Raman spectroscopy is a powerful analytical technique for measuring chemical mixtures, and since its discovery in the 1920s, it has revolutionized process analysis. The fact that it is non-destructive, and its sampling flexibility allow it to be used very advantageously in process monitoring situations. Although Raman spectrometers have many advantages over other spectroscopic technologies, awareness about their advantages is lacking and must be demonstrated for process analytics customers, especially in emerging markets. Ultimately, analytical equipment manufacturers that conduct demonstrations, training, and workshops with practical examples in different measurement applications will be well-positioned to help process analytics customers realize the potential advantages of Raman spectroscopy solutions.
To address this need, this blog post will talk about using Tornado’s next-generation Raman analyzers as real-time process tools for in-line measurement within the pharmaceutical manufacturing and bioprocessing space.
A valuable tool for qualitative and quantitative chemical analysis
Raman spectroscopy is a valuable tool for qualitative and quantitative chemical analysis as the technology offers flexible sampling interfaces, adjustable sampling parameters, and high spectral specificity to detect, distinguish and quantify multiple components in a chemical matrix. Raman spectrometer systems are highly compatible with process monitoring applications as fiber optics can be used to interface the analyzer with the sample measurement location(s), providing essential flexibility for in-line monitoring. The applicability of Raman ranges across a variety of industries including pharmaceuticals, bioprocessing, specialty chemical, oil & gas, food and beverage, plastics and polymers, and other chemically related sectors. Typical applications in these industries include real-time monitoring of chemical concentrations, determination of the end state of a reaction, or detection of low-level contaminants. Detailed analysis provided by Raman spectroscopy helps customers understand a multitude of process-related issues, improving production efficiency, optimizing reaction yields, and alerting operators when a process has deviated from its specifications.
Although throughput and spectral resolution are the key performance parameters for Raman spectroscopy, most existing spectrometers cannot deliver both at the same time, limiting their usefulness in most process scenarios. In contrast, Tornado’s proprietary HTVS™ technology offers high performance with respect to both throughput and resolution, thus leading to better sensitivity (low detection limits) and measurement speed that is 10 times to 30 times faster than competitors’ solutions.
With the performance advantage that HTVS™ offers, Tornado can help customers with difficult analyses that would not be feasible with conventional Raman systems. Accuracy and sensitivity make a substantial difference in the chemical constituents of a mixture present at levels measured in parts per million (ppm). To give one specific example, one of Tornado’s customers needed to know when their reactant level had reached 400 ppm, but the existing Raman equipment on the market could not measure accurately at that level in the short time required. Tornado’s HyperFlux™ PRO Plus enabled the customer to not only detect the reactant at this low level but also quantify its concentration with an accuracy of about 30 ppm, which made a critical difference in achieving proper process control. Tornado’s ability to deliver a solution enabled the company to meet an extremely challenging requirement to improve their process and control it better.
Choosing the right Raman analyzer
In order to ensure the right instrument is chosen to complement each unique production environment, a thorough evaluation process is required. Users need to understand what they really need from their Raman instrument and should assess a number of parameters, such as:
- Are my materials Raman-active?
- Where in the process can I benefit from Raman measurements?
- Will the instrument(s) integrate with my process infrastructure?
- Will I need to change my existing processes to implement a new technology?
Raman as a PAT tool for bioprocessing
There was a study from a trade journal a few years back and PAT scientists in the bioprocessing area were asked what PAT tool was sufficiently interesting to them such that they would like to learn more about it. More than 50% said Raman while the next technique garnered 25% of the votes. Raman is a tool at which people are looking very closely because of all of the advantages cited earlier in that article.
Raman provides molecular specificity for quantitative analysis and is ideal for upstream processing because of its insensitivity to water. The way Tornado designs its HTVS™ technology is attractive because of shorter collection times, better accuracy, and or better limits of detection. Raman can also provide excellent molecular specificity in downstream processing, unlike competing spectroscopic modalities.
As an additional advantage, Raman can be multiplexed to allow monitoring of multiple reactors with one spectrometer. Tornado’s Raman analyzer can be multiplexed for use with up to 8 channels.
In recent years, there has been an enormous amount of change in pharmaceutical manufacturing. Regulatory support, along with scientific and financial benefits, are key elements in the widespread adoption of QbD (Quality by Design) and PAT. A shift to QbD has encouraged new risk-based approaches in real-time testing, continuous manufacturing, and data process control. Real-time, in-process analytics have a crucial role in ensuring product quality and enabling in-process corrections. Raman is attractive for its defined and specific spectral features and compatibility with aqueous environments for in-process measurements. For many years, these features have been harnessed to better understand pharmaceutical small molecule crystallization and processing.
Measurements you can trust
Nothing is more expensive than a process analyzer that fails to deliver the measurement quality you need. If you are a process development chemist or process engineer and work with a lot of process analyzers, you will undoubtedly have realized that there are some that are more reliable than others, and you’ve learned to trust which is reliable. If your process is truly important, then your business or organization cannot afford to use anything but the best methods and equipment. It’s tempting to settle for older technologies or lesser performing instruments that are “good enough” but making this sort of compromise leaves you vulnerable to the “unknown unknowns” – aspects or issues in your process about which you are completely unaware. That is why it is crucial to understand your processes to the greatest extent possible and to employ ongoing monitoring using superior tools like Tornado Raman. A great analogy comes from the Japanese word, wakaru. This word means both to divide and to understand. Understanding comes from dividing things into pieces, understanding the pieces, and then putting them back into a mosaic to understand the bigger picture about what is happening. Raman can help you to understand the pieces of your process to eventually synthesize the big picture about the factors that affect it. If you understand what affects it, that sheds light on the aspects of the process that require attention so that they can be controlled.
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