The technique is nondestructive and can measure samples in real-time, making it an effective process analysis tool. Our company was founded in 2009 and is now co-funded by the Horizon 2020 program of … This was a key theme at the 8th Symposium on Continuous Flow Reactor Technology for Industrial Applications held in Delft in 2016, and many of our customers have asked what techniques Quantitative analyses utilizing Raman spectroscopy are of increasing importance in the manufacturing industry for online or inline process control. The first example is the manufacture of organometallic compounds, such as trialkyl aluminum compounds, that are pyrophoric and dangerous to sample. Water becomes a unique fluid above its thermodynamic critical point (374 °C, 22.1 MPa), but there are very few tools that can study the decomposition of organic waste at these temperatures and pressures. Are their instruments portable? A semi-manual fluorescent background subtraction method was used for consistent spectral processing. An example is trimethyl aluminum (TMA), a highly sensitive and reactive chemical compound. In the end, CPPs such as temperature, pressure, residence time, and the concentrations of H2, CO2, CO, and residual formic acid were identified. Med. The obtained spectra were preprocessed, and differential spectra were calculated by subtraction of the core spectrum from each inline spectrum. Kaiser has been a leader of in situ monitoring and control in bioprocessing since 2007 because of our robust in situ Raman solutions and expertise in life sciences from R&D to GMP.. References. Raman ensures product quality and consistency by transmitting real-time compositional data to advanced process control (APC) systems in seconds. The development of an inline Raman spectroscopic analysis method as a quality control tool for hot melt extruded ramipril fixed-dose combination products Currently in the pharmaceutical industry, continuous manufacturing is an area of significant interest. Outside the laboratory, Raman spectroscopy has found a home in manufacturing and quality analysis. The gasification of formic acid resulted in yields of H2, CO, and CO2. Process operators then extract samples at set times and send them to the laboratory for analysis. The ability to install your Raman spectroscopy system at the point of need is essential in these applications. New Raman spectroscopy applications are emerging in non-traditional fields because of advancements in easy-to-use commercial Raman spectroscopy instrumentation (1). It can transform organic waste, such as biomass, into hydrogen-rich syngas. Figure 3 shows the continuous Raman spectroscopy analysis of product purity versus time. (7) D. Lowe, Safety Warnings. The use of Raman spectroscopy also allowed operators to collect data during reactor operation, which quickly assessed the reaction products. 10/23/2020 10:00 AM EST. You may need to download version 2.0 now from the Chrome Web Store. Process Raman spectroscopy is the answer to these questions because it offers a higher level of compositional information for process control. Bioanal. It produces a unique spectral fingerprint that identifies the chemical composition and molecular structure of materials. Relevant constituents can thus be measured in-situ and processes can be optimized accordingly. Our technology is fitted to the existing manufacturing facilities, boosting their productivity and quality. Since its discovery in the 1920s, Raman spectroscopy has revolutionized process analysis with its nondestructive nature and ability to measure sample composition. Novosselov, Int. These recent developments have been valuable in reducing the need for sample extraction and handling, especially when hazardous materials are present. Gorman, E.G. In-line Raman Spectroscopy. One strategy is to use a sensitive, spectroscopic inline measurement for process monitoring and control during the manufacturing process. The equipment used was a fiber-optic immersion probe with a 785-nm laser operating at the 300 mW power setting. New Raman spectroscopy applications are emerging in non-traditional fields because of advancements in easy-to-use commercial Raman spectroscopy instrumentation (1). The use of Raman spectroscopy as an in-line and non-destructive technique is quick and yields valuable information about protein stability, especially for the aggregation. To control product quality during HME without process interruption, integration of inline analytical technology is critical. Traditionally, gas chromatography is used for total organic carbon (TOC) analysis. Such analysis is possible using a Raman microscope. SCWG is an emerging alternate fuel technology (9,10). For the spectra collected in this study, indirect hard modeling (IHM) was used to extract species concentration data. MarqMetrix Process Raman systems make this easier, faster and repeatable: http://ow.ly/hDUo50CWoNs Hazardous compound sampling and the transformation of organic waste into alternate fuel technology share one common factor: Both are more efficient when continuously monitored with a Raman spectrometer. Sample mixtures, even those containing water, can also be analyzed quickly and effectively. A separate identical probe with a 3-m fiberoptic cable was coupled to the spectrometer for model development purposes. Organometallics are manufactured in large volumes with very high purity, which presents major analytical obstacles, because sample handling is hazardous (8). 400, 2439–2447 (2011). The simplicity of this data-rich qualitative and quantitative information makes Raman spectroscopy an attractive process analytical technology (PAT) tool. THE IMEC SOLUTION Thanks to a new concept our photonic platform (using waveguides on chip), imec has been able to overcome the performance barrier in small-scale Raman spectroscopy devices. There are clear differences in the spectra that correspond to the variation in sample purity. • Robustness of this technique can be substantially improved by combining this analysi… When used in an industrial setting, Raman spectroscopy can increase process efficiency and understanding. In biopharmaceutical industry, inline process control, particularly using Raman spectroscopy, provides substantial benefits to ensure maximum product yield and to increase the level of process automation. These recent developments have been valuable in reducing the need for sample extraction and handling, especially when hazardous materials are present. Baradez, D. Biziato, E. Hassan, and D. Marshall, Front. Raman spectroscopy systems are the new analytical tools to control processes by measuring critical process parameters (CPPs). 5(47), 1–14 (2018). measurement solution for research and development, manufacturing, and quality control. In this example, process Raman spectroscopy was used in the analysis of the kinetics of decomposition of formic acid in sub- and supercritical water. A Raman microscope couples a Raman spectrometer to a standard optical microscope, allowing high magnification visualization of a sample and Raman analysis with a microscopic laser spot. For in-line measurements, a fibre-optic Raman Dynisco probe was connected into the die head (Fig. Another way to prevent getting this page in the future is to use Privacy Pass. J. Hydrog. This cable was connected to a Hastelloy C-276 BallProbe, mounted into the process with flanges, and installed. ProCellics™ – First In-Line and Real-Time Bioprocess Raman Analyzer Grenoble, FRANCE, November 14, 2017 – ProCellics™, first In-Line and Real-Time Bioprocess Raman Analyzer, is a RESOLUTION Spectra Systems product. These substances do not travel well and could potentially be dangerous to the person sampling or handling them (6). The Analyst 2015, 140 (3) , 854-859. Figure 2 shows the statistical results for the cross-validation with both a regression line (Figure 2a) and target line alongside the plot of error versus the number of PLS factors (Figure 2b). CPPs for optimizing yields and the product composition are temperature, pressure, concentration, residence time, reactor concentration, reaction pathway, and catalysis (5). 3b), to monitor the API concentration of the melt before it is extruded out through the die. Transl. De Beer, C. Bodson, B. Dejaegher, B. Walczak, P. Vercruysse, A. Burggraeve, A. Lemos, L. Delattre, Y. Vander Heyden, J.P. Remon, C. Vervaet, and W.R.G. Science Translational Medicine has called TMA reactions “the most notorious fireball in all of chemistry” (7). With improvements in lasers, optics, and detectors, Raman spectroscopy has developed into a powerful. (2) M.O. 409, 637–649 (2017). Solid-state Raman spectroscopy has all of the above attributes and no requirement for a sophisticated sampling system, making the installation of such a system relatively straightforward. (4) “What is Multivariate Analysis?” Camo Analytics (Oslo, Norway, 2019). By utilizing online Raman spectroscopy, as opposed to traditional offline monitoring, manufacturers can significantly reduce cost and risk while improving efficiency. A solid-state Raman spectrometer will allow you to take Raman out of the laboratory and into production. In addition, the evolution of Raman spectrometers and probes reveals that Raman equipment has long had a reputation for being expensive, cumbersome, and difficult to use. Raman Microspectroscopy In general terms, a Raman spectrometer is integrated with a Raman microscope. Raman spectroscopy is commonly used in chemistry to provide a structural fingerprint by which molecules can be identified. This study demonstrates feasibility of using in-line Raman spectroscopy method for monitoring aggregation of therapeutic proteins as a function of formulation and process variables - especially in the cases where soluble protein aggregates are formed. The utility of Raman for in-line, real-time process monitoring and control is demonstrated for content uniformity. Raman spectroscopy systems are the new analytical tools to control processes by measuring critical process parameters (CPPs). A Raman signal is straightforward to interpret: The distribution of the spectral peaks describes the molecule’s composition while the signal intensity correlates linearly with concentration. (3) T.R.M. A total of 10 experimental conditions were tested in a day, demonstrating the potential for expediting future gasification studies with more complex model compounds. Advancements in the stability and portability of certain Raman systems demonstrate that this technology can be moved out of the traditional laboratory and installe. Lewis, Anal. In some applications, the usage of two probes to monitor two production lines at the same time is possible with one system. Monitoring of the crystallization of zeolite LTA using Raman and chemometric tools. However, temperature, pressure, reactions, and molecular interactions can cause non-linear spectral behavior. Published in the November 2020 issue of, Raman spectroscopy is no longer reserved for just laboratory use. This article reviews two industrial applications that have successfully used Raman spectroscopy as a PAT tool: The first industrial application is the manufacture and sampling of highly sensitive and reactive trialkyl aluminum compounds. Still today the usage is limited to a small application area. At ColVisTec, we provide inline spectroscopy process control in extruders for pharmaceutical, chemical, coating, polymer and plastic extrusion via inline UV-Vis, NIR, Raman spectroscopy solutions. Decisions to adjust operational parameters are made based using these well-timed insights. This action allows calibration without an extensive set of known mixture spectra that are challenging to produce for a two-phase effluent stream of a reacting system. The spectral data were preprocessed using a first derivative and standard normal variate (SNV) treatment to correct for additive and multiplicative baseline effects and to enhance resolution. This ex situ analytical method is time-consuming and expensive to operate because reactor conditions can only be changed from run-to-run, and the system requires carrier gas, column maintenance, and regular maintenance to maintain optimal performance. The November 2020 issue of Spectroscopy is available here. Normalization ensured comparability between the spectral data of the different cores. Five spectra, each with a total integration time of 20 s, were collected and averaged for each operational condition— signal averaging provided an acceptable signal-to-noise ratio for identifying minor constituents. Just laboratory use learn about the value of process Raman spectroscopy was used to extract species concentration.... New Raman spectroscopy in metal-coated hollow glass fibres however, temperature, pressure,,! Second is the answer to these questions because it offers a higher level of compositional information process... 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