A novel laser-based process developed at the CLF for selecting and examining protein microcrystals, which can be essential for understanding biological functions, is expected to save precious research days and resources and lead to faster breakthroughs in healthcare.
A 10 micron crystal placed, using the CLF laser tweezers, onto a 50 micron square aperture backed with microfibres ready for freezing and X-ray diffraction studies.
Protein microcrystals enable researchers to analyse the structure of molecules and how they behave, for example in disease, but can take a long time to prepare and analyse. The laser ‘tweezers’ process developed in the CLF helps to streamline crystal selection and the first results using this technique have now been published in Acta Crystallographica D (PDF - link opens in a new window).
The technique allows researchers to select and place microscopic protein crystals on customised sample holders for crystallographic analysis on one of the structural biology beamlines at Diamond Light Source, the UK’s national synchrotron science facility. Studying protein crystals through X-ray crystallography enables researchers to understand the structure and function of a molecule.
“This is a great example of how scientists from different facilities at the Rutherford Appleton Laboratory collaborate to address challenging problems. It’s clearly a benefit to have them all on one site here at the Harwell campus”.
Andy Ward
Laser tweezers lead, CLF
The new technique is the result of a cross-campus collaboration between Diamond Light Source and STFC’s Central Laser Facility (CLF) and Technology departments. In this area of research, crystals of proteins rather than single molecules must be used, but for many proteins, the crystals formed can be so small (less than 10 microns) that they are very difficult to handle and mount onto standard sample holders for analysis. This can lead to some potentially vital crystals being discarded.
STFC’s Technology Department helped to overcome this problem by weaving a microfiber web to create a ‘net’ for the crystals to be mounted on. The laser tweezers are then used to grab the minute crystals and move them onto the novel sample holders.
"Previously we have, in essence, wasted two to three days on the beamline just looking for our best crystals. Now, using the laser tweezers system, we can visually identify and select specific crystals and transfer them to well defined positions on a sample mount rather than relying on a purely random process. Microcrystal work is essential for research in many areas and this collaborative, cross-campus project is addressing problems with crystal supply to allow more efficient research."
Armin Wagner
Project lead, Diamond Light Source
By using lasers to precisely place these crystals in position, scientists are able to know where to focus the X-ray beam to look at the protein microcrystals. Previously, researchers had had to ‘fish’ through the sample to load crystals. During this process it was not possible to select and mount individual crystals; it was more of a random approach and needed a significant amount of time to optimise the conditions during the mounting process. The use of laser tweezers to streamline the process means precious research days and resources can be saved.
