Tiny reflectors boost sensing a billion

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 DTI funded trial screening of tears with NHS and mesophotonics 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