Open-loop control of the biomass concentration within the growth phase of recombinant protein production processes

Jenzsch, Marco; Gnoth, Stefan; Beck, Matthias; Kleinschmidt, Martin; Simutis, Rimvydas; Lübbert, Α.

doi:10.1016/j.jbiotec.2006.06.004

Cited by 69 publications

(44 citation statements)

References 2 publications

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“…Thus, the optimum leucine utilization of E. coli K12 ER2507 as y X/Leu = 19.8 g CDM (g leucine) −1 was achieved at the lowest examined leucine and glucose concentrations in the cultivation medium above zero. These findings highlight the necessity for a new HCDC strategy, presented as iHCDC lacking the initial batch phase with high glucose concentration to reduce acetate formation and increased process reproducibility as investigated by Jenzsch et al [14]. Supplying amino acids with the base iHCDC allows the cultivation of amino acid auxotrophic strains up to high cell densities.…”

Section: Discussionmentioning

confidence: 84%

An improved high cell density cultivation—iHCDC—strategy for leucine auxotrophic Escherichia coli K12 ER2507

Beckmann

Hohmann

Eickmeyer

et al. 2017

Engineering in Life Sciences

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An improved high cell density cultivation-iHCDC-strategy for leucine auxotrophic Escherichia coli K12 ER2507Fed-batch processes are commonly used tools in high cell density cultivation of Escherichia coli. However, the setup of a fed-batch process can be challenging, especially when working with genetically modified strains. This work deals with the design of a specific strategy for the leucine auxotrophic E. coli strain K12 ER2507 that is of interest for arabinose-inducible gene expression systems due to its ara-14 mutation. To set up this process the optimum yield coefficient of biomass from leucine was determined by use of a design of experiments tool. Unfortunately, the yield coefficient is negatively influenced by both leucine and glucose concentrations. Furthermore, an inhibitory effect of leucine reduced the specific growth rate even at low concentration. Under consideration of these problems, an improved high cell density cultivation (iHCDC) for E. coli K12 ER2507 was established. The start medium was set up without any C-source to omit a batch phase with high glucose concentration and substrate feeding was initiated directly upon inoculation. Due to the poor solubility of leucine in feed medium, the amino acid was dissolved in the base. With the improved high cell density cultivation process a final cell density of more than 90 g/L was obtained reproducibly.

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Section: Discussionmentioning

confidence: 84%

An improved high cell density cultivation—iHCDC—strategy for leucine auxotrophic Escherichia coli K12 ER2507

Beckmann

Hohmann

Eickmeyer

et al. 2017

Engineering in Life Sciences

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“…The quality attributes of the seed culture that contribute most to undesirable production phase variability in product yield and quality are batch-to-batch differences in biomass concentration and specific biomass growth rate, thus PAT strategies that target these cell culture attributes would prove useful. For example, Jenzsch et al (2006) induced a seed organism to exert feedback control via control of biomass growth rate. Control of growth rate dampens process and subsequent product variability.…”

Section: Seed Train and Inoculationmentioning

confidence: 99%

“…The cell culture process also generates a variety of other real-time data from cell culture (not product) attributes (Nyberg et al, 2008) that could in theory be exploited for control if sufficient process understanding exists. For example, some researchers have successfully applied ''artificial neural networks'' to oxygen uptake rate data to estimate total biomass, a cell culture attribute that can impact the ultimate product (Jenzsch et al, 2006). Another recent application involved development of in-line probes for dielectric spectroscopic measurement of viable cell volume for bioreactor control (Carvell and Dowd, 2006).…”

Section: Read Et Al: Pat For Biopharmaceutical Productsmentioning

confidence: 99%

Process analytical technology (PAT) for biopharmaceutical products: Part I. concepts and applications

Read¹,

Park²,

Shah³

et al. 2009

Biotech & Bioengineering

201

118

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Process analytical technology (PAT) has been gaining momentum in the biotech community due to the potential for continuous real-time quality assurance resulting in improved operational control and compliance. In this two part series, we address PAT as it applies to processes that produce biotech therapeutic products. In the first part, we address evolution of the underlying concepts and applications in biopharmaceutical manufacturing. We also present a literature review of applications in the areas of upstream and downstream processing to illustrate how implementation of PAT can help realize advanced approaches to ensuring product quality in real time. In the second part, we will explore similar applications in the areas of drug product manufacturing, rapid microbiology, and chemometrics as well as evolution of PAT in biotech processing.

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“…That is why they are interesting testing benches for non-linear and intelligent control techniques. Several techniques have been proposed [1][2][3] and tested by simulation, but only few have been implemented on real bioprocesses.…”

Section: Introductionmentioning

confidence: 99%

Intelligent Techniques for Fed-Batch Bioprocess Control

Caramihai

Severin

2011

KEM

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-Bioprocesses are appreciated as difficult to control because their dynamic behavior is highly nonlinear and time varying, in particular, when they are operating in fed batch mode. For this kind of bioprocess where the mathematical model contains many structured and unstructured uncertainties, we try to combine different intelligent techniques based on natural syllogisms of these techniques. In order to obtain a high bioprocess productivity it is essential to accord the benefits of the classical control strategy (i.e. the analytical determination of the optimum) with the subjective bioprocess characterization (due to the human expert) in order to diminish the on line information scarcity. The research objective of this study was to develop an appropriate control method for a new complex bioprocess and to implement it on a laboratory plant. Hence, an intelligent control structure has been designed in order to produce biomass and to maximize the specific growth rate..

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Open-loop control of the biomass concentration within the growth phase of recombinant protein production processes

Cited by 69 publications

References 2 publications

An improved high cell density cultivation—iHCDC—strategy for leucine auxotrophic Escherichia coli K12 ER2507

An improved high cell density cultivation—iHCDC—strategy for leucine auxotrophic Escherichia coli K12 ER2507

Process analytical technology (PAT) for biopharmaceutical products: Part I. concepts and applications

Intelligent Techniques for Fed-Batch Bioprocess Control

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