Article Reference
M. Drobot, Speciality Chemicals Magazine, 2012, 32 (5)

Speciality Chemicals Continuous flow microreactors
in nanoparticle synthesis article

Speciality Chemicals Article “Continuous flow microreactors in nanoparticle synthesis”


Although the pharmaceuticals industry has been the main driving force behind the rise of flow chemistry since early 2000, other chemicals-related industries have now taken an interest in this new laboratory technique. For years, organic synthesis has been the main focus of all research work conducted on flow chemistry equipment and the advantages offered by flow chemistry are now well established and documented.1-3 Other fields– such as biofuels, petrochemistry and nanoparticles – can also benefit from these same advantages.

Syrris has seen growing demand for Asia, its latest flow system (pictured below), from companies and universities specialising in nanoparticle synthesis. In addition, there has been an increasing number of publications on the subject of continuous formation of nanoparticles, quantum dots and colloidal metals.

Automated Asia Flow Chemistry System

Nowadays, nanoparticles are used in a wide range of fields because of their physical and chemical properties, resulting in a growing demand that challenges chemists to provide a reliable supply of large amounts of good quality nanoparticles.

Various chemical methods have been applied to produce nanoparticles in batch, but these all present problems: non-homogeneity in mixing, the importance of ageing, the difficulty of accurate temperature control and questionable reproducibility from batch to batch. Often a batch process relies as much on the skill of the chemist as on the chemistry itself.

All of these issues become even more difficult to address when scaling up the manufacturing. Flow chemistry offers a number of advantages that help to overcome these challenges, notably fast and reproducible mixing, excellent temperature control, the ability to carry out pressurised reactions, modularity and easy scale-up.


Accurate reaction control

One of the key characteristics of a flow chemistry system is the very small diameter of its internal wetted channels, which are typically in the range of 0.3-1 mm. This has a huge impact on both the quality of mixing and temperature control in microreactors.

The flow conditions in a system are defined by the Reynolds number (Re), i.e. the mean viscosity of fluid multiplied by characteristic dimension and divided by kinematic viscosity. For a low Reynolds number (below 4,000), flow conditions are laminar; for a high Reynolds number, they are turbulent. In a flow system, the channel dimension results in the Reynolds number always being small (usually <100), therefore flow conditions are always laminar.

Microreactor size (µl) Total flow rate (µl/min) Estimated mixing volume (µl) Estimated mixing time (secs) Residence time (mins)
1 62.5 60 3.3 3.30 1.04
2 62.5 240 6.6 1.65 0.26
3 250 240 12.6 3.15 1.04
4 250 1000 5.6 0.34 0.25
5 250 5000 5.6 0.07 0.05
6 1000 240 19.8 4.95 4.17
7 1000 1000 19.8 1.19 1.00
8 1000 5000 19.8 0.24 0.20

Table. 1 – Phenolphthalein & sodium hydroxide mixing tests


Under laminar flow conditions, mixing is diffusion-limited and extremely fast. Typically, in a Syrris microreactor the mixing is in the order of 1-5 seconds (Table 1). It is also very reproducible, as the shape of the microreactor does not change and no physical stirrer is involved.

Syrris Micromixer

Syrris Micromixer

The mixing time can be reduced even further to below one second, by using specially designed microreactors called micromixer chips (pictured right). This makes the micromixer chip a reactor of choice for nanoparticle synthesis protocols, where mixing is a critical parameter.

The small diameter of the microreactor channels also means that its surface-to-volume ratio is extremely high. This results in excellent heat transfer and fast, efficient temperature control and response. Not only is there no temperature gradient – as seen in a batch reactor – but any exotherm or endotherm is very quickly absorbed, maintaining a homogeneous temperature throughout the microreactor.

Prof. Seeberger and co-workers at the Max Planck Institute of Colloids & Interfaces noted the key role played by precise control over experimental conditions in a paper describing a process for continuous quantum dot synthesis in a glass microreactor.4 The quantum dots synthesised in flow by Seeberger’s group have a much narrower particle distribution than those obtained using a similar batch protocol. This trend has also been shown by Fitzner and co-workers for the preparation of colloidal gold in a flow microreactor.5

More recently, a continuous synthesis protocol for the synthesis of iron nanoparticles has been developed in Syrris’s laboratory. Here, the size of the particle is critical, as it determines its paramagnetic characteristics. Performing the synthesis in microreactors allowed ultra-fast mixing and, subsequently, the formation of fine magnetic iron nanoparticles with better quality and reproducibility than in batch synthesis.6


Process flexibility

Other advantages of using a flow system for making nanoparticles include easy scalability, the modularity of the system and the ability to carry out high pressure reactions and multi-step processes.

A flow chemistry system consisting of a pump, a microreactor and a pressure controller is a good starting point for nanoparticle synthesis. This system will allow the user to run a series of experiments to determine the best reaction conditions. Once the optimised reaction conditions have been established, the same set-up is used to synthesise multi-gram quantities of nanoparticles continuously in suspension.

By adding an autosampler and automating the system via software, the system’s capabilities are expanded and it becomes ideal for process optimisation and the study of reaction parameters. A series of experiments can quickly be set up, run automatically and all the samples collected separately for analysis. Fitzner and co-workers used this kind of set-up to study the effect of reaction temperature on the particle size distribution of colloidal gold.5

Flow chemistry systems are also very easily and safely pressurised using a back pressure regulator. This allows solvents to be heated above their boiling point, which is commonly called ‘superheating’, thus increasing the reaction kinetics and creating ultra-fast reaction conditions. On top of this, pressurising the system minimises any degassing effect that might occur when a reaction produces gas as a by-product.

Finally, microreactors and flow chemistry are ideal for multi-step processes, commonly called ‘telescoping synthesis’. By simply connecting the output of the first reactor to the input of a second, a two-step reaction can be set up. Seeberger’s group used this flow chemistry benefit in their quantum dot process. First, cadmium-selenium nanoparticles were formed in a microreactor, then the nanoparticles were covered with zinc sulphide in a second microreactor connected in series. This two-step reaction was run as one continuous process, therefore saving time and manual effort.4



Flow chemistry is as an effective technology for the optimisation of nanoparticle reactions and their large-scale synthesis. Among the key advantages of flow chemistry which can assist the nanoparticle industry are excellent reaction control, flexibility and easy scale-up. These benefits are of such importance that, in the near future, continuous-flow is likely to become the method of choice for nanoparticle synthesis.



  1. M. Drobot, Speciality Chemicals Magazine 2011, 31(6)
  2. C. Wiles & P. Watts, Green Chemistry 2012, 14, 38-54
  3. L. Malet-Sanz & F. Susanne, J. Med. Chem., forthcoming
  4. P. Laurino, R. Kikkeri & P.H. Seeberger, Nature 2011, 6, 1209-1220
  5. M. Wojnicki, K. Paclawski, M. Lutyblocho, K. Fitzner, P. Oakley & A. Stretton, Rudy I Metale Niezelane 2009, 12
  6. – a video of the experiment