Raman spectroscopy volume requirements

Raman spectroscopy s sensitivity to the local molecular enviromnent means that it can be correlated to other material properties besides concentration, such as polymorph form, particle size, or polymer crystallinity. This is a powerful advantage, but it can complicate the development and interpretation of calibration models. For example, if a model is built to predict composition, it can appear to fail if the sample particle size distribution does not match what was used in the calibration set. Some models that appear to fail in the field may actually reflect a change in some aspect of the sample that was not sufficiently varied or represented in the calibration set. It is important to identify any differences between laboratory and plant conditions and perform a series of experiments to test the impact of those factors on the spectra and thus the field robustness of any models. This applies not only to physical parameters like flow rate, turbulence, particulates, temperature, crystal size and shape, and pressure, but also to the presence and concentration of minor constituents and expected contaminants. The significance of some of these parameters may be related to the volume of material probed, so factors that are significant in a microspectroscopy mode may not be when using a WAl probe or transmission mode. Regardless, the large calibration data sets required to address these variables can be burdensome. 

Multiwavelength spectroscopy of biofluids provides several advantages over chemical assays that are not particular to Raman spectroscopy. First, all measurements are performed on the same sample volume, since multiple chemicals concentrations can be computed from a single spectrum. There is typically just one optical sensor unit or cartridge required. In multi-chemical assays, the sample must be separated into subvolumes that are sent to different single-chemical sensor units. This increases the volume of sample needed, the complexity of the sample s path through the analyzer, and the number of sensor units needed. 

An important development in Raman spectroscopy has been the coupling cf the spectrometer to an optical microscope. This allows the chemical and structural analysis described above to be applied to sample volumes only 1 across [38]. No more sample preparation is required than that for optical microscopy, and the microscope itself can be used to locate and record the area which is analyzed. This has obvious practical application to the characterization of small impurities or dispersed phases in polymer samples. This instrument, which may be called the micro-Raman spectrometer, the Raman microprobe or the Molecular Optics Laser Examiner [39] has also been applied to the study of mechanical properties in polymer fibers and composites. It can act as a non-invasive strain gauge with 1 fim resolution, and this type of work has recently been reviewed by Meier and Kip [40]. Even if the sample is large and homogeneous, there may be advantages in using the micro-Raman instrument. The microscope... 

Raman spectroscopy is widely used as a diagnostic tool for the evaluation of diamond crystals and CVD diamond films. The technique is popular because each carbon allotrope displays a clearly identifiable Raman signature, it is nondestructive (when the correct laser irradiation parameters are chosen), requires little or no specimen preparation, and can be made confocal so that micrometer volumes can be sampled. Raman scattering from single-crystal, CVD diamond films, and ND has recently been reviewed in Refs. 87,88. 

Several techniques are usually employed to study the strain in QD layers. Raman spectroscopy and high-resolution X-ray diffraction, on the one hand, can be routinely used to address this issue, but the data obtained are averaged over the entire volume of the dots. High-resolution transmission electron microscopy (HRTEM), on the other hand, provides information at the monolayer scale, but the technique requires extensive sample preparation that may induce an extra relaxation owing to thin foil effects the data gathered are local and may not reflect the structure of the whole sample. Medium energy ion scattering (MEIS) appears as an alternative no preparation is needed. 

A detailed account of polymorphism and its relevance in the pharmaceutical industry is given elsewhere in this volume and in the literature [42,46,47]. This section will focus on the use of vibrational spectroscopy as a technique for solid-state analysis. However, it should be noted that these techniques must be used as an integral part of a multidisciplinary approach to solid-state characterisation since various physical analytical techniques offer complimentary information when compared to each other. The most suitable technique will depend on the compound, and the objectives and requirements of the analysis. Techniques commonly used in solid-state analysis include crystallographic methods (single crystal and powder diffraction), thermal methods (e.g. differential scanning calorimetry, thermogravimetry, solution calorimetry) and stmctural methods (IR, Raman and solid-state NMR spectroscopies). Comprehensive reviews on solid-state analysis using a wide variety of techniques are available in the literature [39,42,47-49]. 

Chemical analysis of polymers typically deals with monomers or functional groups rather than constituent atoms. Thermal infrared and laser optical Raman spectrometry are the typical tools (36) (see Test Methods Vibrational Spectroscopy), but frequently, specific specimen size or form is required. For physical properties, mechanical and sonic/ultrasonic NDT methods are available (see above). Molecular mass distribution and related properties of polymers, or fiber or particle volume fraction and distribution for PMC, are usually determined destructively (see Test Methods). 

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