Nicholas Pieczonka and Ricardo Aroca of the University of Windsor in Canada use Raman scattering to look at one molecule in a million

Molecules close to metallic nanoparticles show enhanced Raman scattering

Single molecule spectroscopy (SMS) uncovers the information and behaviour that is lost when measuring an ensemble of molecules. To be able to detect the spectroscopic signal from a solitary molecule, it must have extraordinary absorption or emission properties. And so, the majority of SMS work has been accomplished by measuring the fluorescence of molecules with exceptional luminescence abilities. But the molecular information and the class of molecules that can be probed through fluorescence are limited.

Raman scattering (RS), the inelastic scattering of light from molecules, is an alternative optical spectroscopy that provides a vibrational spectrum, a true characterisation of any stable electronic state. It is rich in information and can be applied to virtually any type of chemical species. It is not always an efficient process; however its cousin, resonance RS, can be orders of magnitude more intense.

Just over 30 years ago, scientists discovered that a molecule's Raman signal could be greatly enhanced by putting it close to metallic nanoparticles. They found that the source of the enhancement was the intense fields provided by the localised surface plasmon resonances (LSPR), or waves of electrons, that occur when the nanoparticles are excited by light. The new physical phenomenon delivered several new analytical techniques, including surface-enhanced Raman scattering (SERS) and surface-enhanced resonance Raman scattering (SERRS). Several groups expanded the potential for SER(R)S even further by demonstrating that certain nanostructures provide intense field enhancements, known as hot spots, that are large enough for single molecule detection.

Today, there is a vast body of work that illustrates both the promise and the inherent challenges in SM-SER(R)S. Only two metals (silver and gold) and a handful of nanostructures (aggregated colloids, metal island films and scanning tunnelling microscopy (STM) tips) have demonstrated SM sensitivity. Also, investigations have revealed a very strong dependence between the scattering ability of the molecule and the type of nanostructures that can be used. Molecules that are relatively weak scatterers require nanostructures that can support hot spots, whereas for strong scatterers, single plasmon supporting structures, such as STM tips, will do.

A daunting challenge to SM-SER(R)S is that, in many instances, SM detection depends critically on the structure of the molecule for selective adsorption, particularly onto hot spots. And although ensemble SERS has been observed for all types of molecular systems, SM-SER(R)S has been observed only for a very limited selection of chemical structures, in particular molecules containing electron-rich moieties.

Scientists are developing a greater understanding of the underlying features of the Raman signal measured for a single molecule. At present, the most common signature that supports the claim that the recorded spectrum comes from a single molecule is fluctuations of the signal. This includes variations in the frequency, bandwidth, relative intensity and, sometimes, an on-and-off behaviour of the spectrum. These dynamics hold a wealth of information that is waiting to be untapped.

The use of plasmon supporting nanostructures for SM-SER(R)S is still at an early stage of development and holds enormous promise for potential applications. The future of SM-SER(R)S will demand a great deal of effort from experimentalists and theorists but this will be justified by the application of SMS in areas of nanoscience and ultrasensitive chemical analysis. The most important implications and fascinating applications may come from the advancement of our understanding of plasmonics. The interaction of molecular systems with confined electromagnetic waves in metallic nanostructures is clearly an exciting subject of study and will no doubt be the source of new knowledge in SM-SER(R)S.

Read Pieczonka and Aroca's tutorial review 'Single molecule analysis by surfaced-enhanced Raman scattering' in issue 5, a SERS thematic issue of  Chemical Society Reviews.