Analysis and control of genetic toggle switches subject to periodic multi-input stimulation

In this letter, we analyze a genetic toggle switch recently studied in the literature where the expression of two repressor proteins can be tuned by controlling two different inputs, namely the concentration of two inducer molecules in the growth medium of the cells. Specifically, we investigate the dynamics of this system when subject to pulse-width modulated (PWM) input. We provide an analytical model that captures qualitatively the experimental observations reported in the literature and approximates its asymptotic behavior. We also discuss the effect that the system parameters have on the prediction accuracy of the model. Moreover, we propose a possible external control strategy to regulate the mean value of the fluorescence of the reporter proteins when the cells are subject to such periodic forcing.Comment: Preprint accepted for publication on L-CSS (First submission 31.05.2018, accepted 21.08.2018

Ratiometric control for differentiation of cell populations endowed with synthetic toggle switches

We consider the problem of regulating by means of external control inputs the ratio of two cell populations. Specifically, we assume that these two cellular populations are composed of cells belonging to the same strain which embeds some bistable memory mechanism, e.g. a genetic toggle switch, allowing them to switch role from one population to another in response to some inputs. We present three control strategies to regulate the populations' ratio to arbitrary desired values which take also into account realistic physical and technological constraints occurring in experimental microfluidic platforms. The designed controllers are then validated in-silico using stochastic agent-based simulations.Comment: Accepted to CDC'201