Scientists have managed to increase the resolution of a standard optical microscope by around 20 times, opening up the possibility of directly observing living cellular processes.
By seeing exactly how viruses and other pathogens hijack cells, it may be possible to exploit weak links in their lifecycles and develop targeted treatments.
The method uses microspheres in the sample preparation to resolve to around 50 nanometres — surpassing what was assumed to be a theoretical limit of 200nm, which corresponds to the smallest wavelength of visible light.
The micro-particles form a layer acting like a second lens — exploiting the unusual behaviour of light at boundaries and a phenomenon called internally reflecting evanescent waves.
While not quite achieving the resolving power of electron microscopy, the technique has some distinct advantages in practice, as Prof Lin of Manchester University’s School of Mechanical, Aerospace and Civil Engineering explained.
‘With electron microscopy the cells have to be killed before they can be observed and you can only see the surface. Preparation is very difficult, you have to dehydrate and treat them and it requires a vacuum chamber, which is very expensive. A standard electron microscope costs around half a million pounds whereas a standard optical microscope is around £20,000,’ he said.
With the new method the microparticles are in a solution that can simply be incubated with the living sample then viewed with existing optical microscopes. The microparticles self-assemble on the surface of cells as a single layer, allowing amplified light to pass through into the internal structure of the cell.
Prof Lin said the technique allows the study of various biological processes and mechanisms at a level never before achieved.
‘At the moment it’s all guess work — inferences made from indirect observations. Now we can see [cellular processes] directly and this opens up new territory,’ said Lin.
The team believes it can use the microscope to detect far smaller images in the future. The new method has no theoretical limit in the size of feature that can be seen.
As well as biomedical applications, the scientists will be able to examine anodised aluminium oxide nano-structures, and nano-patterns on Blue-Ray disks, which could open up enhanced storage solutions.