Microfluidic magnetic particles manipulation

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.

Nanoscale superparamagnetic composite particles for biomedical applications

Mathieu Chastellain

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 ...

EPFL2004

Manipulation of Self-Assembled Structures of Magnetic Beads for Microfluidic Mixing and Assaying

Martinus Gijs, Amar Rida

We present an original concept of manipulation of magnetic microbeads in a microchannel. It is based on the dynamic motion of a self-assembled structure of ferrimagnetic beads that are retained within a microfluidic flow using a local alternating magnetic field. The latter 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, and is at the basis of very efficient liquid mixing. The principle is demonstrated using a microfluidic chip made of poly(methyl methacrylate) with integrated soft ferromagnetic plate structures. The latter are part of an electromagnetic circuit and serve to locally apply a magnetic field over the section of the microchannel. Starting from a laminar flow pattern of parallel fluorescein dye and nonfluorescent liquid streams, we demonstrate a 95% mixing efficiency using a mixing length of only 400 m and at liquid flows of the order of 0.5 cm/s. 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.

2004

Growth and magnetism of 2D bimetallic nanostructures

Géraud Moulas

This thesis addresses the growth and magnetic characterization of 2D bimetallic nanostructures deposited by atomic beam epitaxy (ABE) on Pt(111). These structures possess both tunable high perpendicular magnetic anisotropy (PMA) and magnetic moment. These properties make them appealing as model systems in order to learn how to control the properties of the futures media used in magnetic data storage. Our study combined two in situ measurements techniques : variable-temperature scanning tunneling microscopy (VT-STM) as a local probe allows insight on the morphology of nanostructures, while magneto-optic Kerr effect (MOKE) is a spatially integrating technique giving access to the variation of the overall magnetization of a sample. The first part of this work focuses on the growth of iron on the Pt(111) surface. Growth was investigated on the atomic scale as a function of the substrate temperature in the case of low coverages. We have fitted the mean cluster size as a function of the annealing temperature with mean field rate equations for diffusion-controlled growth. The activation parameters for monomer, dimer and trimer diffusion could be inferred from this procedure. The formation of monatomic Fe wires has also been evidenced on the temperature range 160 K–260 K. The origin of their formation was discussed. In a second part, we have made use of our knowledge on the growth of cobalt and iron on Pt(111) in order to fabricate "core-shell" Co nanostructures of which density, size and shape were controlled. Therefore, we could realized both compact and ramified structures within the size range 800–1800 atoms. The study of the mechanism of magnetization reversal of these model structures has revealed a strong size and shape dependence. This is due to the shape-induced non-uniformity of the local magnetization and the number of pinning centers. The conclusions are that ramified structures with arms longer than 150 Å reverse their magnetization by nucleation and domain-wall motion while compact structures reverse coherently their magnetization. The third part deals with the magnetic properties of one monolayer thick bimetallic "Co core-shell" nanostructures on Pt(111). The blocking temperature TB marks the transition between superparamagnetic and blocked states and is inferred from the magnetic anisotropy. Here, we performed magnetic zero-field susceptibility measurements so as to determine TB in our samples. From our experiments, we show the possibility to make up a fine tuning of the nanostructure magnetic anisotropy and overall magnetization. In the case of the FexCo1-x alloy, TB adopt a bell-shape with x and exhibit a maximum at x = 0:5. The various lateral and vertical interfaces between Co from one side and Fe, Pt or Pd from the other side are at the origin of substantial TB variation. Those variations are inferred from the symmetry breaking and the strong hybridization between the d orbitals of these elements.