We studied the migration of nonmagnetic, submicrometer polystyrene beads submerged in a magnetic fluid in the presence of nonuniform magnetic fields as a potential method for size-based separation of submicrometer, nonmagnetic species. Since the polystyrene beads are much larger than the magnetic fluid nanoparticles, the magnetic fluid was treated as a one-component continuum with respect to the beads. We found that the polystyrene beads will migrate in the direction of decreasing magnetic fields and will focus over a region where the magnetic field or its gradient vanishes, as predicted by our model. The concentration profiles predicted by our model, which has no adjustable or fitted parameters, agree reasonably well with the experimental data both qualitatively and quantitatively. / Singapore-MIT Alliance (SMA)

The objective of the research in this dissertation is to develop microsystem based separation technologies for whole cell cancer analysis using human whole blood as the input sample. This research work is carried out with two different approaches; one based on a miniaturized cascade magnetophoresis system and a second based on dielectrophoresis. The miniaturized systems can be fabricated using MEMS technologies combined with plastic fabrication techniques. The design, fabrication, packaging, and characterization of several versions of the magnetophoresis and dielectrophoresis microsystems for whole cell cancer analysis in human whole blood sample are presented. The developed magnetophoresis systems have demonstrated improved throughput in the removal of RBC from a human whole blood sample and its application to the separation of tagged cancer cells based on their surface expression level of a specific protein. The dielectrophoresis microsystem has successfully shown the ability to steer a blood stream between two outlets and to separate WBCs or cancer cells from a human whole blood sample. The developed microsystem based separation technologies can be further applied to the development of integrated system for cancer detection and treatments.

<p>This thesis will investigate previously unexplored concepts in magnetic manipulation including controlling the assembly of magnetic and nonmagnetic particles either in bulk fluid or near a substrate. Both uniform glass interfaces and substrates with magnetic microstructures are considered. The main goal of this work is to discuss new strategies for implementing magnetic assembly systems that are capable of exquisitely controlling the positions and orientations of single-component as well as multi-component particle suspensions, including both magnetic and non-magnetic particles. This work primarily focuses on controlling spherical particles; however, there are also several demonstrations of controlling anisotropically shaped particles, such as microrods and Janus colloids. </p><p> Throughout this work, both conventional magnetophoresis and inverse magnetophoresis techniques were employed, the latter relying on ferrofluid, i.e. a suspension of magnetic nanoparticles in a nonmagnetic carrier fluid, which provides a strong magnetic permeability in the surrounding fluid in order to manipulate effectively non-magnetic materials. In each system it was found that the dimensionless ratio between magnetic energy and thermal energy could be successfully used to describe the degree of control over the positions and orientations of the particles. One general conclusion drawn from this work is that the ferrofluid can be modeled with a bulk effective permeability for length scales on the order of 100 nm. This greatly reduces modeling requirements since ferrofluid is a complex collection of discrete nanoparticles, and not a homogenous fluid. It was discovered that the effective magnetic permeability was often much larger than expected, and this effect was attributed to particle aggregation which is inherent in these systems. In nearly all cases, these interactions caused the ferrofluid to behave as though the nanoparticles were clustered with an effective diameter about twice the real diameter.</p><p> The principle purpose of this thesis is to present novel systems which offer the ability to manipulate and orient multi-component spherical or anisotropic particle suspensions near surfaces or in the bulk fluid. First, a novel chip-based technique for transport and separation of magnetic microparticles is discussed. Then, the manipulation of magnetic nanoparticles, for which Brownian diffusion is a significant factor, is explored and modeled. Parallel systems of nonmagnetic particles suspended in ferrofluid are also considered in the context of forming steady state concentration gradients. Next, systems of particles interacting with planar glass interfaces are analyzed, modeled, and a novel application is developed to study the interactions between antigen-antibody pairs by using the self-repulsion of non-magnetic beads away from a ferrofluid/glass interface. This thesis also focuses on studying the ability to manipulate particles in the bulk fluid. First, simple dipole-dipole aggregation phenomenon is studied in suspensions of both nonmagnetic polystyrene particles and endothelial cells. For the sizes of particles considered in these studies, currently accepted diffusion limited aggregation models could not explain the observed behavior, and a new theory was proposed. Next, this thesis analyzed the interactions that exist in multi-component magnetic and nonmagnetic particle suspensions, which led to a variety of novel and interesting colloidal assemblies. This thesis finally discusses the manipulation of anisotropic particles, namely, the ability to control the orientation of particles including both aligning nonmagnetic rods in ferrofluid as well as achieving near-holonomic control of Janus particles with optomagnetic traps. General conclusions of the viability of these techniques are outlined and future studies are proposed in the final chapter.</p> / Dissertation

Made available in DSpace on 2014-07-29T15:07:08Z (GMT). No. of bitstreams: 1 Marcus Carriao dos Santos Dissertacao.pdf: 903168 bytes, checksum: 91f54bc8f60266322bb1f15c18b8d279 (MD5) Previous issue date: 2011-04-13 / In this work a magnetophoretic experiment (MPE) was developed to study the effect of a gradient of magnetic field in the diameter and size dispersivity of nanoparticles in a magnetic fluid (MF). In this experiment, the mass of a permanent magnet is measured by a balance which data varied due to the interaction with the magnetic fluid, which is placed a few centimeters above. Curves of variation of apparent mass of the magnet were obtained as function of time and related to the characteristics of fractions taken from the surface of the MF at different times. The MF consisted of magnetite nanoparticles surface-coated with phosphate. Samples were synthesized by the coprecipitation method and characterization was performed using x-ray diffraction, high resolution transmission electron microscopy (HR-TEM) and vibrating sample magnetometry (VSM). Fractions of the MF were taken during the MPE at five different times. Those fractions were characterized by VSM, from which magnetic diameters were estimated. The magnetic diameters showed a decrease of nanoparticle size in the surface of the MF sample submitted to MPE for longer times of exposure to the field gradient. These same fractions were characterized by HR-TEM and histograms of nanoparticles size distribution were made. Studies of mean and modal (obtained by lognormal fit) diameters had confirmed the behavior indicated by the magnetic diameters showing a decrease of size as function of time. Studies of standard deviation and full width at half maximum (obtained by lognormal fit) had shown a decrease in dispersivity. However, studies of the &#963; factor were inconclusive, since no significant variations were found for nanoparticles at the experimental size range. Indeed, the MPE results had shown a variation of 16.02% in modal diameter (Dmodal), 14.63% in mean diameter, 30.90% in standard deviation e 33.33% in full width at half maximum between the original sample and the part which was exposed to gradient magnetic field by 60 hours, of fluid with largest initial diameter (Dmodal = 9.24±0.08 nm and &#963;=0.238±0.009). In addition magnetohyperthemia experiments at 300 kHz were obtained for each sample. Higher specific absorption rates were found for larger particle sizes, which have important applications for cancer treatment. Therefore, we concluded that the magnetophoretic experiment can be used to select the magnetic fluids properties, due to diameter and size standard deviation control, for several technological, environmental and biomedical applications. / Neste trabalho foi desenvolvido um experimento magnetoforético (EMF) para estudar o efeito de um gradiente de campo magnético sobre o diâmetro e dispersão de tamanhos de nanopartículas em fluidos magnéticos (FM). Neste experimento, a massa de um imã permanente é medida por uma balança enquanto varia graças à interação com o FM, colocado alguns centímetros acima. Curvas de variação da massa aparente do imã foram obtidas em função do tempo e relacionadas às características de alíquotas retiradas da superfície do FM em tempos distintos. Os fluidos eram constituídos de nanopartículas de magnetita recobertas com fosfato. As amostras foram sintetizadas pelo método de coprecipitação e caracterizadas por difratometria de raios-x, microscopia eletrônica de transmissão de alta resolução (HR-TEM) e magnetometria de amostra vibrante (VSM). Foram retiradas alíquotas do EMF em cinco intervalos de tempo distintos. Essas alíquotas também foram caracterizadas por VSM e foram estimados diâmetros magnéticos a partir delas. Os diâmetros magnéticos mostraram uma diminuição do tamanho das nanopartículas na superfície da amostra submetida ao EMF para tempos maiores de exposição ao gradiente de campo. Essas mesmas alíquotas foram ainda caracterizadas por HR-TEM e foram construídos histogramas com os tamanhos das nanopartículas. Estudos dos diâmetros médios e modais (obtido pelo ajuste lognormal) confirmaram o comportamento estimado pelos diâmetros magnéticos e mostraram a diminuição do tamanho das nanopartículas em função do tempo. O estudo dos desvios padrão e da largura a meia altura (obtido pelo ajuste lognormal) indicaram uma diminuição da dispersão. O estudo do fator &#963; (parâmetro do ajuste lognormal) foi inconclusivo, não apresentando variações significativas na faixa de tamanhos estudada. Os resultados mostraram que o EMF produziu uma variação de 16,02% no diâmetro modal (Dmodal), 14,63% no diâmetro médio, 30,90% no desvio padrão e 33,33% na largura a meia altura entre a amostra original e a alíquota exposta ao gradiente de campo por 60 horas, para o fluido de maior diâmetro inicial (Dmodal = 9,24±0,08 nm e &#963;=0,238±0,009). Estudos de magnetohipertermia foram realizados a 300kHz para as alíquotas estudadas. Foram encontradas taxa de absorção específicas (SAR) maiores para sistemas com nanopartículas maiores, propriedade muito importante nas aplicações relacionadas ao tratamento de câncer. Portanto, conclui-se que o experimento magnetoforético pode ser utilizado para selecionar propriedades de fluidos magnéticos, por meio do controle do diâmetro e desvio padrão de tamanhos, para diversas aplicações tecnológicas, ambientais e biomédicas.

No description available.

No description available.

No description available.

Les micro et nanoparticules magnétiques sont de plus en plus utilisées en biologie et en médecine, pour une large gamme d'applications. Plusieurs applications utilisent le piégeage et le guidage de ces billes sous l'effet d'un champ et d'un gradient de champ magnétique. Dans la plupart des applications, le champ magnétique est macroscopique, créé par un aimant ou un électro-aimant. L'intégration plus poussée est souvent envisagée, dans les articles scientifiques, par des microbobines ou par des éléments magnétiques doux. Ceux-ci doivent alors être polarisés par un champ externe (de nouveau, un électroaimant ou un aimant).Les micro-aimants mis au point à l'Institut Néel permettent d'obtenir les mêmes inductions que les meilleurs aimants du marché et, par conséquent, de par la réduction d'échelle, des gradients de champ intenses et donc des forces volumiques très conséquentes. Ils sont, de plus, favorables à l'autonomie et à la stabilité du système.Ce travail propose d'utiliser ces micro-aimants pour des applications en diagnostic In Vitro afin de tirer parti des forces volumiques importantes issues des micro-aimants et de la facilité d'utilisation de telles sources de champ magnétiques pour l'utilisateur.Ces premières constatations nous ont permis de mettre un place un test de type ELISA en une seule étape. Grâce à ces avantages, il a été possible d'utiliser des nanoparticules magnétiques à la place des classiques microparticules comme rapporté dans l'état de l'art. Ces nanoparticules, fonctionnalisables par des anticorps permettent entre autre d'augmenter le rapport surface sur volume phénomène très favorable à la sensibilité des tests de diagnostic In Vitro. De plus, les nanoparticules étant de petite taille, il est possible d'augmenter fortement leur concentration et de favoriser ainsi la capture de ces particules par les micro-aimants grâce à un mécanisme d'interaction fluide/particule et in fine la cinétique du test.Un autre avantage des micro-aimants permanents est la possibilité de contrôler le champ magnétique sur des distances micrométrique. Cela ouvre la voie à des tests de diagnostic sans lavage, simples et sensibles. Enfin, tous ces avantages ont été combinés à ceux de la microfluidique pour permettre l'émergence de test portables tout en restant efficaces. Pour cela l'autonomie intrinsèque aux micro-aimants permanents sera un avantage incontestable. / The range of applications for magnetic micro- and nanoparticles is constantly expanding, in particular in medicine and biology. A number of applications involve particle trapping and deviation under the effect of a magnetic field and field gradient. In most publications, the required magnetic fields are produced either using soft magnetic elements polarized by an external magnetic field, electromagnets or bulk permanent magnets.Micromagnets produce high fields and favor autonomy and stability while downscaling leads to an increase of field gradients and consequently increase strongly the forces.Micromagnets developped at the Neel Institute produce magnetic induction as good as the best macro-magnets. Therefore, thanks to scale reduction laws, high field gradients and therefore intense forces can be obtained. Moreover, these magnets can easily be integrated in micro systems such as BioMEMS.The purpose of this work is to use these micromagnets to develop in vitro immunoassays.. An innovative system based on superparamagnetic nanoparticles attraction by micromagnets was developed in order to perform a “one step” ELISA.Nanoparticles can be functionalized with antibodies, increasing the surface/volume ratio, and therefore the test sensitivity. Thanks to their small size, the nanoparticles concentration can be increased, and a fluid/particles interaction optimizes their capture by the micromagnets. This phenomena is favorable to immunoassay's kinetics.A micrometric control of the magnetic field is possible thanks to micromagnets: this allows to design simple and sensitive immunoassays that need no washing steps. Finally, these properties combined to microfluidics is used to design of point of care and sensitive immunoassays.

Many scientists and engineers are turning to lab-on-a-chip systems for cheaper and high throughput analysis of chemical reactions and biomolecular interactions. In this work, we developed several lab-on-a-chip modules based on novel manipulations of individual microbeads inside microchannels. The first manipulation method employs arrays of soft ferromagnetic patterns fabricated inside a microfluidic channel and subjected to an external rotating magnetic field. We demonstrated that the system can be used to assemble individual beads (1-3µm) from a flow of suspended beads into a regular array on the chip, hence improving the integrated electrochemical detection of biomolecules bound to the bead surface. In addition, the microbeads can follow the external magnet rotating at very high speeds and simultaneously orbit around individual soft magnets on the chip. We employed this manipulation mode for efficient sample mixing in continuous microflow. Furthermore, we discovered a simple but effective way of transporting the microbeads on-chip in the rotating field. Selective transport of microbeads with different size was also realized, providing a platform for effective sample separation on a chip. The second manipulation method integrates magnetic and dielectrophoretic manipulations of the same microbeads. The device combines tapered conducting wires and fingered electrodes to generate desirable magnetic and electric fields, respectively. By externally programming the magnetic attraction and dielectrophoretic repulsion forces, out-of-plane oscillation of the microbeads across the channel height was realized. Furthermore, we demonstrated the tweezing of microbeads in liquid with high spatial resolutions by fine-tuning the net force from magnetic attraction and dielectrophoretic repulsion of the beads. The high-resolution control of the out-of-plane motion of the microbeads has led to the invention of massively parallel biomolecular tweezers.

Les puces microfluidiques sont des éléments clés pour la manipulation et l'analyse de solutions et d'échantillons biologiques. Elles facilitent les études aux échelles microscopiques et sont le fondement du concept de laboratoire sur puce, à la pointe des diagnostics médicaux. L'objectif de ces travaux de thèse a été d'explorer les possibilités fonctionnelles offertes par les architectures microfluidiques 3D, dans le cadre du développement d'outils diagnostiques reposant sur le tri, le marquage et la manipulation de cellules. Ces fonctions ont été validées sur des sous-populations de monocytes, qui sont des marqueurs de maladies inflammatoires. Afin de couvrir une chaîne cohérente d'étapes nécessaires au prétraitement des échantillons biologiques complexes, trois fonctions complémentaires ont été étudiées : le tri par taille par filtration hydrodynamique, le tri immunologique par séparation magnétique et le marquage sur puce par microparticules magnétiques. En vue d'effectuer des réactions de marquage (sondes fluorescentes ou microbilles magnétiques), un micro-mélangeur reposant sur la séparation et recombinaison de flux (transformation du boulanger) a été fabriqué et caractérisé. Des expériences de test des dispositifs pour les mélanges fluorescéine/eau et cellules/microbilles sont proposées, ainsi que les modèles analytiques et numériques associés. De nouvelles approches de tri par taille par filtration hydrodynamique ont été étudiées, en réalisant des structures 3D en "bypass", qui rendent possible une stratégie de mélange adaptée aux cellules et particules. Un modèle analytique des écoulements et de l'efficacité de tri et de mélange est proposé, ainsi qu'une caractérisation des dispositifs. Il a été de plus démontré que cette approche permettait également de réaliser la séparation d'espèces sub-micrométriques comme les microparticules sanguines. Tous les systèmes microfluidiques 3D ont été obtenus par une technique originale d'empilement (laminage) de films secs photosensibles, réduisant nettement le temps de micro-fabrication et compatibles avec les procédés standards. Cette technique de fabrication permet également l'intégration de micro-sources magnétiques dans les laboratoires sur puce par la réalisation de micro-bobines planaires sous des canaux microfluidiques. En couplant les effets des micro-bobines intégrées aux champs générés par des aimants extérieurs, nous apportons la preuve de concept de systèmes pour la séparation, la déviation et le piégeage de microbilles magnétiques. Les modèles (champs et force magnétiques) et la caractérisation des dispositifs seront présentés. Nous aborderons également la réalisation d'instrumentation spécifique (source de courant) pour l'actionnement des bobines, permettant le contrôle (temporel et en intensité) des champs magnétiques appliqués. / Microfluidic chips are key elements for solutions and biological samples handling and analysis. They are enablers for micro-scale studies and are the cornerstone of lab on chips, at the cutting edge of medical diagnostics. The aim of this thesis work was to explore functional possibilities offered by 3D microfluidic architectures for the development of diagnostic tools relying on cell sorting, tagging and handling. These functions were investigated on monocytes sub-populations, which are markers for many inflammatory diseases. In order to cover a consistent series of necessary steps for complex biological samples pretreatment, three additional functions were studied: size sorting with hydrodynamic filtration, immuno-isolation by magnetic separation, and on-chip tagging with magnetic microparticles. To perform tagging reactions, a micromixer based on diffusion and flow split and recombination (baker's transform) was fabricated and characterized. Analytical (diffusion) and numerical (diffusion-advection) models are showed, together with test experiments on the devices for mixing reactions of fluorescein/water and cells/microbeads. New approaches of hydrodynamic filtration based size sorting were investigated by devising 3D bypass structures, that allow developing a mixing strategy (tagging reactions) suited to cells and particles. An analytical model for flows and sorting efficiency is introduced and compared to the devices characterization. Furthermore, it was shown that this approach also enables sorting of sub-micron particles (like blood microparticles). All 3D microfluidic systems were obtained thanks to an original dry film photoresist stacking (lamination) technique, dramatically reducing micro-fabrication time, even though compatible with standard process. This fabrication technique also enables magnetic micro-sources integration in lab on chips by realizing planar micro-coils underneath microfluidic channels. By coupling the effects of integrated micro-coils to the fields generated by external magnets, we brought the proof of concept of systems dedicated to trapping, focusing and separating (in flow) magnetic microbeads. Models (magnetic fields and forces) are described along with devices characterization. Conception of specific instrumentation (current source) for micro-coils actuation is also shown, as it allows time and intensity control over applied magnetic fields.