For decades now, conventional sinusoidal signals have been exclusively used in magnetic hyperthermia as the only alternating magnetic field waveform to excite magnetic nanoparticles. However, there are no theoretical nor experimental reasons that prevent the use of different waveforms. The only justifiable motive behind using the sinusoidal signal is its availability and the facility to produce it. Following the development of a configurable alternating magnetic field generator, we aim to study the effect of various waveforms on the heat production effectiveness of magnetic nanoparticles, seeking to prove that signals with more significant slope values, such as the trapezoidal and almost-square signals, allow the nanoparticles to reach higher efficiency in heat generation. Furthermore, we seek to point out that the nanoparticle power dissipation is dependent on the waveform’s slope and not only the frequency, magnetic field intensity and the nanoparticle size. The experimental results showed a remarkably higher heat production performance of the nanoparticles when exposed to trapezoidal and almost-square signals than conventional sinusoidal signals. We conclude that the nanoparticles respond better to the trapezoidal and almost-square signals. On the other hand, the experimental results were used to calculate the normalized power dissipation value and prove its dependency on the slope. However, adjustments are necessary to the coil before proceeding with in vitro and in vivo studies to handle the magnetic fields required.

This article shows the use of a high-frequency Full-Bridge inverter to design an alternating magnetic field generator for experimental studies on anti-cancer treatment with magnetic nanoparticles. In magnetic hyperthermia, nanoparticles are used to raise the pathological cancerous cell's temperature high enough to induce their death by apoptosis, but not as high as to destroy them by thermal ablation of the whole tissue volume, consequently leaving healthy cells alive. Conventionally, sinusoidal alternating magnetic fields are used to heat the nanoparticles, which can be more easily produced than other waveforms. However, there are no theoretical nor experimental reasons to choose the sinusoidal waveform. This work aims to develop an improved power system to study the effect of different waveforms of the magnetic field on heat production when exciting magnetic nanoparticles, aiming at demonstrating that other waveforms can be much more efficient in producing heat than conventional sinusoids. To prove our hypothesis, we designed an inverter able to generate four waveforms at high frequencies and a fifth sinusoidal signal derived by a resonant capacitor, in the range of 100 kHz to 1 MHz and up to 10 mT of peak intensity. Also, we used SiC devices to process high currents at high switching frequencies efficiently. Additionally, to enhance the system efficiency, Zero-Voltage Switching is used to reduce switching losses and minimize electromagnetic noise and interference. The experimental results obtained with non-sinusoidal waveforms have shown a remarkable performance improvement compared to classical sine wave excitation. The nanoparticles' heat dissipation depends on the applied alternating magnetic field's signal slope, signal frequency, and peak field intensity. We conclude that further work deserves to be done to find the optimum work conditions in function of the used particle and biological environment to test if this type of magnetic field generator could overcome the conventional system's performance.

Viscosity variation in human fluids, such as Synovial Fluid (SF) or Cerebrospinal Fluid (CSF), can be used as a diagnostic factor; however, the sample volume obtained for analysis is usually small, making it difficult to measure its viscosity. On the other hand, Quartz Crystal Resonators (QCR) have been used widely in sensing applications due to their accuracy, cost, and size. This work provides the design and validation of a new viscosity measurement system based on quartz crystal resonators for low volume fluids, leading to the development of a sensor called “ViSQCT” as a prototype for a new medical diagnostic tool. The proposed method is based on measuring the resonance frequency at the crystal’s maximum conductance point through a frequency sweep, where crystals with 10 MHz fundamental resonance frequency were used. For validation purposes, artificial fluids were developed to simulate SFs and CFs in healthy and pathological conditions as experiment phantoms. A commercial QCR based system was also used for validation since its methodology differs from ours. A conventional rotational viscometer was used as a reference for calibration purposes. ViSQCT demonstrates the capability to measure the sample’s viscosity differentiation between healthy and pathological fluid phantoms and shows that it can be used as a basis for a diagnostic method of several pathologies related to the studied biological fluids. However, some performance differences between both QCR-based systems compared to the reference system deserves further investigation.

Although optical hyperthermia could be a promising anticancer therapy, the need for high concentrations of light-absorbing metal nanoparticles and high-intensity lasers, or large exposure times, could discourage its use due to the toxicity that they could imply. In this article, we explore a possible role of silica microparticles that have high biocompatibility and that scatter light, when used in combination with conventional nanoparticles, to reduce those high concentrations of particles and/or those intense laser beams, in order to improve the biocompatibility of the overall procedure. Our underlying hypothesis is that the scattering of light caused by the microparticles would increase the optical density of the irradiated volume due to the production of multiple reflections of the incident light: the nanoparticles present in the same volume would absorb more energy from the laser than without the presence of silica particles, resulting either in higher heat production or in the need for less laser power or absorbing particles for the same required temperature rise. Testing this new optical hyperthermia procedure, based on the use of a mixture of silica and metallic particles, we have measured cell mortality in vitro experiments with murine glioma (CT-2A) and mouse osteoblastic (MC3T3-E1) cell lines. We have used gold nanorods (GNRs) that absorb light with a wavelength of 808 nm, which are conventional in optical hyperthermia, and silica microparticles spheres (hereinafter referred to as SMSs) with a diameter size to scatter the light of this wavelength. The obtained results confirm our initial hypothesis, because a high mortality rate is achieved with reduced concentrations of GNR. We found a difference in mortality between CT2A cancer cells and cells considered non-cancer MC3T3, maintaining the same conditions, which gives indications that this technique possibly improves the efficiency in the cell survival. This might be related with differences in the proliferation rate. Since the experiments were carried out in the 2D dimensions of the Petri dishes, due to sedimentation of the silica particles at the bottom, whilst light scattering is a 3D phenomenon, a large amount of the energy provided by the laser escapes outside the medium. Therefore, better results might be expected when applying this methodology in tissues, which are 3D structures, where the multiple reflections of light we believe will produce higher optical density in comparison to the conventional case of no using scattering particles. Accordingly, further studies deserve to be carried out in this line of work in order to improve the optical hyperthermia technique.

In magnetic hyperthermia, nanoparticles are used to raise the pathological cancerous cell's temperature high enough to induce their death by apoptosis, but not as high as to destroy them by thermal ablation of the whole tissue volume, consequently leaving healthy cells alive. For decades, conventional sinusoidal signals have been exclusively used in magnetic hyperthermia as the only alternating magnetic field waveform to excite magnetic nanoparticles. However, there are no theoretical nor experimental reasons that prevent the use of different waveforms. Therefore, the only justifiable motive behind using the sinusoidal is its availability and production facility, although other waveforms might have higher efficiency. We aim to study the effect of various waveforms on the heat production effectiveness of magnetic nanoparticles, seeking to prove that signals with more significant slope values allow the nanoparticles to reach higher efficiency in heat generation than conventional sinusoids. But first, a configurable alternating magnetic field generator has to be developed to generate high-power high-frequency signals. This thesis shows the use of a high-frequency Full-Bridge inverter to design an alternating magnetic field generator for experimental studies on anti-cancer treatment with magnetic nanoparticles. The designed inverter described in this work can generate four waveforms at high frequencies and a fifth sinusoidal signal derived by a resonant capacitor, in the range of 100kHz to 1MHz and up to 10mT of peak intensity. Also, we used SiC devices to process high currents at high switching frequencies efficiently. Additionally, to enhance the system efficiency, Zero-Voltage Switching is used to reduce switching losses and minimize electromagnetic noise and interference. Once the development was concluded, we started the validation experiments. We sought to point out the dependency of the nanoparticle power dissipation on the waveform's slope, not only the frequency, magnetic field intensity, and the nanoparticle size. The experimental results showed the nanoparticles' higher heat production performance when exposed to trapezoidal and almost-square signals by 45.73 and 71.49% at best, respectively, over the conventional sinusoidal signals. Hence, the nanoparticles' heat dissipation depends on the applied alternating magnetic field's signal slope, signal frequency, and peak field intensity. However, adjustments are necessary to the coil before proceeding with in vitro and in vivo studies to handle the magnetic fields required. Hence, further work deserves to be done to find the optimum work conditions in function of the used particle and biological environment, which might lead us to surpass the 71.49% superiority over the conventional waveforms. The development of another device based on the magnetic hyperthermia design is described in this work. Although it was an alternating magnetic field generator, yet it operated at a low frequency, able to generate 6 different waveforms at frequencies between 1 and 50Hz, to be used in nanorobotics applications. However, it was limited to device development, and no validation experiments were done. On the other hand, the optimization and validation of a breast cancer hyperthermia applicator was conducted during a short-term scientific mission as a visiting scientist at the ERASMUS Medical Center’s hyperthermia team of the Radiation Oncology department. RESUMEN En la hipertermia magnética, las nanopartículas se utilizan para elevar la temperatura de la célula cancerosa patológica lo suficiente como para inducir su muerte por apoptosis, pero no tanto como para destruirla por ablación térmica de todo el volumen de tejido, dejando vivas las células sanas. Durante décadas, las señales sinusoidales convencionales se han utilizado exclusivamente en hipertermia magnética como la única forma de onda de campo magnético alterno para excitar nanopartículas magnéticas. Sin embargo, no existen razones teóricas ni experimentales que impidan el uso de diferentes formas de onda. Por lo tanto, el único motivo justificable detrás del uso de la sinusoidal es su disponibilidad y capacidad de producción, aunque otras formas de onda pueden tener una mayor eficiencia. Nuestro objetivo es estudiar el efecto de diversas formas de onda sobre la eficacia de producción de calor de las nanopartículas magnéticas, buscando demostrar que las señales con pendiente más significativos permiten que las nanopartículas alcancen una mayor eficiencia en la generación de calor que las sinusoides convencionales. Pero primero, se debe desarrollar un generador de campo magnético alterno configurable para generar señales de alta frecuencia de alta potencia. Esta tesis muestra el uso de un inversor de puente completo de alta frecuencia para diseñar un generador de campo magnético alterno para estudios experimentales sobre el tratamiento anticanceroso con nanopartículas magnéticas. El inversor que se describe en este trabajo puede generar cuatro formas de onda a altas frecuencias y una quinta señal sinusoidal derivada de un condensador resonante, en el rango de 100kHz a 1MHz y hasta 10mT de intensidad pico. Además, usamos dispositivos de SiC para procesar altas corrientes a altas frecuencias de conmutación de manera eficiente. Además, para mejorar la eficiencia del sistema, la conmutación de voltaje cero se utiliza para reducir las pérdidas de conmutación y minimizar el ruido y las interferencias electromagnéticas. Una vez concluido el desarrollo, iniciamos los experimentos de validación. Buscamos señalar la dependencia de la disipación de potencia de las nanopartículas en la pendiente de la forma de onda, no solo en la frecuencia, la intensidad del campo magnético y...