Exchange biased delta-E effect enables the detection of low frequency pT magnetic fields with simultaneous localization.

Delta-E effect sensors are based on magnetoelectric resonators that detune in a magnetic field due to the delta-E effect of the magnetostrictive material. In recent years, such sensors have shown the potential to detect small amplitude and low-frequency magnetic fields. Yet, they all require external magnetic bias fields for optimal operation, which is highly detrimental to their application. Here, we solve this problem by combining the delta-E effect with exchange biased multilayers and operate the resonator in a low-loss torsion mode. It is comprehensively analyzed experimentally and theoretically using various kinds of models. Due to the exchange bias, no external magnetic bias fields are required, but still low detection limits down to [Formula: see text] at 25 Hz are achieved. The potential of this concept is demonstrated with a new operating scheme that permits simultaneous measurement and localization, which is especially desirable for typical biomedical inverse solution problems. The sensor is localized with a minimum spatial resolution of 1 cm while measuring a low-frequency magnetic test signal that can be well reconstructed. Overall, we demonstrate that this class of magnetic field sensors is a significant step towards first biomedical applications and compact large number sensor arrays.

Microfabricated bioelectrodes on self-expandable NiTi thin film devices for implants and diagnostic instruments.

State of the art minimally invasive treatments and diagnostics of neurological and cardiovascular diseases demand for flexible instruments and implants that enable sensing and stimulation of bioelectric signals. Besides medical applications, implantable bioelectronic brain-computer interfaces are envisioned as the next step in communication and data transfer. Conventional microelectrode arrays used for these types of applications are based on polymer substrates that are not suitable for biostable, rigid and self-expanding devices. Here, we present fully integrated bioelectrodes on superelastic NiTi carriers fabricated by microsystem technology processes. The insulation between the metallic NiTi structure and the Pt electrode layer is realized by different oxide layers (SiOx, TaOx and Yttrium stabilized Zirconia YSZ). Key properties of bioelectronic implants such as dissolution in body fluids, biocompatibility, mechanical properties and bioelectrical sensing/stimulation capabilities have been investigated by in vitro methods. Particular devices with YSZ are biostable and biocompatible, enabling sensing and stimulation. The major advantage of this system is the combination of medically approved materials and novel fabrication technology that enables miniaturization and integration beyond the state-of-the-art processes. The results demonstrate that this functionalization of superelastic NiTi is an enabling technology for the development of new kinds of bioelectronic devices.

Converse Magnetoelectric Composite Resonator for Sensing Small Magnetic Fields.

Magnetoelectric (ME) thin film composites consisting of sputtered piezoelectric (PE) and magnetostrictive (MS) layers enable for measurements of magnetic fields passively, i.e. an AC magnetic field directly generates an ME voltage by mechanical coupling of the MS deformation to the PE phase. In order to achieve high field sensitivities a magnetic bias field is necessary to operate at the maximum piezomagnetic coefficient of the MS phase, harnessing mechanical resonances further enhances this direct ME effect size. Despite being able to detect very small AC field amplitudes, exploiting mechanical resonances directly, implies a limitation to available signal bandwidth along with the inherent inability to detect DC or very low frequency magnetic fields. The presented work demonstrates converse ME modulation of thin film Si cantilever composites of mesoscopic dimensions (25 mm × 2.45 mm × 0.35 mm), employing piezoelectric AlN and magnetostrictive FeCoSiB films of 2 µm thickness each. A high frequency mechanical resonance at about 515 kHz leads to strong induced voltages in a surrounding pickup coil with matched self-resonance, leading to field sensitivities up to 64 kV/T. A DC limit of detection of 210 pT/Hz1/2 as well as about 70 pT/Hz1/2 at 10 Hz, without the need for a magnetic bias field, pave the way towards biomagnetic applications.

The impact of O2/Ar ratio on morphology and functional properties in reactive sputtering of metal oxide thin films.

Morphology is a critical parameter for various thin film applications, influencing properties like wetting, catalytic performance and sensing efficiency. In this work, we report on the impact of oxygen partial flow on the morphology of ceramic thin films deposited by pulsed DC reactive magnetron sputtering. The influence of O2/Ar ratio was studied on three different model systems, namely Al2O3, CuO and TiO2. The availability of oxygen during reactive sputtering is a key parameter for a versatile tailoring of thin film morphology over a broad range of nanostructures. TiO2 thin films with high photocatalytic performance (up to 95% conversion in 7 h) were prepared, exhibiting a network of nanoscopic cracks between columnar anatase structures. In contrast, amorphous thin films without such crack networks and with high resiliency to crystallization even up to 950 °C were obtained for Al2O3. Finally, we report on CuO thin films with well aligned crystalline nanocolumns and outstanding gas sensing performance for volatile organic compounds as well as hydrogen gas, showing gas responses up to 35% and fast response in the range of a few seconds.

A systematic analysis of orphan cyclins reveals CNTD2 as a new oncogenic driver in lung cancer.

As lung cancer has increased to the most common cause of cancer death worldwide, prognostic biomarkers and effective targeted treatments remain lacking despite advances based on patients' stratification. Multiple core cyclins, best known as drivers of cell proliferation, are commonly deregulated in lung cancer where they may serve as oncogenes. The recent expansion of the cyclin family raises the question whether new members might play oncogenic roles as well. Here, we investigated the protein levels of eight atypical cyclins in lung cancer cell lines and formalin-fixed and paraffin-embedded (FFPE) human tumors, as well as their functional role in lung cancer cells. Of the new cyclins evaluated, CNTD2 was significantly overexpressed in lung cancer compared to adjacent normal tissue, and exhibited a predominant nuclear location. CNTD2 overexpression increased lung cancer cell viability, Ki-67 intensity and clonogenicity and promoted lung cancer cell migration. Accordingly, CNTD2 enhanced tumor growth in vivo on A549 xenograft models. Finally, the analysis of gene expression data revealed a high correlation between elevated levels of CNTD2 and decreased overall survival in lung cancer patients. Our results reveal CNTD2 as a new oncogenic driver in lung cancer, suggesting value as a prognostic biomarker and therapeutic target in this disease.

Functional NiTi grids for in situ straining in the TEM.

In situ measurements are a pivotal extension of conventional transmission electron microscopy (TEM). By means of the shape memory alloy NiTi thin film Functional Grids were produced for in situ straining as alternative or at least complement of expensive commercial holders. Due to the martensite-austenite transition temperature straining effects can be observed by use of customary heating holders in the range of 50 to 100°C. The grids can be produced in diversified designs to fit for different strain situations. Micro tensile tests were performed and compared with finite element simulations to estimate the applied forces on the sample and to predict the functionality of different grid designs. As a first example of this Functional Grid technology, we demonstrate the impact of applying a strain to a network of ZnO tetrapods.

Effect of crystallographic compatibility and grain size on the functional fatigue of sputtered TiNiCuCo thin films.

The positive influence of crystallographic compatibility on the thermal transformation stability has been already investigated extensively in the literature. However, its influence on the stability of the shape memory effect or superelasticity used in actual applications is still unresolved. In this investigation sputtered films of a highly compatible TiNiCuCo composition with a transformation matrix middle eigenvalue of 1±0.01 are exposed to thermal as well as to superelastic cycling. In agreement with previous results the thermal transformation of this alloy is with a temperature shift of less than 0.1 K for 40 cycles very stable; on the other hand, superelastic degradation behaviour was found to depend strongly on heat treatment parameters. To reveal the transformation dissimilarities between the differently heat-treated samples, the microstructure has been analysed by transmission electron microscopy, in situ stress polarization microscopy and synchrotron analysis. It is found that good crystallographic stability is not a sufficient criterion to avoid defect generation which guarantees high superelastic stability. For the investigated alloy, a small grain size was identified as the determining factor which increases the yield strength of the composition and decreases the functional degradation during superelastic cycling.This article is part of the themed issue 'Taking the temperature of phase transitions in cool materials'.

Microstructured Nickel-Titanium Thin Film Leaflets for Hybrid Tissue Engineered Heart Valves Fabricated by Magnetron Sputter Deposition.

Heart valves are constantly exposed to high dynamic loading and are prone to degeneration. Therefore, it is a challenge to develop a durable heart valve substitute. A promising approach in heart valve engineering is the development of hybrid scaffolds which are composed of a mechanically strong inorganic mesh enclosed by valvular tissue. In order to engineer an efficient, durable and very thin heart valve for transcatheter implantations, we developed a fabrication process for microstructured heart valve leaflets made from a nickel-titanium (NiTi) thin film shape memory alloy. To examine the capability of microstructured NiTi thin film as a matrix scaffold for tissue engineered hybrid heart valves, leaflets were successfully seeded with smooth muscle cells (SMCs). In vitro pulsatile hydrodynamic testing of the NiTi thin film valve leaflets demonstrated that the SMC layer significantly improved the diastolic sufficiency of the microstructured leaflets, without affecting the systolic efficiency. Compared to an established porcine reference valve model, magnetron sputtered NiTi thin film material demonstrated its suitability for hybrid tissue engineered heart valves.

Cell adhesion on NiTi thin film sputter-deposited meshes.

Scaffolds for tissue engineering enable the possibility to fabricate and form biomedical implants in vitro, which fulfill special functionality in vivo. In this study, free-standing Nickel­Titanium(NiTi) thin film mesheswere produced by means of magnetron sputter deposition.Meshes contained precisely defined rhombic holes in the size of 440 to 1309 µm2 and a strut width ranging from 5.3 to 9.2 µm. The effective mechanical properties of the microstructured superelastic NiTi thin film were examined by tensile testing. These results will be adapted for the design of the holes in the film. The influence of hole and strut dimensions on the adhesion of sheep autologous cells (CD133+) was studied after 24 h and after seven days of incubation. Optical analysis using fluorescence microscopy and scanning electron microscopy showed that cell adhesion depends on the structural parameters of the mesh. After 7 days in cell culture a large part of the mesh was covered with aligned fibrous material. Cell adhesion is particularly facilitated on meshes with small rhombic holes of 440 µm2 and a strut width of 5.3 µm. Our results demonstrate that free-standing NiTi thin film meshes have a promising potential for applicationsin cardiovascular tissue engineering, particularly for the fabrication of heart valves.

Magnetic moment investigation by frequency mixing techniques.

Gas turbines and other large industrial equipment are subjected to high-temperature oxidation and corrosion. Research and development of efficient protective coatings is the main task in the field. Also, knowledge about the depletion state of the coating during the operation time is important. To date, practical nondestructive methods for the measurement of the depletion state do not exist. By integrating magnetic phases into the coating, the condition of the coating can be determined by measuring its magnetic properties. In this paper, a new technique using frequency mixing is proposed to investigate the thickness of the coatings based on their magnetic properties. A sensor system is designed and tested on specific magnetic coatings. New approaches are proposed to overcome the dependency of the measurement on the distance between coil and sample that all noncontact techniques face. The novelty is a low cost sensor with high sensibility and selectivity which can provide very high signal-to-noise ratios. Prospects and limitations are discussed for future use of the sensor in industrial applications.

Combination of a SAW-biosensor with MALDI mass spectrometric analysis.

A S-sens K5 surface acoustic wave biosensor was coupled with mass spectrometry (SAW-MS) for the analysis of a protein complex consisting of human blood clotting cascade factor alpha-thrombin and human antithrombin III, a specific blood plasma inhibitor of thrombin. Specific binding of antithrombin III to thrombin was recorded as a function of time with a S-sens K5 biosensor. Two out of five elements of the sensor chip were used as references. To the remaining three elements coated with RNA anti-thrombin aptamers, thrombin and antithrombin III were bound consecutively. The biosensor measures mass changes on the chip surface showing that 20% of about 400fmol/cm2 thrombin formed a complex with the 1.7-times larger antithrombin III. Mass spectrometry (MS) was applied to identify the bound proteins. Sensor chips with aptamer-captured (1) thrombin and (2) thrombin-antithrombin III complex (TAT-complex) were digested with proteases on the sensor element and subsequently identified by peptide mass fingerprint (PMF) with matrix assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectrometry. A significant identification of thrombin was achieved by measuring the entire digest with MALDI-ToF MS directly from the sensor chip surface. For the significant identification of both proteins in the TAT-complex, the proteolytic peptides had to be separated by nano-capillary-HPLC prior to MALDI-ToF MS. SAW-MS is applicable to protein interaction analysis as in functional proteomics and to miniaturized diagnostics.

Analysis of proteolytic degradation of a crude protein mixture using a surface acoustic wave sensor.

Degradation of a crude protein mixture by proteases with pH optima from acidic to basic was followed in real time using a surface acoustic wave biosensor in Love-wave geometry. Proteases EC 3.4.23.18 from Aspergillus saitoi, EC 3.4.21.62 from Bacillus licheniformis, and Novozyme from Bacillus sp. have been used. Kinetic constants extracted from the curves resulted for comparable protease concentrations in maximal degradation rates between 1.1 x 10(-2) and 1.5 x 10(-2)s(-1). For the three proteases investigated, similar amounts of up to about two-thirds of the estimated 28 ng/cm2 bound molecules were proteolyzed. The residual material not degraded by the proteases was removed from the surface with 0.5% SDS. The analysis of the sensor signal allows: (1) estimation of the total mass of protein bound to the sensor surface and of the degradable fraction; (2) extraction of the pure mass signal; and (3) kinetic evaluation.

First experimental test of a new monochromated and aberration-corrected 200 kV field-emission scanning transmission electron microscope.

The first 200 kV scanning transmission electron microscope (STEM) with an imaging energy filter, a monochromator and a corrector for the spherical aberration (Cs-corrector) of the illumination system has been built and tested. The STEM/TEM concept with Koehler illumination allows to switch easily between STEM mode for analytical and TEM mode for high-resolution or in situ studies. The Cs-corrector allows the use of large illumination angles for retaining a sufficiently high beam current despite the intensity loss in the monochromator. With the monochromator on and a 3 microm slit in the dispersion plane that gives 0.26 eV full-width at half-maximum (FWHM) energy resolution we have obtained so far an electron beam smaller than 0.20 nm in diameter (FWHM as measured by scanning the spot quickly over the CCD) which contains 7 pA current and, according to simulations, should be around 0.12 nm in true size. A high-angle annular dark field (ADF) image with isotropic resolution better than 0.28 nm has been recorded with the monochromator in the above configuration and the Cs-corrector on. The beam current is still somewhat low for electron energy-loss spectroscopy (EELS) but is expected to increase substantially by optimising the condenser set-up and using a somewhat larger condenser aperture.

Monitoring complex formation in the blood-coagulation cascade using aptamer-coated SAW sensors.

Specific binding of the anticoagulants heparin and antithrombin III to the blood clotting cascade factor human thrombin was recorded as a function of time with a Love-wave biosensor array consisting of five sensor elements. Two of the sensor elements were used as references. Three sensor elements were coated with RNA or DNA aptamers for specific binding of human thrombin. The affinity between the aptamers and thrombin, measured using the biosensor, was within the same range as the value of K(D) measured by filter binding experiments. Consecutive binding of the thrombin inhibitors heparin, antithrombin III or the heparin-antithrombin III complex to the immobilized thrombin molecules, and binding of a ternary complex of heparin, anithrombin III, and thrombin to aptamers was evaluated. The experiments showed attenuation of binding to thrombin due to heparin-antithrombin III complex formation. Binding of heparin activated the formation of the inhibitory complex of antithrombin III with thrombin about 2.7-fold. Binding of the DNA aptamer to exosite II appeared to inhibit heparin binding to exosite I.