On-line biomass monitoring by capacitance measurement

Fehrenbach, Ralf; Comberbach, M.; Pétré, Jean

doi:10.1016/0168-1656(92)90077-m

Cited by 90 publications

(34 citation statements)

References 8 publications

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“…2,7,37 C M was in more recent studies found to be depending on viability and physiological state. 22,24 It also changes after viral infection and increases significantly after overexpression of cation channels, 30,49 being particularly affected by processes directly concerning cellular membrane properties, for example, exocytosis (loss of microvilli), viral release, and apoptosis. 20,29,38 One study reports that changes in C M might, in combination with a rather small drop in cell size, be responsible for changes in permittivity.…”

Section: Multifrequency Permittivity Measurements and Analysis Of Calmentioning

confidence: 99%

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Multifrequency permittivity measurements enable on‐line monitoring of changes in intracellular conductivity due to nutrient limitations during batch cultivations of CHO cells

Ansorge

Esteban

Schmid

2009

Biotechnology Progress

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Lab and pilot scale batch cultivations of a CHO K1/dhfr À host cell line were conducted to evaluate on-line multifrequency permittivity measurements as a process monitoring tool. The b-dispersion parameters such as the characteristic frequency (f C ) and the permittivity increment (De max ) were calculated on-line from the permittivity spectra. The dual-frequency permittivity signal correlated well with the off-line measured biovolume and the viable cell density. A significant drop in permittivity was monitored at the transition from exponential growth to a phase with reduced growth rate. Although not reflected in off-line biovolume measurements, this decrease coincided with a drop in OUR and was probably caused by the depletion of glutamine and a metabolic shift occurring at the same time. Sudden changes in cell density, cell size, viability, capacitance per membrane area (C M ), and effects caused by medium conductivity (r m ) could be excluded as reasons for the decrease in permittivity. After analysis of the process data, a drop in f C as a result of a fall in intracellular conductivity (r i ) was identified as responsible for the observed changes in the dual-frequency permittivity signal. It is hypothesized that the b-dispersion parameter f C is indicative of changes in nutrient availability that have an impact on intracellular conductivity r i . On-line permittivity measurements consequently not only reflect the biovolume but also the physiological state of mammalian cell cultures. These findings should pave the way for a better understanding of the intracellular state of cells and render permittivity measurements an important tool in process development and control.

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Section: Multifrequency Permittivity Measurements and Analysis Of Calmentioning

confidence: 99%

“…21 Permittivity measurements do also reflect changes in cell physiology which has been demonstrated for a wide variety of cell types. 5,9,13,[22][23][24] Cell physiology is most commonly described by the term ''physiological state.'' This term is defined by several variables that impart significant information about the cellular state.…”

Section: Introductionmentioning

confidence: 99%

Multifrequency permittivity measurements enable on‐line monitoring of changes in intracellular conductivity due to nutrient limitations during batch cultivations of CHO cells

Ansorge

Esteban

Schmid

2009

Biotechnology Progress

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“…Examples include cell cultivation on solid surfaces, on microcarriers in suspension, on porous glass carriers in fluidized bed reactors, and on porous discs in a fixed bed reactor. Reviewed cell types include bacteria, yeast, mammalian, and insect cells [Carvell, 2008, Carvell and Dowd, 2006, Ducommun et al, 2001, Fehrenbach et al, 1992, Noll and Biselli, 1998, Sarra et al, 1996, Zeiser et al, 1999.…”

Section: Impedance Spectroscopy As a Tool For Patmentioning

confidence: 99%

Process control in cell culture technology using dielectric spectroscopy

Justice¹,

Brix

Freimark³

et al. 2011

Biotechnology Advances

106

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“…Permittivity is a direct measure of the membrane enclosed volume fraction or biovolume of the cell suspension. These measurements also reflect changes in cell physiology which has been demonstrated for several cell types (Fehrenbach et al 1992;Noll and Biselli 1998;Zeiser et al 2000;Ducommun et al 2002;Cannizzaro et al 2003;Sarrafzadeh et al 2005).…”

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confidence: 99%

On-line monitoring of responses to nutrient feed additions by multi-frequency permittivity measurements in fed-batch cultivations of CHO cells

2010

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Changes in the nutrient availability of mammalian cell cultures are reflected in the bdispersion parameter characteristic frequency (f C ) and the on-line dual frequency permittivity signal. Multifrequency permittivity measurements were therefore evaluated in fed-batch cultivations of two different CHO cell lines. Similar responses to nutrient depletions and discontinuous feed additions were monitored in different cultivation phases and experimental setups. Sudden increases in permittivity and f C occurred when feed additions were conducted. A constant or declining permittivity value in combination with a decrease in f C indicated nutrient limitations. f C correlated well with changes in oxygen uptake rate when cell diameter remained constant, indicating that metabolic activity is reflected in the value of f C . When significant cell size changes occurred during the cultivations, the analysis of the b-dispersion parameters was rendered complex. For the application of our findings in other systems it will be hence required to conduct additional off-line measurements. Based on these results, it is hypothesized that multi-frequency permittivity measurements can give information on the intracellular or physiological state in fed-batch mode. Similar observations were made when using different cell lines and feeding strategies, indicating that the findings are transferable to other cell lines and systems. The results should lead to an improved understanding of routine fed-batch processes. Additional studies are, however, required to explore how these observations can be used for fed-batch process development and optimization.

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On-line biomass monitoring by capacitance measurement

Cited by 90 publications

References 8 publications

Multifrequency permittivity measurements enable on‐line monitoring of changes in intracellular conductivity due to nutrient limitations during batch cultivations of CHO cells

Multifrequency permittivity measurements enable on‐line monitoring of changes in intracellular conductivity due to nutrient limitations during batch cultivations of CHO cells

Process control in cell culture technology using dielectric spectroscopy

On-line monitoring of responses to nutrient feed additions by multi-frequency permittivity measurements in fed-batch cultivations of CHO cells

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