A 'Molecular Microscope'

Molecular microscope An Alzheimer’s disease plaque in brain tissue

Dr Neville Freeman, Dr Gerry Ronan, Dr Simon Carrington, Dr Louise Peel and Ms Jo Maltby.
Farfield Sensors Ltd.

Professor David Allsop.
Lancaster University.

Studying changes in the structure of biologically important molecules in real time can give revealing insights into mechanisms involved in diseases such as Alzheimer's, breast cancer and heart disease amongst others. A new 'molecular microscope' is able to study molecules in the highest possible detail, recording changes smaller than 0.1 angstroms (onehundredth of a nanometre) - considerably smaller than the size of the molecule's constituent atoms.

Proteins are very large complex molecules that can fold into a variety of different shapes or conformations. This 3D shape is extremely important and can radically affect the protein's properties. Misfolded proteins are the source of prion-based diseases - the suspected infective agent for diseases such as BSE in cows and Creutzfeldt-Jakob disease in humans - and the 'sticky balls' of proteins that are prevalent in Alzheimer's and similar diseases.

How these 'rogue' proteins behave on a molecular level is key to understanding the disease mechanisms and possibly developing novel and effective therapeutic methods. The sensitivity of the Farfield 'molecular microscope' allows researchers to detect changes in proteins ranging from large-scale alterations in their shape to subtle responses to the binding of a very small molecule or a metal ion.

This breakthrough technique uses the principle of optical interference, as illustrated by Thomas Young's classic double slit experiment, where two light sources are made to interact (or interfere) with each other to produce a 'fringe' pattern to demonstrate the wave-like nature of light. In the Farfield Sensor system the two slits are replaced by two waveguides and the light source is a laser. A waveguide is an optical structure which guides light. The two waveguides effectively split the laser light source, which recombines in the same way as in the double slit experiment, to form an interference fringe when the light reemerges. In the instrument one of the waveguides is the reference waveguide and is completely enclosed whilst the second 'sensing' waveguide has an open side o

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