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Scottish researchers building 'super microscope'

New tool to investigate Alzheimer's and cancer

Researchers at the University of St Andrews have received a grant of £750,000 to develop a new type of microscope they hope will become a powerful tool for cell researchers investigating Alzheimer's, cancer and other diseases.

The microscope will be the first of its kind to let scientists perform several tasks from within a single instrument, including imaging, sorting and separating cells, said Kishan Dholakia, the St. Andrews professor leading the project. Such a tool would reduce the risk of cell contamination because samples would not have to be moved between different pieces of equipment, he said.

The microscope is also unusual in its use of advanced optical techniques to manipulate cells without actually touching them, further reducing contamination risk. By shining certain patterns of laser light on cells as they flow through a channel on a sample slide, the researchers have figured out how to sort cells into, for example, red and white blood cells, or cancerous and noncancerous cells. The laser acts as "a miniature tractor beam, if you like, or a sieve," Dholakia said.

"Before, imagine that you had to examine each cell one by one to separate them. Now you have a little flow, or river, of cells. It's like having footballs and tennis balls mixed together in a river. You shine a light pattern into the water and the footballs don't move, they are deflected or held, and the tennis balls flow straight through," he said.

A beam of laser light of a different colour is also used to breach the surface of a cell, causing its membrane to open up momentarily so that a foreign gene or medicine can be inserted. This ability to "punch holes" in cells will be another of the microscope's functions.

Light can move matter because photons in a beam of light carry momentum. This has been known for more than 30 years but is really coming to the fore only now, Dholakia said. When an atom emits or absorbs a photon its momentum changes in accordance with Newton's laws of motion. The upshot is that there are certain forces that, "for small objects, will be sufficient to allow optical manipulation of matter," he explained in a paper he cowrote in 2002. The scientists refer to such manipulation as "optical trapping".

Dholakia's team expects the microscope – or workstation, as they call it – to be ready for use in about two years. It will be built around an existing microscope, most likely Nikon's TE2000E confocal system, Dholakia said. Nikon is a sponsor of the project. Other components include compact laser systems not typically found in microscopes, including short pulse, violet diode and infra red lasers.

The first version of the microscope will be about the size of a 20in televison and require quite powerful lasers, but the goal is to develop a system that could be re-created and sold commercially. Subsequent versions may be smaller and could employ lasers no more powerful than those found in a CD player, Dholakia said.

The project draws on research by St Andrew's academics, including physicist professor Wilson Sibbett, cancer researcher professor Andrew Riches, and Dr Frank Gunn-Moore, a neurobiologist investigating how nerve cells are affected by neurodegenerative diseases like Alzheimer's. Dholakia is head of the Optical Trapping Group at the university's School of Physics and Astronomy and is pioneering a number of cell-based research techniques based on light.

The grant was awarded by the Engineering and Physical Sciences Research Council, a UK government funding agency.

St. Andrew's has two research projects lined up for the system, in the areas of Alzheimer's disease and cancer. But it welcomes other scientists doing cell research to come to the university and use its apparatus, Dholakia said. "We'd be delighted for other people to contact us with real problems at the cellular-scale level," he said.


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