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

## TL;DR

This paper develops and validates three control strategies to regulate the ratio of two cell populations with genetic toggle switches, considering practical constraints, using stochastic simulations.

## Contribution

It introduces novel control methods for cell population ratios that incorporate realistic experimental constraints and validates them through in-silico simulations.

## Key findings

- Successful regulation of cell population ratios in simulation.
- Control strategies accommodate physical and technological constraints.
- Validated effectiveness of controllers in stochastic agent-based models.

## Abstract

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.