What is the best way to image biological macromolecules at the structural/atomic level? And another question—what will be the best way to image those molecules? Those are key questions for understanding biological functions at a cellular level; and yet the image techniques that we can use—x-ray crystallography and transmission electron microscopy—damage the molecules as they gather the data for imaging, making it difficult to image the molecules in (or at least close to) their natural state.

In a recent article for Advanced Structural and Chemical Imaging, Ray Egerton at the University of Alberta discusses the challenges facing biochemical macromolecule imaging.

X-ray free-electron laser imaging

One approach developed to solve this problem involves gathering enough data to image the molecule before the imaging beam destroys it. Researchers found that using short x-ray laser pulses (between 50 and 100 femtoseconds) allowed them to collect enough diffraction data to construct molecular images before the molecules get destroyed. Which sounds great, except for one problem: There are today only 6 free electron laser facilities in the world.

Electron pulse imaging

On the other hand, electron beam sources are compact and inexpensive, compared with free electron lasers. Technology for rapid (500 femtosecond) and high energy (Mega electron Volt or MeV) pulses have been developed, and the magnetic lenses in transmission electron microscopes (TEM) can resolve the beam to less than .2 nanometers.

Challenges

So why wouldn’t electron pulse imaging be the easy answer? Because, put simply electrons obviously have charge, and having charge, they have Coulomb repulsion between them, and the repulsions and other electrical effects make lens focusing problematic. That said, development of future electron sources could help mitigate these challenges.

You can read the entire article in Advanced Structural and Chemical Imaging here.