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Continuous flow microreactors in nanoparticle synthesis

Continuous Flow

While the pharmaceutical industry has been the primary driver of flow chemistry growth since its inception in the early 2000s, other chemical-related industries are now showing interest in this modern lab technique. Organic synthesis has been the main priority of all studies carried out on flow chemistry equipment, and the benefits and reasons to perform flow chemistry are now well known and recorded. It is worth noting that these advantages can also be extended to other fields such as biofuels, petrochemistry, and nanoparticle synthesis.

After its launch in 2012, Syrris has seen a demand increase for its Syrris Asia Flow Chemistry System from companies and universities specialising in nanoparticle synthesis. Furthermore, the continuous formation of nanoparticles, quantum dots, and colloidal metals has been the subject of a growing number of publications.

Because of their physical and chemical properties, nanoparticles are now used in a wide range of industries, posing an increasing need for chemists to have a reliable supply of huge quantities of good quality nanoparticles.

Several chemical processes have been used to make batches of nanoparticles, but each has its own set of issues, including non-homogeneity in mixing, the importance of ageing, the difficulties of maintaining precise temperature control and dubious batch to batch reproducibility. A batch process always depends on the chemist’s expertise as much as the chemistry itself.

When scaling up the production, all of these problems become even more complex to resolve. Flow chemistry provides many benefits which help to overcome these difficulties, quick and reproducible mixing, excellent control of temperature, the ability to perform pressurised reactions, modularity and simple scale-up.

Precise reaction control in nanoparticle synthesis

One of the key attributes of a flow chemistry system, which impacts both the mixing quality and temperature control in microreactors,  is the tiny diameter of its internal wet channels, usually between 0.3-1 mm 0.3-1 mm.

Reynolds number (Re) defines the conditions of the flow in a system 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, whereas, for a high Reynolds number, the conditions are turbulent. In a continuous flow chemistry system, the dimension of the channel results in the Reynolds number always being small (usually <100), consequently flow conditions are always laminar.

Microreactor size (µL)

Total flow rate (µL/min)

Estimated mixing volume (µL)

Estimated mixing time (secs)

Residence time (mins)


























































Mixing is diffusion-limited and extremely fast under laminar flow conditions. The mixing time in a Syrris microreactor, the mixing is normally between 1 and 5 seconds. It is also very reproducible because the microreactor’s shape remains the same and there is no physical stirrer involved.

If specially designed microreactors (micromixer chips) are used, it is possible to decrease the mixing time even more, to below 1 second, making the micromixer chip a reactor of choice for nanoparticle synthesis protocols, where mixing is a vital parameter.

The microreactor channel’s small diameter also ensures that their surface-to-volume ratio is extremely high, resulting in excellent heat transfer and also fast, accurate temperature control and response. Unlike in a batch reactor, there is no temperature gradient and every exotherm or endotherm is easily absorbed, ensuring that the temperature remains constant in the microreactor.

In a paper outlining a method for continuous quantum dot synthesis in a glass microreactor, Prof. Seeberger and co-workers at the Max Planck Institute of Colloids & Interfaces emphasised the importance of precise control over experimental conditions. The quantum dots synthesized in continuous flow by Seeberger’s group have a much narrower particle distribution than those produced 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

Recently, chemists from the Syrris laboratory developed a continuous synthesis protocol for the synthesis of iron nanoparticles, where the particle size is paramount to determine its paramagnetic characteristics. The synthesis was performed in microreactors, which allowed for ultra-fast mixing and, as a result, the formation of fine magnetic iron nanoparticles with better quality and reproducibility than in batch synthesis.

Process flexibility in continuous flow

Another benefit of using a continuous flow chemistry 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.

For nanoparticle synthesis, a flow chemistry system consisting of a syringe pump, a microreactor, and a pressure controller is a good place to start, as the user would be able to run a series of tests to determine the right reaction conditions. Once the optimized reaction conditions have been established, the same set-up is used to synthesise multi-gram quantities of nanoparticles continuously in suspension.

It is possible to extend the system’s capabilities by incorporating an autosampler and automating the system with software, making it suitable for process optimisation and the analysis of reaction parameters. A number of experiments can quickly be set up, performed automatically and all samples collected separately for analysis. This type of set-up was used by Fitzner and co-workers to investigate the influence of reaction temperature on the particle size distribution of colloidal gold.

The use of a back pressure regulator ensures flow chemistry systems can be pressurised quickly and safely, enabling solvents to be heated past their boiling point, a process known as ‘superheating’, which improves reaction kinetics and allows for ultra-fast reaction conditions. Furthermore, pressurising the system avoids any degassing that may occur when a reaction creates gas as a by-product.

Finally, microreactors and flow chemistry are perfect for multi-step processes, also known as ‘telescoping synthesis’. A two-step reaction can be set up by simply joining the output of the first reactor to the input of a second. In their quantum dot process, Seeberger’s team took advantage of this flow chemistry feature. In one microreactor, cadmium-selenium nanoparticles were formed,  then zinc sulphide was applied to the nanoparticles in a second microreactor connected in series. This two-step reaction was carried out as one continuous process, saving time and effort.


Flow chemistry has proven to be an effective technology for optimising nanoparticle reactions and their large-scale synthesis. Excellent reaction control, flexibility and easy scale-up are just a few of the benefits of flow chemistry that can help the nanoparticle industry. These advantages are so significant that continuous-flow is likely to soon become the method of choice for nanoparticle synthesis.

Watch the experiment in the video below:

Want to know more?

If you would like to get more familiar with flow chemistry before going in too deep, be sure to read our blog post about Flow Chemistry Basics & Key Elements. For more information on Flow Chemistry and how it could improve your processes, contact our Sales Team today.

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