Microbubbles as Heterogeneous Nucleation Sites for Crystallization in Continuous Microfluidic Devices
- Naghmeh FatemiNaghmeh FatemiKU Leuven, Department of Chemical Engineering, 3001 Leuven, BelgiumMore by Naghmeh Fatemi
- ,
- Zhengya Dong
- ,
- Tom Van GervenTom Van GervenKU Leuven, Department of Chemical Engineering, 3001 Leuven, BelgiumMore by Tom Van Gerven
- , and
- Simon Kuhn*Simon Kuhn*Simon Kuhn. E-mail: [email protected]KU Leuven, Department of Chemical Engineering, 3001 Leuven, BelgiumMore by Simon Kuhn
Abstract

Injecting a stream of microbubbles and thereby introducing a heterogeneous interface is proposed for enhancing nucleation and controlling particle formation in continuous microfluidic devices. Different gas and liquid flow rates were investigated to establish the two-phase flow regime map and to identify the optimum characteristics for microbubble flow. Subsequently, the effect of microbubbles was studied for the cooling crystallization of paracetamol. An enhanced nucleation rate compared to that in the operation without bubbles was observed and the presence of microbubbles results in the formation of more crystals, which indicates that nucleation is faster than that in operation without bubbles, i.e., the metastable zone width is reduced. Determining the crystal yield confirmed that a larger mass of crystals is obtained in a two-phase flow with microbubbles. Furthermore, results showed that the presence of microbubbles allows crystallizing continuously without clogging of the microreactor.
Cited By
This article is cited by 29 publications.
- Cedric Devos, Elena Brozzi, Tom Van Gerven, Simon Kuhn. Characterization of a Modular Microfluidic Section for Seeded Nucleation in Multiphase Flow. Organic Process Research & Development 2023, 27
(2)
, 311-321. https://doi.org/10.1021/acs.oprd.2c00341
- Astrid I. Seifert, Justin Simons, Jan Gutsch, Kerstin Wohlgemuth. Inert Gassing Crystallization for Improved Product Separation of Oleo-Chemicals toward an Efficient Circular Economy. Organic Process Research & Development 2023, 27
(1)
, 136-147. https://doi.org/10.1021/acs.oprd.2c00312
- Symeon V. Savvopoulos, Spyros S. Voutetakis, Simon Kuhn, Dimitris Ipsakis. Theoretical Feedback Control Scheme for the Ultrasound-Assisted Continuous Antisolvent Crystallization of Aspirin in a Tubular Crystallizer. Industrial & Engineering Chemistry Research 2021, 60
(17)
, 6221-6234. https://doi.org/10.1021/acs.iecr.1c00227
- Cedric Devos, Tom Van Gerven, Simon Kuhn. A Review of Experimental Methods for Nucleation Rate Determination in Large-Volume Batch and Microfluidic Crystallization. Crystal Growth & Design 2021, 21
(4)
, 2541-2565. https://doi.org/10.1021/acs.cgd.0c01606
- Symeon V. Savvopoulos, Mohammed N. Hussain, Tom Van Gerven, Simon Kuhn. Theoretical Study of the Scalability of a Sonicated Continuous Crystallizer for the Production of Aspirin. Industrial & Engineering Chemistry Research 2020, 59
(45)
, 19952-19963. https://doi.org/10.1021/acs.iecr.0c03975
- Symeon
V. Savvopoulos, Mohammed N. Hussain, Jeroen Jordens, Steffen Waldherr, Tom Van Gerven, Simon Kuhn. A Mathematical Model of the Ultrasound-Assisted Continuous Tubular Crystallization of Aspirin. Crystal Growth & Design 2019, 19
(9)
, 5111-5122. https://doi.org/10.1021/acs.cgd.9b00466
- Angel Chyi En We, Arash Zamyadi, Anthony D. Stickland, Bradley O. Clarke, Stefano Freguia. A review of foam fractionation for the removal of per- and polyfluoroalkyl substances (PFAS) from aqueous matrices. Journal of Hazardous Materials 2024, 465 , 133182. https://doi.org/10.1016/j.jhazmat.2023.133182
- Chuanxiao Cheng, Zheng Wang, Yanqiu Xiao, Tianyi Song, Tingxiang Jin, Jiasong Shi, Jianxiu Liu, Shiquan Zhu, Tian Qi, Wenfeng Hu, Jun Zhang, Jie Ma, Yuexin Han, Yaoli Ma, Lunxiang Zhang. Synergistic effect of ultrasound combined with bubble enhanced rapid nucleation and growth of methane hydrate. Fuel 2024, 360 , 130483. https://doi.org/10.1016/j.fuel.2023.130483
- Lan Liao, Yao-Mian Chen, Jin-Peng Yang, Murtaza Ali, Xin-Xin Pang, Rong-Zeng Pan, Ze-Ling Huang, Xin-An Zeng. Application of hydrogen-assisted freezing technology: Promises and challenges. Trends in Food Science & Technology 2023, 142 , 104223. https://doi.org/10.1016/j.tifs.2023.104223
- Wenqing Tian, Oladayo Ogunyinka, Charlie Oretti, H. C. Hemaka Bandulasena, Chris Rielly, Huaiyu Yang. Protein crystallisation with gas microbubbles as soft template in a microfluidic device. Molecular Systems Design & Engineering 2023, 8
(10)
, 1275-1285. https://doi.org/10.1039/D3ME00058C
- Da-Yeon Kang, Jin-Hyun Kim. Elucidation of the Role of Gas Bubbles in the Fractional Precipitation of Paclitaxel. Biotechnology and Bioprocess Engineering 2023, 28
(5)
, 853-861. https://doi.org/10.1007/s12257-023-0115-3
- Hyunji Oh, Jin-Hyun Kim. Effect of Gas Bubble Characteristics on Fractional Precipitation of (+)-dihydromyricetin. KSBB Journal 2023, 38
(3)
, 169-176. https://doi.org/10.7841/ksbbj.2023.38.3.169
- Rohit Chauhan, Nitin Minocha, Paria Coliaie, Priyanka G. Singh, Akshay Korde, Manish S. Kelkar, Marianne Langston, Chengxiang Liu, Neda Nazemifard, Daniel Patience, Dimitri Skliar, Nandkishor K. Nere, Meenesh R. Singh. Emerging microfluidic platforms for crystallization process development. Chemical Engineering Research and Design 2023, 197 , 908-930. https://doi.org/10.1016/j.cherd.2023.08.021
- Junhong Pang, Jiaxing He, Ziqi Deng, Wenbin Chen, Shunli Chen, Shaofei Ni, David Lee Phillips, Zhengya Dong, Li Dang, Ming‐De Li. Boosting Ultrafast
Trans‐Cis
Photoisomerization and Intersystem Crossing in Nanocrystals of Double‐Bond Photoswitching Molecules. Advanced Optical Materials 2023, 11
(16)
https://doi.org/10.1002/adom.202300028
- Neelesh Nandan, Jose V. Parambil. Cooling Crystallization of Paracetamol in a Slug-Flow Crystallizer with Silicone Oil as Continuous Phase. Crystals 2023, 13
(7)
, 1094. https://doi.org/10.3390/cryst13071094
- Isaac D. Tegladza, Guihong Lin, Chang Liu, Xuehong Gu. Control of crystal nucleation, size and morphology using micro−/nanobubbles as green additives – a review. Separation and Purification Technology 2023, 311 , 123232. https://doi.org/10.1016/j.seppur.2023.123232
- Zhiyong Jing, Yaxin Lin, Chuanxiao Cheng, Xiaonan Li, Jianxiu Liu, Tingxiang Jin, Wenfeng Hu, Yaoli Ma, Jiayi Zhao, Shijie Wang. Fast Formation of Hydrate Induced by Micro-Nano Bubbles: A Review of Current Status. Processes 2023, 11
(4)
, 1019. https://doi.org/10.3390/pr11041019
- Mohamed E.A. Ali, Rayan Alghanayem, Aislinn Varela, Marion Bellier, François Perreault. Scaling mitigation in direct contact membrane distillation using air microbubbles. Desalination 2023, 549 , 116348. https://doi.org/10.1016/j.desal.2022.116348
- Christian Holtze, Ralf Boehling. Batch or flow chemistry? – a current industrial opinion on process selection. Current Opinion in Chemical Engineering 2022, 36 , 100798. https://doi.org/10.1016/j.coche.2022.100798
- Fan Wang, Xinran Xia, Yuan Lv, Chuanxiao Cheng, Lei Yang, Lunxiang Zhang, Jiafei Zhao, Yongchen Song. Experimental study on the thermodynamic performance of a novel tetrabutylammonium bromide hydrate cold storage system. Journal of Energy Storage 2022, 48 , 103980. https://doi.org/10.1016/j.est.2022.103980
- Kentaro Atsukawa, Shuntaro Amari, Hiroshi Takiyama. Effect of aeration operation on crystallization induction time of melt with the difficulty of nucleation. Journal of Industrial and Engineering Chemistry 2022, 106 , 69-73. https://doi.org/10.1016/j.jiec.2021.10.023
- Naghmeh Fatemi, Cedric Devos, Tom Van Gerven, Simon Kuhn. Continuous crystallization of paracetamol exploiting gas–liquid flow in modular nucleation and growth stages. Chemical Engineering Science 2022, 248 , 117095. https://doi.org/10.1016/j.ces.2021.117095
- Mriganka Mondal, Sandip Roy, Mamata Mukhopadhyay. Process intensification of cooling crystallization of cholesterol from acetone solution using CO2 gas bubbles: Experiments and modeling. Chemical Engineering and Processing - Process Intensification 2022, 172 , 108794. https://doi.org/10.1016/j.cep.2022.108794
- Lixia Shen, Mingyan Dang. Recent advances in melt crystallization, towards process intensification and technique development. CrystEngComm 2022, 4 https://doi.org/10.1039/D2CE00022A
- William B. Zimmerman. Towards a microbubble condenser: Dispersed microbubble mediation of additional heat transfer in aqueous solutions due to phase change dynamics in airlift vessels. Chemical Engineering Science 2021, 238 , 116618. https://doi.org/10.1016/j.ces.2021.116618
- Chuanxiao Cheng, Fan Wang, Tian Qi, Peiyuan Xu, Quanguo Zhang, Zhiping Zhang, Chao He, Jun Zhang, Jili Zheng, Jiafei Zhao, Hanquan Zhang, Bo Xiao. Depressurization-induced changes in memory effect of hydrate reformation correlated with sediment morphology. Energy 2021, 217 , 119374. https://doi.org/10.1016/j.energy.2020.119374
- Alexandra Cantarano, Denis Testemale, Sonia de Sousa Nobre, Audrey Potdevin, Rémy Bruyère, Aude Barbara, Jean-Louis Hazemann, Alain Ibanez, Géraldine Dantelle. Twofold advantage of gas bubbling for the advanced solvothermal preparation of efficient YAG:Ce nanophosphors. Journal of Materials Chemistry C 2020, 8
(27)
, 9382-9390. https://doi.org/10.1039/D0TC02347G
- Masakazu Matsumoto, Yoshinari Wada, Ryo Otsu, Naoki Kobayashi, Masaki Okada. Controlling nucleation and crystal growth during reactive crystallization of monosodium urate monohydrate from simulated synovial fluid by N2 fine bubble injection. Journal of Crystal Growth 2020, 539 , 125622. https://doi.org/10.1016/j.jcrysgro.2020.125622
- Naghmeh Fatemi, Cedric Devos, Glenn De Cordt, Tom Van Gerven, Simon Kuhn. Effect of Sodium Dodecyl Sulfate on the Continuous Crystallization in Microfluidic Devices Using Microbubbles. Chemical Engineering & Technology 2019, 42
(10)
, 2105-2112. https://doi.org/10.1002/ceat.201900172