Researchers at the University of Illinois Urbana-Champaign developed a technique to see and count viruses or proteins from a sample in real time. The technique, which is fast, low-cost and uses no chemicals or dyes, could be used to develop a new class of devices for rapid diagnostics and viral load monitoring. These devices would potentially be effective in quickly diagnosing viruses such as HIV and the virus that causes COVID-19.

The new technique is called Photonics Resonator Interferometric Scattering Microscopy, or PRISM.

"We have developed a new form of microscopy that amplifies the interaction between light and biological materials. We can use it for very rapid and sensitive forms of diagnostic testing, and also as a very powerful tool for understanding biological processes at the scale of individual items, like counting individual proteins or recording individual protein interactions," said study leader Brian Cunningham, chair of electrical and computer engineering and a member of the Holonyak Micro and Nanotechnology Lab and the Carl R. Woese Institute for Genomic Biology at Illinois.

PRISM uses photonic crystal, a nanostructured glass surface that reflects only one wavelength of light. This differs from optical microscopes, in which light bounces off any molecules or viruses it encounters on a slide and creates a signal. For developing PRISM, the team designed and made a crystal that reflects only red light, so the light from a red laser would be amplified.

The researchers used the virus associated with COVID-19 to verify the technique, which successfully detected individual coronaviruses traveling along the surface of the slide. It also was able to detect individual proteins including ferritin and fibrinogen. This technique allows for study of biological targets, such as watching proteins interact, in their natural state.

PRISM for COVID-19 detection. At top, concept art. Bottom left, a microscope image of a single virus on the photonic crystal surface. Bottom right, a PRISM image with six viruses detected. Source: L. Brian StaufferPRISM for COVID-19 detection. At top, concept art. Bottom left, a microscope image of a single virus on the photonic crystal surface. Bottom right, a PRISM image with six viruses detected. Source: L. Brian Stauffer

"It takes 10 seconds to get a measurement, and in that time we can count the number of viruses captured on the sensor," Cunningham said. "It's a single-step detection method that works at room temperature. It is also fast, very sensitive and low cost. It's very different from the standard way we do viral testing now, which involves breaking open the viruses, extracting their genetic material and putting it through a chemical amplification process so we can detect it. That method, called PCR, is accurate and sensitive, but it requires time, specialized equipment and trained technicians."

The next step is incorporating PRISM technology into portable, rapid diagnostic devices for COVID-19 and HIV viral load monitoring. Cunningham’s group is looking into prototype devices that incorporate filters for blood samples and condensation chambers for breath tests.

The research is published in Nature Communications.

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