Modeling and Control of Single-Cell Migration Induced by a Chemoattractant-Loaded Microbead.

Cell migration plays an essential role in cancer cell study. Investigation of a novel method for controlling cell migration movement can help develop new therapeutic strategies. In this paper, a chemoattractant-loaded microbead, which is controlled by optical tweezers, is used to stimulate a target cell to accomplish automated migration along a desired path while avoiding obstacles. Models of both tweezers-bead and bead-cell interactions are investigated. A dual closed-loop control strategy is proposed, which includes an inner tweezers-bead control loop and an outer bead-cell control loop. A proportional-integral feedback plus feedforward controller is used to control the inner loop, and an active disturbance rejection controller is used for the outer loop, which can address the cell migration modeling errors and unknown external disturbances. A traffic rule based on interference-clearing mechanism is also proposed to reduce external disturbances on the system by preventing other particles from interfering with the migration process. The effectiveness of the proposed control approach is verified by simulations and experiments on migrating leukemia cancer cells.