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There are many instances when the structure of a weakly-scattering spinningobject in flight must be determined to high resolution. Examples range fromcomets to nanoparticles and single molecules. The latter two instances are thesubject of intense current interest. Substantial progress has recently beenmade in illuminating spinning single particles in flight with powerful X-raybursts to determine their structure with the ultimate goal of determining thestructure of single molecules. However, proposals to reconstruct the molecularstructure from diffraction "snapshots" of unknown orientation require ~1000xmore signal than available from next-generation sources. Using a new approach,we demonstrate the recovery of the structure of a weakly scatteringmacromolecule at the anticipated next-generation X-ray source intensities. Ourwork closes a critical gap in determining the structure of single molecules andnanoparticles by X-ray methods, and opens the way to reconstructing thestructure of spinning, or randomly-oriented objects at extremely low signallevels. Other potential applications include low-dose electron microscopy,ultra-low-signal tomography of non-stationary objects without orientationalinformation, and the study of heavenly bodies.

Structure from Fleeting Illumination of Faint Spinning Objects in Flight with Application to Single Molecules