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Details of Grant 

EPSRC Reference: EP/C52389X/1
Title: 2D Attogram Surface Plasmon Imaging
Principal Investigator: Shaw, Professor AM
Other Investigators:
Somekh, Professor M Barnes, Professor WL Sambles, Professor JR
O'Shea, Professor P
Researcher Co-Investigators:
Project Partners:
Department: Chemistry
Organisation: University of Exeter
Scheme: Standard Research (Pre-FEC)
Starts: 01 September 2005 Ends: 28 February 2010 Value (£): 2,950,714
EPSRC Research Topic Classifications:
Instrumentation Eng. & Dev.
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:  
Summary on Grant Application Form
There are two obvious ways to do science: either have an idea and work on it in the hope that it's a good idea, or have many ideas and try to sort out those which are most likely to be good ideas, before spending a lot of time on one idea which may not be so good after all. The process of testing, or screening, ideas is difficult: the more you have, the more tests you need to apply in order to separate one good idea from many bad ones. Many of the medicinal drugs used today developed from an idea, the earliest ideas were sometimes lucky, as in the case of penicillin, but almost all have involved a lot of research and hundreds of millions of pounds worth of effort. Scientists are now able to produced millions of potentially useful drug molecules that are either randomly generated or are variations on a theme. Unfortunately this is of no value unless you can test them reliably; it is impossible to know which ones may have a future in therapeutic medicine, nor or later. We are proposing to build a new instrument based on techniques which will help us select just one or two specific molecules from a whole cocktail by offering them tethered 'target' molecules to bind to, and in doing so to produce a detectable signal when they are in contact with one another. We can already do this with very small particles of gold containing perhaps only a few thousand atoms. Gold doesn't behave as expected on this so-called nanometer scale and it has some useful properties. It is a good conductor of heat and electricity because gold atoms have many electrons that are free to move around inside the metal. If you shine a laser at the particles the free electrons form a wave, or 'plasmon' that washes along the surface of the particle. Putting a protein molecule on the surface changes the way the plasmon behaves so you can see when molecules have bound to the surface. Recently we've shown that the particles are very sensitive to binding, if they touch each other forming hot spots. We are going to set about building a fixed array of hot spots on which we will put a known drug target, called a receptor. When the receptor in the hotspot binds with a new potential drug we will see a signal indicating a change in the plasmon. To know that the discovery is real, we will look at how the flash changes in time. We have three ways of looking at this and all require a very fast and sensitive camera to capture the event. The first part of our work then is to develop the best camera we can; this will push us to the limit of what we know. We will also develop ways of making very regular lines of hot spots; we want to put down 1 million hotspots in a very small area. This is also hard - image 1 million pots of chemicals that all have to be put in exactly the right place. The next job is to put down the right biological molecule on top of the hotspots and then watch what happens during the binding event. The speed of recognition between the target and hotspot is very important, if we succeed we will be able to screen most drugs in a pharmaceutical company's collection in just a few days, and say how well the drug sticks to the target - all vital information. Our new technique will help those trying to understand better the connection between disease, individual genetic make-up and effective treatment. Other possible applications include development of techniques to monitor the health of water supplies, taking samples of water before and after treatment to remove particular toxins or poisons to check how well the clean up has worked. Being able to screen lots of things very rapidly will change the way we go about improving our knowledge of the biology that controls us and the natural world we live in.
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Organisation Website: http://www.ex.ac.uk