Testing method can distinguish severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) types with 100% accuracy and even predict case severity and immunity against variants.
Biomedical engineers at Duke University in the USA have developed a device that detects coronavirus disease (COVID-19) antibodies as well as biomarkers that distinguish between antibodies produced in response to SARS-CoV-2 and four other coronaviruses with complete accuracy.
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A newly adapted platform could be crucial in the fight against SARS-CoV-2 and its variants
The flexible, cost-effective, and accurate "D4 assay" platform has been adapted by scientists at Duke University to help distinguish infection patterns from different variants of SARS-CoV-2.
The "D4 assay" describes a platform for point-of-care clinical diagnosis based on 4 Ds. Specifically, the D4 assay involves four sequential events: (1) Dispense (droplet of blood); (2) Dissolve (printed reagents on chip); (3) Diffuse (across the surface); and (4) Detect (binding event).
The D4 technology uses a polymer brush coating that acts as a sort of non-stick coating to stop anything but the desired biomarkers from attaching to the test slide when wet, providing a highly effective particle filter making the screening process extremely sensitive. Indeed, D4's key antibody (Ab) consists of microarrays that can yield quantitative results with picomolar sensitivity within 30 minutes.
The current version of the platform does not need any electricity to process. With just a drop of blood and biomolecular lubricant, the automatic test runs in a matter of minutes, yielding results that can be read with a detector roughly the size of a very thick iPad.
Recently, the platform has been shown to detect Ebola infections a day earlier than the standard polymerase chain reaction (PCR) test. And now, researchers say the results show how flexible the technology can be to adapt to other current or future diseases, including SARS-CoV-2.
The D4 assay took six years to develop, but when the WHO declared the outbreak a pandemic, we began working to compress all of that work into a few months so we could explore how the test could be used as a public health tool," 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 when a portable, fast and cost-effective diagnostic would be most useful."
The team of researchers got to work to adapt the D4 assay for COVID-19. They showed that the test could distinguish between antibodies produced in response to SARS-CoV-2 and four other coronaviruses with 100% accuracy.
Data was procured on 3 parts of SARS-CoV-2 to test the efficacy of the assay; a subunit of the spike protein, a binding domain within the spike protein and the nucleocapsid protein that packages the virus's RNA.
Results showed that the assay spotted antibodies in all 31 tested patients, reported 41 false positives from healthy individuals and antibodies from 18 samples from individuals infected with 4 other coronaviruses.
A key tool to identify, track, and address the advent of emerging variants
"There's lots of questions from people about whether or not they're protected from new variants of COVID-19, and our test could answer some of those," states Jake Heggestad, a PhD student working in the Chilkoti lab who developed the chip for the test.
We believe that our platform should be able to distinguish between whether people have antibodies that can neutralize emerging variants of concern or if those antibodies aren't going to be protective against new variants," says the team.
Based upon the preliminary findings, researchers are now attempting to determine if this easy-to-use, energy-independent, point-of-care device can be used to predict the severity of a COVID-19 infection or a person's immunity against variants of the virus.
It is clear that adapting assay methods could prove particularly valuable in tracking the emergence of potential variants, particularly in areas of high infection rates.
We're platform builders, so we're working to show ways this technology can be easily modified to do different things," said David Kinnamon, a graduate student, who developed the liquid handling system for the test. "We're showing this single platform can work as a diagnostic, assess 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."
The promising results from the present study offer a new candidate to integrate into widespread testing policies for current and future disease outbreaks, particularly those with high mutation potential or rapid infection. This is particularly true since the D4 assay provides a cost-effective and reliable method that can be made widely available.
Indeed, Heggestad describes the platform as " super user-friendly and transportable," adding. "It's one thing to do all of this in a centralized facility like Duke, but it's another to be able to do large-scale testing and get good, sensitive results in remote locations around the world."
The challenge, therefore, remains as to how best to integrate such testing on larger scales.
- Multiplexed, Quantitative Serological Profiling of COVID-19 from Blood by a Point-Of-Care Test," 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, Ashutosh Chilkoti. Science Advances, June 25, 2021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654894/.