Microfluidic-driven viral infection on cell cultures: Theoretical and experimental study

Advanced cell culture systems creating a controlled and predictable microenvironment together with computational modeling may be useful tools to optimize the eciency of cell infections. In this paper, we will present a phenomenological study of a virus-host infection system, and the development of a multilayered microfuidic platform used to accurately tune the virus delivery from a diusive-limited regime to a convective-dominated regime. Mathematical models predicted the convective-diusive regimes developed within the system itself and determined the dominating mass transport phenomena. Adenoviral vectors (AdVs) carrying the EGFP transgene were used at dierent multiplicities of infection (MOI) to infect multiple cell types, both in standard static and in perfused conditions. Our results validate the mathematical models and demonstrate how the infection processes through perfusion via microfuidic platform led to an enhancement of adenoviral infection efficiency even at low MOIs. This was particularly evident at the longer time points, since the establishment of steady-state condition guaranteed a constant viral concentration close to cells, thus strengthening the efciency of infection. Finally, we introduced the concept of eective MOI, a more appropriate variable for microfuidic infections that considers the number of adenoviruses in solution per cell at a certain time.