McMaster Sentinel NSERC

Rising to the challenge

Numerous food safety issues underscore the
urgent importance of the work that the Sentinel
Bioactive Paper Network has taken on.

The Sentinel Network, through the development of bioactive paper, is helping to find answers to growing fears over pathogens in our food, water and air

In late December, the National Post carried a front page story with a headline that read: "Don't eat your veggies." Part of a series examining issues "that will shape the way we live," the report described the public's growing fears over pathogens found in everyday foods.

The rising tide of public concern is understandable, given an alarming surge of food-linked illnesses. In the late summer of 2006, California spinach tainted with E. coli bacteria killed three people and made 200 others sick. Three months later, another E. coli outbreak was traced to food served by the Taco Bell restaurant chain. Those reports came in the wake of 2005 spate of salmonellosis, triggered by tainted bean sprouts, in which 600 people in Ontario fell ill.

It's not just food-borne contamination that has people worried. In 2000, E. coli contamination of the Walkerton, Ontario water supply killed seven people and raised public concern about the safety of tap water. The spread of a parasite called cryptosporidium in the water supply in North Battleford, Saskatchewan in 2001 made thousands ill and further heightened fears. In 2003, the emergence of Severe Acute Respiratory Syndrome (SARS), which killed 44 Canadians, made people all too aware of just how quickly viruses can be passed from person to person. And in the post 9-11 world, there is always the threat of bioterrorism.

For Dr. Robert Pelton, these life-threatening outbreaks underscore the urgent importance of the work that the Sentinel Bioactive Paper Network has taken on: finding innovative ways to use paper to protect the public from pathogens.

Dr. Pelton and his Sentinel co-founders (Dr. T.G.M. van de Ven at McGill University, Dr. Richard Kerekes at the University of British Columbia and Dr. J. Christopher Hall at the University of Guelph) created the Network in 2005 to bring leading-edge research underway at Canadian universities to the attention of key players in the Canadian pulp and paper industry. The goal is to develop bioactive paper products that can detect, repel or deactivate pathogens found in food, water and air.

International leadership

Bioactive paper is a research field in which Canada leads, thanks in large part to the Sentinel Network's direct predecessors: the Mechanical Wood-Pulps Network, a 12-year member of the federally funded Networks of Centres of Excellence program, and PAPIER , the Canadian Pulp and Paper Network for Innovation in Education and Research.

Those organizations nurtured collaborative, multidisciplinary efforts to meet the challenges of the pulp and paper industry. It's an approach that the Sentinel Network - with its 27 professors and adjuncts working on 23 research projects at 10 universities across Canada - has integrated into everything it does. With $10-million in funding over five years from the Natural Sciences and Engineering Research Council of Canada, 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.

"From an academic research point of view, I think Canada is ahead of everybody else," says Dr. Pelton, who serves as Scientific Director of the Network and is the Canada Research Chair in Interfacial Technologies at McMaster University. "Certainly, from a public sector/academic perspective, there is no group anywhere in the world today like the Sentinel Network. The idea is to get moving quickly and try to keep the lead."

Economic impact

Much is at stake. Beyond meeting an increasingly important public health need, the ability to develop a range of bioactive paper products - food wrap that could signal the presence of salmonella, water filters that capture E. coli or a face masks that emit an odor on contact with a virus - could have huge implications for a Canadian economy that is inextricably linked to the pulp and paper industry.

When people think of what drives the natural resource component of the Canadian economy in the 21st century, the tendency is to look to Alberta and think about oil and gas. But the pulp and paper industry, though not enjoying the same kind of powerhouse days of the past - is still a major contributor to the Canadian balance sheet.

"The industry is incredibly important to the Canadian economy," says Dr. Pelton. "You only have to drive around northern Quebec and northern Ontario and New Brunswick - almost anywhere across Canada. Many of the towns outside of the major population centres are there because of paper mills."

The pulp and paper industry in Canada is poised to rise to the challenge. While the past few years have seen the Canadian industry streamline itself to deal with increased global competition, it also has become an environmental leader - as shown by the early adoption of totally chlorine-free (TCF) mill technologies. As the Globe and Mail recently pointed out, sustainable forest practices adopted by Canadian firms "will continue to shine favourably in key U.S. markets." The industry also has been actively investigating the possibility of developing higher value products and building new markets.

Dr. Pelton sees a convergence in the public's need for protection from pathogens and the Canadian industry's readiness to establish itself as not just a producer of raw materials and commodity products - kraft pulp and newsprint - but a provider of value-added, knowledge-economy goods.

"Our Canadian operating companies have recognized the need to get into higher-value products," says Dr. Pelton. "This is driving their interest in the Sentinel Network: they want to come up with new products that are worth a lot more than newsprint. Bioactive paper is certainly a great opportunity."

Taking a multidisciplinary approach

Dr. Hall, the Sentinel Network's Bio Science Theme Leader and a Canada Research Chair in Recombinant Antibody Technology at the University of Guelph, was drawn to the Network by Dr. Pelton's vision for applying bio science expertise to paper-making.

"The thing about Sentinel is that the people who put it together are paper experts," says Dr. Hall. "They understand cellulose, paper structure, paper function and the surface properties of paper. Probably two-thirds of the Network is made up of paper people. The other one-third is biological scientists. We didn't previously know one another. Bob Pelton said, ‘We know a lot about paper and the biologists/biochemists know a lot about capture and detection agents, so let's put the two together.' Then, we brought the paper industry to the table and the industry bought in because they could see the potential value of results derived from Sentinel for their future development."

Sentinel's multidisciplinary approach - and its advocacy for bridging the gap between university research and industry application - fits with the mission of its host centre, Hamilton Ontario's, McMaster University.

"This is totally consistent and completely coincides with McMaster's strengths, with McMaster's commitment to multidisciplinary research and McMaster's evolving commitment to commercialization," says Dr. Mamdouh Shoukri, the university's Vice-President of Research and International Affairs. "It is everything that McMaster stands for."

What makes the Sentinel Network so effective is the research talent it has recruited, says Dr. Pelton. "We had the luxury of seeking out the very best. We were very strategic about recruiting the top people in Canada."

That said, the road ahead is not easy. Developing bioactive paper products is not a quick fix to a current problem, says Dr. Pelton. "The fact that this hasn't been done yet, that bioactive paper products haven't been developed, is not because people are not trying. There are some serious scientific challenges to overcome - especially in the area of pathogen detection."

With its industry partners, the Sentinel Network is encouraging research in paper products aimed at the detection of pathogens and their deactivation. Around the world, considerable work has already been done on deactivation. There are already paper wipes that disinfect and Kimberly-Clark has come out with an anti-viral Kleenex which it claims can kill 99% of cold and flu viruses.

"There is a huge amount of literature on antibacterial surfaces," says Dr. Pelton. "There are lots of patents on everything from running shoe liners to paper products, so you could argue there is a fair amount of disinfection, antibacterial technology out there now.

"What's not there at all - which, in computer jargon, is the killer application - 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 dip into water and detect a pathogen. That will be the real breakthrough innovation. It will be the leapfrog jump into doing something that's never been done before."

The Sentinel Bioactive Paper Network, which is funded through 2010, is looking longer-term to find ways to make itself sustainable as it takes on the pathogen challenge and helps the pulp and paper industry chart its future.

"All the researchers are pushing hard and there is much that looks promising," says Dr. Pelton. "We see early signs of results such as patent applications and inventions disclosures - and there are a number of those going on now - so I am excited that in the next couple of years Canadians are going to see things moving towards the technology development stage."

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The final hurdle (to market)

The network financially supports critical
tasks that are beyond the normal scope of
academic research but are essential in
triggering private sector investment.

Sentinel's Technology Transfer Fund will help innovations make the leap over obstacles between the laboratory and the licensing agreement

Potential is never something to waste, especially in challenging times. As the pulp and paper industry reinvents itself in the 21st century, wasting valuable research that could be turned into life-enriching, profit-making products is not in anyone's interest.

That's why the Sentinel Bioactive Paper Network created the Technology Transfer Fund - to financially support critical tasks that are beyond the normal scope of academic research but are essential in triggering private sector investment. The fund helps researchers to clear the final hurdle in transferring their technology out of the lab and into the hands of an industry partner.

"The funds might support preparing a prototype," says Sentinel Network's Managing Director George Rosenberg, "or it could be a pilot trial the Network supports. It's the intermediate step between the lab tests and a scaled-up industry trial."

Before buying in on an innovative product or process, industry partners need "a sense of confidence that the technology is going to work," says Dr. Rosenberg. "Before industry enters into licensing negotiations with the universities, they want a proof of concept. This fund is designed to make that happen."

Sentinel has set aside $400,000 over five years for the Technology Transfer Fund. "It's not a huge amount of money," says Dr. Rosenberg. "Generally, we expect it will amount to about $20,000 per project - money that will help the university researcher conduct some critical experiments necessary for the industry partner to make a decision."

Dr. Peter Lancaster, Scientific Advisor for Fibre Sciences R&D at Weyerhaeuser Co., sees the Technology Transfer Fund as a key step in turning research innovation to industry application.

"We're always looking for new product areas," says Dr. Lancaster, Chair of Sentinel's Technology Exploitation Committee. "From the industry point of view, this gives us something that we haven't had before. We're trying to design new products and this gives us the tools. We can take advantage of research that most industries wouldn't do in-house because it's a little too upstream. We can take that and move forward."

Dr. Rosenberg says Sentinel currently is looking at proposals for projects that need this kind of funding. "We're just starting this program up. We have two target dates for submitting proposals, so we're expecting our first batch of proposals. We have several technologies coming forward."

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Q & A

Dr. John Kadla, recently returned to
Canada as the Canadian Research Chair
in Advanced Biomaterials at the
University of British Columbia (UBC).

Dr. John Kadla, the Canadian Research Chair in Advanced Biomaterials at the University of British Columbia (UBC) recently joined the Sentinel Bioactive Paper Network to work on nanoscale fibrous structures. His return to Canada after working in the United States is an example of the reverse brain drain process in practice. He took time recently to answer these questions about his Sentinel work.

Question: You did your B.Sc. at UBC, and then did your doctoral work at North Carolina State University (NCSU). Is this (joining the Sentinel Network) all part of a return to Canada?

Dr. Kadla: Yes, I received my B.Sc. in Chemistry/Biochemistry from UBC and got my PhD in 1997 from NCSU in wood chemistry. After postdoctoral work at the University of North Carolina at Chapel Hill (polymer chemistry), I went back to NCSU as an assistant professor/associate professor. Then in 2003 I was approached to apply for a Canada Research Chair at UBC.

Question: You are a wood chemist. Why did you join the Sentinel Network?

Dr. Kadla: Dr. Richard Kerekes (Professor Emeritus in Pulp and Paper Engineering at UBC) brought me into the Network. I had known Dick for many years while I was at NCSU. When I came back, we started to discuss research and he invited me to collaborate with him on his Sentinel project. I was well aware of the Sentinel Network and was very interested in it because of the nature of the Network and my own research interests, so I quickly accepted Dick's invitation.

I feel this (the Sentinel Network) is a perfect example of what Canada does right: getting top researchers in academia and industry together and facilitating training, research and development. I am very honoured to have the opportunity to interact with some of the best scientists in the world in this field.

Question: Can you explain your Nanoscale Fibrous Structures through Electrospinning of Novel Cellulosic Systems project?

Dr. Kadla: As part of the Network, we are interested in developing novel substrates for various bioactive applications. Electrospinning is an emerging technique for producing non-woven fibrous materials with various properties and potential applications.

Question: What applications do you see for this research?

Dr. Kadla: Using these techniques we hope to develop non-woven cellulosic networks for filtration and membrane applications. When coupled with bioencapsulation, they could also lead to biosensor applications. Although some research has been published using various cellulose esters and the like, there is no systematic study looking at cellulose and cellulosics (effect of molecular weight, regiospecificity of modification, blends etc.), so this will be one of the first steps in our project. Electrospun fibres (polyolefin's) are being produced for filtration applications - but none yet to my knowledge using cellulose.

Question: Are you working with industry partners on this project?

Dr. Kadla: We have had some interest shown from one of the Network industry partners, but this is a new project - we're just starting.




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The next generation

Sentinel student Jason (Junhai) Lin
works on bioactive paper's
development in a McMaster lab.

The Sentinel Bioactive Paper Network gives incentive to young researchers to come to Canada to train and explore

To secure a strong future for the next generation of pulp and paper products, the Sentinel Bioactive Paper Network needs help from the best young minds from across Canada - and across the world.

That's why developing the next generation of bioactive paper professionals is a key component of Sentinel's mandate. It's also why people like Junhai (Jason) Lin, a Chinese student working with Dr. Robert Pelton at McMaster University, and Laura Ciovica, a Romanian PhD student at McGill University, are attracted to the Network.

"The overall level of technology in China is less advanced than in many Western countries," says Mr. Lin, a Masters of Science student who is working on Sentinel's Paper Surface Chemistry and Bioactivity project. "I want to learn more about modern concepts and technologies."

Working with Sentinel has many benefits for students, says Mr. Lin: "The nature of bioactive paper products is multidisciplinary, so the student who works within the group can obtain extensive knowledge and intensive training in several areas, such as biochemistry, physical chemistry and detection methods. It's good for our future development."

Ms. Ciovica studied and worked in Finland for 10 years. Her decision to come to Canada and do research with the Sentinel Network is especially interesting, given that Finland is widely regarded as a leader in pulp and paper innovation. Canada, she says, simply offered more opportunities.

"I had heard of Sentinel from my supervisor when I applied for graduate studies at McGill," says Ms. Ciovica, who is working with Dr. T.G.M. van de Ven on Sentinel's Pathogen Capture by Bioactive Paper in Water project. "The project seemed very interesting and I have always wanted to work in biochemistry and microbiology."

She says her Sentinel experience and Canadian graduate studies will help her gain "a thorough understanding of biological applications of paper and cellulose fibres" while allowing her to get experience working in related fields, such as microbiology.

Mr. Lin and Ms. Ciovica agree that the work Sentinel is doing to promote research into and development of bioactive paper products could bolster Canada's pulp and paper industry. "There could be a major breakthrough in pathogen detection," says Ms. Ciovica. It would come from a renewable source and it would be biodegradable. There would be lots of possible applications for this."




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The future is now

Sentinel investigator, Dr. Huining Xiao,
has developed polymer-based
antimicrobial cellulose fibres that
can kill bacterial pathogens.

A Sentinel investigator at the University of New Brunswick has tweaked industry interest in making polymer-binding paper that kills pathogens

Although the Sentinel Bioactive Paper Network is only in its second year of operation, its efforts in transferring novel technology to industry are about to pay off in a range of revolutionary new paper products.

Dr. Huining Xiao, a professor in the Department of Chemical Engineering at the University of New Brunswick (UNB) and a Sentinel investigator, has developed polymer-based antimicrobial cellulose fibres that can kill bacterial pathogens. Better yet, he has found a way to bind the antimicrobial polymers or compounds to paper.

"The results demonstrated that the polymer-modified fibres are promising," says Dr. Xiao. "There are very practical applications and there is very strong industrial interest."

Beyond the multi-billion-dollar market in paper tissues and towels, pathogen-killing paper has great potential for use as food wrap, pharmaceutical packaging, hospital face masks, water and air filters, and banknotes.

"We're in the process of filing a patent application in the United States for the polymer itself as well as the method for producing antimicrobial paper products," says David Foord, UNB's Director of Intellectual Property.

Dr. Xiao's team is in the final stage of "proof of concept" testing of the polymers and the application processes, after which licensing agreements with Sentinel's partner companies will be negotiated. One company is confident it can have an antimicrobial paper product, based on Dr. Xiao's invention, in production this year.

"The partnership activity is very healthy," says Dr. Xiao, who has spent much of his career investigating the development of functional polymers for papermaking and paper-binding compounds to deactivate bacteria and viruses.

Mr. Foord said the Sentinel Network has been instrumental in linking Dr. Xiao's innovation with interested industry partners.

"It has provided the researchers, the university and the industry partners with a common understanding of the technology transfer process. This, in itself, is very useful. More importantly, it has offered an opportunity for face-to-face meetings with prospective users from around North America and the world."




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Old idea, new application

An image of a listeria phage. With the emergence
of superbugs and increasing public concern about
salmonella, E. coli and other bacteria found in
foods, scientists are serious about how to use
bacteriophages to protect human health.

A Sentinel scientist is updating a Canadian-born microbiologist's innovation to find ways to detect harmful bacteria found in our food, water and air

To appreciate the cutting edge work that the University of Guelph's Dr. Mansel Griffiths is doing to apply pathogen-detecting "phages" to paper, a brief bit of history - including an often overlooked Canadian connection - is required.

"Phages" or, more accurately, "bacteriophages" have been around since early in the 20th century. The term bacteriophage actually was coined by the Canadian-born microbiologist Félix d'Hérelle when he announced he had discovered "an invisible, antagonistic microbe of the dysentery bacillus" in 1917.

A phage, in simple terms, is a virus that kills bacteria. Following attachment to the surface of a bacterial cell, a phage can take over the cell's genetic machinery and produce new copies of itself inside the cell. After reaching critical mass, the phage breaks open the bacterial cell and destroys it.

Despite the strong Canadian connection, the use of phages never caught on in the West where, during the Second World War, antibiotics became the weapons of choice against bacterial infection. The Russians and medical scientists in other Eastern European countries, however, have been using phages successfully for more than six decades. With the emergence of superbugs - and increasing public concern about salmonella, E. coli and other bacteria found in foods - scientists here are taking a serious second look at how to use bacteriophages to protect human health.

Dr. Griffiths, an internationally respected microbiologist, leads the Sentinel Phages for Sensing and Binding project, which is focused on fixing phages onto paper to detect the presence of bacteria. The applications are considerable: food wrap with a built-in phage could change colour on contact with salmonella or E. coli, alerting the grocer not to sell it or warning the consumer not to eat it. Filter paper could be developed to give food processors a less-expensive, real-time way to tell if their products have become contaminated. Water filters could be created to alert inspectors to the presence of cryptosporidium. Air filters could trigger awareness of bacteria bearing Legionnaires' disease.

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. But Dr. Griffiths is optimistic: "We have isolated phages against a number of common foodborne pathogens. The next step is to characterize some of those phages and identify ways we can stick them onto paper. It isn't too far from reality."




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