The ‘gold standard’ polymerase chain reaction (PCR) tests for COVID-19 take more than an hour to process. A lateral flow test takes 30 minutes to get a result and the results are less reliable. Biosciences PhD student Jake Carter has created a new test that gives reliable results in under five minutes.
Jake, studying at Birmingham University, used his time at home during the first lockdown to build on his academic work in assays. He got support from his supervisors, university colleagues, the business hosting his placement and the wider research community.
The new test uses a technique which they have named Reverse Transcriptase Free EXPAR (RTF-EXPAR). It is now being tested by the NHS. Jake and the team are currently exploring how to make the test easier to deploy and looking at its potential for other diseases.
About the project
Jake Carter’s research had gone well, papers were in and he could have concentrated on the write-up. But as his co-supervisor, Professor Tim Dafforn from the School of Biosciences, explains, “He said he wanted to make a difference and create a COVID-19 assay. He went into the lab and, though we provided the intellectual support, he has been incredible.”
Jake’s two co-supervisors, Professor Dafforn and Professor Jim Tucker from the School of Chemistry, were frustrated by the lack of activity to mobilise the academic sector. There was nowhere to create and shape ideas like Jake’s to tackle the national public health emergency.
Generating ideas in town hall meetings
Along with several BBSRC and UKRI grants for their research, Professor Dafforn has received a BBSRC Enterprise Fellowship to spin-off Linear Diagnostics, a business developing a platform that will perform diagnostic testing without the need for laboratory facilities. He has also held positions in the Department for Business, Energy and Industrial Strategy (BEIS). This experience and their connections meant they were well placed to organise a series of town hall style meetings for academics, including Jake, to address the pandemic.
“I knew we had the intellectual capacity in the UK to do something, and we needed to find a way to self-organise, so we did it ourselves,” recounts Tim. “We thought we could do something, so we set up a group in the Midlands. It was like a community group. By the time we were finished, we were having meetings with 40 or so scientists from all sorts of different areas, just brainstorming ideas and trying to link up.”
He was keen the meetings be as inclusive as possible: “When we had those first meetings, we didn’t consider whether people would be useful; we just considered people who might be of the right mind to have some exciting ideas.”
Those meetings strengthened the Birmingham team’s resolve to develop a new and faster assay. As part of Jake’s Doctoral Training Programme, he had completed a work placement with Linear Diagnostics Ltd to better understand the practical aspects of assay research and to increase his bioscience skills. The relationships and skills he had developed with the team there now meant he could turn to them for their knowledge and advice around building upon his research.
New test uses standard equipment and lower temperatures
The new test gives a sample-to-signal time of under 10 minutes, even for low viral levels where current lateral flow tests are less effective.
The team used a three-way comparison study to confirm that their method is just as sensitive, but faster, than both the gold standard PCR test and loop-mediated isothermal amplification (LAMP) tests which are currently used in hospital settings. PCR tests use a reverse transcriptase enzyme to convert RNA to DNA as the first step, then use a DNA polymerase enzyme to copy the DNA, ‘amplifying’ the material many times over to detectable levels.
The method developed by Jake uses very short, single strands of DNA that recognise and bind to the viral RNA rather than copying it. Then they use EXPAR as a way to amplify the DNA, which avoids the heating and cooling cycles needed for PCR, with shorter strands making it faster than LAMP.
The entire test can be run on standard laboratory equipment at lower temperatures. Tucker is enthusiastic about the improvements this offers testing regimes, saying “This is an extremely promising approach to developing a rapid, accurate test which could increase NHS testing capability by up to five times.”
Impacts of the project
Jake’s project has the potential to contribute to a range of positive outcomes, not all of them directly-related to COVID-19.
Testing for COVID-19 and a range of RNA-based conditions
Jake has worked with the University of Birmingham Enterprise to file a patent application. He’s currently seeking funding for the next step – testing thousands of samples to confirm the findings before the test can be adopted by the NHS. The results are looking promising, with no cross-reaction with the majority of other respiratory pathogens and better sensitivity than PCR and LAMP tests.
The team expect that, in the long-term, the use of the RTF-EXPAR technology will be extended for use with other RNA-based viruses and infectious agents, as well as other diseases, including some cancers.
Living with COVID-19
But impacts aren’t limited to the potential in hospitals to identify the virus. Professor Andrew Beggs of the University’s Institute of Cancer and Genomic Sciences evaluates diagnostic tests for the Department of Health and Social Care and is now supporting Jake to take the test through to the next stage.
He sees the importance of such a rapid test for opening up the economy – particularly in terms of offices, sport, retail and entertainment. “Mass events like Birmingham 2022 Commonwealth Games and big concerts and sports gatherings would benefit enormously from having a rapid and reliable test for competitors and visitors, with almost instant results,” he said.
Inspiring students and staff who are interested in entrepreneurship
This potential has made the story of global interest but the focus on the West Midlands was no surprise to Professor Dafforn, who noted that Birmingham has the largest collection of med-tech companies in the UK. The importance of the story and connection to the city, the university, and Jake has also inspired others. As Tim adds: “My undergrads were asking me to give updates on Jake’s assay, they requested extra tutorials.”
Jake says: “We didn’t know this would work, but we gave it a go. If you get caught up in making it work perfectly in theory, you slow everything down. We had about 80% of a plan, and then we tried it. It quickly evolved into something really good. If we kept thinking about it, we could still be thinking about it today.”
Tim is of the view that, compared to funding projects, supporting scientists to get together is cheap. He says: “In any emergency, the limitation on what comes out is the communication between people. The more people talk, the more likely a solution will be found.”
Find out more
Top image: A lateral flow test takes longer and is less accurate than the new test. Credit: Getty Images.