Sound, light sources and the thrill of glimpsing the future

March 1, 2013 by Marc Allaire, Allen M. Orville & Alexei S. Soares
Members of the Photon Sciences Directorate team who collaborated in developing the acoustic droplet ejection system at the X25 beamline at Brookhaven Lab's National Synchrotron Light Source: (far left) Marc Allaire, (front row, from right) Rick Jackimowicz, Anthony Kuczewski, Christian Roessler, (back row, from right) Annie Héroux, Allen M. Orville (also of the Biosciences Department), and Alexei S. Soares

Scientific research is a process fraught with fits and starts, dead-ends, dashed dreams, unexpected turns, and the occasional exhilarating insight. As scientists, many of us continue along our career path in part because of those rare moments of joy felt when contributing to the frontiers of science. We experienced one of those rare moments this past January at the National Synchrotron Light Source (NSLS) X25 beamline, when we successfully tested a new method to collect data from protein crystals—by using sound waves to eject the crystals through the air into an X-ray beam.

For decades now, preparing microscopic protein crystals to collect data was done typically by hand with a microscope, and lassoing a crystal out of its liquid environment required great skill. After that was done, the sample would be transported from the lab to a beamline end station and then mechanically transferred into the X-ray beam, where we collected data to determine the of complex .

In contrast, this new method—called acoustic droplet ejection (ADE)—employs pulsed to eject crystals encased in a droplet from their source into the X-ray beam. This can be done with great precision, at high speeds, and without touching the crystals at all. We theorized that this was in fact possible back in 2008, but we were overcome with joy when, last month, we observed the first X-ray from crystals with our new, automated ADE method.

ADE in action at Brookhaven Lab, and beyond

We tested our ADE system at the X25 beamline by depositing slurries of protein crystals—whose diameters are measured in millionths of a meter—onto a sheet of X-ray transparent plastic. With these protein crystals affixed to the plastic, we were able to confirm that the quality of data from the X-ray diffraction process was not compromised at all compared to traditional approaches.

Our ADE system enables us to mount a sample and record X-ray diffraction patterns every few seconds. This is significantly faster than the current methods that require several minutes per sample. When necessary, this ADE method is powerful enough to deliver hundreds of crystal-containing droplets every second.

This video is not supported by your browser at this time.
Look, no hands! A pulsed sound wave ejects a droplet containing the microcrystal sample. The sample becomes affixed to an X-ray transparent sheet of plastic, positioned in the path of the X-ray beamline to determine the atomic structure of complex macromolecules. This hands-free technique is significantly faster than current methods.

Commercial ADE systems are available for drug discovery and genomics pipelines, and are large, boxy objects about half the size of a refrigerator. The system we constructed is much smaller and modular, making it the first ADE instrument that can work within the tight space constraints of most beamlines at a synchrotron. We anticipate that these methods will be vital for scientists at modern facilities such as the future II (NSLS-II) and the existing Linac Coherent Light Source (LCLS) at SLAC National Accelerator Laboratory.

Vaporization? the X-ray exposure challenge at modern light sources

At a proposed beamline at NSLS-II, an X-ray beam focused to one micrometer will destroy in about 50 milliseconds, requiring very fast sample delivery and data collection. The problem intensifies at the LCLS, where individual sub-micrometer-sized crystals are imaged with X-rays pulsed at 70 quadrillionths of a second before the are vaporized. The bottom line is that a lot of precious X-rays are lost without more efficient ways to deliver samples.

It's too early to test the ADE system at NSLS-II, but at the LCLS, our ADE-based injector will deliver microcrystals more than one hundred times per second, in synchrony with the facility's X-ray pulse structure. Our ultimate goal is to minimize the amount of sample needed by using drop-on-demand ADE methods, making sure that each droplet is hit by an X-ray pulse.

In addition to our collaborators at Brookhaven, we have expanded our team to continue experiments beyond the X25 at NSLS. The larger group now includes staff members at the LCLS, Stanford Synchrotron Radiation Light Source, Lawrence Berkeley National Laboratory, and Labcyte Inc. This expanded group will provide critical expertise when we deploy our acoustic sample delivery methods at the LCLS in June 2013.

Explore further: Fastest X-ray images of tiny biological crystals

Related Stories

Fastest X-ray images of tiny biological crystals

January 5, 2012

( -- An international research team headed by DESY scientists from the Center for Free-Electron Laser Science (CFEL) in Hamburg, Germany, has recorded the shortest X-ray exposure of a protein crystal ever achieved. ...

Organic crystals put laser focus on magnetism

July 27, 2012

( -- In the first successful experiment of its type at SLAC's Linac Coherent Light Source, scientists used terahertz frequencies of light to change the magnetic state of a sample and then measured those changes with ...

NSLS helps fine-tune vision of new NASA telescope array

August 6, 2012

( -- This summer, NASA is deploying NuSTAR, an array of focusing telescopes that will map the sky in the high-energy X-ray region of the electromagnetic spectrum. These maps will allow scientists to study black holes, ...

A new approach for solving protein structures

September 6, 2012

(—Using synchrotron x-ray beams to solve the molecular structures of proteins and other large biological molecules has yielded many advances in medicine, such as drug therapies for cancer. Improvements in the techniques ...

New tool puts LCLS X-ray crystallography on a diet

October 30, 2012

A tiny device invented at SLAC National Accelerator Laboratory will make it much easier for scientists to determine the structures of important, delicate proteins by greatly reducing the amount of protein needed for study.

Recommended for you

Exploring the physics of a chocolate fountain

November 24, 2015

A mathematics student has worked out the secrets of how chocolate behaves in a chocolate fountain, answering the age-old question of why the falling 'curtain' of chocolate surprisingly pulls inwards rather than going straight ...

SLAC theorist explains quantum gravity

November 19, 2015

Our world is ruled by four fundamental forces: the gravitational pull of massive objects, the electromagnetic interaction between electric charges, the strong nuclear interaction holding atomic nuclei together and the weak ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.