Physics Of Imaging

The imaging techniques that are currently available — including X-ray crystallography, cryo-EM and super-resolution microscopy — all started as cutting-edge research in physics. In addition to these established imaging technologies our physics program is conducting cutting-edge research in emerging fields largely driven by the recent development of X-ray Free Electron Laser (XFEL) facilities.

Our physics program is involved with the Single Particle Imaging (SPI) initiative that is being driven by LCLS to realise the long held ambition of determining the structure of biomolecules in their native state without crystallisation.

Interaction physics:

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Image sourced from SLAC national accelerator laboratory

The earlier suggestions that free electron lasers could be used to image biomolecules emphasised the brightness of the pulses to increase the number of scattered photons. There are, however, many other processes that occur when a pulse interacts with matter. Photons are absorbed exciting inner shell electrons into the continuum. The internal structure of the molecules then rearranges emitting more electrons and photons the molecule then becomes highly charge recapturing some of the emitted electrons. Finally, the molecule explodes. Very little is known about the detailed descriptions of these processes in systems as complex as biomolecules.

Sample handling and delivery

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The experimental setup at the ID13 microfocus beamline. (a) (1) Microscope focused on the jet. (2) LCP injector with (3) nozzle close to the beamstop. (b) A view of the LCP nozzle as seen through the microscope. LCP was extruded towards the left as viewed in this projection, and the X-ray beam hits the stream at a distance of 40 µm from the end of the coned capillary. The capillary ID is 50 µm. A co-flowing gas stream (green arrows) keeps the LCP stream straight. (c) Schematic diagram of the setup. The water used to drive the injector is shown in blue, the LCP in red and the gas in green. (d) An SMX diffraction pattern from a bR microcrystal, with visible Bragg spots extending out to 2.2 Å resolution. [Nogly, P., James, D., Wang, D., White, T. A., Zatsepin, N., Shilova, A., Nelson, G., Liu, H., Johansson, L., Heymann, M., Jaeger, K., Metz, M., Wickstrand, C., Wu, W., Båth, P., Berntsen, P., Oberthuer, D., Panneels, V., Cherezov, V., Chapman, H., Schertler, G., Neutze, R., Spence, J., Moraes, I., Burghammer, M., Standfuss, J. and Weierstall, U. (2015). IUCrJ, 2, 168-176.   doi:10.1107/S2052252514026487]

One of the greatest challenges is coordinating the interception of the target sample by the XFEL pulse. In particular we wish to image biomolecules in a state as close to their natural environment as possible. While crystallography has been the backbone of structural biology for over 60 years the ideal scenario would deliver hydrated samples in their natural confirmations to the pulses for imaging in a non-crystalline state.

Theme Leaders:

Sample handling and delivery: Keith Nugent and Brian Abbey

Interaction physics: Harry Quiney