TY - JOUR A1 - Schöning, Michael Josef A1 - Bronder, Thomas A1 - Wu, Chunsheng A1 - Scheja, Sabrina A1 - Jessing, Max A1 - Metzger-Boddien, Christoph A1 - Keusgen, Michael A1 - Poghossian, Arshak T1 - Label-Free DNA Detection with Capacitive Field-Effect Devices—Challenges and Opportunities JF - Proceedings N2 - Field-effect EIS (electrolyte-insulator-semiconductor) sensors modified with a positively charged weak polyelectrolyte layer have been applied for the electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization by the intrinsic molecular charge. The EIS sensors are able to detect the existence of target DNA amplicons in PCR (polymerase chain reaction) samples and thus, can be used as tool for a quick verification of DNA amplification and the successful PCR process. Due to their miniaturized setup, compatibility with advanced micro- and nanotechnologies, and ability to detect biomolecules by their intrinsic molecular charge, those sensors can serve as possible platform for the development of label-free DNA chips. Possible application fields as well as challenges and limitations will be discussed. Y1 - 2017 U6 - https://doi.org/10.3390/proceedings1080719 SN - 2504-3900 N1 - This article belongs to the Proceedings of "Proceedings of the 5th International Symposium on Sensor Science (I3S 2017)" VL - 1 IS - 8 SP - Artikel 719 PB - MDPI CY - Basel ER - TY - JOUR A1 - Richter, Charlotte A1 - Braunstein, Bjoern A1 - Winnard, Andrew A1 - Nasser, Mona A1 - Weber, T. T1 - Human Biomechanical and Cardiopulmonary Responses to Partial Gravity – A Systematic Review JF - Frontiers in physiology Y1 - 2017 U6 - https://doi.org/10.3389/fphys.2017.00583 IS - 8, article 583 ER - TY - JOUR A1 - Horbach, Andreas A1 - Duong, Minh Tuan A1 - Staat, Manfred T1 - Modelling of compressible and orthotropic surgical mesh implants based on optical deformation measurement JF - Journal of the mechanical behavior of biomedical materials Y1 - 2017 U6 - https://doi.org/10.1016/j.jmbbm.2017.06.012 SN - 1751-6161 VL - 74 SP - 400 EP - 410 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Molinnus, Denise A1 - Poghossian, Arshak A1 - Keusgen, Michael A1 - Katz, Evgeny A1 - Schöning, Michael Josef T1 - Coupling of Biomolecular Logic Gates with Electronic Transducers: From Single Enzyme Logic Gates to Sense/Act/Treat Chips JF - Electroanalysis N2 - The integration of biomolecular logic principles with electronic transducers allows designing novel digital biosensors with direct electrical output, logically triggered drug-release, and closed-loop sense/act/treat systems. This opens new opportunities for advanced personalized medicine in the context of theranostics. In the present work, we will discuss selected examples of recent developments in the field of interfacing enzyme logic gates with electrodes and semiconductor field-effect devices. Special attention is given to an enzyme OR/Reset logic gate based on a capacitive field-effect electrolyte-insulator-semiconductor sensor modified with a multi-enzyme membrane. Further examples are a digital adrenaline biosensor based on an AND logic gate with binary YES/NO output and an integrated closed-loop sense/act/treat system comprising an amperometric glucose sensor, a hydrogel actuator, and an insulin (drug) sensor. Y1 - 2017 U6 - https://doi.org/10.1002/elan.201700208 SN - 1521-4109 VL - 29 IS - 8 SP - 1840 EP - 1849 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Katz, Evgeny A1 - Poghossian, Arshak A1 - Schöning, Michael Josef T1 - Enzyme-based logic gates and circuits - analytical applications and interfacing with electronics JF - Analytical and Bioanalytical Chemistry N2 - The paper is an overview of enzyme-based logic gates and their short circuits, with specific examples of Boolean AND and OR gates, and concatenated logic gates composed of multi-step enzyme-biocatalyzed reactions. Noise formation in the biocatalytic reactions and its decrease by adding a “filter” system, converting convex to sigmoid response function, are discussed. Despite the fact that the enzyme-based logic gates are primarily considered as components of future biomolecular computing systems, their biosensing applications are promising for immediate practical use. Analytical use of the enzyme logic systems in biomedical and forensic applications is discussed and exemplified with the logic analysis of biomarkers of various injuries, e.g., liver injury, and with analysis of biomarkers characteristic of different ethnicity found in blood samples on a crime scene. Interfacing of enzyme logic systems with modified electrodes and semiconductor devices is discussed, giving particular attention to the interfaces functionalized with signal-responsive materials. Future perspectives in the design of the biomolecular logic systems and their applications are discussed in the conclusion. Y1 - 2017 U6 - https://doi.org/10.1007/s00216-016-0079-7 SN - 1618-2650 VL - 409 SP - 81 EP - 94 PB - Springer CY - Berlin ER - TY - JOUR A1 - Baringhaus, Ludwig A1 - Gaigall, Daniel T1 - Hotelling’s T² tests in paired and independent survey samples: An efficiency comparison JF - Journal of Multivariate Analysis N2 - Hotelling’s T² tests in paired and independent survey samples are compared using the traditional asymptotic efficiency concepts of Hodges–Lehmann, Bahadur and Pitman, as well as through criteria based on the volumes of corresponding confidence regions. Conditions characterizing the superiority of a procedure are given in terms of population canonical correlation type coefficients. Statistical tests for checking these conditions are developed. Test statistics based on the eigenvalues of a symmetrized sample cross-covariance matrix are suggested, as well as test statistics based on sample canonical correlation type coefficients. Y1 - 2017 U6 - https://doi.org/10.1016/j.jmva.2016.11.004 SN - 0047-259X VL - 2017 IS - 154 SP - 177 EP - 198 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Laack, Walter van T1 - Neurophysiologisch ist das nicht alles zu erklären : Nahtoderfahrungen aus wissenschaftlicher Sicht JF - Der Allgemeinarzt Y1 - 2017 SN - 0172-7249 VL - 38 IS - 1 SP - 4 EP - 7 PB - Universimed Deutschland GmbH CY - Mainz ER - TY - JOUR A1 - Baringhaus, Ludwig A1 - Gaigall, Daniel T1 - On Hotelling’s T² test in a special paired sample case JF - Communications in Statistics - Theory and Methods N2 - In a special paired sample case, Hotelling’s T² test based on the differences of the paired random vectors is the likelihood ratio test for testing the hypothesis that the paired random vectors have the same mean; with respect to a special group of affine linear transformations it is the uniformly most powerful invariant test for the general alternative of a difference in mean. We present an elementary straightforward proof of this result. The likelihood ratio test for testing the hypothesis that the covariance structure is of the assumed special form is derived and discussed. Applications to real data are given. KW - complete block symmetry KW - Hotelling’s T² test KW - likelihood ratio test KW - uniformly most powerful invariant test Y1 - 2017 U6 - https://doi.org/10.1080/03610926.2017.1408828 SN - 1532-415X VL - 48 IS - 2 SP - 257 EP - 267 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Jung, Alexander A1 - Müller, Wolfram A1 - Staat, Manfred T1 - Wind and fairness in ski jumping: A computer modelling analysis JF - Journal of Biomechanics N2 - Wind is closely associated with the discussion of fairness in ski jumping. To counter-act its influence on the jump length, the International Ski Federation (FIS) has introduced a wind compensation approach. We applied three differently accurate computer models of the flight phase with wind (M1, M2, and M3) to study the jump length effects of various wind scenarios. The previously used model M1 is accurate for wind blowing in direction of the flight path, but inaccuracies are to be expected for wind directions deviating from the tangent to the flight path. M2 considers the change of airflow direction, but it does not consider the associated change in the angle of attack of the skis which additionally modifies drag and lift area time functions. M3 predicts the length effect for all wind directions within the plane of the flight trajectory without any mathematical simplification. Prediction errors of M3 are determined only by the quality of the input data: wind velocity, drag and lift area functions, take-off velocity, and weight. For comparing the three models, drag and lift area functions of an optimized reference jump were used. Results obtained with M2, which is much easier to handle than M3, did not deviate noticeably when compared to predictions of the reference model M3. Therefore, we suggest to use M2 in future applications. A comparison of M2 predictions with the FIS wind compensation system showed substantial discrepancies, for instance: in the first flight phase, tailwind can increase jump length, and headwind can decrease it; this is opposite of what had been anticipated before and is not considered in the current wind compensation system in ski jumping. Y1 - 2018 U6 - https://doi.org/10.1016/j.jbiomech.2018.05.001 SN - 0021-9290 IS - 75 SP - 147 EP - 153 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Jung, Alexander A1 - Staat, Manfred A1 - Müller, Wolfram T1 - Corrigendum to “Flight style optimization in ski jumping on normal, large, and ski flying hills” [J. Biomech 47 (2014) 716–722] JF - Journals of Biomechanics Y1 - 2018 U6 - https://doi.org/10.1016/j.jbiomech.2018.02.001 SN - 0021-9290 N1 - refers to Journal of Biomechanics Vol 47, Issue 3, Pages 716-722: https://doi.org/10.1016/j.jbiomech.2013.11.021 SP - 313 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Bhattarai, Aroj A1 - Jabbari, Medisa A1 - Anding, Ralf A1 - Staat, Manfred T1 - Surgical treatment of vaginal vault prolapse using different prosthetic mesh implants: a finite element analysis JF - tm - Technisches Messen N2 - Particularly multiparous elderly women may suffer from vaginal vault prolapse after hysterectomy due to weak support from lax apical ligaments. A decreased amount of estrogen and progesterone in older age is assumed to remodel the collagen thereby reducing tissue stiffness. Sacrocolpopexy is either performed as open or laparoscopic surgery using prosthetic mesh implants to substitute lax ligaments. Y-shaped mesh models (DynaMesh, Gynemesh, and Ultrapro) are implanted in a 3D female pelvic floor finite element model in the extraperitoneal space from the vaginal cuff to the first sacral (S1) bone below promontory. Numerical simulations are conducted during Valsalva maneuver with weakened tissues modeled by reduced tissue stiffness. Tissues are modeled as incompressible, isotropic hyperelastic materials whereas the meshes are modeled either as orthotropic linear elastic or as isotropic hyperlastic materials. The positions of the vaginal cuff and the bladder base are calculated from the pubococcygeal line for female pelvic floor at rest, for prolapse and after repair using the three meshes. Due to mesh mechanics and mesh pore deformation along the loaded direction, the DynaMesh with regular rectangular mesh pores is found to provide better mechanical support to the organs than the Gynemesh and the Ultrapro with irregular hexagonal mesh pores. Insbesondere ältere, mehrgebährende Frauen leiden häufiger an einem Scheidenvorfall nach einer Hysterektomie aufgrund der schwachen Unterstützung durch laxe apikale Bänder. Es wird angenommen, dass eine verringerte Menge an Östrogen und Progesteron im höheren Alter das Kollagen umformt, wodurch die Gewebesteifigkeit reduziert wird. Die Sakrokolpopexie ist eine offene oder laparoskopische Operation, die mit prothetischen Netzimplantaten durchgeführt wird, um laxe Bänder zu ersetzen. Y-förmige Netzmodelle (DynaMesh, Gynemesh und Ultrapro) werden in einem 3D-Modell des weiblichen Beckenbodens im extraperitonealen Raum vom Vaginalstumpf bis zum Promontorium implantiert. Numerische Simulationen werden während des Valsalva-Manövers mit geschwächtem Gewebe durchgeführt, das durch eine reduzierte Gewebesteifigkeit modelliert wird. Die Gewebe werden als inkompressible, isotrop hyperelastische Materialien modelliert, während die Netze entweder als orthotrope linear elastische oder als isotrope hyperlastische Materialien modelliert werden. Die Positionen des Vaginalstumpfs, der Blase und der Harnröhrenachse werden anhand der Pubococcygeallinie aus der Ruhelage, für den Prolaps und nach der Reparatur unter Verwendung der drei Netze berechnet. Aufgrund der Netzmechanik und der Netzporenverformung bietet das DynaMesh mit regelmäßigen rechteckigen Netzporen eine bessere mechanische Unterstützung und eine Neupositionierung des Scheidengewölbes, der Blase und der Urethraachse als Gynemesh und Ultrapro mit unregelmäßigen hexagonalen Netzporen. Y1 - 2018 U6 - https://doi.org/10.1515/teme-2017-0115 SN - 2196-7113 VL - 85 IS - 5 SP - 331 EP - 342 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Birgel, Stefan A1 - Leschinger, Tim A1 - Wegmann, Kilian A1 - Staat, Manfred T1 - Calculation of muscle forces and joint reaction loads in the shoulder area via an OpenSim based computer model JF - tm - Technisches Messen N2 - Using the OpenSim software and verified anatomical data, a computer model for the calculation of biomechanical parameters is developed and used to determine the effect of a reattachment of the Supraspinatus muscle with a medial displacement of the muscle attachment point, which may be necessary for a rupture of the supraspinatus tendon. The results include the influence of the operation on basic biomechanical parameters such as the lever arm, as well as the calculated the muscle activations for the supraspinatus and deltoid. In addition, the influence on joint stability is examined by an analysis of the joint reaction force. The study provides a detailed description of the used model, as well as medical findings to a reattachment of the supraspinatus. Mit der Software OpenSim und überprüften anatomischen Daten wird ein Computermodell zur Berechnung von biomechanischen Parametern entwickelt und genutzt, um den Effekt einer Refixierung des Supraspinatusmuskels mit einer medialen Verschiebung des Muskelansatzpunktes zu ermitteln, wie sie unter anderem nach einem Riss der Supraspinatussehne notwendig sein kann. Die Ergebnisse umfassen hierbei den Einfluss der Operation auf grundlegende biomechanische Parameter wie den Hebelarm sowie die berechneten Muskelaktivierungen für den Supraspinatus und Deltoideus. Zusätzlich wird der Einfluss auf die Gelenkstabilität betrachtet und durch eine Analyse der Gelenkreaktionskraft untersucht. Die Studie bietet eine detaillierte Beschreibung des genutzten Modells, sowie medizinische Erkenntnisse zu einer Refixierung des Supraspinatus. Y1 - 2018 U6 - https://doi.org/10.1515/teme-2017-0114 SN - 2196-7113 VL - 85 IS - 5 SP - 321 EP - 330 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Bhattarai, Aroj A1 - Staat, Manfred T1 - Modelling of Soft Connective Tissues to Investigate Female Pelvic Floor Dysfunctions JF - Computational and Mathematical Methods in Medicine N2 - After menopause, decreased levels of estrogen and progesterone remodel the collagen of the soft tissues thereby reducing their stiffness. Stress urinary incontinence is associated with involuntary urine leakage due to pathological movement of the pelvic organs resulting from lax suspension system, fasciae, and ligaments. This study compares the changes in the orientation and position of the female pelvic organs due to weakened fasciae, ligaments, and their combined laxity. A mixture theory weighted by respective volume fraction of elastin-collagen fibre compound (5%), adipose tissue (85%), and smooth muscle (5%) is adopted to characterize the mechanical behaviour of the fascia. The load carrying response (other than the functional response to the pelvic organs) of each fascia component, pelvic organs, muscles, and ligaments are assumed to be isotropic, hyperelastic, and incompressible. Finite element simulations are conducted during Valsalva manoeuvre with weakened tissues modelled by reduced tissue stiffness. A significant dislocation of the urethrovesical junction is observed due to weakness of the fascia (13.89 mm) compared to the ligaments (5.47 mm). The dynamics of the pelvic floor observed in this study during Valsalva manoeuvre is associated with urethral-bladder hypermobility, greater levator plate angulation, and positive Q-tip test which are observed in incontinent females. Y1 - 2018 U6 - https://doi.org/10.1155/2018/9518076 SN - 1748-6718 VL - 2018 IS - Article ID 9518076 SP - 1 EP - 16 PB - Hindawi CY - New York, NY ER - TY - JOUR A1 - Digel, Ilya A1 - Wehlitz, V. A1 - Kayser, Peter A1 - Figiel-Lange, A. A1 - Bassam, R. A1 - Rundstedt, F. von T1 - Suspension depletion approach for exemption of infected Solanum jasminoides cells from pospiviroids JF - Plant Pathology N2 - Despite numerous studies, viroid elimination from infected plants remains a very challenging task. This study introduces for the first time a novel ‘suspension depletion’ approach for exemption of Solanum jasminoides plants from viroids. The proposed method implies initial establishment of suspension cultures of the infected plant cells. The suspended cells were then physically treated (mild thermotherapy, 33 °C), which presumably delayed the replication of the viroid. The viroid concentration in the treated biomass was monitored weekly using pospiviroid-specific PCR. After 10–12 weeks of continuous treatment, a sufficient decrease in viroid concentration was observed such that the infection became undetectable by PCR. The treated single cells then gave rise to microcolonies on a solid culture medium and the obtained viroid-negative clones were further promoted to regenerate into viroid-free plants. Three years of accumulated experimental data suggests feasibility, broad applicability, and good efficacy of the proposed approach. Y1 - 2018 U6 - https://doi.org/10.1111/ppa.12750 SN - 1365-3059 VL - 67 IS - 2 SP - 358 EP - 365 PB - Wiley CY - Oxford ER - TY - JOUR A1 - Welden, Rene A1 - Scheja, Sabrina A1 - Schöning, Michael Josef A1 - Wagner, Patrick A1 - Wagner, Torsten T1 - Electrochemical Evaluation of Light‐Addressable Electrodes Based on TiO2 for the Integration in Lab‐on‐Chip Systems JF - physica status solidi a : applications and materials sciences N2 - In lab-on-chip systems, electrodes are important for the manipulation (e.g., cell stimulation, electrolysis) within such systems. An alternative to commonly used electrode structures can be a light-addressable electrode. Here, due to the photoelectric effect, the conducting area can be adjusted by modification of the illumination area which enables a flexible control of the electrode. In this work, titanium dioxide based light-addressable electrodes are fabricated by a sol–gel technique and a spin-coating process, to deposit a thin film on a fluorine-doped tin oxide glass. To characterize the fabricated electrodes, the thickness, and morphological structure are measured by a profilometer and a scanning electron microscope. For the electrochemical behavior, the dark current and the photocurrent are determined for various film thicknesses. For the spatial resolution behavior, the dependency of the photocurrent while changing the area of the illuminated area is studied. Furthermore, the addressing of single fluid compartments in a three-chamber system, which is added to the electrode, is demonstrated. Y1 - 2018 U6 - https://doi.org/10.1002/pssa.201800150 SN - 1862-6319 VL - 215 IS - 15 SP - Article number 1800150 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Jildeh, Zaid B. A1 - Oberländer, Jan A1 - Kirchner, Patrick A1 - Wagner, Patrick H. A1 - Schöning, Michael Josef T1 - Thermocatalytic Behavior of Manganese (IV) Oxide as Nanoporous Material on the Dissociation of a Gas Mixture Containing Hydrogen Peroxide JF - Nanomaterials N2 - In this article, we present an overview on the thermocatalytic reaction of hydrogen peroxide (H₂O₂) gas on a manganese (IV) oxide (MnO₂) catalytic structure. The principle of operation and manufacturing techniques are introduced for a calorimetric H₂O₂ gas sensor based on porous MnO₂. Results from surface analyses by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) of the catalytic material provide indication of the H₂O₂ dissociation reaction schemes. The correlation between theory and the experiments is documented in numerical models of the catalytic reaction. The aim of the numerical models is to provide further information on the reaction kinetics and performance enhancement of the porous MnO₂ catalyst. Y1 - 2018 U6 - https://doi.org/10.3390/nano8040262 SN - 2079-4991 VL - 8 IS - 4 PB - MDPI CY - Basel ER - TY - JOUR A1 - Pilas, Johanna A1 - Yazici, Y. A1 - Selmer, Thorsten A1 - Keusgen, M. A1 - Schöning, Michael Josef T1 - Application of a portable multi-analyte biosensor for organic acid determination in silage JF - Sensors N2 - Multi-analyte biosensors may offer the opportunity to perform cost-effective and rapid analysis with reduced sample volume, as compared to electrochemical biosensing of each analyte individually. This work describes the development of an enzyme-based biosensor system for multi-parametric determination of four different organic acids. The biosensor array comprises five working electrodes for simultaneous sensing of ethanol, formate, d-lactate, and l-lactate, and an integrated counter electrode. Storage stability of the biosensor was evaluated under different conditions (stored at +4 °C in buffer solution and dry at −21 °C, +4 °C, and room temperature) over a period of 140 days. After repeated and regular application, the individual sensing electrodes exhibited the best stability when stored at −21 °C. Furthermore, measurements in silage samples (maize and sugarcane silage) were conducted with the portable biosensor system. Comparison with a conventional photometric technique demonstrated successful employment for rapid monitoring of complex media. Y1 - 2018 U6 - https://doi.org/10.3390/s18051470 SN - 1424-8220 VL - 18 IS - 5 PB - MDPI CY - Basel ER - TY - JOUR A1 - Dantism, Shahriar A1 - Röhlen, Desiree A1 - Wagner, Torsten A1 - Wagner, Patrick A1 - Schöning, Michael Josef T1 - Optimization of Cell-Based Multi-Chamber LAPS Measurements Utilizing FPGA-Controlled Laser-Diode Modules JF - physica status solidi a : applications and materials sciences N2 - A light-addressable potentiometric sensor (LAPS) is a field-effect-based potentiometric device, which detects concentration changes of an analyte solution on the sensor surface in a spatially resolved way. It uses a light source to generate electron–hole pairs inside the semiconductor, which are separated in the depletion region due to an applied bias voltage across the sensor structure and hence, a surface-potential-dependent photocurrent can be read out. However, depending on the beam angle of the light source, scattering effects can occur, which influence the recorded signal in LAPS-based differential measurements. To solve this problem, a novel illumination unit based on a field programmable gate array (FPGA) consisting of 16 small-sized tunable infrared laser-diode modules (LDMs) is developed. Due to the improved focus of the LDMs with a beam angle of only 2 mrad, undesirable scattering effects are minimized. Escherichia coli (E. coli) K12 bacteria are used as a test microorganism to study the extracellular acidification on the sensor surface. Furthermore, a salt bridge chamber is built up and integrated with the LAPS system enabling multi-chamber differential measurements with a single Ag/AgCl reference electrode. Y1 - 2018 U6 - https://doi.org/10.1002/pssa.201800058 SN - 1862-6319 VL - 215 IS - 15 SP - Article number 1800058 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Vahidpour, Farnoosh A1 - Oberländer, Jan A1 - Schöning, Michael Josef T1 - Flexible Calorimetric Gas Sensors for Detection of a Broad Concentration Range of Gaseous Hydrogen Peroxide: A Step Forward to Online Monitoring of Food-Package Sterilization Processes JF - Phys. Status Solidi A N2 - In this study, flexible calorimetric gas sensors are developed for specificdetection of gaseous hydrogen peroxide (H₂O₂) over a wide concentrationrange, which is used in sterilization processes for aseptic packaging industry.The flexibility of these sensors is an advantage for identifying the chemical components of the sterilant on the corners of the food boxes, so-called “coldspots”, as critical locations in aseptic packaging, which are of great importance. These sensors are fabricated on flexible polyimide films by means of thin-film technique. Thin layers of titanium and platinum have been deposited on polyimide to define the conductive structures of the sensors. To detect the high-temperature evaporated H₂O₂, a differential temperature set-up is proposed. The sensors are evaluated in a laboratory-scaled sterilizationsystem to simulate the sterilization process. The concentration range of the evaporated H₂O₂ from 0 to 7.7% v/v was defined and the sensors have successfully detected high as well as low H₂O₂ concentrations with a sensitivity of 5.04 °C/% v/v. The characterizations of the sensors confirm their precise fabrication, high sensitivity and the novelty of low H₂O₂ concentration detections for future inline monitoring of food-package sterilization. Y1 - 2018 U6 - https://doi.org/10.1002/pssa.201800044 VL - 215 IS - 15 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Engelmann, Ulrich M. A1 - Roeth, Anjali A.J. A1 - Eberbeck, Dietmar A1 - Buhl, Eva Miriam A1 - Neumann, Ulf Peter A1 - Schmitz-Rode, Thomas A1 - Slabu, Ioana T1 - Combining Bulk Temperature and Nanoheating Enables Advanced Magnetic Fluid Hyperthermia Efficacy on Pancreatic Tumor Cells JF - Scientific Reports N2 - 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. Y1 - 2018 U6 - https://doi.org/10.1038/s41598-018-31553-9 SN - 2045-2322 VL - 8 IS - 1 SP - Article number 13210 PB - Springer Nature CY - Cham ER -