Abstract
Single-use (SU) bioreactors are being increasingly used in production processes based on animal (i.e. mammalian and insect) and human cells. They are particularly suitable for the production of high-value products on small and medium scales, and in cases where fast and safe production is a requirement. Thus, it is not surprising that SU bioreactors have established themselves for screening studies, cell expansions, and product expressions where they are used for the production of pre-clinical and clinical samples of therapeutic antibodies and preventive vaccines. Furthermore, recent publications have revealed the potential of SU bioreactors for the production of cell therapeutics using human mesenchymal stem cells (hMSCs).
This chapter provides a perspective on current developments in SU bioreactors and their main applications. After briefly introducing the reader to the basics of SU bioreactor technology (terminology, historical milestones and characteristics compared to their reusable counterparts) an overview of the categories of currently available SU bioreactor types is provided. SU bioreactor instrumentation is then examined, before discussing well-established and novel applications of SU bioreactors for animal and human cells. This includes descriptions of the engineering characteristics of often-used types of SU bioreactors, covering wave-mixed, stirred, orbitally shaken systems and fixed-bed systems. In this context, the scaling-up of geometrically and non-geometrically similar SU bioreactors is also addressed.
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Abbreviations
- 1D:
-
One-dimensional
- 2D:
-
Two-dimensional
- 3D:
-
Three-dimensional
- bDtBPP:
-
Bis(2,4-di-tert-butyl phenyl) phosphate
- BEVS:
-
Baculovirus expression vector system
- CFD:
-
Computational fluid dynamics
- CHO:
-
Chinese Hamster Ovary (cells)
- CMO:
-
Contract manufacturing organization
- DoE:
-
Design of experiments
- DO:
-
Dissolved oxygen
- EDR:
-
Energy dissipation rate
- EVA:
-
Ethylene vinyl acetate
- hMSCs:
-
Human mesenchymal stem cells
- hADSCs:
-
Human adipose-derived mesenchymal stem cells
- hBM-hMSCs:
-
Human bone(marrow)-derived mesenchymal stem cells
- HPTS:
-
Hydroxypyrene trisulfonate acid
- LED:
-
Light-emitting diode
- mAbs:
-
Monoclonal antibodies
- MDCK:
-
Madin-Darby Canine Kidney (cells)
- MEMS:
-
Micro-electro-mechanical systems
- NK:
-
Natural killer (cells)
- PE:
-
Polyethylene
- PET:
-
Polyethylene terephthalate
- PIV:
-
Particle image velocimetry
- pO2 :
-
Partial pressure of oxygen
- pCO2 :
-
Partial pressure of carbon dioxide
- PTFE:
-
Polytetrafluoroethylene
- PVC:
-
Polyvinylchloride
- QbD:
-
Quality by Design
- RANS:
-
Reynolds averaged Navier-Stokes (equations)
- RFID:
-
Radio-frequency identification
- RT:
-
Ruston turbine
- SBI:
-
Segment blade impeller
- Sf-9:
-
Spodoptera frugiperda (subclone 9)
- SU:
-
Single-use
- TBPP:
-
Tris(2,4-di-tert-butylphenyl) phosphite
- VLP:
-
Virus-like particle
- WCB:
-
Working cell bank
- WVB:
-
Working virus bank
- WFI:
-
Water for injections
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Acknowledgments
The authors would like to thank M.Sc. Carmen Schirmaier and B.Sc. Valentin Jossen for the experimental work with the hADSCs in the Mobius® CellReady 3 L bioreactor and the MC suspension investigations. Gerhard Greller (Sartorius Stedim Biotech) and Mark Selker (Finesse Solutions, Inc.) we thank for the fruitful discussions.
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Kaiser, S.C., Kraume, M., Eibl, D., Eibl, R. (2015). Single-Use Bioreactors for Animal and Human Cells. In: Al-Rubeai, M. (eds) Animal Cell Culture. Cell Engineering, vol 9. Springer, Cham. https://doi.org/10.1007/978-3-319-10320-4_14
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