Raman spectroscopy is an incredibly robust tool for the identification of many classes of chemical compounds in materials. In pharmaceuticals, Raman plays an integral role in quality control and drug design1,2 and Raman is also a widely used technique in the life sciences and for process monitoring.3,4

What makes Raman spectroscopy so powerful for molecular identification and quantification is that every molecular species has a unique spectral ‘fingerprint’. Raman spectroscopy works by measuring the energy change of photons scattered from the sample, which correspond to the electronic or vibrational energy spacings in the molecule of interest.

Normally Raman spectroscopy is performed with an intense laser source. When the light is focused on the sample, some photons will be scattered elastically, meaning the scattered photons have the same frequency as the incident photons. Other photons will undergo inelastic scattering and so have a smaller or larger frequency than the incident photon. If the scattered photon is shifted to higher frequency (or shorter wavelength or higher energy) shift is known as the anti-Stokes shift, or if it is shifted to lower frequencies, it is known as the Stokes shift.

Measurement Challenges

While Raman spectroscopy has become a widely adopted tool, even for field measurements,5 one of the challenges when designing instruments for Raman spectroscopy is the weak nature of the Raman process. The majority of photons that interact with the sample will be elastically scattered (sometimes also called Rayleigh scattering) and the probability of undergoing inelastic scattering is often orders of magnitude smaller.

As the inelastically scattered photons are what provide information on the vibrational or electronic structure of the molecule and therefore what is needed for molecular identification and quantification, a Raman spectroscopy needs to be designed with detecting these weak signals in mind.

Another challenge for Raman spectroscopy is that, while Raman signal is stronger with shorter excitation wavelengths, shorter excitation wavelengths have a greater probability of promoting electronic transitions in the molecule that can lead to fluorescence processes. Fluorescence from a sample can give rise to very broad background signals which can obscure the weak features of interest.

Optical Filters for Raman Spectroscopy

The ‘fingerprint’ region of the Raman spectrum that provides the richest information for chemical identification may be separated by less than a hundred wavenumbers from the excitation frequency of the laser used. A common approach in Raman spectroscopy to improve the signal-to-noise of the Raman features is to use filters to block any residual excitation frequencies/elastic scattering signal, fluorescence or other unwanted scattering.

However, if cut-off filters are to be used for fingerprint Raman, they need not only a very high optical density to block the excitation source but also a sharp cut-off so they do not attenuate any Raman signals close to the excitation lines.

Finding the right filters with the ideal properties for Raman spectroscopy can be very challenging, and this is where working with experts like us can benefit you. Iridian Spectral Technologies has worked with many partners to provide the right components for both high-precision and handheld Raman instruments and knows many of the challenges that instrumentation in this area faces.

Handheld Devices

When it comes to the design of handheld Raman instruments, environmental robustness and a small footprint are often of chief concern when choosing the right filters for a spectrometer. The ability to have custom-designed components or with custom mounting solutions can be very advantageous in achieving the right design specifications for a handheld instrument.

Another challenge of measuring in real-world environments is that materials are often scanned with light arriving at wider angles of incidence (AOI) than in laboratory environments where the sample would be in a fixed position. Collimation may also be more challenging in small-footprint field instruments, and so the optical filters need to be able to cope with a broader range of input conditions.

References

1. de Jesus, J. I. S. da S., Löbenberg, R., & Bou-Chacra, N. A. (2020). Raman spectroscopy for quantitative analysis in the pharmaceutical industry. Journal of Pharmacy and Pharmaceutical Sciences, 23(1), 24–46. https://doi.org/10.18433/jpps30649
2. Paudel, A., Raijada, D., & Rantanen, J. (2015). Raman spectroscopy in pharmaceutical product design ☆. Advanced Drug Delivery Reviews, 89, 3–20. https://doi.org/10.1016/j.addr.2015.04.003
3. Esmonde-White, K. A., Cuellar, M., Uerpmann, C., Lenain, B., & Lewis, I. R. (2017). Raman spectroscopy as a process analytical technology for pharmaceutical manufacturing and bioprocessing. Analytical and Bioanalytical Chemistry, 409(3), 637–649. https://doi.org/10.1007/s00216-016-9824-1
4. McAvan, B. S., Bowsher, L. A., Powell, T., O’Hara, J. F., Spitali, M., Goodacre, R., & Doig, A. J. (2020). Raman Spectroscopy to Monitor Post-Translational Modifications and Degradation in Monoclonal Antibody Therapeutics. Analytical Chemistry, 92(15), 10381–10389. https://doi.org/10.1021/acs.analchem.0c00627
5. Sorak, D., Herberholz, L., Iwascek, S., Altinpinar, S., Pfeifer, F., & Siesler, H. W. (2012). New developments and applications of handheld raman, mid-infrared, and near-infrared spectrometers. Applied Spectroscopy Reviews, 47(2), 83–115. https://doi.org/10.1080/05704928.2011.625748