Process Intensification Based on Nano-Structured Carbon Carrier Materials and Disposable Devices

This study describes the evaluation of an improved method for high yield production of biological compounds (i.e. recombinant proteins, monoclonal antibodies, vaccines, vectors, etc.) in disposable cultivation systems. Adherent CHO-DP12 cells, secreting recombinant human IgG1, were grown in roller bottles containing novel bio-mimicking and self regulating nano-structured CarboScale (R) carrier materials. The underlying material properties of the carrier potentially comprises a specifically optimized micro-environment for cell growth and expression of recombinant proteins. The specifically designed surfaces of CarboScale (R) comprise in-vivo-like nano-textures together with chemial surface charges that foster cell attachment and growth, subsequently resulting in an increase of cell densities and cell productivity. Compared to roller bottles without CarboScale (R) carrier the intensification of the cultivation process allowed to increase the cell densities by more than 700%. In parallel, the relative medium consumption per unit of harvested IgG1 was reduced by 50%. One essential factor for providing an ideal micro-environment is based on the pH buffering capacity of the carbon carrier used that keeps the initial pH-value within physiologic ranges constant over time even under excess of cell or biomass. Another mechanism is based on chemical adsorption and desorption of oxygen in exchange of carbon dioxide. A long term high density cell culture (up to 5.3 x 10(6) cells/ml) under stable and safe conditions could be established in a cultivation system without any external control.