Stirred-tank reactor system

Abstract

The present invention relates to a stirred-tank reactor system and methods of preparing such systems. The present invention further encompasses the use of the stirred-tank reactor system as a disposable bioreactor and in kits with disposable elements.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a stirred-tank reactor system and methods of preparing such systems. The present invention further encompasses the use of the stirred-tank reactor system as a disposable bioreactor and in kits with disposable elements. BACKGROUND OF THE INVENTION [0002] A bioreactor or fermenter is a container used for fermentation, enzymatic reactions, cell culture, biologicals, chemicals, biopharmaceuticals, tissue engineering, microorganisms, plant metabolites, food production and the like. Bioreactors vary in size from benchtop fermenters to stand-alone units of various sizes. The stringent asepsis requirements for sterile production in bioreactors usually requires elaborate systems to achieve the desired product volumes. Consequently, the production of products in aseptic bioreactors is costly which provides the motivation for pursuing improved systems. [0003] Conventional bioreactors perfuse nutrient media through a single type of ...

AI Technical Summary

Benefits of technology

[0008] The present invention provides a stirred-tank reactor system with disposable elements, such as a flexible plastic bag with an attached bearing, shaft, and impeller assembly. The instant invention further relates to the use of this novel stirred-tank reactor system as a disposable bioreactor and in kits with disposable elements. The advantages of the present invention are numerous. Particularly, the stirred-tank reactor system may be pre-sterilized and does not require a steam-in-place (SIP) or clean-in-place (CIP) environment for changing from batch to batch or product to product in a culture or production system. As such, the system requires less regulatory control by assuring zero batch-to-batch contamination and can, thus, be operated at a considerable cost-advantage and with minimal or no preparation prior to use. In addition, the system is a true stirred-tank reactor system unlike other disposable reactors systems. This provides the added advantage that the instant invention offers a hydrodynamic environment that can be scaled to various sizes similar to conventional non-disposable reactor systems. Since the system does not require cleaning or sterilizing it combines a flexible, easy-to-use, true stirred-tank reactor environment with zero cross-contamination during the cell culture or production process.

Problems solved by technology

Consequently, the production of products in aseptic bioreactors is costly which provides the motivation for pursuing improved systems.

The various disadvantages of such bioreactors include heterogeneous cell mass, difficult procurement of representative cell growth samples, poor performance due to inefficient oxygenation and an inability to control oxygen levels, and problems with contamination of cell cultures.

Moreover, micro-environmental factors such as pH cannot be effectively controlled and a mixed culture or co-culture of cells is not possible.

However, occasional contamination of cell cultures and an inability to control pH levels effectively remain consistent problems.

The expense of producing cells, biopharmaceuticals, biologicals and the like in aseptic bioreactors is exacerbated by the required cleaning, sterilization and validation of the standard bioreactors (i.e., stainless steel or glass reactors).

Although this system provides a disposable liner, the head plate and the interior chamber still require cleaning and sterilization.

However, the cell culture chamber is limited to use within a controlled gas environment.

Particularly, the cell culture chamber has no support apparatus and is thus limited to small volumes.

Furthermore, the chamber does not provide an inlet and an outlet for media to be constantly pumped into and out of the chamber during rotation.

However, since there is no solid housing that support the bags, the bags become cumbersome and difficult to handle as they increase in size.

Furthermore, the wave action within the rocking bag creates damaging turbulent forces.

Images