Cell-culture bioreactors

Aimins, Henzler HJ (1993) Aeration in Cell Culture Bioreactors. In Rehm HJ, Reed G, PiihJer A StadJer P Biotechnology VCH 3 219... 

Using large- and small-volume samples, mixed with synthetically produced samples, excellent values were developed. Samples were analyzed for alanine, glucose, glutamine, and leucine in samples removed from an Sf-9 insect cell culture bioreactor. It was seen that purely synthetic standards led to poor predictions of actual runs. The best results were achieved from mixed — actual and synthetic — samples. 

Wu J, Goosen MFA (1995), Evaluation of the killing volume of gas bubbles in sparged animal cell culture bioreactors, Enzyme Microb. Technol. 17 1036-1042. 

Assuming a minimum 12% inoculum volume, what size of laboratory vessel would be required to initiate the seeding of a 20,000-L full-scale cell-culture bioreactor ... 

Johnson M, Andre G, Chavarie C Archambault J (1990) Oxygen transfer rates in a mammalian cell culture bioreactor equipped with a cell-lift impeller. Biotechnology and Bioengineering 35 43-49. 

Shi Y, Ryu DDY Park SH (1992) Performance of mammalian cell culture bioreactor with a new impeller. Biotechnology and Bioengineering 40 260-270. 

A typical cell culture bioreactor available from all fermenter suppliers is conceptually similar to the familiar bacterial fermenter apart from modifications such as a marine (not turbine) impeller, curved or convex base for better miring at low speeds and water-jacket - not immersion heater - temperature control (to avoid localized heating at low stirrer speeds). 

In this overview an explanation has been given for the wide and complex range of cell culture bioreactor systems that are available. This is to put some perspective on the ones that are described in more detail in the following chapters. The selection of a suitable system follows the adage horses for courses , i.e. a process is selected that fulfils the particular criteria for the cell, product, scale and quantity required, plus the resources in facilities, manpower and experience that are available. 

Bierau, H. Perani, A. Al-Rubeai, M. Emery, A.N. A comparison of intensive cell culture bioreactors operating with hybridomas modified for inhibited apoptotic response. J. Biotechnol. 

Cherry RS, Papoutsakis ET (1988) Physical mechanisms of cell damage in microcarrier cell culture bioreactors. Biotechnol. Bioeng., 32 1001-1014. 

Fenge C, LUllau E. (2006) Cell culture bioreactors. In Ozturk SS, Hu WS, editors. Cell culture technology for pharmaceutical and cell-based therapies. Taylor Francis, New York, USA. p 155-224. 

Hollow fiber membranes (HFMs) formed via phase inversion methods exhibit specific physicochemical characteristics and generally favorable surface and mechanical properties. Due to these properties the HFMs can be used in diverse applications including ultrafiltration, gas separation, dialysis, cell culture, bioreactors, and tissue engineering. Most artificial kidneys are based on hollow fiber membranes. Blood is circulated through the center of the fiber, while isotonic saline, the dialysate, is pumped countercurrently around the outside of the fibers. Urea, creatinine, and other low-molecular weight metabolites in the blood diffuse across the fiber wall and are removed with the saline solution. 

Continuous flow operation of a bioreactor such that the cells are recycled or retained within the reactor, is sometimes known as perfusion culture. Many different kinds of devices are available for cell retention and recyele. These devices may be loeated within or outside the bioreactor vessel. External sedimentation tanks (Fig. 23b) are often used to recycle biomass in wastewater treatment processes. External and internal enhanced-rate sedimentors are also employed in animal cell culture bioreactors, as shown in Fig. 26a, b. Because of the small differences in... 

GMP versus Non-GMP Operation As mentioned earlier, cell-culture bioreactors... 

GMP cell-culture bioreactors are often placed in a class D or even class C cleanroom, even though the process is closed and there is no regulatory requirement for it. However, cell cultures often run for many weeks as perfusion culture, and thus mitigating the risk of contamination is considered a justification for the selected cleanroom environment. For maintenance and cleaning purpose, it is desired to move the majority of technical installations into a nonclassified technical space with only access to vessel ports and probes from within the clean... 

A single impeller may be sufficient in a vessel as long as the liquid level does not exceed 1-1.25 times the vessel diameter as might be the case for cell-culture bioreactors. Higher microbial bioreactors are typically equipped with several impellers (see Figure 1.15) and usually operated at high speed, resulting in tip velocities of 3 m s . ... 

Great progress was achieved in the past decades regarding the development of mammalian cell culture technology [2,34,98-102]. Nevertheless, the design and layout of cultivation systems and bioreactors have to meet cell-specific demands due to the special characteristics of these cells. Selection of a suitable type of cell culture bioreactor system and/or an appropriate operation mode (batch, fed-batch, or perfusion) is affected by technical, biological, economical, and regulatory considerations. 

Brotherton, J.D. and Chau, P.C. (1996) Modeling of axial-flow hollow fiber cell culture bioreactors. Biotechnol Progr.,... 

Medium Biomaterials for Hematopoietic Cell Culture Bioreactors for Hematopoietic Cell Culture... 

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