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Campylobacter jejuni is the leading bacterial food-borne pathogen in Europe. Despite the accepted limits of cultural detection of the fastidious bacterium, the “gold standard” in food microbiology is still the determination of colony-forming units (CFU). As an alternative, a live/dead differentiating qPCR has been established, using propidium monoazide (PMA) as DNA-intercalating crosslink agent for inactivating DNA from dead, membrane-compromised cells. The PMA treatment was combined with the addition of an internal sample process control (ISPC), i.e. a known number of dead C. sputorum cells to the samples. The ISPC enables i), monitoring the effective reduction of dead cell signal by the light-activated DNA-intercalating dye PMA, and ii), compensation for potential DNA losses during processing. Here, we optimized the method for routine application and performed a full validation of the method according to ISO 16140-2:2016(E) for the quantification of live thermophilic Campylobacter spp. in meat rinses against the classical enumeration method ISO 10272-2:2017. In order to render the method applicable and cost-effective for practical application, the ISPC was lyophilized to be distributable to routine laboratories. In addition, a triplex qPCR was established to simultaneously quantify thermophilic Campylobacter, the ISPC and an internal amplification control (IAC). Its performance was statistically similar to the two duplex qPCRs up to a contamination level of 4.7 log10 Campylobacter per ml of meat rinse. The limit of quantification (LOQ) of the alternative method was around 20 genomic equivalents per PCR reaction, i.e. 2.3 log10 live Campylobacter per ml of sample. The alternative method passed a relative trueness study, confirming the robustness against different meat rinses, and displayed sufficient accuracy within the limits set in ISO 16140-2:2016(E). Finally, the method was validated in an interlaboratory ring trial, confirming that the alternative method was f

Multiple factors contribute to the development and progression of breast cancer. Markers of tumor growth and invasion, cell death, immune activation, and angiogenesis can be assessed in parallel by a novel multiplex immunoassay panel. The diagnostic performance of a multiplex cancer biomarker magnetic bead panel comprising 24 tumor associated parameters was evaluated in sera of 154 women including 77 patients with breast cancer, 10 with precancerous lesions, 31 with benign breast diseases, and 36 healthy controls. Marker levels were log-transformed for variance stabilization. Significance testing was done using t-test or Wilcoxon rank-sum test with correction of p values for multiple testing. Furthermore, receiver operating characteristic analyses were performed. Serum levels of several biomarkers were significantly (p0.001) higher in cancer patients than in healthy controls, particularly alpha-fetoprotein, cancer antigen 15-3, cancer antigen 19-9, migration inhibitory factor, carcinoembryonic antigen, cancer antigen 125, hepatocyte growth factor, soluble Fas, tumor necrosis factor-, stem cell factor, and osteopontin. As most markers were also elevated in benign breast diseases, only cancer antigen 15-3 showed significant differences to cancer patients (p0.001). The resulting areas under the curve in receiver operating characteristic curves for discrimination between benign and malignant breast diseases achieved 0.71 with a sensitivity of 33.8% at 95% specificity. Multiplexing enables parallel analysis of different biomarker classes for cancer detection. Established cancer antigen 15-3 proved to be most relevant for differential diagnosis.

ORMOCERR®s are organic-inorganic hybrid polymers. Since their material properties can be tailored precisely during synthesis, they are suitable for a wide range of applications in dielectric and optical microelectronics. This thesis reports on process development of ORMOCERR®s for Sequentially Build-Up (SBU) test vehicles, suitable for both electrical and optical interconnect. Furthermore, this work includes materials characterization, such as refractive index studies (system B59:V32), optical loss measurements (systems B59:V32 and B59:B66), and surface characterization through contact angle measurement and surface energy estimation (systems B59:V32 and B59:B66). Process development for a high-frequency test vehicle was performed applying a newly developed dielectric material of the ORMOCER® class. Dielectric layers in a total thickness of 80 μm were build-up on a common FR4 substrate, applying photolithographic processes and moderate process temperatures of below 433 K. The loss tangent and the permittivity of the material were measured to be 0.024 (loss tangent) and 3.05 (permittivity) over the entire frequency range 10 GHz to 40 GHz. The compatibility of the material to standard processes of the PCB industry was proven. Furthermore, a possibility for cost reduction in high-frequency MCM applications was shown, through the possibility of using low-cost substrates. The concept of a “flexible manufacture approach” for large-area panel optical backplane interconnects was introduced. Here, a 101.6 mm x 101.6 mm photolithographic mask is to be stepped-out over a large-area panel substrate (up to 609.6 mm x 609.6 mm). The goal is to be able to create a large amount of continuous and unique waveguide patterns over the whole area with a small portfolio of masks, thus being able to minimize excess costs. In practice continuous waveguide patterns were created over an area of 204.8 mm x 204.8 mm on a large-are panel (609.6 mm x 609.6 mm), using a large-are mask aligner and a

A flexible approach to producing optical interconnects on 609.6 * 609.6 mm large-area panels is demonstrated. Stepwise projection patterning from 101.6 * 101.6 mm masks has generated optical waveguide patterns over the whole panel using large-area projection lithography equipment. The waveguide routing design allows optical waveguides on different 101.6 * 101.6 mm tiles to be interconnected. Four different waveguide connecting geometries in the border region between tiles have been fabricated and tested. Multimode waveguides from inorganic-organic hybrid polymers (ORMOCER) (cross section: = 50 µm * 10 µm) with refractive index step between core and cladding ?n = 0.01 were produced. The index step was adjusted by mixing two diffrent ORMOCER systems. The materials show good adhesion to numerous substrates, such as glass and silicon. Application concepts such as flexible manufacturing of optoelectrical hybrid backplanes with two-dimensional interconnect, a three-dimensional optical interconnect with optical vias, and a hybrid backplane with the optical interconnect in a strip-format on a separate plane right above the electrical plane are proposed. Promising new technologies are presented along with preliminary demonstrativ viability. © 2006 IEEE.

Upon processing waveguide structures by using the ORMOCER materials ORMOCORE as core material, and a mixture of ORMOCORE and ORMOCER-III (refractive index tuning agent) as cladding material, dewetting effects of the core layer from the cladding layer were observed. A similar phenomenon was observed for a mixture of ORMOCORE and ORMOCLAD which was used as comparative refractive index tuning material. In order to use these material combinations for large-area panel (LAP) processing, a pretreatment or activation of surfaces is necessary but hard to realize. However, the addition of small amounts of ORMOCER-III or ORMOCLAD, respectively, to the core layer material, prevented the dewetting phenomenon. The objective of this, however, is to minimize the content of refractive index tuning agent in the core layer by retaining a good wetting behavior during multilayer processing. Wet film stability tests and contact angle measurements of these ORMOCER systems in various compositions on another ORMOCER surface of a specific cladding material composition were performed on a hotplate. Furthermore, contact angles of droplets formed by deionized water, formamide, and di-iodomethane on cured surfaces of these ORMOCER systems in a wide range of compositions were characterized, and surface tensions were calculated. By adding 0.1 wt% of ORMOCER-III or 5 wt% ORMOCLAD, respectively, to the pure ORMOCORE solution, the dewetting phenomenon was eliminated, while simultaneously the refractive index was affected only to a minor degree and no changes in the optical loss could be detected. It was shown that by adding ORMOCER-III or ORMOCLAD to pure ORMOCORE, the surface tension of the compound system was reduced. In comparison to silanization or gasplasma treatment to overcome dewetting effects in microelectronics multilayer processing, the investigated mixing method eliminates process steps and thus costs, and opens new process routes for LAP processing. © 2006 IEEE.

In this paper, recent literature on the discussion on high-speed backplanes with optical, electrical, and mixed solutions, as well as on polymer-waveguide systems suitable for implementation on printed circuit boards (PCBs), is reviewed from the point of view of their optical losses. The reevaluation of the optical power budget for realistic high-speed optical polymer-waveguide links on backplanes showed that signal amplification is necessary to boost the signal, which resulted in an additional literature review on advances in optical amplifiers based on silicon bench technology available. Finally, a concept study of an active optical waveguide amplifier device, based on planar optical waveguide amplifiers and semiconductor optical amplifiers, was performed. The amplification device can be flip-chip mounted on the backplane to compensate for optical losses due to signal routing, which increases the overall degree of freedom in waveguide routing on high-density interconnects for backplanes. The hybrid concept design guarantees compatibility with the processes of the PCB industry. © 2006 IEEE.

Requirements of higher performance, reduced size, weight and cost of high-frequency (HF) devices has led to the search for new: materials, material combinations, methods, processes and production equipment. Efficient technologies for producing HF-circuits and integral passives are looked for. Also of interest are integrated packaging solutions for high frequency electrical packaging and optical interconnects and packaging. Sequentially build up multi-layers have been deposited on a low cost FR-4 epoxy substrate. The dielectric layers consist of a photo-patternable inorganic-organic hybrid polymer (ORMOCER) and the metallization is Cu. An UV-exposure equipment enabling projection patterning with 5 μm resolution have been used. The produced microstrip lines, ring resonators, vias, stacked capacitors and filters have been characterized at frequencies from 1 to 40 GHz showing the potential of the new dielectric materials and processing technologies for microwave applications.

The main objective of this thesis is to discuss and demonstrate optical interconnect technologies. These can be used to enhance the data throughput capacity of future printed circuit boards and backplanes, i.e. exchange Copper conductors with light conductors. A large area panel sequential build up (SEU) technology of light waveguides on industry standard FR4 like large area panels (609.6 mm * 609.6 mm) has therefore been developed for interconnect distances typically above 10 cm. Another objective has been to study the same or similar materials and thin film process technologies for high-frequency (HF) packaging and HF-devices, to also prepare for future integrated optical and HF-packaging. High performance embedded integral passive components (resistors, capacitors, inductors) with new material and process technologies is part of this strategy. An overview on the state-of-the-art of optical backplanes, micro mirror technology for in-/ out-coupling of light to/ from the optical waveguides is given. This includes free space optical interconnect, buried wave guides, on-top of printed circuit board waveguides, flex-foil based approaches, and bi-directional approaches. An update is given concerning materials useful to fulfill these approaches. Recent literature related to polymer materials suitable for optical interconnect is overviewed including data for optical loss (>. = 800/ 1300/ 1550 nm) and thermal stability. Polymer host materials suitable for rare earth light amplifying materials are also overviewed. Polymer and sol-gel based devices working at wavelengths >. = 600/ 1064/ 1550 nm have been found so far, but in general devices for>. = 800/ 1300 nm seems to be missing. For the implementation of optical waveguide amplifiers on optical backplanes a flip-chip approach was proposed. A flexible approach of producing optical interconnects on 609.6 mm * 609.6 mm large area panels has been demonstrated. Stepwise projection patterning from 101.6 mm * 101.6 mm ma