Ulrich Behrendt

Industrial production of monoclonal antibodies and therapeutic proteins by dialysis fermentation

A novel and powerful fermentation method is reported for the large-scale growth of mammalian cells and their secreted products. The system described illustrates many of the advantages of conventional batch fermentation processes but in addition has been shown to yield cell densities in excess of 1×107 cells/ml with concomitant increase in product concentration.

Mass spectrometry: a tool for on-line monitoring of animal cell cultures

The magnetic sector mass spectrometer is able to detect oxygen uptake and carbon dioxide production rates from animal cell cultivations performed in 101 biorectors. Such data have not been available with the use of classic exhaust gas analysis applying paramagnetic analyzers and infra-red sensors due to the insensitivity of the apparatus available. In the course of the present work we were able to demonstrate, that the oxygen uptake rate correlates to the number of viable cells. Additionally oxygen uptake rates supplied on-line information about the actual physiology of the cells: When the rates changed during the cultivation process, this immediately indicated the occurrence of limitations of components in the medium. The information could be useful in timing key events, such as performing splits or harvesting the bioreactor.

A high density culture system for the in-vitro production of human and mouse monoclonal antibodies

A simple high density cell culture system is described which demonstrates many of the features of commercially available hollow-fibre systems, but without the need to invest in a dedicated system. The system has been shown to achieve product concentrations of up to 40-fold greater than that obtained in batch culture making gram production of MAbs possible with considerable saving on serum costs.

Simulation of Cell Cycle Dependent Growth and Metabolism in Animal Cell Fermentation

Abstract Growth and metabolism of mouse-mouse hybridoma cell lines were simulated with the help of a structured model based on the segregated fractions of cell cycle. This model uses constant metabolic rates for the different phases of cell cycle. The change of specific rates from the whole cell population during cultivation is modelled by the shift between cycling and resting phases, which is dependent from the culture conditions. Simulation of the cell cycle dependent growth was performed and compared for batch, dialysis, continuous and split batch fermentation processes.