Cell culture media

The right system for perfect cell performance

Cell cultures require specific media. The key to generating good cell activity and growth curves lies in the recipe and the correct formulation of the contents. Once this mixture has been found, correct processing plays a decisive role. The dry medium must be homogeneous, both in particle size and mixing ratio, in order to not only dissolve quickly but also to ensure the same and correct composition in every single dose. The careful and hygienic processing of the cell culture media guarantees their high quality. The production systems used must be flexible and efficient if new batches are to be produced every day. This naturally means a simple and quick cleaning process.

Vertical design of the equipment

High degree of flexibility for a large number of formulations

A great challenge in preparing cell culture media lies in the virtually endless choice in recipes with a wide range of components, different bulk densities, particle sizes or flow properties. This requires a universal system that takes into account all of the process steps from formulation, pre-mixing, grinding and post-mixing through to packaging.

The technology from the Hosokawa Group starts immediately after formulation, integrating the core technologies of mixing and grinding into a seamless process. This ensures the production of high-quality media. After formulation, the materials are poured into the pre-mixer. The homogenised material is then dosed into the UPZ fine impact mill. This can be mounted on the post-mixer. That is where collection then occurs, and if necessary further materials can be added. After a further homogenisation step, the end product is packed into the contamination-free packaging unit. The vertical design of the equipment arrangement provides a high degree of flexibility for a large number of formulations:

Closed loop inert system
Temperature-controlled grinding (down to -40°C)
High mixing accuracy
Closed packaging
Integrated cleaning

Core processes mixing and grinding from one single source
Cooled fine grinding with the Hosokawa Alpine fine impact mill
Gentle but simultaneously intensive mixing in the conical Nauta mixer
Integrated, automatic system cleaning
Maximum degree of automation

Highest mixing accuracy without contamination

Gentle yet intensive mixing in the Nauta conical mixer

The Nauta conical screw mixer from our Dutch partner Hosokawa Micron B.V. extremely efficient due to its convective technology. This allows it to gently combine the mixture with maximum accuracy but without damaging the structure.

To avoid cross-contamination between batches and in accordance with cGMP hygiene standards, the Nauta mixer is equipped with a semi or full convex cover (welded in one piece to the vessel), flushable seals and a special internal design. Cleaning is carried out by means of removable or stationary spray balls that wet all of the internal surfaces including the nozzles.

Key advantages of the Nauta mixer:

Maximum mixing accuracy
Gentle mixing without damaging the product
Flexible batch sizes between 15 and 100%
Hygienic design for an outstanding cleaning process
No separation during discharge

Fine grinding of challenging materials

Cryogenic fine grinding in the Hosokawa Alpine fine impact mills

The fine impact mill UPZ is used for fine and ultra-fine grinding and covers a range from approximately 20 to 1500 μm. A variety of grinding inserts are available for this type of mill, depending on the product and the required grain size. The aeration effect of the rotor ensures a cool grinding process and a fine-grained end product with good flow properties. In the production of cell culture media, the UPZ mill is typically equipped with pin discs for finely ground and homogeneous products up to 90% < 20 - 150 μm. The ground product has a steep particle size distribution and is easily mixed.

A suitable solution for the formulation of special cell culture media is the Contraplex CW II pin mill with counter-rotating pin discs and the option of low-temperature grinding with LN₂ cooling (down to -40°C).

Key advantages of the Hosokawa Alpine fine impact mills:

Steep particle size distribution
Grinding under low temperatures
Hygienic design for an outstanding cleaning process

Integrated, automatic system cleaning

Clinically clean and flexible in use

Systems for preparing cell cultures must be flexible and efficient if new batches with different recipes are to be manufactured every day. That is why cleaning options play a decisive role in the selection of suitable process equipment.

Hosokawa mixers and mills are designed to prevent contamination. The vertical, aseptic design with a high-quality surface finish and the conical mixing vessels with a fixed connection to the mill guarantee maximum product recovery.

However, some contamination can simply not be avoided, even if all of the necessary precautions are taken. For this reason, spray nozzles are positioned at strategic locations for wet cleaning of the production line. This wets everything and guarantees a thorough cleaning from top to bottom.

The spray nozzles clean the surfaces using a combination of impact and releasing action: from the pre-mixer and the mill to the post-mixer and the packaging unit. After the wet cleaning process, all of the components are dried from top to bottom with hot air, utilising the stack effect.

The highest degree of automation

Reliable automation under pharmaceutical standards

The production line is controlled by a fully automatic control system that meets the highest pharmaceutical standards such as FDA, cGMP and GAMP.

Reliable solutions by means of integrated systems

From premixing to packaging

The decisive factor is the processing – from the preliminary mix to the packaging – in a seamless process. An integrated approach to a process solution is essential. It prevents accidental contact with oxygen, moisture and germs from the environment. Short processing times under cool conditions safeguard the quality of the ingredients. A high degree of automation in the process – especially for cleaning and drying – creates reliability and flexibility and makes it possible to manufacture a wide variety of media with one system, regardless of whether in batches of a few kilograms or on the scale of several tons. Already today, the Hosokawa Alpine process for the manufacture of dry media for cell cultures has become the industry standard and simultaneously a guarantee for high-grade media quality.