More than a year into navigating life in a pandemic, most are familiar with their Covid-19 testing options. Rapid antigen tests, which detect bits of the coronavirus, can deliver results in under 30 minutes, but at about 85 percent accuracy, they aren’t reliable enough to help a person decide whether to show up to a group event. On the other hand, PCR tests are the gold standard for accuracy, but they take days to return results.
Researchers at Northwestern University, however, are aiming to provide the best of both worlds, thanks to a new device called DASH. To run a test with DASH (short for Diagnostic Analyzer for Specific Hybridization), someone would gather a nasal swab sample, snap the tip of the swab into a plastic cartridge, and then insert the cartridge into the cereal-box sized device. The device would then run PCR and give a Covid-19 test result within 15 minutes.
The National Institutes of Health’s RADx program has funded research on about five dozen technologies that could improve clinical lab tests, home-based tests and point-of-care tests for Covid-19, DASH included. Minute Molecular, the company developing the device, has high hopes for it as an efficient and accurate means of testing people at schools, workplaces and sports stadiums.
“They’re one of the companies in the point-of-care PCR bin, which we think is critical because that’s going to be the most accurate test you can get out there in a rapid fashion,” says Todd Merchak, a biomedical engineer with the National Institute of Biomedical Imaging and Bioengineering and co-lead of the RADx program. “It should catch even low levels of the virus in your saliva or nasal sample. That's critical for screening.”
Public health experts use screening to proactively keep an eye out for cases of Covid-19. It’s different than diagnosis, which is when an individual person feels sick and seeks out a doctor who can identify their illness and provide a plan for treatment. Screening can happen at places other than a doctor’s office—like before a shift of a front-line job or a flight—and involves testing people who may not realize that they are carrying the virus.
An infected person spreads the virus most before they develop symptoms of Covid-19, which makes the virus “insidious,” says molecular pathologist Justin Sanders, who co-leads the Covid-19 testing program, TRACE, at Oregon State University and is not involved in DASH. “So screening of asymptomatic people, and identifying potential folks who are infected and could lead to additional chains of transmission, isolating them and quarantining contacts is just absolutely vital.”
Right now, the fastest and easiest tests to run are rapid antigen tests. These tests are good at spotting people who are carrying a lot of the virus, which would make them very likely to infect another person. But antigen tests aren’t sensitive enough to return a positive result when someone is early in their infection and has a low amount of virus. That is a problem because that small amount of virus can multiply and become highly transmissible.
PCR tests are better at giving positive results for someone with a small amount of virus. But because it can take days to get back the results of a PCR test, the infection could still have a chance to grow and spread. It's best to spot a viral infection when it’s small so that the person can self-isolate before the virus has a chance to infect someone else.
“A lot of the issues with PCR in the earlier parts of the pandemic weren't really about how long it took to do the test [in the lab],” says Sally McFall, the chief scientific officer of Minute Molecular and a biomedical engineering professor at Northwestern University. Clinics have to ship their samples to the nearest testing lab, and then rely on a limited number of trained personnel to conduct the tests, so it’s this bottleneck that causes delays.
DASH is a point-of-care test. That means the same person who swabs your nose would also run the test with DASH and give the results, cutting out the time-consuming logistical steps. And the PCR process itself is also much shorter.
“From end to end, a classical lab-based PCR test, like what we run here, would take more like three hours,” says Sanders. “A 15-minute PCR at a point of care is pretty remarkable. That's a very short time frame to run that reaction to completion and detection. I think that's pretty cool.”
PCR stands for polymerase chain reaction, and it’s a standard lab procedure that has been around since 1985. PCR is used to make copies of short, specific sequences of genetic code. During a cool phase, a protein latches onto the genetic code of the virus and creates a short copy. Then a warm phase causes all of the chemicals to disconnect from each other and spread out in the pool of liquid. Alternating cool and warm phases make the number of copies grow exponentially—as long as genetic material from the virus was present in the first place.
DASH is able to extract the viral genetic information from the swab in ten minutes, and then move the sample to another chamber to run 40 cycles of PCR in just five minutes. The device measures the amount of genetic material in the cartridge while the process is running, and it displays the positive or negative result on a screen. Minute Molecular aims to make the test cheap and easy to use wherever someone might need a quick, accurate Covid-19 test.
When McFall and her colleague David Kelso first developed DASH in 2017, they imagined it as a tool to diagnose sexually transmitted diseases for people in low resource settings, where it can be difficult to get test results and a treatment plan to a person several days after they visit a doctor. But when the pandemic began in 2020, the team pivoted to apply the technology to Covid-19 testing.
“It was pretty much all hands on deck, focusing on trying to develop things as fast as possible so that we could try to make an impact on the pandemic,” says McFall. “Scientifically, it’s not any different [compared to the pre-Covid research]. It’s just that it’s like trying to build an airplane while you’re flying it.”
The team currently has ten prototype DASH devices that they are testing to ensure that they are as accurate as standard, lab-based PCR tests. Throughout the development of the device, the team has had to closely follow new research on coronavirus variants to ensure that DASH can spot those infections.
“You want to show that your results are as robust as possible in various settings, and in the case of point-of-care tests like this, a relatively untrained operator can actually operate the instrument,” says Sanders. He also notes that it will be important to make sure that DASH can adjust to possible shortages of the plastics and chemicals used in the cartridges.
Minute Molecular plans to apply for emergency use authorization from the U.S. Food and Drug Administration over the summer and submit data about DASH to a peer-reviewed publication. If the company receives the emergency use authorization, it can begin manufacturing DASH devices and cartridges. Walter Narajowski, chief operating officer of Minute Molecular, estimates that 1,500 DASH devices will be able to support one million tests per month.
The devices could be useful anywhere that a relatively small group of people are entering a space where transmission is very likely, or in rural clinics that face challenges getting their testing samples to a lab that can run standard PCR. The group size is limited by the fact that each DASH unit can only run one test at a time, and at 15 minutes per test, that time will add up, even if the venue has many units running simultaneously.
DASH might be used to screen front-line workers, like those in health care or grocery stores, before beginning a shift, because they come in contact with so many people each day. Or it could be used to test members of a sports team before a game. It wouldn’t be practical to use DASH to test an entire stadium audience for that game, says Sanders. DASH could also provide a back-up to rapid antigen tests that give ambiguous results, says Merchak.
DASH is designed to remain useful even after the Covid-19 pandemic wanes. Only a few parts of the cartridge need to be adjusted to test for the presence of different microbes, like influenza viruses.
“It's been built with robustness and…other respiratory viruses in mind,” says Merchak. “So these aren't just for the pandemic. These will hopefully benefit the population and health care years ahead.”