Continuous flow microreactors in nanoparticle synthesis | Syrris

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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


3-dimensional molecular nanosystems | PhysOrg

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Professor Julius Vancso, of the MESA+ Institute for Nanotechnology, works on the use of polymers in the targeted delivery of medication and in the acceleration of chemical reactions. Together with others in his group (Materials Science and Technology of Polymers), Prof. Vancso develops polymers with specific properties.

Prof. Julius Vancso’s group is working on polymers for use in a variety of nanotechnological applications. Prof. Vancso heads the Materials Science and Technology of Polymers research group at the MESA+ Institute for Nanotechnology.
Polymers are long-chain molecules made up of a number of smaller molecules, or monomers. The researchers are increasingly able to influence the structure of these molecules and to use them in combination with metal or semiconductor nanoparticles in complex structured systems.


Until recently, scientists were restricted to manipulating the surfaces of single molecules. “However, with current technology, we are increasingly able to manipulate and investigate structures in three dimensions” says Prof. Vancso.


The scientists manipulate these polymers and combine them with metal or semiconductor nanoparticles. As a result, these combinations of nanosystems acquire new properties. The researchers are able to build functional nanostructures, using macromolecular “glue” to combine semiconducting nanostructures and hold them in place.

Self-organizing nanostructures

In other projects, Prof. Vancso and his colleagues from MESA+, Prof. Huskens, Prof. Reinhoudt, and Prof. Subramaniam, control events at the molecular level using a combination of self-organizing nanostructures. The strong interdisciplinary collaboration found within MESA+ is a key factor in complex projects of this kind”, notes Prof. Vancso. Polymers and light-emitting semiconducting nanocrystals are used to construct functional structures, layer by layer. These molecular nanostructures can be used to target drug release within the body, or to locate tumours very precisely, for example. “However, the polymers can also be used in micro reactors, for example. There they combine with tiny metal particles to form brush-like structures, allowing the researchers to greatly accelerate the rate of chemical reactions” adds Prof. Vancso.

Fluorescent structures

Prof. Vancso and various colleagues from MESA+ and Singapore recently published an article in the renowned scientific journal Small, on the use of fluorescent nanocrystals. In this study, special fluorescent nanocrystals were added to the polymers. When exposed to UV radiation, these semiconductor particles emit light. You can then change the colour of that light by adding other molecules. “Here, the polymers are used as biomarkers. Biomarkers can be used to make highly specific observations of molecules, or to locate tumours more effectively. This is because the biomarkers bind to tumour cells and emit light. Doctors can use this technique to locate tumours more accurately,” explains Prof. Vancso.

Programmable microreactor – the “H”-microreactor

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The main unit of our system, the Chemical Microprocessor – ChµP is an electronically programmable microfluidic chip equipped with microelectrodes, fluidic channels and chambers, linked to a reconfigurable electronic chip. The microelectrodes are the actuator components for the “H”-shaped reaction-chamber (see also the right microscopic image) described here. Furthermore, the ChµP contains a standard field-programmable-gate-array (FPGA, Spartan2 Xilinx) to control a maximum number of electrodes individually. With this intimate control of biochemical processes a precondition for “live control” comes within reach, that the seamless integration of computer technology and biology occur in both directions simultaneously. This involves both the real time detection and data analysis of the biomolecular system and the active control of biomolecules in a hybrid system.

The schematic view illustrates an electronic-regulated chamber for an artificial cell connected to chemical supply and drain with two IO channels of 1.1 µm in height and regulated by two gold electrodes placed below each I/O. The reaction chamber, micro-moulded (SU-8 master) in PDMS with a size of 34.8 by 60 µm diameter, is effectively decoupled from the hydrodynamic flow of the supply and drain channels, while the programmable electrodes enable adjustable bulk electroosmotic flow (EOF) and electrophoresis.[1] The entire structure forms a basis of a system of programmable microfluidic networks used for electronic programming of Chemistry.







microscopic view of two “H”-reaction chambers