iCELLis™, the world's first fully integrated high-cell density bioreactor is designed to simplify your process, by combining the advantages of single-use technologies with the benefits of a fixed-bed system. Thanks to its compact design - for a quick implementation and more ease of use – iCELLis represents the new generation single-use bioreactors.
Central to the iCELLis bioreactor technology is the use of a compact fixed-bed, filled with custom macrocarriers. This matrix is made of medical grade polyester microfibers and provides in only 25L volume, up to 500m² growth area available to the cells. This surface is equivalent to the surface of 3000 Roller Bottles (1700cm² each). iCELLis bioreactors are supplied pre-packed with macrocarriers. Compared to standard stirred tank bioreactor using microcarriers, the iCELLis technology leads to a dramatic simplification of cell culture process. It enables to avoid delicate and time consuming manual operations: sterilization and hydration of microcarriers, and bead-to-bead transfers from preculture to final process.
With the biomass multiplication occurring in the fixed-bed, iCELLis bioreactors can be inoculated at very low density. The number and volume of pre-culture steps are reduced considerably: 20 Roller Bottles (1700 cm²) are can be sufficient to inoculate an iCELLis 500 bioreactor (500 m² of available surface to the cells). As a consequence of this process simplification, manual operations and associated costs are reduced dramatically.
Evenly-distributed media circulation is achieved by a built-in magnetic drive impeller, ensuring low shear stress and high cell viability. The cell culture medium flows through the fixed-bed from the bottom to the top. At the top, the medium falls as a thin film down the outer wall where it takes up O2 to maintain high KL.a. in the bioreactor. This unique waterfall oxygenation, together with a gentle agitation and biomass immobilization, enables compact iCELLis to achieve and maintain high-cell densities, equaling the productivity of much larger stirred tank units.
Process simplification, from vial thawing to final product, is at the heart of the iCELLis platform. As cells are immobilized in the fixed-bed and iCELLis operates in perfusion mode, there is no need for centrifugation to harvest the cells, which simplifies further the downstream process. Last but not least, in order to reduce process development time, the perfusion device is integrated into the iCELLis™ skid.
iCellis Nano volumes
|Surface area Low (m2)||0.53||1.06||2.6|
|Surface area High (m2)||0.8||1.6||4|
Configurations of iCELLis bioreactors at small scale
|Low Compaction||High Compaction|
The fixed-bed design of the iCELLis system makes it the perfect solution for process intensification, providing a large cell growth surface area while keeping the volumes very small. In only 25L of volume, iCELLis accommodates up to 500m2 of growth area, which, when compared with available surfaces of multitray systems and roller bottles, corresponds to a huge reduction in volumes. The iCELLis 500/500m2 is equivalent to 794 cell stacks with 10 trays and 5,882 Roller Bottles at 850cm2 each.
In addition to volume reduction, the use of a filled, fixed-bed in the iCELLis system enables higher specific productivity than in classical systems. To demonstrate the impact of iCELLis bioreactors on cell densities and productivity, many cultures were performed with several cell lines. Results clearly highlight that the growth matrix inside the iCELLis system is a favored growth environment which, together with controlled cell culture parameters, can significantly increase the biomass amplification, as well as the number of viral particles produced by each cell (specific pro-ductivity). Additional experiments demonstrated that iCELLis bioreactors require limited adaptation protocols and enable easy, straightforward scale-up for the majority of mammalian cell lines.
Table 3: Cell densities and specific productivities achieved with iCELLis systems (several mammalian cell lines). Comparison is with multitray systems/Roller Bottles.
Process simplification, from pre culture steps to final product:
Inoculation at very low cell density, simplifying seed trains operations as no intermediate bioreactor is required
Fixed-bed design avoids numerous operations involved by the use of µbeads,
Standard process designed for quick implementation (less than one year),
Linear scalability, from R&D scale to manufacturing scale,
Compact high-cell-density fixed-bed bioreactor:
Up to 500m² growth area in only 25L volume – equivalent to 3000 Roller Bottles (1700cm² each)
Dramatic decrease of operations costs and investments:
Single-use bioreactor made up USP Class VI rigid plastic to ensure process reliability