Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Structure from fleeting illumination of faint spinning objects in flight


Moves are afoot to illuminate particles in flight with powerful X-ray bursts, to determine the structure of single molecules, viruses and nanoparticles. This would circumvent important limitations of current techniques, including the need to condense molecules into pure crystals. Proposals to reconstruct the molecular structure from diffraction ‘snapshots’ of unknown orientation, however, require 1,000 times more signal than available from next-generation sources. Using a new approach, we demonstrate the recovery of the structure of a weakly scattering macromolecule at the anticipated next-generation X-ray source intensities. Our work closes a critical gap in determining the structure of single molecules and nanoparticles by X-ray methods, and opens the way to reconstructing the structure of spinning, or randomly oriented objects at extremely low signal levels.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Diffracted intensity.
Figure 2: Latent and manifest spaces.
Figure 3: Orientation recovery.
Figure 4: Structure recovery.

Similar content being viewed by others


  1. Solem, J. C. & Baldwin, G. C. Microholography of living organisms. Science 218, 229–235 (1982).

    Article  ADS  Google Scholar 

  2. Neutze, R., Wouts, R., van der Spoel, D., Weckert, E. & Hajdu, J. Potential for biomolecular imaging with femtosecond X-ray pulses. Nature 406, 752–757 (2000).

    Article  ADS  Google Scholar 

  3. Miao, J., Hodgson, K. O. & Sayre, D. Extending the methodology of X-ray crystallography to allow imaging of micrometer-sized non-crystalline specimens. Proc. Natl Acad. Sci. 98, 6641–6645 (2001).

    Article  ADS  Google Scholar 

  4. Huldt, G., Szőke, A. & Hajdu, J. Diffraction imaging of single particles and biomolecules. J. Struct. Biol. 144, 219–227 (2003).

    Article  Google Scholar 

  5. Gaffney, K. J. & Chapman, H. N. Imaging atomic structure and dynamics with ultrafast X-ray scattering. Science 316, 1444–1448 (2007).

    Article  ADS  Google Scholar 

  6. Chapman, H. N. et al. Femtosecond diffractive imaging with a soft-X-ray free-electron laser. Nature Phys. 2, 839–843 (2006).

    Article  ADS  Google Scholar 

  7. Chapman, H. N. et al. Femtosecond time-delay X-ray holography. Nature 448, 676–679 (2007).

    Article  ADS  Google Scholar 

  8. Gerchberg, R. W. & Saxton, W. O. A practical algorithm for the determination of the phase from image and diffraction plane pictures. Optik 35, 237–246 (1972).

    Google Scholar 

  9. Fienup, J. R. Reconstruction of an object from the modulus of its Fourier transform. Opt. Lett. 3, 27–29 (1978).

    Article  ADS  Google Scholar 

  10. Sayre, D. in Imaging Processes Coherence in Physics Vol. 112 (eds Schlenker, M. et al.) 229–235 (Lecture Notes in Physics, Springer, 1980).

    Book  Google Scholar 

  11. Miao, J., Charalambous, P., Kirz, J. & Sayre, D. Extending the methodology of X-ray crystallography to allow imaging of micrometer-sized non-crystalline specimens. Nature 400, 342–344 (1999).

    Article  ADS  Google Scholar 

  12. Shneerson, V. L., Ourmazd, A. & Saldin, D. K. Crystallography without crystals. I. The common-line method for assembling a three-dimensional diffraction volume from single-particle scattering. Acta Crystallogr. A 64, 303–315 (2008).

    Article  ADS  Google Scholar 

  13. Bortel, G. & Faigel, G. Classification of continuous diffraction patterns: A numerical study. J. Struct. Biol. 158, 10–18 (2007).

    Article  Google Scholar 

  14. Honda, S., Yamasaki, K., Sawada, Y. & Morii, H. 10 residue folded peptide designed by segment statistics. Structure 12, 1507–1518 (2004).

    Article  Google Scholar 

  15. Tenenbaum, J. B., de Silva, V. & Langford, J. C. A global geometric framework for nonlinear dimensionality reduction. Science 290, 2319–2323 (2000).

    Article  ADS  Google Scholar 

  16. Donoho, D. L. & Grimes, C. Hessian eigenmaps: Locally linear embedding techniques for high-dimensional data. Proc. Natl Acad. Sci. 100, 5591–5596 (2003).

    Article  ADS  MathSciNet  Google Scholar 

  17. Bishop, C. M. Neural Networks for Pattern Recognition (Oxford Univ. Press, 1995).

    MATH  Google Scholar 

  18. Bishop, C. M. in Learning in Graphical Models (ed. Jordan, M. I.) 371–403 (MIT Press, 1999).

    Google Scholar 

  19. Svensen, J. F. M. The Generative Topographic Mapping. Thesis, Aston Univ. (1998).

  20. Bishop, C. M. & Tipping, M. E. A hierarchical latent variable model for data visualization. IEEE Trans. Pattern Recognition Machine Intelligence 20, 281–293 (1998).

    Article  Google Scholar 

  21. Howard, R. E., Jackel, L. D. & Graf, H. P. Electronic neural networks. J. Am. Telephone Telegraph Co. 67, 58–64 (1988).

    Google Scholar 

  22. Kuipers, J. B. Quaternions and Rotation Sequences (Princeton Univ. Press, 1999).

    MATH  Google Scholar 

  23. Oszlányi, G. & Sütő, A. Ab initio structure solution by charge flipping. Acta Crystallogr. A 60, 134–141 (2004).

    Article  ADS  Google Scholar 

  24. Oszlányi, G. & Sütő, A. Ab initio structure solution by charge flipping. II. Use of weak reflections. Acta Crystallogr. A 61, 147–152 (2005).

    Article  ADS  Google Scholar 

  25. Neutze, R., Huldt, G., Hajdu, J. & van der Spoel, D. Potential impact of an X-ray free electron laser on structural biology. Rad. Phys. Chem 71, 905–916 (2004).

    Article  ADS  Google Scholar 

  26. Jurek, Z., Faigel, G. & Tegze, M. Dynamics in a cluster under the influence of intense femtosecond hard X-ray pulses. Eur. Phys. J. D 29, 217–229 (2004).

    Article  ADS  Google Scholar 

Download references


We acknowledge valuable discussions with M. Schmidt and P. Schwander. We are grateful to V. Elser for stimulating us to think about general methods for determining orientations, and to D. Starodub for the suggestion to consider the application of our approach to multicrystalline materials.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Abbas Ourmazd.

Supplementary information

Supplementary Information

Supplementary Informations (PDF 487 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fung, R., Shneerson, V., Saldin, D. et al. Structure from fleeting illumination of faint spinning objects in flight. Nature Phys 5, 64–67 (2009).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing