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A reliable, painless, affordable and convenient Antigen Rapid Test (ART) kit may soon be in the market, thanks to the combined efforts of experts from the SingHealth Duke-NUS Academic Medical Centre (AMC) and National University of Singapore (NUS). Find out how their collaboration might change the COVID-19 testing game, with long-tail benefits for Medicine of tomorrow.
In the Swiss cheese model, human systems are likened to multiple slices of Swiss cheese. Individual slices may have gaps, but when put together, each slice covers the holes in another, ultimately allowing the stack of cheese to form a strong defence.
In the case of the COVID-19 pandemic, what might these “slices” be? Social distancing measures, vaccinations, treatment and testing, Professor Soo Khee Chee, Benjamin Sheares Professor in Academic Medicine at the SingHealth Duke-NUS Oncology Academic Clinical Programme and a Senior Advisor to Duke-NUS Medical School, shared.
Recognising the need to reinforce each “slice” of our defence, a team of clinician scientists and researchers from Duke-NUS, Singapore General Hospital (SGH), National Cancer Centre Singapore (NCCS) and National University of Singapore (NUS) came together to develop a saliva-based Antigen Rapid Test (ART) kit, dubbed the Parallel Amplified Saliva rapid POint-of-caRe Test (PASPORT).
Having team members hailed from different backgrounds was pivotal at driving the innovation process.
Prof Soo brought a wealth of experience investigating the role of salivary antigens in detecting cancer, while Professor Ooi Eng Eong, Professor from the Duke-NUS Emerging Infections Diseases (EID) programme and Professor Jenny Low, Senior Consultant from SGH’s Department of Infectious Diseases contributed their knowledge and experience in viral disease detection and rapid bench-to-bedside translation of new vaccines and therapeutics.
As ART kits rely on nanoparticles to bind to the virus, Dr Danny Tng, a Medical Officer at SGH and Adjunct Research Fellow from the Duke-NUS EID Programme, and Professor Zhang Yong, from the Department of Biomedical Engineering at NUS, were crucial for their expertise in nanomaterials for viral antigen detection.
Finally, Associate Professor Melvin Chua, Senior Consultant, Division of Radiation Oncology at NCCS, provided his expertise on diagnostic testing and development from his experiences in developing molecular tests for Head and Neck Cancers.
“The success of this multi-institution partnership is yet another example that the combined knowledge and skillsets of six is far better and stronger than one,” Prof Low shared.
She added: “It is with such a collaboration, that we were able to overcome the challenges and rapidly translate our discovery into an intervention which we now hope will benefit society.”
One major breakthrough is how PASPORT has overcome limitations that existing saliva-based ART kits have, and achieved a true positive rate of 97 per cent without the use of fasting saliva —a figure close to the gold standard of Polymerase Chain Reaction (PCR) tests.
The team shared that existing saliva-based ART kits in the market are currently not used in Singapore because results become very inaccurate once a person has consumed food or drinks. This means they are only effective if used early in the morning or after a period of fasting, which is impractical.
To overcome this, the team designed PASPORT to use nanoparticles in two stages. The first stage is similar to regular ARTs: a set of nanoparticles binds to the virus to create the red test line. In the second, additional nanoparticles will bind to the first set, amplifying the “signal”, even if the viral load is low.
Another area PASPORT stands out is in its use of ACE2 proteins to capture the virus.
ACE2 “receptor”, or the angiotensin-converting enzyme 2, is a protein present on the surface of many human cell types. It acts as a doorway for the coronavirus to enter our cells by using its spike protein to bind to ACE2, similar to a lock and key. As the virus evolves over time, it improves its “key” to fit the “lock” better, Prof Ooi explained. By employing ACE2 proteins in the testing, PASPORT therefore becomes even more sensitive to new virus variants, he said.
Case in point: “When the Delta variant first came out, we were cautious, but we proved that our test was just as good for capturing that,” Prof Chua recalled. “We might need to evolve the tests for further versions, but it is unlikely that this will become an issue!”
Convenience, speed and accuracy aside, Prof Soo is quick to add that the PASPORT’s narrative goes far beyond the story of “just another rapid antigen test coming to the market”.
It also a story of collaboration, he said, enthusiastically reminiscing how he met Dr Tng, who is also the lead investigator for PASPORT, back when Dr Tng was still a first-year medical student. Dr Tng’s passion for research stood out and Prof Soo gave him an opportunity to work using saliva antigens to detect tumours—which paved the way for his latest work on PASPORT.
Examples like this are what SingHealth Duke-NUS AMC wants to achieve, Prof Soo said. “We want to get medical graduates and young clinicians excited about research, and to provide them with mentorship from scientists across disciplines, so as to facilitate collaborations, and eventually bring research from bench to bedside,” said Prof Soo.
Even today, the journey of collaboration and discovery continues, and as SingHealth and Duke-NUS have entered into a license agreement with Singapore-based company, Digital Life Line Pte Ltd—with hope that PASPORT will be ready for market within the next three to six months— the SingHealth Duke-NUS AMC team is already hard at work translating the technology for the testing of other infectious diseases.
Dr Tng shared: “We can use this kit for other applications, such as other infectious diseases, oncology—essentially, for any pathology with protein as a marker!”
This perhaps is a silver lining in the pandemic thus far—that in these turbulent times, individuals and organisations alike will stand united to increase our systems of resilience, not just for COVID-19, but for the healthcare of tomorrow.