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

Pieter Jan Theodoor Brorens¹, Marcel Ottens¹, Cees Haringa¹

¹Faculty of Applied Sciences, Department of Biotechnology, Delft University of Technology, Delft, Netherlands.

Biotechnology and Bioengineering

|July 14, 2026

Summary

This study compares bioreactor designs for cultivated meat production, finding that stirred tank reactors and airlift reactors show promise for scale-up. The research provides a framework to accelerate bioreactor selection for sustainable meat alternatives.

Keywords:

Monte Carlo simulation bioreactor design cultivated meat scale‐up timescale analysis

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Area of Science:

Biotechnology
Chemical Engineering
Food Science

Background:

Cultivated meat offers a sustainable alternative to conventional livestock.
Scaling up cultivated meat production faces significant bioreactor design challenges for mammalian cell suspension cultures.

Purpose of the Study:

To comparatively analyze stirred tank reactors (STRs), bubble columns (BCs), and airlift reactors (ALRs) for large-scale cultivated meat production.
To develop a predictive framework for evaluating bioreactor performance and identifying scale-up limitations.

Main Methods:

A Monte Carlo-based framework combined with timescale analysis was used to evaluate mixing and gas-liquid mass transfer.
Simulations assessed reactor performance up to 160 m³ against constraints like oxygen transfer, CO2 accumulation, and cell damage.
Hypothetical killing volume (HKV) modeled bubble-induced cell damage.

Main Results:

Mixing and oxygen transfer are primary limitations across all reactor types at large scales.
Bubble columns and airlift reactors face additional constraints related to gas-phase depletion and downcomer residence times.
Incorporating shear protectants like Pluronic F-68 and geometric optimization of STRs/ALRs significantly improved predicted performance, reaching up to 119 g L⁻¹.

Conclusions:

The developed framework enables rapid screening of bioreactor designs without complex mass balance calculations.
This approach provides insights into scale-up risks and guides experimental validation for cultivated meat process development.
Optimized STRs and ALRs show potential for efficient, large-scale cultivated meat production.