Just two small purple dots: Canadian paper innovation holds promise for improved global health safety.

They were just two small purple dots, but their appearance on a cardboard dipstick at a demonstration in Ottawa in May 2007 signified a promising new avenue for Canadian scientific research. The demonstration showed the viability of bioactive paper--paper that can be treated to react physically to pathogens in the air, in water, or food, and either detect, deactivate, or destroy them.

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Bioactive paper has many potential uses. It could be made into food packaging that changes colour when it detects salmonella. Or face masks that let frontline medical personnel see immediately whether they have come into contact with a dangerous virus. Or swabs that tell a consumer at a glance whether a fruit or vegetable has been sprayed with a banned pesticide.

At a time when the safety of the food supply is under increasing scrutiny, when memories of the deadly E. coli health crisis in Walkerton, ON, are still fresh, and when fears of bioterrorism or a flu pandemic are ever-present, this made-in-Canada technology holds promise as a safe, inexpensive, and easy-to-use public health tool that can improve the lives of people around the world. It also offers potential economic benefits by creating new value-added products for one of the country's key employment sectors--the Canadian pulp and paper industry.

The search for bioactive paper is being led by the Sentinel Bioactive Paper Network, a consortium made up of researchers from 11 Canadian universities, nine industry partners, and federal and provincial government agencies.

Sentinel's goal is the development as soon as possible of paper-based products containing biologically active chemicals that will ultimately protect against food-, water-, and airborne illnesses. These illnesses strike millions of people around the world each year.

"We want something that's going to become as prevalent as the bar code on packaging," said Robert Pelton, MCIC, Sentinel's scientific director and a professor of chemical engineering at McMaster University.

Sentinel grew out of the SARS epidemic that hit Canada in 2003. As the epidemic was winding down, Pelton, a specialist in pulp and paper research, began talking to colleagues about what could be done to deal with future health threats. The network was created two years later by Pelton, T. G. M. van de Ven of McGill University, Richard Kerekes, FCIC, of The University of British Columbia, and J. Christopher Hall of the University of Guelph.

"Our first goal was to bring leading edge research underway at Canadian universities to the attention of key players in the Canadian pulp and paper industry," said George Rosenberg, FCIC, managing director of Sentinel. He is a strong advocate for bridging the gap between university research and industry application. "We recruited an elite team of Canada's top academic researchers, including nine Canada Research Chairs, three NSERC industrial chairs, and an endowed chair." Sentinel is a collaborative, multidisciplinary effort involving 28 professors and adjuncts with backgrounds in life science, surface science, and material science.

With $10.5 million in funding over five years from the Natural Sciences and Engineering Research Council of Canada (NSERC), the Ontario Centres of Excellence, and nine key industry players, the network is well positioned to help Canada lead the world in the development of bioactive paper products.

Why bioactive paper instead of, say, bioactive plastic? Because paper is flexible, thin, cheap, easy to produce from a renewable resource, and easy to work with. It's also porous, allowing it to absorb the chemicals that make it bioactive.

Sentinel's research focuses on four technology platforms:

* achieving rapid pathogen detection on bioactive paper;

* producing optimized substrates on bioactive paper;

* developing high-speed biopolymer printing, coating and impregnation techniques; and

* evaluating new pathogen barriers as well as new methods of pathogen capture and deactivation.

A demonstration was held at the National Research Council Canada Institute for Biological Sciences during Sentinel's annual meeting in Ottawa. It showed one way reactive agents could be bound to paper. The demonstration was conducted by John Brennan, MCIC, Canada Research Chair in Bioanalytical Chemistry and a professor in the department of chemistry at McMaster University, and Roger Luckham, a graduate student at McMaster in bioanalytical chemistry. Their test used gold nanoparticles that were co-entrapped with an enzyme in a sol-gel-based silica material printed on a paper dipstick. The presence of target analytes in samples caused the enzyme to deposit gold salts onto the nanoparticles, forming small purple dots on the dipstick.

It was the first demonstrated proof that gold nanoparticles could be grown when entrapped in silica. It was also the first report of sol-gel-based "inks" being used to produce a dipstick-based assay.

The test is quick and simple. It takes about five minutes and no equipment is required beyond the paper strip and a small bottle of liquid to which the analyte sample is added. Even detection is easy. Results can be seen with the naked eye.

"What we've been doing is developing a method to get the colour to change," said Brennan, whose area of specialty is immobilizing proteins on surfaces. "You don't want paper that you have to put into a fancy instrument to get your answer."

Applied research into bioactive paper is still in the early stages. One issue is getting the coating onto paper or cardboard quickly and inexpensively. One concept being explored is spraying the coating using inkjet printers, offering the possibility of a cost-effective technology that could be applied anywhere in the world.

Another hurdle is pathogen detection, and the Sentinel Bioactive Paper Network is encouraging research in paper products focused on this issue. Considerable work has already been done on deactivation. For example, there are already paper wipes that disinfect and Kimberly-Clark has come out with an anti-viral Kleenex[R] that claims to kill 99 percent of cold and flu viruses.

"There is a huge amount of literature on antibacterial surfaces," said Pelton. "There are lots of patents on everything from running shoe liners to paper products. "What's not there at all is pathogen detection. That is where I see the potential. No one has come up with the equivalent of something like pH paper, a litmus test that you can clip into water and detect a pathogen. That will be the real breakthrough innovation."

In the area of pathogen detection, work is being done by the University of Guelph's Mansel Griffiths on the possibility of fixing pathogen-detecting bacteriophages to paper.

Bacteriophages are viruses that kill bacteria. They attach themselves to the surface of a bacterial cell, take over the cell's genetic machinery, and produce new copies of themselves inside the cell. After reaching critical mass, the phages break open the bacterial cell and destroy it. Griffiths leads the Sentinel Phages for Sensing and Binding project, which is focused on fixing phages onto paper to detect the presence of bacteria. The challenge is to genetically manipulate the phage so that it both adheres to the paper and sends out an alert when a specific bacterium is present. Another challenge with bioactive paper products is that biodetection is very specific, so the paper would be engineered to detect a specific virus or bacterium.

There are countless pathogens out there--and potentially countless different products. However, Pelton noted that a paper could conceivably be created that would identify five or six of the world's major killers. So even if it didn't detect most of the pathogens, it could detect the ones that cause the most problems.

Pelton said he hopes that bioactive paper products will be available in five years. He expects it will be about ten years before the concept is fully implemented to the point that it's being used in food packaging and in grocery stores.

That's also because in addition to the science, there are regulatory issues to deal with. "It takes a long time to do these things. To get from the lab to the grocery store is a long path. The basic research is to solve the hard problems. It's the job of our partners to generate products."

But Sentinel's industry partners stand to profit from the process. That's because in addition to its obvious impact on health, the development of bioactive paper has important implications for Canada's pulp and paper sector. The industry is a major player in the Canadian economy and is particularly important in communities outside the major population centres.

Pelton sees a convergence between the public's need for protection and the industry's readiness to establish itself as a provider of value-added, knowledge-economy goods.

"It offers the opportunity to develop new and value-added paper products," said Peter Ham, vice-president, product development and technology at Tembec Inc., and chair of Sentinel's board of directors. "The Canadian pulp and paper and forest products industry is facing an exceptional period," he said, referring to the confluence of high energy costs, a high dollar, increasing international competition, and a downturn in the U.S. housing industry. "The development of value-added products offers the industry the opportunity to continue to compete in difficult markets," Ham said.