Magnetic nanoparticles have great potential in the biomedical and diagnostics field. Due to their small size, the particles have a high surface-to-volume ratio which enables for biofunctionalisation with different molecular probes. This makes itpossible to target them against a wide variety of biomarkers. In this project, the aim was to develop a magnetic nanoparticle-based DNA detection method with respectto sensitivity by employing circle-to-circle amplification, which is an extension of rolling circle amplification, in order to increase the assay sensitivity. The method provides high specificity due to the use of padlock probes for amplification. The project included testing and optimising the protocol used for DNA amplification and detection with a synthetic target, which involved testing different padlock probes, incubation times and incubation temperatures. Lastly, the method was tested on a biological target. It has recently been shown that specific aggregation occurs between magnetic nanoparticles and DNA, which enables for a visual readout strategy sincethe aggregates are visible to the naked eye. Initial testing of the method yielded asensitivity of about 100 attomoles. The achieved sensitivity after the optimisation work was 1 attomole of both synthetic and biological DNA targets. This is an improvement compared to the 400 attomoles that has previously been reported with one round of rolling circle amplification. The results can be used in further development of the naked-eye DNA detection method towards the realisation of a commercially attractive bioanalytical device.

L’objectif de cette thèse est la fabrication d’un microdispositif magnétique pour la détection et la manipulation d’éléments biologiques à base de nanoparticules magnétiques en conditions microfluidiques. Il a pour but d’intégrer des fonctions de base de contrôle et détection magnétique, pour atteindre des mesures spécifiques, stables, rapides et reproductibles. En effet, la technique d’immunodosage couplée à des nanoparticules magnétiques, bien connue dans la littérature, nécessite un contrôle du déplacement de ces dernières pour les fonctionnaliser efficacement et créer un complexe biologique encapsulant une molécule cible (biomarqueur). Dans notre cas une molécule modèle pour le domaine de la biodéfense a été utilisée : l’ovalbumine. Pour contrôler le champ magnétique nécessaire pour la capture des complexes magnétiques, nous avons opté pour l’utilisation de microbobines intégrées aux dispositifs fluidiques et comparé cette technique originale avec d’autres plus conventionnelles. Pour détecter un complexe biologique, la fluorescence est largement utilisée en biologie, mais cette technique ne permet pas une intégration complète pour un dispositif autonome. Dans cette optique, nous proposons la détection des complexes à base de nanoparticules magnétiques en relevant la variation de l’inductance d’un microcircuit magnétique refermant une chambre microfluidique contenant ces complexes immunologiques. Le dimensionnement des microbobines de contrôle par simulation a permis de déterminer les paramètres permettant d’obtenir le champ magnétique le plus adapté au contrôle des complexes biologiques. Dans le cas des microbobines utilisées pour la détection, des branches magnétiques micrométriques ont été insérées autour des microbobines pour créer un circuit de détection magnétique encore plus sensible. La réalisation de ces dispositifs a impliqué l’intégration de matériaux et de structures de nature fortement hétérogène, et leur assemblage a nécessité de résoudre de nombreux verrous technologiques. L’enjeu a été de déterminer l’ensemble des étapes successives et nécessaires pour un procédé de microfabrication fiable et reproductible. Pour montrer l’intérêt des dispositifs de capture des nanoparticules magnétiques, des tests immunologiques ont été réalisés tout d’abord en microtubes pour les comparer à ceux réalisés dans un circuit fluidique à l’aide d’aimant externe puis de microbobines intégrées. Dans ce dernier cas, une optimisation considérable a été validée en termes de réduction de temps d’incubation, de reproductibilité des mesures et de limites de détection équivalentes à l’état de l’art pour l’ovalbumine. Pour le dispositif de détection magnétique, des premières expériences de caractérisation électrique ainsi que des études en concentration de nanoparticules magnétiques ont été réalisées et comparées aux résultats obtenus par simulation. Pour la preuve de concept, un démonstrateur de détection de complexes magnétiques a été également finalisé validant la possibilité d’intégration du microcircuit magnétique dans un dispositif fluidique. Il a validé également l’obtention d’une gamme de sensibilité remarquable corrélée à la présence des complexes magnétiques. Ses caractéristiques ont été confrontées à celles obtenues par les simulations et discutées en tenant compte de toutes les étapes critiques du procédé de microfabrication. / RésuméThe objective of this thesis is the fabrication of a magnetic microdevice for the detection and manipulation of biological elements based on magnetic nanoparticles under microfluidic conditions. It aims to integrate basic functions of control and magnetic detection, to achieve specific, stable, fast and reproducible measurements. Indeed, the immunoassay technique coupled to magnetic nanoparticles, well known in the literature, requires a control of the displacement of magnetic nanoparticles to effectively functionalize them and create a biological complex to encapsulate a target molecule (biomarker). In our case, a model molecule for the field of biodefense was used: ovalbumin. To control the magnetic field which is necessary for the capture of magnetic complexes, we opted for the use of microcoils integrated in the fluidic devices and compared this original technique with other more conventional ones. To detect a biological complex, fluorescence is widely used in biology, but this technique does not allow a complete integration for an autonomous device. In this context, we propose the detection of complexes based on magnetic nanoparticles by observing the variation of the inductance of a magnetic microcircuit closing a microfluidic chamber containing these immunological complexes. The design of the control microcoils by simulation made it possible to determine the parameters allowing to obtain the most adapted magnetic field to the control of the biological complexes. In the case of microcoils used for detection, micrometric magnetic branches were inserted around the microcoils to create an even more sensitive magnetic sensing circuit. The realization of these devices involved the integration of materials and structures of highly heterogeneous nature, and their assembly has required to solve many technological locks. The challenge was to determine all the successive and necessary steps for a reliable and reproducible microfabrication process. To show the interest of magnetic nanoparticle capture devices, immunoassays were first performed in microtubes to compare with those made in a fluid circuit using external magnet and integrated microcoils. In the latter case, considerable optimization has been validated in terms of reduction of incubation time, reproducibility of measurements and detection limits equivalent to the state of the art for ovalbumin. For the magnetic detection device, first experiments of electrical characterization as well as concentration studies of magnetic nanoparticles were carried out and compared to the results obtained by simulation. For the proof of concept, a demonstrator of detection of magnetic complexes was also finalized validating the possibility of integration of the magnetic microcircuit in a fluidic device. It has also validated obtaining a remarkable range of sensitivity correlated with the presence of magnetic complexes. Its characteristics were compared to those obtained by the simulations and discussed taking into account all the critical steps of the microfabrication process.

No description available.

In this dissertation a study of enhanced hyperthermia for cancer treatment through the use of magnetic nanoparticles is presented. Hyperthermia has been in use for many years, as a potential alternative method in cancer treatment, and high frequency microwave radiation has been used successfully to raise the tumor temperature to around 42°C in superficial tumors without causing damage to surrounding healthy tissues. Magnetic fluid hyperthermia involves the use of magnetic nanoparticles injected into the tumor before exposure to microwave radiation. The magnetic energy in the nanoparticles is converted into heat allowing for a more rapid rise of temperature in the tumor to the desired level. In addition, the nanoparticles allow the electromagnetic absorption to be focused in the tumor and can be used to treat deep tumors in organs, such as the liver. Iron oxide magnetic nanoparticles were considered for this study as they are non-toxic and bio-compatible. For the case of breast cancer, the values for the temperature and specific absorption rate (SAR) in the tumor and in the healthy tissue were obtained through simulations and validated by measurement done on phantom models. Various characteristics of the nanoparticles such as radius, magnetic susceptibility and concentration were considered. In order to take the effect of the blood flow, which causes cooling and helps maintain the body temperature, various blood perfusion rates for a tumor in the liver were studied. A human male model in SEMCAD X, in which blood flow can be adjusted, was used for simulations. The tumor was injected with the nanoparticles and the change in temperature upon exposure to electromagnetic radiation was observed. The simulated results were compared with measured results on a liver phantom model in which saline solution was used to model blood flow. There was good agreement between the measured and simulated results.

No description available.

The superior properties of carbon nanotubes (CNTs) are best manifest in bulk materials when the CNTs are organized in tandem and embedded in a continuous matrix. Decorating the CNTs with magnetic nanoparticles (MNPs) facilitates their expedient organization with a magnetic field. One of the most convenient methods for their decoration is to first treat the CNTs with oxidative acids, and then coprecipitated MNPs in situ. This method results magnetized CNTs that are covalently functionalized with the MNPs. The associated destruction in the CNTs required running a comparative study of this protocol to identify the influence of the acid treatment on the decoration of multiwalled CNTs (MWNTs). Further, we explore means to tune the physical properties of these magnetized CNTs (mMWNTs) by varying the (1) MNP material composition, and (2) MNP:MWNT (w/w) magnetization weight ratio (γ). The resulted composite materials (mMWNTs) are utilized to synthesize a novel and hitherto unreported class of colloidal suspensions (MCCs) for which the dispersed phase, which consists of MWNTs decorated with MNPs, is both magnetoresponsive and electrically conductive. Synthesis of the dispersed phase merges processes for producing ferrofluids and mMWNTs. Later, these MCCs are adapted and engineered to produce a biological ink containing MWNTs that are twice functionalized, first with MNPs and thereafter with the anti-c-Myc monoclonal antibodies (Abs). The ink is pipetted and dynamically self-organized by an external magnetic field into a dense electrically conducting sensor strip that measures the decrease in current when a sample containing c-Myc antigens (Ags) is deposited on it. On the other side, a nondestructive methods to magnetize MWNTs and provide a means to remotely manipulate them is through the electroless deposition of magnetic nickel nanoparticles on their surfaces. The noncovalent bonds between Ni nanoparticles and MWNTs produce a Ni-MWNT hybrid material (NiCH) that is electrically conductive and has an enhanced magnetic susceptibility and elastic modulus. Raising γ (Ni:MWNT weight ratios) increases the coating layer thickness, which influences the NiCH magnetic properties and tunes its elastic modulus. The NiCH was used to fabricate Ni-MWNT macrostructures and tune their morphologies by changing the direction of an applied magnetic field. Leveraging the hydrophilic Ni-MWNT outer surface, a water-based conductive ink was created and used to print a conductive path that had an electrical resistivity of 5.9 Ωm, illustrating the potential of this material for printing electronic circuits. Further, the NiCHs are introduced into an epoxy matrix at low 0.25-1% volume fractions and aligned along the direction of an applied magnetic field, which produces anisotropic bulk properties. However, nanoparticles aligned in perpendicular directions in sequential layers result in an effectively isotropic composite material. Furthermore, the subsequent annealing of the NiCH in the presence of air oxidizes nickel to nickel oxide whereas carbon is released as gaseous carbon dioxide, which leads to a novel approach for the fabrication of nickel oxide nanotubes (NiONTs) based on MWNTs as a sacrificial template. New chelating polyelectrolytes are used as dispersing agents to achieve high colloidal stability both for NiCH and NiONTs. A gravimetric specific capacitance of 245.3 F g-1 and areal capacitance of 3.28 F cm-2 at a scan rate of 2 mV s-1 is achieved with an electrode fabricated using nickel oxide nanotubes as the active element with a mass loading of 24.1 mg/cm2. / Thesis / Doctor of Philosophy (PhD) / The superior properties of carbon nanotubes (CNTs) are best manifested in bulk materials when the CNTs are organized axially and in tandem, and embedded in a continuous matrix. Decorating the CNTs with magnetic nanoparticles (MNPs) facilitates their organization through “action from a distance” with a magnetic field. The attachment of MNPs to the surfaces of CNTs can be realized through covalent or non-covalent (i.e. physical) bonding. This work develops both methodologies to investigate how the physical properties of magnetized CNT (mCNT) can be tuned and produce new CNT-based nanostructures for particular applications. First, mCNTs are utilized to synthesize a hitherto unreported class of colloidal suspensions based on which a magnetic bio-ink is fabricated to print a fast-response biological sensor. Next, nickel-coated CNTs prepared using electroless deposition are used in the form of a filler at low volume fractions in an epoxy matrix, where they are aligned along multiple-direction using a magnetic field, producing either anisotropic or isotropic bulk properties on demand. Finally, subsequent annealing of nickel-coated CNTs in air oxidizes nickel to nickel oxide while carbon is released in the form of gaseous carbon dioxide. This leads to another novel approach for the fabrication of nickel oxide nanotubes, which are demonstrated to be an alternate viable material to fabricate electrodes for use in supercapacitors.

Nanotechnology has made it possible to create materials with unique properties. This development offers new opportunities and overcomes challenges for many thermal transport applications. Yet, it requires a more fundamental scientific understanding of nanoscale transport. This thesis emphasizes how simulation, mathematical, and numerical methods can lead to more grounded studies of nanoscale thermal transport for biological and physical applications. For instance, magnetic fluid hyperthermia (MFH), an emerging cancer treatment, is a noninvasive method to selectively destroy a tumor by heating a ferrofluid-impregnated malignant tissue with minimal damage to the surrounding healthy tissue. We model the problem by considering an idealized spherical tumor that is surrounded by healthy tissue. The dispersed magnetic nanoparticles in the tumor are excited by an AC magnetic field to generate heat. The temperature distribution during MFH is investigated through a bioheat transfer relation which indicates that the P\'eclet, Joule, and Fourier numbers are the more influential parameters that determine the heating during such a thermotherapy. Thus, we show that a fundamental parametric investigation of the heating of soft materials can provide pathways for optimal MFH design. Since ferrofluid materials themselves play a key role in heating, we examine six materials that are being considered as candidates for MFH use. These are simulated to investigate the heating of ferrofluid-loaded tumors. We show that iron-platinum, magnetite, and maghemite are viable MFH candidates since they are able to provide the desired heating of a tumor which will destroy it while keeping the surrounding healthy tissues at a relatively safe temperature. Recent advances in the synthesis and nanofabrication of electron devices have lead to diminishing feature sizes. This has in turn increased the power dissipation per unit area that is required to cool the devices, leading to a serious thermal management challenge. The phonon thermal conductivity is an important material property because of its role in thermal energy transport in semiconductors. A higher thermal conductivity material is capable of removing more heat since higher frequency phonons are able to travel through it. In this thesis, the effects of surface stress on the lattice thermal conductivity are presented for a silicon nanowire. Based on a continuum approach, a phonon dispersion relation is derived for a nanowire that is under surface stress and the phonon relaxation time is employed to subsequently determine its thermal conductivity. The surface stress is found to significantly influence the phonon dispersion and thus the Debye temperature. Consequently, the phonon thermal conductivity decreases with increasing surface stress. Different magnitudes of surface stress could arise from various material coatings and through different nanofabrication processes, effects of which are generally unclear and not considered. Our results show how such variations in surface stress can be gainfully used in phonon engineering and to manipulate the thermal conductivity of a nanomaterial. The thermal transport during thermoelectric cooling is also an important property since thermoelectric devices are compact, reliable, easy to control, use no refrigerants and require lower maintenance than do more traditional refrigeration devices. We focus on the Thomson effect that occurs when there is a current flow in the presence of a temperature gradient in the material, and investigate its influence on an intrinsic silicon nanowire cooler. The temperature dependence of the Thomson effect has a significant influence on the cooling temperature. We also consider thermal nonequilibrium between electrons and phonons over the carrier cooling length in the nanowire. The results show that a strong energy exchange between electrons and phonons lowers the cooling performance, suggesting useful strategies for thermoelectric device design. / Ph. D.

Two-dimensional (2D) nanoscale confinement effects on poly(ε-caprolactone) (PCL) crystallization were probed through crystallization studies of PCL-b-poly(tert-butyl acrylate) (PCL-b-PtBA) copolymers, PCL with bulky tri-tert-butyl ester endgroups (PCL triesters), PCL with triacid end groups (PCL triacids), and magnetic nanoparticles stabilized by PCL triacid (PCL MNPs) at the air/water (A/W) interface. Thermodynamic analyses of surface pressure-area per monomer (Π−A)) isotherms for the Langmuir films at the A/W interface showed that PCL-b-PtBA copolymers, PCL triheads and PCL MNPs all formed homogenous monolayers below the dynamic collapse pressure of PCL, Π_C ~11 mN•m⁻¹. For compression past the collapse point, the PCL monolayers underwent a phase transition to three-dimensional (3D) crystals and the nanoscale confinements impacted the PCL crystalline morphologies. Studies of PCL-b-PtBA copolymers revealed that the morphologies of the LB-films became smaller and transitioned to dendrites with defects, stripes and finally nano-scale cylindrical features as the block length of PtBA increased. For the case of PCL triester, irregularly shaped crystals formed at the A/W interface and this was attributed to the accumulation of bulky tert-butyl ester groups around the crystal growth fronts. In contrast, regular, nearly round-shaped lamellar crystals were obtained for PCL triacids. These morphological differences between PCL triacids and PCL triesters were molar mass dependent and attributed to differences in dipole density and the submersion of carboxylic acid groups in the subphase. Nonetheless, enhanced uniformity for PCL triacid crystals was not retained once the polymers were tethered to the spherical surface of a PCL MNP. Instead, the PCL MNPs exhibited small irregularly shaped crystals. This nano-scale confinement effect on the surface morphology at the A/W interface was also molar mass dependent. For the small molar mass PCL MNPs, two layers of collapsed nanoparticles were observed. In a later chapter, studies of polyethylene glycol (PEG) surfactant adsorption onto phospholipid bilayers through quartz crystal microbalance with dissipation monitoring (QCM-D) measurements revealed a strong dependence of the adsorption and desorption kinetics on hydrophobic tail group structure. PEG surfactants with a single linear alkyl tail inserted and saturated the bilayer surface quickly and the surfactants had relatively fast desorption rates. In contrast, PEG lipids, including dioleoyl PEG lipids and cholesterol PEGs, demonstrated slower adsorption and desorption kinetics. The interactions of Pluronics and Nonoxynol surfactants with phospholipid bilayers were also studied. Pluronics showed no apparent affinity for the phospholipid bilayer, while the Nonoxynol surfactants damaged the lipid bilayers as PEG chain length decreased. / Ph. D.

No / Cd3P2 quantum dots (QDs) have been synthesized in both aqueous and high boiling point surfactant solutions via a gas-bubbling method. The synthesized QDs exhibit photoluminescent wavelengths spanning across the visible red to the near-infrared (NIR) spectral region. Two types of shell materials, SiO2 nanobeads and PS micro-spheres, have been employed to encapsulate the Cd3P2 QDs which provide protecting layers against physiological solutions. The coating layers are proven to enhance the optical and chemical stability of Cd3P2 QDs, and make the fluorescent particles capable of sustaining long-term photo-oxidation. To demonstrate the applicability of the bio-labelling, the fluorescent composite particles (PS@QDs, SiO2@QDs) were injected into a culture medium of colorectal carcinoma (LoVo) cells. The results demonstrated that the PS@QDs exhibited a brighter fluorescence, but the SiO2@QDs provided a better photostability which consequently led to long-term cancer cell detection as well as a much lower release of toxic Cd2+ into the PBS solutions.

Μαγνητικά νανοσωματίδια οξειδίων του σιδήρου παρασκευάσθηκαν μέσω της αλκαλικής συμπύκνωσης και ελεγχόμενης καταβύθισης συμπλόκων ιόντων FeII, υπό την παρουσία τυχαίου συμπολυμερούς PAA-co-MA. Οι παράμετροι της σύνθεσης μεταβλήθηκαν με σκοπό την απομόνωση προϊόντων που να εμφανίζουν τις καλύτερες μαγνητικές ιδιότητες. Όλα τα προϊόντα εμφάνισαν υψηλή κολλοειδή σταθερότητα σε υδατικά μέσα χαμηλής ιοντικής ισχύος, ενώ ο σιδηρομαγνητικός τους χαρακτήρας έδειξε να ποικίλει από ασθενής μέχρι αρκετά ισχυρός, όπως προέκυψε μετά τον χαρακτηρισμό τους με μαγνητοφόρηση και μαγνητική υπερθερμία με εναλλασόμενο μαγνητικό πεδίο. Το μέσο μέγεθος των νανοκρυσταλλιτών ήταν διαφορετικό σε κάθε προϊόν κυμαινόμενο από περίπου 3 έως 14 nm, όπως προσδιορίστηκε μέσω XRD. Η ανάλυση με ΤΕΜ έδειξε ότι στο προϊόν που εμφανίζει τις καλύτερες μαγνητικές ιδιότητες σχηματίζονται πλειάδες νανοσωματιδίων πυκνής διάταξης, και στις οποίες αποδίδεται η βελτιωμένη απόκριση σε μαγνητικά πεδία. Τα άλλα προϊόντα εμφάνισαν μικρότερα μεγέθη κρυσταλλιτών και διαφορετικά δομικά χαρακτηριστικά. Τα κολλοειδή καταβυθίζονταν κατόπιν αύξησης της ιοντικής ισχύος του διαλύτη. Για τον λόγο αυτό αποφασίστηκε η μελέτη της αντίδρασης σύζευξης των εξωτερικών καρβοξυλικών ομάδων του πολυμερικού φλοιού με mPEG-NH2, δεδομένου ότι η PEG αυξάνει σημαντικά τη σταθερότητα των κολλοειδών. Παρά το γεγονός ότι χρησιμοποιήθηκαν κοινά αντιδραστήρια σύζευξης, μόνο υπό πολύ ειδικές συνθήκες η απόδοση της αντίδρασης ήταν ικανοποιητική, οπότε και προέκυψαν σταθερά κολλοειδή σε συνθήκες υψηλής ιοντικής ισχύος. Τέλος, τα προϊόντα αξιολογήθηκαν για την ικανότητά τους να επάγουν υπερθερμία και μελετήθηκε ο χρόνος χαλάρωσης Τ2, ο οποίος σχετίζεται άμεσα με την ενίσχυση της αντίθεσης στην απεικόνιση μέσω μαγνητικού συντονισμού. Τέλος, ένα από τα προϊόντα, μελετήθηκε in vitro και in νίνο, προκειμένου να αξιολογηθεί η βιοσυμβατότητα του. Τα συστήματα αυτά παρουσιάζουν πολύ ενδιαφέρουσες ιδιότητες ώστε να τροποποιηθούν και να μελετηθούν περεταίρω ως θεραπευτικά ή/και διαγνωστικά νανοϋλικά. / Μagnetic nanoparticles of iron oxides were synthesized through condensation and controlled precipitation of a FeII complex, in alkaline environment, in the presence of a random copolymer PAA-co-MA, as polymeric corona. The synthetic parameters were varied with the aim of isolating products exhibiting the best magnetic properties. All products displayed high colloidal stability in low ionic strength aqueous media, while their ferromagnetic properties varied from weak to quite strong, as deduced after the characterization with magnetophoresis and magnetic hyperthermia with alternating magnetic field. The average crystallite size, as determined through XRD, varied from 8 to 14 nm depending on the product. TEM analysis showed that the product displaying the best magnetic properties formed clusters of densely packed nanocrystallites, leading to interesting superstructural motifs. All the other products displayed smaller crystallite sizes and different structural characteristics. The colloids precipitated upon increase of the ionic strength of the solvent (H2O) with NaCl. Therefore, it was decided to study the conjugation of the outer carboxyl groups of the polymeric corona with mPEG-NH2, since PEG is known to increase significantly the stability of colloids. Despite the fact that common conjugation reagents were used, only under specific conditions the yied of the reaction was appropriately high in order the resultant colloids to be stable in a high ionic strength (isotonic) medium. Finally the products were evaluated for their performance in magnetic hyperthermia and for contrast enhancement in magnetic resonance imaging, by studying the T2 relaxation time. One of the products was furthermore studied by in vitro and in vivo systems, in order to evaluate its biocompatibility. These colloidal systems exhibit very interesting properties in order to be further modified and studied as therapeutic and / or diagnostic (theragnostic) nanomaterials.