Dynamic Modeling And Control Of Cell Migration Using A Robot-Tweezers Cell Manipulation System

Cell migration is a fundamental biological phenomenon that plays a crucial role in a variety of physiological and pathological processes. Over the past few decades, numerous research studies on cell migration have been performed. However, information is still limited on the mechanisms underlying this complex process. The lack of an efficient cell manipulation tool at the single-cell level hinders the quantitative analysis of cell chemotaxis. In this thesis, a cell migration inducing system with robotically controlled optical tweezers is developed. This system enables the study of cell migration mechanisms. This thesis is performed according to the following perspectives.First, an approach that utilizes optical tweezers manipulation to stimulate cell migration is proposed. Specially fabricated polylactic-co-glycolic acid beads are used in this approach. These beads can release chemoattractant molecules in the liquid environment to form a concentration gradient. Optical tweezers are used as micro-manipulators on the microsource beads to stimulate cell migration. This approach mimics the in vivo environment to stimulate cell migration in vitro. Experiments are performed to demonstrate the effectiveness of the proposed approach.Second, the cell migration mechanisms are probed by using an optical tweezers-based cell manipulation system. A unique method that can quantitatively measure the cell protrusion force is developed based on the platform. A cell migration model is developed and includes the following aspects:the forces affecting the cell are analyzed, and a dynamic model of the migrating cell is developed; and a theoretical model that explicitly reveals the relationship between the cell migration velocity and gradient is proposed. This model explains for the first time how concentration affects cell motility.Third, an autonomous cell migration control system with robotically controlled optical tweezers is developed. The control strategy utilizes the natural features of the cell by stimulating cell migration in a concentration gradient field. A geometric model is established, and a unified controller is designed. With the proposed controller, the microsource beads can be confined near the cell to stimulate cell migration, thereby avoiding collisions in the manipulation. Simulations and experiments are performed to demonstrate the effectiveness of the proposed approach. In summary, the proposed optical tweezers-based cell manipulation tool provides a novel approach for investigating cell migration. Measurement of the protrusion force provides insights into the mechanisms of cell migration. The development of the migration model reveals the relationship between the concentration gradient and cell motility. The automatic cell migration control system not only benefits biological research on cell migration but is also the first step toward the development of migration-based applications in biomedical engineering. This thesis will contribute to the current knowledge on cell migration mechanisms and lay a solid foundation for the further development of target therapy.