The shortage of food and freshwater sources threatens human health and environmental sustainability. Spirulina grown in seawater-based media as a healthy food is promising and environmentally friendly. This study used three machine learning techniques to identify important cultivation parameters and their hidden interrelationships and optimize the biomass yield of Spirulina grown in seawater-based media. Through optimization of hyperparameters and features, eXtreme Gradient Boosting, along with the recursive feature elimination (RFE) model demonstrated optimal performance and identified 28 important features. Among them, illumination intensity and initial pH value were critical determinants of biomass, which impacted other features. Specifically, high initial pH values (>9.0) mainly increased biomass but also increased nutrient sedimentation and ammonia (NH3) losses. Both batch and continuous additions could decrease nutrient losses by increasing their availability in the seawater-based media. When illumination intensity exceeded 200 μmol photons/m2/s, it amplified the growth of Spirulina by mitigating the light attenuation caused by a high initial inoculum level and counteracted the negative effect of low temperature (<25 °C). In large-scale cultivation, production efficiency would be reduced if illumination was not maintained at a high level. High salinity and sodium bicarbonate (NaHCO3) addition promoted carbohydrate accumulation, but suitable dilution could keep the required protein content in Spirulina with relatively low media and production costs. These findings reveal the interactive influence of cultivation parameters on biomass yield and help us determine the optimal cultivation conditions for large-scale cultivation of Spirulina-based seawater system based on a developed graphical user interface website.
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