HEK293 Cell-Based Bioprocess Development at Bench Scale by Means of Online Monitoring in Shake Flasks (RAMOS and SFR)

Methods Mol Biol. 2020:2095:83-103. doi: 10.1007/978-1-0716-0191-4_6.

Abstract

The platforms for bioprocess development have been developed in parallel to the needs of the manufacturing industry of biopharmaceuticals, aiming to ensure the quality and safety of their products. In this sense, Quality by Design (QbD) and Process Analytical Technology (PAT) have become the pillars for quality control and quality assurance.A new combination of Shake Flask Reader (SFR) and Respiration Activity Monitoring System for online determination of OTR and CTR (RAMOS) allows online monitoring of main culture parameters needed for bioprocess development (pH, pO2, OTR, CTR, and QR) as presented below. Eventually, a case study of the application of the combination of SFR-RAMOS system is presented. The case study discloses the optimization of HEK293 cells cultures through the manipulation of their metabolic behavior.

Keywords: Bioprocess optimization; Culture monitoring; Glucose and lactate co-consumption; HEK293 cells; Metabolic phases; OTR; Ramos; SFR.

MeSH terms

  • Batch Cell Culture Techniques / instrumentation*
  • Batch Cell Culture Techniques / methods*
  • Bioreactors
  • Cell Count
  • Cell Respiration
  • Cell Survival / physiology
  • Culture Media / chemistry
  • Culture Media / metabolism*
  • Glucose / metabolism
  • HEK293 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Lactic Acid / metabolism
  • Oxygen

Substances

  • Culture Media
  • Lactic Acid
  • Glucose
  • Oxygen