从电子电离到原位电离:质谱技术在化学反应在线监控中的应用进展
Mass Spectrometry for Online Reaction Monitoring: A Technological Journey from Electron Ionization to Ambient Ionization
DOI: 10.12677/aac.2026.161003, PDF,    科研立项经费支持
作者: 潘美芸, 尹轩磊, 李京桥, 韩忠保*, 于 湛:沈阳师范大学化学化工学院,辽宁 沈阳
关键词: 离子源质谱原位监测实时分析化学反应Ion Source Mass Spectrometry In-Situ Monitoring Real-Time Analysis Chemical Reaction
摘要: 目前质谱技术已成为化学反应在线监测的关键手段,传统方法常因采样延迟、前处理复杂及添加额外有机溶剂对反应体系的干扰,获取的反应机制难以反映真实的反应过程;而现代质谱技术借助多样化的电离方式,实现了从高真空到常压、从溶液到固体表面、从微量到宏观体系的原位、实时与无干扰监测。各类电离技术如电子电离(EI)、常压化学电离(APCI)、电喷雾电离(ESI)等,共同构成了适应不同反应类型的分析平台。它们不仅能够实现对反应物、中间体与产物的连续追踪,还能在近乎自然的反应条件下揭示反应路径与机理,广泛应用于催化、有机合成、生物转化、环境降解等领域。未来,该技术将进一步向更高时空分辨率、智能联用等方向发展。
Abstract: Mass spectrometry has become a key analytical tool for the online monitoring of chemical reactions. Conventional approaches often suffer from sampling delays, labor-intensive pretreatment procedures, and perturbations to the reaction system caused by the introduction of additional organic solvents, making it difficult to obtain the true chemical reaction mechanism. In contrast, modern mass spectrometric techniques, enabled by diverse ionization strategies, allow in situ, real-time, and minimally invasive monitoring across a wide range of conditions, spanning from high vacuum to atmospheric pressure, from solutions to solid surfaces, and from trace amounts to macroscopic systems. Ionization methods such as electron ionization (EI), atmospheric pressure chemical ionization (APCI), and electrospray ionization (ESI) collectively constitute versatile analytical platforms adaptable to different reaction types. These techniques enable continuous tracking of reactants, intermediates, and products, while revealing reaction pathways and mechanisms under near-native reaction conditions. As a result, mass spectrometry has been widely applied in catalysis, organic synthesis, biotransformation, and environmental degradation studies. Looking forward, further advances are expected toward higher spatiotemporal resolution and intelligent hybrid analytical systems.
文章引用:潘美芸, 尹轩磊, 李京桥, 韩忠保, 于湛. 从电子电离到原位电离:质谱技术在化学反应在线监控中的应用进展[J]. 分析化学进展, 2026, 16(1): 18-28. https://doi.org/10.12677/aac.2026.161003

参考文献

[1] Brown, T.A., Chen, H. and Zare, R.N. (2015) Identification of Fleeting Electrochemical Reaction Intermediates Using Desorption Electrospray Ionization Mass Spectrometry. Journal of the American Chemical Society, 137, 7274-7277. [Google Scholar] [CrossRef] [PubMed]
[2] Petucci, C., Diffendal, J., Kaufman, D., Mekonnen, B., Terefenko, G. and Musselman, B. (2007) Direct Analysis in Real Time for Reaction Monitoring in Drug Discovery. Analytical Chemistry, 79, 5064-5070. [Google Scholar] [CrossRef] [PubMed]
[3] Resende, S.F., Teodoro, J.A.R., Binatti, I., Gouveia, R.L., Oliveira, B.S. and Augusti, R. (2017) On-Surface Photocatalytic Degradation of Methylene Blue: In Situ Monitoring by Paper Spray Ionization Mass Spectrometry. International Journal of Mass Spectrometry, 418, 107-111. [Google Scholar] [CrossRef
[4] Yu, Z., Chen, L.C., Erra‐Balsells, R., Nonami, H. and Hiraoka, K. (2010) Real‐Time Reaction Monitoring by Probe Electrospray Ionization Mass Spectrometry. Rapid Communications in Mass Spectrometry, 24, 1507-1513. [Google Scholar] [CrossRef] [PubMed]
[5] Canela, M.C., Alberici, R.M., Sofia, R.C.R., Eberlin, M.N. and Jardim, W.F. (1999) Destruction of Malodorous Compounds Using Heterogeneous Photocatalysis. Environmental Science & Technology, 33, 2788-2792. [Google Scholar] [CrossRef
[6] Nuño, M., Ball, R.J. and Bowen, C.R. (2014) Study of Solid/Gas Phase Photocatalytic Reactions by Electron Ionization Mass Spectrometry. Journal of Mass Spectrometry, 49, 716-726. [Google Scholar] [CrossRef] [PubMed]
[7] Tarkiainen, V., Kotiaho, T., Mattila, I., Virkajarvi, I., Aristidou, A. and Ketola, R. (2005) On-Line Monitoring of Continuous Beer Fermentation Process Using Automatic Membrane Inlet Mass Spectrometric System. Talanta, 65, 1254-1263. [Google Scholar] [CrossRef] [PubMed]
[8] Bastidas-Oyanedel, J., Mohd-Zaki, Z., Pratt, S., Steyer, J. and Batstone, D.J. (2010) Development of Membrane Inlet Mass Spectrometry for Examination of Fermentation Processes. Talanta, 83, 482-492. [Google Scholar] [CrossRef] [PubMed]
[9] Hsieh, C., Chao, C., Mong, K.T. and Chen, Y. (2012) Online Monitoring of Chemical Reactions by Contactless Atmospheric Pressure Ionization Mass Spectrometry. Journal of Mass Spectrometry, 47, 586-590. [Google Scholar] [CrossRef] [PubMed]
[10] Zhu, Z., Bartmess, J.E., McNally, M.E., Hoffman, R.M., Cook, K.D. and Song, L. (2012) Quantitative Real-Time Monitoring of Chemical Reactions by Autosampling Flow Injection Analysis Coupled with Atmospheric Pressure Chemical Ionization Mass Spectrometry. Analytical Chemistry, 84, 7547-7554. [Google Scholar] [CrossRef] [PubMed]
[11] Chen, X., Zhu, L., Cui, C., Zhu, Y., Zhou, Z. and Qi, F. (2020) In Situ Atmospheric Pressure Photoionization Mass Spectrometric Monitoring of Initial Pyrolysis Products of Biomass in Real Time. Analytical Chemistry, 92, 603-606. [Google Scholar] [CrossRef] [PubMed]
[12] Fenn, J.B., Mann, M., Meng, C.K., Wong, S.F. and Whitehouse, C.M. (1989) Electrospray Ionization for Mass Spectrometry of Large Biomolecules. Science, 246, 64-71. [Google Scholar] [CrossRef] [PubMed]
[13] Dalmázio, I., Santos, L.S., Lopes, R.P., Eberlin, M.N. and Augusti, R. (2005) Advanced Oxidation of Caffeine in Water: On-Line and Real-Time Monitoring by Electrospray Ionization Mass Spectrometry. Environmental Science & Technology, 39, 5982-5988. [Google Scholar] [CrossRef] [PubMed]
[14] Dalmázio, I., de Urzedo, A.P.F.M., Alves, T.M.A., Catharino, R.R., Eberlin, M.N., Nascentes, C.C., et al. (2007) Electrospray Ionization Mass Spectrometry Monitoring of Indigo Carmine Degradation by Advanced Oxidative Processes. Journal of Mass Spectrometry, 42, 1273-1278. [Google Scholar] [CrossRef] [PubMed]
[15] Paz-Schmidt, R.A., Bonrath, W. and Plattner, D.A. (2009) Online ESI-MS Analysis of Reactions under High Pressure. Analytical Chemistry, 81, 3665-3668. [Google Scholar] [CrossRef] [PubMed]
[16] Wilm, M. and Mann, M. (1996) Analytical Properties of the Nanoelectrospray Ion Source. Analytical Chemistry, 68, 1-8. [Google Scholar] [CrossRef] [PubMed]
[17] Kirby, A.E. and Wheeler, A.R. (2013) Microfluidic Origami: A New Device Format for In-Line Reaction Monitoring by Nanoelectrospray Ionization Mass Spectrometry. Lab on a Chip, 13, Article 2533. [Google Scholar] [CrossRef] [PubMed]
[18] Yang, Y., Han, F., Ouyang, J., Zhao, Y., Han, J. and Na, N. (2016) In-Situ Nanoelectrospray for High-Throughput Screening of Enzymes and Real-Time Monitoring of Reactions. Analytica Chimica Acta, 902, 135-141. [Google Scholar] [CrossRef] [PubMed]
[19] van Geenen, F.A.M.G., Franssen, M.C.R., Miikkulainen, V., Ritala, M., Zuilhof, H., Kostiainen, R., et al. (2019) TiO2 Photocatalyzed Oxidation of Drugs Studied by Laser Ablation Electrospray Ionization Mass Spectrometry. Journal of the American Society for Mass Spectrometry, 30, 639-646. [Google Scholar] [CrossRef] [PubMed]
[20] Chen, H. and Zenobi, R. (2008) Neutral Desorption Sampling of Biological Surfaces for Rapid Chemical Characterization by Extractive Electrospray Ionization Mass Spectrometry. Nature Protocols, 3, 1467-1475. [Google Scholar] [CrossRef] [PubMed]
[21] Zhu, L., Gamez, G., Chen, H.W., Huang, H.X., Chingin, K. and Zenobi, R. (2008) Real‐Time, On‐Line Monitoring of Organic Chemical Reactions Using Extractive Electrospray Ionization Tandem Mass Spectrometry. Rapid Communications in Mass Spectrometry, 22, 2993-2998. [Google Scholar] [CrossRef] [PubMed]
[22] McCullough, B.J., Bristow, T., O'Connor, G. and Hopley, C. (2011) On‐Line Reaction Monitoring by Extractive Electrospray Ionisation. Rapid Communications in Mass Spectrometry, 25, 1445-1451. [Google Scholar] [CrossRef] [PubMed]
[23] Zhang, X., Pei, M., Wu, D., Yang, S. and Le, Z. (2019) Real-Time Monitoring of the Reaction between Aniline and Acetonylacetone Using Extractive Electorspray Ionization Tandem Mass Spectrometry. Scientific Reports, 9, Article No. 19279. [Google Scholar] [CrossRef] [PubMed]
[24] Cheng, C., Yuan, C., Cheng, S., Huang, M., Chang, H., Cheng, T., et al. (2008) Electrospray-Assisted Laser Desorption/Ionization Mass Spectrometry for Continuously Monitoring the States of Ongoing Chemical Reactions in Organic or Aqueous Solution under Ambient Conditions. Analytical Chemistry, 80, 7699-7705. [Google Scholar] [CrossRef] [PubMed]
[25] da Silva, J.C.C., Reis Teodoro, J.A., Afonso, R.J.d.C.F., Aquino, S.F. and Augusti, R. (2014) Photodegradation of Bisphenol a in Aqueous Medium: Monitoring and Identification of By‐Products by Liquid Chromatography Coupled to High‐Resolution Mass Spectrometry. Rapid Communications in Mass Spectrometry, 28, 987-994. [Google Scholar] [CrossRef] [PubMed]
[26] Hsu, F., Liu, T., Laskar, A.H., Shiea, J. and Huang, M. (2014) Gravitational Sampling Electrospray Ionization Mass Spectrometry for Real‐Time Reaction Monitoring. Rapid Communications in Mass Spectrometry, 28, 1979-1986. [Google Scholar] [CrossRef] [PubMed]
[27] Yan, X., Sokol, E., Li, X., Li, G., Xu, S. and Cooks, R.G. (2014) On‐Line Reaction Monitoring and Mechanistic Studies by Mass Spectrometry: Negishi Cross‐Coupling, Hydrogenolysis, and Reductive Amination. Angewandte Chemie International Edition, 53, 5931-5935. [Google Scholar] [CrossRef] [PubMed]
[28] Lee, J.K., Kim, S., Nam, H.G. and Zare, R.N. (2015) Microdroplet Fusion Mass Spectrometry for Fast Reaction Kinetics. Proceedings of the National Academy of Sciences, 112, 3898-3903. [Google Scholar] [CrossRef] [PubMed]
[29] Lin, S., Lo, T., Kuo, F. and Chen, Y. (2014) Real Time Monitoring of Accelerated Chemical Reactions by Ultrasonication‐Assisted Spray Ionization Mass Spectrometry. Journal of Mass Spectrometry, 49, 50-56. [Google Scholar] [CrossRef] [PubMed]
[30] Liu, J., Wang, H., Manicke, N.E., Lin, J., Cooks, R.G. and Ouyang, Z. (2010) Development, Characterization, and Application of Paper Spray Ionization. Analytical Chemistry, 82, 2463-2471. [Google Scholar] [CrossRef] [PubMed]
[31] Liu, W., Mao, S., Wu, J. and Lin, J. (2013) Development and Applications of Paper-Based Electrospray Ionization-Mass Spectrometry for Monitoring of Sequentially Generated Droplets. The Analyst, 138, Article 2163. [Google Scholar] [CrossRef] [PubMed]
[32] Yan, X., Augusti, R., Li, X. and Cooks, R.G. (2013) Chemical Reactivity Assessment Using Reactive Paper Spray Ionization Mass Spectrometry: The Katritzky Reaction. ChemPlusChem, 78, 1142-1148. [Google Scholar] [CrossRef] [PubMed]
[33] Banerjee, S., Basheer, C. and Zare, R.N. (2016) A Study of Heterogeneous Catalysis by Nanoparticle‐Embedded Paper‐spray Ionization Mass Spectrometry. Angewandte Chemie International Edition, 55, 12807-12811. [Google Scholar] [CrossRef] [PubMed]
[34] Li, J., Dewald, H.D. and Chen, H. (2009) Online Coupling of Electrochemical Reactions with Liquid Sample Desorption Electrospray Ionization-Mass Spectrometry. Analytical Chemistry, 81, 9716-9722. [Google Scholar] [CrossRef] [PubMed]
[35] Zheng, Q., Liu, Y., Chen, Q., Hu, M., Helmy, R., Sherer, E.C., et al. (2015) Capture of Reactive Monophosphine-Ligated Palladium(0) Intermediates by Mass Spectrometry. Journal of the American Chemical Society, 137, 14035-14038. [Google Scholar] [CrossRef] [PubMed]
[36] Brown, T.A., Hosseini-Nassab, N., Chen, H. and Zare, R.N. (2016) Observation of Electrochemically Generated Nitrenium Ions by Desorption Electrospray Ionization Mass Spectrometry. Chemical Science, 7, 329-332. [Google Scholar] [CrossRef] [PubMed]
[37] Brown, T.A., Chen, H. and Zare, R.N. (2015) Detection of the Short‐Lived Radical Cation Intermediate in the Electrooxidation of N, N‐Dimethylaniline by Mass Spectrometry. Angewandte Chemie, 127, 11335-11337. [Google Scholar] [CrossRef
[38] Yu, Z., Chen, L.C., Mandal, M.K., Nonami, H., Erra-Balsells, R. and Hiraoka, K. (2012) Online Electrospray Ionization Mass Spectrometric Monitoring of Protease-Catalyzed Reactions in Real Time. Journal of the American Society for Mass Spectrometry, 23, 728-735. [Google Scholar] [CrossRef] [PubMed]
[39] Han, Z., Gu, X., Wang, S., Liu, L., Wang, Y., Zhao, Z., et al. (2020) Time-Resolved in Situ Monitoring of Photocatalytic Reactions by Probe Electrospray Ionization Mass Spectrometry. The Analyst, 145, 3313-3319. [Google Scholar] [CrossRef] [PubMed]
[40] Jiang, J., Zhang, H., Li, M., Dulay, M.T., Ingram, A.J., Li, N., et al. (2015) Droplet Spray Ionization from a Glass Microscope Slide: Real-Time Monitoring of Ethylene Polymerization. Analytical Chemistry, 87, 8057-8062. [Google Scholar] [CrossRef] [PubMed]
[41] Zhang, H., Li, N., Zhao, D., Jiang, J. and You, H. (2017) Substrate-Coated Illumination Droplet Spray Ionization: Real-Time Monitoring of Photocatalytic Reactions. Journal of the American Society for Mass Spectrometry, 28, 1939-1946. [Google Scholar] [CrossRef] [PubMed]
[42] Jansson, E.T., Dulay, M.T. and Zare, R.N. (2016) Monitoring Enzymatic Reactions in Real Time Using Venturi Easy Ambient Sonic-Spray Ionization Mass Spectrometry. Analytical Chemistry, 88, 6195-6198. [Google Scholar] [CrossRef] [PubMed]
[43] Santos, V.G., Regiani, T., Dias, F.F.G., Romão, W., Jara, J.L.P., Klitzke, C.F., et al. (2011) Venturi Easy Ambient Sonic-Spray Ionization. Analytical Chemistry, 83, 1375-1380. [Google Scholar] [CrossRef] [PubMed]
[44] Harper, J.D., Charipar, N.A., Mulligan, C.C., Zhang, X., Cooks, R.G. and Ouyang, Z. (2008) Low-Temperature Plasma Probe for Ambient Desorption Ionization. Analytical Chemistry, 80, 9097-9104. [Google Scholar] [CrossRef] [PubMed]
[45] Ma, X., Zhang, S., Lin, Z., Liu, Y., Xing, Z., Yang, C., et al. (2009) Real-Time Monitoring of Chemical Reactions by Mass Spectrometry Utilizing a Low-Temperature Plasma Probe. The Analyst, 134, Article 1863. [Google Scholar] [CrossRef] [PubMed]
[46] Zeng, N., Long, Z., Wang, Y., Sun, J., Ouyang, J. and Na, N. (2019) An Acetone Sensor Based on Plasma-Assisted Cataluminescence and Mechanism Studies by Online Ionizations. Analytical Chemistry, 91, 15763-15768. [Google Scholar] [CrossRef] [PubMed]
[47] Cody, R.B., Laramée, J.A. and Durst, H.D. (2005) Versatile New Ion Source for the Analysis of Materials in Open Air under Ambient Conditions. Analytical Chemistry, 77, 2297-2302. [Google Scholar] [CrossRef] [PubMed]
[48] Schwartz-Narbonne, H., Wang, C., Zhou, S., Abbatt, J.P.D. and Faust, J. (2019) Heterogeneous Chlorination of Squalene and Oleic Acid. Environmental Science & Technology, 53, 1217-1224. [Google Scholar] [CrossRef] [PubMed]
[49] Orendorz, A., Ziegler, C. and Gnaser, H. (2008) Photocatalytic Decomposition of Methylene Blue and 4-Chlorophenol on Nanocrystalline TiO2 Films under UV Illumination: A ToF-Sims Study. Applied Surface Science, 255, 1011-1014. [Google Scholar] [CrossRef
[50] Pei, J., Kang, Y. and Huang, G. (2014) Reactive Intermediate Detection in Real Time via Paper Assisted Thermal Ionization Mass Spectrometry. The Analyst, 139, 5354-5357. [Google Scholar] [CrossRef] [PubMed]