The growth of a magnesioferrite precipitate in iron doped (˜lOOOOppm wt.) magnesium oxide crystals, heat treated at 973K in oxygen, is studied with torque, magnetisation and magnetic resonance measurements. The torque and magnetisation results are in agreement with a model which assumes that the precipitate grows by diffusion limited Ostwald ripening.The effects of the particle size distribution and cubic magnetocrystalline anisotropy of the orientated octahedral precipitate particles on the magnetisation and torque curves are calculated. A magnetometrie demagnetisation tensor is defined for assemblies of orientated dipoles, its variation with the assembly size is investigated and used to calculate the longitudinal demagnetisation factors of octahedra. The ferromagnetic resonance spectra obtained were not in agreement with the generally used theory of de Biasi and Devezas (J. Appl. Phys. (1978)49, 2466). A new theory, based on a spin Hamiltonian, of the FMR response of an anisotropic superparamagnet is proposed and compared with some of the experimental spectra.

A microfluidic-based inductance sensor operating at 1.5 GHz is presented that can detect single 4.5 μm superparamagnetic particles flowing in a microfluidic channel. The particles are detected as they pass over a micron-sized planar gold loop electrode, with a maximum signal-to-noise ratio of 26.3 dB for an 80 μm/s flow rate; the magnetic beads are simultaneously observed with microscope images. The sensor consists of a coupled-line resonator and microwave interferometric system coupled to the loop electrode that is integrated within a polydimethylsiloxane-on-glass microfluidic chip assembly. A time-averaged inductance change caused by a single particle is related to the real part of its magnetic Clausius-Mossotti factor. The effective real part of the magnetic permeability for a particular particle is estimated to be 1.13 at 1.5 GHz. The sensor detects magnetic particles in flow and does not require an external biasing magnetic field, which distinguishes it from other magnetic microparticle sensors.

A microfluidic-based inductance sensor operating at 1.5 GHz is presented that can detect single 4.5 μm superparamagnetic particles flowing in a microfluidic channel. The particles are detected as they pass over a micron-sized planar gold loop electrode, with a maximum signal-to-noise ratio of 26.3 dB for an 80 μm/s flow rate; the magnetic beads are simultaneously observed with microscope images. The sensor consists of a coupled-line resonator and microwave interferometric system coupled to the loop electrode that is integrated within a polydimethylsiloxane-on-glass microfluidic chip assembly. A time-averaged inductance change caused by a single particle is related to the real part of its magnetic Clausius-Mossotti factor. The effective real part of the magnetic permeability for a particular particle is estimated to be 1.13 at 1.5 GHz. The sensor detects magnetic particles in flow and does not require an external biasing magnetic field, which distinguishes it from other magnetic microparticle sensors.

This work deals with a preparation of superparamagnetic nano- and microparticles with hydrophilic surfaces for bioapplications. The wok is divided into three parts in consonance with experimentally solved problem. First part describes a choice and an optimalization of synthesis of iron oxides nanoparticles with appropriate toxicological, morphological and physico-chemical properties, which surface can be post synthetically modified. Maghemite - γ-Fe2O3 particles were prepared by consequent oxidation of mangnetite - Fe3O4 as an initial substance for a preparation of materials for diagnostics and separations. A conventional alkaline coprecipitation method of magnetite preparation was modified to produce nanoparticles with narrowed size distribution without use of surfactants during their synthesis. Prepared maghemite nanoparticles were cca. 6 nm in diameter and their saturation magnetization was Ms ~ 70 A·m2 ·kg-1 . Such observed value is far higher in comparison with the state of the art and argues thus a proposition the Ms depends not on the preparation method, but only on the nanoparticles size. Maghemite nanoparticles morphology was evaluated by picture analysis of SEM and TEM micrographs, hydrodynamic size and zetapotential was measured with DLS. The structure of the maghemite was confirmed with...

Primary barriers to drug delivery include mucus and biofilms, which can hinder drug and gene delivery by several orders of magnitude, preventing effective therapeutic effects. By understanding the physical and chemical properties of these ubiquitous barriers, one may employ drug delivery approaches, such as design of nanoparticle and microparticle systems, to attempt to overcome the transport barriers. Nanoparticles are a growing interest in drug delivery, specifically as drug carriers, though most will become entrapped within these extracellular barriers further limiting their desired affects. Previous studies have generally manipulated the surface chemistries or size of these nanoparticles to allow for nearly a 2-fold increase in passive diffusion through barriers. To expand the current ideas of overcoming these barriers, studies in presented in this dissertation were performed using a type of active nanoparticle, superparamagnetic iron oxide nanoparticles. It was first investigated whether these particles would disrupt extracellular barriers under an oscillating magnetic field, which resulted in a 2-fold increased diffusion of particles upon biopolymer breakage. Secondly, influences of an external static magnetic field on diffusion of these nanoparticles through model barriers were determined. Both of these methods resulted in higher fold increases, reaching up to 28-fold compared to 2-fold as described in the literature. Next an examination of drug permeation enhancement in models of extracellular barriers by nanoparticle interactions was performed, using a passive mechanism as found in the literature. With a range of different nanoparticles including diesel particulate matter, barrier function was disrupted resulting in a 5-fold increase in drug permeation. To further manipulate drug diffusion an assisted delivery systems was observed, where magnetic nanoparticles could influence un-associated drug diffusion, resulting in 4-fold increase in drug diffusion. Finally formulations of nanosuspensions were created for aerosol delivery and their performance evaluated in vitro. A dry powder formulation containing drug and nanoparticles was formulated using a spray-drying technique. Upon barrier deposition studies using the dry powder formulation, permeation rates were determined resulting in a 2-fold increase for nanoparticle permeation. When drug diffusion was determined up to a 54-fold increase in drug was seen when co-delivered with nanoparticles, compared to controls containing only drug. / text

Les dispersions col·loïdals, un terme encunyat pel científic escocès Thomas Graham el 1861, han estat objecte d’interès en diferents àrees científiques durant més d'un segle. Una dispersió col·loïdal es caracteritza per l’existència d'una fase dispersa uniformement distribuïda dins un medi dispersiu. Diferents compostos entren dins aquesta categoria, com els aerosols (fum, boira, núvols o pols), les escumes, les emulsions (maionesa o llet) o els gels (mantega o melmelada). Les millores recents en la síntesi de partícules i l'estabilitat col·loïdal han impulsat la millora en el disseny de nous col·loides, conferint-los les propietats requerides en cada aplicació. Entre la gran varietat de dispersions col·loïdals (existents en la naturalesa o dissenyades per l'home), hem estudiat un tipus singular de dispersions on les partícules col·loïdals mostren un comportament superparamagnetic anomenades dispersions col·loïdals superparamagnètiques. En aquestes dispersions, sorgeixen característiques sorprenents quan un camp magnètic extern és aplicat, com a conseqüència del balanç entre les interaccions característiques entre col·loides i la interacció magnètica anisotròpica dipol-dipol entre les partícules col·loïdals constituents. Al llarg d'aquesta tesi s'ha utilitzat diferents models teòrics i de simulació per tractar diferents fenòmens que apareixen en aquestes dispersions col·loïdals superparamagnètiques. Per una banda, hem mostrat com l’aplicació de camps magnètics uniformes a aquestes dispersions indueix l’agregació reversible de les partícules superparamagnètiques. A la vista dels models teòrics i simulacions, hem proposat un nou criteri basat en les propietats físiques de les dispersions col·loïdals per predir la formació d'agregats, i la seva validesa s'ha discutit comparant el comportament predit amb resultats experimentals. Hem aportat evidencies de la existència d'un estat d'equilibri on els agregats assoleixen una distribució de mides estable, un fet ja suggerit amb anterioritat però establert sense prou claredat. També ens hem centrat en la descripció de la cinètica de creixement d'aquests agregats i en la seva implicació en diferents fenòmens observats experimentalment. La necessitat d'assolir escales de temps grans, com en certes situacions experimentals, ha motivat el desenvolupament de nous models i estratègies de simulació per reduir els temps de càlcul requerits en simulacions estàndard. Hem presentat un nou model de simulació que proporciona un mètode fiable i més ràpid per descriure la formació d'estructures en forma de cadena que apareixen en dispersions superparamagnètiques. El model ha estat validat comparant-ne els resultats obtinguts amb altres resultats de simulacions estàndard de Dinàmica de Langevin i s'ha aplicat a situacions experimentals, com ara el temps de relaxació T2 dels protons en solucions aquoses de nanopartícules superparamagnètiques. Mencionar també que aquest model de simulació ha estat implementat i el corresponent programari s’ha posat a disposició de la comunitat científica de forma gratuïta, concebut com una eina de simulació que pot ser ampliada fàcilment per resoldre altres problemes d’interès. Per altra banda, també hem discutit diferents efectes que sorgeixen com a conseqüència de l’aplicació de camps magnètics inhomogenis a aquestes dispersions superparamagnètiques. En concret, hem estudiat el moviment de les partícules magnètiques disperses en fluids a través de camps magnètics inhomogenis, el que es coneix com magnetoforesi. Per a tal efecte, hem centrat els esforços en la descripció de la separació magnètica de col·loides mitjançant l’aplicació de gradients de camp magnètic uniformes, des de dispersions superparamagnètiques a mescles de col·loides amb diferent resposta magnètica. Hem validat aquests models teòrics comparant-los amb simulacions per ordinador i n’hem discutit la seva utilitat comparant-ne les prediccions amb resultats experimentals. L’anàlisi racional d'aquests resultats proporciona un marc idoni per a millorar el disseny i el rendiment de diferents separadors magnètics, així com plantejar noves estratègies de separació, com per exemple la separació cooperativa en dispersions superparamagnètiques. Existeixen, encara, problemes oberts que esperem que aquest treball ajudi a afrontar com, per exemple, entendre la interconnexió entre les estructures induïdes en dispersions superparamagnètiques i la seva dinàmica d’agregació. Aquest és un aspecte important en una gran varietat d'aplicacions industrials i de laboratori com són els processos de separació magnètica, tractament d’aigües residuals i eliminació de contaminants, immunoassaigs en aplicacions clíniques o la creació de nous materials supramoleculars. Tanmateix, esperem que els resultats que es presenten al llarg d'aquest document encoratgin nous estudis dins el camp de col·loides magnètics, ja sigui perfeccionant els resultats i mètodes aquí presentats o contribuint al desenvolupament de noves estratègies per afrontar problemes encara per resoldre. / Colloidal dispersions, a term coined by the Scottish scientist Thomas Graham in 1861, have been the subject of interest in different scientific areas during more than a century. A colloidal dispersion is characterized by the existence of a dispersed phase uniformly distributed throughout a dispersion medium. Many different compounds fall in this category like aerosols (smog, fog, clouds or dust), foams, emulsions (mayonnaise or milk) or gels (butter or jelly). Recent improvements in particle synthesis and colloidal stability have boosted the controlled design of new colloids on demand, targeting the required properties for each application. Among the large variety of different colloidal dispersions (either found in nature or man-made), we have studied a singular type of such dispersions where the colloids have a superparamagnetic behavior called superparamagnetic colloidal dispersions. In these dispersions, surprising features arise under the application of an external magnetic field, as a consequence of the interplay between characteristic colloidal interactions and the anisotropic magnetic dipole-dipole interaction between their constituent colloidal particles. Along this thesis we have used different theoretical and simulation methods to discuss a number of phenomena appearing in superparamagnetic colloidal dispersions. On the one hand, we have shown that the application of a uniform magnetic field to such dispersions may induce the reversible aggregation of superparamagnetic particles. In view of theoretical models and computer simulations, a new criterion based on the physical properties of the colloidal dispersion has been proposed to predict the formation of aggregates, and its validity has been discussed by comparing the predicted behavior with experimental results. We have provided evidences of the existence of an equilibrium state, where aggregate sizes acquire a steady distribution, an issue previously suggested but unclear up to now. We have also focused our attention on the growth kinetics of the aggregates and its implications in different phenomena observed in experiments. The need to reach the large time scales of some experiments has motivated the development of new models and simulation strategies to overcome the large time consuming calculations required in standard simulations. We have presented a new simulation model that provides a faster and reliable approach to address the formation of chain-like structures in superparamagnetic dispersions. The model has been validated by direct comparison with standard Langevin Dynamics simulations and has been applied to experimental situations like the T2 relaxation time of protons in aqueous solutions of superparamagnetic nanoparticles. Let us mention that the simulation model has been implemented and the corresponding computer code is free and available to the scientific community, envisaged as a new modeling tool readily extensible to other problems of interest. On the other hand, we have analyzed different effects arising as a consequence of the application of inhomogeneous magnetic fields to such superparamagnetic dispersions. Specifically, we have studied the controlled motion of magnetic particles dispersed in a liquid medium by using inhomogeneous magnetic fields, what is known as magnetophoresis. To do so, we have focused the efforts on the description of the magnetic separation of colloids by the application of uniform magnetic field gradients, from superparamagnetic dispersions to mixtures of colloids with different magnetic response. We have validated the theoretical models adopted against computer simulations and we have discussed their usefulness by comparing the predictions obtained with experimental results. The rational analysis of these results provides a proper starting framework to enhance the design and performance of different magnetic separators, as well as to shape new separation strategies, like the cooperative magnetophoretic separation in superparamagnetic dispersions. There exists, of course, open problems that we hope this work will help to deal with. For instance, a better understanding of the interplay between the induced structures in superparamagnetic dispersions and their aggregation kinetics. This is an important issue in a vast variety of industrial and lab applications as, for example, in magnetic separation-based processes, waste-water treatment and pollutant removal, immunoassays in clinical applications or in the assisted assembly of new supramolecular materials. Nevertheless, we hope that the results presented along this document could encourage further studies in magnetic colloids science, either refining the results and approaches provided here or developing new strategies to face unsolved problems.

[Truncated abstract] In the past decade, the synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) has received considerable attention due to their potential applications in biomedical fields. However, success in size and shape control of the SPIONs has been mostly achieved through organic routes using large quantities of toxic or/and expensive precursors in organic reaction medium at high reaction temperature. This has limited the biomedical applications of SPIONs and therefore, development of a synthetic method under aqueous condition that is reproducible, scalable, environmentally benign, and economically feasible for industrial production is of paramount importance in order to fully realise their practical applications. Spinning Disc Processing (SDP) has been used to synthesise superparamagnetic magnetite (Fe3O4) nanoparticles at room temperature via a modified chemical precipitation method under continuous flow condition and offer a potential alternative to be applied to SPIONs production. SDP has extremely rapid mixing under plug flow conditions, effective heat and mass transfer, allowing high throughput with low wastage solvent efficiency. The synthesis process involves passing ammonia gas over a thin aqueous film of Fe2+/3+ which is introduced through a jet feed close to the centre of a rapidly rotating disc (500-2500 rpm). Synthetic parameters such as precursor concentrations, temperature, flow rate, disc speed, and surface texture influence the particle sizes. ... Magnetic silica microspheres are receiving great attention for possible applications in magnetic targeting drug delivery, bioseparation and enzyme isolation. However, the current available methods for preparation suffer from the setback of low loading of Fe3O4 nanoparticles in the silica microsphere, which result in low magnetic moment, thereby limiting their practical applications. Therefore it is of considerable importance to develop new alternative synthetic methods for fabricating magnetic silica microspheres with high magnetic nanoparticles loading. Superparamagentic Fe3O4 nanoparticles (8-10 nm diameter) and curcumin have been encapsulated in mesoporous silica in a simple multiplestep self assembly approach process with high Fe3O4 nanoparticles loading (37%). The synthesis involves loading of curcumin in the Cetyltrimethylammonium bromide (CTAB) micellar rod in the presence of superparamagnetic Fe3O4 nanoparticles via a parallel synergistic approach. The synthesised magnetic mesoporous silica composite material is stable, superparamagnetic with high saturation magnetisation before and after curcumin leaching experiment. Under physiological pH in phosphate buffer, the curcumin is slowly released over several days. These magnetic mesoporous silica are expected to have great potential as targeted drug delivery systems.

Depuis quelques années, notre laboratoire développe des nanoparticules lipidiques bicompartimentées originales produites par homogénéisation haute pression, un procédé transposable à grande échelle, à partir d’excipients pharmaceutiques validés par différentes pharmacopées (Eur., USP, JP). Ces particules appartiennent ainsi à la famille des nano-objets Janus puisqu’elles sont organisées en deux sous-structures juxtaposées : une moitié est constituée d’une gouttelette huileuse alors que l’autre moitié est composée d’une structure vésiculaire et renferme un cœur aqueux délimité par une bicouche phospholipidique. En plus de la biocompatibilité intrinsèque des lipides constituants, un tel système représente un outil potentiellement très intéressant et valorisable du point de vue pharmaceutique et biomédical capable d’incorporer séparément et de co-véhiculer des substances hydrophiles et lipophiles aux activités distinctes, par exemple un agent d’imagerie médical et un principe actif pour coupler diagnostique et thérapie. Ici, nous nous sommes intéressés à charger les nanoparticules Janus avec un fluide magnétique composé de nanocristaux d’oxyde de fer (ferrofluide, FF), actif en tant qu’agent de contraste efficace en IRM, étant magnétiquement contrôlable et permettant d’envisager un traitement par hyperthermie. Tour à tour, des FF hydrophiles ou lipophiles compatibles avec le procédé de production ont été développés en étudiant différentes voies de stabilisation des nanocristaux en fonction du compartiment d’encapsulation. / In recent years, our team has developed original compartmented lipid nanometer-sized particles produced by high pressure homogenization, a scalable process, with pharmaceutically approved excipients. The particles actually belong to the family of Janus nano-objects as they are organized in two juxtaposed substructures : one half is a droplet of liquid-state lipids while the other half is vesicle-like and encloses an aqueous core delimited by a phospholipid-containing bilayer shell. Added to the intrinsic biocompatibility of the constituting lipids, such a system provides a potentially very valuable tool in pharmaceutical and biomedical fields, able to separately incorporate and co-convey hydrophilic and lipophilic substances with distinct activities, for example, a medical imaging agent and a drug for coupling diagnosis and therapy. Here, we are interested in loading Janus nanoparticles with a magnetic fluid composed of superparamagnetic iron oxide nanocrystals (ferrofluid, FF), indeed as efficient contrast agent for MRI, being magnetically targetable and providing ability for hyperthermia treatment. Alternately, hydrophilic or lipophilic FF compatible with the production process have been developed by investigating different stabilization pathways of the nanocrystals depending on the encapsulation compartment.

New electrochemical methods were developed to fabricate superparamagnetic organic-inorganic nanocomposites. The methods were based on the electrosynthesis of (gamma)Fe2O3, Mn3O4 and NiFe2O4 in situ in a polymer matrix. Various composite materials were developed using new electrochemical strategies, which were based on the use of strong and weak polyelectrolytes and polymer-metal ion complexes. The deposited films were studied by XRD, TG, DTA, SEM and AFM. The results show that cathodic deposits with thickness of several microns can be obtained on various conductive substrates. The results reveal that the weight percentage of inorganic phase in the deposits reduced with the increase of the polymer concentration in the electrochemical bath solution. The particle size distribution was measured by HRTEM and evaluated by theoretical models interpreting the magnetic measurement data. The two methods are in good agreement with each other. The results show that the average particle sizes of Mn3O4 and (gamma)-Fe2O3 can be adjusted by the selection of polymers with different functional properties, the polymer concentration in the solutions and annealing temperatures. The particle size distribution in the developed composites followed the lognormal distribution. A double-lognormal distribution was required to interpret the magnetization data of the system containing strong interparticle interactions, and to interpret the double-peak phenomenon observed in the imaginary part of the susceptibility in some nanocomposites. DC magnetization and AC susceptibility measurements were used to study the relationship between the magnetic properties .and the average particle size by studying the superparamagnetic behavior and ferrimagnetic phase transitions of (gamma)-Fe2O3 and Mn3O4 nanoparticles in the temperature range of 2 K - 300 K. The results show that the blocking temperature TB is mainly controlled by the average particle size of the nanoparticles, and increasing the average particle size results in an upward shift of the TB. One observes no frequency dependence of TB, which indicates strong interparticle interaction in the nanoparticle assembly, in agreement with the structural results. The results revealed superparamagnetic behavior in Mn3O4 nanoparticles below the ferrimagnetic Néel temperature TN, and that TB was identified by a peak in the temperature lower than the ferrimagnetic transition peak marked by TN in the AC measurement. It is found that both TB and TN of Mn3O4 depend on the average particle size, and reducing the average particle size of Mn3O4 from 3.5 nm to 2.8 run results in a shift of TB from 14 K to 7 K, and TN from 36 K to 31 K (bulk Mn3O4 TN= 42 K) / Thesis / Doctor of Philosophy (PhD)

Materials on the nanoscale have very interesting properties. Hence, they are commonly used for a variety of applications such as drug delivery, bio-imaging and sensing devices. Moreover, coating these particles with other materials forming core@shell or Janus particles can further enhance their properties. However, for the particles to be used in medical and electronic devices, their properties such as size, shape and composition need to be precisely controlled. In this PhD., an emulsification technique was chosen to investigate the synthesis of nanoparticles; it is a simple process, does not require any harsh chemicals or temperature and is fast. Emulsification occurs when two or more immiscible liquids and surfactants are mixed. Here, emulsion droplets were produced using a microfluidic device which allowed for the creation of uniform droplets. These were employed as templates to synthesise and assemble nanomaterials. The main aim of the Ph.D. was to develop a droplet based synthesis process to generate nanoparticles and then assemble them into core@shell particles. This Ph.D., starts by synthesising Fe3O4 nanoparticles (~ 12 nm) and assembling them into microparticles (~ 1µm 2µm) using emulsion droplets as microreactors. By tuning the surfactant, droplet size and evaporation rate of the dispersed phase, microparticles of varying shapes and sizes, such as spherical or crumbled shapes, were produced. When these particles are compared with the commercially available particles, the magnetic content of the in-house particles, or sometimes referred to as Loughborough University Enterprises Ltd. (LUEL), are much higher and more uniform, hence resulting in faster separation when used for extraction of analytes. LUEL particles were supplied as part of commercial collaboration. The use of Pickering emulsions were then explored to create core@shell particles using gold nanoparticles instead of a surfactant to produce gold shells and the addition of pre-synthesised Fe3O4 nanoparticles results in Fe3O4@Au core@shell particles. This is the first time Pickering emulsions were used to produce Fe3O4@Au core@shell particles (~ 1.5 µm) within a microfluidic device. However, the shells were not uniform in thickness. In order to improve the coverage, nanoparticles were synthesised in situ at the droplet interface. By placing the gold chloride (AuCl4-) in the continuous phase and by varying the concentration of the electron donor in hexane droplet, single crystal gold nanoparticles and platelets were formed. The reaction is spontaneous at room temperature, creating gold nanoparticles at the interface of the emulsion droplet. The size and shape of the gold nanoparticles were controlled by varying the concentration of the reactants and the size of the droplets. By adding pre-synthesised particles (Fe3O4 nanoparticles) to the droplet, Au@Fe3O4 core@shell particles were formed with an approximate size of 250 nm. The same concept of forming core@shell particles using gold nanoparticles was further expanded by using other metal ions; palladium and silver. Unlike gold, palladium and silver only formed spherical nanoparticles, no platelets were observed. The addition of preformed iron oxide nanoparticles to the palladium results in core@shell particles. However, in the case of silver, no core@shell particles were formed. The study of the rate of reaction was conducted to understand the details of the mechanism. Overall, the process developed in this Ph.D. study allows for the facile synthesis of core@shell particles in a rapid, high throughput reaction. In the future, it is believed it could be scaled up for commercial purposes.