Michel Bergeron, MD, is speaking (with a pleasing French accent) about creating a genomic point-of-care device to detect infectious disease. Step away from the technical details, however—real-time PCR, microfluidics, microfabrication, biosensors, nanotechnology, bioinformatics—and his words could easily fit into a country ballad.
“It takes so long to make something to go fast,” says Dr. Bergeron, professor of microbiology and infectious diseases and founder and director of the Infectious Diseases Research Centre of Laval University, Québec City. And: “It’s complex work to make something be simple.”
He stops short of saying something like, “It took a great big man to make me feel real small.” But you get the idea. Dr. Bergeron’s work is a study in contrasts. He wants to revolutionize the way physicians detect infectious disease, and along the way he and his colleagues at both the university research center and at his company, GenePOC, have faced no shortage of challenges.
In diagnostics, the easy-looking end point is hard to achieve. For Dr. Bergeron, who planned to unveil his latest instrument at the Next Generation Dx Summit, being held Aug. 21–23 in Washington, DC, it’s been a 10-year journey to create a centrifugal disposable device for POC analysis.
This isn’t the first time Dr. Bergeron has carried the standard for DNA-based rapid testing. In the past he and his colleagues at IDI (a company Dr. Bergeron founded and BD eventually purchased) developed a handful of FDA-approved rapid tests for group B Streptococcus, MRSA, and C. difficile, among others. (See “Physician with a vision has his eye on a chip,” CAP TODAY, March 2006.)
Dr. Bergeron has continued to chip away at what he calls the diagnostic cycle. With his latest device, he aims to shorten even more the time between sampling the patient and acting on test results. “This is a pure, practical thing that happens every day,” says Dr. Bergeron. The lag time varies—it can take anywhere from 10 minutes to several hours to get a patient sample to the laboratory, he observes—and “is a major problem for hospitals.” Ideally, he says, “We could have results on the spot.”
His solution is a near-patient, real-time PCR miniaturized device that he says would be easy for almost anyone to operate, whether at bedside, in the ER, or in physicians’ offices. It’s based on a microfluidic system of interconnected reservoirs and channels that allows for sequential analyses. (He’s also working on a miniature microarray device, whose development is further off.)
Dr. Bergeron says the device resembles a compact disc, one that reads DNA instead of music, though he insists there’s nothing retro about the device. “The CD is a concept that’s simple for people to understand,” he says. “But this is a genomic point-of-care device.” Each disc is divided into eight areas—imagine slices of a pie—with each handling one clinical sample. For now, the device can perform up to 96 analyses on eight different samples.
He likes to make another comparison as well, calling the device the “Nespresso of genomics.” Dr. Bergeron is homing in on the coffee capsules and the ease with which they can be inserted into the coffee maker. But they also eliminate the coffee drinker’s ritual of buying and grinding beans and producing a pot of coffee. Dr. Bergeron clearly identifies with this sense of the revolutionary, and the barriers, if not barricades, that need to be overcome to bring about a change in culture.
The first challenge, he says, is creating confidence among a new device’s users. “Are these assays as efficient as culture?” he asks. “That can be solved with good science and comparing the new approach with the standard technique.” Gene- POC plans to start its first preclinical trial this fall, at Laval University. Dr. Bergeron hopes to enroll 500 pregnant women, which should identify 100 to 150 patients who are positive for group B strep, “a model that we know very well.” It’s also an area where there is a great need for a POC test, he says.
The technical challenges have been considerable as well, including that aforementioned goal of simplification. Early on, the goal was to make “the perfect machine,” he recalls, sounding a little like the Steve Jobs of point of care.
It’s one thing to extract DNA for sample preparation, he says. “But then you can say, ‘I want to purify the DNA, make it perfectly clean.’ This is nice for specific analysis in research.” But as their work continued, Dr. Bergeron and his colleagues conceded DNA purity was less crucial for clinical diagnostics. They simply needed to detect DNA that was present. “So we started with a system that was much more complicated than it needed to be. And then we made it less complicated, to operate in the microfluidic system.”
They also revised their notions of sensitivity. Initially they wanted to be able to detect as little as one microbe for all samples. While that might be necessary for blood samples, it’s not needed for respiratory viral infections or urinary tract infections. “But you try to be perfect,” Dr. Bergeron says.
They’ve since backed away from this desire for perfection. But other technical challenges remained. Not only were they trying to devise a new assay, but also a new instrument on which to run the assay. As Dr. Bergeron puts it, “We had to learn the trade as we went along.”
A microfluidic approach requires multiple chemical valves, which meant an immersion in the world of—with a nod to Benjamin Braddock—plastics. “It took us working with world experts in plastics to realize that, in fact, finding the right plastic is not that easy,” Dr. Bergeron says. “But finally we found one.”
Operating, and manufacturing, the valve system has also been extremely complicated. “Nobody had done this before,” he says.
Now that the major technical challenges have been overcome, Dr. Bergeron will begin to pursue the more typical challenges of bringing a new medical device to market. The company will likely meet with the FDA in December or next January to discuss an approval path. He says he’s confident that “things are going to go well.” But truth be told, he rarely, if ever, sounds anything less than confident, almost bordering on effervescent, when he talks about revolutionizing POC diagnostics.
The revolution has been underway since the advent of real-time PCR. Early on in his work, he says, his biggest skeptics were fellow microbiologists, who couldn’t fathom the impact of DNA on clinical diagnostics. Older microbiologists “know what DNA is, of course, but they’ve never played with it.” Younger microbiologists will have no trouble embracing novel applications.
The eventual reach could be huge, he says. “Point of care for infectious disease will be an area of great growth in the future.” The reason is simple: Without rapid tests, physicians must make decisions without needed information in hand. And now, he says, it’s time for the sun to set, if not on the Empire, then on this aspect of empirical medicine.
Karen Titus is CAP TODAY contributing editor and co-managing editor.