Plasmonic biosensors make highly sensitive diagnostic devices
8 July 2014
A new type of highly-sensitive and low-cost sensor, called a
plasmonic biosensor, could detect a range of biomarkers that
diagnose diseases at an early stage.
Biomarkers, which are chemicals such as proteins in blood or
saliva, for example, whose presence or abnormal concentration is
caused by a disease. Biomarkers can indicate the presence of
diseases long before the appearance of symptoms. However, currently
the detection of these molecules still requires specialised
laboratories and is costly.
The EU-funded research project called NANOANTENNA, which
completed in March 2013, developed a plasmonic nanobiosensor for the
detection of proteins. It consists of nanoantennas, tiny gold rods
about 100 to 200 nanometres long and 60 to 80 nm wide. By shining
light onto such a nanoantenna, the electrons inside start
oscillating, amplifying the light radiation in hot spots on the
antenna, explains Pietro Giuseppe Gucciardi, a physicist at the
Institute for Chemical-Physical Processes, affiliated with the
Italian National Research Council CNR, in Messina, Sicily.
Diagram showing nanoscale gold rods (nanoantennas)
with bioreceptors and proteins (biomarkers).
During the 1990s’ researchers found that plasmons, tiny waves of
electrons in metallic surfaces that appear when such surfaces are
illuminated, also amplify the light in an area close to that
surface. In biosensors, protein molecules are identified by
irradiating them with infrared light and by analysing the spectrum
of the light they emit, known as a Raman spectrum. If these
molecules are close to nanoparticles, the plasmons in the
nanoparticles enhance the Raman signal coming from the protein
molecules by several orders of magnitude.
The nanoantennas developed in this project only enhance the
emitted Raman signal if the biomolecules are close to the hot spots.
Therefore, the molecules have to be trapped to be detected. To do
so, the researchers attached fragments of DNA engineered to
recognise specific proteins, termed bioreceptors, to the
nanoantennas. When these nanoantennas with bioreceptors are
incubated in a solution that contains the biomarkers, the biomarkers
become attached to the nanoantennas. When, subsequently, these
nanoantennas are illuminated with light, they show the Raman
fingerprints of both the bioreceptor and the biomarker.
"It is important to fund this research because it will be a
component of future medicine," says Alexandre Brolo, professor of
chemistry specialised in nanotechnology research, who has been
developing plasmonic biosensors at the University of Victoria,
British Columbia, Canada. He also believes that such approach will
make medical care more cost effective. "You want something that is
very cheap and is not going to put a big burden on the healthcare
system," says Brolo.
"Small, compact and autonomous devices with the same features in
terms of sensitivity and robustness as current commercial
instrumentation based on plasmonics are still needed," says Maria
Carmen Estévez, a researcher at the Catalan Institute of Nanoscience
and Nanotechnology in Bellaterra, Spain. The "end-users" of these
biosensors have to understand that the development of these devices
by researchers in many disciplines is a long process, notes Estévez.
She adds that these biosensors will need to be integrated with
optical components, with electronics for reading out the
measurements, software to process all data, and rely on the use of
microfluidics to prepare and process the sample.
Youris.com asked Pietro Giuseppe Gucciardi about the kind of
improvements this new technology could bring to biosensors:
Do the molecules to be detected have to be trapped by these
Yes, we make the nanoantennas functional by attaching
bioreceptors to their surfaces. We use fragments of DNA, so-called
haptomers, which are engineered to recognise and trap specific
proteins, such as manganese superoxide dismutase (MnSOD), a
biomarker for several types of cancers. The nanoantennas are
incubated with a solution containing biomarker molecules that become
attached to the bioreceptors on the nanoantennas. When they are
illuminated with light, we get the vibrational fingerprints of both
the bioreceptors and the attached biomarkers.
As a proof of concept, we incubated the functionalised
nanoantennas with MnSOD, and with BSA (bovine serum albumin, which
does not attach to the bioreceptors). We found that we could only
detect vibrational fingerprints of MnSOD.
What is the advantage of using such approach compared to
other testing methods?
Typically, kits that are now available are based on fluorescence
and you have a sensitivity going to extremely small scale, down to
one nanomolar, or even one picomolar. But the real advantage is that
with the nanoantennas we can reach a sensitivity of a femtomolar.
And what is fascinating is that we even have proof of concept that
you can detect single molecules by their vibrational fingerprint.
The other advantage of this approach is that the detection method,
Raman spectroscopy, does not require staining of the target
molecules, it is label free.
Are biosensor kits using nanoantennas now available for clinical
No, our project finished in March 2013. And our aim was to
deliver a proof of concept. We will first have to implement the
technology in a microfluidic circuit, a biochip, in which we can
test biofluids, such as saliva or blood. This biochip should be
combined with a spectrometer that should be portable. For the moment
we have a table-top spectrometer linked to a computer. We should aim
at developing a suitcase spectrometer based on optical fibres.