Institut für Chemie und Bioanalytik
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Publikation 3D human liver microtissues vs. 2D monolayer culture as an in vitro tool for compound testing(10/2018) Messner, Catherine; Prestigiacomo, Vincenzo; Mannino, Salvatore; Mauch, Linda; Suter-Dick, Laura06 - PräsentationPublikation 3D printed microfluidic modules. Passive mixers and cells encapsulation in alginate(De Gruyter, 02.09.2022) Dalcanale, Federico; Caj, Michaela; Schuler, Felix; Ganeshanathan, Kireedan; Suter-Dick, LauraPassive mixers and droplet generation microfluidic chip modules were designed and manufactured using a commercial SLA 3D-printer. The mixing modules were designed specifically for 3D-printing and evaluated using FEM modeling. The co-flow droplet generator was used for cancer cells encapsulation and drug potency evaluation.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation A Biocatalytic Nanomaterial for the Label-Free Detection of Virus-Like Particles(Wiley, 2017) Sykora, Sabine; Correro, Maria Rita; Moridi, Negar; Belliot, Gaël; Pothier, Pierre; Dudal, Yves; Corvini, Philippe; Shahgaldian, PatrickThe design of nanomaterials that are capable of specific and sensitive biomolecular recognition is an on-going challenge in the chemical and biochemical sciences. A number of sophisticated artificial systems have been designed to specifically recognize a variety of targets. However, methods based on natural biomolecular detection systems using antibodies are often superior. Besides greater affinity and selectivity, antibodies can be easily coupled to enzymatic systems that act as signal amplifiers, thus permitting impressively low detection limits. The possibility to translate this concept to artificial recognition systems remains limited due to design incompatibilities. Here we describe the synthesis of a synthetic nanomaterial capable of specific biomolecular detection by using an internal biocatalytic colorimetric detection and amplification system. The design of this nanomaterial relies on the ability to accurately grow hybrid protein-organosilica layers at the surface of silica nanoparticles. The method allows for label-free detection and quantification of targets at picomolar concentrations.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation A cyclodextrin-based polymer (CDP) for sensing diclofenac in water(Elsevier, 15.12.2015) Xiao, Pu; Weibel, Nicolas; Dudal, Yves; Corvini, Philippe; Shahgaldian, Patrick01A - Beitrag in wissenschaftlicher ZeitschriftPublikation A method for side effect analysis based on electricfield simulations for intraoperative test stimulation in deep brain stimulation surgery(2015) Pison, Daniela; Alonso, Fabiola; Wårdell, Karin; Shah, Ashesh; Coste, Jérôme; Lemaire, Jean-Jaques; Schkommodau, Erik; Hemm-Ode, Simone04B - Beitrag KonferenzschriftPublikation A new concept of liquid membranes in Taylor flow. Performance for lactic acid removal(Elsevier, 05/2019) Pérez, Alan; Fontalvo, JavierA liquid membrane in Taylor flow regime is a novel alternative kind of contact in three-phase flow for liquid membranes that preserves the advantages of conventional emulsion liquid membranes while overcomes the stability problems of emulsion systems. As a proof of concept, this work presents experimental results of a liquid membrane in Taylor flow for lactic acid removal. Several operating conditions, such as injection times, delay times and flow of the membrane phase were tested for a channel length and inner diameter of 348.8 cm and 2.5 mm, respectively. The lactic acid removal is mainly affected by the driving force of lactic acid concentrations between donor droplets and the membrane interface, and the space-time. Thus, the lactic acid removal process through the liquid membrane in Taylor flow is enhanced at low injection times and high droplet velocity considering that enough space-time is provided. This technology results promising as an alternative to conventional liquid membranes and the intensification of chemical and fermentative processes.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation A perfused in vitro human iPSC-derived blood–brain barrier faithfully mimics transferrin receptor-mediated transcytosis of therapeutic antibodies(Springer, 2023) Burgio, Floriana; Gaiser, Carine; Brady, Kevin; Gatta, Viviana; Class, Reiner; Schrage, Ramona; Suter-Dick, LauraDelivering biologics to elicit a therapeutic response in the central nervous system (CNS) remains challenging due to the presence of the blood brain barrier (BBB). Receptor-mediated transcytosis is a strategy to improve brain exposure after systemic drug administration. The availability of a clinically relevant in vitro BBB model is crucial to investigate transcytosis pathways and to predict the penetration of biologics into the CNS. We created a perfused human in vitro BBB model made of induced pluripotent stem cells (iPSC)-derived brain microvascular endothelial cells (BMEC) for studying transferrin receptor-mediated transcytosis. iPSC-derived BMEC were seeded in the top channel of a three-lane microfluidic device (OrganoPlate®). After 2 days in culture, the established cell model exhibited relevant BBB features, including physiological transendothelial electrical resistance in a transwell setting (1500 Ω*cm), reduced apparent permeability (Papp) to the fluorescence tracer Lucifer yellow (20-fold less than cell-free chips), expression of key BBB markers such as tight junctions proteins, transporters, receptors and functional P-gp efflux pump. Moreover, the model exhibited functional transferrin receptor-mediated uptake and transcytosis. To assess selective transferrin receptor-mediated transcytosis, a mixture of anti-human transferrin receptor (MEM-189) and control (sheep IgG anti-bovine serum albumin) antibodies was perfused in the top channel for 2 h. The Papp of MEM-189 was 11-fold higher than that of the control antibody, demonstrating facilitated receptor-mediated transcytosis. Compared to published work reporting a 2-fold ratio, this result is remarkable and establishes the suitability of our model for exploring receptor-mediated transcytosis and screening of antibodies for putative brain shuttle application. A perfused in vitro human model made of iPSC-derived BMEC with the chief characteristics (barrier tightness, functionality) of the human BBB can be applied to study transferrin receptor (TfR)-mediated transcytosis of therapeutic antibodies. This may bring critical advances in drug shuttle technology. Graphical abstract generated with biorender.com.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation A three-dimensional, human co-culture model for the study of mechanisms in Alzheimer's disease(07/2018) Suter-Dick, Laura; Gaiser, Carine06 - PräsentationPublikation A Two‐Dimensional Polymer Synthesized at the Air/Water Interface(Wiley, 06/2018) Müller, Vivian; Hinaut, Antoine; Moradi, Mina; Jung, Thomas A.; Shahgaldian, Patrick; Möhwald, Helmuth; Hofer, Greogor; Kröger, Martin; King, Benjamin T.; Meyer, Ernst; Glatzel, Thilo; Schlüter, Dieter A.; Baljozovic, MilosA trifunctional, partially fluorinated anthracene‐substituted triptycene monomer was spread at an air/water interface into a monolayer, which was transformed into a long‐range‐ordered 2D polymer by irradiation with a standard UV lamp. The polymer was analyzed by Brewster angle microscopy, scanning tunneling microscopy measurements, and non‐contact atomic force microscopy, which confirmed the generation of a network structure with lattice parameters that are virtually identical to a structural model network based on X‐ray diffractometry of a closely related 2D polymer. The nc‐AFM images highlight the long‐range order over areas of at least 300×300 nm2. As required for a 2D polymer, the pore sizes are monodisperse, except for the regions where the network is somewhat stretched because it spans over protrusions. Together with a previous report on the nature of the cross‐links in this network, the structural information provided herein leaves no doubt that a 2D polymer has been synthesized under ambient conditions at an air/water interface.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation A UHPLC–MS/MS method for the quantification of 7α-hydroxy-4-cholesten-3-one to assist in diagnosis of bile acid malabsorption(Elsevier, 01/2017) Prost, Jean-Christophe; Brunner, Félix; Grob, Christian; Berchtold, Christian; Schlotterbeck, Götz; Bovet, Cédric; Largiadèr, Carlo R.; Fiedler, Georg Martin; Juillerat, PascalBile acids malabsorption (BAM) is encountered in numerous gastrointestinal pathologies and is a good example of a treatable cause of watery diarrhea after ileal resection. The gold standard for diagnosing BAM is the selenium homocholic acid taurine test (SeHCAT), an expensive and complex analysis. An alternative method is the quantification of 7α-hydroxy-4-cholesten-3-one (C4). Here, we present a simple, ultra high-performance liquid chromatography–tandem mass spectrometry method to measure C4 in human serum. To avoid time consuming sample preparation (e.g., derivatization, solid phase extraction), we used absorption chemistry-based extraction plates. This method demonstrates a lower limit of quantification of 5 ng/mL and is linear over a concentration range from 5 to 300 ng/mL (R2 = 0.9977). Inaccuracy and imprecision were less than 15%. The validated method is currently used for routine measurement of C4 from serum in patients to confirm BAM diagnosis.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Absorption and metabolism of the natural sweeteners erythritol and xylitol in humans. A dose-ranging study(MDPI, 30.08.2022) Wölnerhanssen, Bettina K.; Meyer-Gerspach, Anne Christin; Bordier, Valentine; Teysseire, Valentine; Senner, Frank; Schlotterbeck, Götz; Drewe, Jürgen; Beglinger, ChristophThe natural sweeteners erythritol and xylitol might be helpful to reduce sugar consumption and therefore prevent obesity and diabetes. The aim of the present study was to determine the absorption and metabolization into erythronate of different concentrations of erythritol and xylitol. Seventeen healthy lean participants received intragastric solutions of 10, 25, or 50 g erythritol or 7, 17, or 35 g xylitol on three study days in a randomized order. The study was double blinded with respect to the doses administered. We assessed plasma concentrations of erythritol, xylitol, and erythronate at fixed time intervals after administration with gas chromatography-mass spectrometry. We found: (i) a dose-dependent and saturable absorption of erythritol, (ii) a very low absorption of xylitol, (iii) a dose-dependent metabolization of erythritol into erythronate, and (iv) no metabolization of xylitol into erythronate. The implications of the metabolization of erythritol into erythronate for human health remain to be determined and more research in this area is needed.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation AhR-Mediated Effects of Dioxins on liver in zebrafish embryos(11/2018) Yan, Lu; Zenker, Armin; Suter-Dick, Laura06 - PräsentationPublikation Allosteric targeting resolves limitations of earlier LFA-1 directed modalities(Elsevier, 05/2023) Mancuso, Riccardo V.; Schneider, Gisbert; Hürzeler Müller, Marianne; Gut, Martin; Zurflüh, Jonas; Breitenstein, Werner; Bouitbir, Jamal; Reisen, Felix; Atz, Kenneth; Ehrhardt, Claus; Duthaler, Urs; Gygax, Daniel; Schmidt, Albrecht G.; Krähenbühl, Stephan; Weitz-Schmidt, Gabriele01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Altered (neo-) lacto series glycolipid biosynthesis impairs α2-6 sialylation on N-glycoproteins in ovarian cancer cells(Nature, 30.03.2017) Alam, Shahidul; Anugraham, Merrina; Huang, Yen-Lin; Kohler, Reto; Hettich, Timm; Winkelbach, Katharina; Grether, Yasmin; Nunez Lopez, Monica; Khasbiullina, Nailia; Bovin, Nicolai V.; Schlotterbeck, Götz; Jacob, FrancisThe (neo-) lacto series glycosphingolipids (nsGSLs) comprise of glycan epitopes that are present as blood group antigens, act as primary receptors for human pathogens and are also increasingly associated with malignant diseases. Beta-1, 3-N-acetyl-glucosaminyl-transferase 5 (B3GNT5) is suggested as the key glycosyltransferase for the biosynthesis of nsGSLs. In this study, we investigated the impact of CRISPR-Cas9 -mediated gene disruption of B3GNT5 (∆B3GNT5) on the expression of glycosphingolipids and N-glycoproteins by utilizing immunostaining and glycomics-based PGC-UHPLC-ESI-QTOF-MS/MS profiling. ∆B3GNT5 cells lost nsGSL expression coinciding with reduction of α2-6 sialylation on N-glycoproteins. In contrast, disruption of B4GALNT1, a glycosyltransferase for ganglio series GSLs did not affect α2-6 sialylation on N-glycoproteins. We further profiled all known α2-6 sialyltransferase-encoding genes and showed that the loss of α2-6 sialylation is due to silencing of ST6GAL1 expression in ∆B3GNT5 cells. These results demonstrate that nsGSLs are part of a complex network affecting N-glycosylation in ovarian cancer cells.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Amino acid composition of nanofibrillar self-assembling peptide hydrogels affects responses of periodontal tissue cells in vitro(Dove Medical Press, 10/2018) Koch, Franziska; Wolff, Anne; Mathes, Stephanie; Pieles, Uwe; Saxer, Sina; Kreikemeyer, Bernd; Peters, KirstenThe regeneration of tissue defects at the interface between soft and hard tissue, eg, in the periodontium, poses a challenge due to the divergent tissue requirements. A class of biomaterials that may support the regeneration at the soft-to-hard tissue interface are self-assembling peptides (SAPs), as their physicochemical and mechanical properties can be rationally designed to meet tissue requirements.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation An Acute Ocfentanil Fatality: A Case Report with Postmortem Concentrations(Oxford University Press, 2016) Dussy, Franz; Hangartner, Sarah; Hamberg, Cornelia; Berchtold, Christoph; Scherer, Ulrich; Schlotterbeck, Götz; Wyler, David; Briellmann, ThomasA 24-year-old man known to consume illegal drugs was found dead in his apartment. A reclosable plastic zipper bag containing several hundred milligrams of a brown powder was found close to the dead body and the first assumption of the investigators was death due to heroin intoxication. Therefore, a legal autopsy was ordered. The following toxicological analysis revealed ocfentanil in urine and in the brown powder. Four different approaches for the determination of the ocfentanil concentrations in peripheral whole blood are described. Enrichment of ocfentanil from the powder was realized. With this reference, it was possible to determine the ocfentanil concentration in the seized powder to be 0.91%. Concentrations of ocfentanil were also determined in the sampled body fluids using the standard addition procedure. In peripheral blood 9.1 µg/L, in heart blood 27.9 µg/L and in urine 480 µg/L were measured. In addition, the antidepressant citalopram, the neuroleptic quetiapine and cannabinoids were found in urine and subsequently quantified in peripheral blood.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation An origami like 3D patterned cellulose-based scaffold for bioengineering cardiovascular applications(Springer, 2023) Rodriguez, Gabriela Melo; Trueb, Donata; Köser, Joachim; Schoelkopf, Joachim; Gullo, MaurizioIn this work we describe the manufacturing of cellulosic, cell compatible scaffolds with an inherent 3D origami crease pattern for applications in cardiac tissue engineering. Different cellulosic materials were studied, among them cotton linters, fibers obtained from eucalyptus, pine, spruce and lyocell. Formed sheets made of cotton linters were chosen for further study due to the highest biocompatibility and mechanical properties best suited for cardiomyocytes in wet and dry conditions: E - modulus of 0.8 GPa, tensile strength of 4.7 MPa and tensile strength in wet environment of 2.28 MPa. Cell alignment is desired to achieve directional contraction of the cardiac tissue, and several options were investigated to achieve fiber alignment, e.g. a dynamic sheet former and Rapid Köthen sheet former. Although the orientation was minimal, cells cultured on the cellulose fibers grew and aligned along the fibers. Origami inspired crease patterns were applied to the cellulose scaffolds in order to introduce directional flexibility beneficial for cardiac contraction. The transfer of a Miura-ori crease pattern was successfully applied in two ways: folding of the dried sheet between PET foils pre-formed in a 3D printed mold, and in situ wet fiber molding on a 3D-patterned mesh mounted in the sheet former’s sieve section. The latter approach enables upscaling for potential mass production.01A - Beitrag in wissenschaftlicher ZeitschriftPublikation Antibacterial Active Glass(25.02.2016) Köser, Joachim; Pieles, Uwe; Meier, Pascal; Widmer, A.06 - PräsentationPublikation Antimicrobial Polyethylene through Melt Compounding with Quaternary Ammonium Salts(Hindawi Publishing Corporation, 04/2017) Rossetti, Fernanda; Siegmann, Konstantin; Köser, Joachim; Wegner, Irene; Keskin, Ismail; Schlotterbeck, Götz; Winkler, MartinSelected mono- and bicationic quats were compounded with polyethylene. The physicochemical surface properties, leaching behavior, and antibacterial activity of such modified samples were investigated. Contact angle measurements and fluorescein binding assays showed the presence of quaternary ammonium groups at the surface. After storing the samples in 50°C warm water for 30 days, several were still antimicrobially active. No correlation between the number of exposed N+ head groups after leaching and the antibacterial activity was observed. There is however a qualitative correlation of the antibacterial activity with the contact angles and surface concentrations of N+ before leaching/storing in warm water.01A - Beitrag in wissenschaftlicher Zeitschrift