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Introduction Occipital nerve stimulation (ONS) is used to treat therapy-resistant chronic migraine. Clinical use has resulted in a wide intraindividual and interindividual variation of clinical efficacy. The aim of this study was to analyze a potential relationship between sociodemographic variables, headache parameters, perceived sensory quality, perceived sensory location, as well as clinical efficacy. Methods Thirty-two subjects (21.9% male, mean age 45.77 years) suffering from chronic migraine refractory to other treatment and therefore treated with ONS were included in this study. We used a computer-based imaging method for mapping the ONS-induced perceived sensory location, the perceived spatial sensory field size, as well as the perceived sensory quality in a long-term course over 21 months in weekly time intervals. Additionally, the effect of ONS on the migraine headache was documented weekly by the participants using a verbal rating scale. Over the observation period, a total of 808 individual weekly data sets were recorded and a potential relationship between ONS-induced perceptions and headache parameters could be analyzed. Results We found that 48.9% of stimulation intervals were reported as effective by patients. Women displayed a significantly higher responder rate than men. The reported effectiveness did not differ depending on age, the average number of migraine days per month, the MIDAS score, or the duration of the migraine disorder prior to ONS treatment. Implantation with trial period led to significantly lower responder rates than without the trial period. The most frequently perceived sensory quality of “tingling” was found significantly more frequently in non-responders than in responders. Responders displayed significantly lower pleasantness scores for their reported perceptions than non-responders. Sensations that were spatially perceived above the line connecting the external acoustic meati with the external occipital protuberance (MOP line) led to patients reporting a positive clinical effect significantly more frequently than sensations spatially perceived below the MOP line. Spatially small fields of sensory perception were correlated with a higher responder rate than those covering broader areas. Conclusions The ONS-induced sensory location, the size of the spatial sensory field, as well as the sensory quality are significantly correlated with the reported clinical effectiveness. The results suggest that besides surgical technique, the individual and continuous programming of the stimulation parameters is clinically relevant in increasing the therapeutic effectiveness.

For the realization of advanced bio-microsystems for medical applications such as implants, fabrication processes require the usage of biocompatible materials only. Especially for the encapsulation and hermetic sealing, e. g. of microfluidic structures, a biocompatible wafer bonding process is necessary. Additionally, the ongoing integration of new and temperature sensitive materials in micro systems, such as biomolecules, requires bonding processes with low bonding temperatures only. However, when choosing the wafer bonding process, additional criteria are a high reliability, since the bonding is critical for the operation of the chip, as well as the applicability on 6” and 8” wafer level in order to fabricate a high number of devices at low costs. In order to fulfill all these requirements, we propose an adhesive bonding process, which uses Parylene C as intermediate layer. Parylene C is a thermoplastic polymer, which is ISO 10993 certified as biocompatible and biostable, chemically inert against all common acids, bases and solvents, as well as a low permeable and optical transparent. In addition and in contrast to other established bond adhesives, such as SU8, the Parylene layers are deposited by CVD, and offer a very high three dimensional conformity as well as a very high homogeneity without any pinholes. Furthermore, due to its chemical inertness, Paryleneis compatible with a variety of established microtechnologies. Previous studies prove that adhesive bonding using Parylene C is feasible. However, these works are limited to 4” wafer level and the bonding provides only low tensile strengths, e. g. 10 MPa. [1-7] Our presented Parylene based adhesive bonding technology uses a 0.5 µm to 10 µm Parylene C layer, which is deposited on 6” and 8” wafers and can be patterned optionally by an oxygen plasma without leaving residues. A subsequent thermal and adhesive bonding process at temperatures of 280°C to 300°C as well as moderate wafer contact pressures are performed to successfully bond the wafers. Within our study, different materials combinations for the bond interface, e. g. silicon - silicon, silicon - silicon dioxide, silicon – glass, silicon – silicon nitride, and silicon – aluminum were investigated. Doing so, only one wafer was coated with Parylene. Additionally, bonding processes were performed with two Parylene coated wafers, and hence, a Parylene - Parylene bond interface. Since almost all materials, established in microsystem technologies can be coated with Parylene, this enables the usage of this bonding process for a high variety of material combinations and particularly materials, which were not investigated by our study. The focus of the experiments was the investigation and optimization of a feasible parameter range in respect of the bonding time, bonding temperature, wafer contact pressure, and Parylene thickness. The characterization of the bonding process was performed using Parylene test structures of squared geometry and different width. The bonding process was analyzed by IR imaging to determine voids and defects. Afterwards the wafers were diced into chips, centering the Parylene frame. The investigation of tensile and shear strengths proved a high reliability of the bonding but also a strong dependency on the bonding parameters. The tensile strength reached up to 35 MPa was improved by a factor of 3 compared to previous studies, the shear strength reached up to 80 MPa Furthermore, the impact of thermal and mechanical shocks as well as long-time load on the tensile strength was investigated. Finally, cross-sections of the bonded chips were analyzed by SEM. The results prove that the Parylene frame structure was still intact after bonding and not flattened due to bonding. Furthermore, the hermetic properties of the Parylene bonds were investigated. Doing so, the Helium leakage rate was determined to < 1∙10-7 mbar ∙ l/s. The study was completed by the investigation of the bonding process on three dimensional structures, which refers to bonding over patterned metal but also bonding of cavities without previous pattern of the Parylene. Finally, after successfully bonding the test frames, the established bonding process was applied on a real microsystem. References: [1] M. Kurihara, et al., IEEE MEMS 2012 (Paris, France) pp 196-9 [2] Y.-C. Yen, et al., IEEE MEMS 2012 (Paris, France) pp 381-384 [3] Q. Shu, et al., International Conference on Solid-State and Integrated-Circuit Technology 2009 (Beijing, China) [4] D. P. Poenar, et al., Sens. Actuators, A 139, 2007, 162–71 [5] A. T. Ciftlik et al., J. Micromech. Microeng. 21, 2011, 35011 [6] D. Ziegler, et al., J. Microelectromech. Syst. 15 (6), 2006, 1477–82 [7] H.-S. Noh, et al., J. Microelectromech. Syst. 14, 2004, 625–31

High-performance acceleration sensors acquire increasing relevance for process monitoring and crash detection. In this regard, a newly developed sensor system is realised comprising an 8 kHz and a 20 kHz high-acceleration MEMS-based sensor. This research presents proof of functionality of the sensor system conducting cutting experiments and impulse detection tests. For cutting tests, a 42CrMo4 steel grade is machined with cemented carbide milling tools. The process data indicate that distinct cutting processes stages and crash related impulses can be recognised reliably. As general functionality is proven, the sensor system can be evolved for industrial process monitoring and crash detection applications.

Next to powders, inks, and microelectronics, many technologies that carry the attribute nano in their name are still waiting for their breakthrough and wide acceptance in engineering and industry. At least nanofabrication technologies are the subject of a vivid track in research and development in a variety of scientific fields but yet most of them are mainly invisible in everyday products. This paper aims to describe three inspiring examples of research work in the area of nanopatterning and systems integration at the micro-nano interface to motivate applications with new and unprecedented functionalities. The application examples comprise the fields of bio-inspired computing, optoelectronic sensing, and spectral imaging. First, network-based biocomputing uses biological agents in a nanopatterned fluidic channel system and opens horizons for energy-efficient solutions to complex mathematical problems. Second, nanoelectronic devices based on carbon nanotubes (CNTs) have emerged because of the outstanding mechanical, electronic, and optical properties of the CNTs. The adaptivity of nanostructures to the world of biological molecules and other nanoscopic building blocks such as quantum dots and nanoparticles enables novel, even personalized, devices and technical solutions. Third, early-on ""nano"" fame has been devoted to optical effects-the authors here discuss an advanced integrated micro-opto-mechanical system on a micromirror plate forming a Fabry-Pérot Interferometer.

This report focuses on the self organized nanostructure formation on Si (0 0 1) by erosion with low energy Kr + ions with simultaneous incorporation of metallic atoms, in particular Fe. The incorporation of Fe is thought to play an important role in the formation of some features. In the experimental set-up used here the Fe atoms come from the sputtering of a cylindrical stainless steel target situated between the source and the sample holder. It is demonstrated how the Fe flux can be regulated by operational parameters of the ion source. It is shown that two different ripple modes, one perpendicular to the ion beam projection on the surface and the other parallel, were formed at near normal incidence ( α = 20°) with ion energy between 300 eV and 2000 eV and a fluence of 6.7 × 10 18 cm −2 . The perpendicular mode ripples dominated the topography when E ion = 2000 eV, while the parallel mode ripples were the main features observed when E ion = 300 eV. The correlation of Fe concentration with ion sources parameters and resulting topography is analyzed. It is demonstrated that a certain Fe concentration is necessary for the formation of ripples that are oriented perpendicular to the ion beam and that the Fe concentration alone does not determine the evolving topography.

This report focuses on the effect of simultaneous Fe incorporation in the self-organized pattern formation on Si(001) by low-energy ion-beam sputtering. Experimental observations giving evidence for the correlation between different ion-beam parameters, Fe concentration on the substrate, and the resulting topography are shown. It was observed that the incorporation of Fe affects the evolution of the topography and it is a requisite for the formation of ripples at near-normal incidence. It is shown also that Fe is not homogeneously distributed on the surface, but there is a higher concentration at the crests of the ripples than at the valleys. For the experimental setup used for this study, the Fe flux that reaches the surface is determined mainly by the acceleration voltage (U acc), while the ion energy (E ion) and ion-beam incidence angle (α) control the concentration of Fe in the steady state. The adjustment of these operational parameters of the ion source enables the fine-tuning of surface patterns.

Robot supported minimally invasive interventions are state of the art in operating theatres. To increase the accuracy of surgical instrument positioning, high-precision motion tracking systems are required. The miniaturization of microelectromechanical systems (MEMS) facilitates the placing of orientation detection sensors close to the mounting of the surgical instrument to enhance positioning accuracy. A high resolution inclination sensor was developed using the innovative approach of laser-micro-welding. Trench sizes down to 800 nm are fabricated with more than 6-fold increase in aspect ratios (structure depth to electrode gap) compared to sensors without gap reduction. Electrical and physical tests as well as finite-element-simulations were performed. An increased sensitivity from 7.2 fF/° up to 60 fF/° was verified for the sensor with reduced electrode gap and a customized ASIC.

We prepared conductive, polycrystalline or amorphous Cu1.05Cr0.89 Mg0.05O2 films on a-plane sapphire substrates by pulsed laser deposition under different O2 partial pressure and substrate temperature. Hall measurements were performed to study the majority carrier type in these films. Polycrystalline Cu1.05Cr0.89 Mg0.05O2 is n-type conducting at 290 K, while in amorphous Cu1.05Cr0.89 Mg0.05O2 the type of majority charge carriers changes from electrons to holes at around 270 K. Interestingly, the structure has little influence on the magnetic properties of the films. A clear antiferromagnetic to paramagnetic transition was observed in both polycrystalline and amorphous Cu1.05Cr0.89 Mg0.05O2 films at 25 K. Similar electrical properties to Cu1.05Cr0.89 Mg0.05O2 film were observed for Cu0.96Cr0.95 Mg0.05Mn0.04O2 in dependence on the structure, while only paramagnetic without antiferromagnetic ordering was observed down to 5 K. Large negative magnetoresistance of 27% at 20 K was observed at 6 T in amorphous Cu1.05Cr0.89 Mg0.05O2 film.

Zn 90 Mn 7.5 Cu 2.5 O 100 films have been prepared on a-plane sapphire substrates by pulsed laser deposition. Paramagnetism mainly caused by Mn 2+ ions was observed in the films from room temperature down to 2 K. Magnetotransport properties (magnetoresistance (MR) and Hall effect) were studied from 5 K to 290 K up to a field of 6 T. Negative MR was observed at temperature above 100 K. Low field positive MR and high field negative MR was observed at 5 K. Clear anomalous Hall effect with a kink at low field was observed below 20 K, indicating that there exist two different scattering mechanisms for the Mn 2+ and Cu 2+ ions.

This paper presents a new technology, which allows the reduction of the micro dimensional trench width below the technological limitations of the Deep Reactive Ion Etching (DRIE) process. The high-accuracy and high-throughput femtosecond laser-micro-welding of aluminum was performed for the first time by Micro Electrical Mechanical System (MEMS) fabrication to realize this permanent trench width reduction. Therefore, this technology has been applied for the electrode gap reduction of high precision vibration sensors, based on the capacitive working principle, resulting in a fourfold improvement of the sensitivity without changing the size of the sensor chip itself.

ZnCoO : Al, ZnCoO : (Al,Cu), and reference samples without Co have been grown by pulsed laser deposition to investigate the influence of Co-dopants and Cu-codopants on the magneto transport properties of ZnO. Positive magnetoresistance and anomalous Hall effect have been observed for ZnCoO : (Al,Cu). Versatile theoretical approaches for modelling positive magnetoresistance in ZnO-based diluted magnetic semiconductors are still to be developed. Negative magnetoresistance due to the scattering of spin-polarized charge carriers at isolated magnetic impurities has been observed in ZnO : (Al,Cu) without Co-dopants and successfully modelled. Cu-codopants enhance the positive and negative magnetoresistance in ZnCoO : Al and ZnO : Al, respectively, by one order of magnitude.

We report on the high-pressure pulsed laser deposition growth of zinc oxide nanowires containing about 0.2 at.% Co and 0.5 at.% Mn by NiO and Au catalyst. Scanning electron microscopy and X-ray diffraction measurements revealed arrays of parallel-standing nanowires with hexagonal cross section and uniform in-plane epitaxial relations without rotational domains. Elemental analysis was carried out using particle induced X-ray emission and Q-band electron spin resonance. The valence of the incorporated Mn was determined to be 2+. Atomic and magnetic force microscopy measurements indicate that Mn is incorporated preferentially at the nanowire boundaries.

In biomedical research the distributions of physiologically or pathologically active elements around or in a certain structure (e.g. tangles, plaques or different cell types) are often of great interest. Therefore, μPIXE analyses are applied to yield quantitative and spatially resolved concentration images of the elements of interest. However, the localisation of the structures to be examined is sometimes scarcely practicable or even impossible. This paper proposes a method of localising the areas of interest for μPIXE analysis. The method is based on the application of a suitable antibody tagged with a single elemental marker (e.g. Ni, Co, Cd, Ag or Au). The antibody then binds selectively to the structures of interest. The elemental marker is detectable via μPIXE, thus, showing finally the structure of interest via the bound antibody. The versatility of the antibodies in combination with the easily applied marker facilitates the localisation of a variety of structures in both light microscopy and μPIXE-imaging. The method is demonstrated on several cellular and subcellular structures in the brain. The elemental concentrations of two consecutive slices, one stained with Ni-enhanced antibody, the other unstained control, are compared to show the feasibility of trace elemental analysis for particular elements in spite if immunohistochemical structure identification. It has to be stated that the proposed technique will not work for free diffusing elements (like Na, Cl, K and Ca) whose concentrations can be altered by wet sample preparation.

Background Within the last years, occipital nerve stimulation (ONS) has proven to be an important method in the treatment of severe therapy-resistant neurological pain disorders. The correspondence between lead placement as well as possible stimulation parameters and the resulting stimulation effects remains unclear. Objective The method aims to directly relate the neuromodulatory mechanisms with the clinical treatment results, to achieve insight in the mode of action of neuromodulation, to identify the most effective stimulation sets and to optimize individual treatment effects. Methods We describe a new computer-based imaging method for mapping the spatial, cognitive and affective sensory effects of ONS. The procedure allows a quantitative and qualitative analysis of the relationship between lead positioning, the stimulation settings as well as the sensory and clinical stimulation effects. Conclusion A regular mapping of stimulation and sensory parameters allows a coordinated monitoring. The stimulation results can be reviewed and compared with regards to clinical effectiveness.

The applications of inertial sensors have a wide variety in terms of accuracy and costs. A new technology approach is joining higher sensor accuracy and lower production costs by using a new Interposer / sensor interconnect technology applied on 300 mm wafer diameter without changing the sensor element itself. The higher accuracy is mainly covered by a multiple point program: (1) stress less assembly due interface silicon Interposer to silicon MEMS; (2) better Signal to Noise Ratio (SNR) by polymer redistribution layer on the interposer (due to better wiring geometry and less parasitic capacities / inductivities); (3) reduction of mechanical stress by using flexible bar springs for mechanical decoupling of sensor and Interposer substrate; (4) additional stress reduction by using a polymer layer for mechanical decoupling of metal redistribution layer (RDL) and Interposer substrate. The cost efficiency even in small scale serial production based on: (1) 300 mm multi project wafer technology including warehouse ready system packaging; (2) a new MEMS contact technology, which gives technical benefit, smaller dimensions and simplifies the assembly of MEMS and ASIC (which are placed on a 2.5D-Interposer in order to enable a System In Package (SiP) as well as for higher sensor accuracy); (3) the flexible ASIC feature enables the integration of different MEMS with analogue signal output; (4) minor costs for integration of different sensors into the existing package. The heterogeneous 3D integration is a key enabler and justifies the additional process steps (mainly TSV-processing, thin wafer handling) by implementing the advantages of the polymer RDL. This integration approach results leads to improved mechanical and electrical properties. This paper will give an overview about the current achievements in the SIMEIT-project, which are predestined to improve the accuracy of different MEMS-applications with analogue signal transfer to the ASIC as well as MEMS-applications with need of stress less integration.

Background Many children with chronic disease use complementary therapies. Anthroposophic treatment for paediatric chronic disease is provided by physicians and differs from conventional treatment in the use of special therapies (art therapy, eurythmy movement exercises, rhythmical massage therapy) and special medications. We studied clinical outcomes in children with chronic diseases under anthroposophic treatment in routine outpatient settings. Methods In conjunction with a health benefit program, consecutive outpatients starting anthroposophic treatment for any chronic disease participated in a prospective cohort study. Main outcome was disease severity (Disease and Symptom Scores, physicians' and caregivers' assessment on numerical rating scales 0–10). Disease Score was documented after 0, 6, and 12 months, Symptom Score after 0, 3, 6, 12, 18, and 24 months. Results A total of 435 patients were included. Mean age was 8.2 years (standard deviation 3.3, range 1.0–16.9 years). Most common indications were mental disorders (46.2% of patients; primarily hyperkinetic, emotional, and developmental disorders), respiratory disorders (14.0%), and neurological disorders (5.7%). Median disease duration at baseline was 3.0 years (interquartile range 1.0–5.0 years). The anthroposophic treatment modalities used were medications (69.2% of patients), eurythmy therapy (54.7%), art therapy (11.3%), and rhythmical massage therapy (6.7%). Median number of eurythmy/art/massage therapy sessions was 12 (interquartile range 10–20), median therapy duration was 118 days (interquartile range 78–189 days). From baseline to six-month follow-up, Disease Score improved by average 3.00 points (95% confidence interval 2.76–3.24 points, p < 0.001) and Symptom Score improved by 2.41 points (95% confidence interval 2.16–2.66 points, p < 0.001). These improvements were maintained until the last follow-up. Symptom Score improved similarly in patients not using adjunctive non-anthroposophic therapies within the first six study months. Conclusion Children under anthroposophic treatment had long-term improvement of chronic disease symptoms. Although the pre-post design of the present study does not allow for conclusions about comparative effectiveness, study findings suggest that anthroposophic therapies may play a beneficial role in the long-term care of children with chronic illness.

Homoepitaxial MgxZn1−xO:P thin films with variable magnesium content (x

The transport properties of phosphorous-doped ZnO thin films, grown by pulsed-laser deposition on thermally pretreated hydrothermally grown ZnO single-crystal substrates, are reported. The ZnO:P thin films show very good morphological and structural properties as confirmed by atomic force microscopy (AFM), high resolution x-ray diffraction, and Rutherford backscattering (RBS) channeling. Steps of height c/2 are visible in AFM investigations for all samples. For an oxygen partial pressure of 0.1 mbar, two-dimensional growth was found. RBS channeling of a ZnO:P film shows a minimum yield of 0.034 which is comparable to that of an annealed substrate (0.033). Hall effect measurements revealed that all films are n-type for the present growth conditions. Peak mobilities of 800 cm^2/Vs have been observed around 70 K, in line with the high structural quality of the samples. Room-temperature mobility in ZnO:P is up to 170 cm^2/Vs.

Nd and Mn were codoped into ZnO films which have been grown on a-plane sapphire substrates by pulsed laser deposition with the thickness ranging between 46 and 971 nm. The room temperature resistivity of the codoped films is independent of film thickness. Large positive magnetoresistance and clear anomalous Hall effect were observed at 5 K. Ferromagnetism with clear hysteresis up to 290 K was observed. Codoping is suggested to be an efficient method to introduce energy levels in the ZnO band gap to mediate the electron spins of the magnetic doping ions.

ZnO films were prepared by pulsed laser deposition on a-plane sapphire substrates under N2 atmosphere. Ferromagnetic loops were obtained with the superconducting quantum interference device at room temperature, which indicate a Curie temperature much above room temperature. No clear ferromagnetism was observed in intentionally Cu-doped ZnO films. This excludes that Cu doping into ZnO plays a key role in tuning the ferromagnetism in ZnO. 8.8% negative magnetoresistance probed at 5K at 60kOe on ferromagnetic ZnO proves the lack of s-d exchange interaction. Anomalous Hall effect (AHE) was observed in ferromagnetic ZnO as well as in nonferromagnetic Cu-doped ZnO films, indicating that AHE does not uniquely prove ferromagnetism. The observed ferromagnetism in ZnO is attributed to intrinsic defects.