Frederic Zenhausern, PhD, working in lab
Frederic Zenhausern, PhD, working in lab

Researchers to Develop Device to Accurately and Quickly Detect COVID-19

Teresa Joseph
Teresa Joseph
Frederic Zenhausern, PhD, working in lab
Frederic Zenhausern, PhD, working in lab
The Center for Applied NanoBioscience and Medicine Awarded Grant from NASA to Develop Prototype by September 2020

Amid the coronavirus pandemic, a team of researchers at the University of Arizona College of Medicine – Phoenix are developing a device that will easily and accurately detect COVID-19 in a matter of minutes.

The Center for Applied NanoBioscience and Medicine, directed by Frederic Zenhausern, PhD, has received a grant to extend the development of its current space-based health monitoring system to build a prototype for COVID-19 testing by September 2020. The grant for $150,000 is from the Translational Research Institute (TRISH) through NASA Cooperative Agreement NNX16AO69A. Dr. Zenhausern’s lab is working on the project with Dr. Pierre Cosson at the University of Geneva in Switzerland, and Dr. David Aucoin at the University of Nevada in Reno.

“As cases of the virus continue to increase across the globe, specifically in Arizona, the need for a rapid diagnostic test for the COVID-19 virus is crucial,” Dr. Zenhausern said.

“TRISH is pleased to see progress on the technology Dr. Zenhausern and his team are making for fast and accurate COVID-19 detection,” Kristin Fabre, PhD, chief scientist at TRISH. “This demonstrates how tools developed for deep space missions, designed specifically to address unknown medical needs, are being applied to address the COVID pandemic.”

Currently, the test on market takes several days to get results, due to the requirement for being processed with large automated instrument at centralized laboratories, like Sonora Quest or LabCorp.

Dr. Zenhausern’s lab is developing a Vertical Flow Assay diagnostic system that can combine genes and antibodies directed to specific viral components of the SARS-Cov-2 onto a paper membrane through which biological fluids can flow and antigen interactions can be detected by the light scattering from gold nanoparticles whose imaging is directly interfaced with a smartphone. A user will self-collect a small finger-prick of blood or a spit of saliva, and then the liquid will be pushed through the paper membrane. Essentially, the device will take a picture of the array of spots from multiplex molecules onto the paper, which then can be analyzed by an algorithm on a cloud server prior to being sent back to the users in less than 15 minutes, telling them if they’ve been exposed to the virus.

“Our goal is to get a more accurate, comprehensive and faster test out there,” Dr. Zenhausern said. “Testing is extremely important. If we had this kind of device, we would have the capability to test for SARS-COV-2 infection sooner and faster, and we could provide more information moving forward in guiding medical countermeasures for reducing fatalities, better managing health care resources, while bringing people back to safer work environments.”

At present, polymerase chain reaction (PCR) and antibody testing are the two major ways that health care systems are testing for COVID-19, and a majority of tests use the gold standard PCR — which detects genetic information of the virus (the RNA) at high sensitivity with less than 200 copies of the virus in a sample; but PCR can only detect if someone is actively infected with the virus, and cannot detect post exposure to the infection. PCR testing for the virus typically includes a nasal swab, which involves a soft brush going up the nose for a few seconds to collect cells and fluids along the passageway.

Unlike PCR, antibody tests can detect proteins if someone has been previously infected, but recovered from the virus. However, the sensitivity and specificity are limited. The team is using recombinant antigen production technology, which provides a synthetic alternative to the long inoculation of animal models over several months to generate antibodies against the virus. Dr. Zenhausern’s team, comprised of Jerome Lacombe, PhD, and Jian Gu, PhD, partnered with researchers in Geneva who are working to design and validate a pipeline of antibodies against the various proteins of the viral components.

For example, the spike proteins (S) on the surface of the SARS-COV-2, its membrane protein (M), the nucleo-capsid (N) and the envelope (E) proteins. The team also designed smaller antibody fragments or “nanobodies,” which can be very stable and specific. These reagents have been made available as open source for research and the team has already reported in the literature over a dozen antibodies against COVID N, S, E or M proteins. These biomarkers from the different domains of the virus are typically printed into arrays of spots onto the vertical flow assay membrane, so the biological fluid can be flown through the thickness of the paper and provide enhanced limit of detection by more than 100 times over standard lateral flow immunoassay, such as the common tests commercially available for other health conditions.

“Through our device, we are combining the benefit of both platforms by increasing capabilities of looking at a much broader panel of disease signatures while significantly increasing the test sensitivity by orders of magnitude,” Dr. Zenhausern said.

A vertical flow assay test is when the biofluids go toward and through the thickness of the paper, not by capillarity along the length of the test strip. This changes the mechanisms of fluidics and physics, which allows testing to look at multiple biomarkers for a wider range of pathogens, instead of just looking at one target biomarker. “It’s much faster and more sensitive,” Dr. Zenhausern said, “while the volume of the samples can be tuned from a small droplet of blood to a large volume of saliva or urine allowing us to detect low abundance target pathogens without the need for pre-concentrating the specimen prior to run a test.”

Already in Arizona and other parts of the world, scientists have discovered a mutated strain of the coronavirus. Mutations can impact diagnostics, but a unique aspect of this platform is the ability to add or modify biomarkers to the test with a high-quality control and fast turn-around-time for production. As more antibodies against coronavirus are detected and as scientists continue to find mutated strains of the virus, researchers can add these markers to the platform and turn it into a large-scale production in the matter of a few weeks.

According to Dr. Zenhausern, due to the current health crisis, we will need to have rapid testing everywhere that is less invasive and readily deployable at home for more personalized diagnostics.

“Through this technology, we could deliver point of care diagnostics in a parking lot, hospital emergency room, in an outpatient clinic and at a pharmacy, or even at home, that could run the test in several minutes while delivering secure results,” Dr. Zenhausern said.

Dr. Zenhausern hopes that this platform improves diagnostics not only for COVID-19, but for other viruses and conditions. His team is using a similar technology platform to detect pathogens and Tier 1 biothreats in the Armed Forces, and has worked with NASA TRISH to improve diagnostics for radiation exposure in deep space mission to Mars. Any kind of biological signature, this device could potentially detect. Besides diagnostics, there is also significant potential for building viral nanoparticles as future therapeutic treatment and vaccines.

About the College

Founded in 2007, the University of Arizona College of Medicine – Phoenix inspires and trains exemplary physicians, scientists and leaders to optimize health and health care in Arizona and beyond. By cultivating collaborative research locally and globally, the college accelerates discovery in a number of critical areas — including cancer, stroke, traumatic brain injury and cardiovascular disease. Championed as a student-centric campus, the college has graduated 593 physicians, all of whom received exceptional training from nine clinical partners and more than 2,400 diverse faculty members. As the anchor to the Phoenix Biomedical Campus, which is projected to have an economic impact of $3.1 billion by 2025, the college prides itself on engaging with the community, fostering education, inclusion, access and advocacy.