Cambridge researchers have developed a new test that “hunts” for multiple respiratory viruses at once using single strands of DNA as a “bait”, and gives highly accurate results in less than an hour.
The test uses a DNA “nanobait” to detect most common respiratory viruses – including influenza, rhinovirus, RSV and COVID-19 – at the same time. By comparison, PCR tests, while highly specific and highly accurate, can only test for one virus at a time and take many hours to return a result.
While many common respiratory viruses have similar symptoms, they require different treatments. By testing for multiple viruses at once, the researchers say their test will ensure patients get the right treatment quickly and could also reduce unwarranted use of antibiotics.
In addition, the tests can be used anywhere, and can be easily modified to detect different bacteria and viruses, including potentially new variants of SARS-CoV-2, the virus that causes COVID-19. The results are reported in the journal Nature’s Nanotechnology.
Winter cold, flu and RSV season has arrived in the Northern Hemisphere, and healthcare workers must make quick decisions about treatment when patients arrive at the hospital or clinic.
“Many respiratory viruses have similar symptoms but require different treatments: we wanted to see if we could search for multiple viruses in parallel,” said Philip Boskovitch of the Cavendish Laboratory in Cambridge, first author of the research paper. “According to the World Health Organization, respiratory viruses are the cause of death in 20% of children who die under the age of five. If you can come up with a test that can quickly and accurately detect multiple viruses, that could make a difference.”
For Bošković, the research is also personal: As a toddler, he was in the hospital for about a month with a high temperature. Doctors could not figure out the cause of his illness until a PCR machine became available.
“A good diagnosis is key to good treatment,” said Boskovitch, a PhD student at St John’s College, Cambridge. “People come into the hospital needing treatment and they may be carrying multiple different viruses, but unless you can differentiate between the different viruses, there is a risk that patients may receive incorrect treatment.”
PCR tests are powerful, sensitive, and accurate, but they require copying a piece of the genome millions of times, which takes many hours.
The Cambridge researchers wanted to develop a test that would use RNA to detect viruses directly, without the need to copy the genome, but with a sensitivity high enough to be useful in a healthcare setting.
Co-author Professor Stephen Baker, from the Cambridge Institute of Therapeutic Immunology and Infectious Diseases, said: “For patients, we know that rapid diagnosis improves their outcome, so being able to quickly detect an infectious agent can save their lives.” “For healthcare workers, such a test could be used anywhere, in the UK or anywhere low or middle-income, helping to ensure patients get the right treatment quickly and reduce unexplained antibiotic use.”
The researchers based their test on structures built from double strands of DNA with single strands dangling. These single strands are the “bait”: they are programmed to “catch” specific regions in the RNA of the target viruses. The nanobaits are then passed through very small holes called nanopores. Nanopore sensing is like a tape reader that converts molecular structures into digital information in milliseconds. The structure of each nanobite reveals the target virus or its variant.
The researchers showed that the test can be easily reprogrammed to distinguish between viral variants, including variants of the virus that causes COVID-19. This approach allows close to 100% specificity due to the accuracy of the programmable nanobait structures.
“This work elegantly uses a new technique to solve many of the existing limitations at once,” said Becker. “One of the things we struggle with is the rapid and accurate identification of the organisms causing the infection. This technology is a potential game-changer; a fast, low-cost diagnostic platform that is simple and can be used anywhere on any sample.”
The technology has been patented by Cambridge Enterprise, the university’s marketing arm, and co-author Professor Ulrich Keyser co-founded a company, Cambridge Nucleomics, focused on RNA detection at single-molecule resolution.
“Nanobait is based on DNA nanotechnology and will allow many more exciting applications in the future,” said Keizer, who works in the Cavendish Laboratory. “For commercial applications and rollouts to the public, we will have to convert our nanopore platform into a handheld device.”
“Bringing together researchers from medicine, physics, engineering and chemistry has helped us come up with a truly meaningful solution to a difficult problem,” said Bošković, who was awarded a 2022 PhD by the Cambridge Applied Research Society for the work.
The research was supported in part by the European Research Council, Winton Program for Sustainability Physics, St John’s College, UK Research and Innovation (UKRI), Wellcome and the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research. center.