A new technique for detecting viruses works by listening to them
TREATING viral diseases is notoriously hard. One reason is that for many such diseases, the amount of virus in a patient's bloodstream (known as the viral load) has to be monitored carefully in order to work out the appropriate drug dose.
At the moment this is often done by quantitative PCR, which uses an enzyme called polymerase to “amplify” part of a virus's genetic material by repeated duplication, until it is chemically detectable. But quantitative PCR is time-consuming; and in viral diseases time is often of the essence. Now a technique described in Nature Biotechnology by Matthew Cooper and his colleagues at Cambridge University may provide that essential time.
Instead of detecting viruses chemically, Dr Cooper listens for them. To do this, he and his colleagues use an apparatus called a quartz crystal microbalance.
The balance is a disc made of a polished quartz crystal, with two electrodes attached to it. Sending an electric current of the right frequency through the quartz causes it to resonate, much as a soprano singing at the proper pitch can shatter a champagne glass. By increasing the voltage—the equivalent of singing louder—the team can make the crystal oscillate more and more violently.
As the vibrations grow, anything attached to the quartz will eventually be thrown off. It is possible to measure exactly how much was initially weighing down the crystal by listening to the sounds of the objects departing, using the crystal itself as a microphone. The extra vibration caused by a departing object generates a current in the quartz, and this can be measured via the electrodes. If the objects in question are virus particles, an estimate of their number can then be made.
The trick is to make the viruses stick to the quartz in the first place. To do this, the team coated it with chromium, gold and mercaptoundecanoic acid. This unlikely combination of chemicals made the quartz, in turn, chemically attractive to antibodies. And, since antibodies can be tweaked so that they stick to one particular sort of virus alone, that means that the quartz can be made virus specific.
To prove their point, Dr Cooper and his colleagues chose a virus called type 1 herpes simplex (HSV1), which causes cold sores. After running a fluid containing HSV1 over the quartz crystal, they were able to measure the presence on it of anything from one to 1m viral particles.
The concentration of the virus in the fluid can then be worked out from the number of viral particles that stick to the quartz. Naturally, this is easier to do with the experimental solution that the team used than with blood, saliva or other bodily fluids. So far, HSV1 samples diluted in calf serum, to mimic such real-life samples, give a signal that is only a quarter of that from the original test fluid. Dr Cooper thinks this is because proteins in the serum are blocking some of the binding sites on the crystal. Yet even when the waters are muddied with serum, a discernible signal emerges. So, once the system is refined, the group expects to be able to detect and quantify viral load from clinical samples.
The researchers are now trying to develop their discovery into a practical, portable device. Success would make for a big improvement in the treatment of diseases that are frustrating to deal with today.