The D3 Group: A story of innovation
The Disease Diagnostics and Development (D3) Group at The Research Institute of St. Joe’s, led by Dr. David Bulir, has been hard at work developing innovative solutions to the biggest challenges involved in COVID-19 diagnostic testing. Large-scale testing continues to offer the best opportunity of reducing the spread of the virus.
The D3 Group began working on testing solutions in January 2020. Scientists had just published the full genome of the pathogen responsible for COVID-19 – a novel coronavirus called SARS-CoV-2. Dr. David Bulir, a physician and researcher in the D3 Group, began developing a molecular test for this new virus. Knowing that it was likely to mutate as it continued its race across the continents, he designed his molecular test – called an assay – to detect a region of the virus that was believed to be relatively stable.
Just as predicted, SARS-CoV-2 experienced several mutations. Thankfully, Dr. Bulir’s robust assay remained effective in detecting the mutated forms of the virus. The assay was also designed to detect and differentiate between eight other respiratory viruses, including influenza A/B and SARS-CoV-1 (the virus that caused the SARS outbreak of 2003).
Dr. David Bulir works on robotic liquid handling robots to accelerate COVID-19 testing capabilities.
By March 2020, the D3 Group had acquired two high-throughput liquid handling robots, which would be used to increase test processing to thousands of samples per day. These two Hamilton Microlab STAR units enabled Dr. Bulir’s new assay and the D3 Group to begin the next phase of development – sample pooling to further increase testing capacity.
The Hamilton Regional Laboratory Medicine Program (HRLMP) is responsible for processing diagnostic tests for St. Joseph’s Healthcare Hamilton, Hamilton Health Sciences, and other partnering clinics in the Hamilton region. Early on, the HRLMP worked with the D3 Group to implement Dr. Bulir’s assay. By April 2020, the assay was licensed for confirmatory testing, eliminating the need to send positive samples to Hamilton Public Health. Ultimately, this helped to conserve scarce testing supplies.
What is sample pooling?
By combining samples into batches of two, four, or even eight and testing them as a single specimen, sample pooling offers massive increases in throughput since the majority of tests are negative. Any positive batches are re-tested individually to isolate the positive sample.
Just as supplies of personal protective equipment became scarce during the first wave of the virus, so too did the supply of critical laboratory materials as demand for testing skyrocketed. Key producers of specimen swabs, transport materials, and lab reagents were not prepared to meet the needs brought on by a global pandemic, and labs everywhere faced imminent supply chain issues that threatened their ability to sustain long-term testing. Luckily, the D3 Group had been working on solutions to these supply challenges.
In April 2020, the D3 Group was awarded funding from the Juravinski Research Institute. Hamilton philanthropists Margaret and Charles Juravinski announced a new $3.3 million gift to accelerate COVID-19 research in Hamilton.
In Dire Straits
“Never in a million years would I have thought I’d be unable to find swabs,” explains Dr. Bulir. Obtaining common testing supplies presented a major challenge to labs everywhere.
The team began to secure alternative suppliers that would not only allow testing to continue, but to reliably expand to the capacity across the whole province as the virus spread. In a race against time, researchers led a major effort towards supply chain independence. They worked relentlessly to secure a new supplier of flocked swabs, which were validated at St. Joe’s research lab as well as other labs in Ontario for use in COVID-19 diagnostic testing.
But swabs are only one piece of the puzzle. Specimen tubes contain a liquid called the transport medium, which preserves the integrity of the sample. This was another crucial aspect that was in short supply. As demand for commonly used transport media increased, many suppliers were not able to provide while others increased dramatically in price.
“Our most standard transport medium was not available, and the cost of our alternate transport medium increased substantially, so we hastily began searching for a reliable and affordable solution,” says Dr. Bulir. “Ultimately, we decided to develop our own transport medium in our lab, and the McMaster Molecular Medium (MMM) was born.”
Many commonly used transport media do not inactivate the samples, creating an exposure risk for lab technicians who must manually inactivate each sample in a biosafety cabinet before processing them. By design, the MMM inactivates samples in the tube at the point of collection, reducing risk to lab technicians and simplifying and speeding up the testing process. Samples can then be loaded directly onto liquid handling machines for immediate processing.
Through the McMaster Industry Liaison Office, D3 Group partnered with Bay Area Health Trust to license the rights to production and sales of the MMM for research and clinical purposes, ensuring a steady supply would be available.
Specimen tubes containing the newly developed McMaster Molecular Medium are prepared for processing.
Working Day and Night
“All aspects of our existing test processes were disrupted by unprecedented challenges,” explains Dr. Gail Martin, Executive Director of The Research Institute. “We had to work fast to develop innovative solutions designed for deployment in real-world settings. This meant long shifts with few or no days off – but it was work that continues to have a profound effect on our community.”
The D3 Group also worked with an interdisciplinary team of researchers and industry professionals in Ontario to produce required plastic components for the in-lab testing process. The design, fabrication, testing, and scaling of production for these materials usually takes 3 to 4 months. Fortunately, they managed to achieve these goals in only 5 weeks.
The innovative solutions developed by the D3 Group have impacted labs across Ontario, since each solution was designed with the entire province in mind. Even health authorities from outside of Ontario were reaching out to the D3 Group to improve testing in their own jurisdictions.
One prime example of this enormous impact is from Shared Hospital Laboratory (SHL), which had a weeks-long testing backlog affecting six Toronto hospitals. They were receiving specimens in nearly a dozen different types of transport media and tube formats, slowing down the testing process. By September 2020, the number of daily samples arriving at SHL had skyrocketed, and the need to manually inactivate each specimen exacerbated the problem. That’s when, with the help of Dr. Bulir, they switched to the MMM.
“Prior to implementing the MMM, we struggled to complete 3,500 to 4,000 tests per day,” says Dr. Christy Vermeiren, deputy director of SHL. “We rolled out the revamped workflow, eliminated the preprocessing bottleneck, and redeployed staff. The following day we completed just over 5,200 tests and then 6,500 tests the day after that – all with our existing staff complement. It’s a win-win-win.”
SHL managed to clear their backlog within 48 hours of implementing new protocols, which included the MMM as their standardized transport medium.
The D3 Group worked diligently to secure, validate, and translate their solutions to labs across Ontario and beyond.
The solutions developed by the D3 Group have also been used in several clinical research projects. One study, conducted during Ontario’s first wave of the virus, saw researchers partnering with Hamilton’s Shelter Health Network to perform surveillance testing on vulnerable populations. Researchers were able to monitor and help control the spread of COVID-19 among groups of people experiencing homelessness in Hamilton.
In September 2020, a novel pilot study of incoming travellers was conducted in partnership with Air Canada, the Greater Toronto Airports Authority, and McMaster HealthLabs. Researchers performed thousands of COVID-19 tests on incoming international travellers, collecting samples at Pearson Airport. Participants also submitted self-collected samples at 7 and 14 days after their arrival during their mandated quarantine period. The study was later boosted by a $2.5 million grant from Health Canada and the Canadian Institutes of Health Research.
Interim results of this study, released in November 2020, showed that only 1 percent of incoming travellers tested positive for SARS-CoV-2. Of those positive cases, 70 percent were detected during the initial test at the airport. Self-collected samples taken 7 days after arrival found 30 percent of positive cases, and samples taken 14 days after arrival found less than 10 percent of all positive cases.
The Research Institute worked with McMaster HealthLabs to conduct COVID-19 testing on arriving international travellers at Pearson Airport.
With several vaccines now being distributed in Canada and around the world, there is light at the end of the tunnel. Yet fast and accurate COVID-19 testing will remain key to fighting the pandemic, as mass vaccinations will take time. Testing will also remain critical in limiting the size of outbreaks in low-income countries where access to vaccines is delayed or hampered.
By developing critical diagnostic solutions and ensuring Ontario has the supplies it needs to continue testing, the D3 Group is further proof that St. Joe’s conducts research that changes lives.