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U of Montreal Team Develops Fast Electrochemical Sensor for Multiplexed Protein Marker Detection

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NEW YORK (GenomeWeb) — Researchers from the University of Montreal have developed a DNA-based electrochemical sensor that can detect the presence of multiple protein markers in whole blood in less than 10 minutes. 

The sensor could serve as the basis of a point-of-care device to diagnose a range of diseases and conditions including cancer, allergies, autoimmune diseases, and sexually transmitted diseases, according to its inventors. 

The technology, described in a paper published earlier this month in the Journal of the American Chemical Society, is based on a steric hindrance mechanism featuring a redox-labeled signaling DNA strand and a gold electrode that contains the complementary "capturing" DNA sequence at high surface density. Once the two strands bond, the signaling strands generate a large electrochemical signal by bringing the redox labels close to the electrode surface. Steric hindrance prevents too many copies of this strand from hitting the surface and makes for a quick read of the results.

The researchers tested for two proteins — an antibody and streptavidin —  and designed two 16-base signaling strands labeled at the 3' end with methylene blue and at the 5' end with the small hapten digoxigenin or biotin, which were recognized by the anti-digoxigenin 13 and streptavidin, respectively. They then immobilized the complementary 16-base DNA capturing strand to a gold electrode at high surface coverage. 

Alexis Vallée-Bélisle, professor in the department of chemistry at the University of Montreal and corresponding author on the study, said he and his colleagues began work on this electrochemistry sensor to try to solve a problem that they’d been seeing when trying to detect antibodies in whole blood. "We noticed that the proteins were running into each other," he said. So they found a way to limit the number of proteins that made it on the sensor surface using steric hindrance. 

The researchers were able to show that their electrochemical sensor enabled the one-step detection of four different macromolecules directly in whole blood quickly (in less than 10 minutes) and with sensitivity to low-nano molecular concentrations. They also noted in the paper that their results suggest the sensor could be adapted to support the use of peptides and other small ligands as recognition elements, and may enable multiplexed detection of numerous target proteins simultaneously in a sample due to the unique ability of DNA to create numerous specific capturing-signaling pairs. 

Vallée-Bélisle told GenomeWeb that the sensor has commercialization potential, but it's not the only electrochemical diagnostic test out there. One of the most common ones is the dipstick test, such as the ones used for pregnancy tests or HIV diagnosis.  "Actually, in the US, they have been approved for HIV testing," he said. "They work pretty well in five minutes." 

The catch with these tests is that although they are fast and inexpensive, they are only able to test for one antibody. "They are hardly multi-flexible," said Vallée-Bélisle. "They are just qualitative. They will tell you yes or no, but there is no gradation of how much of the disease you have." In their paper the researchers noted several quantitative methods, including enzyme-linked immunosorbent assays, Western blots, and polarization assays, but they are multi-step, wash- and reagent-intensive processes that necessitate specialized technicians and require several hours before completion.

The electrochemical sensor, on the other hand, has the potential to quickly detect many different antibodies at once.

The major limitation of the test is the current dominance in diagnostic testing of using a complete virus to test for disease. The design of the test doesn't really work well for this and instead is better designed to work smaller pieces of a virus.  Vallée-Bélisle said there is a lot of literature about such an approach, but it hasn't yet shifted into general practice. 

The other difficulty for commercializing the product lies in finding the best niche for it, Vallée-Bélisle said. "The emergency room would be one of these," he noted. "They have five minutes to make these decisions [about treatment]." The ability to take a drop of blood and provide a diagnosis that can better inform treatment decisions would have a big impact, he said. 

He also sees potential in the field of personalized medicine, specifically for determining drug dosages for every individual. Currently, healthcare providers "take the weight of the individual [to calculate dosages] but everyone degrades the drug at a different rate," said Vallée-Bélisle. To have the ability to check for concentration and toxicity while taking a new medication would greatly improve its efficacy and safety for patients, he said. This would be especially true if it could be used as a tool that would allow patients to test their blood concentrations at home, not unlike the tests diabetics use to test their glucose levels. 

Univalor, a university technology transfer organization and commercial partner of the University of Montreal, supports the project and has filed a patent application to protect the technology. Patricia Escoffier, project manager at Univalor, said in a statement, "We are convinced that this rapid and easily multiplexed biosensor could significantly improve patient's health by providing new point-of-care diagnostics for a wide variety of diseases." However, Vallée-Bélisle indicated that the group is still looking for industrial partners to commercialize the technology. 

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