Publications

Rocking Aspergillus

Morphology-controlled cultivation of Niger Aspergillus

Disposable Bioreactors

A new type of rocking bioreactor

Vero Cell Culture

Comparison of Cell Growth and metabolism on two different rocking type bioreactors

ABSTRACT

Filamentous fungi including Aspergillus niger are cell factories for the production of organic acids, proteins and bioactive compounds. Traditionally, stirred-tank reactors (STRs) are used to cultivate them under highly reproducible conditions ensuring optimum oxygen uptake and high growth rates. However, agitation via mechanical stirring causes high shear forces, thus affecting fungal physiology and macromorphologies.Two-dimensional rocking-motion wave mixed bioreactor cultivations could offer a viable alternative to fungal cultivations in STRs, as comparable gas mass transfer is generally achievable while deploying lower friction and shear forces. The aim of this study was thus to investigate for the first time the consequences of wave-mixed cultivations on the growth, macromorphology and product formation of A. niger.

ABSTRACT

Single-use bioreactors (SUBs) show clear benefits compared to the traditional fixed glass and steel bioreactor equipment used for bioprocessing.

Several types of SUBs have been introduced, where rocking-type systems and tank liners are predominantly used. The rocking-type bioreactors are restricted in use to mammalian cell cultures. To date, stirred-type SUBs have only been applied for mammalian cell culture as well. A new type of rocking bioreactor, the CELL-tainer®, is capable of generating high mass-transfer coefficients and opens up the potential of application of SUBs in high-intensity cell cultures as well as in microbial cultures.

ABSTRACT

Rapid cell and virus cultivation was done in disposable bioreactors. The CELL-tainer® bioreactor has a 2 dimensional rocking movement with a vertical movement and horizontal displacement, enabling a high mass-transfer.

Mixing times were studied in both the CELL-tainer® and the BIOSTAT® CultiBag RM bioreactor. The conditions for cultivation of Vero cells in the CELL-tainer® bioreactor were chosen based on comparable mixing times.

Vero cells grown on Cytodex 1 microcarriers were cultivated in the CELL-tainer® and in the BIOSTAT® CultiBag. Both bioreactors were controlled with regard to t°, pH and % dissolved oxygen. Vero cell growth and polio virus production in both bioreactors was comparable.

Two dimensional rocking disposable bioreactor culture

Application of a two-dimensional disposable rocking bioreactor to bacterial fermentation

Single-use bioreactors in industry

Comparison of Cell Growth and metabolism on two different rocking type bioreactors

Wave disposable bioreactors

Cultivation of cells and micro-organisms in wave-mixed disposable bag bioreactors at different scales

ABSTRACT

Disposable rocking bioreactors (RBs) are widely employed for cultivation of recombinant mammalian and insect cell lines, although the perception of inadequate mass transfer has prevented their application to bioprocesses based on microbial platforms. In this study, one-dimensional (1D) and two-dimensional (2D) RBs were assessed and compared with the conventional stirred tank reactor (STR) for recombinant therapeutic protein production in Escherichia coli. Our results show that oxygen mass transfer was comparable between the 1D RB and STR at low working volume (WV), declining linearly with increasing WV, and was highest in the 2D RB for all tested WVs with the maximum mass transfer coefficient (kLa) at 3 L WV.

ABSTRACT

For almost 40 years, bioprocess engineers have focused on stirred tank bioreactor technology. But many have concluded that a plastic bag can be effective and that the results achieved with cultures in a single-use bioreactor are comparable with the results achieved in the glass or stainless-steel stirred tank bioreactor. This article describes experiments performed in the bag type single-use bioreactor that suggest it is a versatile multipurpose culture tool and yields results at least comparable with those as achieved in the traditional stirred tank bioreactor.

ABSTRACT

Disposable bioreactors have gained an increasing importance in recent years in the pharmaceutical production. Wave‐mixed reactors were among the first systems which were applied. In contrast to stirred tank reactors, wave‐mixed bioreactors are characterized by low shear forces while the gas exchange is realized by the large gas‐liquid interface. Oxygen transfer rates obtained are often in a range between 50 and 300 h–1. By applying nutrient‐limiting fed‐batch cultivations, in which the oxygen consumption of a culture is controlled, bacteria can be also cultivated in wave‐mixed reactors. This article describes the successful scale‐up of an Escherichia colifed‐batch cultivation from the 12‐L to the 120‐L scale using a disposable bioreactor, in which a final biomass concentration of 45 g L–1 was obtained.