CelliGen™ 310 The Universal
Stirred-Tank Bioreactor System

Video: Critical Considerations for Selecting
a Fermentor or Bioreactor Vendor

Production of Secreted Products with a Fibrous-Bed Basket

Immoblized Cell Culture
When secreted products are required, an optional fibrous-bed basket may be selected for mass production of both anchorage-dependent and suspension cultures. Whether your need is antibodies from hybridoma, thrombolytic proteins from SF9 cells or a variety of secreted proteins from recombinant CHO cells, the basket system can optimize productivity. Cells quickly adhere to the positively charged disks where high yields of cells are shielded from turbulence, allowing higher stirring rates and increased oxygen transfer. Suspension cultures may likewise be immobilized on the disks where they can grow more profusely than in suspension.

The gentle rotation of the impeller ports creates a negative pressure inside the hollow impeller shaft that becomes the driving force in the circulation of the medium. Oxygenated medium circulates throughout the basket, continuously saturating the cell bed.

Cell Perfusion Facility
Immobilized cells growing in perfusion serve as a renewable catalyst for the continuous production of proteins as fresh medium washes secreted products into the cell-free environment. Having a high surface-to-volume ratio, the disks provide three-dimensional growth within the fibers, achieving high yields even when low serum levels or serum-free media are used.

Scale-up Capability
The geometry of the CelliGen 310 bioreactor facilitates scale-up to commercial levels. Unlike Air-Lift, Hollow Fiber and other bioreactors, the fibrous-bed basket has the potential for reproducible scale-up to commercial production because of the low pressure drop across the basket and the low mass transfer resistance. CelliGen 310 can also be used to optimize perfusion rates in large-scale operations by adjustment of user-defined variables through NBS' optional bioprocessing software.

Multi-Faceted Capabilities
Building on the success of the original CelliGen and CelliGen Plus bioreactors, New Brunswick Scientific has combined the stirred-tank Cell-Lift bioreactor with packed-bed technologies to satisfy virtually any application in the culture of animal cells.

Determination of Cellmass
In addition to the standard D.O. probe that is supplied, a second D.O. probe may be ordered with NBS' software (both optional) for real-time determination of cell density. Using both sensors, the D.O. concentration can be measured above and below the cell bed, enabling oxygen uptake rate to be computed continuously as an aid in process optimization.

Control of temperature, stirring, pH, D.O., level/antifoam, nutrient addition, harvest and gas flow rates are maintained via programmable setpoints displayed on an 8" master screen. CelliGen 310 is PC-compatible and may be driven with optional BioCommand software for data logging and real-time graphics. The software allows you to create user-defined calculated variables for control of such parameters as glucose consumption and oxygen uptake rates.

CelliGen 310 offers the versatility of four types of interchangeable impellers, three different air delivery systems and three interchangeable bioreactors, all microprocessor-controlled and enhanced by computer compatibility.

Simplified Operation
The fibrous-bed basket concept offers many advantages over traditional stirred-tank systems. Cells are completely protected from the shear of rotating impellers and sparged gas while products are easily harvested from the cell-free medium.

Instead of using spin filters that can become clogged, or external profusion systems for recirculation of viable cells through peristaltic pumps; and instead of filtering secreted products from cell suspensions, metabolites released by trapped cells are separated right at the source, simplifying removal of product from the spent medium. Even cellular debris from lysed cells are retained in the fibers, simplifying downstream processing.

Operation of CelliGen 310 with the Fibrous-Bed Basket

Simple to Use
Fibrous-Bed Basket (H) is loaded with polyester disks. The vessel is filled with deionized water or PBS solution and then autoclaved. Following sterilization, the liquid is replaced with growth medium saturating the disk bed (E). Temperature, pH, D.O., etc. are set prior to inoculation using a slow stirring rate to promote cell attachment. Then, agitation is increased and perfusion is initiated by adding fresh medium (A) and harvesting metabolic products from the cell-free medium above the basket (D). Impeller rotation creates negative pressure in the draft-tube (G), causing medium to circulate uniformly in a continuous loop. Adjustment of the harvest tube controls liquid level (B). A ring sparger (not visible), is located inside the impeller aeration chamber (F), oxygenating the medium flowing through the impeller. Sparged gas confined to the remote chamber is absorbed by the nutrient medium which continuously washes over the immobilized cells. With cell entrapment, no hollow fiber filtration is required for off-line separation of cells from the broth, enabling long-term production without danger of clogging.