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Altinel, Berk; Asghar, Ehtisham; Berlt, Philipp; Buddappagari, Sreehari; Bornkessel, Christian; Singh, Jasmeet; Hein, Matthias
Practical aspects of automotive measurements and virtual-drive testing. - In: Modern automotive antenna measurements, (2022), S. 221-246

Apte, Gurunath; Hirtz, Michael Manfred; Nguyen, Thi-Huong
FluidFM-based fabrication of nanopatterns: promising surfaces for platelet storage application. - In: ACS applied materials & interfaces, ISSN 1944-8252, Bd. 14 (2022), 21, S. 24133-24143

Platelets are cell fragments from megakaryocytes devoid of the cell nucleus. They are highly sensitive and easily activated by nonphysiological surfaces. Activated platelets have an intrinsic mechanism to release various proteins that participate in multiple pathways, initiating the platelet activation cascade. Surface-induced platelet activation is a challenge encountered during platelet storage, which eventually leads to aggregation of platelets and can thereby result in the degradation of the platelet concentrates. We have previously reported that surface-induced platelet activation can be minimized by either modifying their contact surfaces with polymers or introducing nanogroove patterns underneath the platelets. Here, we investigated the response of platelets to various nanotopographical surfaces printed using fluidic force microscopy (FluidFM). We found that the hemispherical array (grid) and hexagonal tile (hive) structures caused a reduction of surface stiffness, which leads to an inhibition of platelet adhesion. Our results reveal that nanopatterns enable the inhibition of platelet activation on surfaces, thus implying that development in nanotexturing of storage bags can extend the lifetime of platelet concentrates.



https://doi.org/10.1021/acsami.2c03459
Chen, Li-Yu; Khan, Nida; Lindenbauer, Annerose; Nguyen, Thi-Huong
When will Fondaparinux induce thrombocytopenia?. - In: Bioconjugate chemistry, ISSN 1520-4812, Bd. 33 (2022), 8, S. 1574-1583

The pentasaccharide Fondaparinux, a synthetic selective factor Xa inhibitor, is one of the safest anticoagulants in the heparin family that is recommended as an alternative drug for patients with hypersensitivity to other drugs such as heparin-induced thrombocytopenia (HIT). However, some observations of Fondaparinux-induced thrombocytopenia (FIT) have been reported while others claimed that FIT does not occur in patients with fondaparinux therapy, indicating that the mechanism of FIT remains controversial. Here, we utilized different methodologies including dynamic light scattering, immunosorbent and platelet aggregation assays, confocal laser scanning microscopy, and flow cytometry to gain insights into FIT. We found that at a certain concentration, Fondaparinux formed sufficient large and stable complexes with PF4 that facilitated binding of the HIT-like monoclonal KKO antibody and enhanced platelet aggregation and activation. We proposed a model to describe the role of Fondaparinux concentration in the formation of complexes with platelet factor 4 and how it promotes the binding of KKO. Our results clarify controversial observations of FIT in patients as each contains a dissimilar PF4:Fondaparinux concentration ratio.



https://doi.org/10.1021/acs.bioconjchem.2c00316
Chen, Li-Yu; Schirmer, Uwe; Widder, Miriam; Gruel, Yves; Rollin, Jérôme; Zipfel, Peter F.; Nguyen, Thi-Huong
Breast cancer cell-based ELISA: a potential material for better detection of heparin-induced thrombocytopenia antibodies. - In: Journal of materials chemistry, ISSN 2050-7518, Bd. 10 (2022), 38, S. 7708-7716

Heparin-induced thrombocytopenia (HIT) is caused by newly formed platelet-activating antibodies against complexes formed between platelet factor 4 (PF4) and heparin (H). HIT can result in life-threatening complications; thus, early detection of HIT antibodies is crucial for the treatment of the disease. The enzyme-linked immune absorbance assay (ELISA) for the identification of HIT antibodies is widely used in many laboratories, but in general, this test provides only ∼50% accuracy while other methods show multiple limitations. Here, we developed a new cell-based ELISA to improve the detection of HIT antibodies. Instead of immobilizing PF4 or PF4/H complexes directly onto a plate as in the standard ELISA, we added the complexes on breast cancer cells, i.e., cell line MDA-MB-231, and applied the same protocol for antibody detection. Using confocal laser scanning microscopy and flow cytometry for the characterization of bound complexes, we identified two types of HIT-mimicked antibodies (KKO and 1E12), which were able to differentiate from the non-HIT antibody (RTO). PF4-treated MDA-MB-231 cells allowed binding of HIT-mimicked antibodies better than PF4/H complexes. With human sera, the cell-based ELISA allowed better differentiation of clinically relevant from non-clinically relevant HIT antibodies as compared with the standard ELISA. Our findings provide a potential approach that contributes to the development of better assays for the detection of HIT antibodies.



https://doi.org/10.1039/D2TB01228F
Schemberg, Jörg; El Abbassi, Abdelouahad; Lindenbauer, Annerose; Chen, Li-Yu; Grodrian, Andreas; Nakos, Xenia; Apte, Gurunath; Khan, Nida; Kraupner, Alexander; Nguyen, Thi-Huong; Gastrock, Gunter
Synthesis of biocompatible superparamagnetic iron oxide nanoparticles (SPION) under different microfluidic regimes. - In: ACS applied materials & interfaces, ISSN 1944-8252, Bd. 14 (2022), 42, S. 48011-48028

Superparamagnetic iron oxide nanoparticles (SPION) have a great potential in both diagnostic and therapeutic applications as they provide contrast in magnetic resonance imaging techniques and allow magnetic hyperthermia and drug delivery. Though various types of SPION are commercially available, efforts to improve the quality of SPION are highly in demand. Here, we describe a strategy for optimization of SPION synthesis under microfluidics using the coprecipitation approach. Synthesis parameters such as temperature, pH, iron salt concentration, and coating materials were investigated in continuous and segmented flows. Continuous flow allowed synthesizing particles of a smaller size and higher stability than segmented flow, while both conditions improved the quality of particles compared to batch synthesis. The most stable particles were obtained at a synthesis condition of 6.5 M NH4OH base, iron salt (Fe2+/Fe3+) concentration ratio of 4.3/8.6, carboxymethyl dextran coating of 20 mg/mL, and temperature of 70 ˚C. The synthesized SPION exhibited a good efficiency in labeling of human platelets and did not impair cells. Our study under flow conditions provides an optimal protocol for the synthesis of better and biocompatible SPION that contributes to the development of nanoparticles for medical applications.



https://doi.org/10.1021/acsami.2c13156
Berganza, Eider; Apte, Gurunath; Vasantham, Srivatsan K.; Nguyen, Thi-Huong; Hirtz, Michael Manfred
Integration of biofunctional molecules into 3D-printed polymeric micro-/nanostructures. - In: Polymers, ISSN 2073-4360, Bd. 14 (2022), 7, 1327, S. 1-12

Three-dimensional printing at the micro-/nanoscale represents a new challenge in research and development to achieve direct printing down to nanometre-sized objects. Here, FluidFM, a combination of microfluidics with atomic force microscopy, offers attractive options to fabricate hierarchical polymer structures at different scales. However, little is known about the effect of the substrate on the printed structures and the integration of (bio)functional groups into the polymer inks. In this study, we printed micro-/nanostructures on surfaces with different wetting properties, and integrated molecules with different functional groups (rhodamine as a fluorescent label and biotin as a binding tag for proteins) into the base polymer ink. The substrate wetting properties strongly affected the printing results, in that the lateral feature sizes increased with increasing substrate hydrophilicity. Overall, ink modification only caused minor changes in the stiffness of the printed structures. This shows the generality of the approach, as significant changes in the mechanical properties on chemical functionalization could be confounders in bioapplications. The retained functionality of the obtained structures after UV curing was demonstrated by selective binding of streptavidin to the printed structures. The ability to incorporate binding tags to achieve specific interactions between relevant proteins and the fabricated micro-/nanostructures, without compromising the mechanical properties, paves a way for numerous bio and sensing applications. Additional flexibility is obtained by tuning the substrate properties for feature size control, and the option to obtain functionalized printed structures without post-processing procedures will contribute to the development of 3D printing for biological applications, using FluidFM and similar dispensing techniques.



https://doi.org/10.3390/polym14071327
Szturo, Karolina; Haueisen, Jens; Piatek, Lukasz
MSLO - melanocytic skin lesion ontology. - In: Digital medicine, ISSN 2226-8561, Bd. 8 (2022), 1, 29, S. 1-9

Background and Purpose: Malignant melanoma is a high-grade skin cancer with high feasibility to metastasize to both regional and distant sites when detected late. Therefore, it is crucial to diagnose this type of cancer at an early stage to ensure effective treatment. The identification of melanocytic lesions is a difficult issue, even for experienced experts. The current development of information technology, particularly related to image analysis and machine learning, is an opportunity to support the work of specialists and detect malignant melanoma more effectively. The aim of this work is to present a melanocytic skin lesion ontology (MLSO) structure, which serves as a basis for a melanoma diagnosis system and includes the formalization of the experts' and literature knowledge. Subjects and Methods: MLSO describes the most commonly used melanoma assessing strategies: Argenziano's (also known as the 7-point checklist), Menzies', and Stolz's (based on the ABCD rule) strategies as well as Chaos and Clues. Results: In this work, a case study was conducted on the description of a dermatoscopic digital image of a melanocytic skin nevus. The nevus was evaluated according to all of the strategies included in the MLSO, and inferences were made based on these strategies. The analyzed lesion was classified as a benign nevus since no malignancy was indicated by any of the applied strategies. Conclusion: Initial results indicate the usefulness of MLSO in diagnosing skin cancer. A significant advantage of MLSO is that it provides results obtained using four strategies. Therefore, the results are more objective and the possible errors may be avoided. The MLSO structure is still developing and will be implemented into an automated skin cancer diagnosis system.



https://doi.org/10.4103/digm.digm_18_22
Schaaf, Peter; Zyabkin, Dmitry
Mössbauer spectroscopy. - In: Reference module in materials science and materials engineering, (2022), insges. 14 S.

The current chapter provides the reader with a general introduction of Mössbauer effect following by its unique utilization, which became known as Mössbauer spectroscopy. Mössbauer spectroscopy is based on the recoilless emission and following resonant absorption of gamma radiation by atomic nuclei and has been at the scientific forefront of physics, chemistry, biology, mineralogy for more than 60 years. Soon after the discovery of the Mössbauer effect, it became obvious that this effect can be used to study various properties of materials on a microscopic scale via hyperfine interactions with an unprecedented resolution. This was the beginning of a new analytical tool - Mössbauer spectroscopy. Today, it has developed into a standard analytical technique used in many laboratories and big research facilities. The current chapter provides the reader with a general introduction, explains the underlying hyperfine interactions and gives examples of the possible application of the method.



https://doi.org/10.1016/B978-0-323-90800-9.00137-2
Cao, Yu; Wu, Yanjie; Tang, Xin; Zhou, Qi; Stapf, Siegfried; Mattea, Carlos; Li, Wei
Long-term efficiency for reducing entanglements of nascent polyethylene by a polystyrene-modified Ziegler-Natta catalyst. - In: Journal of applied polymer science, ISSN 1097-4628, Bd. 139 (2022), 11, 51790, S. 1-10

The weakly entangled ultrahigh molecular weight polyethylene (UHMWPE) was synthesized by a Ziegler-Natta catalyst, where the titanium tetrachloride was anchored on the polystyrene (PS)-modified silica. The PS chains were successfully incorporated into silica hierarchical pores even with the size less than 10 nm through the in situ free-radical polymerization of styrene. The self-diffusion coefficient and crystallization of probing molecules inside the pores were investigated by the pulsed field gradient NMR and thermoporosimetry to address the swollen behavior of incorporated PS blocks. This PS blocks compartmentalized the polyethylene chains, where the less entangled UHMWPE was synthesized with an exceptional activity at 70˚C. The ubiquitous PS isolators effectively hindered the formation of chains overlaps during the polymerization, showing a long-term efficiency to reduce the entanglements of nascent UHMWPE even at 4 h of polymerization The toughness/stiffness/strength balance of weakly entangled UHMWPE was significantly improved.



https://doi.org/10.1002/app.51790
Römer, Florian; Kirchhof, Jan; Krieg, Fabian; Pérez, Eduardo
Compressed Sensing: from big data to relevant data. - In: Handbook of Nondestructive Evaluation 4.0, (2022), S. 329-352

Though the ever-increasing availability of digital data in the context of NDE 4.0 is mostly considered a blessing, it can turn to a curse quite rapidly: managing large amounts of data puts a burden on the sensor devices in terms of sampling and transmission, the networks, as well as the server infrastructure in terms of storing, maintaining, and accessing the data. Yet, NDE data can be highly redundant so the storage of massive amounts of data may indeed be wasteful. This is the main reason why focusing on relevant data as early as possible in the NDE process is highly advocated in the context of NDE 4.0. This chapter introduces Compressed Sensing as a potential approach to put this vision to practice. Compressed Sensing theory has shown that sampling signals with sampling rates that are significantly below the Shannon-Nyquist rate is possible without loss of information, provided that prior knowledge about the signals to be acquired is available. In fact, we may sample as low as the actual information rate if our prior knowledge is sufficiently accurate. In the NDE 4.0 context, prior knowledge can stem from the known inspection task and geometry but it can also include previous recordings of the same piece (such as in Structural Health Monitoring), information stored in the digital product memory along the products’ life cycle, or predictions generated through the products’ digital twins. In addition to data reduction, reconstruction algorithms developed in the Compressed Sensing community can be applied for enhanced processing of NDE data, providing added value in terms of accuracy or reliability. The chapter introduces Compressed Sensing basics and gives some concrete examples of its application in the NDE 4.0 context, in particular for ultrasound.