Milieux de culture cellulaire

La bonne installation, clé d’une culture cellulaire réussie

Les cultures cellulaires exigent des milieux spécifiques. L’art d’obtenir une bonne activité cellulaire et de bonnes courbes de croissance réside dans la recette et la formulation des ingrédients. Une fois le mélange trouvé, le traitement adéquat joue un rôle décisif. Le milieu sec doit être homogène tant du point de vue de la taille des particules que des proportions du mélange afin qu’il se dissolve rapidement et ait simultanément une composition identique à chaque dose. Le traitement doux et hygiénique des milieux de culture cellulaire garantit leur qualité. Dans le même temps, les installations de production doivent être flexibles et efficaces afin de pouvoir fabriquer de nouveaux lots quotidiennement. Cela implique bien sûr un nettoyage facile et rapide.

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

Processus de base : mélange et broyage à partir d’une source unique
Broyage fin refroidi dans le broyeur fin à impact Hosokawa Alpine
Mélange doux mais intensif dans le mélangeur conique Nauta®
Nettoyage intégré et automatique du système
Degré d’automatisation optimale

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.

Des solutions fiables grâce à des systèmes intégrés

Le facteur décisif est le traitement - du prémélange à l’emballage - dans un processus continu. Une approche intégrée de la solution du processus est essentielle. Il empêche tout contact indésirable avec l’oxygène, l’humidité et les germes présents dans l’environnement. Des temps de traitement courts dans des conditions conditionnées et fraîches garantissent la qualité des ingrédients. Le haut degré d’automatisation du processus, en particulier du nettoyage et du séchage, est source de sécurité et de flexibilité et permet de produire une grande variété de supports sur un seul système, que ce soit par lots de quelques kilogrammes ou à l’échelle d’une tonne. Par exemple, le procédé Hosokawa Alpine pour la production de milieux secs pour les cultures cellulaires est devenu une norme industrielle et une garantie de milieux de haute qualité.