Systems and methods for treating media in large-scale bioreactors can include a method of using a large-scale bioreactor system. The method can include (a) mixing a mixture of at least cells, and media in a bioreactor, and (b) removing a portion of the media through an output port of the bioreactor. The method can also include (c) retaining the cells within the bioreactor using a screen covering the port. The method can also include (d) receiving a second media, which may in some examples include the portion of the first media removed from the bioreactor, into a media preparation container external to the bioreactor, (e) treating the second media within the media preparation container to produce oxygenated media within a threshold pH range, and (f) introducing the oxygenated media into the bioreactor using a return port of the bioreactor.