Diagnostics 96% Sensitivity of
miSHERLOCK test, making it highly comparable with PCR
Harvard Wyss Institute and Massachusetts Institute of Technology
reaction chamber in order to test for a range of viruses within a single sample. The CovidNudge device provides this functionality with 72 microwells, all of which can be spotted with different samples and reagents. The benefits of doing this include differential diagnosis of symptoms that could be caused by SARS-CoV-2, influenza or respiratory syncytial virus (RSV). Importantly for the current situation, they can also screen for variants of the same virus. Similarly, the minimally instrumented specific high-sensitivity enzymatic reporter unlocking (miSHERLOCK) test, developed by Harvard Wyss Institute and Massachusetts Institute of Technology scientists, allows users to carry out three assays at once. The product, which is based on previous work from one of the latter institution’s professors, James J Collins, is referred to by its creators as a “one-pot reaction”. This is because the recombinase polymerase amplification (RPA) step that takes place in lieu of PCR, along with the detection step performed using the CRISPR Cas12a enzyme, happen at the same temperature. A colour change prompted by an embedded fluorescence chemical indicates a positive or negative result an hour after sample collection. The researchers say the test had a sensitivity of 96% and a specificity of 95% in testing, making it highly comparable with PCR. The original test devised by Collins and now sold through his company Sherlock Biosciences, uses the traditional brain-prodding approach to obtain a nasopharyngeal swab. However, the team behind miSHERLOCK added a step to disable enzymes called salivary nucleases, which destroy nucleic acids, allowing it to detect the virus in spit alone. “We wanted as few user steps as possible to make sure there wouldn’t be any sources of contamination,” says Devora Najjar, a research assistant in the Collins Lab at MIT and one of the lead authors on the paper behind miSHERLOCK. “Even the addition of somebody opening it up and dropping a dipstick in is something we wanted to avoid.” This and other aspects of the test were designed with resource-limited locations in mind, with all components coming to just $15. But, as fellow lead author Xiao Tan, clinical fellow in the Collins lab and instructor in gastroenterology at Massachusetts General Hospital, points out, the pandemic has proven how easily the simple things we rely on for testing can become scarce when demand rises quickly. “Our aim was to make a wholly self-contained device that can be used in low-resource settings, but it’s very apparent that resource-rich settings can also become resource-limited settings very quickly,” he says. “This was very clearly illustrated by the fact that we couldn’t get simple swabs or viral transport media, things that are so basic they would never have been thought to be bottlenecks for testing.”
34 Decentralised accuracy
The miSHERLOCK and CovidNudge testing platforms are united by a common goal – to decentralise testing. In hospitals, CovidNudge does this by obtaining a result directly from a sample and storing the data in the cloud. From here, the information can be accessed by the hospital and sent to relevant government agencies to help establish prevalence statistics. On the other hand, miSHERLOCK comes paired with a smartphone app that uses the device’s camera to indicate a positive or negative test from the colour of the liquid in the test tube. In this case, the application itself transmits the data to relevant external bodies.
One of the motivations behind miSHERLOCK is that, by decentralising the data-gathering process, it can help governments and health services direct vaccines and boosters to the areas with the highest rates of transmission. The device is currently being pitched as a cheaper and more accurate home testing kit than the alternatives on the market in the US right now, though it is yet to receive FDA approval. Rose Lee, visiting scholar at the Collins Lab and paediatric infectious disease specialist at Boston Children’s Hospital, as well as a lead author on the study, believes miSHERLOCK could also play a valuable role in hospitals due to its ability to detect Covid variants. “We know some therapies, like the monoclonal antibodies we give to patients, can be affected by the variant,” she explains. In fact, the UK and US paused the use of two monoclonal antibodies – bamlanivimab and etesevimab – in June this year after it was discovered that the P.1/Gamma variant (first identified in Brazil) and the B.1.351/Beta variant (first identified in South Africa) rendered the treatment ineffective. As the virus keeps mutating, Lee notes that “clinicians could use [variant] data not just for broader epidemiology and surveillance purposes… but also to help them manage each patient”.
Despite the high sensitivity of its own device, the team behind miSHERLOCK are quick to emphasise that less sensitive assays like lateral flow tests still have a role to play in ending the pandemic. “In a perfect world, our testing would be very quick, sensitive and specific – and able to be shared everywhere,” says Najjar. “But there’s a realisation, especially by people in the research and clinical fields, that we don’t live in that world yet. Instead, we have to make testing work with the tools that we have.” Toumazou looks at it from the other direction. Antigen-based diagnostics are important for frequent at-home testing, but he believes there’s no replacement for the accuracy given by RT-PCR. “Democratising PCR is what was missing from the moonshot,” he says. “There’s a category that CovidNudge and other technologies fall into that cover that middle slot of being out of the lab, but not in the home. We can bring that to the mass with current technologies for the next wave or even the next pandemic.”
Practical Patient Care /
www.practical-patient-care.com
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