FDmiX. Mixing rethought.

Whether coffee with milk or tea with sugar: we are faced with the mixing of substances on an everyday basis. It is always a matter of mixing two or more substances with each other through the use of motion. The goal is always to achieve a mixture that is as homogeneous as possible. This is easy to achieve with coffee and milk. With a salad dressing made from vinegar and oil, on the other hand, the two ingredients are immiscible, so it takes only a short time for the mixture to separate. What is certainly tolerable with a salad dressing can have a lasting effect on the efficacy of a drug.
A lot therefore depends on the mixing quality and speed when it comes to process engineering. Numerous processes have therefore been established in process engineering to achieve sufficient mixing quality in the shortest possible time. Depending on the application, scaling up the process from low to higher throughputs in particular represents a major challenge.
One example is the production of nanoparticles, such as those used in mRNA vaccines. For these drugs, the active ingredient is encapsulated in a kind of protective shell so that the active ingredient is released at the right place. For this purpose, the active ingredient is dissolved in a liquid (buffer solution) and mixed with another solution (e.g. lipid or polymer solutions). Once these two liquids are mixed, nanoparticles are formed that encapsulate the active ingredient. The faster and more homogeneous this mixture is, the higher the quality of the particles.

For laboratory use, so-called microfluidics can be used, which produce very good and fast mixing, but only allow a very low throughput. For industrial scale, on the other hand, there are so-called impinging mixers (also called T-mixers or Y-mixers), which allow a high throughput, but at the cost and expense of the mixing quality. This shows the fundamental problem with the upscaling of laboratory processes to series production. The situation is very similar with so-called nanoemulsions, in which a stable emulsion of otherwise immiscible substances such as water and oil is produced.
We were able to bridge the gap between mixing quality and throughput together with the Institute for Production Technology of the Fraunhofer Society based on our OsciJet technology. The resulting FDmiX platform allows consistent mixing quality and speed from laboratory use to series production and has already been successfully tested for the production of lipid and polymer nanoparticles, as well as nanoemulsion. It has been shown that the mixing quality is superior to many conventional systems. The mixers are available in different size classes and are all characterized by high robustness, very short mixing times, minimal risk of clogging and wide process windows. This makes them suitable for a wide range of applications.

Experimental mixing visualization.

FDmiX mixing systems. Our products.


The system for fundamental research on LNP/polymer nanoparticles


For rapid formulation development of LNP/polymer nanoparticles

Curiosity Multi-Use

For rapid formulation development of LNP/polymer nanoparticles with different payloads

Application examples

The FDmiX platform can be used for a wide range of mixing applications, as the system is extremely robust, delivers short mixing times and nearly provides the same mixing quality over the entire flow range. Thus, the system can be used quite generally for so-called continuous flow chemistry, i.e. for chemical reactions (e.g. precipitation processes) that are not carried out in individual batch productions but in a continuously flowing stream. In addition, the FDmiX platform is suitable for the production of nanoemulsions, i.e. the generation of a stable mixture of otherwise immiscible substances, such as water and oil. Finally, the system can also be used to encapsulate mRNA and other substances in lipid- and polymer-based nanoparticles.

Continuous Flow Chemistry


The Corona pandemic created a breakthrough for vaccines based on mRNA (messenger ribonucleic acid) vaccines. In this novel method, the active ingredients are encapsulated in a protective coating so that they can be released undamaged at the target site and not broken down by the body on the way there. This method allows the targeted release of active ingredients and thus completely new therapies. The difficulty here lies not only in the production, but also in the encapsulation of the active ingredient. In order to further advance the development of mRNA-based drugs, the German Federal Ministry of Economics and Climate Protection (BMWK) has therefore launched a funding call (link) for research into encapsulation processes for mRNA drugs and vaccines.
Together with a highly specialized consortium, we submitted an application for encapsulation with chitosans and other excipients. Our project “Targeted and long-term release of active ingredients encapsulated in chitosan particles”, or Zielwirk for short, was approved at the beginning of 2023 and has the task of researching and optimizing the nanocapsulation of active ingredients with chitosan and other excipients over the next three years.
In addition to new chitosan developments from the world leader in pharmaceutical chitosans, Heppe Medical Chitosan GmbH, FDX is developing the mixing technology to quickly and efficiently form the chitosan nanoparticles loaded with the active ingredients. The companies are supported by Martin Luther University Halle and Fraunhofer IPK. The University of Halle’s Pharmaceutical Institute, headed by Prof. Mäder and specializing in drug delivery systems, is researching the efficacy, stability and toxicology of the formulations, while Fraunhofer IPK is contributing its know-how for the optimal alignment of the production technologies.

Learn more on the project page: zielwirk.de


At the heart of the FDmiX platform is an OsciJet nozzle, as shown schematically on the right. ❶ shows an OsciJet nozzle as we would perceive it with the naked eye.  Since the human eye is generally too slow, it seems that the visible spray pattern is apparently no different from that of a flat spray nozzle. However, this is only due to our perception capabilities. If you look at the process in time resolution, you will see that a jet inside the nozzle is positioned on one of the sides in the main chamber ❷. If you follow the jet through the main chamber, you can see that a small part of the jet is deflected into a side channel before leaving the nozzle. At the end of the side channel, this meets the main jet again and pushes it to the other side ❸. As a result, the main jet oscillates continuously from one side to the other. ❹ shows the beam pattern as it looks in time resolution. [more on how it works]

The figure on the left shows an FDmiX mixer/reactor. The mixer consists of a base plate into which an OsciJet nozzle and a mixing chamber are milled and a lid, which we have not shown here. The base and lid are bolted together via eight large holes to withstand even the highest pressures. To the left of the metal plate, the actual mixer is shown schematically.
One of the components to be mixed is introduced into the system at ① and then flows into the OsciJet nozzle. As it flows through the OsciJet nozzle, the component is caused to vibrate. The second component is introduced at ② perpendicular to the mixer and then meets the oscillating jet of the first component at ③. The high-frequency vibration now ensures that the first component interacts quasi abruptly with the second component and is then transported further into the mixing chamber. The mixture then leaves the outlet ④ further downstream of the mixing chamber.

FDmiX. Mixing Faster Than Lightning.

Nanotechnology has seen significant progress in the cosmetic and pharmaceutical industries in recent years. Not least, the pandemic has impressively demonstrated the effectiveness of drug delivery systems based on nanoparticles and sparked the discussion on mRNA-based drugs, revealing considerable potential. In addition to mRNA drugs, other nanosystems (nanoparticles, liposomes, nanoemulsions, nanocrystals, etc.) also show great potential in other fields. Skin creams based on nanoemulsions are also now widely used in the cosmetic field. In many cases, the rapid mixing of fluids is essential for these nanosystems. The quality of the mixing not only determines the quality of the products, but ultimately also their effectiveness. So-called microfluidics are often used for the production of small quantities. These are characterized by small structures in which capillary forces usually dominate. This is accompanied by the fact that in these very small structures, the frictional forces largely determine the inertial forces, which leads to laminar flows, i.e. flows without significant cross-exchange. The lack of cross-exchange makes mixing more difficult. The advantage of this method is that the processes can be controlled very well. The disadvantage is that a mixing process established in this way cannot simply be transferred to a larger scale. Thus, impinging mixers, also known as T- or Y-pieces, in which the mixing mechanism is not primarily based on diffusion, are often used in series production. For substances that do not interact, this can sometimes be neglected, but as soon as chemical processes play a role, the mixing mechanism and the associated time scales are essential for the resulting properties. This highlights the challenges of upscaling in nanosystems production.

These can be circumvented if, in principle, the same mixing mechanism is used for mixing two fluids. As described above, the mixing of the FDmiX platform is based on a scalable principle. The oscillating flow of one substance through the OsciJet meets the flow of the second substance perpendicularly and thus produces a good mixture very quickly. The mixing times here are in the millisecond range and are thus faster than lightning. Since the OsciJet nozzles can be scaled up without any problems, this also makes it easy to scale up a laboratory process. In internal tests, we were thus able to demonstrate that, particularly in lipid nanocapsulation, i.e. the encapsulation of an active ingredient with a lipid shell, the resulting particles are significantly smaller and more homogeneous, and the particle size can even be adjusted. The FDmiX platform is particularly well suited for the production of nanoparticles and -emulsions, in precipitation processes and many other mixing processes.

The videos below show mixing experiments that we performed using the transmitted light method. In the impinging mixer, shown in the video on the left, that the two phases collide and then flow down vertically parallel to each other and concentration differences can be seen quite clearly. The FDmiX mixer on the right, on the other hand, shows a much more homogeneous image.

FDmiX. Specifications.

In pursuit of development, we have designed and tested mixers for different pressure and flow rates. Our mixers are suitable for mixing processes from a few milliliters up to several liters per minute.

As an example, we present a set of results. In general, the FDmiX mixers have shown in the tests that they can produce excellent nanoparticles over a wide range of flow rates and are able to produce

  • smaller particles (~10-20% smaller than impinging mixers),
  • lower scattering (PDI <0.1 as measured with a Zetasizer), and
  • provide high encapsulation efficiency and particle integrity.

You can find a study “Optimizing GMP Manufacturing of Lipid Nanoparticles” employing the FDmiX platform at Lonza’s website.


Geometries for mixing processes from < 1 ml/min up to > 5000 ml/min


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FDmiX. From Lab to Fab.


Customers. Our References.

With the FDmiX system, we offer our customers an attractive technology for cGMP encapsulation of mRNA products. Our results with this technology – also when encapsulating other nucleic acids – show clear advantages for a predictable scale-up of our processes. In addition, quality attributes that are important for stability are favorably influenced. (Torsten Schmidt, Head of BU mRNA, Lonza AG)
In pilot tests conducted by RCPE’s Nanomanufacturing Research Group, the FDmiX technology platform provided promising results for the fabrication of PLGA nanoparticles through simple process control.
(Univ.-Prof. Mag. pharm. Dr. rer. nat. Eva Roblegg)

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