TY - JOUR A1 - Dadfar, Dryed Mohammadali A1 - Camozzi, Denise A1 - Darguzyte, Milita A1 - Roemhild, Karolin A1 - Varvarà, Paola A1 - Metselaar, Josbert A1 - Banala, Srinivas A1 - Straub, Marcel A1 - Güver, Nihan A1 - Engelmann, Ulrich M. A1 - Slabu, Ioana A1 - Buhl, Miriam A1 - Leusen, Jan van A1 - Kögerler, Paul A1 - Hermanns-Sachweh, Benita A1 - Schulz, Volkmar A1 - Kiessling, Fabian A1 - Lammers, Twan T1 - Size-isolation of superparamagnetic iron oxide nanoparticles improves MRI, MPI and hyperthermia performance JF - Journal of Nanobiotechnology N2 - Superparamagnetic iron oxide nanoparticles (SPION) are extensively used for magnetic resonance imaging (MRI) and magnetic particle imaging (MPI), as well as for magnetic fluid hyperthermia (MFH). We here describe a sequential centrifugation protocol to obtain SPION with well-defined sizes from a polydisperse SPION starting formulation, synthesized using the routinely employed co-precipitation technique. Transmission electron microscopy, dynamic light scattering and nanoparticle tracking analyses show that the SPION fractions obtained upon size-isolation are well-defined and almost monodisperse. MRI, MPI and MFH analyses demonstrate improved imaging and hyperthermia performance for size-isolated SPION as compared to the polydisperse starting mixture, as well as to commercial and clinically used iron oxide nanoparticle formulations, such as Resovist® and Sinerem®. The size-isolation protocol presented here may help to identify SPION with optimal properties for diagnostic, therapeutic and theranostic applications. Y1 - 2020 U6 - http://dx.doi.org/10.1186/s12951-020-0580-1 SN - 1477-3155 VL - 18 IS - Article number 22 SP - 1 EP - 13 PB - Nature Portfolio ER - TY - JOUR A1 - Hugenroth, Kristin A1 - Borchardt, Ralf A1 - Ritter, Philine A1 - Groß‑Hardt, Sascha A1 - Meyns, Bart A1 - Verbelen, Tom A1 - Steinseifer, Ulrich A1 - Kaufmann, Tim A. S. A1 - Engelmann, Ulrich M. T1 - Optimizing cerebral perfusion and hemodynamics during cardiopulmonary bypass through cannula design combining in silico, in vitro and in vivo input JF - Scientific Reports N2 - Cardiopulmonary bypass (CPB) is a standard technique for cardiac surgery, but comes with the risk of severe neurological complications (e.g. stroke) caused by embolisms and/or reduced cerebral perfusion. We report on an aortic cannula prototype design (optiCAN) with helical outflow and jet-splitting dispersion tip that could reduce the risk of embolic events and restores cerebral perfusion to 97.5% of physiological flow during CPB in vivo, whereas a commercial curved-tip cannula yields 74.6%. In further in vitro comparison, pressure loss and hemolysis parameters of optiCAN remain unaffected. Results are reproducibly confirmed in silico for an exemplary human aortic anatomy via computational fluid dynamics (CFD) simulations. Based on CFD simulations, we firstly show that optiCAN design improves aortic root washout, which reduces the risk of thromboembolism. Secondly, we identify regions of the aortic intima with increased risk of plaque release by correlating areas of enhanced plaque growth and high wall shear stresses (WSS). From this we propose another easy-to-manufacture cannula design (opti2CAN) that decreases areas burdened by high WSS, while preserving physiological cerebral flow and favorable hemodynamics. With this novel cannula design, we propose a cannulation option to reduce neurological complications and the prevalence of stroke in high-risk patients after CPB. Y1 - 2021 U6 - http://dx.doi.org/10.1038/s41598-021-96397-2 SN - 2045-2322 VL - 11 IS - Art. No. 16800 SP - 1 EP - 12 PB - Springer CY - Berlin ER - TY - JOUR A1 - Engelmann, Ulrich M. A1 - Simsek, Beril A1 - Shalaby, Ahmed A1 - Krause, Hans-Joachim T1 - Key contributors to signal generation in frequency mixing magnetic detection (FMMD): an in silico study JF - Sensors N2 - Frequency mixing magnetic detection (FMMD) is a sensitive and selective technique to detect magnetic nanoparticles (MNPs) serving as probes for binding biological targets. Its principle relies on the nonlinear magnetic relaxation dynamics of a particle ensemble interacting with a dual frequency external magnetic field. In order to increase its sensitivity, lower its limit of detection and overall improve its applicability in biosensing, matching combinations of external field parameters and internal particle properties are being sought to advance FMMD. In this study, we systematically probe the aforementioned interaction with coupled Néel–Brownian dynamic relaxation simulations to examine how key MNP properties as well as applied field parameters affect the frequency mixing signal generation. It is found that the core size of MNPs dominates their nonlinear magnetic response, with the strongest contributions from the largest particles. The drive field amplitude dominates the shape of the field-dependent response, whereas effective anisotropy and hydrodynamic size of the particles only weakly influence the signal generation in FMMD. For tailoring the MNP properties and parameters of the setup towards optimal FMMD signal generation, our findings suggest choosing large particles of core sizes dc > 25 nm nm with narrow size distributions (σ < 0.1) to minimize the required drive field amplitude. This allows potential improvements of FMMD as a stand-alone application, as well as advances in magnetic particle imaging, hyperthermia and magnetic immunoassays. KW - key performance indicators KW - magnetic biosensing KW - coupled Néel–Brownian relaxation dynamics KW - frequency mixing magnetic detection KW - magnetic relaxation KW - micromagnetic simulation KW - magnetic nanoparticles Y1 - 2024 U6 - http://dx.doi.org/10.3390/s24061945 SN - 1424-8220 N1 - This article belongs to the Special Issue "Advances in Magnetic Sensors and Their Applications" VL - 24 IS - 6 PB - MDPI CY - Basel ER - TY - JOUR A1 - Grundlach, Michael A1 - Baumann, Martin A1 - Engelmann, Ulrich M. ED - Dössel, Olaf T1 - How Multimodal Examinations Can Increase Sustainable Student Gain by Aligning Teaching and Assessment JF - Current Directions in Biomedical Engineering N2 - Modern industry and multi-discipline projects require highly trained individuals with resilient science and engineering back-grounds. Graduates must be able to agilely apply excellent theoretical knowledge in their subject matter as well as essential practical “hands-on” knowledge of diverse working processes to solve complex problems. To meet these demands, university education follows the concept of Constructive Alignment and thus increasingly adopts the teaching of necessary practical skills to the actual industry requirements and assessment routines. However, a systematic approach to coherently align these three central teaching demands is strangely absent from current university curricula. We demonstrate the feasibility of implementing practical assessments in a regular theory-based examination, thus defining the term “blended assessment”. We assessed a course for natural science and engineering students pursuing a career in biomedical engineering, and evaluated the benefit of blended assessment exams for students and lecturers. Our controlled study assessed the physiological background of electrocardiograms (ECGs), the practical measurement of ECG curves, and their interpretation of basic pathologic alterations. To study on long time effects, students have been assessed on the topic twice with a time lag of 6 months. Our findings suggest a significant improvement in student gain with respect to practical skills and theoretical knowledge. The results of the reassessments support these outcomes. From the lecturers ́ point of view, blended assessment complements practical training courses while keeping organizational effort manageable. We consider blended assessment a viable tool for providing an improved student gain, industry-ready education format that should be evaluated and established further to prepare university graduates optimally for their future careers. KW - constructive alignment KW - examination KW - long-term retention KW - multimodal KW - practical learning Y1 - 2021 SN - 2364-5504 U6 - http://dx.doi.org/10.1515/cdbme-2021-2019 VL - 7 IS - 7/2 SP - 73 EP - 76 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Engelmann, Ulrich M. A1 - Shalaby, Ahmed A1 - Shasha, Carolyn A1 - Krishnan, Kannan M. A1 - Krause, Hans-Joachim T1 - Comparative modeling of frequency mixing measurements of magnetic nanoparticles using micromagnetic simulations and Langevin theory JF - Nanomaterials N2 - Dual frequency magnetic excitation of magnetic nanoparticles (MNP) enables enhanced biosensing applications. This was studied from an experimental and theoretical perspective: nonlinear sum-frequency components of MNP exposed to dual-frequency magnetic excitation were measured as a function of static magnetic offset field. The Langevin model in thermodynamic equilibrium was fitted to the experimental data to derive parameters of the lognormal core size distribution. These parameters were subsequently used as inputs for micromagnetic Monte-Carlo (MC)-simulations. From the hysteresis loops obtained from MC-simulations, sum-frequency components were numerically demodulated and compared with both experiment and Langevin model predictions. From the latter, we derived that approximately 90% of the frequency mixing magnetic response signal is generated by the largest 10% of MNP. We therefore suggest that small particles do not contribute to the frequency mixing signal, which is supported by MC-simulation results. Both theoretical approaches describe the experimental signal shapes well, but with notable differences between experiment and micromagnetic simulations. These deviations could result from Brownian relaxations which are, albeit experimentally inhibited, included in MC-simulation, or (yet unconsidered) cluster-effects of MNP, or inaccurately derived input for MC-simulations, because the largest particles dominate the experimental signal but concurrently do not fulfill the precondition of thermodynamic equilibrium required by Langevin theory. KW - Magnetic nanoparticles KW - Frequency mixing magnetic detection KW - Langevin theory KW - Micromagnetic simulation KW - Nonequilibrium dynamics Y1 - 2021 SN - 2079-4991 U6 - http://dx.doi.org/10.3390/nano11051257 N1 - This article belongs to the Special Issue Applications and Properties of Magnetic Nanoparticles VL - 11 IS - 5 SP - 1 EP - 16 PB - MDPI CY - Basel 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 - http://dx.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 - TY - JOUR A1 - Engelmann, Ulrich M. A1 - Buhl, Eva Miriam A1 - Baumann, Martin A1 - Schmitz-Rode, Thomas A1 - Slabu, Ioana T1 - Agglomeration of magnetic nanoparticles and its effects on magnetic hyperthermia JF - Current Directions in Biomedical Engineering Y1 - 2017 U6 - http://dx.doi.org/10.1515/cdbme-2017-0096 SN - 2364-5504 VL - 3 IS - 2 SP - 457 EP - 460 PB - De Gruyter CY - Berlin ER -