Process control Raman techniques

The lower absorptivities and stronger light sources allow for deeper penetration into the process broth centimeters vs. millimeters. NIR was also the first spectroscopic technique used for process control by large numbers of chemical manufacturers. As a consequence, more equipment and expertise are available for NIR applications than for MIR or Raman. 

Natural products, from plants and foods to rocks and minerals, are complicated systems, but their analysis by Raman spectroscopy is a growing area. Most examples come from quality control laboratories, motivated to replace current time-consuming sample preparation and analysis steps with a less labor-intensive, faster technique but most authors anticipated the eventual application to process control. Often a method will be practiced in a trading house or customs facility to distinguish between items perceived to be of different qualities, and thus prices. 

In recent years, Raman spectroscopy has undergone a major transformation from a specialist laboratory technique to a practical analytical tool. This change was driven on several parallel fronts by dramatic advances in laser instrumentation, detectors, spectrometers, and optical filter technology. This resulted in the advent of a new generation of compact and robust Raman instruments with improved sensitivity and flexibility. These devices could be operated for the first time by non-specialists outside the laboratory environment. Indeed, Raman spectroscopy is now found in the chemical and pharmaceutical industries for process control and has very recently been introduced into hospitals. Handheld instruments are used in forensic and other security applications and battery-operated versions for field use are found in environmental and geological studies. 

Outside of the occasional system calibration and model verification tests, the routine maintenance burden of a Raman system is quite low. Optical windows may need to be cleaned, though automatic window cleaning systems can be implemented if it is a known issue. The most likely maintenance activity is laser replacement. Some systems have a backup laser that turns on automatically if the primary laser fails. This lessens the impact of a failure if the unit is being used for closed-loop process control. With a quality instrument and well-developed models, process Raman installations need less maintenance than many competing techniques. 

Rapid advances in semiconductor techrwlogy, including thin film formation by deposition, interface preparation or microstructuring, demand characterization techniques that provide understanding of the fundamental processes involved, including information on structural order—disorder and spatial inhomogeneity. Raman spectroscopy is used both in process control and quality assessment [34]. Typical examples of semiconductor applications are composition determination, analysis of crystal structure, surface and interface analysis, phase determination, doping, point defects, temperature influence and mechanical stress. 

New approaches to analyze essential oils by vibrational spectroscopy using attenuated re ec-tion (AIR) IR spectroscopy and NIR-FT-Raman spectroscopy have recently been published by Baranska et al. (2005) and numerous papers cited therein. The main components of an essential oil can be identi ed by both spectroscopic techniques using the spectra of pure oil constituents as references. The spectroscopic analysis is based on characteristic key bands of the individual constituents and made it, for example, possible to discriminate the oil pro les of several eucalyptus species. As can be taken from this paper, valuable information can be obtained as a result of the combined application of ATR-IR and NIR-FT-Raman spectroscopy. Based on reference GC measurements, valuable calibration equations have been developed for numerous essential oil plants and related essential oils in order to quantify the amount of individual oil constituents applying different suitable chemometric algorithms. Main advantages of those techniques are their ability to control the quality of essential oils very fast and easily and, above all, their ability to quantify and analyze the main constituents of essential oils in situ, that means in living plant tissues without any isolation process, since both techniques are not destructive. 

Process analytical technology (PAT) can be developed early in development with a line of sight to commercial process control (ICH Qll 2011a). Easily integrated into the process equipment, as shown in Fig. 7.1, the application of in-line probes can provide unique opportunities to monitor processes in line. Spectroscopic techniques such as ultraviolet/visible (UV/VIS), near-infrared (NIR), and Raman can be utilized in line at the extmder die to ensure critical quality attributes (CQAs) such as composition and amorphous conversion of the API. Validation of these techniques at the pilot scale and transfer to the commercial scale allow for efficient manufacture of commercial material in a continuous manner and the implementation of a process control strategy that enables material outside the design space to be diverted to waste... 

FT-Raman spectrometers are now being superseded by polychromators equipped with CCD array detectors and NIR diode laser excitation. These instmments allow spectra to be measured in a few seconds. The new generation of instrumentation has helped to establish Raman spectroscopy as a routine analytical technique, with industrial process-control applications. Portable process Raman analysers enable both in-line and at-line measurements. 

Principles and Characteristics As already indicated in Chp. 1.2.3, Raman scattering induced by radiation (UV/VIS/NIR lasers) in gas, liquid or solid samples contains information about molecular vibrations. Raman specfioscopy (RS) was restricted for a long time primarily to academic research and was a technique rarely used outside the research laboratory. Within an industrial spectroscopy laboratory, two of the more significant advances in recent years have been the allying of FT-Raman and FTIR capabilities, coupled with the availability of multivariate data analysis software. Raman process control (in-line, on-line, in situ, onsite) is now taking off with various robust commercial instrumental systems equipped with stable laser sources, stable and sensitive CCD detectors, inexpensive fibre optics, etc. With easy interfacing with process streams and easy multiplexing with normal (remote) spectrometers the technique is expected to have impact on product and process quality. 

In process control systems it is essential to develop rapid on-line monitoring techniques to acquire structural parameters such as crystallinity, and orientation. By controlling these structural parameters the end use properties may be influenced which are essentially defined by these parameters. In order to use laser Raman spectroscopy for such purposes, calibration systems need to be developed using an independent technique. 

Raman spectroscopy is relatively new as an in-process technique, yet several applications in routine analytics, quality and process control in various branches of industry (food, pharmaceutics, mineral... 

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