Ultra-sensitive biosensor could accelerate disease diagnosis

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Researchers at the Polytechnic Institute of New York University (NYU-Poly) have created an ultra-sensitive biosensor capable of identifying the smallest single virus particles in solution.

It is claimed the advance could change early disease detection in a point-of-care setting and reduce test result waiting times from weeks to minutes.

Stephen Arnold, university professor of applied physics and member of the Othmer-Jacobs Department of Chemical and Biomolecular Engineering, and researchers of NYU-Poly’s MicroParticle PhotoPhysics Laboratory for BioPhotonics (MP3L) reported their findings in the most recent issue of Applied Physics Letters.

According to a statement, their technique is a major advance in a series of experiments to devise a diagnostic method sensitive enough to detect and size a single virus particle in a doctor’s office or field clinic, without the need for special assay preparations or conditions. Normally, such assessment requires the virus to be measured in the vacuum environment of an electron microscope, which adds time, complexity and cost.

Instead, the researchers were able to detect the smallest RNA virus particle MS2, with a mass of six attograms, by amplifying the sensitivity of a biosensor.

Within it, light from a tuneable laser is guided down a fibre-optic cable, where its intensity is measured by a detector on the far end. A small glass sphere is brought into contact with the fibre, diverting the light’s path and causing it to orbit within the sphere. This change is recorded as a resonant dip in the transmission through the fibre. When a viral particle makes contact with the sphere, it changes the sphere’s properties, resulting in a detectable shift in resonance frequency.

The smaller the particle, the harder it is to record these changes. Viruses such as influenza are fairly large and have been successfully detected with similar sensors in the past, but many viruses such as Polio are far smaller, as are antibody proteins, and these require increased sensitivity. 

Arnold and his co-researchers achieved this by attaching gold nano-receptors to the resonant microsphere. These receptors are plasmonic and enhance the electric field nearby, making small disturbances easier to detect. Each gold ‘hot spot’ is treated with specific molecules to which proteins or viruses are attracted and bind. 

In experiments, the researchers are said to have successfully detected the smallest RNA virus in solution and are now aiming to detect single proteins, which would represent a major step towards early disease detection.

‘When the body encounters a foreign agent, it responds by producing massive quantities of antibody proteins, which outnumber the virus. If we can identify and detect these single proteins, we can diagnose the presence of a virus far earlier, speeding treatment,’ Arnold said. ‘This also opens up a new realm of possibilities in proteomics. All cancers generate markers and if we have a test that can detect a single marker at the protein level, it doesn’t get more sensitive than that.’ 

This patent-pending technology, co-authored with postdoctoral fellow Siyka Shopova and graduate student Raaj Rajmangal, is ultimately designed for a point-of-care device capable of detecting viruses or disease markers in blood, saliva or urine.

Testing for commercial applications is already under way.