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Silicon tuning fork provides early detection of prion diseases

By David Robson, 11-Mar-2008

Related topics: Processing

A silicon tuning fork that changes pitch in the presence of deadly prions could provide an early detection of diseases such as bovine spongiform encephalopathy (BSE) and its human counterpart Creutzfeldt-Jacob disease (CJD).

The new technique, developed by researchers from Cornell University, is reportedly up to 1,000 times more sensitive than previous techniques. It is also quicker, more reliable, and does not rely on an autopsy sample.

The sensor consists of a 200nm thin film layer of low-stress silicon nitride covering a thermally oxidised silicon wafer. The silicon nitride conducts heats more easily than the silicon dioxide layer underneath, which is much more insulating. When excited by a 405nm diode laser beam, the two layers heat and expand at different rates, causing the resonator to vibrate very slightly.

The resonator is covered in prion-specific antibodies, which bind to the prions and fix them to the sensor. This causes a slight change in mass of the resonator, which in turn alters the resonant frequency, as objects with a greater mass tend to vibrate with a lower resonant frequency. By detecting this change in resonant frequency using a laser interferometer, scientists can determine the change in mass, which indicates quantity of prions attached to the sensor.

The prions by themselves are not heavy enough to cause a big difference in the resonant frequency of the resonator, meaning that only very large quantities could be detected, so the scientists amplified the effect by adding heavier nanoparticles to the mixture that bind to the prions attached to the resonator. This produced a larger mass increase of the resonator for each prion detected, ultimately allowing the device to detect much lower levels of prions than had previously been possible.

"Our detection limit is 2 ng/mL, which is an improvement of two to three orders of magnitude over currently approved detection techniques," said Madhukar Varshney, one of the researchers who worked on the paper, to be published this month in Analytical Chemistry. "Another advantage of this technique is the small size of the sensors. At this scale, resonators can be fabricated in arrays and several measurements per chip can be made in order to improve the statistics of detection and decrease false negatives and positives."

"For the fabrication [of this device] there were a couple of challenges - the selection of the materials, thickness, and uniformity of these materials across all the resonators on the chip during fabrication, and the selection of the most appropriate shape of the resonators," he revealed.

It is hoped that the ability to detect very low levels of these pathogens in food sources will prepare quality control labs to take early action to prevent the spread of these deadly diseases. It could also be used in hospitals to provide an early diagnoses of the dieases in patients. Varshney believes the sensor could also be used to improve national security. "These sensors have potential to detect multiple biomolecules that will be highly useful in counter terrorism efforts."