Implementation and modeling of in situ magnetic hyperthermia

Health-care associated infections (HAIs) on medical implant surfaces present a unique challenge to physicians due to their existence in the biofilm phenotype which defends the pathogen from antibiotics and the host’s own immune system. A 2004 study in the U.S. showed that 2 to 4% of implanted devices become infected and must be treated via surgical explantation—a process that is both expensive and dangerous for the patient. A potential, alternative strategy to antibiotics and surgery is to use heat delivered wirelessly by a magnetic coating. This thermal treatment strategy has the potential to kill these HAIs directly on the implanted surface and without the patient requiring surgery.

This thesis introduces an iron oxide nanoparticle composite coating that is wirelessly heated using energy converted from an alternating magnetic field. Iron oxide nanoparticle composites are demonstrated to be remotely heated in both hydrophilic and hydrophobic polymer composites. In designing the composite coating, multiple parameters were investigated for how they impact the normalized heating rate of the material. Specifically, the amount of iron in the coating, the coating thickness, the polymer type, and the orientation of the coating relative to the applied magnetic field were investigated. Power output was shown to increase proportionally with iron loading whereas nearly two times the amount of power output was observed for the same coatings positioned parallel to magnetic field lines versus those positioned perpendicular—a result believed to be due to magnetic shielding from neighboring particles.

Microscope slides coated with 226 µm of composite delivered up to 10.9 W cm⁻² of power when loaded with 30.0% Fe and positioned parallel in a 2.3 kA m⁻¹AMF. Pseudomonas aeruginosa biofilms were grown directly on these coatings and heated for times ranging from 1 to 30 min and temperatures from 50 to 80 °C. Less than one order of magnitude of cell death was observed for temperatures less than 60 °C and heat shock times less than 5 min. Up to six orders of magnitude reduction in viable bacteria were observed for the most extreme heat shock (80 °C for 30 min).

Introducing this wirelessly heated composite into the body has the potential to kill harmful bacteria but at the risk of thermally damaging the surrounding tissue and organs if the treatment is not designed and predicted intelligently. Thermal energy will propagate differently depending on the surrounding heat sink, with convective heat sinks (i.e. those due to blood flow) requiring much more power to reach the same surface temperature than a conduction-only heat sink. To study how heat is transferred in biological tissues, a robust, poly(vinyl alcohol) tissue phantom was developed that can be poured to accommodate any geometry, is volume stable in water and under thermal stress, and can be modified with inert particle fillers to adjust its thermal conductivity from 0.475 to 0.795 W m⁻¹°C⁻¹. In vitro heat transfer was measured through this hydrogel tissue phantom with at least 10 °C of temperature rise, penetrating 5 mm of tissue in less than 120 sec for an 80 °C boundary condition.

A computational model was used to solve three-dimensional energy transfer through a combined fluid mimic/tissue mimic heat sink spanning the same surface boundary condition. The model was validated with experimental models using a custom designed heat transfer station. This scenario is applicable in the instance where the same coating is subject to starkly different heat sinks: half subject to convective heat loss, half to conductive heat loss. Based on these conditions, a magnetic coating would need to be designed that has a power gradient up to 15 times larger on the fluid half versus the other.