Modeling Living Cells Within Microfluidic Systems Using Cellular Automata Models

Abstract

Several computational models, both continuum and discrete, allow for the simulation of collective cell behaviors in connection with challenges linked to disease modeling and understanding. Normally, discrete cell modelling employs quasi-infinite or boundary-less 2D lattices, hence modeling collective cell behaviors in Petri dish-like environments. The advent of lab- and organ-on-a-chip devices proves that the information obtained from 2D cell cultures, upon Petri dishes, differs importantly from the results obtained in more biomimetic micro-fluidic environments, made of interconnected chambers and channels. However, discrete cell modelling within lab- and organ-on-a-chip devices, to our knowledge, is not yet found in the literature, although it may prove useful for designing and optimizing these types of systems. Consequently, in this study we focus on the establishment of a direct connection between the computer-aided designs (CAD) of microfluidic systems, especially labs- and organs-on-chips (and their multi-chamber and multi-channel structures), and the lattices for discrete cell modeling approaches aimed at the simulation of collective cell interactions, whose boundaries are defined directly from the CAD models. We illustrate the proposal using a quite straightforward cellular automata model, apply it to simulating cells with different growth rates, within a selected set of microsystem designs, and validate it by tuning the growth rates with the support of cell culture experiments and by checking the results with a real microfluidic system.

Large Area Microfluidic Bioreactor for Production of Recombinant Protein

“…On day 7, the growth culture medium with 5% (v/v) FBS was changed to the production medium with 0.5% (v/v) FBS, and samples were collected from the output of the device to determine the concentration of functional antibodies by specific indirect ELISA. The morphology of most cells was fusiform, with the appearance of borders that suggest a strong adhesion to the floor of the LM bioreactor [49], reaching 18 days of culture, a longer culture time than has been previously reported in the literature for microfluidic devices [28,45,[50][51][52][53].…”

“…The morphology of most cells was fusiform, with the appearance of borders that suggest a strong adhesion to the floor of the LM bioreactor [ 49 ], reaching 18 days of culture, a longer culture time than has been previously reported in the literature for microfluidic devices [ 28 , 45 , 50 , 51 , 52 , 53 ].…”

Skin-on-a-Chip Technology: Microengineering Physiologically Relevant In Vitro Skin Models

“…Hernando et al showed the importance of performing in silico studies for design optimization by modeling cell behaviors in OoC devices with different channel geometries. The group reported that the cell culture time required to fully exploit their OoC could be reduced by redesigning the chip’s inlet channel and chamber network [ 80 ]. Zahorodny-Burke et al used numerical simulations to evaluate the impact of the chip’s materials on the oxygen concentration in cell culture.…”

Glomerulus-on-a-Chip: Current Insights and Future Potential Towards Recapitulating Selectively Permeable Filtration Systems

“…This collaboration would ensure the definition of the confidence intervals for the data of GoC, the establishment of the predictive models for drug discovery research, and thus, the reduction of the development costs in drug discovery research. 102 , 103 …”