Millions of diabetes patients use inexpensive glucometers to track their blood sugar. Now, scientists are seeking to adapt that technology for COVID-19 testing, underscoring the new possibilities of glucometer-based diagnostics at a time of rising medical costs.

A study published March 1 in Biosensors and Bioelectronics details the new glucometer approach, which can pick up on very low levels of coronavirus from saliva. It hinges on a short stretch of DNA known as an aptamer, which can bind to a specific protein on the virus the way an antibody binds to an antigen. The aptamer starts out lightly wrapped in its complementary antisense strand, a non-coding template DNA strand normally used to produce messenger RNA. If the virus is around, the aptamer prefers its protein antigen on the virus over the antisense strand.

When the aptamer binds to the virus, the aptamer changes shape. This causes it to jettison the antisense nucleic acid strand, which has been cleverly equipped with an enzyme known as invertase. This enzyme is what lets the researchers use a glucometer — invertase reacts with sucrose to make lots of glucose. The glucometer can detect that glucose, which correlates with how much virus is in the patient's saliva.

"Most tests that read things quantitatively or with a digital readout require a relatively expensive piece of equipment," Eliah Aronoff-Spencer, a researcher at the University of California, San Diego, and a coauthor of the paper, explained to The Academic Times. "This method would allow you to detect almost any substrate with a cheap glucometer anywhere in the world. Many people have done pieces of this innovation, and we've put it together, I think for the first time, for COVID."

According to Aronoff-Spencer, the innovation builds on past research by other scientists, who have used glucometers to detect influenza and other diseases. "We pushed the technology a little bit further," he said. "It's a new field. We'll see if people use these or realize that those glucometers are very cheap and could be rebranded as low-cost diagnostics readers."

Health care costs are increasing rapidly around the world, particularly in middle- and low-income countries. Innovations that capitalize on inexpensive existing technologies could help to curb this spending, although commercialization remains a challenge.

This team's system was reported to be extremely accurate and specific — and at just $3.20 per test, it was cheaper than every alternative to which they compared it. Yet Aronoff-Spencer says these data should be taken with a grain of salt, at least when it comes to using the test in the real world.

"We're comparing our results on a relatively limited study, in which we got everything right, but that doesn't mean we would always get everything right in the future," Aronoff-Spencer said. "In preliminary testing, it was really promising. It was on par with the best results out there."

The team has continued to develop their innovation. "We've built a cool little all-in-one saliva and biospecimen collection device," Aronoff-Spencer explained. "We have an upcoming paper where we show some more enhancements in terms of workflow."

"Going from a laboratory project to a tested thing that works with humans in the way it's intended, not the way you tried to make it work, during an important public health crisis — that's really hard," Aronoff-Spencer added. The team previously received funding for test technology development from the National Institutes of Health Rapid Acceleration of Diagnostics (RADx) Tech program. This financing came at a time of rapid development in COVID diagnostics, including through the tracking of liquid waste.

Since drafting their article for Biosensors and Bioelectronics, the team has made some changes to their platform, including switching from magnetic beads to a filtration system. "It makes it a lot easier to get the same amount of samples transferred in a cogent way without a lot of variability," Aronoff-Spencer said. He and his colleagues are also working to integrate a low-cost heating element, which is needed to make the invertase work efficiently.

The system can also be contaminated by glucose and other "nonspecific stuff" in saliva, according to Aronoff-Spencer. If people eat before being tested, their saliva could contain higher levels of glucose, potentially skewing the results. "We have people fast," he said. "The real question is, will people fast, and will they remember if they fasted?"

Still, Aronoff-Spencer is hopeful: "I think something in the technology's going to get used or lead to something that gets used. And I think it's going to happen in months or a year and not years."

The paper, "Hitting the diagnostic sweet spot: Point-of-care SARS-CoV-2 salivary antigen testing with an off-the-shelf glucometer," published March 1 in Biosensors and Bioelectronics, was authored by Naveen K. Singh, Aaron F. Carlin, Celestine Magallanes, Sydney C. Morgan, Louise C. Laurent, Eliah S. Aronoff-Spencer, and Drew A. Hall, University of California, San Diego; and Partha Ray, University of California, San Diego Health.