ReactRaman In-Situ Analysis

Understand Reaction Kinetics, Polymorph Transitions, and Mechanisms to Optimize Process Variables

In-situ Raman spectrometers enable scientists to measure reaction and process trends in real time, providing highly specific information about kinetics, polymorph transitions, mechanisms, and the influence of critical process parameters (CPP). With ReactRaman™, users directly track the concentration of both solid and liquid reactants, intermediates, products, and crystal forms as they change over the course of the experiment.

ReactRaman provides critical information to scientists as they research, develop, and optimize reactions and processes.

ReactRaman 802L

A high-performance Raman spectrometer optimized for in-situ analysis, coupled with an intuitive, integrated software platform ensures reliable and high-quality reaction information from every experiment.

From data collection to analysis, ReactRaman with iC Raman™ software brings compositional analysis to every lab. Automated parameter selection provides accurate data collection, enabling scientists to get confident results. Right first time, every time, in every process for every user.

Fixed and Interchangable Raman Probes and Optics

Immersion probe- and flow-based sampling technologies enable scientists to study liquid and solid phase chemistry in batch or continuous flow configurations. Fit-for-purpose Raman probes enable use over a wide range of temperatures, pressures, and chemistries. View our Raman probe and optic options including:

Inline Raman flow cells
Raman immersion probes
Non-contact Raman probes

Comprehensive Reaction Understanding

In order to understand chemical reactions, chemists use Raman spectrometers to address the following:

When does the reaction start? When does the reaction stop?
What intermediates are being produced?
What are the reaction kinetics, mechanisms, or crystallization processes?
Did it react as expected? Did any by-products form, and why?
What happens if reaction temperature, dosing rates, or mixing rates change?

Continuous monitoring with in-situ Raman spectrometers allows users to trend components over time — making it easier to answer critical questions for reaction and process optimization.

Safety in Every Lab

With safety interlocks and four visual indicators, users work safely and can easily identify when the laser is in use. ReactRaman and iC Raman will activate the laser only when all of the following interlock conditions are satisfied:

SmartConnect™ Raman probe with electronic verification ensures connection to the spectrometer unit for safe operation
Sampling optic is securely attached to the probe head
Fiber conduit is intact
Front panel laser key is in the ON position
Remote interlock engaged (i.e., for door, room, or reactor lid)

Small Footprint, Big Performance

Class-leading performance with excellent stability and sensitivity in a compact, stackable package.

Deployment can be anywhere in the lab for batch or flow. A single robust connector guarantees alignment every time and inherent safety ensures worry-free measurements.

ReactRaman takes up little space and was designed to be stackable with other benchtop instruments for even more compact layouts.

Comprehensive Raman Analysis and Understanding

In-Situ Raman Probes

Probe- and flow-based sampling technologies enable scientists to study liquid and solid phase chemistry in batch or continuous flow applications. Designed for purpose sampling options enable use over a wide range of temperatures, pressures, and chemistries.

One Click Analytics™

Designed specifically for time-resolved reaction analysis, iC Raman™ software combines a peak picking algorithm with functional group intelligence to drastically reduce analysis time. Read more

Reaction Analysis Experts

As a company METTLER TOLEDO has over 30 years of experience dedicated to advancing reaction analysis. This is our focus and our passion. We built this expertise into our fit-for-purpose Raman spectrometers.

ReactRaman works in a wide range of chemistries and conditions. Common applications include:

Polymorph Detection in Carbamazepine

Reveal process mechanisms
In this example, ReactRaman™ follows the conversion of Carbamazepine anhydrate to the dihydrate form while showing the full transformation time.

Provide insight into distinguishing polymorphs
At times, polymorphs cannot be identified visibly. ReactRaman provides molecular information to help users understand more from their crystallization processes.

Measure form stability
Conversion of polymorphs can be monitored providing insight into stability of products.

Track progress for better yield and purity
Confirmation of optimal reaction or crystallization endpoint.

Quickly determine kinetics
First order reaction kinetics in one experiment.

polymorph detection using raman spectrometer

An Integrated Approach for Comprehensive Understanding and Control

The ReactRaman™ spectrometer is part of an integrated family of products, which includes:

ReactIR™ in-situ FTIR spectrometer
EasyViewer™ particle size analyzer to view and measure particles in situ and in real time
EasyMax™, OptiMax™, and RX-10 chemical synthesis reactors

Designed specifically for chemical and process development, these tools are combined with the iC Software Suite to provide comprehensive process understanding and control.

Raman Spectrometer FAQs

What is a Raman probe?

A Raman probe is the device used in Raman spectroscopy to connect the spectrometer to the sample. There are three common probe types that provide flexibility in the sample interface. These are for immersion, non-contact, and flow. The most common configuration is the immersion probe designed to be inserted into a reactor containing the reaction sample. If the chemistry is corrosive or needs to be sealed, it is often preferable to use a non-contact Raman probe positioned outside of a site window looking into the reactor. For flow applications, the flow cell can be coupled in-line to make continuous measurements.

How do you use a Raman probe?

Simply connect the Raman probe SmartConnector to the spectrometer base unit. Then considering the type of sample to be measured, connect the sample interface end of the probe — an immersion probe into a reactor, a flow cell into a bypass loop or flow path, and a non-contact Raman optic at a site glass or window to remotely observe the reaction. Once the connection is complete, use iC Raman software to optimize the data acquisition parameters and set up the experiment profile.

What is Raman spectroscopy?

If you are new to Raman spectroscopy, please check out our Raman spectroscopy resource page for information, including:

Learn more about Raman spectroscopy.

Is Raman or FTIR better for my application?

Raman and FTIR spectrometers both provide molecular information about the structure and composition of chemical and biological samples. Due to the fundamental principles that govern each of these vibrational techniques, the spectra are different and as a result, it is considered that they provide complementary information. Frequently one technique will prove a better choice, depending on the nature of the application.

Learn more about Raman vs. FTIR spectroscopy.

Raman Spectrometer Resources

In-situ Raman Spectroscopy in Journal Publications

Below is a selection of publications featuring Raman spectrometers

Yan, Z., Wang, Y., Xu, D., Yang, J., Wang, X., Luo, T., & Zhang, Z. (2023b). Hydrolysis mechanism of Water-Soluble ammonium polyphosphate affected by zinc ions. ACS Omega, 8(20), 17573–17582. https://doi.org/10.1021/acsomega.2c07642
Yang, L., Zhang, Y., Liu, P., Wang, C., Qu, Y., Cheng, J., & Yang, C. (2022). Kinetics and population balance modeling of antisolvent crystallization of polymorphic indomethacin. Chemical Engineering Journal, 428, 132591. https://doi.org/10.1016/j.cej.2021.132591
Marzijarani, N. S., Fine, A., Dalby, S. M., Gangam, R., Poudyal, S., Behre, T., Ekkati, A. R., Armstrong, B. A., Shultz, C. S., Dance, Z. E. X., & Stone, K. H. (2021). Manufacturing Process Development for Belzutifan, Part 4: Nitrogen Flow Criticality for Transfer Hydrogenation Control. Organic Process Research & Development, 26(3), 533–542. https://doi.org/10.1021/acs.oprd.1c00231
Wang, Y., Zheng, S. G., Yang, W., Zhou, R., He, Q., Radjenovic, P. M., Dong, J., Li, S., Zheng, J., Yang, Z., Attard, G. A., Pan, F., Tian, Z., & Li, J. (2021b). In situ Raman spectroscopy reveals the structure and dissociation of interfacial water. Nature, 600(7887), 81–85. https://doi.org/10.1038/s41586-021-04068-z
Wu, Y., Zhang, H., Wang, N., Chen, T., & Liu, Y. (2021). A Study on the Crystal Transformation Relationships of Valacyclovir Hydrochloride Polymorphs: Sesquihydrate, Form I, and Form II. Crystal Research and Technology, 2100084. https://doi.org/10.1002/crat.202100084
Fang, C., Gong, J., Wu, S., Wang, J., & Gao, Z. (2020). Ultrasound-assisted intensified crystallization of L-glutamic acid: Crystal nucleation and polymorph transformation. Ultrasonics Sonochemistry, 68, 105227. https://doi.org/10.1016/j.ultsonch.2020.105227
Østergaard, I., De Diego, H. L., Qu, H., & Nagy, Z. K. (2020). Risk-Based Operation of a Continuous Mixed-Suspension-Mixed-Product-Removal Antisolvent Crystallization Process for Polymorphic Control. Organic Process Research & Development, 24(12), 2840–2852. https://doi.org/10.1021/acs.oprd.0c00368
Wang, Y. X., Yu, J., Wang, Y., Chen, Z., Dong, L., Cai, R., Hong, M., Long, X., & Yang, S. (2020). In situ templating synthesis of mesoporous Ni–Fe electrocatalyst for oxygen evolution reaction. RSC Advances, 10(39), 23321–23330. https://doi.org/10.1039/d0ra03111a
Zhang, S., Zhou, L., Yang, W., Xie, C., Yang, X., Hou, B., Hao, H., Zhou, L., Bao, Y., & Yin, Q. (2020). An Investigation into the Morphology Evolution of Ethyl Vanillin with the Presence of a Polymer Additive. Crystal Growth & Design, 20(3), 1609–1617. https://doi.org/10.1021/acs.cgd.9b01341
Mei, C., Deshmukh, S. S., Cronin, J. T., Cong, S., Chapman, D. P., Lazaris, N., Sampaleanu, L. M., Schacht, U., Drolet-Vives, K., Ore, M. O., Morin, S., Carpick, B., Balmer, M., & Kirkitadze, M. (2019). Aluminum Phosphate Vaccine Adjuvant: Analysis of Composition and Size Using Off-Line and In-Line Tools. Computational and Structural Biotechnology Journal, 17, 1184–1194. https://doi.org/10.1016/j.csbj.2019.08.003
Nagy, B., Farkas, A., Gyürkés, M., Komaromy-Hiller, S., Démuth, B., Szabó, B. T., Nusser, D., Nagy, Z. K., & Marosi, G. (2017). In-line Raman spectroscopic monitoring and feedback control of a continuous twin-screw pharmaceutical powder blending and tableting process. International Journal of Pharmaceutics, 530(1–2), 21–29. https://doi.org/10.1016/j.ijpharm.2017.07.041
Tong, Y., Zhang, P., Dang, L., & Wei, H. (2016b). Monitoring of cocrystallization of ethenzamide–saccharin: Insight into kinetic process by in situ Raman spectroscopy. Chemical Engineering Research and Design, 109, 249–257. https://doi.org/10.1016/j.cherd.2016.01.032
Hänchen, M., Prigiobbe, V., Baciocchi, R., & Mazzotti, M. (2008). Precipitation in the Mg-carbonate system—effects of temperature and CO2 pressure. Chemical Engineering Science, 63(4), 1012–1028. https://doi.org/10.1016/j.ces.2007.09.052

Below is a selection of publications featuring Raman spectrometers

Yan, Z., Wang, Y., Xu, D., Yang, J., Wang, X., Luo, T., & Zhang, Z. (2023b). Hydrolysis mechanism of Water-Soluble ammonium polyphosphate affected by zinc ions. ACS Omega, 8(20), 17573–17582. https://doi.org/10.1021/acsomega.2c07642
Yang, L., Zhang, Y., Liu, P., Wang, C., Qu, Y., Cheng, J., & Yang, C. (2022). Kinetics and population balance modeling of antisolvent crystallization of polymorphic indomethacin. Chemical Engineering Journal, 428, 132591. https://doi.org/10.1016/j.cej.2021.132591
Marzijarani, N. S., Fine, A., Dalby, S. M., Gangam, R., Poudyal, S., Behre, T., Ekkati, A. R., Armstrong, B. A., Shultz, C. S., Dance, Z. E. X., & Stone, K. H. (2021). Manufacturing Process Development for Belzutifan, Part 4: Nitrogen Flow Criticality for Transfer Hydrogenation Control. Organic Process Research & Development, 26(3), 533–542. https://doi.org/10.1021/acs.oprd.1c00231
Wang, Y., Zheng, S. G., Yang, W., Zhou, R., He, Q., Radjenovic, P. M., Dong, J., Li, S., Zheng, J., Yang, Z., Attard, G. A., Pan, F., Tian, Z., & Li, J. (2021b). In situ Raman spectroscopy reveals the structure and dissociation of interfacial water. Nature, 600(7887), 81–85. https://doi.org/10.1038/s41586-021-04068-z
Wu, Y., Zhang, H., Wang, N., Chen, T., & Liu, Y. (2021). A Study on the Crystal Transformation Relationships of Valacyclovir Hydrochloride Polymorphs: Sesquihydrate, Form I, and Form II. Crystal Research and Technology, 2100084. https://doi.org/10.1002/crat.202100084
Fang, C., Gong, J., Wu, S., Wang, J., & Gao, Z. (2020). Ultrasound-assisted intensified crystallization of L-glutamic acid: Crystal nucleation and polymorph transformation. Ultrasonics Sonochemistry, 68, 105227. https://doi.org/10.1016/j.ultsonch.2020.105227
Østergaard, I., De Diego, H. L., Qu, H., & Nagy, Z. K. (2020). Risk-Based Operation of a Continuous Mixed-Suspension-Mixed-Product-Removal Antisolvent Crystallization Process for Polymorphic Control. Organic Process Research & Development, 24(12), 2840–2852. https://doi.org/10.1021/acs.oprd.0c00368
Wang, Y. X., Yu, J., Wang, Y., Chen, Z., Dong, L., Cai, R., Hong, M., Long, X., & Yang, S. (2020). In situ templating synthesis of mesoporous Ni–Fe electrocatalyst for oxygen evolution reaction. RSC Advances, 10(39), 23321–23330. https://doi.org/10.1039/d0ra03111a
Zhang, S., Zhou, L., Yang, W., Xie, C., Yang, X., Hou, B., Hao, H., Zhou, L., Bao, Y., & Yin, Q. (2020). An Investigation into the Morphology Evolution of Ethyl Vanillin with the Presence of a Polymer Additive. Crystal Growth & Design, 20(3), 1609–1617. https://doi.org/10.1021/acs.cgd.9b01341
Mei, C., Deshmukh, S. S., Cronin, J. T., Cong, S., Chapman, D. P., Lazaris, N., Sampaleanu, L. M., Schacht, U., Drolet-Vives, K., Ore, M. O., Morin, S., Carpick, B., Balmer, M., & Kirkitadze, M. (2019). Aluminum Phosphate Vaccine Adjuvant: Analysis of Composition and Size Using Off-Line and In-Line Tools. Computational and Structural Biotechnology Journal, 17, 1184–1194. https://doi.org/10.1016/j.csbj.2019.08.003
Nagy, B., Farkas, A., Gyürkés, M., Komaromy-Hiller, S., Démuth, B., Szabó, B. T., Nusser, D., Nagy, Z. K., & Marosi, G. (2017). In-line Raman spectroscopic monitoring and feedback control of a continuous twin-screw pharmaceutical powder blending and tableting process. International Journal of Pharmaceutics, 530(1–2), 21–29. https://doi.org/10.1016/j.ijpharm.2017.07.041
Tong, Y., Zhang, P., Dang, L., & Wei, H. (2016b). Monitoring of cocrystallization of ethenzamide–saccharin: Insight into kinetic process by in situ Raman spectroscopy. Chemical Engineering Research and Design, 109, 249–257. https://doi.org/10.1016/j.cherd.2016.01.032
Hänchen, M., Prigiobbe, V., Baciocchi, R., & Mazzotti, M. (2008). Precipitation in the Mg-carbonate system—effects of temperature and CO2 pressure. Chemical Engineering Science, 63(4), 1012–1028. https://doi.org/10.1016/j.ces.2007.09.052

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