The recent acquisition of Jeol's latest 300 kV field emission Transmission Electron Microscope (TEM), the JEM-3200FS, by Indiana University in the US for studying viruses is symptomatic of the ever increasing need for structural information about viruses to aid in the drug discovery process.
"There is a lot of interest in refining the picture of viruses and marrying that structural information from electron microscopy with the genomics field to see how mutations affect their shape and infectivity," said Dr Michael Kersker, Jeol USA's vice president and TEM product manager.
According to Kersker the field is growing enormously as it has the potential to solve very difficult questions.
He said that sales of these instruments were increasing by about 15 to 20 per cent a year, with the limiting factor being the number of people that are trained to carry out the research.
According to Dr Jaap Brink, TEM biological applications manager at Jeol, the use of electron microscopes to study viruses took off in the late 1980s with researchers looking at the structure of viruses in their native state.
The implementation of cryoTEM over the past 10 years has allowed researchers to push the boundaries to very high resolutions.
The images gained using the technique yield a projection of the entire 3D object which is viewed as a 2D projection.
Brink explained that the key to using the technique to study the 3D shape of a particle is in retrieving the lost 3D information.
"Because particles orient themselves in a random orientation, by imaging multiple particles you can reconstitute the data in 3D," he said.
"This then turns into a big computational puzzle to put the information back together."
First efforts used this technique to reconstruct a virus using between 20 and 30 negatively stained particles.
"People now do this routinely to reconstruct particles down to 0.5nm using between 50,000 and 100,000 particles which could take up to a year to collect," continued Brink.
He explained that the problem then becomes how you can automate the process as operators can not sit behind an instrument 24 hours a day, as well as the samples needing to be kept intact during that time frame.
"You can also take a single particle and tilt it to get an idea of the 3D image, and with the new piezo-driven stages you can get very precise information as the motors can be controlled to the sub-angstrom level," said Kersker.
Brink explained to LabTechnologist.com that electron microscopy has allowed researchers to study the various different epitopes of viruses and see which are the most virulent.
"If you bind an antivirus to viruses you can study how their infectivity changes and use this in drug discovery processes," said Brink.
He explained that the technique was used to study the rotavirus, a leading cause of child death in the third world.
It was found that antibodies are located on the distal tips that protrude from the virus - giving researchers a better understanding of how to create new drugs to fight the virus.
"These studies have become a blueprint to answer how a virus' structure affects its infectivity, how it gets into the cell and gets poised to enter the membrane - this is very, very important in understanding how drugs work" said Kersker.