If you are at an office or shared network, you can ask the network administrator to run a scan across the network looking for misconfigured or infected devices. Energy 44, 31745–31756 (2019). Raman spectroscopy is no longer reserved for just laboratory use. Inline liquid measurements are critical to chemical, petrochemical, and small molecule pharmaceutical processes. Are their instruments portable? Traditionally, gas chromatography is used for total organic carbon (TOC) analysis. Raman ensures product quality and consistency by transmitting real-time compositional data to advanced process control (APC) systems in seconds. Results are updated once per minute, and process operators make key decisions that ensure product quality and consistency while reducing cycle times (Figure 3). Raman spectroscopy can help industries overcome difficult production hurdles and improve product quality. Raman instrumentation and a MarqMetrix immersion BallProbe were located immediately after the heat exchanger (optical cell in Figure 4) to allow for in situ monitoring of the product species in the quenched effluent stream. Quantitative analyses utilizing Raman spectroscopy are of increasing importance in the manufacturing industry for online or inline process control. Raman spectroscopy systems are the new analytical tools to control processes by measuring critical process parameters (CPPs). Inline Kaiser Raman gives real-time chemical measurements without needing to send a technician to the field and collect a sample from the stream. In this application, in-line, noninvasive Raman spectroscopy was used to monitor blended granule uniformity prior to tablet compression. 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. Robustness of this technique can be substantially improved by combining this analysi… 10/23/2020 10:00 AM EST. These recent developments have been valuable in reducing the need for sample extraction and handling, especially when hazardous materials are present. 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. 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). 400, 2439–2447 (2011). The ongoing cost expressed as the total cost of ownership is negligible, given the stability and reliability of factory-calibrated process Raman systems. The BioPAT ® Spectro offers access to Raman spectroscopy analysis in high throughput process development, supporting faster Raman model building and accelerating scale-up into commercial manufacturing. Process Raman spectroscopy can address manufacturing challenges in various industries: How does one obtain actionable, real-time insights for production? A semi-manual fluorescent background subtraction method was used for consistent spectral processing. The results show that in-line Raman spectroscopy is a viable technique for monitoring the progress of particle size reduction during wet media milling. For in-line measurements, a fibre-optic Raman Dynisco probe was connected into the die head (Fig. 532nm laser excitation is a common wavelength chosen for Raman spectroscopy. Esmonde-White, M. Cuellar, C Uerpmann, B. Lenain, and I.R. Med. Businesses desire production insights to facilitate real-time decisions that may ultimately give them an advantage over their competitors. The first example is the manufacture of organometallic compounds, such as trialkyl aluminum compounds, that are pyrophoric and dangerous to sample. Figure 3 shows the continuous Raman spectroscopy analysis of product purity versus time. If you are on a personal connection, like at home, you can run an anti-virus scan on your device to make sure it is not infected with malware. The ability to install your Raman spectroscopy system at the point of need is essential in these applications. Taking a Raman measurement is as simple as shining a laser onto a sample. 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. Still today the usage is limited to a small application area. The use of Raman spectroscopy also allowed operators to collect data during reactor operation, which quickly assessed the reaction products. In-line Raman spectra were collected using the Raman Rxn2 spectrometer from Kaiser Optical Systems (2019). An alternative methodology is to extract one pure sample from the plant and “spike” it with known impurities to create a sample set, consisting of 18 samples specified by a design of experiments (DoE) approach. Figure 1 shows the Raman spectra of the finished organometallic product with a 90% pure sample. Lewis, Anal. It produces a unique spectral fingerprint that identifies the chemical composition and molecular structure of materials. More recently, technological improvements in lasers, optics, and detectors have made Raman faster and more accessible to both scientists and nonexperts for real-time inline analysis. Normalization ensured comparability between the spectral data of the different cores. Process Raman spectroscopy is the answer to these questions because it offers a higher level of compositional information for process control. Raman spectroscopy was used to accurately monitor the in situ liquid and gaseous products in the effluent stream. In the end, CPPs such as temperature, pressure, residence time, and the concentrations of H2, CO2, CO, and residual formic acid were identified. 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. The immersion probe’s sapphire ball lens focuses the laser into the sample flow. Your IP: 217.182.85.9 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. A cross-validation technique was used to ensure realistic error statistics were calculated. Novosselov, Int. The November 2020 issue of Spectroscopy is available here. Reinhall, and I.V. When applied in manufacturing processes, Raman spectroscopy provides results in seconds, transmitted to an advanced process control (APC) system to increase process understanding and efficiency, ensuring product quality and consistency. • You may need to download version 2.0 now from the Chrome Web Store. 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. Therefore, the aim of this work is to investigate whether proxy measurements using inline vibrational spectroscopy, e.g., near-infrared (NIR), mid-infrared (MIR), and Raman, can be used to predict the viscosity of micellar liquids. As a measurement technology, it is reliable, easy to interpret, and process-ready. Raman spectroscopy can also help control and fine-tune processes based on fast, real-time feedback to improve critical quality attributes (5). It can collect and preprocess molecular compositional data to build a chemometric model for CPPs (3,4). Raman spectroscopy (/ ˈ r ɑː m ən /); (named after Indian physicist C. V. Raman) is a spectroscopic technique typically used to determine vibrational modes of molecules, although rotational and other low-frequency modes of systems may also be observed. With improvements in lasers, optics, and detectors, Raman spectroscopy has developed into a powerful measurement solution for research and development, manufacturing, and quality control. Raman spectroscopy can be used for microscopic analysis, with a spatial resolution in the order of 0.5-1 µm. The DoE sample set used for calibration was stored in glass vials under nitrogen, and Raman spectra were collected using a contact-free probe measuring through the vial. Raman systems have proven valuable for analyzing and controlling product quality in industries such as pharmaceuticals, biopharmaceuticals, polymers, semiconductors, oil and gas, alternate fuels, and fine art. 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. For the spectra collected in this study, indirect hard modeling (IHM) was used to extract species concentration data. • 48(3), 772–779 (2008). There is little to no sample preparation required when using Raman spectroscopy. In-line Raman Spectroscopy. They are used as catalysts and as intermediates in both the laboratory and in the industry. A spectrometer collects and measures the Raman scattered photons, creating a unique spectral fingerprint. The standard procedure for method development is collecting inline Raman spectra at regular intervals with accurate time and date stamps. The second is the transformation of organic waste into alternate fuels. Raman spectroscopy is an established PAT tool. Installation of a solid-state process Raman spectroscopy system is straightforward, and it does not require a sophisticated sampling system. More recently, Raman spectroscopy has been successfully applied to inline monitoring of animal cell bioreactor cultures [63, 65, 67]. This is known as “process Raman spectroscopy.”. Trace gas and dynamic process monitoring by Raman spectroscopy in metal-coated hollow glass fibres. Published in the November 2020 issue of, Raman spectroscopy is no longer reserved for just laboratory use. Such analysis is possible using a Raman microscope. In a study conducted by professor Igor V. Novosselov at the University of Washington, the decomposition of formic acid was monitored in a continuous sub- and supercritical water reactor at temperatures between 300 and 430 ºC, at a pressure of 25 MPa, with a residence time between 4–65 s, and a feedstock concentration of 3.5 wt%. With improvements in lasers, optics, and detectors, Raman spectroscopy has developed into a powerful. It is based on inline UV-Vis, NIR, and Raman spectroscopy. Outside the laboratory, Raman spectroscopy has found a home in manufacturing and quality analysis. 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. LabRAM Soleil™ New Confocal Raman Microscope from HORIBA Scientific Your ideal lab companion. 5(47), 1–14 (2018). A process Raman system has considerable operator health and safety benefits. Raman spectroscopy is an attractive inline quality characterization and quantification tool for nanomanufacturing because of its nondestructive nature, fast data acquisition speed, and ability to provide detailed material information. J. Hydrog. Rasmussen, V. Maheshwari, J.C. Kramlich, P.G. TMA is known for its exceptional degree of pyrophoricity. (8) B. Zachhuber, G. Ramer, A. Hobro, E. T.H. The difficulty lies in measuring this property directly in the process via on or inline technologies. The overall technology is easy to control and use. There were minor changes to integration time because longer lengths of optical fiber were used, and the analysis was subsequently performed using third-party process control software (Camo Analytics Process Pulse II) for model execution, visualization, and transmission of results via fieldbus to the plant process control system. In this example, the measurement of organometallic purity was performed with process Raman spectroscopy. 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 Sample mixtures, even those containing water, can also be analyzed quickly and effectively. Rather than using classic The use of an inline or online measurement tool is imperative to understand CPPs and study the effects of these parameters on the reaction kinetics. The manufacturer used an average of all five spectra to calculate product yield. Process operators then extract samples at set times and send them to the laboratory for analysis. Calibration was accomplished by using the least-squares optimization of stoichiometric atom balances for the collected spectra. This article focuses on two examples of Raman’s safety and time benefits in process control. When used in an industrial setting, Raman spectroscopy can increase process efficiency and understanding. This list continues to grow as more industries learn about the value of process Raman spectroscopy. Before taking Raman spectroscopy out of the laboratory, manufacturers looking to adopt process Raman spectroscopy technology in their production lines must consider several factors: Are their Raman spectroscopy systems easy to install and maintain? Outside the laboratory, Raman spectroscopy has found a home in manufacturing and quality analysis. These substances do not travel well and could potentially be dangerous to the person sampling or handling them (6). (7) D. Lowe, Safety Warnings. The MVDA algorithm used was partial least squares (PLS). These recent developments have been valuable in reducing the need for sample extraction and handling, especially when hazardous materials are present. Our company was founded in 2009 and is now co-funded by the Horizon 2020 program of … As a result, Raman is now a powerful measurement solution for research and development, manufacturing, and quality control. Manufacturers handling hazardous materials in their production facilities face unique analytical challenges when it comes to the collection of samples for laboratory analysis. Process operators set control limits, alarms, and warnings on the process control system. Given the ease of use, simplicity of data analysis, first principles compositional information, and versatility, Raman spectroscopy is an excellent tool for industrial process analysis and control. In situ process Raman spectroscopy makes it possible to continuously monitor and identify gasification products such as H2, CO2, and CO in real-time. Raman spectroscopy has been demonstrated to help manufacturers overcome this challenge. Acquisition parameters set the integration time to 230 mS and the laser power to 450 mW. Cloudflare Ray ID: 60afaa12af130820 (2) M.O. Biomed. (3) T.R.M. #raman #manufacturingtechnology #inlineanalysis, By Brian Marquardt, Ph.D, MarqMetrix Founder & CEO,  and Bharat Mankani, Ph.D, MarqMetrix Application Specialist. Our technology is fitted to the existing manufacturing facilities, boosting their productivity and quality. Reinhall, and I.V. (1) K.A. Chrysostom, and B. Lendl, Anal. Continuous measurements from infrared spectrometers are used for obtaining reaction profiles to calculate reaction rates. Advancements in the stability and portability of certain Raman systems demonstrate that this technology can be moved out of the traditional laboratory and installed at the point of need with little to no maintenance. Decisions to adjust operational parameters are made based using these well-timed insights. 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. Since its discovery in the 1920s, Raman spectroscopy has revolutionized process analysis with its nondestructive nature and ability to measure sample composition. Pinkard, D.J. In manufacturing, timing can impact everything, from development to the time it takes to get a product to market. In some applications, the usage of two probes to monitor two production lines at the same time is possible with one system. Organometallics are manufactured in large volumes with very high purity, which presents major analytical obstacles, because sample handling is hazardous (8). It produces a unique spectral fingerprint that identifies the chemical composition and molecular structure of materials. 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. Advancements in the stability and portability of certain Raman systems demonstrate that this technology can be moved out of the traditional laboratory and installe. It offers a GMP user-friendly and easily deployed Process Analytical Technology (PAT) solution. 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. SCWG is an emerging alternate fuel technology (9,10). (5) “Process analytical technologies: a unique data management challenge,” Optimal Industrial Automation Ltd. (Bristol, United Kingdom, 2012). The Analyst 2015, 140 (3) , 854-859. In this case, that traditional methodology is not possible because the sample has an extremely reactive nature. A separate identical probe with a 3-m fiberoptic cable was coupled to the spectrometer for model development purposes. Baradez, D. Biziato, E. Hassan, and D. Marshall, Front. The manufacturer coupled a MarqMetrix Raman spectrometer with a laser excitation of 785 nm to 100 m of high-grade armored fiberoptic cable. The experimental conditions of the supercritical water reactor and the gasified formic acid were as follows: Continuous temperatures hovered between 300 and 430 °C; a pressure of 25 MPa was maintained; residence times stayed between 4 and 65 s; and a feedstock concentration was set at 3.6 wt%. Raman spectroscopy was used to predict the application of coatings on three different tablet cores using PLS regression. 3b), to monitor the API concentration of the melt before it is extruded out through the die. 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. Science Translational Medicine has called TMA reactions “the most notorious fireball in all of chemistry” (7). A Raman measurement can be collected in seconds for most organic substances. This combination ensures maximum sample variance with a minimum number of samples, and a purity range of 90 to 99.9%. However, these benefits are dependent on the type of equipment a business ultimately chooses to use. 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. Businesses desire production insights to facilitate real-time decisions that may ultimately give them an advantage over their competitors now! 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