Use of glucose consumption rate (GCR) as a tool to monitor and control animal cell production processes in packed-bed bioreactors

Meuwly, F.; Papp, F.; Ruffieux, P.-A.; Bernard, A.; Kadouri, A.; Stockar, Urs von

doi:10.1016/j.jbiotec.2005.08.005

Cited by 19 publications

(11 citation statements)

References 29 publications

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“…Different concepts can be applied to determine the perfusion rate • (i) based on the cell density or cell specific perfusion rate (CSPR) • (ii) based on the availability of a main substrate in the culture • (iii) based on the concentration of a by-product in the culture • a combination of some or all items (i), (ii), (iii) When the perfusion process has been optimized resulting in a well-balanced process with efficient substrate usage and at steady state, (i), (ii) and (iii) converge. Hence a process, which has been developed for instance based on (i) can be controlled using (ii) for manufacturing as Meuwly reported (Meuwly et al 2006). …”

Section: Perfusion Rate Strategymentioning

confidence: 99%

“…The control of the perfusion rate can be based on the consumption of a main substrate present in the medium such as the glucose (Dowd et al 2001;Wang et al 2002;Meuwly et al 2006). From daily glucose concentration measurement, the perfusion rate is increased or decreased in order to maintain the residual glucose concentration constant in the culture.…”

Section: Perfusion Rate Strategy Based On Main Substrate Measurementmentioning

confidence: 99%

“…Several groups have reported monitoring the cell density indirectly by monitoring the consumption of oxygen or glucose (Kyung et al 1994;Meuwly et al 2006). …”

Section: Indirect Evaluation Of the Biomass Based On The Cell Metabolismmentioning

confidence: 99%

“…Cell arrest obtained by hypothermia or addition of a chemical, e.g. butyrate, has been reported for perfusion; given that the cell specific productivity is comparable or increased and that the protein quality is correct or improved (Ducommun et al 2002a;Chotteau et al 2001;Chen et al 2004;Kim et al 2004;Angepat et al 2005;Oh et al 2005;Meuwly et al 2006;Ahn et al 2008;Zhang et al 2014a). Another advantage of lowering the temperature under 35.5 C is that the proteolytic activity is lower compared to 37 C (Chuppa et al 1997).…”

Section: Cell Arrestmentioning

confidence: 99%

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Perfusion Processes

Chotteau

2014

Cell Engineering

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The interest for perfusion is increasing nowadays. This new focus has emerged from a synergy of a demand for disposable equipment and the availability of robust cell separation device, as well as the need for higher flexibility and lower investment cost. The cell separation devices mostly used today are based on filtration, i.e. alternating flow filtration, tangential flow filtration, spin-filter, or acceleration/gravity, i.e. inclined settler, centrifuge, acoustic settler. This paper gives an introduction to the basic concepts of perfusion and its practical implementation. It reviews the actual cell separation devices and describes the approaches used in the field to develop and optimize the perfusion processes.

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Section: Perfusion Rate Strategymentioning

confidence: 99%

Section: Perfusion Rate Strategy Based On Main Substrate Measurementmentioning

confidence: 99%

“…Several groups have reported monitoring the cell density indirectly by monitoring the consumption of oxygen or glucose (Kyung et al 1994;Meuwly et al 2006). …”

Section: Indirect Evaluation Of the Biomass Based On The Cell Metabolismmentioning

confidence: 99%

Section: Cell Arrestmentioning

confidence: 99%

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Perfusion Processes

Chotteau

2014

Cell Engineering

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“…As a solution to the lack of direct CQA measurements some studies use information on culture parameters that can conveniently be measured to indirectly estimate CQAs in fermentation and biopharmaceutical bioreactors (Dorresteijn et al, 1996;Junker and Wang, 2006;Meuwly et al, 2006;Papas et al, 2007), but applications for TE bioreactors and especially for perfusion bioreactors are limited. For example, Santoro et al (2011) used isothermal microcalorimeters in a static culture system to correlate heat production caused by biological processes to cell number and proliferation rate.…”

Section: Introductionmentioning

confidence: 99%

Model‐based cell number quantification using online single‐oxygen sensor data for tissue engineering perfusion bioreactors

Lambrechts

Papantoniou

Sonnaert

et al. 2014

Biotech & Bioengineering

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Online and non-invasive quantification of critical tissue engineering (TE) construct quality attributes in TE bioreactors is indispensable for the cost-effective up-scaling and automation of cellular construct manufacturing. However, appropriate monitoring techniques for cellular constructs in bioreactors are still lacking. This study presents a generic and robust approach to determine cell number and metabolic activity of cell-based TE constructs in perfusion bioreactors based on single oxygen sensor data in dynamic perfusion conditions. A data-based mechanistic modeling technique was used that is able to correlate the number of cells within the scaffold (R(2) = 0.80) and the metabolic activity of the cells (R(2) = 0.82) to the dynamics of the oxygen response to step changes in the perfusion rate. This generic non-destructive measurement technique is effective for a large range of cells, from as low as 1.0 × 10(5) cells to potentially multiple millions of cells, and can open-up new possibilities for effective bioprocess monitoring.

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NMR metabolomics to study the metabolic response of human osteoblasts to non‐poled and poled poly (L‐lactic) acid

Araújo

Carneiro

Marinho

et al. 2019

Magnetic Reson in Chemistry

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Untargeted nuclear magnetic resonance (NMR) metabolomics was employed, for the first time to our knowledge, to characterize the metabolome of human osteoblast (HOb) cells and extracts in the presence of non‐poled or negatively poled poly‐L‐lactic acid (PLLA). The metabolic response of these cells to this polymer, extensively used in bone regeneration strategies, may potentially translate into useful markers indicative of in vivo biomaterial performance. We present preliminary results of multivariate and univariate analysis of NMR spectra, which have shown the complementarity of lysed cells and extracts in terms of information on cell metabolome, and unveil that, irrespective of poling state, PLLA‐grown cells seem to experience enhanced oxidative stress and activated energy metabolism, at the cost of storage lipids and glucose. Possible changes in protein and nucleic acid metabolisms were also suggested, as well as enhanced membrane biosynthesis. Therefore, the presence of PLLA seems to trigger cell catabolism and anti‐oxidative protective mechanisms in HOb cells, while directing them towards cellular growth. This was not sufficient, however, to lead to a visible cell proliferation enhancement in the presence of PLLA, although a qualitative tendency for negatively poled PLLA to be more effective in sustaining cell growth than non‐poled PLLA was suggested. These preliminary results indicate the potential of NMR metabolomics in enlightening cell metabolism in response to biomaterials and their properties, justifying further studies of the fine effects of poled PLLA on these and other cells of significance in tissue regeneration strategies.

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Use of glucose consumption rate (GCR) as a tool to monitor and control animal cell production processes in packed-bed bioreactors

Cited by 19 publications

References 29 publications

Perfusion Processes

Perfusion Processes

Model‐based cell number quantification using online single‐oxygen sensor data for tissue engineering perfusion bioreactors

NMR metabolomics to study the metabolic response of human osteoblasts to non‐poled and poled poly (L‐lactic) acid

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