TY - JOUR A1 - Henken, F. E. A1 - Oosterhuis, K. A1 - Öhlschläger, Peter A1 - Bosch, L. A1 - Hooijberg, E. A1 - Haanen, J. B. A. G. A1 - Steenbergen, R. D. M. T1 - Preclinical safety evaluation of DNA vaccines encoding modified HPV16 E6 and E7 JF - Vaccine N2 - Persistent infection with high-risk human papillomaviruses (hrHPV) can result in the formation of anogenital cancers. As hrHPV proteins E6 and E7 are required for cancer initiation and maintenance, they are ideal targets for immunotherapeutic interventions. Previously, we have described the development of DNA vaccines for the induction of HPV16 E6 and E7 specific T cell immunity. These vaccines consist of ‘gene-shuffled’ (SH) versions of HPV16 E6 and E7 that were fused to Tetanus Toxin Fragment C domain 1 (TTFC) and were named TTFC-E6SH and TTFC-E7SH. Gene-shuffling was performed to avoid the risk of inducing malignant transformation at the vaccination site. Here, we describe the preclinical safety evaluation of these candidate vaccines by analysis of their transforming capacity in vitro using established murine fibroblasts (NIH 3T3 cells) and primary human foreskin keratinocytes (HFKs). We demonstrate that neither ectopic expression of TTFC-E6SH and TTFC-E7SH alone or in combination enabled NIH 3T3 cells to form colonies in soft agar. In contrast, expression of HPV16 E6WT and E7WT alone or in combination resulted in effective transformation. Similarly, retroviral transduction of HFKs from three independent donors with both TTFC-E6SH and TTFC-E7SH alone or in combination did not show any signs of immortalization. In contrast, the combined expression of E6WT and E7WT induced immortalization in HFKs from all donors. Based on these results we consider it justified to proceed to clinical evaluation of DNA vaccines encoding TTFC-E6SH and TTFC-E7SH in patients with HPV16 associated (pre)malignancies. Y1 - 2012 U6 - https://doi.org/10.1016/j.vaccine.2012.04.013 SN - 0264-410X VL - 30 IS - 28 SP - 4259 EP - 4266 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Immel, Timo A1 - Grützke, Martin A1 - Späte, Anne-Katrin A1 - Groth, Ulrich A1 - Öhlschläger, Peter A1 - Huhn, Thomas T1 - Synthesis and X-ray structure analysis of a heptacoordinate titanium(IV)-bis-chelate with enhanced in vivo antitumor efficacy JF - Chemical Communications N2 - Chelate stabilization of a titanium(IV)–salan alkoxide by ligand exchange with 2,6-pyridinedicarboxylic acid (dipic) resulted in heptacoordinate complex 3 which is not redox-active, stable on silica gel and has increased aqueous stability. 3 is highly toxic in HeLa S3 and Hep G2 and has enhanced antitumor efficacy in a mouse cervical-cancer model. Y1 - 2012 U6 - https://doi.org/10.1039/C2CC31624B SN - 1364-548X VL - 48 IS - 46 SP - 5790 EP - 5792 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Oberländer, Jan A1 - Kirchner, Patrick A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Strategies in developing thin-film sensors for monitoring aseptic food processes : Theoretical considerations and investigations of passivation materials JF - Electrochimica Acta N2 - The sterilization of packages in aseptic food processes is highly significant to maintain a consumer-safe product with extended shelf-life. Today, the sterilization of food packages is predominantly accomplished by gaseous hydrogen peroxide (H2O2) in combination with heat. In order to monitor this sterilization process, calorimetric gas sensors as differential set-up of two platinum temperature sensors representing a catalytically active (additionally deposition of MnO2) and a passive segment have been recently developed. The temperature rise of the exothermic decomposition serves as an indicator of the present H2O2 concentration. In the present work, a theoretical approach considering the sensor’s thermochemistry and physical transport phenomena was formulated to evaluate the temperature rise based on the energy content of gaseous H2O2. In a further part of this work, three polymers have been analyzed with respect to their application as passivation materials. The examined polymers are photoresist SU-8, perfluoroalkoxy (PFA) and fluorinated ethylene propylene (FEP). Thermal analyses by means of differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) have been conducted to determine the operation limits of the polymers. The overall chemical resistance and stability of the polymers against the harsh environmental conditions during the sterilization process have been examined by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Y1 - 2015 U6 - https://doi.org/10.1016/j.electacta.2015.06.126 SN - 0013-4686 VL - 183 SP - 130 EP - 136 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Murib, M. S. A1 - Yeap, W. S. A1 - Eurlings, Y. A1 - Grinsven, B. van A1 - Boyen, H.-G. A1 - Conings, B. A1 - Michiels, L. A1 - Ameloot, M. A1 - Carleer, R. A1 - Warmer, J. A1 - Kaul, P. A1 - Haenen, K. A1 - Schöning, Michael Josef A1 - Ceuninck, W. de A1 - Wagner, P. T1 - Heat-transfer based characterization of DNA on synthetic sapphire chips JF - Sensors and Actuators B: Chemical N2 - In this study, we show that synthetic sapphire (Al₂O₃), an established implant material, can also serve as a platform material for biosensors comparable to nanocrystalline diamond. Sapphire chips, beads, and powder were first modified with (3-aminopropyl) triethoxysilane (APTES), followed by succinic anhydride (SA), and finally single-stranded probe DNA was EDC coupled to the functionalized layer. The presence of the APTES-SA layer on sapphire powders was confirmed by thermogravimetric analyis and Fourier-transform infrared spectroscopy. Using planar sapphire chips as substrates and X-ray photoelectron spectroscopy (XPS) as surface-sensitive tool, the sequence of individual layers was analyzed with respect to their chemical state, enabling the quantification of areal densities of the involved molecular units. Fluorescence microscopy was used to demonstrate the hybridization of fluorescently tagged target DNA to the probe DNA, including denaturation- and re-hybridization experiments. Due to its high thermal conductivity, synthetic sapphire is especially suitable as a chip material for the heat-transfer method, which was employed to distinguish complementary- and non-complementary DNA duplexes containing single-nucleotide polymorphisms. These results indicate that it is possible to detect mutations electronically with a chemically resilient and electrically insulating chip material. Y1 - 2016 U6 - https://doi.org/10.1016/j.snb.2016.02.027 SN - 0925-4005 VL - 230 IS - 230 SP - 260 EP - 271 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Breuer, Lars A1 - Raue, Markus A1 - Mang, Thomas A1 - Schöning, Michael Josef A1 - Thoelen, Ronald A1 - Wagner, Torsten T1 - Light-stimulated hydrogel actuators with incorporated graphene oxide for microfluidic applications T2 - 12. Dresdner Sensor-Symposium 2015 Y1 - 2015 U6 - https://doi.org/10.5162/12dss2015/P5.8 SP - 206 EP - 209 ER - TY - CHAP A1 - Oberländer, Jan A1 - Jildeh, Zaid B. A1 - Kirchner, Patrick A1 - Wendeler, Luisa A1 - Bromm, Alexander A1 - Iken, Heiko A1 - Wagner, Patrick A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Experimental and numerical evaluation of interdigitated electrode array for monitoring gaseous sterilization processes T2 - 12. Dresdner Sensor-Symposium 2015 Y1 - 2015 U6 - https://doi.org/10.5162/12dss2015/P3.11 SP - 163 EP - 168 ER - TY - JOUR A1 - Miyamato, Ko-ichiro A1 - Sakakita, Sakura A1 - Wagner, Torsten A1 - Schöning, Michael Josef A1 - Yoshinobu, Tatsuo T1 - Application of chemical imaging sensor to in-situ pH imaging in the vicinity of a corroding metal surface JF - Electrochimica Acta N2 - The chemical imaging sensor was applied to in-situ pH imaging of the solution in the vicinity of a corroding surface of stainless steel under potentiostatic polarization. A test piece of polished stainless steel was placed on the sensing surface leaving a narrow gap filled with artificial seawater and the stainless steel was corroded under polarization. The pH images obtained during polarization showed correspondence between the region of lower pH and the site of corrosion. It was also found that the pH value in the gap became as low as 2 by polarization, which triggered corrosion. Y1 - 2015 U6 - https://doi.org/10.1016/j.electacta.2015.07.184 SN - 0013-4686 VL - 183 SP - 137 EP - 142 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Hamad, E. M. A1 - Bilatto, S. E. R. A1 - Adly, N. Y. A1 - Correa, D. S. A1 - Wolfrum, B. A1 - Schöning, Michael Josef A1 - Offenhäusser, A. A1 - Yakushenko, A. T1 - Inkjet printing of UV-curable adhesive and dielectric inks for microfluidic devices JF - Lab on a Chip N2 - Bonding of polymer-based microfluidics to polymer substrates still poses a challenge for Lab-On-a-Chip applications. Especially, when sensing elements are incorporated, patterned deposition of adhesives with curing at ambient conditions is required. Here, we demonstrate a fabrication method for fully printed microfluidic systems with sensing elements using inkjet and stereolithographic 3D-printing. Y1 - 2016 U6 - https://doi.org/10.1039/C5LC01195G SN - 1473-0189 VL - 16 IS - 1 SP - 70 EP - 74 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Miyamoto, Ko-ichiro A1 - Yu, Bing A1 - Isoda, Hiroko A1 - Wagner, Torsten A1 - Schöning, Michael Josef A1 - Yoshinobu, Tatsuo T1 - Visualization of the recovery process of defects in a cultured cell layer by chemical imaging sensor JF - Sensors and Actuators B: Chemical N2 - The chemical imaging sensor is a field-effect sensor which is able to visualize both the distribution of ions (in LAPS mode) and the distribution of impedance (in SPIM mode) in the sample. In this study, a novel cell assay is proposed, in which the chemical imaging sensor operated in SPIM mode is applied to monitor the recovery of defects in a cell layer brought into proximity of the sensing surface. A reduced impedance at a defect formed artificially in a cell layer was successfully visualized in a photocurrent image. The cell layer was cultured over two weeks, during which the temporal change of the photocurrent distribution corresponding to the recovery of the defect was observed. Y1 - 2016 U6 - https://doi.org/10.1016/j.snb.2016.04.018 SN - 0925-4005 VL - 236 SP - 965 EP - 969 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Dantism, Shahriar A1 - Takenaga, Shoko A1 - Wagner, Patrick A1 - Wagner, Torsten A1 - Schöning, Michael Josef T1 - Determination of the extracellular acidification of Escherichia coli K12 with a multi-​chamber-​based LAPS system JF - Physica status solidi (a) N2 - On-line monitoring of the metabolic activity of microorganisms involved in intermediate stages of biogas production plays an important role to avoid undesirable “down times” during the biogas production. In order to control this process, an on-chip differential measuring system based on the light-addressable potentiometric sensor (LAPS) principle combined with a 3D-printed multi-chamber structure has been realized. As a test microorganism, Escherichia coli K12 (E. coli K12) were used for cell-based measurements. Multi-chamber structures were developed to determine the metabolic activity of E. coli K12 in suspension for a different number of cells, responding to the addition of a constant or variable amount of glucose concentrations, enabling differential and simultaneous measurements. Y1 - 2016 U6 - https://doi.org/10.1002/pssa.201533043 SN - 1862-6300 VL - 213 IS - 6 SP - 1479 EP - 1485 PB - Wiley-VCH CY - Weinheim ER -