New COVID-19 Test Distinguishes SARS-CoV-2 From Other Coronaviruses With 100% Accuracy

This point-of-care device uses the physics of fluids to draw a few drops of blood and biomedical lubricant through the components to test for COVID-19 antibodies and biomarkers without the need for electricity. Credit: Jake Heggestad

Platform could also predict severity of COVID-19 cases and immunity to variants.

Duke University biomedical engineers have demonstrated a tablet-sized device that can reliably detect multiple COVID-19 antibodies and biomarkers simultaneously.

Early results show that the test can distinguish with 100% accuracy between antibodies produced in response to SARS-CoV-2 and four other coronaviruses.

The researchers are now investigating whether the easy-to-use, energy-independent point-of-care device could be used to predict the severity of a COVID-19 infection or a person’s immunity to variants of the virus.

Having also recently shown that the same “D4 assay” platform can detect Ebola infections a day earlier than the gold standard polymerase chain reaction (PCR) test, the researchers say the results show how flexible the technology can be to adapt to. adapt to other current or future diseases.

The results were published online in Science Advances on June 25, 2021.

The D4 assay is read by this tablet-sized battery-powered scope, allowing the whole thing to be tossed in a backpack and used at the point of care with minimal resources. Credit: Jake Heggestad

“Development of the D4 test took six years, but when the WHO declared the outbreak a pandemic, we started to compress all that work into a few months so that we could explore how the test could be used as a tool for the public health.” said Ashutosh Chilkoti, the Alan L. Kaganov Distinguished Professor and Chair of Biomedical Engineering at Duke. “Our test is designed to be both adaptable and truly point-of-care, and this is clearly a scenario where portable, rapid and cost-effective diagnosis would be most helpful.”

The technology is based on a polymer brush coating that acts as a kind of non-stick coating to prevent all but the desired biomarkers from adhering to the test slide when wet. The high effectiveness of this non-stick coating makes the D4 assay incredibly sensitive to even low levels of its targets. The approach allows researchers to print different molecular traps on different parts of the slide to capture multiple biomarkers at once.

The current version of the platform also features small, patterned tunnels that use the physics of fluids to pull samples through the channels without the need for electricity. With just a drop of blood and a drop of biomolecular lubricant, the test runs autonomously in a matter of minutes and can be read with a detector about the size of a very thick iPad.

“The detector is battery powered and the test requires no power at all, so you can throw the whole thing in a backpack and really test it at the point-of-care with minimal resources,” said Jason Liu, a PhD student working in the field. Chilkoti lab that designed and built the detector.

In the current study, the researchers tested the D4 assay’s ability to detect and quantify antibodies produced against three parts of the COVID-19 virus — a subunit of the spike protein, a binding domain within the spike protein. protein that attaches to cells, and the nucleocapsid protein that packages the virus’s RNA. The test was able to detect the antibodies in all 31 patients tested with severe cases of COVID-19 after two weeks. It also reported zero false positives in 41 samples taken from healthy people before the pandemic began, as well as 18 samples taken from individuals infected with four other widespread coronaviruses.

With the pandemic slowing in the United States and hundreds of other COVID-19 antibody tests in development, the researchers don’t believe this particular test is likely to be deployed in large numbers. But they say the platform’s proven accuracy and flexibility make it a prime candidate for development into other types of testing or for use in future outbreaks.

For example, the platform could potentially test whether or not people have immunity to the various strains of COVID-19 that continue to emerge.

“There are a lot of questions from people about whether or not they are protected against new variants of COVID-19, and our test could answer some of them,” said Jake Heggestad, a PhD student who works in the Chilkoti lab and developed the chip. before the test. “We believe our platform should be able to distinguish whether people have antibodies that can neutralize emerging variants of concern or whether those antibodies are not protective against new variants.”

The researchers are also developing the platform into a test for multiple prognostic markers of COVID-19 that together could indicate whether a patient is likely to have a severe case of the disease.

“We’re platform builders, so we’re working to show how this technology can be easily adapted to do different things,” said David Kinnamon, a graduate student who developed the liquid handling system for the test. “We show that this single platform can work as a diagnosis, assess the immune response after infection, and predict disease outcome, potentially all at the same time. I don’t know of many tests that can do that.”

“And it can all do this on a platform that is super user-friendly and transportable,” says Heggestad. “It’s one thing to do all this in a centralized facility like Duke, but it’s another to do large-scale testing and get good, sensitive results in remote locations around the world.”

Reference: “Multiplex, Quantitative Serological Profiling of COVID-19 from Blood by a Point-of-Care Assay” by Jacob T. Heggestad, David S. Kinnamon, Lyra B. Olson, Jason Liu, Garrett Kelly, Simone A. Wall , Solomon Oshabaheebwa, Zachary Quinn, Cassio M. Fontes, Daniel Y. Joh, Angus M. Hucknall, Carl Pieper, Jack G. Anderson, Ibtehaj A. Naqvi, Lingye Chen, Loretta G. Que, Thomas Oguin III, Smita K. Nair, Bruce A. Sullenger, Christopher W. Woods, Thomas W. Burke, Gregory D. Sempowski, Bryan D. Kraft, and Ashutosh Chilkoti, June 25, 2021, Science Advances.
DOI: 10.1126/sciadv.abg4901

This research was supported by the National Science Foundation (CBET2029361), the National Cancer Institute (P30-CA014236, R01-CA248491, UH3-CA211232), the Department of Defense (W81XWH-16-C-0219), Defense Academy of the United Kingdom (ACC6010469), and the Combat Casualty Care Research Program (W81XWH-17-2-0045).