Translating Blue Light Stimulation From Batch to Perfusion: Process and Intracellular Metabolic Analysis

ABSTRACT

Improving cell‐specific productivity remains a central objective in biopharmaceutical manufacturing. In this study, the effect of blue light illumination on IgG1‐producing CHO DP‐12 cells was systematically evaluated across batch, fed‐batch, and perfusion cultivations in controlled 3 L bioreactor systems. Blue light exposure consistently increased cell‐specific monoclonal antibody productivity by approximately 30%–37% in batch and fed‐batch processes and up to 13% overall (and up to 125% in specific phases) in perfusion cultures, despite variable effects on growth and viable cell density. Metabolic characterization revealed increased lactate production under illumination, while glucose consumption remained almost unchanged. Intracellular metabolite analysis showed no consistent perturbations in central carbon metabolism but indicated generally reduced amino acid pools, suggesting enhanced utilization for protein synthesis. Although adenylate energy charge was slightly reduced in illuminated cultures, values remained within physiologically functional ranges. Notably, redox analysis based on glutathione ratios and redox potential pointed to a more reduced intracellular environment under blue light, contradicting the initial hypothesis of light‐induced oxidative stress. Overall, the data indicate that blue light illumination induces a robust metabolic phenotype characterized by enhanced productivity without detrimental metabolic stress. Given its compatibility with standard bioreactor operation and its non‐invasive nature, optimized blue light exposure represents a promising strategy for process intensification in industrial biopharmaceutical production.