Tom Shelley reports on a discovery that transforms a lab research technique into something suitable for medical and industrial sensing
A fairly simple technique that forms tiny reflective surfaces
– each only a few tens or hundreds of nanometres across
– can enhance the sensitivity of Raman spectroscopy by up to
a billion times.
Raman spectroscopy is used by many research scientists because of
the large amount of information it yields about molecules. But
for every trillion photons of light going through a system, only
one will provide useful information. (See box for more on the
technique.)
Finding a way to boost its efficiency could create a tool for
medical diagnostics – where it is already being trialled
– and possibly for industrial sensing and anti-chemical and
biological threat applications.
Professor Martin Fleischmann, the Southampton University based
scientist best known for his role in the ‘cold fusion’
controversy, found that the Raman effect was greatly enhanced
close to a rough metal surface, giving rise to a technique called
Surface Enhanced Raman Spectroscopy (SERS). A later team of
researchers at the University has since come up with a way of
engineering the right kind of roughness to enhance the effect
further.Professor Phil Bartlett, deputy head of the School of
Research at Southampton, explained that his team starts with tiny
polystyrene spheres, commercially available in standard sizes
down to 50nm. These are laid down on a flat surface using the
retreating meniscus of evaporating water as a flat substrate. The
surface is then metal plated, usually with gold, so that the
metal builds up between the spheres, after which they are
dissolved away, to leave either partially spherical,
hemispherical or nearly complete spherical cavities, depending on
the time at which the metal plating process is stopped.
“The way the nanobowls work is rather like an opal,”
Prof Bartlett explained. “Laser light at 785nm excites
plasmons. Plasmons are where electrons in a solid surface are
sent rippling in a similar way to ripples on a pond. Molecules at
or near the surface red shift the plasmons corresponding to the
molecular vibrations.”
Because the light tends to get stuck in small pockets – in
the nanobowls – it gets funnelled into the molecules,
enhancing the Raman spectroscopy signatures by up to a billion
times. The effect is increased by having the nanobowls in regular
arrays.
The other, more important consequence of having regular arrays is
that it makes the measurements reproducible. Previously, the
enhancement effect was impossible to control reliably, making it
useless for real world applications.
For researchers, the technique is exciting because only molecules
close to the surface show up in the detected spectrum. This is of
great interest in studies of catalysis. Prof Bartlett said that
it responds to the presence of a mere 90 million individual
molecules – a tiny amount in molecular terms.
Because SERS works with very small samples and can identify very
specific molecules, the technique is also proving to be of
interest in medical diagnosis. A collaborative research project
between Southampton University, Mesophotonics and Gloucestershire
Hospitals NHS Foundation Trust is the recipient of a £750,000
grant from the DTI’s Industry Technology Programme.
Mesophotonics is the company spun out of Southampton University
to commercially exploit earlier and slightly different
nanostructured surfaces for SERS which it markets under the name
Klarite. The Klarite products currently on offer use arrays of
pyramidal pits produced by lithography.
“This gives them similar, but different, optical properties
to the nanobowls,” says Prof Bartlett.
The initial phase of the research is focussing on identifying
virus particles in tear drops from patients with conjunctivitis,
a disease notoriously hard to diagnose because both viral and
anti bacterial strands produce similar symptoms. If incorrectly
diagnosed, wrong treatment can result in long-term infection and
in some cases, blindness. There are more than 840,000 cases per
year in the UK and it is estimated that real-time, cost effective
diagnosis could save the NHS £471m over 10 years in terms of
savings in drugs, laboratory time and the number of patient
visits.
Prof Bartlett told Eureka that this Raman technique can
distinguish between viral and bacterial infections in the eye.
“Viral infections lead to the presence of a lot of DNA in
the fluid. Bacteria introduce less DNA, but cause changes in the
enzymes in the tear, which can also be identified,” he says.
Dr Nick Stone of Gloucestershire Royal Hospital has pioneered the
use of Raman spectroscopy in medical diagnosis for more than nine
years.
“Tear film is of great clinical diagnostic value but in the
past there was no way to detect the extremely low concentration
of viral particles,” he says. “The increased
sensitivity provided by Photonic Crystal SERS substrates such as
Klarite enables us to separate the characteristic Raman signature
from background noise and natural fluorescence.
“If successful, the project could enable the technique to be
used for early diagnosis of a range of other diseases including
hepatitis, HIV, diabetes and Chlamydia.”
The instrumentation being trialled is described as “simple
and low cost”. The project is to run until January 2008.
It is also seen as a good technique for identifying toxins in
foods and traces of pollutants, and adds a new tool for chemical
detection, in addition to devices such as solid state
electrochemical sensors which are usually not very sensitive and
are usually specific to one chemical substance per device. It may
also have applications in combating chemical and biological
threats.
University of
Southampton Optoelectronics Research Centre
Mesophotonics
Background to Raman
Raman spectroscopy was discovered by Indian physicist CV Raman in
1928, and it earned him a Nobel prize in 1930. Light of a single
wavelength, nowadays invariably supplied by a laser, is shone
through a specimen – usually a liquid. Most of the light is
either scattered or emerges unchanged. But in some cases, the
wavelength is increased or decreased. Molecular bond vibrations,
rotations or other excitations either absorb or give out energy
so that the energy – and thus the wavelength – of the
photons are shifted up or down. This shift helps to identify the
molecules within the system and what is happening to them.
Wavelengths close to the laser line, changed only by elastic
Rayleigh scattering are filtered out and those in a certain
spectral window away from the laser line are sent to a detector.
Pointers
* Substrate increases sensitivity of Raman spectroscopy by up to
a billion times
* Raman spectroscopy can be used to identify many different types
of molecules without having to know what to look for in advance
* Equipment is still in development, but commercial versions
could be simple to use and low cost
For more technical
developments see www.eurekamagazine.co.uk