REPURPOSING TECHNOLOGY: WHEN EXPLOSIVE DETECTION MORPHS INTO VIRUS DETECTION

REPURPOSING TECHNOLOGY: WHEN EXPLOSIVE DETECTION MORPHS INTO VIRUS DETECTION

The current coronavirus epidemic has changed the way in which we live our lives, but it has also provided us with an opportunity to innovate. Manufacturing plants around the globe are reinventing themselves, and their production lines have been adapted to assemble goods their workforces could not have imagined producing six months ago. Ventilators for intensive care units, personal protective equipment (PPE) for hospitals and frontline personnel, and hand sanitiser quickly became the orders of the day. And industry responded. In Japan, electronics firm Sharp commenced production of face masks; in Wales, Penderyn switched from distilling award-winning whisky to churning out 10,000 litres per week of hand sanitiser of 80% alcohol strength; and Formula 1 motor racing teams – Mercedes, McLaren, Red Bull and Williams – all transitioned from manufacturing automotive parts to ventilators.

As the aviation industry attempts to recover, it too must think outside the box. And, with the assistance of academia and manufacturers, it can. Explosive trace detection technology can, for example, just as easily morph into virus detection technology. Both require samples – the former usually obtained by a swab, the latter by either a swab or, as with a breathalyser, capturing a sample of a passenger’s breath – but the analytical process can, with some modification, detect either. In Australia, the University of Tasmania has been at the forefront of research into explosive detection solutions, especially with regard to the identification of homemade explosives that most technologies fail to recognise. Over the last few months, the UTas team has turned its attention to the detection of bio threats and is already working on the production of a commercially viable solution that could be deployed in airports.

Prof. Michael Breadmore leads the team in Hobart and explains how the transition can be achieved.

Whilst trace virus detection technology development is still a work in progress, the successful repurposing of technology has already been demonstrated by Penderyn, in Wales, who switched from distilling award-winning whisky to churning out 10,000 litres per week of hand sanitiser of 80% alcohol strength. (Credit: Penderyn Distillery)
Whilst trace virus detection technology development is still a work in progress, the successful repurposing of technology has already been demonstrated by Penderyn, in Wales, who switched from distilling award-winning whisky to churning out 10,000 litres per week of hand sanitiser of 80% alcohol strength. (Credit: Penderyn Distillery)

It has only taken a few months since the first outbreak of COVID-19 in China for the global aviation industry to be brought to its knees. Countries shut down their borders to international travellers and ceased domestic travel in an effort to minimise the spread of the virus and to protect their healthcare systems. The only incident that has so dramatically impacted the industry – although perhaps not as significantly – were the attacks of 11th September, now almost 20 years ago. After that, the U.S. and the rest of the world have successfully managed to defend their borders and people from many other terrorist attacks. Much of the credit goes to the technological repurposing of established detection systems in other markets, and the expertise of many government-backed commercial enterprises in applying other technologies to the problem at hand; for example, the repurposing of healthcare imaging systems for the application of baggage screening.

Prof. Michael Breadmore (centre) and University of Tasmania PhD students,  Mostafa Adel Atia Abuzeid (left) and Pavan Kumar Chadalawada,  developing the trace virus detection technology  (Credit: University of Tasmania)
Prof. Michael Breadmore (centre) and University of Tasmania PhD students,
Mostafa Adel Atia Abuzeid (left) and Pavan Kumar Chadalawada,
developing the trace virus detection technology
(Credit: University of Tasmania)

Today, in the midst of a pandemic, the enemy is an invisible bio-threat, and as the world continues to battle COVID-19, global citizens are imagining with trepidation what life will be like once their countries and the rest of the world has reopened. Countries with a few isolated cases of coronavirus, such as Australia, New Zealand, and Taiwan, must grapple with how to safely reopen their borders. Meanwhile, other countries around the world are still either seeing daily increases in infection, e.g. Brazil (at the time of writing) or infection rates decreasing but the numbers of those carrying the virus threatening a ‘second wave’ (e.g. UK at the time of writing). Social distancing and extensive sanitisation have become the norm for minimising transmission, but there is no true way to measure their impact other than to watch the rates of infection, which take several days to weeks to register. The next round of COVID-19 legislation includes, not only increased funding for individual testing, but also the funding of new programmes for viral trace detection technology and environmental screening. The combination and triangulation of contact tracing, human testing and environmental testing will be essential to enable a swift response to outbreaks of this and any future viruses and pandemics.

“…asymptomatic carriers, or ‘Typhoid Marys’, can shed significant amounts of virus, unwittingly contaminating the areas that they come into contact with…”

Unlike 9/11, the implementation of testing is not restricted to the aviation checkpoint. It is detection capability that needs to be implemented everywhere for everyone; from the local restauranteur keen to establish the cleanliness of their dining room through to the health of their staff, all the way to, in the aviation arena, the airport operators, airlines, security personnel and travelling public. The virus is also spread in a number of ways. According to a recent study from the National Institute of Health (NIH) and the Centre for Disease Control (CDC) in the United States, the virus is detectable in the air as droplets for up to three hours, and up to four hours on copper, up to 24 hours on cardboard, and up to two to three days on plastic and stainless steel. We all want and need to feel secure that our environment, the people around us and the activity of travelling are safe and monitored as such.

Robert Redfield, director of the CDC, warned that a second and third wave of COVID-19 will be more dangerous because it is likely to coincide with the start of flu season in the northern hemisphere. Iran is already in the midst of its second wave, and international experts already suggest that this pandemic could last 18-24 months with repeated flare-ups as the northern and southern hemispheres transit through their winter and summer seasons globally. The key to opening the global economy again is air travel, but this will only be possible when we can mitigate the risk of further transmissions. Technology implementation and stringent identification and containment of this and future viruses in the aviation environment are key. After all, this is the predominant means by which the pandemic spread so efficiently from the end of 2019 until global borders were closed.

In an airport environment, trace virus detection in combination with other embedded detection and cleaning systems, will be able to reassure global citizens that they are safe, that the areas they interact with are clean and that the risk of transmission through surface and human contact is minimised. The implementation of these technologies in combination with contact tracing and testing will also allow the government to identify new outbreaks at checkpoints and transmission by travellers through border crossings; a challenge that needs to be closely managed and monitored to allow international travel to begin safely again.

This invisible attacker is difficult to detect and is continuing to mutate as scientists’ race to find a vaccine. To fight this and any future viruses, we must treat it as a biothreat – a national security threat – and attack it from every angle. It is critical that governments around the globe capitalise on innovative solutions to find the virus and eliminate it. Funding is needed to make sure every city, school, hospital, military base, grocery store, restaurant, airport, mall, or commercial enterprise can detect the presence of the virus. The inability to detect the virus will keep global citizens at home and employees furloughed waiting to return to work. As the pandemic temporarily plateaus, virus detection and environmental screening can lead the effort to prove cleanliness in public and private sector venues, enabling society to resume daily functions and repair the international economy by encouraging global air travel again.

State of Play

Aside from a 14-day enforced isolation, the most widespread approach employed to minimise transmission of COVID-19 (and other infectious diseases) has been to monitor the temperature of every person. This has been used routinely throughout Asia for many years, despite the debate surrounding the effectiveness of this approach given the prevalence of asymptomatic carriers. There are also fieldable COVID-19 tests available, many of which rely on non-reproducible, and often quite uncomfortable or invasive, sample collection and therefore present higher than expected false alarm rates. This in turn can provide misleading results and a false sense of security for those that have tested negative. In many cases, the asymptomatic carriers present in exactly this way. These tests can be effective, but they miss the critical exposure route of environmental surfaces. Recent studies published by the CDC demonstrate that these asymptomatic carriers, or ‘Typhoid Marys’, can shed significant amounts of virus, unwittingly contaminating the areas that they come into contact with. Whilst the primary means of transmission is through air droplets, it is known that transmission via surfaces is also possible and therefore a huge risk to the travelling public.

“…the gold standard for virus detection is by quantitative polymerase chain reaction (qPCR)…”

To date, there is still no way to detect and verify the absence or presence of SARS-CoV-2 (the strain of coronavirus causing COVID-19) on surfaces in the field. The NIH determined that most secondary cases of the virus transmission of SARS-CoV-2 are occurring in community settings that are not cleaned to the same rigorous protocol as healthcare settings. The virus lives on surfaces and continues to infect for quite a while. With the world recently reaching its 9.5 millionth case of COVID-19, the inability to reliably test humans and certify the lack of the presence of the SARS-CoV-2 will continue to have a serious economic impact on the world, immobilising a fearful population for the foreseeable future. It is critical to have a tool to analyse surface contamination in order to help stop the spread of the virus.

Mostafa Adel Atia Abuzeid (left) and Pavan Kumar Chadalawada working in the laboratory  at University of Tasmania (Credit: University of Tasmania)
Mostafa Adel Atia Abuzeid (left) and Pavan Kumar Chadalawada working in the laboratory
at University of Tasmania (Credit: University of Tasmania)

Virus Detection Background

The gold standard for virus detection is by quantitative polymerase chain reaction (qPCR). This requires collection of the sample, lysis (disintegration of virus structure) of the biological material, followed by rapid temperature cycles that doubles the template nucleic acids every cycle to produce a measurable fluorescent signal. Most qPCR assays take a minimum of 20 to 30 minutes to complete for a positive, and longer to confirm a negative response. This timeframe is incompatible with screening, and any attempt to make it quicker often leads to an increase in false positives. Enzyme-linked immunosorbent assays (ELISA) that target proteins are an alternative approach that can be quicker (potentially within five minutes, only requiring a single thermal incubation) but typically suffer from very high false alarms due to non-specific binding of the probe, and cannot match the sensitivity of qPCR.

There is currently no established way to detect viruses in an operationally suitable timeframe for high throughput screening, and new approaches must be developed to address this problem. But we do not have a blank canvas and cannot start from scratch. The timeframe to develop an entirely new technology is usually, at best, several years, and the world currently does not have that long unless a suitable vaccine can be developed. The best approach will be to repurpose existing screening technology to make it suitable for virus detection.

So, what are the options currently available? Well, unfortunately there are not many that are suitable. Most of the technology has been developed around explosives and narcotics detection, using ion mobility spectrometry (IMS), gas chromatography (GC) or spectroscopy (such as Raman or IR). IMS and GC (and GC-MS) require the targets to be volatile – which viruses are not – while Raman and IR do not have sufficient sensitivity or specificity for trace detection. We are not new to dealing with this problem as it is exactly the same one that we solved nearly 15 years ago when we began developing ways to rapidly detect the ingredients that make inorganic explosives. Our solution, at the University of Tasmania (UTas), was to use a different technology base – that of capillary zone electrophoresis.

“…capillary zone electrophoresis (CZE) separates molecules in a liquid by application of a high voltage, and is ideal for the detection of homemade explosives…”

Capillary zone electrophoresis (CZE) separates molecules in a liquid by application of a high voltage, and is ideal for the detection of homemade explosives. It is also an established method for biomolecule analysis, having been initially used to sequence the human genome, and has shown great potential for the detection of complex biological assemblies. The presence of distinctive surface charges and zeta potential allows for the separation of native virus and sub-viral particles, first demonstrated in the 60s for poliovirus. This remained unseen until 1987 when Hjerten et al. demonstrated CZE of the tobacco mosaic virus (which infects plants). Since then, there have been numerous reports on CZE analysis of viruses. There are over a dozen articles by the Institute of Analytical Chemistry, University of Vienna on employment of CZE for analysis and characterisation of viruses, including human rhinovirus type 2 (HRV2), the predominant cause of the common cold. From the Department of Chemistry, University of Ottawa, Canada, CZE is being used for quantification of viruses, which is of critical significance in clinical diagnostics, vaccine development, and environmental contamination assays. This group proposed a cost-effective, robust approach based on CZE for the characterisation and sensitive quantification of intact viruses.

CZE is therefore suitable for virus detection. The question is whether we can again reduce a 30-minute analysis to a single minute in a system that can be operated by an untrained user – which is exactly what the now commercially available product (the GreyScan ETD-100™) that resulted from our CZE work at UTas does for homemade explosives detection.

The TVD-1 Under Development – Aviation Application

Like the explosive detection system (ETD 100TM), what we are currently calling TVD-1 (trace virus detection) will have the performance capability of a laboratory CZE system. It is being designed to be field operational, with the analysis time compressed to a few minutes. The ETD-100™ has been designed for continuous throughput of samples, with low cost consumables, and high degrees of maintainability and robustness being key features of the system. The system is an environmentally and health conscious solution for trace detection with no radioactive components or toxic reagents. The demonstration of virus separation by CZE gives immense confidence that we can design a virus detector that incorporates all these features with appropriate methods development and an ability to be integrated into the current explosives detection platform.

“…we will be able to collect breath samples through a ‘breathalyser’, thus agents can even monitor travellers as they check-in to provide a rapid and non-intrusive means of testing the travelling public…”

breathalyser

The TVD-1 will be transportable, set up and operational within five minutes. It can be used at checkpoints, as a pre-checkpoint screening tool or as an on-demand check in any area that requires testing after cleaning (to demonstrate the absence of a biothreat), or in a suspected outbreak zone. It will look and operate like the current fleet of ETDs that can be found at an airport checkpoint, with red screen and green screen alarms to enable easy-to-use operation and, to that end, will have similar operational commands to ETDs.

Agents from all key stakeholders within the aviation environment would be able to test the areas around them and the people passing through them. This is a critical step in ensuring that the cleaning protocols implemented are effective. This not only builds public confidence in flying again but also prevents the unwitting spread of the disease. All areas within the aviation environment can be tested – from check-in, through the security checkpoint, to the plane itself, the people, food, drinks, goods. Anything that is designated as clean and sterile and free of virus should be able to travel, thereby reducing the risk of transmission. Through clever engineering, we will be able to collect breath samples through a ‘breathalyser’, thus agents can even monitor travellers as they check in to provide a rapid and non-intrusive means of testing the travelling public.

Finally, as international leaders begin to travel again, biological warfare through viral infection is now a real threat to security, and an extra layer of prevention must be instituted. Given that the current strain of COVID-19 can remain on surfaces for an extended period of time, it will become increasingly important to clean-sweep areas for viruses, just as is done for potential explosives traces at the aviation checkpoint. Eventually, proof of cleanliness in venues like airports (high traffic areas, baggage and screening areas, airplanes) and other modes of surface transportation, port authorities, or other mass transit facilities will be necessary. It will be a critical step in protecting security screening agents, surface transportation operators and local, state and federal security partners, and enabling society to return to daily functions, repairing the global economy.

Through the development of a trace virus detector we will enable the public to feel safe again and be able to return to their normal routines. It is critical to be able to demonstrate that cleaning or decontamination protocols have been followed and to encourage trust back into society. This approach to screening and the awareness of capability gap fulfilment will allow the general public to feel safe in environments not under their own control. This will be a critical step in creating confidence in the environment to enable people to assume societal norms, reducing the economic impact of the pandemic.

Members of  Indonesian Police Force and Special Forces during demonstration of GreyScan ETD system prior to 2018 G20 summit  (Credit: GreyScan)
Members of Indonesian Police Force and Special Forces during demonstration of GreyScan ETD system prior to 2018 G20 summit
(Credit: GreyScan)

Michael Breadmore

Prof. Michael Breadmore is Professor of the School of Chemistry at the University of Tasmania in Hobart, Australia. He is also a member of the editorial advisory board of Aviation Security International. In 2019, Breadmore, and his team at UTas, were awarded the Eureka Prize in the category of ‘Outstanding Science in Safeguarding Australia’ – a prestigious national science award – for their work in the detection of homemade explosives.