@article{SteinseiferKashefiHormesetal.2009, author = {Steinseifer, Ulrich and Kashefi, Ali and Hormes, Marcus and Schoberer, Mark and Orlikowsky, Thorsten and Behbahani, Mehdi and Behr, Marek and Schmitz-Rode, Thomas}, title = {Miniaturization of ECMO Systems : Engineering Challenges and Methods}, series = {Artificial Organs. 33 (2009), H. 5}, journal = {Artificial Organs. 33 (2009), H. 5}, isbn = {1525-1594}, pages = {A55 -- A55}, year = {2009}, language = {en} } @article{JansenBehbahaniLaumenetal.2010, author = {Jansen, Sebastian and Behbahani, Mehdi and Laumen, Marco and Kaufmann, Tim and Hormes, Marcus and Schmitz-Rode, Thomas and Behr, Marek and Steinseifer, Ulrich}, title = {3D Stereo-PIV Validation for CFD-Simulation of Steady Flow through the Human Aorta using Rapid-Prototyping techniques}, year = {2010}, language = {en} } @article{JahnkeMenzelDusschotenetal.2009, author = {Jahnke, Siegfried and Menzel, Marion I. and Dusschoten, Dagmar van and Roeb, Gerhard W. and B{\"u}hler, Jonas and Minwuyelet, Senay and Bl{\"u}mler, Peter and Temperton, Vicky M. and Hombach, Thomas and Streun, Matthias and Beer, Simone and Khodaverdi, Maryam and Ziemons, Karl and Coenen, Heinz H. and Schurr, Ulrich}, title = {Combined MRI-PET dissects dynamic changes in plant structures and functions}, series = {The Plant Journal}, volume = {59}, journal = {The Plant Journal}, number = {4}, publisher = {Wiley}, address = {Weinheim}, isbn = {1365-313X}, pages = {634 -- 644}, year = {2009}, abstract = {Unravelling the factors determining the allocation of carbon to various plant organs is one of the great challenges of modern plant biology. Studying allocation under close to natural conditions requires non-invasive methods, which are now becoming available for measuring plants on a par with those developed for humans. By combining magnetic resonance imaging (MRI) and positron emission tomography (PET), we investigated three contrasting root/shoot systems growing in sand or soil, with respect to their structures, transport routes and the translocation dynamics of recently fixed photoassimilates labelled with the short-lived radioactive carbon isotope 11C. Storage organs of sugar beet (Beta vulgaris) and radish plants (Raphanus sativus) were assessed using MRI, providing images of the internal structures of the organs with high spatial resolution, and while species-specific transport sectoralities, properties of assimilate allocation and unloading characteristics were measured using PET. Growth and carbon allocation within complex root systems were monitored in maize plants (Zea mays), and the results may be used to identify factors affecting root growth in natural substrates or in competition with roots of other plants. MRI-PET co-registration opens the door for non-invasive analysis of plant structures and transport processes that may change in response to genomic, developmental or environmental challenges. It is our aim to make the methods applicable for quantitative analyses of plant traits in phenotyping as well as in understanding the dynamics of key processes that are essential to plant performance.}, language = {en} } @article{EngelmannRoethEberbecketal.2018, author = {Engelmann, Ulrich M. and Roeth, Anjali A.J. and Eberbeck, Dietmar and Buhl, Eva Miriam and Neumann, Ulf Peter and Schmitz-Rode, Thomas and Slabu, Ioana}, title = {Combining Bulk Temperature and Nanoheating Enables Advanced Magnetic Fluid Hyperthermia Efficacy on Pancreatic Tumor Cells}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {1}, publisher = {Springer Nature}, address = {Cham}, issn = {2045-2322}, doi = {10.1038/s41598-018-31553-9}, pages = {Article number 13210}, year = {2018}, abstract = {Many efforts are made worldwide to establish magnetic fluid hyperthermia (MFH) as a treatment for organ-confined tumors. However, translation to clinical application hardly succeeds as it still lacks of understanding the mechanisms determining MFH cytotoxic effects. Here, we investigate the intracellular MFH efficacy with respect to different parameters and assess the intracellular cytotoxic effects in detail. For this, MiaPaCa-2 human pancreatic tumor cells and L929 murine fibroblasts were loaded with iron-oxide magnetic nanoparticles (MNP) and exposed to MFH for either 30 min or 90 min. The resulting cytotoxic effects were assessed via clonogenic assay. Our results demonstrate that cell damage depends not only on the obvious parameters bulk temperature and duration of treatment, but most importantly on cell type and thermal energy deposited per cell during MFH treatment. Tumor cell death of 95\% was achieved by depositing an intracellular total thermal energy with about 50\% margin to damage of healthy cells. This is attributed to combined intracellular nanoheating and extracellular bulk heating. Tumor cell damage of up to 86\% was observed for MFH treatment without perceptible bulk temperature rise. Effective heating decreased by up to 65\% after MNP were internalized inside cells.}, language = {en} } @article{EngelmannBuhlDraacketal.2018, author = {Engelmann, Ulrich M. and Buhl, Eva Miriam and Draack, Sebastian and Viereck, Thilo and Frank, and Schmitz-Rode, Thomas and Slabu, Ioana}, title = {Magnetic relaxation of agglomerated and immobilized iron oxide nanoparticles for hyperthermia and imaging applications}, series = {IEEE Magnetic Letters}, volume = {9}, journal = {IEEE Magnetic Letters}, number = {Article number 8519617}, publisher = {IEEE}, address = {New York, NY}, issn = {1949-307X}, doi = {10.1109/LMAG.2018.2879034}, year = {2018}, abstract = {Magnetic nanoparticles (MNPs) are used as therapeutic and diagnostic agents for local delivery of heat and image contrast enhancement in diseased tissue. Besides magnetization, the most important parameter that determines their performance for these applications is their magnetic relaxation, which can be affected when MNPs immobilize and agglomerate inside tissues. In this letter, we investigate different MNP agglomeration states for their magnetic relaxation properties under excitation in alternating fields and relate this to their heating efficiency and imaging properties. With focus on magnetic fluid hyperthermia, two different trends in MNP heating efficiency are measured: an increase by up to 23\% for agglomerated MNP in suspension and a decrease by up to 28\% for mixed states of agglomerated and immobilized MNP, which indicates that immobilization is the dominant effect. The same comparatively moderate effects are obtained for the signal amplitude in magnetic particle spectroscopy.}, language = {en} } @article{EngelmannBuhlBaumannetal.2017, author = {Engelmann, Ulrich M. and Buhl, Eva Miriam and Baumann, Martin and Schmitz-Rode, Thomas and Slabu, Ioana}, title = {Agglomeration of magnetic nanoparticles and its effects on magnetic hyperthermia}, series = {Current Directions in Biomedical Engineering}, volume = {3}, journal = {Current Directions in Biomedical Engineering}, number = {2}, publisher = {De Gruyter}, address = {Berlin}, issn = {2364-5504}, doi = {10.1515/cdbme-2017-0096}, pages = {457 -- 460}, year = {2017}, language = {en} } @article{SlabuRoethEngelmannetal.2019, author = {Slabu, Ioana and Roeth, Anjali A. and Engelmann, Ulrich M. and Wiekhorst, Frank and Buhl, Eva M. and Neumann, Ulf P. and Schmitz-Rode, Thomas}, title = {Modeling of magnetoliposome uptake in human pancreatic tumor cells in vitro}, series = {Nanotechnology}, volume = {30}, journal = {Nanotechnology}, number = {18}, issn = {1361-6528}, doi = {10.1088/1361-6528/ab033e}, pages = {184004}, year = {2019}, language = {en} } @techreport{StoelzleFeixThomasEngelstaedteretal.2021, author = {St{\"o}lzle-Feix, Sonja and Thomas, Ulrich and Engelst{\"a}dter, Max and Goßmann, Matthias and Linder, Peter and Staat, Manfred and Raman, Aravind Hariharan and Jung, Alexander and Fertig, Niels}, title = {Plattformtechnologie f{\"u}r kardiale Sicherheitspharmakologie basierend auf teilsynthetischem Herzmuskelgewebe (FLEXcyte) : gemeinsamer FuE-Abschlussbericht aller Partner des Verbundprojektes : Projektlaufzeit: 01.10.2018 bis 30.09.2020}, publisher = {Nanion Technologies GmbH}, address = {M{\"u}nchen}, doi = {10.2314/KXP:1813208581}, pages = {IV, 85 Seiten, 2 ungez{\"a}hlte Seiten}, year = {2021}, language = {de} } @article{GossmannThomasHorvathetal.2020, author = {Gossmann, Matthias and Thomas, Ulrich and Horv{\´a}th, Andr{\´a}s and Dragicevic, Elena and Stoelzle-Feix, Sonja and Jung, Alexander and Raman, Aravind Hariharan and Staat, Manfred and Linder, Peter}, title = {A higher-throughput approach to investigate cardiac contractility in vitro under physiological mechanical conditions}, series = {Journal of Pharmacological and Toxicological Methods}, volume = {105}, journal = {Journal of Pharmacological and Toxicological Methods}, number = {Article 106843}, publisher = {Elsevier}, address = {New York, NY}, doi = {10.1016/j.vascn.2020.106843}, year = {2020}, language = {en} } @article{BrockhausBehbahaniMurisetal.2021, author = {Brockhaus, Moritz K. and Behbahani, Mehdi and Muris, Farina and Jansen, Sebastian V. and Schmitz- Rode, Thomas and Steinseifer, Ulrich and Clauser, Johanna C.}, title = {In vitro thrombogenicity testing of pulsatile mechanical circulatory support systems: Design and proof-of-concept}, series = {Artificial Organs}, volume = {45}, journal = {Artificial Organs}, number = {12}, publisher = {Wiley}, address = {Weinheim}, issn = {1525-1594}, doi = {10.1111/aor.14046}, pages = {1513 -- 1521}, year = {2021}, abstract = {Thrombogenic complications are a main issue in mechanical circulatory support (MCS). There is no validated in vitro method available to quantitatively assess the thrombogenic performance of pulsatile MCS devices under realistic hemodynamic conditions. The aim of this study is to propose a method to evaluate the thrombogenic potential of new designs without the use of complex in-vivo trials. This study presents a novel in vitro method for reproducible thrombogenicity testing of pulsatile MCS systems using low molecular weight heparinized porcine blood. Blood parameters are continuously measured with full blood thromboelastometry (ROTEM; EXTEM, FIBTEM and a custom-made analysis HEPNATEM). Thrombus formation is optically observed after four hours of testing. The results of three experiments are presented each with two parallel loops. The area of thrombus formation inside the MCS device was reproducible. The implantation of a filter inside the loop catches embolizing thrombi without a measurable increase of platelet activation, allowing conclusions of the place of origin of thrombi inside the device. EXTEM and FIBTEM parameters such as clotting velocity (α) and maximum clot firmness (MCF) show a total decrease by around 6\% with a characteristic kink after 180 minutes. HEPNATEM α and MCF rise within the first 180 minutes indicate a continuously increasing activation level of coagulation. After 180 minutes, the consumption of clotting factors prevails, resulting in a decrease of α and MCF. With the designed mock loop and the presented protocol we are able to identify thrombogenic hot spots inside a pulsatile pump and characterize their thrombogenic potential.}, language = {en} } @article{KnoxBruggemannGossmannetal.2020, author = {Knox, Ronald and Bruggemann, Andrea and Gossmann, Matthias and Thomas, Ulrich and Horv{\´a}th, Andr{\´a}s and Dragicevic, Elena and Stoelzle-Feix, Sonja and Fertig, Niels and Jung, Alexander and Raman, Aravind Hariharan and Staat, Manfred and Linder, Peter}, title = {Combining physiological relevance and throughput for in vitro cardiac contractility measurement}, series = {Biophysical Journal}, volume = {118}, journal = {Biophysical Journal}, number = {Issue 3, Supplement 1}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0006-3495}, doi = {10.1016/j.bpj.2019.11.3104}, pages = {570a}, year = {2020}, abstract = {Despite increasing acceptance of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in safety pharmacology, controversy remains about the physiological relevance of existing in vitro models for their mechanical testing. We hypothesize that existing signs of immaturity of the cell models result from an improper mechanical environment. We cultured hiPSC-CMs in a 96-well format on hyperelastic silicone membranes imitating their native mechanical environment, resulting in physiological responses to compound stimuli.We validated cell responses on the FLEXcyte 96, with a set of reference compounds covering a broad range of cellular targets, including ion channel modulators, adrenergic receptor modulators and kinase inhibitors. Acute (10 - 30 min) and chronic (up to 7 days) effects were investigated. Furthermore, the measurements were complemented with electromechanical models based on electrophysiological recordings of the used cell types.hiPSC-CMs were cultured on freely-swinging, ultra-thin and hyperelastic silicone membranes. The weight of the cell culture medium deflects the membranes downwards. Rhythmic contraction of the hiPSC-CMs resulted in dynamic deflection changes which were quantified by capacitive distance sensing. The cells were cultured for 7 days prior to compound addition. Acute measurements were conducted 10-30 minutes after compound addition in standard culture medium. For chronic treatment, compound-containing medium was replaced daily for up to 7 days. Electrophysiological properties of the employed cell types were recorded by automated patch-clamp (Patchliner) and the results were integrated into the electromechanical model of the system.Calcium channel agonist S Bay K8644 and beta-adrenergic stimulator isoproterenol induced significant positive inotropic responses without additional external stimulation. Kinase inhibitors displayed cardiotoxic effects on a functional level at low concentrations. The system-integrated analysis detected alterations in beating shape as well as frequency and arrhythmic events and we provide a quantitative measure of these.}, language = {en} }