Single Superparamagnetic Bead Detection and Direct Tracing of Bead Position Using Novel Nanocomposite Nano-Hall Sensors

We show that nanocomposite materials consisting of superparamagnetic nanoparticles embedded in a matrix are very good candidates for a novel generation of Hall nanosensors with high spatial and magnetic resolution, capable of detecting superparamagnetic beads suspended at different heights on top of the sensor. Two detection schemes were used: 1) static-the bead was centered on top of the sensor and detected with a combination of ac and dc orthogonal magnetic fields, and 2) dynamic-using nanomanipulation in an electron microscope for moving the bead precisely at different heights above the sensor and using only one magnetic field (ac). The Hall sensors were directly written by focused-electron-beam-induced deposition and the active area was refined by focused ion beam milling. A magnetic field resolution of about 300 mu T(Hz)(-1/2) and a spatial resolution of 230 nm(Hz)(-1/2) were measured. Both resolutions could be improved by at least an order of magnitude with the suppression of the parasitic inductive signals.

Micro and nano tools for magnetic field imaging

Schahrazede-Lila Mouaziz

Scanning probe microscopy has become, nowadays, a branch of microscopy widely used to image surfaces of different specimens. Among the various applications, the magnetic imaging is one of the most exciting scanning probe microscopy techniques. It allows the study of topography of samples at the nanometer scale. The magnetic force microscopy is the best known and the most employed magnetic imaging technique. It has been successfully used for the imaging of various samples but with the major inescapable limitations that it is confined to the surface, non-quantitative and invasive. Techniques such as the scanning Hall probe microscopy (SHPM) and the magnetic resonance force microscopy (MRFM) have emerged, several years later, as promising approaches to overcome these limitations. In this thesis, we present the design, the fabrication and the characterization of, first, micro-Hall sensors on SU-8 cantilevers used for SHPM and, second, of ultrasensitive Si cantilevers used for MRFM experiments. A microfabrication technique has been developed to produce hybrid devices consisting of micro-nano Hall sensors integrated on SU-8 cantilevers. Two materials have been used to produce the Hall sensors. First, bismuth (Bi) was chosen for its low carrier charge density and its negligible surface charge depletion effects so that it should provide sensitive sensors. The second material tested was nickel (Ni), chosen for the dominant effect called the extraordinary Hall effect. The active areas of 5×5, 2×2 and 1×1 µm2 were realized and reproduced with the standard photolithography. Producing submicron Hall sensors required the use of the focused ion beam (FIB) that allowed a decrease of the size of the sensors down to 80×80 nm2. The delicate transferring of the nano sensors on the polymer cantilevers was successful. Bi micro-Hall sensors have shown a fragility making them delicate to handle. However, the Ni micro-Hall sensors had an excellent functionality. Their characterization has shown sensors with a low sensitivity compensated by the high applied current providing a high magnetic field resolution. The magnetic field images were carried out using the Ni micro-Hall sensors. They had a high stability during the imaging experiments. The spatial resolution was set by the sensors active area limited to the micro-meter scale. However, the magnetic field resolution is better than 1 T/√Hz a result comparable to the high resolution offered by the semiconductors. Single crystal silicon cantilevers have been fabricated for use in MRFM experiments. Also, cantilevers with integrated micro-magnets have been successfully produced. The developed microfabrication technique has allowed a high yield production (up to 70%). The softest fabricated cantilevers are 0.34 µm thick, 500 µm long and 10 µm wide. These cantilevers have been characterized under vacuum conditions (1×10-6 mbar). The resonance frequencies and the quality factors were measured using the frequency sweep or noise methods and both provided the same results. The Rayleigh method that we have adapted to the cantilevers geometry, made it possible to estimate the theoretical resonance frequencies with a good approximation and the calculated values fit well with the measured ones. All the cantilevers have a quality factor above 20000 and the force sensitivity achieved was between 10-16 and 10-17 N/√Hz A mathematical model has been developed based on the motion equation of a harmonic oscillator under the influence of a magnetic field. The model was studied to find the expression of the resonance frequency of cantilevers with integrated magnetic tips in the presence of a parallel or a perpendicular magnetic field. The shift in frequency due to the presence of the applied magnetic field depended on the magnetic tip magnetization. The measurement of the frequency shift should permit the calculation of the magnetization of these micro-magnets directly integrated on the cantilevers. The probes that we have realized represent micro and nano tools suitable for the magnetic field imaging that can be done with the SHPM and MRFM techniques.

EPFL2007

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

Beyond the lateral resolution limit by phase imaging

Yann Jérôme Michel Pascal Cotte, Christian Depeursinge, Muhammed Fatih Toy

We present a theory stating how to overcome the classical Rayleigh-resolution limit. It is based upon a new resolution criterion in phase of coherent imaging process and its spatial resolution is thought to be only SNR limited. Recently, the experimental observation of systematically occurring phase singularities in coherent imaging of sub-Rayleigh distanced objects has been reported.1 The phase resolution criterion relies on the unique occurrence of phase singularities. A priori, coherent imaging system's resolution can be extended to Abbe's limit.2 However, by introducing a known phase difference, the lateral as well as the longitudinal resolution can be tremendously enlarged. The experimental setup is based on Digital Holographic Microscopy (DHM), an interferometric method providing access to the complex wave front. In off-axis transmission configuration, sub-wavelength nano-metric holes on a metallic film acts as the customized high-resolution test target. The nano-metric apertures are drilled with focused ion beam (FIB) and controlled by scanning electron microscopy (SEM). In this manner, Rayleighs classical two-point resolution condition can be rebuilt by interfering complex fields emanated from multiple single circular apertures on an opaque metallic film. By introducing different offset phases, enhanced resolution is demonstrated. Furthermore, the measurements can be exploited analytically or within the post processing of sampling a synthetic complex transfer function (CTF).