Robot-Assisted Automated Manipulation of Microparticle in Complex Biological Micro-Environment

Abstract

Rapid advances in biological sciences and nanotechnology have led to the requirement of robotics and automation at micro scale, and thus open up new challenges to robotic manipulation of cells or nanoparticles in micro-environment. Existing manipulation methodologies are designed under ideal conditions without considering system uncertainties or only addressed specified uncertainty issues. In reality, microparticles used in biological research are usually steered in a complex environment with multifarious uncertainties. In this thesis, disturbance observer based robust control methods are developed to precisely manipulate microparticles in cancer treatment related investigation. First, a microparticle equipped with optical tweezers is robotically controlled to mimic cell migration in vivo. Second, a drug-loaded microparticle is steered in endovascular environment to achieve targeted therapy. This study is performed in the three following perspectives.

First, an approach that utilizes optical tweezers manipulation to stimulate cell migration is investigated. 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. Models of both tweezers-bead and bead-cell interactions are analyzed separately. A cascade system framework of stimulating cell migration with optical tweezers controlled chemoattractant-loaded microbead, is established.

Second, a dual closed-loop control strategy is proposed to drive a microsource bead to achieve a proactive cell migration process. The proposed control method can induce the target cell to migrate to a desired area while avoiding obstacles in a concentration gradient field. A disturbance observer based controller of inner-loop and a proportional-integral controller of outer-loop are designed. An interference-clearing mechanism, which is designed to trap interference beads and regulate their motions, helps eliminate the influence of other interference beads. Simulations and experiments are performed to validate the proposed approach.

Third, microparticles capable of propulsion in blood vessel at the micro scale have the promise in increasing the drug delivery efficiency. A model-free backstepping sliding mode controller for navigating a magnetic proposed microparticle in the endovascular environment is established. A high-gain extended disturbance observer is designed to estimate the position of the microparticle and disturbances in real time when the pulsatility and inhomogeneity of blood flows and the influence of the vessel wall are considered. A local-planning trajectory that is smooth and energy-efficient is designed while considering the vessel network constraints and actuation limit.

In summary, disturbance observer-based control method can help solve the biological control problem in complex microenvironment. 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. The proposed controller for microparticle endovascular navigation control does not rely on prior knowledge of blood-velocity distribution and can successfully drive the microparticle along the designed trajectory when environmental disturbances and position measurement error exist. This thesis will contribute to the current knowledge on proactive autonomous aided method for the further development of target therapy.

Date of Award	11 Jun 2018
Original language	English
Awarding Institution	City University of Hong Kong
Supervisor	Dong SUN (Supervisor) & Yong WANG (External Supervisor)