Surface Biological Modification and Cellular Interactions of Magnetic Spinel Nanoparticles Eva Liang-Huang Heintz 191 Pages Directed by Dr. Z. John Zhang The interest in magnetic nanoparticles is multi-dimensional. Fundamentally, it is important to be able to control their magnetic properties and to correlate to specific applications. In biology, magnetic nanoparticles offer promising potential as magnetic carriers or chaperones for magnetic localization and manipulation of therapeutic reagents. The synthesis of superparamagnetic CoFe2-xSmxO4 nanoparticles and the tunability of their magnetic properties by size and composition variations are discussed. An increase in size of CoSm0.19Fe1.81O4 nanoparticles produced an increase in blocking temperature and saturation magnetization, but a non-linear coercitivity response was observed with change in size. By varying the composition, the saturation magnetization of CoFe2-xSmxO4 decreased dramatically while the coercitivity increased when compared to native cobalt spinel ferrite (CoFe2O4) nanoparticles. These results demonstrate how the magnetic properties of cobalt spinel ferrite nanoparticles can be tailored to specific applications. Surface modifications of cobalt spinel ferrite nanoparticles facilitated the conjugation of oligonucleotides. Using a transfection reagent, CoFe2O4 ??igonucleotide conjugates were delivered into mammalian cells. Post transfection, synchronized movement of cells in response to an external magnetic field was observed. This demonstrated the possibility of magnetic manipulation and localization of therapeutic reagents coupled to CoFe2O4 magnetic nanoparticles. Results from this thesis demonstrate the potential role of magnetic spinel nanoparticles in cell biology and will facilitate the progress towards in vivo testing.

<p>This thesis will investigate previously unexplored concepts in magnetic manipulation including controlling the assembly of magnetic and nonmagnetic particles either in bulk fluid or near a substrate. Both uniform glass interfaces and substrates with magnetic microstructures are considered. The main goal of this work is to discuss new strategies for implementing magnetic assembly systems that are capable of exquisitely controlling the positions and orientations of single-component as well as multi-component particle suspensions, including both magnetic and non-magnetic particles. This work primarily focuses on controlling spherical particles; however, there are also several demonstrations of controlling anisotropically shaped particles, such as microrods and Janus colloids. </p><p> Throughout this work, both conventional magnetophoresis and inverse magnetophoresis techniques were employed, the latter relying on ferrofluid, i.e. a suspension of magnetic nanoparticles in a nonmagnetic carrier fluid, which provides a strong magnetic permeability in the surrounding fluid in order to manipulate effectively non-magnetic materials. In each system it was found that the dimensionless ratio between magnetic energy and thermal energy could be successfully used to describe the degree of control over the positions and orientations of the particles. One general conclusion drawn from this work is that the ferrofluid can be modeled with a bulk effective permeability for length scales on the order of 100 nm. This greatly reduces modeling requirements since ferrofluid is a complex collection of discrete nanoparticles, and not a homogenous fluid. It was discovered that the effective magnetic permeability was often much larger than expected, and this effect was attributed to particle aggregation which is inherent in these systems. In nearly all cases, these interactions caused the ferrofluid to behave as though the nanoparticles were clustered with an effective diameter about twice the real diameter.</p><p> The principle purpose of this thesis is to present novel systems which offer the ability to manipulate and orient multi-component spherical or anisotropic particle suspensions near surfaces or in the bulk fluid. First, a novel chip-based technique for transport and separation of magnetic microparticles is discussed. Then, the manipulation of magnetic nanoparticles, for which Brownian diffusion is a significant factor, is explored and modeled. Parallel systems of nonmagnetic particles suspended in ferrofluid are also considered in the context of forming steady state concentration gradients. Next, systems of particles interacting with planar glass interfaces are analyzed, modeled, and a novel application is developed to study the interactions between antigen-antibody pairs by using the self-repulsion of non-magnetic beads away from a ferrofluid/glass interface. This thesis also focuses on studying the ability to manipulate particles in the bulk fluid. First, simple dipole-dipole aggregation phenomenon is studied in suspensions of both nonmagnetic polystyrene particles and endothelial cells. For the sizes of particles considered in these studies, currently accepted diffusion limited aggregation models could not explain the observed behavior, and a new theory was proposed. Next, this thesis analyzed the interactions that exist in multi-component magnetic and nonmagnetic particle suspensions, which led to a variety of novel and interesting colloidal assemblies. This thesis finally discusses the manipulation of anisotropic particles, namely, the ability to control the orientation of particles including both aligning nonmagnetic rods in ferrofluid as well as achieving near-holonomic control of Janus particles with optomagnetic traps. General conclusions of the viability of these techniques are outlined and future studies are proposed in the final chapter.</p> / Dissertation

Les microrobots magnétiques, qui nagent en utilisant des modes de propulsion bio-inspirées, apparaissent très prometteurs pour la manipulation et la caractérisation d'objets à l'échelle microscopique dans des environnements confinés et très restreints, contrairement aux méthodes de micromanipulation classiques. La littérature propose une variété de microrobots avec des formes géométriques et des propriétés magnétiques différentes. Les commandes en mouvement proposées restent cependant simples, peu précises et insuffisamment robustes pour la réalisation de tâches réelles. De plus, il subsiste une incertitude sur le fait que tous ces micronageurs artificiels peuvent accomplir les mêmes tâches avec une performance égale. L'objectif de cette thèse consiste alors à proposer : des commandes de mouvement génériques par asservissement visuel dans l'espace pour tous les types de micronageurs avec des contraintes non holonomes afin d'améliorer les performances de ces micronageurs, un ensemble de critères de comparaison entre des robots avec une topologie ou un mode de propulsion différents pour le choix du micronageur le plus performant pour réaliser une tâche particulière. Des lois de commande de suivi de chemin dans l'espace sont synthétisées et validées expérimentalement sur des nageurs hélicoïdal et flexible sous différentes conditions. Ces robots évoluent dans un fluide à faible nombre de Reynolds, imitant respectivement le mécanisme de locomotion des bactéries et des spermatozoïdes et sont actionnés par un champ magnétique uniforme. Ces deux classes de nageurs possèdent une géométrie et un mode d'actionnement différents. Leurs performances sont ainsi comparées. / Magnetic microrobots, which swim using bio-inspired propulsion modes, appear very promising for manipulation and characterization of objects at microscopic scale inside confined and very restricted environments, unlike conventional micromanipulation methods. The literature proposes a variety of microrobots with different geometric shapes and magnetic properties. However, the motion controls proposed remain simple, imprecise and insufficiently robust for performing real tasks. In addition, there is still uncertainty that all these artificial microswimmers can accomplish the same tasks with equal performance. The objective of this thesis is thus to propose : generic motion controls by visual servoing in space for all kinds of microswimmers with nonholonomic constraints in order to improve the microswimmer performances, a set of comparison criteria between robots with a different topology or propulsion mode for choosing the most efficient microswimmer in order to perform a specific task. Path following control laws in space are synthesized and experimentally validated on helical and flexible swimmers under different conditions. These robots operate in low Reynolds number fluid, imitating respectively bacteria and spermatozoa and are actuated with uniform magnetic field. These two classes of swimmers have different actuation mode and geometric shape. Their performances are thus compared according to the task to be performed, the environment in which the robots evolve and the manufacturing constraints.