RAMAN SUPPLEMENT


Pavel Matousek: The importance of spectral interpretation is indeed diminished in many applications that do not require it. This is a positive move toward permitting its wider use in practical applications as the operator can treat the Raman system as the black box. Although regulatory filings will be often scrutinised for this kind of interpretative understanding.


Ken Williams: Although chemometrics is invaluable in many situations, a huge amount can be accomplished through basic interpre - tation. Functional group analysis may be used to suggest structural elements and the source of an impurity. Comparison of peak areas is often enough to assess the crude composition of a mixture. The principles and benefits of Raman spectroscopy should be taught much more widely to undergraduates across all scientific disciplines.


Mike Kayat: Raman applications cover a broad range from drug discovery to manufacturing, and include identifying polymorphs, monitoring real-time processes, imaging solid dosage formulations, imaging active pharmaceutical ingredients in cells, and diagnostics. Industrial process control instruments will increasingly have embedded Raman spectrometers. The high volume application is ensuring the 100 per cent verification of raw materials with handheld tools which have been calibrated and qualified to meet stringent quality standards. Advanced chemometrics applications in the future will enable analysis of multi-component mixtures with both known and unknown compounds and concentrations. Scientists will be able to develop comprehensive models for interpreting Raman spectra of complex materials including trace level contaminants.


Do you have any guidance on how to choose between dispersive and Fourier transform instruments? Are there any particular applications that work better in a specific configuration?


Ken Williams: If there is little sample fluorescence with ‘conventional’ lasers (to 830 nanometres), a CCD detector has optimum sensitivity, so dispersive technology should be used. If, to overcome fluorescence, a 1064 nanometre laser with InGaAs detector is needed, the choice is between dispersive and FT. If the sample requires microscopy,


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European Pharmaceutical Review Volume 16 | Issue 5 | 2011


then dispersive is more appropriate compared to large area sampling where FT may be better. Dispersive is also advantageous when looking for weak Raman signals in the presence of strong ones (the FT technique distributes noise from the strong peaks across the whole spectrum, making it harder to detect weak peaks).


Mike Kayat: The key decision factors include: sampling type, state and method, required spectral range, resolution and sensitivity, along with physical location and environment. Currently FT IR and NIR instruments are prominent within the pharmaceutical industry, mainly for lab analysis, for specific sample types. However, dispersive Raman analysis is emerging as the more adaptable approach to materials characterisation, for a wide range of sample types and states including high/low temperatures and variable pressures. The continuing miniaturisation of key components like lasers, optical benches, processors and batteries together with lower price points, will drive the high volume adoption of handheld Raman units to achieve 100 per cent screening of raw materials.


Ian Lewis: Fourier Transform instruments, as a group, are suitable for laboratory use only. Dispersive instruments are preferred when:


 the sample is small and diffraction limited spatial performance is necessary (samples between 0.5 and 25 microns). In this case, a dispersive Raman microscope is the best choice


 if the sample is changing during a reaction or is bubbling or its optical properties are changing. In this case, a dispersive analyser with in-situ probes or a PhAT probe is the best choice. FT-Raman instruments are susceptible to artefacts caused by transients changes in the sample


 if the sample is a hazardous area / classified environment then a dispersive analyser and probes with ATEX or FM marking is required


 if the sample is in the gas-phase then a dispersive instrument is preferred. In this case the excitation wavelength should be in the green as this maximises the amount of Raman scattering which is a likely requirement for a low concentration / cross- section gas or vapour-phase sample


 if the sample requires the analysis to


brought to the sample then a fibre-coupled or hand-held dispersive instrument are the preferred choices


 if the sample is present in a dilute solution in water or alcohol then the use of a dispersive instrument avoids the problem of ‘self- absorption’ reported in the literature for FT- Raman quantitation


 if the sample / coating of the sample contain transition metals then the sample / coating should be carefully evaluated during method development to detect non-Raman features which could interfere with quantitation. If no interferences can be detected using multiple excitation wavelengths then either approach can be used


 if Raman imaging or mapping is required then dispersive is the preferred technique


 if the sample is of an unknown purity state, at relative high concentration, and can be handled in a laboratory environment then FT-Raman can be used


 if significant spectral subtraction is required then either analyser if properly calibrated can suffice although the FT instrument has an edge in this case


 if the sample is highly fluorescent then excitation at around 1000 nanometres is necessary. Four years ago, this would automatically mean an FT-Raman approach now however there are dispersive instru - ments which utilise NIR-sensitive InGaAs arrays to allow equivalent measurements either by FT or dispersive approaches


Mike Claybourn: FT-Raman is fine for powder samples and is good if fluorescence is a problem with shorter wavelength lasers. The high laser powers used can damage the sample. FT-Raman is no good for microscopy. Dispersive Raman can be used at many wavelengths targeting the application. Many different accessories and sampling configurations are available to meet end user needs. The main advantage is micron scale analysis and the ability to generate Raman images of a sample.


Pavel Matousek: As a rule of the thumb, if the fluorescence is not an issue with your sample choose a dispersive system as it is likely to perform better. However if the fluorescence is an issue and you cannot detect your spectra, or the spectra are too noisy, then go for FT Raman.


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