ReactRaman In-Situ Reaction Analysis

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

ReactRaman enables scientists to monitor reactions and crystallization processes in situ and in real time, providing highly specific information about reaction kinetics, mechanism, pathways, polymorph transitions, and the influence of reaction variables on the process.

Using ReactRaman, scientists directly track changes in the concentration of solid and liquid reactants, intermediates, products, and crystal forms, in real time throughout the experiment. These information-rich experiments provide insights into reaction mechanisms and the impact of critical process parameters (CPP).

Learn more about in-situ Raman spectroscopy with ReactRaman.

ReactRaman 802L

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

ReactRaman with iC Raman™ software brings compositional analysis to every lab, from data collection to analysis. Automated parameter selection provides reliable and accurate data collection, enabling scientists to have confidence in the results. Right first time, every time, in every process, for every user.

Fixed and Interchangeable Raman Probes and Optics

In-situ Raman probe- and flow-based sampling technologies enable the study of liquid and solid phase chemistry in batch or continuous flow configurations. Fit-for-purpose process Raman probes allow use over a wide range of temperatures, pressures, and chemistries. Our Raman probe and optic options include:

Inline Raman flow cells
Raman immersion probes
Non-contact Raman probes
View all in-situ Raman spectroscopy equipment

Comprehensive Reaction Understanding

To understand chemical reactions, chemists use in-situ ReactRaman to address the following:

When does the reaction start and 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 an in-situ Raman spectrometer allows you to trend components over time, making it easier to answer critical reaction and process optimization questions.

Safety in Every Lab

With five safety interlocks and four visual indicators, you can work safely and 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™ 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.

Portable and easy to deploy anywhere in the lab for batch or flow processes. A single robust connector guarantees alignment every time and inherent safety ensures worry-free measurements.

ReactRaman occupies little space and was designed to be stackable with other laboratory instruments for even more compact layouts.

in situ raman spectrometer with automated lab reactor

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, 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.

Reaction Analysis Experts

METTLER TOLEDO has over 30 years experience dedicated to advancing reaction analysis. This is our focus and our passion. We built this expertise into our newest Raman spectrometer.

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 you understand more about their crystallization processes.

Measure form stability
Conversion of polymorphs can be monitored, providing insight into the stability of products to ensure product quality.

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

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 iC Software Suite to provide comprehensive process understanding and control.

In-Situ Raman Spectroscopy Resources

Reaction Analysis via ReactRaman

Real-Time Kinetic & Mechanistic Insight

Polymer Analysis and Characterization Using ReactRaman Spectroscopy

Raman Spectroscopy to Study Polymerization Reactions

Real-Time Reaction Analysis Guide

A Guide Reviewing the Advantages and Importance of Real-Time Reaction Analysis—A Key Element in Any PAT Strategy

Silicone Polymer Synthesis at Dow Toray Co., LTD

Novel Silicone Synthesis Via Precisely Controlled Polymerization

Maximize Reaction Insight from Every Experiment

Unlock Deeper Understanding of Your Chemical Processes

In-Situ Monitoring of Chemical Reactions

Recent Advances in Organic Chemistry

Crystallization Process Design

New Technologies for Crystallization Process Design

Raman Spectrometer FAQs

What is a Raman probe?

A Raman probe uses laser light to create a "fingerprint" by causing molecules in a sample to vibrate in a specific way when the light hits the sample. The fingerprint is then captured and sent via fiber optic cables to an analyzer, where it is compared to known signals. Raman probes use fibers to deliver the excitation laser beam to the sample and collect the signal, allowing for more flexibility with the sample holder.

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, using a non-contact Raman probe is often preferable outside of a site window looking into the reactor. The flow cell can be coupled in-line for flow applications to make continuous measurements.

How do you use a Raman probe?

Connect the SmartConnect™ Raman probe to the spectrometer base unit. 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.

How does a Raman spectrometer work?

A laser beam from the Raman analyzer is typically directed onto the sample, and the Raman scattered light is collected and returned to the spectrometer.

The resulting Raman spectrum, which represents the intensity of scattered light at different wavelengths, provides information about vibrations within the molecule and can be used to identify substances or study specific molecular interactions.

What is a Raman spectrometer used for?

Raman spectrometers are used for identifying unknown materials and verifying or quantifying known materials. Raman spectroscopy is a non-destructive analysis technique that allows for fast and safe analysis, as no sample preparation is needed and, in some cases, samples can even be analyzed in their original packaging.

Applications of Raman spectroscopy include raw material verification, quality control of incoming goods, identification and analysis of active pharmaceutical ingredients (APIs), additives and excipients, and identification of illicit or counterfeit substances such as drugs.

More applications for laboratory Raman systems:

What is the difference between laboratory and handheld Raman systems?

Handheld Raman systems are typically used for qualitative analysis and identifying unknowns in the field by comparing results against a stored spectral library.

Laboratory Raman systems such as ReactRaman offer better stability, higher resolution, and sensitivity compared to handheld Raman systems. Importantly, with the higher sensitivity of laboratory Raman systems, it is also possible to quantify substances at low concentrations.

Below is a selection of publications featuring in-situ Raman spectroscopy equipment:

Yan, Z., Wang, Y., Xu, D., Yang, J., Wang, X., Luo, T., & Zhang, Z. (2023). 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. (2021). 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. (2016). 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