Diagnostics
of contract manufacturer Jabil Healthcare to meet the increased demand for its product, and with a manufacturing rate of only 1.2 million cartridges per month, it was clear DnaNudge couldn’t be the moonshot solution either. Instead, the boxes and cartridges, which were sold under the product name CovidNudge, found their homes on UK hospital wards, where the morbidity and mortality risk of Covid spreading was much higher than in the wider world. Toumazou says these wards, which typically provide maternity, elective surgery or mental health care, are still using CovidNudge, but the number of orders from the UK government has decreased with the positive impact the vaccines are having.
Mass testing
Above: The CovidNudge test takes place in a small box the size of a toaster and can return results within 90 minutes.
Opening page: The miSHERLOCK test allows users to carry out three assays at once.
An RT-PCR test is the most common form of PCR used to diagnose Covid-19. It only takes between two and three hours of thermocycling to get a result, but that’s not the whole story. There’s also the time it takes to obtain a nasopharyngeal sample, transport it to the nearest available laboratory and prepare the primers and reagents necessary to conduct the test. Add that all together and it’s not unusual to wait two days or more for a Covid test result.
Of course, vaccines supplanted mass testing as the new ‘plan A’ at the start of this year, but with several mutations already increasing transmissibility, there’s still a convincing case for accurate point-of-care tests that can provide a result in hours, not days.
£161m
NudgeBox Covid tests purchased by the UK government in August 2020
UK government 32
PCR in a box Dr Chris Toumazou was an early innovator looking to cut turnaround times and the reliance on laboratories – but his solution was more, not less, PCR. The difference is his PCR test doesn’t take place in a lab, but in a small box about the size of a toaster, in which microfluidic cartridges automatically perform all of the necessary preparation and amplification steps. The device returns results in 90 minutes. As suitable as it might seem, the process wasn’t developed to test for viruses. Instead, it was designed for Toumazou’s consumer business, DnaNudge, which uses PCR to test for genetic variables that contribute to the risk of certain diseases, like obesity and diabetes. “We had a solution before the coronavirus came along,” he says. “The box was designed for PCR thermocycling. It could be a lot smaller [...] but if you want to take what’s done in a laboratory out of the lab, you have to do exactly what’s done in a lab, to the same standard and with the same accuracy.” The UK government was convinced, buying 5,000 NudgeBox units and the additional equipment needed to run 5.8 million tests back in August 2020 for a total of £161m. But DnaNudge had to enlist the capabilities
For mass testing, the UK government opted for lateral flow tests – a cheap to produce assay that uses the same technique found in pregnancy tests to detect SARS-CoV-2. The chorionic gonadotropin (hCG) hormone detected via pregnancy tests tends to be easy to pick up due to the high volume of it present in the urine of pregnant women. However, the viral load present in a Covid swab can vary significantly, and without an amplification method, such tests are always going to be less sensitive to lower viral loads than RT-PCR.
“Departments like the MHRA [Medicines and Healthcare products Regulatory Agency] would never usually consider antigen tests like lateral flow or even LAMP [loop mediated isothermal amplification] tests for Covid because they were so inaccurate,” says Toumazou. “But then we got to a point where beggars couldn’t be choosers, so we had to use these technologies.”
The UK government bought into LAMP technology at the same time it purchased CovidNudge. Specifically, it bought the equipment needed to perform 450,000 LamPORE tests from University of Oxford spin-off company Oxford Nanopore Technologies (ONT). Certain figures suggest this assay, which combines reverse transcription loop mediated isothermal amplification (RT-LAMP) with a DNA sequencing method (nanopore sequencing) developed by ONT, has a sensitivity and specificity equal to that of PCR – but Toumazou says the technology also has disadvantages that limit its use in the current pandemic. “The sequencing takes place in a lab, and there’s no multiplex that can sequence out of the lab and in the community,” he explains. “LAMP works at a fixed temperature, so unless your assays or primers amplify at that fixed temperature, then you can’t put many of them on the chip, whereas thermocycling can amplify many different assays.”
CRISPR
Multiplex analysis refers to the process of mixing several different primers and reagents in the same
Practical Patient Care /
www.practical-patient-care.com
Thomas Angus, Imperial College London
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