Microbioreactor array for full-factorial analysis of provision of multiple soluble factors in cellular...

We report a scalable microbioreactor architecture which uses nested dilution structures to generate a full-factorial array of cell culture conditions. The proof-of-concept microbioreactor array produces all combinations of three concentration levels of two soluble factors (3(2) = 9 unique conditions in total). The full-factorial design is especially useful in optimizing soluble factor treatments and elucidating interaction effects between factors which are otherwise difficult to deconvolute. By nesting hierarchical levels of dilution structures, and designing the device purely by resistive flow (no valves are required), suitable diffusive mixing of growth factors up to 40 kDa is achieved such that the nine culture conditions can be generated and maintained from a minimal number of stock solutions.