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Targeting the LCLS Bullseye

The pending eve of first light at the world's brightest hard X-ray source tends to make one dream. I spend a lot of time dreaming of the ultimate game of darts—biomolecular darts.

One of the most exciting potential applications of the Linac Coherent Light Source is the ability to collect single pulse images of biological and inorganic materials that do not contain periodic structure,1 a requirement of the preceding technique, X-ray crystallography. At minimum, we will be able to take at- or near-atomic resolution two-dimensional images of complex materials, opening up a whole new world of nanoscale imaging with previously-unattainable time resolution. These experiments will have wide reaching implications from nanoscale manufacturing to energy production and human health.

This type of "FLASH" diffraction imaging was first reported in December 2006, using 25 femtosecond pulses from the soft X-ray free-electron laser in Hamburg, or FLASH, to image an object carved into a thin membrane.2 This experiment provided the foundations for an array of new applications of coherent X-ray diffractive imaging, ranging from femtosecond time-delay3 and massively parallel holography4 to monitoring nanoscale dynamics5 and single-particle imaging of encapsulated biomolecular complexes,6 cells, ellipsoidal nanoparticles and flame- or powder-dispersed aerosols.

One of the key experimental challenges in extending these techniques to the LCLS is raised by the very narrow focus of the LCLS beam (about 0.1 micrometer diameter), required to attain high-resolution images of single biomolecules and nanoparticles. How do we get the samples into a target area about one thousandth the diameter of a human hair? Conventional single particle, single laser pulse experiments, such as single particle aerosol mass spectrometry, rely on a laser beam diameter of about 400 micrometers to create ions indicative of a particle’s chemical composition. This is more than one hundred million times more interaction area than will be available at LCLS in the long run. In other words, if the 400 micrometer laser beam were the size of a dartboard, aiming for the LCLS target would be like trying to hit a bullseye the size of a pin head.

And so, at the LCLS we get to play the ultimate game of biomolecular darts.

Of course, practice makes perfect so we practice on larger targets. At FLASH we have demonstrated that we can already hit a very small bullseye, a beam diameter of about 30 micrometers. When the LCLS first turns on it will have a beam diameter three to thirty times smaller, at about 1–10 micrometers.

Now, to make things more interesting, imagine that just as a dart was about to hit the bullseye, the entire dartboard disappears. At the LCLS the X-rays arrive 120 times a second, for only about 100 femtoseconds at a time. Even light, traveling at the ultimate speed limit, can travel only about 0.003 centimeters in this short time. This makes the game a bit more challenging. Fortunately, LCLS scientists are not limited to just three darts. We can send in thousands to millions of biomolecular darts per second, hoping we hit the LCLS bullseye. We are also working on timing our biomolecular dart tosses to match the appearance of the "board" and we can use techniques to slow down or speed up our darts as they approach the target. Clearly the great leap in capabilities offered by the ultrashort and ultrafast LCLS pulses will require great leaps in the technology to throw the biomolecular darts.

Fortunately, great challenges tend to fuel the innovation needed to overcome them. We are gathering more LCLS dart players and learning from each other’s experience. We are also building on the experience of aerosol scientists, analytical chemists and biophysicists who have been studying the delivery of biomolecules and microorganisms into vacuum toward lasers and mass spectrometers for decades.

On the horizon we have exciting new developments from several teams engaged in research to improve the efficiency of the delivery of proteins, nanocrystals, cells and viruses into LCLS pulses. For instance, strategies to create a stream of single-file droplets7 or biomolecules trapped in electric fields are in progress. Here at SLAC, PULSE has commenced efforts to develop new technology that will provide precisely timed delivery of samples.

To achieve the full potential provided by the LCLS requires informing and mobilizing the best talent in all scientific fields. If you are interested in applying your skills to the biomolecular darts team, e-mail Mike.

—Mike Bogan
SLAC Today, September 11, 2008


  1. Structural Studies on Single Particles and Biomolecules, in LCLS the First Experiments
  2. Chapman, H. N.; Barty, A.; Bogan, M. J.; Boutet, S.; et al. Nature Physics 2006, 2, 839-843.
  3. Chapman, H. N.; Hau-Riege, S. P.; Bogan, M. J.; Bajt, S.; et al. Nature 2007, 448, 676-679.
  4. Marchesini, S.; Boutet, S.; Sakdinawat, A. E.; Bogan, M. J.; et al. Nature Photonics 2008, 2, 560-563.
  5. Barty, A.; Boutet, S.; Bogan, M. J.; Hau-Riege, S.; et al. Nature Photonics 2008, 2, 415-419.
  6. Bogan, M. J.; Benner, W. H.; Boutet, S.; Rohner, U.; et al. Nano Letters 2008, 8, 310-316.
  7. Weierstall, U.; Doak, R. B.; Spence, J. C. H.; Starodub, D.; et al. Experiments in Fluids 2007, 44, 675-689.