More than a year into the pandemic, many parts of the world are still reeling with multiple waves of infections. For instance, the US, according to a recent report in the Associated Press, is averaging 100,000 new COVID-19 infections daily.
Testing is a key part in this whole exercise but even today, despite plenty of technological advancements, most test samples have to be sent back to laboratories for processing -- a time-consuming procedure.
Now, researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University, the Massachusetts Institute of Technology (MIT), and several Boston-area hospitals have created an inexpensive, CRISPR-based diagnostic test that lets users test themselves for SARS-CoV-2 and different variants of the virus using a sample of their saliva at home. The test requires no extra instrumentation needed.
Called Minimally Instrumented SHERLOCK (or miSHERLOCK), this diagnostic device provides results that can be read and verified on a smartphone app within one hour. According to an official news release, the device successfully distinguished between three different variants of SARS-CoV-2 in experiments, and can be rapidly reconfigured to detect additional variants like the Delta. It can be assembled using a 3D printer and commonly available components for about $15. Re-using the hardware brings the cost of individual assays down to $6 each, the release explains. The device was described in a recently-published study in the journal Science Advances.
The study’s co-first author Rose Lee, M.D. has been working on the front lines of the COVID-19 pandemic for over a year, as an Instructor in pediatrics at the Boston Children’s Hospital with a specialization in infectious diseases, the release adds. Lee’s experiences in the clinic provided inspiration for the project that would go on to become miSHERLOCK.
“Simple things that used to be ubiquitous in the hospital, like nasopharyngeal swabs, were suddenly hard to get, so routine sample processing procedures were disrupted, which is a big problem in a pandemic setting,” adds Lee, who is also a Visiting Fellow at the Wyss Institute. The research team’s motivation for this project was to eliminate these bottlenecks and provide accurate diagnostics for COVID-19 with less reliance on global supply chains, and could also accurately detect the variants that were starting to emerge, Lee explains in the release.
It also explains why the team opted for saliva rather than nasopharyngeal swab samples as the collection method -- it’s easier for users to collect saliva and studies have shown that the SARS-CoV-2 virus is detectable in saliva for a greater number of days after infection. Unprocessed saliva, however, presents a stumbling block. “It contains enzymes that degrade various molecules, producing a high rate of false positives,” the release adds.
The researchers developed a new technique to solve this issue: first, they added two chemicals called DTT (Dithiothreitol) and EGTA (ethylene glycol tetraacetic acid) to the saliva and heated the sample to 95°C for 3 minutes, which eliminated the false positive signal from the untreated saliva and sliced open any viral particles, the release explains. “They then incorporated a porous membrane that was engineered to trap RNA on its surface, which could finally be added directly to the SHERLOCK reaction to generate a result.”
The device was tested using clinical saliva samples from 27 COVID-19 patients and 21 healthy patients. miSHERLOCK correctly identified COVID-19-positive patients 96% of the time and patients without the disease 95% of the time, the release adds.
The researchers explain that the best thing about this diagnostic device is that it is “entirely modular”. It was designed with low-resource settings in mind: the hardware can be built by anyone with access to a 3D printer. The files and circuitry designs are all publicly available online as well. The device, say researchers, is ready for use in the real world. The next step is to find industrial and manufacturing partners to make it commercially available. “The device costs about $15, but mass production would bring the housing down to about $3. Assays for new targets can be created in about two weeks, enabling the rapid development of tests for new variants of COVID-19 and other diseases,” co-first author Devora Najjar, a research assistant at the MIT Media Lab, explains in the release.