Modelling hybridoma cell growth and metabolism — a comparison of selected models and data

Pörtner, Ralf; Schäfer, Thomas

doi:10.1016/0168-1656(96)01535-0

Cited by 115 publications

(95 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While theoretically feasible, it complicates practical application because a large number of kinetic parameters must be estimated using nonlinear optimization (Pörtner and Schäfer 1996;Tziampazis and Sambanis 1994). For mammalian cell cultures, it is generally accepted that cell specific rates for growth, metabolism, and protein production provide adequate quantitative characterization rather than complex kinetic models.…”

Section: Introductionmentioning

confidence: 99%

Computer programs for modeling mammalian cell batch and fed-batch cultures using logistic equations

Goudar

2012

Cytotechnology

View full text Add to dashboard Cite

A MATLAB Ò toolbox was developed for applying the logistic modeling approach to mammalian cell batch and fed-batch cultures. The programs in the toolbox encompass sensitivity analyses and simulations of the logistic equations in addition to cell specific rate estimation. The toolbox was first used to generate time courses of the sensitivity equations for characterizing the relationship between the logistic variable and the model parameters. Subsequently, the toolbox was used to describe CHO cell data from batch and fed-batch mammalian cell cultures. Cell density, product, glucose, lactate, glutamine, and ammonia data were analyzed for the batch culture while fedbatch analysis included cell density and product concentration. In all instances, experimental data were well described by the logistic equations and the resulting specific rate profiles were representative of the underlying cell physiology. The 6-variable batch culture data set was also used to compare the logistic specific rates with those from polynomial fitting and discrete derivative methods. The polynomial specific rates grossly misrepresented cell behavior in the initial and final stages of culture while those based on discrete derivatives had high variability due to computational artifacts. The utility of logistic specific rates to guide process development activities was demonstrated using specific protein productivity versus growth rate trajectories for the 3 cultures examined in this study. Overall, the computer programs developed in this study enable rapid and robust analysis of data from mammalian cell batch and fed-batch cultures which can help process development and metabolic flux estimation.

show abstract

Section: Introductionmentioning

confidence: 99%

Computer programs for modeling mammalian cell batch and fed-batch cultures using logistic equations

Goudar

2012

Cytotechnology

View full text Add to dashboard Cite

show abstract

“…Alternatively, the kinetics can be modelled by more elaborate kinetics [31,32]. It also includes the oxygen mass transfer to the cells which depends of the k L a coefficient [34]:…”

Section: Figurementioning

confidence: 99%

Scale‐up of cell culture bioreactors using biomechatronic design

Mandenius

Björkman

2012

Biotechnology Journal

View full text Add to dashboard Cite

An alternative approach for scale-up of cell culture bioreactors based on biomechatronic design methodology is suggested.The approach differs from traditional biochemical engineering methodology by applying a sequential design procedure where the needs of the users and alternative design solutions based on the biological and technical functions of the scaled-up bioreactor are derived in functional maps, concept generation charts and scoring and interaction matrices. Basic reactor engineering properties, such mass and heat transfer and kinetics are integrated in the procedure. Examples are provided from production of monoclonal antibody and recombinant protein.

show abstract

“…One of the major problems associated with unstructured models though is their limited applicability to the process conditions and data range they are derived from. However, it has been put forward that the growth of a cell line follows the same kinetics, irrespective of the cultivation mode (Pörtner and Schäfer, 1996). It is, therefore, possible that an unstructured model developed from batch culture data can also describe fed-batch cultures, which are known to increase levels of protein production and are preferred industrially, as long as it is properly validated.…”

Section: Introductionmentioning

confidence: 99%

Systematic development of predictive mathematical models for animal cell cultures

Kontoravdi

Pistikopoulos

Mantalaris

2010

Computers & Chemical Engineering

View full text Add to dashboard Cite

Fed-batch cultures are used in producing monoclonal antibodies industrially. Existing protocols are developed empirically. Model-based tools aiming to improve productivity are useful with model reliability and computational demand being important. Herein, a systematic framework for developing predictive models is presented comprising of model development, global sensitivity analysis, optimal experimental design for parameter estimation, and predictive capability checking. Its efficacy and validity are demonstrated using a fed-batch structured/unstructured model of antibody-secreting hybridoma cultures. Global sensitivity analysis is first used to identify sensitive model parameters (initial values estimated from batch cultures). Information-rich data from an optimally designed fed-batch experiment are then used to estimate these parameters, resulting in good agreement between simulation and experimental results. Finally, the model's predictive capability is confirmed by comparison with an independent set of fed-batch cultures. This approach systematises the process of developing predictive cell culture models at a minimum experimental cost, enabling modelbased control and optimisation.3

show abstract

Modelling hybridoma cell growth and metabolism — a comparison of selected models and data

Cited by 115 publications

References 59 publications

Computer programs for modeling mammalian cell batch and fed-batch cultures using logistic equations

Computer programs for modeling mammalian cell batch and fed-batch cultures using logistic equations

Scale‐up of cell culture bioreactors using biomechatronic design

Systematic development of predictive mathematical models for animal cell cultures

Contact Info

Product

Resources

About