Transfer of ultrasmall iron oxide nanoparticles from human brain-derived endothelial cells to human glioblastoma cells.

Nanoparticles (NPs) are being used or explored for the development of biomedical applications in diagnosis and therapy, including imaging and drug delivery. Therefore, reliable tools are needed to study the behavior of NPs in biological environment, in particular the transport of NPs across biological barriers, including the blood-brain tumor barrier (BBTB), a challenging question. Previous studies have addressed the translocation of NPs of various compositions across cell layers, mostly using only one type of cells. Using a coculture model of the human BBTB, consisting in human cerebral endothelial cells preloaded with ultrasmall superparamagnetic iron oxide nanoparticles (USPIO NPs) and unloaded human glioblastoma cells grown on each side of newly developed ultrathin permeable silicon nitride supports as a model of the human BBTB, we demonstrate for the first time the transfer of USPIO NPs from human brain-derived endothelial cells to glioblastoma cells. The reduced thickness of the permeable mechanical support compares better than commercially available polymeric supports to the thickness of the basement membrane of the cerebral vascular system. These results are the first report supporting the possibility that USPIO NPs could be directly transferred from endothelial cells to glioblastoma cells across a BBTB. Thus, the use of such ultrathin porous supports provides a new in vitro approach to study the delivery of nanotherapeutics to brain cancers. Our results also suggest a novel possibility for nanoparticles to deliver therapeutics to the brain using endothelial to neural cells transfer.

A novel derivative of the chelon desferrioxamine for site-specific conjugation to antibodies.

We describe the preparation of the modified chelator aminooxyacetyl-ferrioxamine, and the replacement of its iron atom by 67Ga at high specific activity. The aminooxy function of this compound was allowed to react with the aldehyde groups generated by the periodate oxidation of the oligosaccharide of a mouse IgG1 monoclonal antibody (MAb) directed against carcino-embryonic antigen (CEA). The use of the aminooxy group allowed a stable bond to be formed between the chelon and the antibody with no need for reduction. Iron was removed from the ferrioxamine moiety and replaced by 67Ga either before or after conjugation of the chelon to the antibody. In either case the labelled antibody was injected into nude mice bearing a human colon carcinoma having the appropriate antigenicity. Unoxidized antibody, labelled with 125I by conventional methods, was co-injected as an internal control. Additional control experiments were carried out with a non-immune IgG using the same 67Ga-labelled modified chelon as above. The in vivo distribution of the modified antibodies was evaluated at various times between 24 and 96 hr after injection. The methods used were gamma-camera imaging and, more quantitatively, gamma-counting of the various organs after dissection. Interestingly, with the metal-chelon-labelled antibody, the intensity and specificity of tumor labelling was comparable and in some cases superior to the results obtained with radio-iodinated antibody. In particular, there was almost no increase in liver and spleen uptake of radioactive metal relative to radio-iodine, contrary to what has been observed with most antibodies labelled with 111In after conjugation with DTPA.

Growth and characterization of CoO ultra thin films

In this report we present the growth process of the cobalt oxide system using reactive electron beam deposition. In that technique, a target of metallic cobalt is evaporated and its atoms are in-flight oxidized in an oxygen rich reactive atmosphere before reaching the surface of the substrate. With a trial and error procedure the deposition parameters have been optimized to obtain the correct stoichiometry and crystalline phase. The evaporation conditions to achieve the correct cobalt oxide salt rock structure, when evaporating over amorphous silicon nitride, are: 525 K of substrate temperature, 2.5·10-4 mbar of oxygen partial pressure and 1 Å/s of evaporation rate. Once the parameters were optimized a set of ultra thin film ranging from samples of 1 nm of nominal thickness to 20nm thick and bulk samples were grown. With the aim to characterize the samples and study their microstructure and morphology, X-ray diffraction, transmission electron microscopy, electron diffraction, energy dispersive X-ray spectroscopy and quasi-adiabatic nanocalorimetry techniques are utilised. The final results show a size dependent effect of the antiferromagnetic transition. Its Néel temperature becomes depressed as the size of the grains forming the layer decreases.

Full Exploration of the Diels–Alder Cycloaddition on Metallofullerenes M3N@C80 (M=Sc, Lu, Gd): The D5h versus Ih Isomer and the Influence of the Metal Cluster

In this work a detailed investigation of the exohedral reactivity of the most important and abundant endohedral metallofullerene (EMF) is provided, that is, Sc3N@Ih-C80 and its D5h counterpart Sc3N@D5h-C80, and the (bio)chemically relevant lutetium- and gadolinium-based M3N@Ih/D5h-C80 EMFs (M=Sc, Lu, Gd). In particular, we analyze the thermodynamics and kinetics of the Diels–Alder cycloaddition of s-cis-1,3-butadiene on all the different bonds of the Ih-C80 and D5h-C80 cages and their endohedral derivatives. First, we discuss the thermodynamic and kinetic aspects of the cycloaddition reaction on the hollow fullerenes and the two isomers of Sc3N@C80. Afterwards, the effect of the nature of the metal nitride is analyzed in detail. In general, our BP86/TZP//BP86/DZP calculations indicate that [5,6] bonds are more reactive than [6,6] bonds for the two isomers. The [5,6] bond D5h-b, which is the most similar to the unique [5,6] bond type in the icosahedral cage, Ih-a, is the most reactive bond in M3N@D5h-C80 regardless of M. Sc3N@C80 and Lu3N@C80 give similar results; the regioselectivity is, however, significantly reduced for the larger and more electropositive M=Gd, as previously found in similar metallofullerenes. Calculations also show that the D5h isomer is more reactive from the kinetic point of view than the Ih one in all cases which is in good agreement with experiments

Focused ion beam scanning electron microscopy in biology.

Since the end of the last millennium, the focused ion beam scanning electron microscopy (FIB-SEM) has progressively found use in biological research. This instrument is a scanning electron microscope (SEM) with an attached gallium ion column and the 2 beams, electrons and ions (FIB) are focused on one coincident point. The main application is the acquisition of three-dimensional data, FIB-SEM tomography. With the ion beam, some nanometres of the surface are removed and the remaining block-face is imaged with the electron beam in a repetitive manner. The instrument can also be used to cut open biological structures to get access to internal structures or to prepare thin lamella for imaging by (cryo-) transmission electron microscopy. Here, we will present an overview of the development of FIB-SEM and discuss a few points about sample preparation and imaging.

Nucleation and growth of GaN nanorods on Si (111) surfaces by plasma-assisted molecular beam epitaxy - The influence of Si- and Mg-doping

The self-assembled growth of GaN nanorods on Si (111) substrates by plasma-assisted molecular beam epitaxy under nitrogen-rich conditions is investigated. An amorphous silicon nitride layer is formed in the initial stage of growth that prevents the formation of a GaN wetting layer. The nucleation time was found to be strongly influenced by the substrate temperature and was more than 30 min for the applied growth conditions. The observed tapering and reduced length of silicon-doped nanorods is explained by enhanced nucleation on nonpolar facets and proves Ga-adatom diffusion on nanorod sidewalls as one contribution to the axial growth. The presence of Mg leads to an increased radial growth rate with a simultaneous decrease of the nanorod length and reduces the nucleation time for high Mg concentrations.

Properties of nitrogen doped silicon films deposited by low-pressure chemical vapor deposition from silane and ammonia

Nitrogen doped silicon (NIDOS) films have been deposited by low-pressure chemical vapor deposition from silane SiH4 and ammonia NH3 at high temperature (750°C) and the influences of the NH3/SiH4 gas ratio on the films deposition rate, refractive index, stoichiometry, microstructure, electrical conductivity, and thermomechanical stress are studied. The chemical species derived from silylene SiH2 into the gaseous phase are shown to be responsible for the deposition of NIDOS and/or (silicon rich) silicon nitride. The competition between these two deposition phenomena leads finally to very high deposition rates (100 nm/min) for low NH3/SiH4 gas ratio (R¿0.1). Moreover, complex variations of NIDOS film properties are evidenced and related to the dual behavior of the nitrogen atom into silicon, either n-type substitutional impurity or insulative intersticial impurity, according to the Si¿N atomic bound. Finally, the use of NIDOS deposition for the realization of microelectromechanical systems is investigated.

Residual Stress Measurement on a MEMS Structure With High-Spatial Resolution

A new approach to the local measurement of residual stress in microstructures is described in this paper. The presented technique takes advantage of the combined milling-imaging features of a focused ion beam (FIB) equipment to scale down the widely known hole drilling method. This method consists of drilling a small hole in a solid with inherent residual stresses and measuring the strains/displacements caused by the local stress release, that takes place around the hole. In the presented case, the displacements caused by the milling are determined by applying digital image correlation (DIC) techniques to high resolution micrographs taken before and after the milling process. The residual stress value is then obtained by fitting the measured displacements to the analytical solution of the displacement fields. The feasibility of this approach has been demonstrated on a micromachined silicon nitride membrane showing that this method has high potential for applications in the field of mechanical characterization of micro/nanoelectromechanical systems.

Electroluminiscence and optical amplification in silicon nanostructures: towards the integration of electronics and photonics

This line of research of my group intends to establish a Silicon technological platform in the field of photonics allowing the development of a wide set of applications. Particularly, what is still lacking in Silicon Photonics is an efficient and integrable light source such an LED or laser. Nanocrystals in silicon oxide or nitride matrices have been recently demonstrated as competitive materials for both active components (electrically and optically driven light emitters and optical amplifiers) and passive ones (waveguides and modulators). The final goal is the achievement of a complete integration of electronic and optical functions in the same CMOS chip. The first part of this paper will introduce the structural and optical properties of LEDs fabricated from silicon nanostructures. The second will treat the interaction of such nanocrystals with rare-earth elements (Er), which lead to an efficient hybrid system emitting in the third window of optical fibers. I will present the fabrication and assessment of optical waveguide amplifiers at 1.54 ¿m for which we have been able to demonstrate recently optical gain in waveguides made from sputtered silicon suboxide materials.

A new and simple variable-angle accessory for infrared specular reflectance

A simple, low-cost accessory (patent pending) with only two flat mirrors and a new variable-angle mechanism has been developed for infrared specular reflectance measurements. The system allows the angles of incidence to be varied continuously from 15° (near normal incidence) to 85° (near grazing angle) without losing the alignment of the accessory. The reflectivity of boron nitride thin films deposited on metallic substrates has been measured at different angles of incidence to demonstrate the utility of this accessory.

Ion assisted deposition of thin films by substrate tuned radio frequency magnetron sputtering

The substrate tuning technique was applied to a radio frequency magnetron sputtering system to obtain a variable substrate bias without an additional source. The dependence of the substrate bias on the value of the external impedance was studied for different values of chamber pressure, gas composition and rf input power. A qualitative explanation of the results is given, based on a simple model, and the role of the stray capacitance is clearly disclosed. Langmuir probe measurements show that this system allows independent control of the ion flux and the ion energy bombarding the growing film. For an argon flow rate of 2.8 sccm and a radio frequency power of 300 W (intermediate values of the range studied) the ion flux incident on the substrate was 1.3 X 1020-m-2-s-1. The maximum ion energy available in these conditions can be varied in the range 30-150 eV. As a practical application of the technique, BN thin films were deposited under different ion bombardment conditions. An ion energy threshold of about 80 eV was found, below which only the hexagonal phase was present in the films, while for higher energies both hexagonal and cubic phase were present. A cubic content of about 60% was found for an ion energy of 120 V.

Electronic structure and properties of AlN

The electronic structure of the wurtzite-type phase of aluminum nitride has been investigated by means of periodic ab initio Hartree-Fock calculations. The binding energy, lattice parameters (a,c), and the internal coordinate (u) have been calculated. All structural parameters are in excellent agreement with the experimental data. The electronic structure and bonding in AlN are analyzed by means of density-of-states projections and electron-density maps. The calculated values of the bulk modulus, its pressure derivative, the optical-phonon frequencies at the center of the Brillouin zone, and the full set of elastic constants are in good agreement with the experimental data.

Electronic structure and properties of AlN

The electronic structure of the wurtzite-type phase of aluminum nitride has been investigated by means of periodic ab initio Hartree-Fock calculations. The binding energy, lattice parameters (a,c), and the internal coordinate (u) have been calculated. All structural parameters are in excellent agreement with the experimental data. The electronic structure and bonding in AlN are analyzed by means of density-of-states projections and electron-density maps. The calculated values of the bulk modulus, its pressure derivative, the optical-phonon frequencies at the center of the Brillouin zone, and the full set of elastic constants are in good agreement with the experimental data.

Si3N4 single-crystal nanowires grown from silicon micro- and nanoparticles near the threshold of passive oxidation

A simple and most promising oxide-assisted catalyst-free method is used to prepare silicon nitride nanowires that give rise to high yield in a short time. After a brief analysis of the state of the art, we reveal the crucial role played by the oxygen partial pressure: when oxygen partial pressure is slightly below the threshold of passive oxidation, a high yield inhibiting the formation of any silica layer covering the nanowires occurs and thanks to the synthesis temperature one can control nanowire dimensions

Ferromagnetic shape memory alloys: structural and thermal properties

The most extensively studied Heusler alloys are those based on the Ni-Mn-Ga system. However, to overcome the high cost of Gallium and the usually low martensitic transformation temperature, the search for Ga-free alloys has been recently attempted, particularly, by introducing In, Sn or Sb. In this work, two alloys (Mn50Ni35.5In14.5 and Ni50Mn35In15) have been obtained by melt spinning. We outline their structural and thermal behaviour. Mn50Ni35.5In14.5 alloy has the transformation above room temperature whereas Ni50Mn35In15 does not have this transformation in the temperature range here analyzed