Perfusion BioReactor System

a MA Fixed Bed BioReactor (MA-FBBR)

The MA Fixed Bed Bioreactor (MA-FBBR) System comprises a mechanically agitated bioreactor and a jacketed column packed with a bed of fibrous porous carriers or the like. The culture fluid is recirculated in one direction or flow in and out alternatively in two directions by an intelligent pump between the mixing vessel and the packed bed column to perform two different oxygenation schemes. All cells are immobilized by attachment or entrapment, and grow on the carriers. For biopharmaceutical applications the cells can be microbial, animal, or insect cells. It is also applicable for suspension and adherent cells because of the flow configuration and the scaffold structure of this system.

The commercial available fibrous porous carriers are Eppendorff's FibraCel and Cescobio's Bionoc II. All of which can retain or immobilize the cells by attachment (for adherent cells), or by entrapment (for suspension cells) in this FBBR system. It is therefore ideal for running perfusion culture to continuously produce biologics with no concern of fouling that is often encountered in other cell retaining devices used for perfusion cultures. When glass beads are used as a carrier, the system can be used to easily grow and harvest cells; and is also fully automated.

Our standard bench-top MA-FBBR system ranges from 1L to 10L working volume in the mixing vessel; and 0.1L to 3L total volume, respectively, in the packed bed column. The scale up is simple and straightforward without the complex issues as other perfusion systems. For systems where the working volume in the mixing vessel exceeds 30L and the volume of the packed bed column exceeds 10L, the system will be custom-made, capable of SIP (sterilization in place), and a Levitroix pump used for one directional recirculation system and pneumatic device for two alternative flow system.

The advantages of our MA-FBBR system over the other fixed bed bioreactors including Eppendorff’s Celligen Plus and Pall’s iCellis are: (1) Simpler construction and easier operation; (2) Carrier can be easier to be sampled during the process due to its external compartment location separated from the large primary medium mixing compartment; (3) Easier for linear scaleup; (4) Easier to change and control the liquid recirculation rate and liquid mixing separately; (4) Easy to control the process parameter including DO and pH; (5) Easy to adopt to a conventional bioreactor; (6) Much less scale limitation of carrier capacity; (7) Easier to change and control the flow patterns for oxygenation scheme.