A simple and fast chemical process developed by scientists in Montreal could allow family doctors to one day use equipment as straightforward and cheap as a diabetic's blood sugar tests to diagnose a range of diseases in minutes from their offices, instead of waiting days for results to come back from a lab.
In the biosensor developed by Montreal researchers, if an an antibody or other protein (green or red) is present, it binds to a DNA strand (green and red spirals), affecting how it then pairs up with its complementary strand on the surface of a gold electrode. A decrease in electrical current results. (Ryan & Peter Allen/University of Montreal)
In a paper in yesterday's issue of the Journal of the American Chemical Society, researchers from the University of Montreal describe a novel way to detect large molecules like antibodies in blood using a quick, one-step process involving electricity and DNA.
The technique could give rise to a proliferation of new so-called point-of-care medical tests — blood tests that can be performed in the field, possibly even by patients themselves, and that yield results in minutes.
"Nowadays if you go see a physician to have a blood test, they'll send you to a clinic. A couple vials of blood will have to be analyzed by a technician with specialized techniques, and the results will only come back a week later," said paper co-author Alexis Vallée-Belisle, a University of Montreal chemistry professor and the Canada Research Chair in bioengineering and bio-nanotechnology.
"What these tests are looking for is antibodies — proteins that are generated by the body in response to viruses or bacteria. The highlight of the technique we developed is you put a drop of blood on our electrodes, and in five or 10 minutes you can know if you have the antibody. And in principle, you can detect any antibody you want."
Vallée-Belisle and his team, working with a chemist from the University of Rome, came up with a way to detect antibodies by having them bind to loose, single strands of DNA. Those single strands then attempt to pair up with nearby complementary strands to form the characteristic DNA double helix.
The researchers designed the single DNA strands so that if no antibodies are present when they bind with their complementary pairs, detectable electrical current flows. But if antibodies are present and attached to the loose strands, the current drops. The drop is so precisely measurable that the test can even be used to determine how much antibody is in a sample, instead of simply indicating its presence or absence.
They call the process "electrochemical steric-hindrance hybridization assay," or eSHHA, because it takes advantage of how the DNA molecules react in the presence of other larger particles, an effect known as "steric hindrance."
Biochemistry professor Kevin Plaxco of the University of California at Santa Barbara, who supervised Vallée-Belisle's previous postdoctoral work and who is himself an expert in electrochemical methods to detect antibodies, called the results "clever" and "very simple and elegant."
"They're detecting the molecules in a way that has some rather interesting advantages," he said Thursday.
There are currently point-of-care antibody tests on the market for diagnosing HIV within minutes, Plaxco pointed out, but they give qualitative yes-or-no results and not nuanced, quantifiable data on how much antibody was found.
That might not be needed for HIV, but it could be useful for doctors treating autoimmune diseases, or for using the eSHHA technique to detect things like how much of a chemotherapy drug a patient is metabolizing so that their dose can be fine-tuned.
STD screening in minutes
The Montreal researchers' method would also allow for simultaneous testing for the presence of more than a dozen different antibodies, meaning one small drop of blood and one quick test would be enough to screen for almost every sexually transmitted disease within minutes, at a doctor's office.
The doctor could then immediately notify the patient and prescribe medication right away if any of the results came back positive.
"Currently a large percentage of people don't come back to see the results, because you need to take another appointment, so you waste a lot of time and a lot of money," Vallée-Bellisle said.
He said so far, his team has shown their method works to detect five different typical "model" proteins and will soon publish research showing they can also detect three of the various HIV antibodies. After that, they're also aiming to detect antibodies for syphilis and herpes.
One of the big advantages of their method is its cost: The electrodes used to detect the electrical current can be had for five to 10 cents each and creating the necessary DNA sequences can be as cheap as $10 for a large enough strand to run "thousands of tests," Vallée-Bellisle said.
"The basic infrastructure for all this is dirt cheap," Plaxco confirmed.
Vallée-Bellisle said the next step in commercializing their findings will be signing up a business partner to work on developing the right niche for their work.
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