The Covid-19 finish line has been pushed down the road this summer as variants continue to emerge and climb the ranks of the Greek alphabet.
Delta, Delta Plus, and now Lambda are spreading rapidly through the U.S. and causing spikes in hospitalization and death — especially among the young and unvaccinated, making rapid and reliable testing infrastructure just as important as ever. This especially goes for underserved communities who may struggle to reach testing facilities or pay for expensive at-home tests.
This is a problem that researchers at the Wyss Institute for Biologically Inspired Engineering in Boston are hoping to solve with a new CRISPR-based Covid-19 test that can transform users' saliva into a fluorescing Covid-19 detector in just 1 hour.
“Early on in the pandemic, we faced a lot of shortages regarding simple supplies like nasal swabs and transport media,” co-first author and Boston Children’s Hospital infectious disease specialist, Rose Lee M.D, tells Inverse. “That was partially the motivation for using a more universal and easier to manage sample type [like saliva.].”
This research was published Friday in the journal Science Advances.
What’s new — During the past year-and-a-half, you might’ve gotten pretty comfortable going to your local pharmacy or clinic to get your nose swabbed for a Covid test and waiting between a few hours and a few days for your result.
But as new variants continue to emerge and move through vulnerable populations rapidly, the authors of this new paper say these solutions aren’t enough.
Namely, because many of these tests still involve an intermediary step that brings a patients’ sample to a lab for processing. Additionally, at-home nasal swab tests are more susceptible to cross-contamination or error because users might struggle to swab themselves accurately.
As an alternative to this standard approach, the team’s new device, called miSHERLOCK (minimally instrumented Specific High-sensitivity Enzymatic Reporter Unlocking), uses just saliva and internal heat and a mix of enzymes to create an easily readable result without any need for lab analysis.
Why it matters — Walking to a busy city center to get a Covid test if you think you might be sick is an inherently risky activity, Devora Najjar, a research assistant at the MIT Media Lab and another co-first author, tells Inverse. This is especially true with fewer people wearing masks or other face coverings. Designing a quick option that a user can fully conduct at home could help lighten this risk.
And as the early pandemic showed us, supply chains for items like nasal swabs are brittle. Creating an option that bypasses these is not only convenient and cheap but could help lessen the burden on existing infrastructure in the future as well, Xiao Tan, another co-first author and clinical fellow in the Wyss Institute, tells Inverse.
How it works — As for how this handheld device (which Tan describes as being equivalent in size to a stack of two playing card decks) it’s as easy as spitting and pushing a button. Although, the science itself is a little more involved.
Helena de Puig, a postdoctoral fellow at the Wyss Institute and MIT, tells Inverse how this all plays out:
- A user spits about two milliliters (or just shy of a quarter teaspoon) into the reception funnel
- This spit then passes through a filter (which concentrates its nucleic acids) and a heat chamber that neutralizes other enzymes in saliva that could create false-positive results
- This saliva sample is then moved over to the “action center” of the device, where you push a button to release the freeze-dried CRISPR reaction
- CRISPR and SHERLOCK then take 55 minutes to locate and snip targeted nucleic acids for different SARS-CoV-2 variants and release a glow of fluorescence to signal their success.
While the results are easy to visually identify (a glow means you do have Covid-19, and no glow means you don’t), there is also a companion app that can use a smartphone’s camera to make this call even easier.
Users can also share their results — which will reveal which variant they have, depending on the assay being tested — with community health services to improve local transmission tracking.
The team validated their device using about 30 saliva samples with some artificially injected with full-length synthetic RNA samples to mimic these variant infections. Saliva samples — especially those with emerging variants — are difficult to come by, but the team hopes to further validate their device with more samples in the future.
From these samples, the team found their device could correctly identify Covid-19 patients 96 percent of the time.
What’s next — In addition to further validating their device down the road, the team also hopes to find an industrial partner that can help them manufacture these devices on a mass scale. With this help, Najjar says the reusable device could be manufactured for as little as $3.
“Designing a platform like this will definitely be something we try to iterate on for future projects for other types of diagnostics,” says Najjar. “[Especially for] people who don't routinely have access to testing facilities.”
Abstract: The COVID-19 pandemic highlights the need for diagnostics that can be rapidly adapted and deployed in a variety of settings. Several SARS-CoV-2 variants have shown worrisome effects on vaccine and treatment efficacy, but no current point-of-care (POC) testing modality allows their specific identification. We have developed miSHERLOCK, a low-cost, CRISPR-based POC diagnostic platform that takes unprocessed patient saliva; extracts, purifies, and concentrates viral RNA; performs amplification and detection reactions; and provides fluorescent visual output with only three user actions and 1 hour from sample input to answer out. miSHERLOCK achieves highly sensitive multiplexed detection of SARS-CoV-2 and mutations associated with variants B.1.1.7, B.1.351, and P.1. Our modularsystem enables easy exchange of assays to address diverse user needs and can be rapidly reconfigured to detect different viruses and variants of concern. An adjunctive smartphone application enables output quantification, automated interpretation, and the possibility of remote, distributed result reporting.