On-line monitoring of an animal cell culture with multi-channel flow injection analysis

Pol, J.J. van der; Spohn, U.; Eberhardt, R.; Gaetgens, Jochem; Biselli, M.; Wandrey, Christian; Tramper, J.

doi:10.1016/0168-1656(94)90132-5

Cited by 20 publications

(2 citation statements)

References 21 publications

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“…In the same way, systems based on chromatographic techniques (ex. HPLC) or flow injection analysis (FIA) coupled with biosensors have been proposed for on‐line measurement of substrates, metabolic by‐products and products concentration, such as glucose, glutamine, lactate, ammonium and antibodies …”

Section: Introductionmentioning

confidence: 99%

Comparison of control strategies for fed‐batch culture of hybridoma cells based on on‐line monitoring of oxygen uptake rate, optical cell density and glucose concentration

Casablancas

Gámez

Lecina

et al. 2013

J of Chemical Tech & Biotech

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BACKGROUND: Improvement of the mammalian cell culture process is based on the implementation of culture strategies with higher productivities, such as fed-batch or perfusion processes. The efficient development of these culture strategies depends strongly on the availability of suitable monitoring tools to determine the activity of cell culture and adjust nutrient feeding correspondingly.RESULTS: In this study oxygen uptake rate (OUR), cell density and glucose concentration on-line monitoring systems are applied to control fed-batch processes. Different combinations of these monitoring systems were used to determine cell growth and metabolic activity of cell culture in order to adjust substrate feeding in a balanced manner. Application of these monitoring tools in fed-batch processes allowed extension of the exponential growth of hybridoma cells up to 2-3-fold and increased antibody productivity from 84 to 168% with respect to conventional batch culture. CONCLUSIONS: The three control strategies tested have been successful in providing improvement of the fed-batch culture of the hybridoma cell line used. Among the different alternatives studied, the use of OUR on-line monitoring to simultaneously determine cell growth and metabolic activity appears to be the best method to adjust substrate feeding owing to its simplicity and robustness.

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Section: Introductionmentioning

confidence: 99%

Comparison of control strategies for fed‐batch culture of hybridoma cells based on on‐line monitoring of oxygen uptake rate, optical cell density and glucose concentration

Casablancas

Gámez

Lecina

et al. 2013

J of Chemical Tech & Biotech

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“…The total carrier volume was 85 ml. The medium as described by Van der Pol et al (1994) was supplemented with 1% (v/v) heat inactivated Fetal Calf Serum (Gibco, Eggenstein, FRG).…”

Section: The Culture Systemmentioning

confidence: 99%

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et al. 1997

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The monoclonal-antibody production of an immobilized hybridoma cell line cultivated in a fluidized-bed reactor was monitored on-line for nearly 900 h. The monoclonal antibody concentration was determined by an immuno affinity-chromatography method (ABICAP). Antibodies directed against the product, e.g. IgG, were immobilized on a micro-porous gel and packed in small columns. After all IgG present in the sample was bound to the immobilized antibodies, unbound proteins were removed by rinsing the column. Elution of the bound antibodies followed and the antibodies were determined by fluorescence. The analytical procedure was automated with a robotic device to enable on-line measurements. The correlation between the on-line determined data and antibody concentrations measured by HPLC was linear.A sampling system was constructed, which was based on a pneumatically actuated in-line membrane valve integrated into the circulation loop of the reactor. Separation of the cells from the sample stream was achieved by a depth filter made of glass-fibre, situated outside the reactor. Rapid obstruction of the filter by cells or cell debris and contamination of the sample system was avoided by intermittent rinsing of the sample system with a chemical solution. The intermittent rinsing of the filter, which had a surface of 4.8 cm(2), resulted in an operational capacity of up to 40 samples (1.0 l total sample volume). Both the sampling system and the analytical device functioned without failure during this long-term culture.The culture temperature was varied between 34 and 40 °C. Raising the temperature from 34 up to 37 °C resulted in a simultaneous increase of growth and specific antibody production rate. Specific metabolic rates of glucose, lactate, glutamine and ammonium stayed constant in this temperature range. A further enhancement of temperature up to 40 °C had a negative effect on the growth rate, whereas the specific monoclonal antibody production rate showed a small increase. The other specific metabolic rates also increased in the temperature range between 38 to 40 °C.

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On‐Line Analysis in Animal Cell Culture

Kretzmer

2000

Encyclopedia of Cell Technology

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On-line monitoring of an animal cell culture with multi-channel flow injection analysis

Cited by 20 publications

References 21 publications

Comparison of control strategies for fed‐batch culture of hybridoma cells based on on‐line monitoring of oxygen uptake rate, optical cell density and glucose concentration

Comparison of control strategies for fed‐batch culture of hybridoma cells based on on‐line monitoring of oxygen uptake rate, optical cell density and glucose concentration

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On‐Line Analysis in Animal Cell Culture

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