1. 20 L’ACTUALITÉ CHIMIQUE CANADIENNE SEPTEMBRE 2007
Canadian paper innovation holds promise for improved global health safety.
Daniel Drolet
T
hey 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.
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 per-
sonnel 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
JUSTTWOSMALLPURPLEDOTS

2. SEPTEMBER 2007 CANADIAN CHEMICAL NEWS 21SEPTEMBER 2
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 Ca-
nadian universities, nine industry partners, and
federal and provincial government agencies.
Sentinel’s goal is the development as soon
as possible of paper-based products contain-
ing biologically active chemicals that will
ultimately protect against food-, water-, and
airborne illnesses. These illnesses strike mil-
lions of people around the world each year.
“We want something that’s going to be-
come as prevalent as the bar code on pack-
aging,” 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 wind-
ing 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 Uni-
versity 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 Cana-
dian pulp and paper industry,” said George
Rosenberg, FCIC, managing director of Sen-
tinel. 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 sci-
ence, and material science.
With $10.5 million in funding over five
years from the Natural Sciences and Engineer-
ing Research Council of Canada (NSERC), the
Ontario Centres of Excellence, and nine key
industry players, the network is well posi-
tioned to help Canada lead the world in the
development of bioactive paper products.
Why bioactive paper instead of, say, bioac-
tive 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 technol-
ogy platforms:
• achieving rapid pathogen detection on
bioactive paper;
• producing optimized substrates on bioac-
tive paper;
• developing high-speed biopolymer
printing, coating and impregnation tech-
niques; 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 Biologi-
cal 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, Can-
ada Research Chair in Bioanalytical Chem-
istry 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 en-
trapped 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 immobi-
lizing proteins on surfaces. “You don’t want
paper that you have to put into a fancy instru-
ment 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 ex-
plored 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 fo-
cused on this issue. Considerable work has
already been done on deactivation. For ex-
ample, there are already paper wipes that dis-
infect and Kimberly-Clark has come out with
an anti-viral Kleenex® 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 run-
ning 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 dip 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 bac-
teria. They attach themselves to the surface
of a bacterial cell, take over the cell’s genetic
machinery, and produce new copies of them-
selves inside the cell. After reaching critical
mass, the phages break open the bacterial
cell and destroy it. Griffiths leads the Senti-
nel Phages for Sensing and Binding project,
which is focused on fixing phages onto paper
to detect the presence of bacteria. The chal-
lenge is to genetically manipulate the phage
so that it both adheres to the paper and sends
out an alert when a specific bacterium is pres-
ent. 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 patho-
gens, 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 sci-
ence, 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

3. 22 L’ACTUALITÉ CHIMIQUE CANADIENNE SEPTEMBRE 2007
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 pro-
cess. 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 communi-
ties outside the major population centres.
Pelton sees a convergence between the public’s need for pro-
tection and the industry’s readiness to establish itself as a pro-
vider 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 di-
rectors. “The Canadian pulp and paper and forest products indus-
try is facing an exceptional period,” he said, referring to the conflu-
ence 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 op-
portunity to continue to compete in difficult markets,” Ham said.
In a keynote speech at Sentinel’s annual meeting, Douglas
MacPherson of Migration Health Consultants spoke of the real and
perceived threats in global public health. Ultimately, he said, the
biggest challenge faced by both the public and front-line workers
is overcoming fear—fear that they might get avian influenza, fear
that their food might be tainted, and fear that the air we all breathe
is making us sick. From that perspective, the development of bio-
active paper would help reduce fear by producing visible evidence
of the presence of pathogens and perhaps even killing them.
Ontario health care workers faced uncertainty about whether
they had been infected during the 2003 SARS epidemic and that
created an aura of fear. Pelton said, “I think the health care work-
ers would have felt a lot more comfortable if they had known when
they were, or weren’t, in contact with the SARS virus.”
For further information on the development of bioactive papers,
visit www.sentinelbioactivepaper.ca.
Daniel Drolet is an Ottawa writer whose work has appeared
in more than two dozen newspapers and magazines across
Canada in the last year.
The Chemistry
of the Test Process
The development of the
colorimetric dipstick bioassay
is based on the printing
of enzyme-doped silica
“inks” containing small gold
nanoparticles that are co-
entrapped with the enzyme
and printed on a paper
substrate.
The bioactive dipstick is
immersed in a solution
containing the test analyte
(a substrate for the enzyme)
and a Au(III) salt. It produces
a product that leads to
reduction of the Au(III) onto
the entrapped nanoparticles,
producing particle growth and
a corresponding increase in
colour intensity. Shades of
colour can be correlated to
the amount of substrate or
enzyme inhibitor present.
This is the first demonstration
that gold nanoparticles can
be grown when entrapped in
silica and the first report of
sol-gel-based inks being used
to produce a dipstick-based
bioassay.
Preliminary results show
that the assay is sufficiently
sensitive to allow detection
of our test compound either
by eye or with a digital
camera and image analysis
software in approximately
five minutes—avoiding the
need for expensive and
sophisticated instrumentation.
John Brennan, MCIC
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