December 2008 - Issue #4
Medical diagnosis at a pinch
Story by Penny Fannin
View articles in related topics: Health & Medical, Optical Physics
Suspended in mid-air, a solitary red blood cell is rotated, stretched and folded in half. Then the light goes out. In darkness, the cell resumes its disc-like shape. But with the light back on, the cell is again subjected to forces that change its shape.
The forces that are able to have such a profound effect on these tiny human cells are produced by laser beams. And the manipulation is possible using delicate laser ‘tweezers’.
Scientists at Swinburne University of Technology’s Centre for Micro-Photonics are exploring the science behind these tweezers to see if they can manipulate the cells with less light but more dexterity. The technology has tremendous potential for medical diagnosis.
The centre’s director Professor Min Gu and Associate Professor Xiaosong Gan are leading a team that recently became the first in the world to demonstrate ‘near field’ laser tweezers. Yet, to understand the significance of this achievement it is important to know how laser tweezers work.
“There is a worldwide competition to see who will be the first person to achieve this nano-optical tweezer ... We are pioneers in this field.”
Professor Min Gu
“Light is composed of a lot of photons,” Professor Gu says. “When a photon hits a target there’s a momentum change, a recoiling force. If the object is very big then this recoiling force won’t have much effect.” But if the object is tiny, say one micrometre, the force is large enough to move the object.
This phenomenon can be particularly well observed when an intense light such as a laser shines through a transparent sphere. When this occurs the light is refracted to one side, exerting a very slight force, which tends to push the sphere in the opposite direction.
Professor Gu says red blood cells, which are fairly transparent, can be manipulated by laser beams almost as if they were tiny glass balls.
A transparent sphere (or red blood cell) illuminated by a narrow laser seeks to remain centered in the laser beam even as the beam moves. The effect can be compared to suspending a table tennis ball in a rising jet of air; because of the Bernoulli effect, the ball remains centered in the jet, even if the jet moves or changes direction.
When a second laser beam is introduced the sphere hovers between the two beams. The beams then act like tweezers and the sphere (or red blood cell) can be manipulated by steering the beams.
Laser tweezers, also called optical tweezers or optical traps, are of particular interest to medical scientists as they can reveal a great deal about cell mechanics without permanently altering the cell, Professor Gu says.
“Red blood cells are the standard model for understanding cell mechanics. If the shape of a red blood cell changes it may be an indication of disease,” he says.
Laser tweezers are frequently used to study interactions between cells and how these interactions might influence disease development. “The benefit of the tweezers is they have a temporary effect. As soon as the laser beam is switched off the cell returns to normal. We can squeeze, bend and rotate the blood cell, all without destroying it.”
Professor Sarah Russell, leader of the immune signalling laboratory at the Peter MacCallum Cancer Centre in Melbourne and a collaborator of Professor Gu’s, says biologists are becoming more aware that factors such as a cell’s shape and orientation in relation to its environment are important to how it develops.
Finding tools that allow these factors to be manipulated so their effects can be determined is therefore imperative. “That’s where laser tweezers will come into play,” she says. “They allow us to manipulate cells in that way … and what’s important there is that the cell is not damaged.”
Professor Russell says laser tweezers will be particularly useful in studying interactions between cells as, at the moment, it is difficult to identify exactly where the interface is between two cells. “Using laser tweezers we could flip the cells so we could see the interface and see things that have never been seen before.”
Laser tweezers were first applied to the biological sciences in the late 1980s when they were used to trap a tobacco mosaic virus and Escherichia coli bacterium. In the 1990s they were used to better understand the miniature motor/propeller assemblies that bacteria and other microbes use to get around. Optical tweezers have also been used to sort cells, move organelles (tiny, specialised organs such as mitochondria) from one place to another within a single living cell, and to move isolated chromosomes on a microscope slide.
Although laser tweezers have been used in biological applications since the late 1980s, they still carry the risk of damaging the cell being analysed. The tweezers also require the use of two laser beams for cell manipulation, which can be difficult to synchronise, Associate Professor Gan says.
This is where Professor Gu and Associate Professor Gan’s demonstration of ‘near field’ laser tweezers is significant.
Near field tweezers use an evanescent wave rather than a propagating wave, which means only one laser beam, not two, is needed to trap and manipulate samples. “With one beam we can achieve all the same mechanical actions – rotating, folding and stretching cells – as with two beams,” Associate Professor Gan says.
“Using the evanescent beam you need significantly less light to achieve the same effect. Too much light can cause functional change and damage the cell, so using less light is better as there’s less phototoxicity.”
Although the scientists have demonstrated the ‘near field’ tweezers on red blood cells their actions have opened a whole new vista for medical science. The tweezers could also be used to manipulate biological samples on the nano-scale – single molecules such as proteins.
“With the near field tweezers we can do a big object like a cell, but the evanescent beam is ideal for small objects like DNA – objects that are one-hundredth the size of a red blood cell,” Associate Professor Gan says.
Professor Gu says money is the only factor stopping the team from laser trapping a single molecule. “There is a worldwide competition to see who will be the first person to achieve this nano-optical tweezer,” he says. “We are pioneers in this field. We have developed the technique, now we have to demonstrate it.”
