Computational evaluation of light propagation in cylindrical bioreactors for optogenetic mammalian cell cultures

Abstract

Optogenetic control of cellular pathways and gene circuits in mammalian cells is a new frontier in mammalian genetic engineering. As a low-cost, tunable, and reversible input, light is highly adept at spatiotemporal, orthogonal regulation of cellular behavior. However, light is absorbed and scattered as it travels through media and cells, and the applicability of optogenetics in larger mammalian bioreactors has not been determined. In this work, we computationally explore the size limit to which optogenetics can be applied in cylindrical bioreactors at relevant height-to-diameter ratios for mammalian cell culture. We model the propagation of light using the radiative transfer equation and consider changes in reactor volume, absorption coefficient, scattering coefficient, and scattering anisotropy. We observed sufficient light penetration for activation for bioreactor sizes of up to 80,000 L with maximal cell densities, with decreasing efficiency for larger bioreactors. For a 100,000 L bioreactor, we determined that lower cell densities of up to 1.5{middle dot}107 cells/mL can be supported. We conclude that optogenetics can be applied to bioreactors at an industrial scale and may be a valuable tool for specific biomanufacturing applications.