BY USING sound to manipulate biological samples on a “lab-on-a-chip”, the dream of rapid – even on-the-spot – chemical analysis and diagnosis of disease has moved closer to reality.
The trick is to induce powerful acoustic waves in a droplet of your target sample on a chip by using something called surface acoustic waves or SAWs. These high-energy sound waves can be used to cause ripples in a piezoelectric material, which can transform voltage into mechanical movement or vice versa. In this case SAWs stimulate movements in fluids, which can be harnessed in various ways (see “Sound streams and good vibrations” and diagram, right).
SAWs have already been deployed in other technologies, such as in the touchscreens of smartphones. They sense your finger by detecting disturbances in the SAWs, for example. However, recent research has pushed the field forward so acoustic waves are being used in a range of analytical tools.
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One of the first people to see the potential of SAWs in chemical analysis was of the University of Augsburg in Germany. When a low-intensity sound enters a fluid, it generates a compression wave, causing the substance’s molecules to wobble backwards and forwards before settling back into their original position. At higher intensities, acoustic waves can cause the molecules in a fluid to move in a stream in the direction of the wave – a phenomenon called acoustic streaming. Wixforth demonstrated that acoustic streaming could be used to mix tiny quantities of biological fluids and went on to found a spin-off company called .
Traditionally, to chemically test such samples, you would have to pump them into rows of wells containing reagents. Mixing sample and reagent is tricky when the quantities are minute, and diffusion is often your only option. Using SAWs to do the mixing can speed up the process as the fluids can be manipulated at will.
The polymerase chain reaction – the standard technique for amplifying genetic material for DNA sequencing and scanning – normally requires a process of repeated reaction cycles of gentle heating and cooling. Wixforth has shown that this effect can be achieved by repeatedly moving a sample droplet between heating elements on a chip, and using SAWs to speed up the reactions through mixing (Lab on a Chip, vol 5, p 308).
Mixing is just the start. By carefully controlling acoustic streaming within a droplet, it is also possible to move and filter droplets entirely on the same chip. Bombard drops with SAWs from multiple angles (see picture) and they can even be made to “jet”, like the ink in an ink-jet printer but without the nozzles, says , a nanophysicist at Monash University in Clayton, Victoria, Australia.
Traditional microfluidic chips can also do these things, but only when hooked up to external pumps. Generating SAWs takes much less power. What’s more the newer technique also has some extra tricks. If you focus the acoustic stream on the sides of a droplet you can also get it to rotate. Spin it hard enough and the droplet behaves like a centrifuge. This is extremely useful if you want to use your chip for blood tests, where the cells need to be separated from the plasma. “It’s like a tornado,” says Yeo. “Normally centrifuges take about 10 minutes, but this takes less than a second.”
“Spin the drop hard enough and it becomes a centrifuge, great for separating cells from plasma in blood tests”
Besides blood tests Yeo is now carrying out research for Australia’s Office of National Security as part of its counter-terrorism programme. The plan is to see if SAW centrifuges and other approaches can safely be used to isolate and detect traces of pathogens, such as anthrax.
Meanwhile, , a bioengineer at the University of Glasgow, UK, has been using SAWs to vaporise droplets. This is a key step in the preparation of samples for mass spectrometry. And it means that you don’t need to add stabilising components to prevent a biological sample from being destroyed during the spectrometry process. With SAWs it is also easier to pinpoint trace elements because there are no stabilisers that might contaminate the sample.
Yeo is also studying the use of SAWs to convert liquids into fine sprays – nebulisation – for use in drug delivery. Asthma inhalers produce a range of different droplet sizes depending on how hard the user breathes in. Larger drops won’t make it into deep lung tissue, while smaller ones may be exhaled, so only about 30 per cent of the drug reaches its target, says Yeo.
He has developed a prototype SAW nebulising chip, which he envisages could be incorporated into an inhaler that would allow a person to deliver the drug efficiently at the push of a button. A nebulising chip would boost the effective dosage to 80 per cent by adjusting SAWs to produce droplets approximately 3 micrometres in diameter. Yeo says this is the ideal droplet size for delivering the drugs into the lungs (Lab on a Chip, vol 9, p 2184).
While SAWs have so far only been used in a handful of chemical analysis technologies, the advances made by Yeo and other researchers suggest that more complex devices are on their way. Lab technicians won’t need to hang up their white coats quite yet, but they are likely to find that their job entails less time indoors.
Sound streams and good vibrations
Piezoelectric materials such as lithium niobate transform electrical energy into mechanical energy, vibrating when an alternating voltage is applied to them. When a pair of comb-shaped electrodes are placed on this material, interleaved so that they don’t touch, they create a shallow electric field, localising the vibrations to a small patch of the surface of the material.
This causes an intense acoustic ripple to propagate across the plane of the surface. When this comes into contact with a droplet sitting on the surface of the material the energy is absorbed by the fluid. Because sound travels faster through solids than liquids, the wave is deflected into the droplet.
Although this energy dissipates quickly, at frequencies of around 10 megahertz it causes an effect called acoustic streaming. Instead of just creating compressive waves, it forces molecules forward to form a stream within the droplet.
Depending on the position, size and direction of these flows, they can create pressure variations sufficient to move, mix or spin the droplet. And if the intensity is increased further the droplet can be made to “jet”, squirting off the surface like a nozzle-less ink-jet printer, or even vaporised.
