Tornado Spectral Systems Raman Spectroscopy System Literature
White Papers and Application Note Summaries (complete form below to request full versions)
Use of High-Throughput Spectroscopy to Monitor Li2CO3 Precipitation: The Potential for Real-Time Monitoring in Li Production
The extraction of lithium from natural resources has increased significantly in recent years due to increased demand. Lithium is valuable in various industries including pharmaceuticals, ceramics and glass, polymers, and lubricants. In this application note, the results demonstrate the exceptional speed, sensitivity, and signal-to-noise ratio of the HyperFlux™ PRO Plus Raman analyzer, and how it can be used to make fast, in-line measurements of lithium carbonate precipitation.
Downstream Protein Purification Optimization by High-Throughput Raman Spectroscopy: Optimizing Purification with Overlapping Peak Profiles
Downstream processing (DSP) is one of the last milestones in biotherapeutic manufacturing, an industry projected to grow by USD $226.61 bn with a CAGR of 11% between 2021-2026. DSP typically accounts for 50-80% of biotherapeutic production costs due to the multiple unit operations involved. The overall manufacturing process stands to benefit greatly by paying particular attention to enhancements in DSP, especially those related to optimization of real-time chemical quantification and characterization. The work shown in this note demonstrates that Tornado’s HTVS™ results in faster and more accurate measurement times for the quantification and characterization of proteins of interest in real-time, providing the user with actionable information to facilitate improved process control and provide optimal purification efficiency.
Residence time distribution in the feed frame of a tablet press for different process parameters using Raman spectroscopy
The HyperFlux™ PRO Plus Raman spectroscopy system was used to monitor and evaluate the effect on the residence time distribution of manufacturing parameters such as throughput, chute height, and feed frame paddle speed.
Residence time distribution (RTD) has become an essential parameter to characterize pharmaceutical manufacturing equipment in continuous manufacturing. This technology has been implemented in several production lines worldwide, as it allows characterization under potential process parameter perturbations to obtain a predictive control strategy. In this work, a Raman probe was integrated to detect low amounts of a tracer, changing many physical parameters such as the throughput, feed frame paddles speed, and the height of the powder bed in the chute connecting the blender with the tablet press. The goal of this work was to determine if a low level of the tracer material (1.5% w/w) is detectable under different manufacturing conditions. Utilizing Tornado Spectral System’s HyperFlux™ PRO Plus with their High Throughput Virtual Slit (HTVS™) technology yielded low signal-to-noise ratios and excellent performance predicting blend compositions as low as 1.5% w/w in the feed frame. These results indicate the robustness of the Tornado Raman system executing an extensive evaluation of a continuous manufacturing line sustaining the performance during ten days of data acquisition. The work shown in this note demonstrates the value added by the specificity of Raman technology. It also demonstrates, in particular, the sensitivity of the Tornado technology in validating the continuous blending and mixing processes for low dosage formulations.
Residence time distribution (RTD) has become an essential parameter to characterize pharmaceutical manufacturing equipment in continuous manufacturing. This technology has been implemented in several production lines worldwide, as it allows characterization under potential process parameter perturbations to obtain a predictive control strategy. In this work, a Raman probe was integrated to detect low amounts of a tracer, changing many physical parameters such as the throughput, feed frame paddles speed, and the height of the powder bed in the chute connecting the blender with the tablet press. The goal of this work was to determine if a low level of the tracer material (1.5% w/w) is detectable under different manufacturing conditions. Utilizing Tornado Spectral System’s HyperFlux™ PRO Plus with their High Throughput Virtual Slit (HTVS™) technology yielded low signal-to-noise ratios and excellent performance predicting blend compositions as low as 1.5% w/w in the feed frame. These results indicate the robustness of the Tornado Raman system executing an extensive evaluation of a continuous manufacturing line sustaining the performance during ten days of data acquisition. The work shown in this note demonstrates the value added by the specificity of Raman technology. It also demonstrates, in particular, the sensitivity of the Tornado technology in validating the continuous blending and mixing processes for low dosage formulations.
High-Throughput Raman Process Monitoring of Downstream Protein Purification
High-performance Raman spectroscopy, made possible by Tornado Spectral Systems’ patented High-Throughput Virtual Slit (HTVS™), enhances Raman signal by increasing photon flux by 10x to 30x as compared to conventional spectrometers. This significant advancement in technology enables faster measurements, lower limits of detection, and/or the use of intrinsically safe lower laser power, when needed. These additional gains in spectral quality and sensitivity uniquely enable success in difficult applications, such as fast measurements of proteins of interest during both upstream and downstream bioprocessing. In this white paper, learn how Tornado’s Raman analyzer is a powerful tool for monitoring downstream protein purification process quality and how it can predict the chromatographic elution concentrations of proteins (BSA and CytC) with a high degree of specificity.
Coupled High-Throughput Raman and Ultrasonic Particle Manipulation for Increased Sensitivity and Selectivity in a Cell Reactor
High-performance Raman spectroscopy, made possible by Tornado Spectral Systems’ patented High-Throughput Virtual Slit (HTVS™), increases Raman signal by delivering an order of magnitude more photons to the detector when compared to conventional spectrometers. This revolutionary improvement in spectrometer throughput and signal strength results in a three-to six-fold increase in signal-to-noise resolution, or a ten-fold decrease in exposure time requirements. This enables faster measurements, lower limits of detection, or the use of intrinsically safe lower laser power, if needed. Furthermore, additional gains in Raman spectrum quality and sensitivity can be achieved via ultrasonic manipulation of particulates in the sample matrix, as described in this white paper.
Real time Raman Analysis for Continuous Flow: Rapid In-Line Analysis of Low Levels of an Analyte
Flow chemistry is used in many aspects of industrial processing including (but not limited to) continuous reaction chemistry, preparation and quantification of feedstocks, and product purification processes. Analytical monitors for flow chemistry processes can provide precise, accurate, and timely measurements to ensure that products or excipients are properly quantified and are being produced with maximum efficiency. However, current spectroscopic tools are limited to bulk analysis and are a bottleneck in many applications. Tornado Spectral Systems HyperFlux™ PRO Plus puts Raman into the forefront of monitoring and controlling these highly dynamic processes. This application note demonstrates the benefit of HTVS™ for in-line method development and real-time predictions of a low-level analyte in a continuous process.
Turbocharging Raman Measurements with High-Throughput Virtual Slit Spectrometers
Although Raman spectroscopy is a powerful and flexible analytical tool, Raman signals are usually quite weak – for most molecules fewer than one Raman scattered photon is generated from one million incident laser photons – so spectrometer efficiency (sensitivity) is of utmost importance. Furthermore, Raman spectral bands are often both narrow and closely spaced. Traditional slit spectrometers require a very narrow input slit to achieve high spectral resolution and therefore have poor optical throughput, limiting their effectiveness in low light level scenarios like Raman spectroscopy. A spectrometer design that incorporates Tornado’s HTVS™ (High-Throughput Virtual Slit) technology avoids this trade-off between sensitivity and spectral resolution and thus enhances overall system performance, making measurement of weak Raman signals a practical reality. A Raman measurement that is intended for quantification needs to be fast, accurate, and precise, encapsulating the best possible resolution in both wavelength and intensity. This white paper describes the proprietary HyperFlux™ optical spectrometer designs developed by Tornado Spectral Systems using its core HTVS™ technology.
Rapid Development of a 9 component Multivariate Calibration for the analysis of Metabolites in Chemically Defined Cell Culture Media
This study assessed the performance of the HyperFlux™ PRO Plus Raman Spectroscopy System (Tornado Spectral Systems) for the quantitative analysis of biochemical components in a simplified chemically defined pseudo growth medium for mammalian cell culture. An experiment was designed to evaluate the ability of inline Raman Spectroscopy to directly measure individual components in a complex mixture at concentrations at or below the limit of quantification of conventional Raman spectrometers. A set of samples with varying amounts of glucose, lactate, glutamine, glutamate, ammonium, arginine, histidine, leucine, and phenylalanine were prepared so that covariance between components was close to zero. The spectral collection and model development were completed in one day. The sample spectra were collected in a morning using fast acquisition times and promising calibrations were developed in the afternoon using basic pre-treatments such as derivatives and normalisation. An assessment by Sanofi UK of the performance of the HyperFlux™ PRO Plus Raman Spectroscopy System for the quantitative analysis of biochemical components in a simplified chemically defined pseudo growth medium for mammalian cell culture.
High Throughput Virtual Slit (HTVS™) Impact on Raman Spectroscopy Limit of Detection (LoD) Performance
Conventional Raman systems have traditionally been limited by a lack of sensitivity due to the design trade-off between resolution and throughput mediated by the input slit of the spectrometer. Tornado’s proprietary high throughput virtual slit (HTVS™) design technique eliminates the spectrometer and associated slit losses while maintaining high spectral resolution, resulting in an order of magnitude improvement in sensitivity. This application note demonstrates the improved detection limits and corresponding minimum required acquisition times of four binary mixtures using Tornado’s HyperFlux™ PRO Plus Inline Raman spectroscopy system. Higher sensitivity is achieved by using HTVS to eliminate the conventional trade-off between spectral resolution and optical throughput.
Improving quality, efficiency, and chemical process economics using HyperFlux™ PRO Plus real-time reaction monitoring
Chemical production and processing is an essential part of modern life and the foundation of numerous industries including pharmaceutical, petrochemical, food & beverage, specialty chemical, and bioprocessing. Continuous in-line real-time measurements can ensure quality, improve efficiency, and enhance economy compared to off-line testing of samples extracted from a process. However, in-line real-time measurements can be challenging to obtain with enough speed and accuracy to be useful. The superior performance of Tornado Spectral System’s HyperFlux™ PRO Plus inline Raman spectroscopy system helps overcome these limitations, making it an ideal solution for chemical reaction monitoring in production line and laboratory settings. In this application note, a major pharmaceutical company needed to monitor the conversion of benzoic anhydride to the corresponding ester. We present how Tornado’s HyperFlux™ PRO Plus provided a fast and accurate monitoring tool to confirm reaction quality and optimize reaction timing.
Real-time determination of EVA crosslinking with Raman spectroscopy during photovoltaic manufacturing
Photovoltaic manufacturers are under increasing pressure to improve quality and reduce cost. One important process and quality parameter is the degree of crosslinking in the ethylene vinyl acetate (EVA) material used as the solar cell embedding material which supports and protects the solar cells. Currently available methods of measuring EVA crosslinking are not capable of real-time in-line measurement due to slow speed, the need to extract samples, and a lack of consistency and precision. Tornado’s HyperFlux™ spectrometer was deployed for Raman analysis to determine the degree of curing of ethylene vinyl acetate (EVA) in a photovoltaic module manufacturing line and was shown to have enough sensitivity and speed to be an effective tool for real-time, in-line quality control and process optimization.
Degree of Cure of Epoxy/Acrylic Photopolymers: Characterization with Raman Spectroscopy and a Modified Phenomenological Model
Photopolymers possess unique capabilities, including the possibility for ambient temperature curing and the potential for control over where and when the polymer cures. These capabilities have given rise to a variety of products and processes including dental materials, contact lenses, coatings, microfluidic device fabrication, tissue engineering matrices, and photolithography. Recent developments in photopolymer technology include monomer mixtures and co-polymers. These applications are limited by our understanding of the photopolymerization process. A means for in situ monitoring of the cure process that would yield distinctive and attributive data would provide a better understanding of the curing process by enabling more accurate cure modeling of these materials. Such capabilities would allow optimal end-point predictions and would also enable process monitoring with instant parameter adjustment feedback. Tornado’s HyperFlux™ spectrometer was deployed for Raman analysis to determine a UV-curing process. The use of the Tornado Raman spectrometer enabled accurate diagnostic tracking of the cure cycle of the Accura® 60 photopolymer.
