With the return of in-person schooling and the Biden administration’s recently-announced vaccine and testing mandate, fast and reliable COVID-19 testing remains a critical component to controlling the pandemic. At-home antigen tests, which can give results within 15 minutes, are now an attractive and convenient option for the public to quickly find out their COVID-19 status. That said, there is a major risk involved — the tests’ results can often be inaccurate.
“Antigen tests are hugely insensitive to early infections when your viral load is low,” said Ping Wang, PhD, a professor of Pathology and Laboratory Medicine in the Perelman School of Medicine at the University of Pennsylvania. “You may test negative and think you’re safe to return to work or school, when in reality, you’re infected and infectious to others.”
To fill the need for rapid and reliable COVID-19 testing, Wang’s lab has developed a rapid antigen test that can detect small loads of SARS-CoV-2 with sensitivity as high as a PCR (polymerase chain reaction) test, which is currently considered the gold standard in the diagnostic community.
The technology works by using a smartphone camera to photograph and measure the size and number of miniature, gas-filled bubbles — called microbubbles — in a chemical reaction using a patient’s nasal swab. Wang and her research team validated their test with clinical nasal swabs from 372 patients and found that it was able to identify 97 percent of positive swabs and 97 percent of negative swabs when compared to PCR methods. Their results were published recently in the journal Clinical Chemistry.
The technology has been submitted to the U.S. Food and Drug Administration (FDA) to request emergency use authorization (EUA) as a lab-developed test. If authorized, it could be used in the management of Penn Medicine patients who have their COVID testing conducted at the HUP laboratory. Wang’s long-term goal is to gather the data required for the test to be FDA-approved for at-home use. If successful, Wang says the rapid test could help to facilitate more frequent, wide-scale testing — and it would help to spot and isolate positive cases more quickly than current antigen tests allow.
“With our test, you can rest assured that it has high consistency with a PCR test. You don’t have to wait for several days until your infection becomes more severe or take several repeated tests to know if you’re positive,” Wang said.
From the Bench to the Bedside
Wang’s research interests are focused on “point-of-care testing,” meaning any diagnostic test that can be performed at home or sites close to care delivery.
In 2018, her team was working to develop a technology that could detect protein biomarkers in a highly sensitive way. Their first proof-of-concept study used the technology to test the level of prostate-specific antigen (PSA) levels in patients who had been diagnosed with prostate cancer and underwent prostatectomies. Since PSA levels are usually very low in this population, detection of early reoccurrence of the disease relies on sensitive measurement of very small increases in PSA concentrations. Wang’s research showed that their microbubble test was highly sensitive in detecting very low levels of PSA.
At the start of 2020, Wang’s group decided to pivot and find out if the test could be used to detect low levels of SARS-CoV-2 during the early days of an infection.
Unlike PCR tests, which amplify small amounts of genetic material, antigen tests work by detecting protein molecules in the virus. The current lateral flow technology that is approved by the Food and Drug Administration’s Emergency Use Authorization to detect SARS-CoV-2 has been around for decades, Wang says. To develop a new, much more sensitive rapid test, her lab built off of years of research in diagnostics.
“In a high sensitivity assay, it’s extremely important to suppress background noises and make sure you detect the very low level of true signal in a sample, so that’s why it is usually very challenging to design,” she said.
An App to Know Your COVID Status
The microbubbling test can be used easily at home with a smartphone. A person swabs his or her nose, dips the swab into a vile of liquid (called a buffer), and then applies a small amount of the sample to a cartridge. The user then takes a photograph of the readout, which is a picture of microbubbles that can be uploaded into a smartphone application also developed in Wang’s lab. The application then uses an algorithm to identify whether the size and number of the microbubbles match a positive or negative COVID-19 test result.
Another advantage of the microbubble test is that it can prevent the indication of false — or lingering —positive results. According to Wang, fragments of virus may be detected in a patient with a PCR test — long after he or she is actually contagious. Wang’s rapid antigen test, by contrast, does not detect these “lingering” fragments, giving patients a more accurate picture of their COVID-19 status. This may be particularly useful for immunocompromised individuals.
As a next step, Wang is working with the Penn Center for Innovation to seek partnerships for commercialization of the technology, as well as a startup company called Instanosis.
But even with the mass commercialization of such a test, it is likely that people would need to pay to purchase a testing kit, since at-home rapid test kits are not currently covered under the federal CARES Act, which makes PCR testing free for all. Ideally, Wang said, rapid test kits would also gain coverage under the federal government.
Moreover, Wang says she hopes that the approval of a more sensitive, rapid COVID-19 test — which could identify positive cases and subsequently save lives — will help to restore public trust in point-of-care diagnostics.
“Point-of-care testing is about making health care more accessible, and it would help to address many of the issues of health disparities that we have seen exacerbated during the pandemic,” Wang said.