Embedding response surfaces in kinetic models predicts microalgae growth across light and nutrient gradients

Microalgae are promising cell factories for sustainable production of biofuel, high-value compounds, and wastewater bioremediation. However, their industrial deployment requires robust prediction of biomass productivity across the wide range of light and nutrient conditions encountered in photobioreactors. Mechanistic models typically assume constant growth parameters, limiting their accuracy across varying cultivation conditions. Conversely, response surface methodology (RSM) captures parameter variability across conditions but lacks dynamics and can yield biologically implausible predictions under untested cultivation conditions. This study introduces a hybrid model that embeds biologically interpretable Monod-type surfaces into a logistic growth model, allowing maximum growth rate and carrying capacity to vary independently and continuously with light intensity and nutrient availability. Validated on 1315 growth curves of Chlamydomonas reinhardtii grown mixotrophically, the model predicts full time series under previously untested light–nutrient combinations at 2 scales: flask (50 mL, R² = 0.94) and microplate (200 µL, R² = 0.84), consistently outperforming three established mechanistic models. Six global parameters replace up to 50 condition-specific ones, substantially reducing the experimental effort. We further demonstrate that microplate-derived parameter surfaces can be mapped onto flask-scale surfaces through simple transformations (R² ≥ 0.94), providing a basis for scale-up from high-throughput data to bench-scale cultivation. The framework offers a practical tool to optimize microalgal cultivation at laboratory scale, with preliminary evidence supporting its transferability across culture volumes.