Biotech Pioneer Is Making a Home Test Kit for Coronavirus

Here's something that sounds decidedly useful right now: A home test kit that anyone could use to see if they have the coronavirus. A kit that's nearly as easy to use as a pregnancy test, and that would give results in half an hour.

It doesn't exist yet, but serial biotech entrepreneur Jonathan Rothberg is working on it.

We've heard from Rothberg before. Over the past two decades, he has founded several genetic sequencing companies that introduced breakthrough technologies, making genome sequencing faster and cheaper. (With one company he made news by sequencing the first individual human genome, that of Jim Watson; he sold another company for US $375 million.) In 2014, Rothberg launched a startup accelerator called 4Catalyzer dedicated to the invention of smart medical devices. The first company to emerge from the accelerator, Butterfly Network, now sells a handheld ultrasound tool that provides readouts on a smartphone screen.

Rothberg announced his interest in a coronavirus test kit in a Twitter thread on 7 March. Initially describing it as a "thought experiment," it quickly became a real project and a driving mission.

"I told my team that the Chinese built a hospital in Wuhan in 10 days so we should be able to develop and deploy a true home test for Covid19 coronavirus in that time," Rothberg tells IEEE Spectrum in an email. "The team is working around the clock to accomplish that goal."

Click here for additional coronavirus coverage

Rothberg says he's having discussions with the Gates Foundation, which has backed some of his other companies and projects. The foundation has embarked on its own effort for at-home coronavirus testing, and Rothberg says the two approaches are complementary.

The Gates Foundation's kits include a nasal swab that people mail back to the lab for analysis on "gold standard" machines, giving them results in a few days. Rothberg's kits would give results on a smartphone in half an hour. However, as he noted in his Twitter comments, his test would be less accurate, occasionally giving both false positive and false negative results.

If the two projects share data, Rothberg says, his team could compare results and get a better understanding of their own kit's accuracy. People who start with Rothberg's kit could also follow up with a Gates Foundation kit to confirm their results.

Rothberg says that researchers from his team and the Gates team are "trying hard to coordinate." And his team has already benefitted from the conversations, he says: "Gates gave us great advice on making our kit easy, and lots of advice on making sure our app guides the user." Rothberg adds in his email that the two organizations have complementary skill sets: "We know how to make kits and amplify DNA :) , they KNOW epidemiology." Rothberg's contact at the foundation couldn't be reached for confirmation before press time.

On Rothberg's side, the work is being led by scientists at Homodeus, a synthetic biology company within the 4Catalyzer accelerator.

Here's how Homodeus's home kit will theoretically work. A person will first use a swab to take a sample of a few cells from the inside of their nose or mouth. They'll dip that swab in a sequence of three tubes, following instructions from the accompanying app. Within each of those three tubes, chemical reactions will take place (more on those below).

The color of the liquid inside the third tube provides answers-it will turn one color (perhaps red) if the process has revealed the presence of the virus, and another color (perhaps green) if the person is in the clear. If the test has malfunctioned, it won't change color at all. The person can use their phone's camera to take a photo of the tube, and the app will give them the results and provide more information.

The test will not detect antibodies, the body's natural defenses that are marshaled to fight the coronavirus. Rothberg says his team decided against that approach because it can take a few days for an infected person to generate enough antibodies to register on a test. He wants a test that would detect the virus immediately, as soon as a person contracts the virus. He also wanted a test that an infected person could take during their recovery to determine when their body had successfully cleared the virus.

For that kind of instant detection, the test must recognize the virus's genetic material. The current coronavirus, officially known as SARS-CoV-2, is made of a single strand of RNA.

Now back to those tubes and the chemical reactions therein. In the kit's first tube, the cells on the swab are broken apart so the genetic material inside is accessible. In the second tube, a molecule called a primer looks for the unique code of the virus's RNA. If the primer does discover the coronavirus's RNA, another process begins that adds a second complementary DNA strand to the RNA, making a double-stranded molecule. The big advantage of this reaction is that DNA molecules are more stable than RNA, and it's easy to make lots of copies of them.

Then the swab goes to the third tube, where customized enzymes will make many copies of the DNA molecule, making it easy to detect. Another set of enzymes in the third tube will handle the color change: One color if the virus's genetic material did start this series of reactions, another color if it wasn't present and no reactions occurred.

"No lab. No technician. No expensive machines. No wait. The designer enzymes do all the work." -Jonathan Rothberg, 4Catalyzer

Rothberg explains that before the coronavirus outbreak, the Homodeus scientists were engineering enzymes to do things like repair genes and eat plastics. Now they're making designer enzymes that "do the entire test that normally takes laboratory technicians and special equipment," Rothberg says. "No lab. No technician. No expensive machines. No wait. The designer enzymes do all the work."

The app that will accompany the test kit will not only guide the user through the testing process, but also automatically submit results to public health authorities. Eric Kabrams, the 4Catalyzer engineer who's leading work on that app, says that data will be shared in a way that complies with strict privacy rules for people's medical data. "Thankfully, the best practices from modern cryptography and data privacy enable solutions that balance these dual objectives of minimizing the virus' spread and protecting sensitive information," he tells Spectrum in an email.

If Rothberg's team succeeds in creating this test kit, the next step will be to get it to academic labs for validation. Rothberg says he expects to have prototypes to send to labs in the next few weeks. "We are already in discussions with Penn and Yale to verify the test at their hospitals and clinical sites as quickly as possible," he says.

The researchers that Rothberg has been speaking with at the University of Pennsylvania and Yale University medical schools couldn't be reached for comment before deadline.

For an outside perspective and reality check, let's hear from Jacqueline Linnes, an assistant professor of biomedical engineering at Purdue University. She has developed a handheld paper device that could be used to detect viruses, including the novel coronavirus.

"Since people would use this at home, the tests need to be especially reliable. [These] tests need to be virtually impossible to mess up." -Jacqueline Linnes, Purdue University

Linnes says that the reactions Rothberg describes sound like standard processes typically conducted in labs under controlled conditions.

"It would be fantastic to be able to do this in home settings although there are a few considerations to make sure the tests work properly for reliable results," she tells Spectrum via email. "Since people would use this at home, the tests need to be especially reliable. Out-of-laboratory waived tests need to be virtually impossible to mess up." Linnes adds that the two-color system would be very helpful for nervous home users, since the colors enable users to differentiate between positive, negative, and test failure results.

As for the considerations, she lists a few. If the tubes aren't sealed, there's a possibility of sample contamination which could interfere with the results. She also notes that users would have to be careful with the timing: "The enzymes are eager to do their jobs so they will sometimes non-specifically amplify DNA," she says. "Especially if the reaction runs for too long, even a negative sample can appear positive." Finally, she says that the test's validators will have to ensure that the test is sensitive enough to screen the general public-if it's only able to detect the high concentrations of the virus found in hospitalized patients, it wouldn't be much help.

Rothberg acknowledges that his team has a big technical challenge: "making this easy enough for people not to mess up." But if they do succeed in making an easy-to-use test that passes expert scrutiny, it will be time to produce it in massive quantities. Rothberg says he's in discussions with manufacturers that could rapidly ramp up production, and that his other companies have existing distribution channels that could help get the tests out quickly. He aims "to make this test widely available across the globe," he says. When asked for a price estimate, he says that, with support from sponsoring organizations, he expects it to be free for anyone who can't afford it.

Besides making the kit, validating it, and manufacturing it, Rothberg's team also has to think through the regulatory requirements. On Twitter, Rothberg said he would seek to get his test kit approved as a "risk assessment" tool, rather than a diagnostic tool that the FDA would classify as a medical device. He tells Spectrum that he expects the FDA to work with him, given the urgency of the situation. "I expect no insurmountable regulatory hurdles," he says, "because we will validate at universities over next few weeks and use manufactures that practice and pass regulated manufacturing requirements."

So when could this at-home test kit be in your home?

"With miracles on our side-weeks to months if we get technical breaks and more molecular biology volunteers to come this weekend to Guilford [Connecticut] and help," Rothberg says. And he has a message for any potential volunteers brave enough to leave their quarantines: "We have guest houses and food."