14 gigaelectronvolts,
a value that will be adjusted from experiment to experiment to
produce the desired range of x-ray frequencies.
electrons then enter an undulator—a vacuum chamber just
5 millimeters across and about 125 meters long and lined with 7,000
magnets arranged in alternating poles. As the electron bunches
move down this narrow channel, the magnetic fields push and pull
on them, causing the bunches to emit x rays. The LCLS undulator
is so tightly focused that x rays emitted by one electron
interact with the electrons in front of it. This interaction causes
the electrons to bunch more tightly, which generates more x rays.
the process repeats, the bunches become smaller and smaller. This
chain reaction is called self-amplification of spontaneous
emission, or SASE (pronounced “sassy”). SASE eventually
saturates the x-ray beam, producing a narrow, coherent beam of
light—a laser. Broadband spontaneous (not coherent) radiation
about 10,000 times brighter than that from any other light source
emerges from the undulator as well.
Livermore-designed optical devices, placed beyond the undulator,
will manipulate the direction, size, energy spread, and duration
of the x-ray beam. They also will diagnose the beam and direct
x rays to one of two halls for use in experiments.
experimental halls, A and B, are located 50 and 400 meters downstream
from the end of the undulator. Experiments requiring
a very narrow, high-energy-density beam will use facilities in
Hall A, while Hall B will house experiments that require lower
of the Linac Coherent Light Source at the Stanford Linear Accelerator
Center. Experimental halls A and B will be to the left, beyond
the photon beam lines.
Optics Bear the Brunt
All the diagnostic equipment on the LCLS is designed to minimize
interference with the beam. “Because the beam is so powerful,” says
Bionta, “our goal is to not put anything in its path, except
a gas attenuator.”
A mask, valves, and movable jawlike slits just beyond the undulator
intercept most of the spontaneous radiation that accompanies the
beam. These devices are designed so that they do not block the
narrow, intensely coherent x-ray beam.
Livermore researchers have been working for several years to understand
the damage that occurs when an LCLS beam encounters optics, diagnostics,
and targets. Several types of simulations, including Monte Carlo
and wave models, helped them fully characterize the x-ray beam.
Armed with these data, Wootton, Bionta, and others began to develop
schemes for imaging such a bright beam.
The concept they selected uses a camera that will be one of the
first diagnostic devices beyond the undulator. In this setup, a
small fraction of the beam’s light is directly reflected
off a thin, polished beryllium foil. Beryllium was chosen for the
foil because it has a low electron density and tends to absorb
few x rays. Beryllium also will be used for many of the reflective
optics at the front end of the system where photon densities are
When the beam reflects off the foil, it strikes the surface of
a 100-micrometer-thick lutetium oxyorthosilicate (LSO) crystal
doped with a 5-micrometer-thick scintillating layer of cerium. “The
LSO crystal is designed to reflect just one-ten-thousandth of the
total light from the beam,” says Bionta. Reflected visible
light is collected by a microscope lens and forms a magnified image
on a charge-coupled device (CCD) camera. The images of a beryllium–aluminum
disk shown below demonstrate the fine resolution of the camera.
novel charge-coupled device camera was designed so that its
images would show features as small as one pixel across. (a–c) These
images of a beryllium–aluminum disk demonstrate the camera’s
resolution. (d, e) In these images, x-ray resolution
is less than or equal to one pixel, as models predicted.
the CCD camera, the team has studied how photons from short-pulse
lasers at various wavelengths interact with different materials.
For example, silicon was irreversibly damaged even at low energy
densities using a laser in the visible wavelength and pulse lengths
similar to those of the LCLS.
the LCLS’s high-energy beam will be a challenge.
The Livermore researchers are developing a new class of tubular
optical devices in which the x-ray beam reflects off the inside
wall. The slight grazing incidence of the beam on the wall of the
lens reduces the absorbed energy considerably. X rays enter the
tube at one end and are reflected once by the highly reflective
interior surface. They then exit from the other end of the tube,
but now the x rays are traveling in a slightly different direction.
focusing element has also been designed for the warm, dense matter
experiments that will take place in Hall A. Warm,
dense matter is an energetic plasma whose density is almost that
of a solid, but it may be as hot as 10,000 kelvins. Scientists
believe this matter may exist in the centers of large planets,
such as Jupiter, and its properties are important to astrophysics
and relevant to the production of inertially confined fusion reactions.
Warm, dense matter will be created in the laboratory by focusing
the x-ray laser’s beam to a 2-micrometer spot in the center
of a sample of solid matter.
focusing element will be a blazed phase lens, as shown in the top
image below. The lens is made of carbon, which has low x-ray
absorption characteristics. Although carbon is not as resistant
as beryllium is to the intense power of the LCLS, it has a higher
refractive power and is easier to machine precisely, allowing more
interesting optical designs. To test the lens design, the research
team had a prototype machined at Livermore’s Large Optics
Diamond Turning Machine (LODTM).
prototype lens is made from a thin disk of aluminum, which has
the same optical properties as carbon. The aluminum lens was
tested at the Stanford Synchrotron Radiation Laboratory. Although
lens performance was limited by the material chosen and the geometry
of the experiment was not ideal, the measured performance closely
matched predictions from simulations.
machinists at the LODTM are trying to make lenses from blocks of
pure beryllium. Beryllium is a challenge to machine because
of its grain structure and because it’s a hazardous material.
In fact, Livermore’s LODTM is one of the few facilities in
the nation authorized to work with it.
the most challenging LCLS diagnostic will be measuring the 230-femtosecond
pulse length. Streak cameras are not an option
because they measure down only to 500 femtoseconds. One potential
device is a fiber-optic interferometer developed by Livermore photonics
experts. The interferometer uses the beam from a continuous-wave
laser to monitor the electronic state of a tiny waveguide inserted
across its measurement arm.
we tested the interferometer at Stanford’s synchrotron,” says
Bionta, “it was sensitive to x rays perturbing the waveguide.
In fact, its response was faster than we could measure with the
synchrotron beam.” Further experiments will be conducted
with shorter-pulse x-ray sources at Livermore and SLAC, to determine
if the device is really fast enough to measure the 230-femtosecond
A prototype blazed phase lens made
of pure aluminum. The pattern was carved using Livermore’s
Large Optics Diamond Turning Machine. Each groove is 18.7
micrometers deep, and the final thickness of the disk is
79 micrometers. In tests of the lens at the Stanford
Synchrotron Radiation Laboratory, (b) measured images closely
Technologies for Experiments
Two general classes of experiments have been proposed for the LCLS.
In the first class, the x-ray beam will be used to probe the sample
without modifying it, which is the current practice for most experiments
with synchrotron sources. For example, scientists can use the x-ray
laser to determine the dynamic behavior of chemical interactions,
essentially by watching the interaction occur on a femtosecond
scale, which has never been possible before.
In the second class of experiments, the LCLS beam will induce nonlinear
photoprocesses, or it will create matter in extreme conditions.
These experiments include creating warm, condensed matter, as previously
described, and determining the structure of macromolecules, by
recording crucial information about a molecule before it is vaporized.
It is in biology that the hard x rays of the free-electron laser
are expected to have the biggest effect. No technique available
today can image the interior of micrometer-size particles in three
dimensions at high resolution. With the LCLS, scientists will be
able to analyze very small samples, from tens of micrometers down
to single molecules.
With third-generation synchrotrons, the low-intensity x rays can
diffract to atomic resolution only when a molecule has been crystallized.
Once a protein has been crystallized, scientists can’t study
its interactions with other biological molecules. Nuclear magnetic
resonance spectroscopy is used to overcome these shortcomings of
x-ray crystallography, but it does not work for larger proteins.
With the LCLS, researchers can study proteins that can’t
be crystallized, such as proteins linked to lipids (fats) and embedded
in cell membranes. The short pulses of the LCLS will also reveal
how some molecules change shape in just a few femtoseconds.
trajectories computed by a hydrodynamic model show a 2-nanometer
protein exploding after it is hit by a 20-femtosecond, 12-kiloelectronvolt
x-ray pulse that is 0.1 micrometer wide. Models indicate that
atomic-resolution imaging can be achieved with pulses shorter
than 20 femtoseconds. They also show that a water tamper
on the protein slows its destruction so that longer pulses
could be used.
the diffraction pattern before the molecules blow up is critical.
X-ray pulses are diffracted by electrons orbiting
the atoms in molecules. By studying the patterns made by these
diffracted rays, biologists can deduce the structure of the molecule
under analysis. Team members have developed a hydrodynamic model
to understand the various interactions between the x-ray beam and
the sample and to verify that the beam’s pulse will end before
the sample begins to be torn apart. The figure to the right shows
results from simulations of a 20-nanometer protein molecule when
it’s hit by an x-ray free-electron laser. Models also indicate
that a water tamper will suppress the explosion, extending the
time range of the diffraction process. Researchers have used simulations
to establish the minimum photon density required to classify diffraction
and have determined that the necessary pulse durations range from
10 to 30 femtoseconds.
to verify the timing of the explosion will be performed at the
Tesla Test Facility (TTF), the proving ground for the TESLA
x-ray free-electron laser that is being designed in Germany. “The
TTF is the only place we have now for testing any of these simulations
experimentally,” says Chapman. “Its wavelength is longer
than the LCLS’s will be, so we can’t get to atomic
resolution. But we can begin to understand how and when damage
team is also exploring ways to get samples into the beam’s
path. “Molecules will be just a few billionths of a meter
wide,” says Wootton. “Somehow, we have to get them
lined up with a beam that’s only slightly larger, a few millionths
of a meter wide and running at the speed of light.”
pulse of the x-ray beam can hit just one sample in its path. Complete
three-dimensional information about a molecule will then
be collected by examining multiple, identical samples, one by one.
One method for acquiring such data is to use some kind of “molecule
gun” to feed samples into the beam path.
alternative method is to tether several protein molecules to a
membrane positioned in the beam’s path. This option, in
which the molecules are oriented the same way, requires a lower
photon density. Says Chapman, “Because in this case we can
now use a lower photon density, which will cause overall less damage,
models show we can use longer pulses where the rate of damage is
reduced.” The team is exploring whether dip-pen nanolithography
can be used to produce this carefully oriented pattern of molecules.
In dip-pen nanolithography, molecules of a protein or other organic
material are deposited on a substrate in a regular pattern.
Livermore researchers who are developing the algorithms to reconstruct
diffraction patterns have been aided by experiments
at the Advanced Light Source, a third-generation synchrotron at
Lawrence Berkeley National Laboratory. One recent experiment, in
collaboration with colleagues from Berkeley and Arizona State University,
used a silicon nitride pyramid decorated with 50-nanometer gold
spheres. These spheres were chosen because they could be well characterized
by other, independent means. As shown below, a reconstructed image
of gold ball clusters compares extremely well with an image obtained
using a scanning electron microscope. “This reconstructed
image is the first true lens-less x-ray image,” says Chapman.
Computer algorithms are being developed
to use diffraction pattern data to reconstruct an image
of the molecule under study. In experiments at Lawrence
Berkeley National Laboratory’s Advanced Light Source, (a)
a reconstructed x-ray image of gold ball clusters compares
extremely well with (b) an image obtained using a field-emission
scanning electron microscope.
the Tip of the Iceberg
Chapman’s team will also conduct experiments at the TTF in
Germany. Those single-shot diffraction experiments will use samples
mounted on a substrate and samples shot across the beam. Samples
will include lithographic test patterns, diatoms, and wet cells.
“With these experiments, we’ll be able to achieve the long-sought
goal of x-ray imaging at resolutions beyond the radiation-damage
limit,” says Chapman. “We hope to get spectacular images.
But they will be just the tip of the iceberg compared to what we
will be able to achieve at the LCLS.”
Key Words: free-electron laser; Linac Coherent Light
Source (LCLS); linear accelerator (linac); protein structure;
Stanford Linear Accelerator Center (SLAC); x-ray laser;
warm, condensed matter.
For further information on LCLS optics, contact Richard Bionta
(925) 423-4846 (firstname.lastname@example.org);
for information on the experiments, contact Henry Chapman (925)
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