Nanoscale superparamagnetic composite particles for biomedical applications

Mathieu Chastellain
EPFL, 2004
EPFL thesis

Abstract

The present thesis report deals about the material scientists contribution to the interdisciplinary European project "MAGNANOMED" involving people having very different backgrounds (physicist, chemists, biochemists, veterinary surgeons, ...). The work carried out was aimed at the development of iron oxide based nanoscale superparamagnetic composite particles for biomedical applications. Particles showing a superparamagnetic behaviour are of particular interest as they are sensitive to magnetic fields without retaining magnetisation after removal of the latter. Not only superparamagnetic particles can be guided, but they also exhibit heating properties when submitted to appropriate alternating magnetic fields. These characteristics make them promising for targeted applications where they could act as careers as well as activators. The local temperature increase can be used for confined control release of linked entities or to modify specific cells activities in a well defined area. Moreover iron oxide nanoparticles can be used for magnetic resonance imaging enhancement. No single sample could meet the requirements imposed by every application mentioned above, so the chosen strategy was first to synthesize and thoroughly characterize iron oxide nanoparticles. In a second step, the particles would serve as primary building blocks for higher order composite structures or "beads" (with one or more iron oxide cores) to be formed according to the specific needs of every particular application. The surface tailoring, so that to ensure the desired properties in physiological media and allow further functionalisation, consisted in an important part of the work. Despite the many works carried out in the field over the past decades, the needs for well controlled biocompatible superparamagnetic beads are not only important but also growing. A focus was made on three specific applications: hyperthermia (controlled heating in a well defined body area by means of an external alternating magnetic field), drug delivery (magnetic targeted drug release) and DNA purification (magnetically driven separation in vitro). A supplementary application called ferrofluid actuated micro pump is also described as it turned out that a synthesis side product could be judiciously used in this field. The achievements realized allowed to define a reproducible and versatile synthesis route, which fulfils the above mentioned criteria as summarised in the following. Iron oxide particles, which physical properties could be well controlled, were shown to generate heat when submitted to an external magnetic field suitable for medical applications. The measured power dissipated could be successfully related to the particles and field characteristics using a theoretical approach and the tremendous influence of particles size distribution was highlighted. Polyvinyl alcohol coated iron oxide particles were produced for drug delivery. Biocompatibility was asserted based on both in vitro and in vivo experiments. The particles bio-distribution could be influenced by means of a constant magnetic field (magnet) and depending on the coating nature (presence of functional groups), the cellular uptake could be controlled. Silica beads with a homogeneous iron oxide particles space distribution were synthesised in view of DNA separation using a novel approach. The bead size could be adjusted in the 20 nanometres up to several microns range. Preliminary classical plasmid automated purification experiments revealed a competitive separation yield. These results are promising in view of the final targeted application in currently developed quicker automated processes. A highly concentrated iron oxide suspension (ferrofluid) showing suitable colloidal stability was successfully applied in micropumps actuated by means of a magnetically induced ferrofluid motion. The obtained pumping characteristics such as backpressure and flow rate were better then described in literature for similar devices using water based ferrofluids. AFM 3D-view of iron oxide particles coated with polyvinyl alcohol, average height 9 nm (left) and Stonehenge monument in Britain, heaviest stone 50 tons (right). "In its day, the construction of Stonehenge was an impressive engineering feat, requiring commitment, time and vast amounts of manual labour" [http://www.britannia.com/ history/h7.html] (see appendix 12.6). Nowadays, this remark still holds for Nano-stonehenge synthesis ...

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https://infoscience.epfl.ch/record/33516?ln=en

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Mathieu Chastellain
EPFL, 2004
EPFL thesis

Abstract

Official source

https://infoscience.epfl.ch/record/33516?ln=en

About this result

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Ferrofluid is a liquid that is attracted to the poles of a magnet. It is a colloidal liquid made of nanoscale ferromagnetic or ferrimagnetic particles suspended in a carrier fluid (usually an organ

A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometime

Magnetism is the class of physical attributes that occur through a magnetic field, which allows objects to attract or repel each other. Because both electric currents and magnetic moments of element

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Process monitoring of alumina nanoparticle synthesis by inductively coupled RF thermal plasma

Jong-Won Shin

Since the first inductively coupled plasma (ICP) torch was developed in the 60's, RF thermal plasmas have found a variety of applications in material processing such as crystal growth, thermal spray coatings, spheroidization and vaporization of refractory materials. In recent decades, inductively coupled thermal plasmas have been used for the synthesis of high purity nanoparticles, thank to their remarkable advantages such as high energy density, variable operating pressures and low product contamination. The formation of nano-sized particles in thermal plasmas particularly using solid refractory precursor is a complex process. Hereby the injected precursor powders are heated by the high temperature of the thermal plasma. The heated powders are vaporized and decomposed into vapor species. During the following cooling, the vapor species are condensed to nano-sized particles. In this synthesis process, characterized by evaporation-condensation, the properties of the synthesized particles such as particle size, size distribution, phases and morphology are affected by various process parameters. Gas pressure, flow rates of the different torch gases, size of the precursor powders and powder loading in the plasma are considered as the influencing process parameters. In order to optimize and control the process for tailor-made nanoparticle synthesis, it is necessary to understand the effects of the process parameters on plasma properties and on the particle-plasma interactions resulting in final properties of the synthesized powders. In the present work, firstly, the enthalpy probe technique, a well-established plasma diagnostic tool for high pressure thermal plasma, has been applied to characterize the inductively coupled Ar-H2 thermal RF plasma used for alumina nanoparticle synthesis at different operating conditions. The plasma enthalpy has been determined, and the plasma temperature under a given gas pressure could subsequently be calculated assuming local thermodynamic equilibrium (LTE), once the gas composition has been determined by mass spectrometry. The gas velocity of the plasma jet could also be obtained by using the Bernoulli equation and stagnation pressure. Secondly, the influence of flow rates of central gas and precursor feed rates on the Al2O3 precursor evaporation has been investigated by process monitoring. Optical emission spectroscopy (OES) and laser light extinction (LE) measurements have been carried out to monitor in-situ the injection of the alumina precursors and to obtain information on the ongoing precursor evaporation. The emission line intensities of the aluminum vapor were used to determine the dependence of process parameters on precursor evaporation. Furthermore, the laser light extinction was used to calculate the number density of non plasma-treated powders, from which the number fraction of evaporated powders could be deduced. The size and morphology of the synthesized particles have been characterized ex-situ. Finally, the influence of quenching conditions on the condensation and formation of the nano-sized alumina particle has been studied by process analysis of the gas phase reactions of alumina. Optical emission spectroscopic was performed at different axial positions to monitor the gas phase reactions of the vaporized particles. Axial profiles of the emission line intensities of the main vapor species of alumina, Al(g) and AlO(g), were compared with the results of the enthalpy probe measurements and the thermal decomposition reactions of alumina found in literature. The results allow explanation of the alumina reactions in the thermal plasma as well as gives indications for the optimal axial position of the quenching gas injection. In addition to the determination of the optimal quenching position, the influence of the flow rates of quenching gas on the nanoparticle formation has been investigated. The synthesis of the submicron alumina using vapor-condensation principle predominantly leads to various thermodynamically metastable crystal structures called transition alumina. Therefore, the occurrence of different transition aluminas is discussed with regards to the flow rates of the quenching gas. The results presented in this thesis show that the synthesis process of the nanoparticle can be described on the basis of experimental results and basic information on the powder materials. The explanation of the influence of process parameters on powder evaporation and nanoparticle formation shows the usefulness of the in-situ plasma process monitoring, and the large potential for optimizing and controlling the nanopowder synthesis process in an inductively coupled RF thermal plasma.

EPFL2006

In this thesis work we propose new concepts of transporting and manipulating magnetic particles on microfluidic scale. The objective is to propose solutions to the problems related to the integration of the magnetic inductive components within a microfluidic network for magnetic particle manipulation. A second part of this work is the study of the physics of magnetic particle pattern formation when a suspension of the particles is subjected to an external magnetic field. The first concept that we propose is based on the dynamic motion of a selfassembled structure of ferromagnetic beads that are retained within a microfluidic flow using a local alternating magnetic field. We show that an alternating magnetic field induces a rotational motion of the magnetic particles, thereby strongly enhancing the fluid perfusion through the magnetic structure that behaves as a dynamic random porous medium. The result is a very strong particle-liquid interaction that can be controlled by adjusting the magnetic field frequency and amplitude, as well as the liquid flow rate. This fact is at the basis of very efficient liquid mixing. We anticipate that the intense interaction between the fluid and magnetic particles with functionalized surfaces holds large potential for the development of future bead-based assays. The second concept is the transport of magnetic particles on microfluidic scales over long-range distances using an array of simple planar coils placed in large static magnetic field. This magnetic field imposes a permanent magnetic moment to the microparticles, so that a very small magnetic field gradient of a simple planar coil is sufficient to displace the microparticles. We demonstrate that the repulsive and attractive magnetic forces generated by adjacent strongly overlapped coils, allow an efficient and well controlled magnetic particle displacement along one-dimensional or two dimensional paths. Finally, we study the dynamics of supraparticles structure (SPS) patterns of a ferromagnetic particle suspension in an alternating magnetic field. We show that the application of an alternating magnetic field to a ferromagnetic particle suspension results in a phase separation of the supraparticles structures (SPS) patterns into periodic structures of columns. Moreover, we investigate the dynamic motion, relative to a microfluidic flow, of such magnetic SPS. The latter are locally manipulated with an alternating magnetic field that is transverse to a microfluidic channel. We show that the SPS in the microchannel are composed of weakly aggregated and open columnar-like structures, allowing large particles surfaces to be in contact with the fluid flow.

EPFL2004

In magnetic confinement devices, the inhomogeneity of the confining magnetic field along a magnetic field line generates the trapping of particles (with low ratio of parallel to perpendicular velocities) within local magnetic wells. One of the consequences of the trapped particles is the generation of a current, known as the bootstrap current (BC), whose direction depends on the nature of the magnetic trapping. The BC provides an extra contribution to the poloidal component of the confining magnetic field. The variation of the poloidal component produces the alteration of the winding of the magnetic field lines around the flux surfaces quantified by the rotational transform ι. When ι reaches low rational values, it can trigger the generation of ideal MHD instabilities. Therefore, the BC may be responsible for the destabilisation of the configuration. This thesis is divided into two parts. In the first part, we present a self-consistent method to calculate the BC and assess its effect on equilibrium and stability in general 3D configurations. This procedure is applied to two reactor-size prototypes (both with plasma volumes ∼ 1000m3): a quasi-axisymmetric (QAS) system and a quasi helically symmetric (QHS) system with magnetic structures that develop BC in opposite directions. The BC increases with the plasma pressure, therefore its relevance is enhanced when dealing with reactor-level scenarios. The behaviour of both prototypes at reactor level values of β ≡ (kinetic plasma pressure)/(magnetic pressure) is assessed, as well as its alteration of the equilibrium and stability. In the QAS prototype, BC-consistent equilibria have been computed up to β = 6.7% and the configuration is shown to be stable up to β = 6.4%. Convergence of self-consistent BC calculations for the QHS case is achieved only up to β = 3.5%, but the configuration is unstable for β ≥ 0.6%. The relevance of symmetry breaking modes of the Fourier expansion of the confining magnetic field on the generation of BC is studied for each prototype. This proves the close relationship between magnetic structure and BC. Having established the potentially dangerous implication of the BC, principally, in reactor prototypes, a method to compensate its harmful effects is proposed in the second part of the thesis. It consists of the modelling of the current driven by externally launched ECWs within the plasma to compensate the effects of the BC. This method is flexible enough to allow the identification of the appropriate scenarios in which to generate the required CD depending on the nature of the confining magnetic field and the specific plasma parameters of the configuration. Both the BC and the CD calculations are included in a self-consistent scheme which leads to the computation of a stable BC+CD-consistent MHD equilibrium. This procedure is applied in this thesis to simulate the required CD to stabilise the QAS and QHS prototypes introduced in the first part. The estimation of the input power required and the effect of the driven current on the final equilibrium of the system is performed for several relevant scenarios and wave polarisations providing various options of stabilising driven currents. Several scenarios have been devised for each prototype in order to drive current at the appropriate location and with the desired direction. Different polarisations and launching conditions have been employed to this purpose. In particular, a HFS launched X2 ECW with an input power of 1.5MW has been shown to drive sufficient current to maintain the rotational transform below the critical value 2/3 at β = 6.4% for the QAS reactor. Correspondingly, in the QHS reactor, an X3-mode ECW of 100KW was sufficient to drive the current required to push the rotational transform below unity near the magnetic axis at β = 3%. Thus, stabilisation of BC-driven instabilities with externally launched ECWs has been achieved for both contrasting configurations. The method proposed in this thesis allows also the utilisation of EBW in the generation of CD. The possible advantages of EBCD for compensation studies are described as well as their possible application to the two prototypes under consideration. The BC+CD procedure is particularly interesting to investigate new magnetic geometries as potential candidates for fusion reactors. With this numerical tool, it is possible to assess the implications of their consistent BC when operating at reactor level. It also allows to quantify how much power would be required to maintain the system MHD stable in these circumstances. Nevertheless, this method is flexible enough to be applicable to any configuration.

EPFL2006

Process monitoring of alumina nanoparticle synthesis by inductively coupled RF thermal plasma

Jong-Won Shin

EPFL2006

EPFL2004

EPFL2006