Bioreactor Analyte Characterization and Intracellular Metabolite Modeling for Understanding Impacts

Bioprocessing is a complex process during which engineered cells are used as manufacturing plants for generating complex protein biotherapeutics. This process has inherent biological variability, and changes in bioreactor conditions and/or process parameters can have unexpected impacts to the cells’ growth parameters and protein product quality. To better understand the relationship between process parameters and product quality, we are developing mass spectrometry-based approaches to quantitate bioreactor media metabolite concentrations and heavy isotopic labelling models to map the intracellular metabolic flux within the cell. The changes in both the extracellular environment and intracellular flux status can then be associated with product quality outcomes using multi-variate data analysis (MVDA) approaches. Along with the mechanistic model for the intracellular metabolic state, these approaches could be used to better predict and maintain production quality outcomes through better controlled bioreactor media conditions.