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Cathedral and Concert Inspire Record-Breaking Biosensor

Scientists are developing an ultrasensitive biosensor into a point-of-care diagnostic platform that they claim can detect and size the smallest virus particle, or potentially a single protein molecule, in a patient’s blood, urine, or saliva sample within minutes. The Whispering Gallery-Mode biosensor developed by researchers at the Polytechnic Institute of New York University (NYU-Poly) derives its name from the Whispering Gallery in the dome of St. Paul’s Cathedral in London, the acoustics of which allows a single whisper to be heard throughout the gallery space.

The amplified biosensor developed by Stephen Arnold, Ph.D., and colleagues effectively measures changes in resonance frequency in a glass sphere as it is contacted by a virus particle or a protein. Experiments reported by Professor Arnold and colleagues showed the platform is capable of detecting MS2, the smallest RNA virus particle known to man, which has a mass of only about 1% that of an influenza virus.

The basic technology underpinning the sensor is thus: Light from a tunable laser is guided down a fiber-optic cable, and its intensity is measured by a detector at the distal end. A small glass sphere is contacted with the fiber, and this diverts the path of the light and causes it to orbit within the sphere. This change is recorded as a resonant dip in transmission through the fiber.

When a virus particle then makes contact with the sphere, it changes the sphere’s properties, causing a detectable shift in resonance frequency. However, the smaller the particle, the harder it becomes to detect and record these changes. This means that previous biosensors based on spherical optical microcavity technology haven’t managed to detect anything smaller than a flu virus because the background noise is just too great, Professor Arnold’s team explains. Large viruses, such as influenza, generate enough of a disturbance to be detected, but smaller particles such as the polio virus, or proteins, require greater sensitivity. To increase sensitivity of such a system further the NYU-Poly team has built in a means to amplify the signal.

They boosted sensitivity to a record-breaking level by effectively pasting gold nanoreceptors onto the resonant microsphere, which act to enhance the surrounding electric field and make even the smallest changes in resonance frequency easier to detect. Each gold nanoreceptor is treated with ligands to which the proteins or viruses bind.

Interestingly, the inspiration for the platform came to professor Arnold during a concert by violinist Itzhak Perlman. “I was watching Perlman play and suddenly I wondered what would happen if a particle of dust landed on one of the strings,” he explains. “The frequency would change slightly, but the shift would be imperceptible. Then I wondered, what if something sticky was on the string that would only respond to certain kinds of dust?”

The NYU-Poly team aims to develop the Whispering Gallery-Mode biosensor technology into a diagnostic and proteomics platform that could be used in the laboratory, field, or doctor’s office to rapidly detect antibodies, virus particles, or even disease-related biomarkers for detecting subtypes of cancer. Professor Arnold et al., describe the biosensor in Applied Physics Letters. Their paper is titled "Taking whispering-gallery mode single virus detection and sizing to the limit."

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