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Johnson Matthey Technol. Rev., 2019, 63, (3), 150

doi:10.1595/205651319x15472048744147

实验室:用于分子合成和材料合成的多相连续流动反应器

Johnson Matthey Technology Review刊登了新的实验室研究专题特写

新加坡国立大学 (NUS) 化学和生物分子工程系副教授 Saif A. Khan 是一名专业的化学工程师,研究范围包括化学反应工程、微流体、微尺度和中尺度流反应器及其在化学和材料学领域的应用。他在 NUS 的研究团队与英国葛兰素史克、美国辉瑞、英国庄信万丰等全球多家工业合作伙伴联合开发了一种可连续制造药品和先进材料的全新微流体“工厂”。Saif A. Khan 还是两家初创公司的联合创始人,这两家公司分别以先进材料制造和眼部给药为核心。他还担任了英国皇家化学学会期刊《Reaction Chemistry and Engineering》的科技编辑以及美国物理学会期刊《生物微流体》的编委会成员。

In the Lab: Multiphase Continuous Flow Reactors for the Synthesis of Molecules and Materials

Johnson Matthey Technology Review features new laboratory research

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Saif A. Khan is an Associate Professor in the Department of Chemical and Biomolecular Engineering at the National University of Singapore (NUS). He is a chemical engineer by training and his research spans the areas of chemical reaction engineering, microfluidics, micro- and mesoscale flow reactors and their applications in chemistry and materials science. His research group at NUS develops new microfluidics-based ‘factories’ for the continuous manufacture of pharmaceuticals and advanced materials in collaboration with several industrial partners worldwide, including GlaxoSmithKline (GSK), UK; Pfizer, USA and Johnson Matthey, UK. He has also co-founded two start-up companies focused on advanced materials manufacture and ophthalmic drug delivery respectively. He serves as a Scientific Editor for the Royal Society of Chemistry (RSC) journal Reaction Chemistry and Engineering and on the Editorial Board of the American Institute of Physics (AIP) journal Biomicrofluidics.

About the Research

Multiphase reactions, which involve reactants in more than one fluid phase (often accompanied by a homogeneous or heterogeneous catalyst), are ubiquitous in the petrochemical, fine chemical and pharmaceutical industries. Reactions such as hydrogenation and oxidation are mainstays in the manufacture of valuable molecules or intermediates. There is also an increasing interest in multiphase reactions promoted by visible light photocatalysis. These reactions typically involve a strong interplay between physical transport processes, such as the transfer of molecules across fluid phases or heat dissipation and intrinsic chemical rate processes. As a result, the rates of industrial processes are often limited by heat and mass transport, especially in batch reactors used in the fine chemical and pharmaceutical industries. Aggressive process conditions (such as high temperatures and pressures) are typically required to achieve viable productivity.

About the Researcher

  • Name: Saif A. Khan

  • Position: Associate Professor of Chemical and Biomolecular Engineering

  • Department: Department of Chemical and Biomolecular Engineering

  • University: National University of Singapore

  • Street: 4 Engineering Drive 4, E5 #02-09

  • City: Singapore

  • Post Code: 117585

  • Email: saifkhan@nus.edu.sg

Milli- or mesoscale multiphase flow reactors, in which the characteristic transverse dimension of the reactor is in the 1–5 mm range (with lengths ranging from 0.1 m to >10 m), offer an exciting alternative to these challenges, especially for industries that produce low-volume and high-value materials. Such reactors offer the benefits of highly controlled multiphase flow patterns and tremendously intensified transport processes, while also allowing production of valuable molecules and materials at the kilograms per day scale with a desktop footprint.

Researchers at Khan Lab are actively engaged in the design and prototyping of multiphase continuous flow reactors and processes for the synthesis of molecules and materials ranging from catalytic nanoparticles to molecular drug crystals. For example, triphasic segmented flow reactors have been developed for highly intensified hydrogenations under ambient conditions with the use of a colloidal metal catalyst (1). A proof of concept eight-fold parallelised system with complete catalyst recovery and recycle has also been demonstrated (2). This reactor concept has been recently deployed for the robust, non-fouling synthesis of catalytically active palladium nanoparticles at the 10 l day–1 scale, in a collaborative project with Johnson Matthey (see Figure 1) (3). This reaction is particularly challenging to control in a conventional flow reactor, given the aggressive reagent (sodium borohydride) used to reduce the aqueous palladium precursor solution; uncontrolled evolution of hydrogen gas typically leads to severe reactor fouling. The highly intensified mass transport in the triphasic flow reactor allows the rapid mixing of reagents and removal of evolved hydrogen gas into co-flowing nitrogen ‘sink’ bubbles, thereby preventing outgassing and fouling.

Fig. 1.

Schematic of a triphasic segmented flow reactor for the continuous synthesis of catalytically active palladium nanoparticles at the ~10 l day–1 scale – Adapted from (3) by permission of The Royal Society of Chemistry

Schematic of a triphasic segmented flow reactor for the continuous synthesis of catalytically active palladium nanoparticles at the ~10 l day–1 scale – Adapted from (3) by permission of The Royal Society of Chemistry

In addition to flow chemistry, methods for the controlled continuous production of microscale solid particles, such as drug products or intermediates, are also a strong focus of research interest at Khan Lab; recent demonstrations in this area include a continuous emulsions to particles process for the production of spherical crystalline drug materials or composites, in collaboration with GSK (4, 5).

Other ongoing projects at Khan Lab include: (a) the development of small-scale reactor systems that allow effective deconvolution of physical and chemical rate processes, thereby enabling the measurement of kinetic data for intrinsically fast multiphase reactions; (b) the design of novel photocatalytic flow reactors that intensify photon flux in light-limited scenarios; and (c) the combination of high throughput microfluidic materials synthesis and machine learning methods to map and learn patterns in complex, non-equilibrium materials synthesis spaces.

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References

  1. 1.
    S. K. Yap, Y. Yuan, L. Zheng, W. K. Wong, J. Zhang, N. Yan and S. A. Khan, Green Chem., 2014, 16, (11), 4654 LINK https://doi.org/10.1039/c4gc01504e
  2. 2.
    S. K. Yap, W. K. Wong, Y. N. X. Ng and S. A. Khan, Chem. Eng. Sci., 2017, 169, 117 LINK https://doi.org/10.1016/j.ces.2016.12.005
  3. 3.
    W. K. Wong, S. K. Yap, Y. C. Lim, S. A. Khan, F. Pelletier and E. C. Corbos, React. Chem. Eng., 2017, 2, (5), 636 LINK https://doi.org/10.1039/c7re00072c
  4. 4.
    Q. E. W. Yeap, L. D. Z. Ng, D. Lai, S. Sharpe, D. Ertl and S. A. Khan, Cryst. Growth Des., 2018, 18, (10), 5727 LINK https://doi.org/10.1021/acs.cgd.8b00728
  5. 5.
    E. W. Q. Yeap, D. Z. L. Ng, D. Lai, D. J. Ertl, S. Sharpe and S. A. Khan, Org. Process Res. Dev., 2019, 23, (1), 93 LINK https://doi.org/10.1021/acs.oprd.8b00314

Acknowledgements

Professor Khan acknowledges the members of his group for all their energy and creativity in envisioning the future of chemical processes. Our work has also benefited greatly from active engagement and input of industry collaborators from GSK, UK; Pfizer, USA and Johnson Matthey, UK.

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