Laser injection

Scientists at Scotland’s St Andrew’s University have developed technology to use non-diffusing laser light as a syringe to inject chemicals or DNA into cells for drug discovery and research.

The technique, known as photoporation, uses light to perforate the cell membrane, allowing foreign agents in the local environment to enter the cell, after which the perforation self-heals.

Photoporation is largely used to target single or small numbers of cells, allowing biologists to prototype and test rarities, such as stem cells. As no other chemicals or electrical fields need to be introduced it is completely sterile, offers single-cell selectivity and, as light is easily reconfigurable, its shape and position can be changed as required.

The project came about when Dr Frank Gunn-Moore from St Andrew’s school of biology approached Prof Kishan Dholakia in the school of physics and astronomy. He suggested that new ways to deliver drugs for neuroscience studies, particularly for Alzheimer’s, were needed. Dholakia had read of research where other groups had tried similar laser techniques but with limited success.

‘The syringe idea is a step beyond this because though light is easy to manufacture through cheap lasers, one of the problems has been to target the precise position of the cell membrane,’ said Dholakia. Though laser light appears to be straight, it actually spreads past the focal point, like sunlight shone through a magnifying glass.

The syringe incorporates novel light-beam shapes that mean the light does not spread. ‘The light travels in a thin, pencil-like beam, which means that when you target the cell it doesn’t matter if you’re not quite sure where the cell membrane is — you can just click and go,’ said Dholakia.

This innovation means that instead of using advanced focusing techniques and specialist laser training, a biologist or clinician could just mouse click on a cell displayed on a screen.

The researchers have developed two versions of the light syringe. One is for use in free space, such as in a standard microscope. ‘We use a special light beam known as a Bessel light beam, which consists of a lot of rings,’ said Dholakia. ‘At the centre it is non-diffracting so doesn’t spread — it’s like a little micro light sabre.’

This is important under a microscope where scientists have to focus the light beam down to millionths of a metre. They would not have to worry where the cell membrane is and whether it is at the focal point or a little on either side.

The second version uses an optical fibre technique that the researchers hope might lead to endoscopic applications and treatment of multiple cells at the same time.

‘Here we etch the end of the fibre into a cone which, though it doesn’t give a Bessel beam, does have a good elongated focus,’ said Dholakia.

Both techniques are well advanced, but more research is needed to optimise them. ‘We’ve just started tissue studies and we’re hoping to attract more academic interest,’ said Dholakia.

‘Now the technology is proven, we’re going to try different cell types, push towards real point-and-click or touch-screen automation and maybe endoscopic and commercial exploitation.’

The team, working with the Bute Medical School at St Andrews, is exploring links with Dundee University for certain cell types, and is seeking to take the technology forward.

So far the main challenges for the researchers have been optimising the laser parameters and the mechanism by which the hole in the cell membrane is opened and rapidly closes.

‘We need to set up a database of different cell types to understand the physical mechanism,’ said Dholakia. ‘If you come with cell X, we might never have tried that, so it’s a little uncertain how well or not it will work.

‘I can say every cell we’ve tried so far has worked, but the laser parameters are different. Cancer cells, for example, have different membrane proteins.’

The team is now looking at ways of making the device more compact and investigating techniques to hit small areas of tissue consisting of up to 1,000 cells, perhaps using optical fibre bundles just millimetres in diameter.

The project runs until 2010, by which time Dholakia would like to have a system on the market, or have partners using a prototype.

‘We want a system that can, at the click of a button, hit anything up to 50 types of cells, all fully characterised. Then we’d like to do some great experiments in cell biology and neuroscience,’ he said.

Berenice Baker