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Feedback control systems01:26

Feedback control systems

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Feedback control systems are categorized in various ways based on their design, analysis, and signal types.
Linear feedback systems are theoretical models that simplify analysis and design. These systems operate under the principle that their output is directly proportional to their input within certain ranges. For instance, an amplifier in a control system behaves linearly as long as the input signal remains within a specific range. However, most physical systems exhibit inherent nonlinearity...
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Automated Raman feed-back control of multiple supplemental feeds to enable an intensified high inoculation density

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This study demonstrates inline Raman spectroscopy for real-time monitoring of biologics manufacturing. This enables automated control of intensified fed-batch cultures, achieving high product titers and cell densities.

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Area of Science:

  • Biotechnology and bioprocessing
  • Process analytical technology (PAT)
  • Mammalian cell culture

Background:

  • Intensified biologics manufacturing processes aim for higher titers and shorter timelines than traditional fed-batch cultures.
  • Implementing intensified processes requires novel control strategies and continuous process monitoring.
  • Chinese hamster ovary (CHO) cell culture is a key platform for biologics production.

Purpose of the Study:

  • To develop and implement a continuous monitoring and automated control strategy for intensified fed-batch CHO cell cultures.
  • To utilize inline Raman spectroscopy for real-time monitoring of critical nutrients and metabolites.
  • To maintain optimal nutrient levels and maximize product concentration in high inoculation density cultures.

Main Methods:

  • Inline Raman spectroscopy was employed for real-time monitoring of glucose, phenylalanine, and methionine concentrations.
  • Partial least squares (PLS) models were developed to correlate spectral data with metabolite concentrations.
  • Automated feed-rate adjustments for three supplemental feeds were implemented based on continuous monitoring data.
  • Five different glutamine synthetase piggyBac® CHO clones were cultured using an intensified high inoculation density fed-batch platform process.

Main Results:

  • Continuous monitoring enabled automated feed-rate adjustments to maintain glucose, phenylalanine, and methionine at desired setpoints.
  • Other nutrient concentrations were maintained at acceptable levels across all cultured clones.
  • High viable cell concentrations were achieved, indicating no detrimental effects from the feeding strategy.
  • Product concentrations between 5 and 8.3 g/L were achieved over 12 days of culture.

Conclusions:

  • Inline Raman spectroscopy coupled with automated control is effective for intensified fed-batch CHO cell cultures.
  • The developed strategy supports high cell densities and achieves significant product concentrations.
  • This approach facilitates efficient and robust biologics manufacturing using intensified processes.