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15 Feb 2007
Optical phenomena are at the heart of a new generation of detectors that can spot viruses in seconds.
With mainstream media and politicians working themselves into a daily lather about bioterrorism and pandemic flu, virus detection is currently right up there on the research agenda. The trouble is, existing detection technologies require laborious sample preparation and take days to produce a result, by which time a subject could already have died or passed on the disease. Now, however, optics-based detection schemes are emerging that can differentiate between viruses within minutes.
One such technique is based on surface-enhanced Raman spectroscopy (SERS) and specially prepared silver nanorods, according to a team from the University of Georgia (Athens, GA). The researchers claim that their method could differentiate between viruses – and even between different strains of the same virus – in less than 60 s (Nano Letters 6 2630). "The SERS technology is useful for detecting near-attomolar [10–18 M] levels of biological reagents or pathogens in real time, without modification of the specimen," explained team member Ralph Tripp.
SERS works by measuring the change in frequency of a near-infrared laser as it scatters off viral DNA or RNA on a metal substrate. This frequency shift is different for each DNA or RNA sequence, allowing scientists to identify a virus from its genetic make-up. The SERS phenomenon is well known, but the signal produced is far too weak to be useful in virus detection. At least that was the case until the UGA team added some carefully prepared silver nanorods to the sample slide.
By doing this, UGA physics professor Yiping Zhao and chemistry professor Richard Dluhy found that they could amplify the signal by factors greater than 108. To achieve an enhancement of this magnitude, rows of silver nanorods have to be placed on the glass slides that hold the sample at an angle of precisely 86° to the slide. "The technique is so powerful that it has the potential to detect a single virus particle," Tripp claimed.
The nanorods are surprisingly cheap and simple to produce, which makes the technique inherently suitable as the basis for a new type of biosensor. The team envisages such a sensor being useful in a variety of situations, including clinical applications, research and biodefence. "You could actually apply it to a person walking off a plane and know if they're infected," said Tripp.
So far the team has shown that its technique works with viruses in cells grown in the lab. The next step is to test it on real biological samples, such as blood, faeces and nasal swabs. The researchers are also working to create an online encyclopaedia of Raman-shift values, so that technicians can identify unknown viruses. "We are developing the SERS platform for the detection of bacteria and toxins, and also applications that involve detecting multiple specimens on a single nanofabricated substrate," revealed Tripp.
The team is currently in the process of spinning out a company via UGA's Georgia BioBusiness Center and exploring ways to mass-produce the nanorods. Tripp predicts that we could see widespread use of the technique within two years.
An alternative take
Meanwhile, researchers at the University of Twente (Enschede, the Netherlands) have developed an alternative virus detector based on optical interferometry. They claim that it can spot viruses and measure their concentration within minutes. And since it needs only a tiny sample of saliva or other body fluid, it could be used as the basis of a hand-held device to screen people in hospitals and emergency clinics quickly (Nano Letters 7 394).
The detector essentially consists of a laser, which is shone through four channels in a silicon substrate. When the four beams exit the silicon they spread out and overlap to create an interference pattern. To spot a particular virus, the researchers attach the appropriate antibodies to one of the four channels and then flow a sample containing the virus through that channel. If the virus attaches to the antibodies, the interference pattern changes, allowing the scientists to estimate its concentration.
So far the team has only tested its sensor with the herpes simplex virus. Making it work with other viruses requires adding different antibodies to the light channel – a capability that will be explored soon. The scientists are also working with Netherlands-based company Paradocs Group to commercialize the invention and have a practical device ready within the next two years. "The goal is to have a small microfluidics device that can test for different diseases simultaneously," said Aurel Ymeti, the lead developer.
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