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Chapter 50 : Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture

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Abstract:

This chapter reviews research on existing and new sampling and sensor technologies for monitoring fermentations and mammalian cell culture in the last decade. New technologies are discussed, as well as advances in existing technologies. Each one of these technologies contributes to enabling process analytical technology (PAT) and increased process understanding. In cell culture processes, some technologies have been developed to automate sampling and analysis from bioreactors. Several studies showed comparability between the manual and automated sampling methods. Automated sampling showed pH results comparable with those of manual sampling, with 80% of the samples showing values within 0.05 pH unit and 100% within 0.1 pH unit. In addition to autosampling systems, another technology that can be used to deliver samples from bioreactors for analysis is flow injection analysis (FIA). The sample is taken using in situ filtration ceramic probes to a detection system based on amperometric, potentiometric, fluorescence, chemiluminescence, turbidity, or absorption measurements. Many companies have developed disposable bioreactors for bacterial fermentations and mammalian cell cultures. Disposable sensors have been used in a number of bioreactor applications, including shake flasks, microplates, miniature bioreactors (MBRs), and single-use bioreactors. Shake flasks are one of the most widely used tools for process development.

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50

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Figures

Image of FIGURE 1a
FIGURE 1a

Nova BioProfile FLEX system. (A) BioProfile FLEX unit (courtesy of John Balsavich, Nova Biomedical). (B) Internal modules (courtesy of John Balsavich, Nova Biomedical). (C) Schematic of fluid flow paths through system. The sample flows from the bioreactor to the RVM to the switching pumping module (SPM) before reaching the BioProfile FLEX. Waste flows from the BioProfile FLEX to the SPM to waste container (W). Cleaning solution (C) and saline flush (F) flow from their respective containers to SPM manifolds to RVM fluidics, following the sample path through the system to the waste container. (Adapted from reference .).

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50
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Image of FIGURE 1b
FIGURE 1b

Nova BioProfile FLEX system. (A) BioProfile FLEX unit (courtesy of John Balsavich, Nova Biomedical). (B) Internal modules (courtesy of John Balsavich, Nova Biomedical). (C) Schematic of fluid flow paths through system. The sample flows from the bioreactor to the RVM to the switching pumping module (SPM) before reaching the BioProfile FLEX. Waste flows from the BioProfile FLEX to the SPM to waste container (W). Cleaning solution (C) and saline flush (F) flow from their respective containers to SPM manifolds to RVM fluidics, following the sample path through the system to the waste container. (Adapted from reference .).

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50
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Image of FIGURE 2
FIGURE 2

Groton ARS System. (A) Schematic of the Groton ARS. Cleaning flow cleans all parts of the unit up to each RVI, including the sampling line to the analytical device. The sample is pulled through the RVI into the sampling valve and then out to an analytical instrument. Adapted from reference . (B) Picture of the ARS system connected to six bioreactors. (Courtesy of Daniel Abramzon, Genentech, Inc.)

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50
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Image of FIGURE 3
FIGURE 3

Regions of the spectra and their wavelengths.

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50
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Image of FIGURE 4
FIGURE 4

Bioreactor with in situ dark-field microscopy probe (IDMP). Adapted from reference .

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50
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Image of FIGURE 5
FIGURE 5

Disposable-sensor applications. (A) Shake flasks (adapted from reference ); (B) microplates (adapted from reference ).

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50
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Image of FIGURE 6
FIGURE 6

Potential steps required for the evaluation and implementation of a new PAT.

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50
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Tables

Generic image for table
TABLE 1

Variables measured using autosampling technologies

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50
Generic image for table
TABLE 2

Summary of NIRS in situ probe monitoring applications

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50
Generic image for table
TABLE 3

Summary of Raman spectroscopy in situ probe monitoring applications

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50
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TABLE 4

Summary of MIRS in situ probe monitoring applications

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50
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TABLE 5

In situ optical density probes in bacterial fermentations and mammalian cell culture applications

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50
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TABLE 6

Disposable-sensor evaluations

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50
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TABLE 7

Multivariable analysis review

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50
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TABLE 8

Examples of new technologies in downstream applications

Citation: Arroyo A. 2010. Advances in Sensor and Sampling Technologies in Fermentation and Mammalian Cell Culture, p 700-718. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch50

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