Continuous Cell Culture

Nicholson, Mary L.; Hampson, Brian; Pugh, Gordon G.; Ho, Chester S.

doi:10.1016/b978-0-409-90123-8.50017-3

Cited by 7 publications

(1 citation statement)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, others have adopted on-line measurement of parameters that reflect cellular metabolism. These include the use of OUR (Fleischaker and Sinskey, 1981;Fleischaker, 1982;Nicholson, Hampson et al, 1991;Kyung, Peshwa et al, 1994;Zhou and Hu, 1994), estimation of the ATP production rate (Fleischacker, 1986;Glacken, 1991) and measurement of lactic acid production (Fleischacker, 1986;Glacken, Fleischaker et al, 1986;Hu and Oberg, 1990;Glacken, 1991;Matanguihan, Pambayun et al, 1993). More recently, direct measurements of glucose using enzymatic and non-enzymatic techniques have been applied (Konstantinov, Tsai et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Untitled

et al. 1999

View full text Add to dashboard Cite

Continuous culture is frequently used in the cultivation of mammalian cells for the manufacturing of recombinant protein pharmaceuticals. In such operations a large volume of medium is turned over each day, especially in the case where cell recycle, or perfusion cultivation, is practiced. In principle, the volumetric throughput of medium can be reduced by using a more concentrated feed while maintaining the same nutrient provision rate. Overall, the medium components are divided into two categories: 'consumable nutrients' and 'unconsumable inorganic bulk salts'. In such fortified medium, the concentrations of consumable nutrients, but not bulk salts, are increased. With a stoichiometrically-balanced medium, the large amount of nutrients fed into the culture is largely consumed by cells to give rise to residual concentrations of these nutrients in their optimal range. However, unless care is taken to initiate the continuous culture, overshoot of nutrients may occur during the transient period. The high nutrient concentration during overshoot may be inhibitory by itself, or the resulting high osmolality may retard the growth. Using a mathematical model that incorporates the growth inhibitory effect of high osmolality we demonstrate such a potentially catastrophic effect of nutrient and osmolality overshoot by simulation. To avoid overshoot a controlled nutrient feeding scheme should be devised at the initiation of continuous culture.

show abstract

Section: Discussionmentioning

confidence: 99%

Untitled

et al. 1999

View full text Add to dashboard Cite

show abstract

On-line monitoring of respiration in recombinant-baculovirus infected and uninfected insect cell bioreactor cultures

Kamen

Bédard

Tom

et al. 1996

Biotechnol. Bioeng.

117

View full text Add to dashboard Cite

Respiration rates in Spodoptera frugiperda (Sf‐9) cell bioreactor cultures were successfully measured on‐line using two methods: The O2 uptake rate (OUR) was determined using gas phase pO2 values imposed by a dissolved oxygen controller and the CO2 evolution rate (CER) was measured using an infrared detector. The measurement methods were accurate, reliable, and relatively inexpensive. The CER was routinely determined in bioreactor cultures used for the production of several recombinant proteins. Simple linear relationships between viable cell densities and both OUR and CER in exponentially growing cultures were used to predict viable cell density. Respiration measurements were also used to follow the progress of baculoviral infections in Sf‐9 cultures. Infection led to increases in volumetric and per‐cell respiration rates. The relationships between respiration and several other culture parameters, including viable cell density, cell protein, cell volume, glucose consumption, lactate production, viral titer, and recombinant β‐galactosidase accumulation, were examined. The extent of the increase in CER following infection and the time postinfection at which maximum CER was attained were negatively correlated with the multiplicity of infection (MOI) at multiplicities below the level required to infect all the cells in a culture. Delays in the respiration peak related to the MOI employed were correlated with delays in the peak in recombinant protein accumulation. DO levels in the range 5–100% did not exert any major effects on viable cell densities, CER, or product titer in cultures infected with a baculovirus expressing recombinant β‐galactosidase. © 1996 John Wiley & Sons, Inc.

show abstract

Cell Culture Bioreactors

Sambanis¹,

Hu²

1993

Biotechnology

View full text Add to dashboard Cite

Continuous Cell Culture

Cited by 7 publications

References 21 publications

Untitled

Untitled

On-line monitoring of respiration in recombinant-baculovirus infected and uninfected insect cell bioreactor cultures

Cell Culture Bioreactors

Contact Info

Product

Resources

About