Scaling challenges in microalgae cultivation: environmental effects on biomass productivity.

Microalgae are photosynthetic microorganisms that can convert CO₂ into valuable biomass for applications such as nutrition, biofuel production, and wastewater treatment. However, scaling from laboratory to industrial volumes remains empirical and costly. Scaling relationships are influenced by cultivation conditions (light, nutrients, reactor geometry), creating complex interactions that complicate bioprocess design. Here, we investigate the environmental dependence of scaling factors using a combined industrial and model-organism approach. We present two complementary case studies addressing distinct aspects of this challenge. Large-scale experiments with the marine oleaginous microalga Nannochloropsis oculata were conducted across photobioreactor volumes from 1 to 285 L under standardized conditions. Results showed relatively stable growth rates across volumes but significant scale- and geometry-dependent biomass productivity variations, indicating that simple volumetric extrapolation is insufficient for industrial design. To systematically explore condition-dependent effects that are impractical to test at large scale, we used Chlamydomonas reinhardtii as a model organism. Cultures grown in microplates (200 µL) and flasks (50 mL) across 25 light–nutrient combinations revealed that scaling factors are not constant: growth rate is highly nonlinear and difficult to scale whereas biomass yield ratios exhibited strong nutrients availability dependence with a linear scaling. These datasets were integrated into a predictive framework combining response surface methodology and dynamic growth models, enabling estimation of growth parameter according to varying environmental factors. This work highlights the need for environment-aware scale-up strategies and provides a methodology to improve multi-scale microalgae cultivation studies.