Medical Applications of the Electron Microscope

Presentation given to Norwich Engineering Society 23rd March 2009 by Dr. Lucy Collinson, Head of Electron Microscopy, Cancer Research UK (London)

Lucy began with a brief description of the work of Cancer Research UK and the location of their establishments, also explaining that the organisation is a charity entirely funded by donations and does not receive any government funding. This was followed by a description of basic cell biology and the nature and effect of cancerous cells. The limitation of the resolution of optical microscopes owing to the wavelength of light and the need for higher resolution to study the way cells function was explained. Resolutions of better than one tenth of a nanometre can be achieved with electron microscopes, whereas conventional optical microscopes can only achieve a resolution of around 200 nanometres.

Using photographs of the Cancer Research UK electron microscopes and functional diagrams, Lucy explained the principles of using magnetically focussed short wavelength electron beams in a vacuum environment to produce high resolution images of specimens. She described both the “transmission” type (TEM) where the image is formed by the electron beam passing through the specimen and onto a detector and the “scanning” type (SEM) where the image is formed by the electron beam being reflected from the surface of the specimen and onto the detector. Photographic film was used to record the images, but modern units employ specialist digital cameras for this purpose. Examples of images were shown to illustrate the additional detail revealed by the higher resolution of the electron microscope, including impressive animated zooming images of neurons. A sample skin cancer image is shown above.

Lucy emphasised that the key to successful electron microscopy is the preparation of specimens. The fact that the cells are placed in a vacuum in the microscope means that they cannot be imaged in their natural state since they would explode owing to internal cell pressure and evaporation of liquids. In the case of the transmission microscope the specimens are stabilised using chemical ‘fixatives’ and stained with heavy metals like osmium and uranium to give contrast in the microscope. The cells also have to be cut into extremely thin sections to allow the electron beam to pass through. A process was described of embedding the specimen in a type of plastic to make them suitable for a vacuum environment and to stabilise the cell structure to enable cutting into thin sections at room temperature.

Since the extremely thin sections required cannot be sliced by hand, a piece of precision equipment known as an “ultramicrotome” is used. This employs a diamond knife to slice the specimens into sections of the set thickness. However, for training purposes, much cheaper, shorter life, glass knives are used to avoid expensive accidents! To prevent damage to the sections they are floated off the knife onto water and lifted off to be placed onto the microscope support grid, frequently this is done using another expensive scientific tool, namely one of the microscopist’s eyelashes!

A more recent development is the Focused Ion Beam/ Scanning Electron Microscope. This is an SEM with an additional ion beam incorporated which is inherently destructive, and can be used to remove layers from the specimen whilst in the microscope. In this way a stack of images can be produced to allow a “three dimensional” image of the structure to be generated. Cancer Research UK do not yet have one of these units, and have been developing the technique for biological samples in collaboration with Dr Andy Bushby of the Nanovision Centre at Queen Mary University London, FEI Company and Zeiss. More on the work of Cancer Research UK in general can be seen on their website: Cancer Research UK and details of the Electron Microscope unit in particular, including more sample images on: More Images