Study highlights advantages of CELLine

By Gregory Roumeliotis

- Last updated on GMT

Related tags Dna

A disposable two-compartment flask bioreactor designed by Swiss
company Integra Biosciences has been shown to minimise production
costs in a new study, as opposed to cell cultivation roller bottles
which are 60 per cent more expensive.

The paper, entitled 'small-scale biomanufacturing benefits from disposable bioreactors', describes the advantages of the CELLine 1000 bioreactor for the production of monoclonal antibodies (MAb) up to yields of 1000 mg, but also points out its benefits may also be applied to the production of other biological products such as recombinant proteins and viral vectors, so that any laboratory with basic cell culture expertise can produce highly concentrated, high quality proteins in a cost efficient way.

The study's author, Fabrizio Baumann, Integra's product manager for cell cultivation, explained to why he believes CELLine 1000 is better than T-flasks and stirred bioreactors.

"You can handle CELLine like a T-flask when it comes to examining the cells but you get much better yields of cells and protein,"​ he said.

"There is a similar two-compartment roller bottle called miniPERM made by Vitro Systems, but it requires a higher skill to use."

The cell density achieved in a CELLine bioreactor is typically one to two orders of magnitude higher than in a conventional culture vessel, the study claims.

Using cell culture systems such as tissue culture flasks, roller and spinner bottles to attain the target yields is often unattractive because of the extra handling time, space requirements and waste disposal problems associated with using large numbers of disposable culture systems.

Therefore, two-compartment cell cultivation bioreactors benefit in terms of disposables, equipment amortisation, medium, serum and labour.

The core element of the CELLine system is the cell compartment, which is formed by two different membranes incorporated into the bottom of the cell-culture flask.

The upper membrane separates the cell compartment from the medium compartment and is made of a semi-permeable cellulose acetate sheet for exchange of metabolites between the two compartments.

The lower membrane is made of gas-permeable silicone and guarantees efficient oxygen and carbon dioxide transfer between the cell compartment and the incubator.

Because the cell compartment is only 2 to 3 mm thick, efficient oxygenation is achieved by simple diffusion, hence avoiding the need for agitation and the resulting detrimental shear stress.

Nutrients smaller than 10 kDa freely diffuse through this dialysis membrane, thereby sustaining cell growth.

Similarly, but in the opposite direction, toxic catabolites cross the dialysis membrane and are removed from the cells' surroundings.

"The cells get trapped in a limited volume, resulting in a thick soup,"​ Baumann said.

"The main application of this bioreactor in pharmaceutical manufacturing is in quality control and we have a major vaccine producing company using the product."

The advantages of CELLine become even stronger when dealing with yields of less than 1mg, where a stirred bioreactor would further augment the costs, due to additional labor and to equipment amortisation.

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