Fluorosurfactants and their application in droplet microreactors: An overview

doi:10.1016/j.cjche.2024.11.001

Abstract

Abstract: Fluorosurfactants play a crucial role in ensuring the stability and uniformity of droplet microreactors, which significantly broaden their applications in chemical and biological research. This review covers structure diversity and functional versatility of fluorosurfactants. Fluorosurfactants can be divided into two basic types according to their structure, linear and dendritic types, which both provides individual advantages. Linear fluorosurfactants are easily synthesized and commercially available, whereas dendritic fluorosurfactants have a branched structure that greatly reduces molecular cross-talk between droplets. Based on the application point of view, fluorosurfactants can be further classified into two categories: reactive and responsive fluorosurfactants. The hydrophilic head of reactive fluorosurfactants contains a reactive functional group, making them very useful in other applications, such as microcapsule preparation or protein crystallization. In contrast, responsive fluorosurfactants would change their properties with respect to external stimuli, such as temperature or light, making them perfect candidates for the on-demand control of droplet behavior. Development of these new classes of fluorosurfactants has expanded the capabilities and applications of droplet microreactors that enables interdisciplinary challenges to be solved.

Key words: Microreactor, Surfactants, Interface, Droplet stability, Linear/dendric surfactants, Reactive/responsive fluorosurfactants

摘要： Fluorosurfactants play a crucial role in ensuring the stability and uniformity of droplet microreactors, which significantly broaden their applications in chemical and biological research. This review covers structure diversity and functional versatility of fluorosurfactants. Fluorosurfactants can be divided into two basic types according to their structure, linear and dendritic types, which both provides individual advantages. Linear fluorosurfactants are easily synthesized and commercially available, whereas dendritic fluorosurfactants have a branched structure that greatly reduces molecular cross-talk between droplets. Based on the application point of view, fluorosurfactants can be further classified into two categories: reactive and responsive fluorosurfactants. The hydrophilic head of reactive fluorosurfactants contains a reactive functional group, making them very useful in other applications, such as microcapsule preparation or protein crystallization. In contrast, responsive fluorosurfactants would change their properties with respect to external stimuli, such as temperature or light, making them perfect candidates for the on-demand control of droplet behavior. Development of these new classes of fluorosurfactants has expanded the capabilities and applications of droplet microreactors that enables interdisciplinary challenges to be solved.

关键词: Microreactor, Surfactants, Interface, Droplet stability, Linear/dendric surfactants, Reactive/responsive fluorosurfactants

Wei Cheng, Huilin Wen, Xiaoqiang Chen, Shaobin Zhang, Ziyi Yu. Fluorosurfactants and their application in droplet microreactors: An overview[J]. Chinese Journal of Chemical Engineering, 2025, 78(2): 314-326.

Wei Cheng, Huilin Wen, Xiaoqiang Chen, Shaobin Zhang, Ziyi Yu. Fluorosurfactants and their application in droplet microreactors: An overview[J]. 中国化学工程学报, 2025, 78(2): 314-326.

References

[1] A.J. DeMello, Control and detection of chemical reactions in microfluidic systems, Nature 442 (7101) (2006) 394-402.
[2] P.L. Suryawanshi, S.P. Gumfekar, B.A. Bhanvase, S.H. Sonawane, M.S. Pimplapure, A review on microreactors: Reactor fabrication, design, and cutting-edge applications, Chem. Eng. Sci. 189 (2018) 431-448.
[3] A.B. Theberge, F. Courtois, Y. Schaerli, M. Fischlechner, C. Abell, F. Hollfelder, W.T.S. Huck, Microdroplets in microfluidics: An evolving platform for discoveries in chemistry and biology, Angew. Chem. Int. Ed. 49 (34) (2010) 5846-5868.
[4] E.Y. Basova, F. Foret, Droplet microfluidics in (bio)chemical analysis, Analyst 140 (1) (2015) 22-38.
[5] Z.K. Chen, S. Kheiri, E.W.K. Young, E. Kumacheva, Trends in droplet microfluidics: From droplet generation to biomedical applications, Langmuir 38 (20) (2022) 6233-6248.
[6] L.B. Liu, N. Xiang, Z.H. Ni, Droplet-based microreactor for the production of micro/nano-materials, Electrophoresis 41 (10-11) (2020) 833-851.
[7] K. Lee, H.R. Lee, Y.H. Kim, J. Park, S. Cho, S. Li, M. Seo, S.Q. Choi, Microdroplet-mediated radical polymerization, ACS Cent. Sci. 8 (9) (2022) 1265-1271.
[8] L.B. Hyman, C.R. Christopher, P.A. Romero, Single-cell nucleic acid profiling in droplets (SNAPD) enables high-throughput analysis of heterogeneous cell populations, Nucleic Acids Res. 49 (18) (2021) e103.
[9] M. Zhang, R. Ettelaie, T. Yan, S.J. Zhang, F.Q. Cheng, B.P. Binks, H.Q. Yang, Ionic liquid droplet microreactor for catalysis reactions not at equilibrium, J. Am. Chem. Soc. 139 (48) (2017) 17387-17396.
[10] L. Frenz, A. El Harrak, M. Pauly, S. Begin-Colin, A.D. Griffiths, J.C. Baret, Droplet-based microreactors for the synthesis of magnetic iron oxide nanoparticles, Angew. Chem. Int. Ed. 47 (36) (2008) 6817-6820.
[11] J.C. Vollenbroek, A.E. Nieuwelink, J.G. Bomer, R.M. Tiggelaar, A. van den Berg, B.M. Weckhuysen, M. Odijk, Droplet microreactor for high-throughput fluorescence-based measurements of single catalyst particle acidity, Microsyst. Nanoeng. 9 (1) (2023) 39.
[12] P. Gruner, B. Riechers, B. Semin, J. Lim, A. Johnston, K. Short, J.C. Baret, Controlling molecular transport in minimal emulsions, Nat. Commun. 7 (1) (2016) 10392.
[13] Y. Skhiri, P. Gruner, B. Semin, Q. Brosseau, D. Pekin, L. Mazutis, V. Goust, F. Kleinschmidt, A. El Harrak, J.B. Hutchison, E. Mayot, J.F. Bartolo, A.D. Griffiths, V. Taly, J.C. Baret, Dynamics of molecular transport by surfactants in emulsions, Soft Matter 8 (41) (2012) 10618-10627.
[14] T. Heida, J.W. Neubauer, M. Seuss, N. Hauck, J. Thiele, A. Fery, Mechanically defined microgels by droplet microfluidics, Macromol. Chem. Phys. 218 (2) (2017) 1600418.
[15] O. Wagner, J. Thiele, M. Weinhart, L. Mazutis, D.A. Weitz, W.T.S. Huck, R. Haag, Biocompatible fluorinated polyglycerols for droplet microfluidics as an alternative to PEG-based copolymer surfactants, Lab Chip 16 (1) (2016) 65-69.
[16] G. Etienne, M. Kessler, E. Amstad, Influence of fluorinated surfactant composition on the stability of emulsion drops, Macromol. Chem. Phys. 218 (2) (2017) 1600365.
[17] G. Woronoff, A. El Harrak, E. Mayot, O. Schicke, O.J. Miller, P. Soumillion, A.D. Griffiths, M. Ryckelynck, New generation of amino coumarin methyl sulfonate-based fluorogenic substrates for amidase assays in droplet-based microfluidic applications, Anal. Chem. 83 (8) (2011) 2852-2857.
[18] F.Y. Chen, Y.H. Zhan, T. Geng, H.Z. Lian, P.S. Xu, C. Lu, Chemical transfection of cells in picoliter aqueous droplets in fluorocarbon oil, Anal. Chem. 83 (22) (2011) 8816-8820.
[19] C.Y. Lin, R.R. Liu, Q. Lou, X.Y. Wang, D. Chen, B.L. Guo, One-step preparation of magnet-responsive amphiphilic nanoparticles for efficient oil collection, Colloids Surf. A Physicochem. Eng. Aspects 694 (2024) 134137.
[20] J.P. Sheng, J.C. Wu, X.H. Yin, Z. Sun, X. Wang, J.L. Zhang, J.H. Tang, Y.T. Ji, J.Y. Song, X.B. Wei, L. Wang, Y.X. Zhao, H. Zhang, T.H. Li, Q. Zhang, X.L. Bai, L. Chen, D. Chen, T.B. Liang, Synergetic treatment of oxygen microcapsules and lenvatinib for enhanced therapy of HCC by alleviating hypoxia condition and activating anti-tumor immunity, Chinese Chem. Lett. 34 (4) (2023) 107738.
[21] Z. Sun, X.X. Yan, Y. Xiao, L.J. Hu, M. Eggersdorfer, D. Chen, Z.Z. Yang, D.A. Weitz, Pickering emulsions stabilized by colloidal surfactants: Role of solid particles, Particuology 64 (2022) 153-163.
[22] H. Jiang, Y.F. Sheng, T. Ngai, Pickering emulsions: Versatility of colloidal particles and recent applications, Curr. Opin. Colloid Interface Sci. 49 (2020) 1-15.
[23] S.M.S. Hussain, A.A. Adewunmi, A. Mahboob, M. Murtaza, X. Zhou, M.S. Kamal, Fluorinated surfactants: A review on recent progress on synthesis and oilfield applications, Adv. Colloid Interface Sci. 303 (2022) 102634.
[24] F. Junge, P.W. Lee, A. Kumar Singh, J. Wasternack, M.P. Pachnicz, R. Haag, C.A. Schalley, Interfaces with fluorinated amphiphiles: Superstructures and microfluidics, Angew. Chem. Int. Ed. 62 (12) (2023) e202213866.
[25] D.J. Holt, R.J. Payne, W.Y. Chow, C. Abell, Fluorosurfactants for microdroplets: Interfacial tension analysis, J. Colloid Interface Sci. 350 (1) (2010) 205-211.
[26] D.J. Holt, R.J. Payne, C. Abell, Synthesis of novel fluorous surfactants for microdroplet stabilisation in fluorous oil streams, J. Fluorine. Chem. 131 (3) (2010) 398-407.
[27] J. Clausell-Tormos, D. Lieber, J.C. Baret, A. El-Harrak, O.J. Miller, L. Frenz, J. Blouwolff, K.J. Humphry, S. Koster, H. Duan, C. Holtze, D.A. Weitz, A.D. Griffiths, C.A. Merten, Droplet-based microfluidic platforms for the encapsulation and screening of Mammalian cells and multicellular organisms, Chem. Biol. 15 (5) (2008) 427-437.
[28] C. Holtze, A.C. Rowat, J.J. Agresti, J.B. Hutchison, F.E. Angile, C.H.J. Schmitz, S. Koster, H. Duan, K.J. Humphry, R.A. Scanga, J.S. Johnson, D. Pisignano, D.A. Weitz, Biocompatible surfactants for water-in-fluorocarbon emulsions, Lab Chip 8 (10) (2008) 1632-1639.
[29] M. Pan, F.J. Lyu, S.K.Y. Tang, Methods to coalesce fluorinated Pickering emulsions, Anal. Methods 9 (31) (2017) 4622-4629.
[30] M.S. Chowdhury, W. Zheng, S. Kumari, J. Heyman, X. Zhang, P. Dey, D.A. Weitz, R. Haag, Dendronized fluorosurfactant for highly stable water-in-fluorinated oil emulsions with minimal inter-droplet transfer of small molecules, Nat. Commun. 10 (1) (2019) 4546.
[31] M.S. Chowdhury, W. Zheng, A.K. Singh, I.L.H. Ong, Y. Hou, J.A. Heyman, A. Faghani, E. Amstad, D.A. Weitz, R. Haag, Linear triglycerol-based fluorosurfactants show high potential for droplet-microfluidics-based biochemical assays, Soft Matter 17 (31) (2021) 7260-7267.
[32] M.S. Chowdhury, X. Zhang, L. Amini, P. Dey, A.K. Singh, A. Faghani, M. Schmueck-Henneresse, R. Haag, Functional surfactants for molecular fishing, capsule creation, and single-cell gene expression, Nanomicro Lett. 13 (1) (2021) 147.
[33] X.K. Li, S.Y. Tang, Y. Zhang, J.Y. Zhu, H. Forgham, C.X. Zhao, C. Zhang, T.P. Davis, R.R. Qiao, Tailored fluorosurfactants through controlled/living radical polymerization for highly stable microfluidic droplet generation, Angew. Chem. Int. Ed. 63 (3) (2024) e202315552.
[34] C.J. DeJournette, J. Kim, H. Medlen, X.P. Li, L.J. Vincent, C.J. Easley, Creating biocompatible oil-water interfaces without synthesis: Direct interactions between primary amines and carboxylated perfluorocarbon surfactants, Anal. Chem. 85 (21) (2013) 10556-10564.
[35] G. Etienne, I.L.H. Ong, E. Amstad, Bioinspired viscoelastic capsules: Delivery vehicles and beyond, Adv. Mater. 31 (27) (2019) e808233.
[36] Q.F. Zhang, S. Savagatrup, P. Kaplonek, P.H. Seeberger, T.M. Swager, Janus emulsions for the detection of bacteria, ACS Cent. Sci. 3 (4) (2017) 309-313.
[37] J.E. Kreutz, L. Li, L.S. Roach, T. Hatakeyama, R.F. Ismagilov, Laterally mobile, functionalized self-assembled monolayers at the fluorous-aqueous interface in a plug-based microfluidic system: Characterization and testing with membrane protein crystallization, J. Am. Chem. Soc. 131 (17) (2009) 6042-6043.
[38] P. Dunkel, Z. Hayat, A. Barosi, N. Bchellaoui, H. Dhimane, P.I. Dalko, A.I. El Abed, Photolysis-driven merging of microdroplets in microfluidic chambers, Lab Chip 16 (8) (2016) 1484-1491.
[39] Z. Hayat, N. Bchellaoui, C. Deo, R. Metivier, N. Bogliotti, J. Xie, M. Buckle, A.I. El Abed, Fast active merging of microdroplets in microfluidic chambers driven by photo-isomerisation of azobenzene based surfactants, Biosensors 9 (4) (2019) 129.
[40] C.F. An, Y.J. Zhang, H.T. Li, H.Y. Zhang, Y.H. Zhang, J.M. Wang, Y. Zhang, F. Cheng, K. Sun, H.N. Wang, Thermo-responsive fluorinated surfactant for on-demand demulsification of microfluidic droplets, Lab Chip 21 (18) (2021) 3412-3419.