Comparative Analysis of Bioreactor Design and Scale-Up for Cultivated Meat Using Monte Carlo-Based Timescale Modeling.

Authors

Pieter Jan Theodoor Brorens, Marcel Ottens, Cees Haringa

Published in

Biotechnology and bioengineering. Jul 14, 2026. Epub Jul 14, 2026.

Abstract

Cultivated meat offers a sustainable alternative to conventional livestock production but faces significant scale-up challenges, particularly in bioreactor design for mammalian cell suspension cultures. This study presents a comparative analysis of stirred tank reactors (STR), bubble columns (BC), and airlift reactors (ALR) to assess their suitability for large-scale cultivated meat production. We introduce a Monte Carlo-based framework combined with timescale analysis to evaluate key mechanisms like mixing and gas-liquid mass transfer across reactor scales up to $160m^3$ . Feasible operating windows were identified by filtering millions of simulated scenarios against constraints such as oxygen transfer, ${\text{CO}}_2$ accumulation, and bubble-induced cell damage, modeled via hypothetical killing volume (HKV). Results indicate that mixing and oxygen transfer are primary limitations for all reactor types, with BCs and ALRs further constrained by gas-phase depletion and downcomer residence times at large scales. Incorporating shear protectants like Pluronic F-68 significantly expands the design space, enabling higher cell concentrations. Geometric optimization of STRs and ALRs improved predicted performance up to $119{\text{g L}}^{-1}$ . This framework enables rapid screening of bioreactor designs without solving full mass balances, providing insights into scale-up risks and guiding experimental validation for cultivated meat process development.

PMID:
42444356
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

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