We describe a systematic approach to model CHO metabolism during biopharmaceutical production across a wide range of cell culture conditions. To this end, we applied the metabolic steady state concept. We analyzed and modeled the production rates of metabolites as a function of the specific growth rate. First, the total number of metabolic steady state phases and the location of the breakpoints...

We introduce here a microfluidic cell culture platform or spheroid culture chamber array (SCCA) that can synthesize, culture, and enable fluorescence imaging of 3D cell aggregates (typically spheroids) directly on-chip while specifying the flow of reagents in each chamber via the use of an array of passive magnetic valves. The SCCA valves demonstrated sufficient resistance to burst (above 100 m...

This paper presents a systems approach to evaluating the potential of integrated continuous bioprocessing for monoclonal antibody (mAb) manufacture across a product's lifecycle from preclinical to commercial manufacture. The economic, operational, and environmental feasibility of alternative continuous manufacturing strategies were evaluated holistically using a prototype UCL decisional tool th...

BACKGROUND Tripeptide glutathione (gamma-glutamyl-L-cysteinyl-glycine) is the most abundant non-protein thiol that protects cells from metabolic and oxidative stresses and is widely used as medicine, food additives and in cosmetic industry. The methylotrophic yeast Hansenula polymorpha is regarded as a rich source of glutathione due to the role of this thiol in detoxifications of key intermedia...

Background Experimental process-development and optimization is expensive and time-consuming. Real optimization by means of design of experiments involves data generation before optimization can be aimed for. This can make the way from process development to process establishment even harder, since academia or start-up research facilities might not have the possibility to generate these data. F...

Tuning recombinant protein expression is an approach which can be successfully employed for increasing the yield of recombinant protein production in high cell density cultures. On the other hand, most of the previous results reported the optimization induction conditions during batch and continuous culture of recombinant E. coli, and consequently fed-batch culture have received less attention....

Improved production costs will accelerate commercialization of polyhydroxyalkanoate (PHA) polymer and PHA-based products. Plant oils are considered favorable feedstocks, due to their high carbon content and relatively low price compared to sugars and other refined carbon feedstocks. Different PHA production strategies were compared using a recombinant strain of Ralstonia eutropha that produces ...

BACKGROUND Bioprocess development of recombinant proteins is time consuming and laborious as many factors influence the accumulation of the product in the soluble and active form. Currently, in most cases the developmental line is characterised by a screening stage which is performed under batch conditions followed by the development of the fed-batch process. Performing the screening already un...

Improved production costs will accelerate commercialization of polyhydroxyalkanoate (PHA) polymer and PHA-based products. Plant oils are considered favorable feedstocks, due to their high carbon content and relatively low price compared to sugars and other refined carbon feedstocks. Different PHA production strategies were compared using a recombinant strain of Ralstonia eutropha that produces ...

Background Fed-batch culture bioprocesses are essential for the production of therapeutic proteins [1]. In these cultures, concentrated feeds are added during cultivation to prevent nutrient depletion and to extend the growth phase, thus increasing product concentration [2]. One limitation arises from the low solubility of some amino acids at high concentrations, in particular tyrosine [3]. Thi...