Device decapsulated (and/or depassivated) – Retest ok – What happened?

One of the very first steps to enter into physical device failure analysis is the device decapsulation. In some cases, an additional depassivation follows to give access to contact needles for internal probing. However, it happens from time-to-time that the device has been cured from its failure behaviour. Such cases often end as non-conclusive analysis result. Our principle investigations and results, however, will help to understand the mechanisms and allow in many “hopeless” cases to draw useful conclusions on the root causes. These are linked in most cases to metal related failures. Besides the “classical case” of touching bond wires, typical root causes are metal filament shorts in the nanometer-order-of magnitude, which can be removed easily by mechanical and/or chemical effects of any delayering procedure. Surface metal shorts may also be generated by bump metal or pad-interface-metallisation-redeposition onto the passivation surface and by metal residue-related recombinations of trimming fuses. In both latter cases, nanometer metal films short-circuit neighbouring pads or fuses in trimming-fuse-arrays. This paper describes these and some second-order mechanisms in detail, which sometimes let the chip recover after decapsulation and/or depassivation.     

Thermal impact of an active 3-D microelectrode array implanted in the brain.

A chronically implantable, wireless neural interface device will require integrating electronic circuitry with the interfacing microelectrodes in order to eliminate wired connections. Since the integrated circuit (IC) dissipates a certain amount of power, it will raise the temperature in surrounding tissues where it is implanted. In this paper, the thermal influence of the integrated 3-D Utah electrode array (UEA) device implanted in the brain was investigated by numerical simulation using finite element analysis (FEA) and by experimental measurement in vitro as well as in vivo. The numerically calculated and experimentally measured temperature increases due to the UEA implantation were in good agreement. The experimentally validated numerical model predicted that the temperature increases linearly with power dissipation through the UEA, with a slope of 0.029 degree C/mW over the power dissipation levels expected to be used. The influences of blood perfusion, brain metabolism, and UEA geometry on tissue heating were also investigated using the numerical model.     

Higher order direct model reference adaptive control with generic uniform ultimate boundedness

This paper proposes a new higher order model reference adaptive control (HO-MRAC) approach following direct adaptive control philosophy, which estimates unknown time-varying parameters. This approach leads to a Lyapunov based conventional MRAC update law, augmented by an observer type parameter predictor dynamics. The predictor dynamics are composed of a stable known part, a feedback of the parameter error and unknown higher order parameters, which are updated using a Lyapunov based adaptive design. So, this HO-MRAC can cope with rapidly changing parameters, due to estimation of their time derivatives. Moreover, for stability analysis, a Lyapunov based generic ultimate boundedness theorem is presented, which allows for a computation of separate bounds for each state vector partition. Furthermore, this theorem formulates the explicit specification of transient and ultimate bounds, reaching time on the ultimate bounds and a set of admissible initial conditions. Two challenging illustrative examples demonstrate the effectiveness of the proposed approach.     

Evaluation of a Novel Thiol–Norbornene-Functionalized Gelatin Hydrogel for Bioprinting of Mesenchymal Stem Cells

Introduction: Three-dimensional bioprinting can be considered as an advancement of the classical tissue engineering concept. For bioprinting, cells have to be dispersed in hydrogels. Recently, a novel semi-synthetic thiolene hydrogel system based on norbornene-functionalized gelatin (GelNB) and thiolated gelatin (GelS) was described that resulted in the photoclick hydrogel GelNB/GelS. In this study, we evaluated the printability and biocompatibility of this hydrogel system towards adipose-tissue-derived mesenchymal stem cells (ASCs). Methods: GelNB/GelS was synthesized with three different crosslinking densities (low, medium and high), resulting in different mechanical properties with moduli of elasticity between 206 Pa and 1383 Pa. These hydrogels were tested for their biocompatibility towards ASCs in terms of their viability, proliferation and differentiation. The extrusion-based bioprinting of ASCs in GelNB/GelS-high was performed to manufacture three-dimensional cubic constructs. Results: All three hydrogels supported the viability, proliferation and chondrogenic differentiation of ASCs to a similar extent. The adipogenic differentiation of ASCs was better supported by the softer hydrogel (GelNB/GelS-low), whereas the osteogenic differentiation was more pronounced in the harder hydrogel (GelNB/GelS-high), indicating that the differentiation fate of ASCs can be influenced via the adaption of the mechanical properties of the GelNB/GelS system. After the ex vivo chondrogenic differentiation and subcutaneous implantation of the bioprinted construct into immunocompromised mice, the production of negatively charged sulfated proteoglycans could be observed with only minimal inflammatory signs in the implanted material. Conclusions: Our results indicate that the GelNB/GelS hydrogels are very well suited for the bioprinting of ASCs and may represent attractive hydrogels for subsequent in vivo tissue engineering applications.     

Elongational creep experiments - A new method for investigations of morphology development in polymer blends

This work is focused on the changes of phase structure in polystyrene/polyethylene blends with up to 15 wt.% of dispersed phase during elongational experiments in creep. In the first part, features of the experiments at constant stress with a special attention to morphology development in polymer blends are discussed. In the second part of the paper the deformation behavior of the dispersed droplets in dependence on applied stress and total strain is studied. It was found that with increasing the initial particle size the formation of homogeneously deformed long fibrils is preferred during the elongation. A maximum deformability of the droplets was observed, which cannot be increased by applying higher stresses, although the affine deformation of the droplets was not reached.     

Thermo-reversible sol–gel transition of TiO2 nanoparticles with surface modified by p-toluene sulfonic acid

In this paper an unprecedent thermo-reversible sol–gel transition for titania nanoparticles dispersed in a solution of p-toluene sulfonic acid (PTSH) in isopropanol is reported. The sol formed by the thermo-hydrolysis at 60 °C of titanium tetraisopropoxide (Ti(OⁱPr)₄) reversibly changes into a turbid gel upon cooling to room temperature. Turbidimetric measurements performed for samples containing different nominal acidity ratios (A = [PTSH]/[Ti]) have evidenced that the gel transformation temperature increases from 20 to 35 °C as the [PTSH]/[Ti] ratio increases from 0.2 to 2.0. SAXS results indicate that the thermo-reversible gelation is associated to a reversible aggregation of a monodisperse set of titania nanoparticles with average gyration radius of ≈2 nm. From the different PTSH species evidenced by Raman spectroscopy and TG/DTA of dried gels we proposed that the thermo-reversible gelation in this systems is induced by the formation of a supramolecular network, in which the protonated surface of nanoparticles is interconnected through cooperative hydrogen bonds between –SO₃ groups of p-toluene sulfonic acid.     

Adapted random sampling patterns for accelerated MRI

Objective  

Variable density random sampling patterns have recently become increasingly popular for accelerated imaging strategies, as they lead to incoherent aliasing artifacts. However, the design of these sampling patterns is still an open problem. Current strategies use model assumptions like polynomials of different order to generate a probability density function that is then used to generate the sampling pattern. This approach relies on the optimization of design parameters which is very time consuming and therefore impractical for daily clinical use.     

Quantification and localization of contrast agents using delta relaxation enhanced magnetic resonance at 1.5?T

Object

Delta relaxation enhanced magnetic resonance (dreMR) is a new imaging technique based on the idea of cycling the magnetic field B ₀ during an imaging sequence. The method determines the field dependency of the relaxation rate (relaxation dispersion dR ₁/dB). This quantity is of particular interest in contrast agent imaging because the parameter can be used to determine contrast agent concentrations and increases the ability to localize the contrast agent.

Materials and methods

In this paper dreMR imaging was implemented on a clinical 1.5?T MR scanner combining conventional MR imaging with fast field-cycling. Two improvements to dreMR theory are presented describing the quantification of contrast agent concentrations from dreMR data and a correction for field-cycling with finite ramp times.

Results

Experiments demonstrate the use of the extended theory and show the measurement of contrast agent concentrations with the dreMR method. A second experiment performs localization of a contrast agent with a significant improvement in comparison to conventional imaging.

Conclusion

dreMR imaging has been extended by a method to quantify contrast agent concentrations and improved for field-cycling with finite ramp times. Robust localization of contrast agents using dreMR imaging has been performed in a sample where conventional imaging delivers inconclusive results.     

Improving the clinical potential of ultra-high field fMRI using a model-free analysis method based on response consistency

Objective

To develop an analysis method that is sensitive to non-model-conform responses often encountered in ultra-high field presurgical planning fMRI. Using the consistency of time courses over a number of experiment repetitions, it should exclude low quality runs and generate activation maps that reflect the reliability of responses.

Materials and methods

7 T fMRI data were acquired from six healthy volunteers: three performing purely motor tasks and three a visuomotor task. These were analysed with the proposed approach (UNBIASED) and the GLM.

Results

UNBIASED results were generally less affected by false positive results than the GLM. Runs that were identified as being of low quality were confirmed to contain little or no activation. In two cases, regions were identified as activated in UNBIASED but not GLM results. Signal changes in these areas were time-locked to the task, but were delayed or transient.

Conclusion

UNBIASED is shown to be a reliable means of identifying consistent task-related signal changes regardless of response timing. In presurgical planning, UNBIASED could be used to rapidly generate reliable maps of the consistency with which eloquent brain regions are activated without recourse to task timing and despite modified hemodynamics.

     

Visualization of immune cell infiltration in experimental viral myocarditis by 19F MRI in vivo

Objective

This paper introduces a new approach permitting for the first time a specific, non-invasive diagnosis of myocarditis by visualizing the infiltration of immune cells into the myocardium.

Materials and methods

The feasibility of this approach is shown in a murine model of viral myocarditis. Our study uses biochemically inert perfluorocarbons (PFCs) known to be taken up by circulating monocytes/macrophages after intravenous injection.

Results

In vivo ¹⁹F MRI at 9.4 T demonstrated that PFC-loaded immune cells infiltrate into inflamed myocardial areas. Because of the lack of any fluorine background in the body, detected ¹⁹F signals of PFCs are highly specific as confirmed ex vivo by flow cytometry and histology.

Conclusion

Since PFCs are a family of compounds previously used clinically as blood substitutes, the technique described in our paper holds the potential as a new imaging modality for the diagnosis of myocarditis in man.