A Contactless and Biocompatible Approach for 3D Active Microrobotic Targeted Drug Delivery

As robotic tools are becoming a fundamental part of present day surgical interventions, microrobotic surgery is steadily approaching clinically-relevant scenarios. In particular, minimally invasive microrobotic targeted drug deliveries are reaching the grasp of the current state-of-the-art technology. However, clinically-relevant issues, such as lack of biocompatibility and dexterity, complicate the clinical application of the results obtained in controlled environments. Consequently, in this work we present a proof-of-concept fully contactless and biocompatible approach for active targeted delivery of a drug-model. In order to achieve full biocompatiblity and contacless actuation, magnetic fields are used for motion control, ultrasound is used for imaging, and induction heating is used for active drug-model release. The presented system is validated in a three-dimensional phantom of human vessels, performing ten trials that mimic targeted drug delivery using a drug-coated microrobot. The system is capable of closed-loop motion control with average velocity and positioning error of 0.3 mm/s and 0.4 mm, respectively. Overall, our findings suggest that the presented approach could augment the current capabilities of microrobotic tools, helping the development of clinically-relevant approaches for active in-vivo targeted drug delivery

Modeling and Control of a Magnetically Levitated Microrobotic System

Magnetically levitated microrobotic systems have shown a great deal of promise for micromanipulation tasks. A new large-gap magnetic suspension system has recently been developed at the University of Waterloo in order to develop microrobotic systems for various applications. In order to achieve motion with the system, a model is needed in order to facilitate the design of various aspects of the system, such as the microrobot and the controller. In order to derive equations of motion for the system attempts were made to characterize the force produced by the magnetic drive unit in terms of a simple analytical equation. The force produced by the magnetic drive unit was estimated with the aid of a finite element model. The derived equations were able to predict the general trend of the force curves, and with sufficient parameter tweaking the error between the force estimated by the finite element model and the force estimated by the analytical equation could be minimized. System models describing the motion of the system in the horizontal and vertical directions are identified and compared to the actual system response. The vertical position response is identified through a least squares parameter estimate of the closed loop response combined with a partial reconstruction of the root locus diagram, with the model structure based on the known dynamics of a simplified form of magnetic levitation. This model was able to provide a reasonable prediction of the system response for a variety of PID controllers under a variety of input conditions. The horizontal models are identified using a least-squares parameter estimate of the open loop characteristics of the system. The horizontal models are able to provide a reasonable prediction of the system response under PD and PID control. Full spatial motion of a microrobot prototype is demonstrated over a working range of 20x22x30 mm3, with PID controller parameters and reference trajectories adjusted to minimize disturbances. The RMS error at steady state is on the order of 0. 020 mm for vertical positioning and 0. 008 mm for horizontal positioning. A linear quadratic regulator implemented for vertical position control was able to reduce the vertical position RMS error to 0. 014 mm

Magnetic Drug Targeting: Developing the Basics

Focusing medicine to disease locations is a needed ability to treat a variety of pathologies. During chemotherapy, for example, typically less than 0.1% of the drugs are taken up by tumor cells, with the remaining 99.9% going into healthy tissue. Physicians often select the dosage by how much a patient can physically withstand rather than by how much is needed to kill all the tumor cells. The ability to actively position medicine, to physically direct and focus it to specific locations in the body, would allow better treatment of not only cancer but many other diseases. Magnetic drug targeting (MDT) harnesses therapeutics attached to magnetizable particles, directing them to disease locations using magnetic fields. Particles injected into the vasculature will circulate throughout the body as the applied magnetic field is used to attempt confinement at target locations. The goal is to use the reservoir of particles in the general circulation and target a specific location by pulling the nanoparticles using magnetic forces. This dissertation adds three main advancements to development of magnetic drug targeting. Chapter 2 develops a comprehensive ferrofluid transport model within any blood vessel and surrounding tissue under an applied magnetic field. Chapter 3 creates a ferrofluid mobility model to predict ferrofluid and drug concentrations within physiologically relevant tissue architectures established from human autopsy samples. Chapter 4 optimizes the applied magnetic fields within the particle mobility models to predict the best treatment scenarios for two classes of chemotherapies for treating future patients with hepatic metastatic breast cancer microtumors

Magnetic-field-induced propulsion of jellyfish-inspired soft robotic swimmers

The multifaceted appearance of soft robots in the form of swimmers, catheters, surgical devices, and drug-carrier vehicles in biomedical and microfluidic applications is ubiquitous today. Jellyfish-inspired soft robotic swimmers (jellyfishbots) have been fabricated and experimentally characterized by several researchers that reported their swimming kinematics and multimodal locomotion. However, the underlying physical mechanisms that govern magnetic-field-induced propulsion are not yet fully understood. Here, we use a robust and efficient computational framework to study the jellyfishbot swimming kinematics and the induced flow field dynamics through numerical simulation. We consider a two-dimensional model jellyfishbot that has flexible lappets, which are symmetric about the jellyfishbot center. These lappets exhibit flexural deformation when subjected to external magnetic fields to displace the surrounding fluid, thereby generating the thrust required for propulsion. We perform a parametric sweep to explore the jellyfishbot kinematic performance for different system parameters—structural, fluidic, and magnetic. In jellyfishbots, the soft magnetic composite elastomeric lappets exhibit temporal and spatial asymmetries when subjected to unsteady external magnetic fields. The average speed is observed to be dependent on both these asymmetries, quantified by the glide magnitude and the net area swept by the lappet tips per swimming cycle, respectively. We observe that a judicious choice of the applied magnetic field and remnant magnetization profile in the jellyfishbot lappets enhances both these asymmetries. Furthermore, the dependence of the jellyfishbot swimming speed upon the net area swept (spatial asymmetry) is twice as high as the dependence of speed on the glide ratio (temporal asymmetry). Finally, functional relationships between the swimming speed and different kinematic parameters and nondimensional numbers are developed. Our results provide guidelines for the design of improved jellyfish-inspired magnetic soft robotic swimmers