Automated Reactor Sampling System | Inline, Unattended Sampling 24/7

Automated Sampling for Chemical Reactions

EasySampler—Critical for Data Rich Experimentation

What is an automated reactor sampling system and how does it work?

automated reactor sampling system

automated reactor sampling system
automated reactor sampling system

EasySampler combines three sampling steps into a single automated operation, sampling the same way, every time to provide reproducible and accurate samples.

  • Accurate sampling starts when the micro-pocket moves out and is immersed within the reaction mixture to ensure a representative sample is taken
  • In-situ quench immediately stops the reaction and ensures the time point is representative
  • Subsequent dilution and dispensing in the vial prepare samples for offline analysis  

These steps allow samples to be highly reproducible and provide representative analytical results. Above all, automated samples can be taken at preprogrammed or scheduled times. 

What is the temperature range of the EasySampler probe?

At atmospheric pressure, EasySampler probes are rated for temperatures in the range of -20 to 140 °C. It is recommended to change sleeves after 100 samples within this temperature range, at atmospheric pressure. For reactions at elevated pressures, between 1.013 bar and 10 bar, the temperature range is 20 to 100 °C. 

Why should I automate my sampling of chemical reactions?

It is understood that sampling chemical reactions for offline analysis use analytical techniques to ascertain reaction status, yield, or impurity profiles. The sampling procedure, sadly, is not always an exact operation and poses difficulties for reactions involving heterogeneous mixtures, high temperatures, slurries, or air-sensitive chemistry. Delays in quenching can also result in extremely varied outcomes as well as erroneous and imprecise analytical data.

By offering an automated and reliable inline technique of acquiring representative samples from reactions, even under challenging circumstances, EasySampler was created to overcome these difficulties. Scientists have been using EasySampler to help their synthetic chemistry and process development work at Pfizer and other pharmaceutical businesses.

I have a reactor from another vendor; can I use EasySampler with this reactor?

Yes, EasySampler can function as a stand-alone device and can be used in any reactor, including tube reactors, round-bottomed flasks, jacked lab reactors (JLR), and automated lab reactors (ALR). Points to consider:

  • All models of EasySampler probes are 9.5 mm in diameter
  • An appropriate adapter should be used to fit the EasySampler probe securely into the reactor port

Can EasySampler be used to sample reactions at elevated pressure?

Yes, EasySampler can sample reactions under pressure if all the following reaction conditions are met: 

  1. Pressure range: 1.013 bar – 10 bar (14.7 – 145 psi) 
  2. Temperature range: 20 to 100 °C 
  3. Reactor volume: up to 2500 mL 
  4. Number of samples per sleeve: 1 reaction (with up to 24 samples)
  5. High-pressure adapter: An appropriate high-pressure adapter (P/N14474404) must be used to securely position the EasySampler probe in the reactor

Note: Use of the EasySampler probe at elevated pressure (between 1.013 bar to 10 bar) will reduce the temperature range to 20 °C to 100 °C, the maximum reactor volume to 2500 mL, and the maximum number of samples per sleeve to 1 reaction (with up to 24 samples).

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Automated Chemical Sampling Systems in Journal Publications

Continued automated sampling with the EasySampler supports reaction and impurity profiling studies. A list of publications from peer-reviewed journals focuses on exciting and novel applications of EasySampler by researchers in both academia and industry to support data-rich experimentation to advance their research.

  • Lomont, J. P., Ralbovsky, N. M., Guza, C., Saha-Shah, A., Burzynski, J., Konietzko, J., Wang, S.-C., McHugh, P. M., Mangion, I., & Smith, J. P. (2022). Process monitoring of polysaccharide deketalization for vaccine bioconjugation development using in situ analytical methodology. Journal of Pharmaceutical and Biomedical Analysis209, 114533. https://doi.org/10.1016/j.jpba.2021.114533
  • Ashworth, I. W., Frodsham, L., Moore, P., & Ronson, T. O. (2021). Evidence of Rate Limiting Proton Transfer in an SNAr Aminolysis in Acetonitrile under Synthetically Relevant Conditions. The Journal of Organic Chemistry. https://doi.org/10.1021/acs.joc.1c017...
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Continued automated sampling with the EasySampler supports reaction and impurity profiling studies. A list of publications from peer-reviewed journals focuses on exciting and novel applications of EasySampler by researchers in both academia and industry to support data-rich experimentation to advance their research.

  • Lomont, J. P., Ralbovsky, N. M., Guza, C., Saha-Shah, A., Burzynski, J., Konietzko, J., Wang, S.-C., McHugh, P. M., Mangion, I., & Smith, J. P. (2022). Process monitoring of polysaccharide deketalization for vaccine bioconjugation development using in situ analytical methodology. Journal of Pharmaceutical and Biomedical Analysis209, 114533. https://doi.org/10.1016/j.jpba.2021.114533
  • Ashworth, I. W., Frodsham, L., Moore, P., & Ronson, T. O. (2021). Evidence of Rate Limiting Proton Transfer in an SNAr Aminolysis in Acetonitrile under Synthetically Relevant Conditions. The Journal of Organic Chemistry. https://doi.org/10.1021/acs.joc.1c01768
  • Pollack, S. R., & Dion, A. (2021). Metal-Free Stereoselective Synthesis of (E)- and (Z)-N-Monosubstituted β-Aminoacrylates via Condensation Reactions of Carbamates. The Journal of Organic Chemistry86(17), 11748–11762. https://doi.org/10.1021/acs.joc.1c01212
  • Zhao, X., Webb, N. J., Muehlfeld, M. P., Stottlemyer, A. L., & Russell, M. W. (2021). Application of a Semiautomated Crystallizer to Study Oiling-Out and Agglomeration Events—A Case Study in Industrial Crystallization Optimization. Organic Process Research & Development25(3), 564–575. https://doi.org/10.1021/acs.oprd.0c00494
  • Jurica, J. A., & McMullen, J. P. (2021). Automation Technologies to Enable Data-Rich Experimentation: Beyond Design of Experiments for Process Modeling in Late-Stage Process Development. Organic Process Research & Development25(2), 282–291. https://doi.org/10.1021/acs.oprd.0c00496
  • Malig, T. C., Yunker, L. P. E., Steiner, S., & Hein, J. E. (2020). Online High-Performance Liquid Chromatography Analysis of Buchwald–Hartwig Aminations from within an Inert Environment. ACS Catalysis10(22), 13236–13244. https://doi.org/10.1021/acscatal.0c03530
  • Malig, T. C., Tan, Y., Wisniewski, S. R., Higman, C. S., Carrasquillo-Flores, R., Ortiz, A., Purdum, G. E., Kolotuchin, S., & Hein, J. E. (2020). Development of a telescoped synthesis of 4-(1H)-cyanoimidazole core accelerated by orthogonal reaction monitoring. Reaction Chemistry & Engineering5(8), 1421–1428. https://doi.org/10.1039/d0re00234h
  • Wang, K., Han, L., Mustakis, J., Li, B., Magano, J., Damon, D. B., Dion, A., Maloney, M. T., Post, R., & Li, R. (2019). Kinetic and Data-Driven Reaction Analysis for Pharmaceutical Process Development. Industrial & Engineering Chemistry Research59(6), 2409–2421. https://doi.org/10.1021/acs.iecr.9b03578
  • Beutner, G. L., Coombs, J. R., Green, R. A., Inankur, B., Lin, D., Qiu, J., Roberts, F., Simmons, E. M., & Wisniewski, S. R. (2019). Palladium-Catalyzed Amidation and Amination of (Hetero)aryl Chlorides under Homogeneous Conditions Enabled by a Soluble DBU/NaTFA Dual-Base System. Organic Process Research & Development23(8), 1529–1537. https://doi.org/10.1021/acs.oprd.9b00196
  • Huffman, M. A., Fryszkowska, A., Alvizo, O., Borra-Garske, M., Campos, K. R., Canada, K. A., Devine, P. N., Duan, D., Forstater, J. H., Grosser, S. T., Halsey, H. M., Hughes, G. J., Jo, J., Joyce, L. A., Kolev, J. N., Liang, J., Maloney, K. M., Mann, B. F., Marshall, N. M., & McLaughlin, M. (2019). Design of an in vitro biocatalytic cascade for the manufacture of islatravir. Science366(6470), 1255–1259. https://doi.org/10.1126/science.aay8484
  • Mennen, S. M., Alhambra, C., Allen, C. L., Barberis, M., Berritt, S., Brandt, T. A., Campbell, A. D., Castañón, J., Cherney, A. H., Christensen, M., Damon, D. B., Eugenio de Diego, J., García-Cerrada, S., García-Losada, P., Haro, R., Janey, J., Leitch, D. C., Li, L., Liu, F., Lobben, P. C., MacMillan, D. W. C., Magano, J., McInturff, E., Monfette, S., Post, R. J., Schultz, D., Sitter, B., Stevens, J. M., Strambeanu, I. I., Twilton, J., Wang, K., & Zajac, M. A. (2019). The Evolution of High-Throughput Experimentation in Pharmaceutical Development and Perspectives on the Future. Organic Process Research & Development23(6), 1213–1242. https://doi.org/10.1021/acs.oprd.9b00140
  • Carter, H. L., Connor, A. W., Hart, R., McCabe, J., McIntyre, A. C., McMillan, A. E., Monks, N. R., Mullen, A. K., Ronson, T. O., Steven, A., Tomasi, S., & Yates, S. D. (2019). Rapid route design of AZD7594. Reaction Chemistry & Engineering4(9), 1658–1673. https://doi.org/10.1039/c9re00118b
  • Zawatzky, K., Grosser, S., & Welch, C. J. (2017). Facile kinetic profiling of chemical reactions using MISER chromatographic analysis. Tetrahedron73(33), 5048–5053. https://doi.org/10.1016/j.tet.2017.05.048
  • Gurung, S. R., Mitchell, C., Huang, J., Jonas, M., Strawser, J. D., Daia, E., Hardy, A., O’Brien, E., Hicks, F., & Papageorgiou, C. D. (2016). Development and Scale-up of an Efficient Miyaura Borylation Process Using Tetrahydroxydiboron. Organic Process Research & Development21(1), 65–74. https://doi.org/10.1021/acs.oprd.6b00345
  • Rougeot, C., Situ, H., Cao, B. H., Vlachos, V., & Hein, J. E. (2017). Automated reaction progress monitoring of heterogeneous reactions: crystallization-induced stereoselectivity in amine-catalyzed aldol reactions. Reaction Chemistry & Engineering2(2), 226–231. https://doi.org/10.1039/c6re00211k
  • Duan, S., Place, D., Perfect, H. H., Ide, N. D., Maloney, M., Sutherland, K., Price Wiglesworth, K. E., Wang, K., Olivier, M., Kong, F., Leeman, K., Blunt, J., Draper, J., McAuliffe, M., O’Sullivan, M., & Lynch, D. (2016). Palbociclib Commercial Manufacturing Process Development. Part I: Control of Regioselectivity in a Grignard-Mediated SNAr Coupling. Organic Process Research & Development, 20(7), 1191–1202. https://doi.org/10.1021/acs.oprd.6b00070
  • Malig, T. C., Koenig, J. D. B., Situ, H., Chehal, N. K., Hultin, P. G., & Hein, J. E. (2017). Real-time HPLC-MS reaction progress monitoring using an automated analytical platform. Reaction Chemistry & Engineering, 2(3), 309–314. https://doi.org/10.1039/c7re00026j
  • Nykaza, T. V., Ramirez, A., Harrison, T. S., Luzung, M. R., & Radosevich, A. T. (2018). Biphilic Organophosphorus-Catalyzed Intramolecular Csp2–H Amination: Evidence for a Nitrenoid in Catalytic Cadogan Cyclizations. Journal of the American Chemical Society, 140(8), 3103–3113. https://doi.org/10.1021/jacs.7b13803
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