While Raman spectroscopy is an excellent technique for quantitative and qualitative analysis of molecular species and materials, its Achilles heel has always been the inherently weak nature of the Raman signal and, on moving to shorter excitation wavelengths, the issue of the competitive fluorescence background.
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The strength of a Raman signal is inversely proportional to the fourth power of the wavelength of the scattered light. In practical terms, this means that the longer the excitation wavelength used to irradiate a sample, the weaker the observed Raman signal.
There are several approaches to increasing the intensity of the scattered Raman signal. One is to use a more intense laser source, though this can be problematic for portable devices or materials that are particularly prone to laser-induced degradation. Another is to use shorter excitation wavelengths, but for strongly fluorescing samples, this can create a background of fluorescence signal that can mask the weak Raman features.
Another approach to increase Raman signal levels when probing the surface of materials is to use a technique called surface-enhanced Raman spectroscopy. Surface-enhanced Raman spectroscopy (SERS) uses a substrate that adheres selectively to the surface of the substrate of interest and enhances the probability of the Raman scattering process.1
SERS has rapidly become a widely adopted technique in a number of fields for probing both simple and complex molecules.2 Recently, it has been extended to look at semiconductor and hybrid materials and one of the big challenges that SERS has overcome is the creation of suitable SERS probes.
As many probes rely on the accurate creation of nanostructures, improvements in high-precision lithography methods have helped increase the number of SERS probes and the viability of the methods for looking at a wider range of chemical species.
SERS Probes
There is a range of different SERS probes now available to enhance the Raman signal levels. Different probes have different mechanisms for enhancing the Raman signal from the sample. Some of the most common mechanisms include chemical enhancement, possibly through the transfer of electrons, modification of the electronic absorbance of the sample, strong coupling behavior and quantum effects.2
SERS probes are typically chosen for their specificity to a given substrate as well as other optical properties, including low fluorescence or photoluminescence.3 SERS probes with low emission quantum yields help produce less background during the measurement and therefore do not diminish the contrast between the signal and the background.
A very traditional SERS probe still capable of achieving significant enhancements of the Raman signal is metal nanoparticles. Gold and silver are two of the most commonly used plasmonic materials for enhancement of the Raman response and this local field enhancement from the metal nanoparticles are widely used in fields such as biomedical imaging.3
Part of the appeal of SERS probes, particularly for biological imaging, is that they can be label-free probes. Many bioimaging techniques such as fluorescence require a tag to be chemically bonded to the substrate of interest, which can potentially distort the structure or alter the properties of the substrate. With metal nanoparticle SERS probes, a suitable substrate just needs to be in close proximity to the probe.
Metal Nanoparticles
Metal nanoparticles make excellent SERS probes as they can achieve a good degree of signal enhancement and it is possible to use ligands to stabilize them in solution. In the same way, ligands can be attached to the nanoparticle's surface to promote stability, the substrates of interest can be attached and additional SERS probes.
Gold shows fantastic biostability and biocompatibility and the highly flexible and customisable nature of gold nanoparticles has made them a popular choice. Nanoparticles often have strong absorbance in the visible and gold can also absorb in the near-infrared region – an excellent wavelength region for performing bioimaging as the ‘biological window’ exists in this spectral range. The biological window means there will be little absorption of the incident near-infrared light for making measurements.
It is even now possible to create ligands that can encapsulate the nanoparticle to overcome issues with the delivery of the nanoparticles into cells.4 Being able to track these biomarkers is an important way of understanding the function of the human body and diseases and gold nanoparticles have been used for in vivo diagnostics and imaging.
Metal nanoparticles have been challenging to synthesize. As their optical properties are size-dependent, controlling the size distribution in a batch can be difficult and ensuring interbatch repeatability can be difficult.
New synthesis approaches are simplifying making nanoparticles with restricted size diversity and others are improving the energy efficiency and environmental impact of such syntheses.5 All of these methods are helping to increase the availability of a wide range of SERS probes and also ensure metal nanoparticles have a viable future use
Metal nanoparticles are an excellent tool for SERS in many imaging applications, from biomedical to materials characterization. The strong Raman signal enhancement makes measurements more straightforward and can help reveal the Raman spectra from samples that would have been previously impossible to see.
References and Further Reading
Nilghaz, A., Mousavi, S. M., Amiri, A., Tian, J., Cao, R., & Wang, X. (2022). Surface-Enhanced Raman Spectroscopy Substrates for Food Safety and Quality Analysis. Journal of Agricultural and Food Chemistry, 70, 5463–5476. https://doi.org/10.1021/acs.jafc.2c00089
Langer, J., Aberasturi, D. J. De, Aizpurua, J., Alvarez-puebla, R. A., Auguie, B., Baumberg, J. J., Bazan, G. C., Bell, S. E. J et al. (2020). Present and Future of Surface-Enhanced Raman Scattering. ACS Nano, 14, 28–117. https://doi.org/10.1021/acsnano.9b04224
Perez-Jimenez, A. I., Lyu, D., Lu, Z., Liu, G., & Ren, B. (2020). Surface-enhanced Raman spectroscopy: benefits, trade-offs and future developments. Chemical Science, 11, 4563–4577. https://doi.org/10.1039/d0sc00809e
Ando, J., & Fujita, K. (2013). Metallic nanoparticles as SERS agents for biomolecular imaging. Current Pharmaceutical Biotechnology, 14(2), 141-149. https://doi.org/10.2174/138920113805219377
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