Canadian team’s sepsis-testing device shows promise in fight against one of the world’s most common killers | Canada Voices

In February, 2023, a Toronto man woke up feeling sick. Within hours, he was in the emergency room, where his lips and fingertips started turning blue. Blood samples were drawn and sent to the lab, and the patient was transferred to intensive care.

By the end of the day, he was dead. He was only 22. “It was so fast,” says Claudia dos Santos, a physician-scientist with Unity Health Toronto’s St. Michael’s Hospital, who treated the patient.

“We got the bloodwork two days later.”

Her patient had pneumonia but died of sepsis, a dangerous condition where the immune system has an extreme reaction to an infection and starts attacking the body’s tissues and organs. Sepsis can kill fast – every hour of delayed treatment increases mortality risk by nearly 8 per cent – but doctors still don’t have good tools for quickly and accurately predicting which patients will develop the life-threatening condition.

This paradox spurred Dr. dos Santos to pull together a team of researchers from across Canada to develop a new molecular-based blood test for predicting sepsis risk with high accuracy – one that can be used with a “lab on a chip” device that spits out results within just three hours.

On Tuesday, the promising results of this collaboration were published in the journal Nature Communications. If the test can be validated by future clinical trials – and eventually made accessible in all resource settings – this new tool could prove “transformative,” says Tex Kissoon, a professor of pediatrics at the University of British Columbia and president of the Global Sepsis Alliance.

“It would be a big deal, there’s no doubt about it,” says Dr. Kissoon, who was not involved with the study. “Our goal has always been to get personalized treatment, and I think that this is where this [new diagnostic test] would be heading to.”

Sepsis causes an estimated 11 million deaths every year, accounting for 20 per cent of global deaths, according to the World Health Organization. In Dr. dos Santos’s downtown Toronto hospital, she sees maybe five or six cases a week, affecting patients with everything from trauma to cancer.

“It is one of the most common things we see, and probably the top reason for ICU admission,” she says.

Part of what makes sepsis so tricky to diagnose and treat is that it’s largely dependent on a person’s unique immune system and how it reacts to infection. The current diagnostic “gold standard” is identifying the pathogen through blood culture, Dr. dos Santos says.

But results are time-consuming and often fail to identify the culprit, according to Dr. Bob Hancock, the UBC Killam Professor of Microbiology and Immunology. He says that most of the currently available diagnostics, like clinical scoring systems, are only accurate about 50 per cent of the time in early-stage sepsis patients. “It’s like a coin flip.”

Dr. dos Santos wanted better. In 2017, she was talking to John Marshall, a University of Toronto professor of surgery and Canadian “luminary” in the field of sepsis, who mentioned a researcher he had recently met.

He was Teodor Veres, a director of research and development with the National Research Council Canada and co-director of the Centre for Research and Applications in Fluidic Technologies (CRAFT).

At the time, Dr. dos Santos had identified some sepsis “biomarkers” – molecules or other characteristics that can be measured to indicate the presence of a condition or disease. But her biomarkers were nucleic acids, which can take up to a day to detect using a common laboratory technique called PCR, she says.

Dr. dos Santos told Dr. Veres that she wanted something faster. “He said to me, ‘I have the technology,’ and that was the PowerBlade.”

The PowerBlade is an instrument that uses microfluidics – a “lab on a chip” technology where miniaturized devices control the movement of fluids.

For diagnosing a condition like sepsis, the PowerBlade can automate laboratory techniques like PCR. Using pressure and centrifugal force (imagine a salad spinner), the PowerBlade can move a drop of blood through a series of tiny tunnels and chambers on a credit card-sized “chip,” where the blood sample is passed through chemicals that extract and amplify nucleic acids like RNA.

Around the time she met Dr. Veres, Dr. dos Santos was also introduced by a colleague to Dr. Hancock. She told him she had found some interesting biomarkers for sepsis. He responded genially that he did, too – only his were better.

Thus began the trio’s cross-country research collaboration. Using machine learning, Dr. Hancock and his team analyzed blood samples from 586 patients to identify a six-gene expression “signature” that flags patients at risk of developing sepsis within 24 hours of clinical presentation. The signature, dubbed “Sepset,” was further validated using data from another 3,178 patients.

“What we’re offering is a way of taking a drop of blood, putting it into a machine, and the machine basically … spits out a recommendation,” says Dr. Hancock, who is also CEO of the company Sepset Biosciences, which is now developing the gene signature test. “This person is 90-per-cent likely to have sepsis, or this patient is 90-per-cent likely not to have sepsis.”

According to their new paper, Sepset was 94-per-cent accurate when tested using the RT-PCR lab technique. With the PowerBlade platform, it was 92 per cent accurate.

Much work lies ahead, including testing and evaluating the prototype in real-world settings. But for Dr. dos Santos, the results of this research collaboration are just the latest step toward finally improving outcomes in sepsis, a condition that has long been under-recognized despite its staggering toll.

“Hopefully, what happened to that patient [from 2023] is a thing of the past and we’re facing a future of hope,” she says. “I think this is a small step in the right direction.”