An evaluation of fed-batch cultivation methods for mammalian cells based on model simulations

Hansen, H. A.; Madsen, N. M.; Emborg, C.

doi:10.1007/bf00369404

Cited by 12 publications

(12 citation statements)

References 20 publications

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“…For detailed discussion of the Batt and Kompala model and its modification refer to [1,2]. The Nielsen model is very suitable for simulations of continuous cultivations but fails to simulate batch or fed-batch cultivations in its original form.…”

Section: Modification Of the Modelsmentioning

confidence: 99%

“…We started our simulations with the same parameters and initial conditions as in [1]: the living cells initial concentration, …”

Section: Simulationsmentioning

confidence: 99%

“…All the fermentation runs started with 1 l initial volume and stopped after 120 h where the occurrence of dead cells makes the models more unreliable [1]. Feed concentrations were for glucose 200 g/l, for glutamine 30 g/l.…”

Section: Simulationsmentioning

confidence: 99%

“…Some time ago we made an evaluation of fed-batch cultivation of hybridoma cells based on simulations of a structured model constructed by Batt and Kompala [1,2]. It was a somewhat surprising result of these simulations, that they did not support an idea of using fed-batch mode for production of monoclonal antibodies.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of mammalian fed-batch cultivations by two different models

Ryszczuk

Emborg

1997

Bioprocess Engineering

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Simulations of fed-batch hybridoma cell cultures were performed with two different models, a new model suggested by Nielsen and an older model suggested by Batt and Kompala. The response of the new Nielsen model was less sensitive to changes in feed concentrations and frequencies than the Batt and Kompala model. The new simulations with the Nielsen model as well as those previously with the Batt and Kompala model indicate, that possible benefits of fed-batch cultivations must be sought in other features than in intrinsic metabolic kinetics. List of symbols N v live cells concentration [ l\1] m N individual cell mass [ng] N d dead cells concentration [l\1] Q glutamine concentration [mM] S glucose concentration [mM] A alanine concentration [nM] L lactate concentration [mM] M ammonia concentration [mM] P MAb concentration [mg /l] V volume [l] q1continous feed [l /h] subscripts: f concentration in the feed for constants and rates see Table 1 and 2

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Section: Modification Of the Modelsmentioning

confidence: 99%

“…We started our simulations with the same parameters and initial conditions as in [1]: the living cells initial concentration, …”

Section: Simulationsmentioning

confidence: 99%

Section: Simulationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of mammalian fed-batch cultivations by two different models

Ryszczuk

Emborg

1997

Bioprocess Engineering

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“…Structured kinetic models have also been proposed to develop feeding strategies in fed batch cultures [1±3]. Hansen et al [6] used model simulation with intermittent feeding to maximize cell growth. The performance improvement was reported with continuous feeding as opposed to intermittent feeding [9].…”

Section: Introductionmentioning

confidence: 99%

Optimization of feed rate profile for the monoclonal antibody production

Lee

Lim

Yoo

et al. 1999

Bioprocess Engineering

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The optimal control algorithm to calculate the optimal feed rate pro®le of nutrient solution containing two limiting nutrients was proposed. Different from other conventional optimization methods, the proposed algorithm calculated the optimal control pro®les for different initial and feed conditions. The singular optimal control algorithm, dynamic programming, and nonsingular transformation algorithm were used for the optimization of simple problems of the 4th order and the performances were compared. With the proposed transformation algorithm, the ®nal MAb concentration increased and the CPU time decreased.For the different initial glucose and glutamine conditions, the optimal control pro®les were calculated with the proposed transformation algorithm. As the initial glutamine concentration increased, the ®nal MAb concentration also increased due to the cell viability increase. This was also applied to the different feed compositions. When the glutamine concentration was increased in the feed stream, the ®nal MAb concentration also increased.

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Cell Growth and Protein Expression Kinetics

Kompala

2000

Encyclopedia of Cell Technology

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An evaluation of fed-batch cultivation methods for mammalian cells based on model simulations

Cited by 12 publications

References 20 publications

Evaluation of mammalian fed-batch cultivations by two different models

Evaluation of mammalian fed-batch cultivations by two different models

Optimization of feed rate profile for the monoclonal antibody production

Cell Growth and Protein Expression Kinetics

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