New research has shown how a smart sensor
chip, able to pick up on subtle differences in glycoprotein molecules,
can improve the accuracy and efficiency of prostate cancer diagnosis.
Researchers at the University of Birmingham believe that the novel
technology will help improve the process of early stage diagnosis.
Glycoprotein molecules, proteins that are covalently bound to one or
more carbohydrate chains, perform a wide range of functions in cell
surfaces, structural tissues and blood. Because of their essential role
in our immune response, they are useful clinical biomarkers for
detecting prostate cancer and other diseases.
The team of chemical engineers and chemists, created a sensor chip
with synthetic receptors along a 2D surface to identify specific,
targeted glycoprotein molecules that are differentiated by their
modified carbohydrate chains.
In doing so, they developed a more accurate and efficient way of
diagnosing prostate cancer than the current tests which rely heavily on
antibodies.
These antibodies are expensive to produce, subject to degeneration
when exposed to environmental changes (such as high temperatures or UV
light) and more importantly, have a high rate of false-positive
readings.
Professor Paula Mendes said, "There are two key benefits here.
Crucially for the patient, it gives a much more accurate reading and
reduces the number of false positive results. Furthermore, our
technology is simple to produce and store, so could feasibly be kept on
the shelf of a doctors' surgery anywhere in the world. It can also be
recycled for multiple uses without losing accuracy."
Most previous research on detecting glycoproteins centered on the
protein of the molecule. Problematically for diagnosis, the protein part
of glycoproteins does not always change if the body is diseased.
The findings, published in the journal Chemical Science,
show how the rate of false readings that come with antibody based
diagnosis can be reduced by the smart technology that focuses on the
carbohydrate part of the molecule.
The complex sugar structure in glycoprotein can be subtly different
between samples from healthy and diseased patients. In order to achieve
more accurate readings, the team wanted to identify the presence of
disease by detecting a particular glycoprotein which has specific sugars
in a specific location in the molecule.
Professor Mendes added, "Biomarkers such as glycoproteins are
essential in diagnostics as they do not rely on symptoms perceived by
the patient, which can be ambiguous or may not appear immediately.
However, the changes in the biomarkers can be incredibly small and
specific and so we need technology that can discriminate between these
subtle differences -- where antibodies are not able to."
To engineering the sensor chip, the team developed a smart surface
with nano-cavities that fit the particular target glycoprotein.
To create the nano-cavities, the sugar part of the prostate cancer
glycoprotein is reacted with a custom-designed molecule that contains a
boron group at one end (the boron linkage forms a reversible bond to the
sugar). The other end of this custom molecule is made to react with
molecules that have been tethered to a gold surface. The glycoprotein is
then bound to the surface via its sugar groups, before the rest of the
surface is blocked with a third molecule.
When the glycoprotein is removed (by breaking the reversible boron
bonds) it leaves behind a perfect cast. Within that cast, there was a
special area with boron-containing molecules that can recognise a
specific set of sugars.
Professor Mendes said, "It is essentially a lock, and the only key
that will fit is the specific prostate cancer glycoprotein that we're
looking for. Other glycoproteins might be the right size, but they won't
be able to bind to the very specific arrangement of boron groups."
Dr John Fossey added, "It's estimated that one in eight men will
suffer from prostate cancer at some point in their life, so there's a
clear need for more accurate diagnosis. By focussing on the sugar, we
appear to have hit the 'sweet spot' for doing just that. Our focus now
is to take this technology and develop it into something accessible to
people across the world."
The team also hope that further investment, and collaboration with
commercial partners, will open the door to adapting the current
technology for other diseases.
Dr Fossey continued, "We believe that this could be applicable to
other diagnostic challenges. Lots of diseases produce specific
glycoproteins, so there are a number of possible avenues to improve the
accuracy of our diagnoses."
Story Source:
The above post is reprinted from
materials provided by
University of Birmingham.
Note: Materials may be edited for content and length.