Nonlinear control of competitive mixed-culture bioreactors via specific cell adhesion

A nonlinear control strategy for continuous biological reactors with competitive mixed-cultures is proposed. The desired operating point, which corresponds to coexistence of the two cell populations, is unstable because the cellular growth rates differ. We utilize specific cell adhesion to separate and selectively recycle the slower growing population in order to stabilize the desired coexistence steady state. The recycle loop is operated periodically so that the adhesion column can be regenerated after each sample is processed. The nonlinear control law is derived by applying input-output linearization to an approximate dynamic model that assumes continuous separation of the cell populations. A nonlinear closed-loop observer is used to generate one-time-delay-ahead predictions of the measured cell concentrations and the unmeasured substrate concentration. The efficacy of the proposed control strategy is evaluated via simulation.