Newspapers may be on their way out – as print
media move online – but paper and printing have
an exciting future in biotechnology. Researchers are
using printing technology to make bioactive surfaces
– paper, plastic and glass coated with ‘bioinks’
containing antibodies, enzymes or DNA. These
functionalised surfaces capture biological analytes
from blood, soil and water, and can be made into
cheap, disposable sensors for the healthcare, food
safety and environmental industries.
According to Tim Claypole, director of the
Welsh Centre for Printing & Coating, the printing
of biological materials has potential as a ‘major
disruptive technology’. Printing biomaterials could
lead to high volume manufacture of disposable
sensors for point of care and home use with low
capital cost, using a variety of bioinks printed on
different surfaces for a wide range of applications.
However, there are challenges in turning
enzymes and antibodies into bioinks. ‘The molecule
must survive the printing process,’ Claypole says.
‘Many are sensitive to shear stress and temperature.’
At the Welsh Centre of Coating and Printing, which
is involved in a number of projects with Swansea’s
new Centre for NanoHealth (CNH), researchers have
been looking at screen, inkjet, aerosol, pad and
flexography printing. ‘It is a challenge to match the
process to the molecule,’ Claypole adds. He predicts
that the screen press will be the ‘workhorse’ of the
new biological printing industry, allowing any ink to
be printed on any surface.
Countries with an established paper industry
are particularly interested in bioactive surfaces. In
Canada, for example, McMaster University heads the
SENTINEL Bioactive Paper Network, composed of 11
universities and seven industrial partners from the
printing, ink and paper sectors. The network wants
to take the applications of paper to a new level, says
scientific director Robert Pelton. ‘We already have
paper that can protect us from pathogens through
filtration or antimicrobial coatings. Now we want
to make paper that can detect pathogens. We are
trying to take some of the low hanging fruit from the
biomedical world and see if we can get it to work
on paper. Our vision is to have biosensors be as
prevalent as printed barcodes on paper.’
While the challenges of selectivity and sensitivity
are shared by all biosensors, some issues are specific
to the combination of paper and biomolecules.
Proteins, including enzymes, tend to fall apart
when aged, dried out or exposed to sunlight. The
SENTINEL researchers are working on four groups
of biomolecules to try to overcome these limitations:
enzymes; antibodies derived from llamas, which are
more stable than human antibodies and which are
genetically modified engineered to have a cellulose
binding domain to bind to paper; DNA aptamers,
which are more stable than regular DNA; and
bacteriophages, which are viruses that can detect
and kill bacteria.
‘The challenge is that we are trying to do this
without equipment,’ says Pelton. ‘Reporting the
sensor’s result is the hardest part of the project. But it
may be that colour reactions on paper can be linked
to cell phones, which are everywhere and generally
have a high resolution camera built in. Phones can
be connected to a computer which would create a
network. There is a lot of excitement over integrating
phones with paper diagnostics and sensors, although
the technical and business challenges are big ones.’
While paper tests are not new, this is a field that is being ‘rediscovered and pushed forward,’
according to John Brennan of McMaster University.
‘Paper has a lot of unique properties – it is scaleable
and disposable. Our idea is to take assays now done
on plastic and bring them onto paper - and also to
discover new paper-based assays.’ In a recent paper
(Analytical Chemistry, 2009, 81, (13), 5474), Brennan
and his team described a paper-based biosensor
for acetylcholinesterase inhibitors, which are wellknown
neurotoxins and a component of bioterror
agents and organophosphorus pesticides.
The enzyme acetylcholinesterase was deposited
on the paper in a sol-gel formulation of biocompatible
silica particles by inkjet printing using equipment
from SENTINEL partner Fujifilm Dimatix. The
system detected two acetylcholinesterase inhibitors,
paraoxon and aflatoxin, with high sensitivity within
five minutes with a standard colour reaction and the
results were reproducible after storage at 4°C for
at least 60 days, making it suitable for use in the
field. Aflatoxins are present in some food moulds,
so the test paper has a potential role in food safety
as well as homeland security and environmental
monitoring.
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