Lonza Group is a Swiss chemicals and biotechnology company, headquartered in Basel. The firm provides a number of products and services to the pharmaceutical and life science industries, including organic fine and performance chemicals, custom manufacturing of biopharmaceuticals, chemical synthesis capabilities and chemicals, detection systems and services for the bioscience sector. Wikipedia.
Lattermann C.,RWTH Aachen |
Funke M.,Lonza Group |
Hansen S.,Evonik Industries |
Diederichs S.,RWTH Aachen |
Buchs J.,RWTH Aachen
Journal of Biological Engineering
Background: Biotechnological screening processes are performed since more than 8 decades in small scale shaken bioreactors like shake flasks or microtiter plates. One of the major issues of such reactors is the sufficient oxygen supply of suspended microorganisms. Oxygen transfer into the bulk liquid can in general be increased by introducing suitable baffles at the reactor wall. However, a comprehensive and systematic characterization of baffled shaken bioreactors has never been carried out so far. Baffles often differ in number, size and shape. The exact geometry of baffles in glass lab ware like shake flasks is very difficult to reproduce from piece to piece due to the hard to control flow behavior of molten glass during manufacturing. Thus, reproducibility of the maximum oxygen transfer capacity in such baffled shake flasks is hardly given.Results: As a first step to systematically elucidate the general effect of different baffle geometries on shaken bioreactor performance, the maximum oxygen transfer capacity (OTRmax) in baffled 48-well microtiter plates as shaken model reactor was characterized. This type of bioreactor made of plastic material was chosen, as the exact geometry of the baffles can be fabricated by highly reproducible laser cutting. As a result, thirty different geometries were investigated regarding their maximum oxygen transfer capacity (OTRmax) and liquid distribution during shaking. The relative perimeter of the cross-section area as new fundamental geometric key parameter is introduced. An empirical correlation for the OTRmax as function of the relative perimeter, shaking frequency and filling volume is derived. For the first time, this correlation allows a systematic description of the maximum oxygen transfer capacity in baffled microtiter plates.Conclusions: Calculated and experimentally determined OTRmax values agree within ± 30% accuracy. Furthermore, undesired out-of-phase operating conditions can be identified by using the relative perimeter as key parameter. Finally, an optimum well geometry characterized by an increased perimeter of 10% compared to the unbaffled round geometry is identified. This study may also assist to comprehensively describe and optimize the baffles of shake flasks in future. © 2014 Lattermann et al.; licensee BioMed Central Ltd. Source
Lorenz H.-M.,TU Bergakademie Freiberg |
Otte D.,TU Bergakademie Freiberg |
Staak D.,Lonza Group |
Repke J.-U.,TU Bergakademie Freiberg
Computer Aided Chemical Engineering
This paper presents a systematic approach for the improvement of existing complex processes in chemical industry in order to increase their efficiency. As a result, modifications of process configurations are developed. Due to their implementation several internal stream compositions may be changed. In order to guarantee all demanded product specifications, new operating points need to be found. Hence, a method based on the global optimization algorithm MIPT has been developed in MatlabTM. The process simulation software ChemCADTM has been linked to MatlabTM in order to solve the optimization problem. The developed method is applied to a complex example process. The influence of changing feed composition on several process variables is pointed out. © 2014 Elsevier B.V. Source
Bawa Z.,Aston University |
Bawa Z.,Astrazeneca |
Routledge S.J.,Aston University |
Jamshad M.,University of Birmingham |
And 7 more authors.
Microbial Cell Factories
Background: Pichia pastoris is a widely-used host for recombinant protein production; expression is typically driven by methanol-inducible alcohol oxidase (AOX) promoters. Recently this system has become an important source of recombinant G protein-coupled receptors (GPCRs) for structural biology and drug discovery. The influence of diverse culture parameters (such as pH, dissolved oxygen concentration, medium composition, antifoam concentration and culture temperature) on productivity has been investigated for a wide range of recombinant proteins in P. pastoris. In contrast, the impact of the pre-induction phases on yield has not been as closely studied. In this study, we examined the pre-induction phases of P. pastoris bioreactor cultivations producing three different recombinant proteins: the GPCR, human A2a adenosine receptor (hA2aR), green fluorescent protein (GFP) and human calcitonin gene-related peptide receptor component protein (as a GFP fusion protein; hCGRP-RCP-GFP).Results: Functional hA2aR was detected in the pre-induction phases of a 1 L bioreactor cultivation of glycerol-grown P. pastoris. In a separate experiment, a glycerol-grown P. pastoris strain secreted soluble GFP prior to methanol addition. When glucose, which has been shown to repress AOX expression, was the pre-induction carbon source, hA2aR and GFP were still produced in the pre-induction phases. Both hA2aR and GFP were also produced in methanol-free cultivations; functional protein yields were maintained or increased after depletion of the carbon source. Analysis of the pre-induction phases of 10 L pilot scale cultivations also demonstrated that pre-induction yields were at least maintained after methanol induction, even in the presence of cytotoxic concentrations of methanol. Additional bioreactor data for hCGRP-RCP-GFP and shake-flask data for GFP, horseradish peroxidase (HRP), the human tetraspanins hCD81 and CD82, and the tight-junction protein human claudin-1, demonstrated that bioreactor but not shake-flask cultivations exhibit recombinant protein production in the pre-induction phases of P. pastoris cultures.Conclusions: The production of recombinant hA2aR, GFP and hCGRP-RCP-GFP can be detected in bioreactor cultivations prior to methanol induction, while this is not the case for shake-flask cultivations of GFP, HRP, hCD81, hCD82 and human claudin-1. This confirms earlier suggestions of leaky expression from AOX promoters, which we report here for both glycerol- and glucose-grown cells in bioreactor cultivations. These findings suggest that the productivity of AOX-dependent bioprocesses is not solely dependent on induction by methanol. We conclude that in order to maximize total yields, pre-induction phase cultivation conditions should be optimized, and that increased specific productivity may result in decreased biomass yields. © 2014 Bawa et al. Source
News Article | July 21, 2015
DUBLIN, July 21, 2015 /PRNewswire/ -- Research and Markets (http://www.researchandmarkets.com/research/xfn43v/cell_culture) has announced the addition of the "Cell Culture Market : Global Industry Analysis, Size, Share, Growth, Trends and Forecast 2014 - 2022" report to their offering. The cell culture market was valued at USD 6,097.0 million in 2013 and is projected to reach USD 11,314.5 million by 2022, expanding at a CAGR of 7.1% from 2014 to 2022. Increasing application areas of cell culture technology in cancer detection, drug discovery and manufacturing of biologics have triggered the growth of this market. In addition, utilization of cell culture in various applications such as developing model systems for research, studies of cellular structures and functions, stem cell research and genetic engineering. Furthermore, huge investment in research and development by life science companies, extensive academic and industry collaborations and innovation in stem cell research have also driven the global cell culture market. Use of cell and tissue culture as model systems for studying cellular mechanisms related to various diseases such as diabetes, Parkinson's and Alzheimer's, and evaluating drug response is one of the most promising applications of this technology. The cell culture market has been segmented into two major product types: consumables and instruments. Cell culture consumables have been further categorized into media, sera and reagents. Cell culture media is likely to be the fastest growing segment owing to increasing preference for animal-derived component free (ADCF) media due to ethical and quality concerns. The instruments segment includes culture systems, incubators, pipetting instruments, roller bottle equipment, biosafety cabinets, cryostorage equipment, and others. Technological innovations in the design and operation of cell culture instruments and rapid adoption of automated culture systems by researchers and manufacturers are the major factors driving the segment. Key players operating in the global cell culture market include Sigma-Aldrich Corporation, BD Biosciences, EMD Millipore, Thermo Fisher Scientific, Inc., GE Healthcare, Lonza Biosciences, VWR International, PromoCell GmbH and Corning Incorporated. The global cell culture market is segmented as follows: - Becton, Dickinson and Company - Corning Life Sciences B.V.- EMD Millipore- GE Healthcare- Lonza Group Ltd. - PromoCell GmbH- Sigma-Aldrich Co. LLC. - Thermo Fisher Scientific, Inc. - VWR International, LLC- Wheaton Industries, Inc.