Published August 13, 2021 | Version v1
Journal article Open

Optimization of muscle cell culture media using nonlinear design of experiments

  • 1. Department of Chemical Engineering, University of California, Davis, California, USA
  • 2. Department of Viticulture and Enology, University of California, Davis, California, USA
  • 3. Departments of Neurobiology, Physiology and Behavior and Physiology and Membrane Biology, University of California, Davis, California, USA


Optimizing media for biological processes, such as those used in tissue engineering and cultivated meat production, is difficult due to the extensive experimentation required, number of media components, nonlinear and interactive responses, and the number of conflicting design objectives. Here we demonstrate the capacity of a nonlinear design-of-experiments (DOE) method to predict optimal media conditions in fewer experiments than a traditional DOE. The approach is based on a hybridization of a coordinate search for local optimization with dynamically adjusted search spaces and a global search method utilizing a truncated genetic algorithm using radial basis functions to store and model prior knowledge. Using this method, we were able to reduce the cost of muscle cell proliferation media while maintaining cell growth 48 h after seeding using 30 common components of typical commercial growth medium in fewer experiments than a traditional DOE (70 vs. 103). While we clearly demonstrated that the experimental optimization algorithm significantly outperforms conventional DOE, due to the choice of a 48 h growth assay weighted by medium cost as an objective function, these findings were limited to performance at a single passage, and did not generalize to growth over multiple passages. This underscores the importance of choosing objective functions that align well with process goals.


This document is the Authors Accepted Manuscript (or "postprint") and may have minor differences from the Version of Record due to final copyedits. The final published version can be accessed at



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