SynbiCITE’s London BioFoundry acts on the WHO recommendation of ‘Test, Test, Test’ to show how throughput can be significantly increased.

Re-thinking the approach to COVID-19 testing

As lock-down around the world continues and the brightest and best biologists and clinicians accelerate efforts to develop a vaccine against the virus, immediate solutions are needed to slow its spread. 

While testing targets are still unmet and scaling up has proved to be very slow, identifying and tracking the spread of virus is a critical factor in efforts to slow the outbreak and potentially lessen its impact. The London BioFoundry, part of SynbiCITE, the UK Innovation and Knowledge Centre for synthetic biology, has demonstrated a new approach by adapting two robotic modules to provide additional testing capacity of up to 4000 COVID-19 tests per day.

Synthetic biology workflows drive higher throughput testing

The approach, led by SynbiCITE co-Director Professor Paul Freemont, originates from the flexible and adaptable nature of automated synthetic biology workflows. Using the ‘design, build, test, learn’ approach that is fundamental to synthetic biology, Professor Freemont and a team from the Dementia Research Institute and Imperial College London, used the London BioFoundry’s Felix robots to design new workflows to carry out COVID-19 virus testing using the standard PCR.

The modular nature of the workflow means that it can be easily scaled up – just one end-to-end assay platform would allow 2000 tests to be run in a 24-hour period. Applying this reconfiguration to additional robotic platforms would further increase capacity and could help regional hospitals and community health services access testing and receive rapid results. The two modules occupy just 2.4m of bench space each and can be operated by one person – making social distancing entirely viable. In addition, the generic robotic technology means that, unlike existing hospital laboratory systems, any reagents can be used, and it is not dependent on a single supplier.

The platform has been validated in just two weeks and has been up and running testing patient samples at, St Mary’s hospital with a second platform at Charing Cross hospital coming on line shortly.

Design, build, test, learn

To build and test, Paul Freemont and team engineered synthetic virus-like particles (sVLPs) to be employed as a SARS-CoV-2 surrogate in diagnostic workflow development and validation.  These consist of a capsid from an E. coli virus, the MS2 bacteriophage, which carries a small section of the SARS-CoV-2 RNA genome. 

Such sVLPs have previously been successfully employed as a diagnostic reference tool for the detection of respiratory viruses such as Influenza A and B as well as SARS-CoV, a close relative of the current SARS-CoV-2 virus. 

After in-house production, the team quantified these particles which allowed them to simulate viral load levels commonly seen in patient samples. 

The team then used its new SARS-CoV-2 sVLPs to test the efficiency of different methods of genome extraction, which is typically the first step in diagnostic testing.  Importantly, the RNA sequence carried inside the sVLPs is complimentary to target probes designed for the detection of the viral genome, therefore the sVLPs can be used for testing the sensitivity of various detection probes and manufacturer kits used for quantitative PCR , which is the second step of the gold standard diagnostic test currently employed for CoV-2 detection. 

“The ability to quickly and safely prototype SARS-CoV-2 diagnostic strategies with the sVLPs allowed us to develop complete automated workflows that were ready for rapid deployment to support patient sample testing in various clinical settings” said Professor Freemont.

We were able to validate the whole process from receipt of clinical samples in their containment facility to the final virus ‘detected’ or ‘not detected’ result both accurately and consistently. The approach can be very easily applied to other platforms meaning it can be quickly scaled up to help regional hospitals and possibly care homes meet daily testing demands.”

Currently, less than 50,000 daily tests for coronavirus are being carried out in the UK, with the government target set at 100,000 per day. The deadline for achieving this is fast approaching. While the government designated super labs have the capacity for ultra-high throughput screening, there is no doubt that local, regionalised testing is a solution that could be readily made available to help carry out the volume of testing that is urgently needed if we hope to see the sign of lock-down being eased soon.—16-march-2020

BBC recorded WHO speech footage:

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