University of Siegen
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Publication Access status: Open Access , Development and Investigation of Polymer Brush-Based Prodrugs and Micropatterned Lipid Bilayer Membranes(2026-09-08)Verbesserte Implantatbeschichtungen werden dringend benötigt, um die Besiedlung durch pathogene Bakterien zu verhindern und damit die Bildung infektionsverursachender Biofilme zu unterbinden. Gleichzeitig sollte die Adhäsion von Wirtszellen gefördert werden, um eine erfolgreiche Integration des Implantats in das umliegende Gewebe zu ermöglichen. Materialien, die diese konkurrierende Besiedlung der Implantatoberfläche – bekannt als „race for the surface“ – zugunsten der Gewebeintegration steuern, müssen dabei hohe biomedizinische Anforderungen erfüllen, darunter Biokompatibilität, Langzeitstabilität und antibakterielle Wirksamkeit. Ziel dieser Arbeit ist es, das Verständnis von Polymerbürsten als biomedizinische Beschichtungen zu vertiefen, indem beide Aspekte des „race for the surface“ systematisch untersucht werden. Im ersten Teil wird die Kombination von Polymerbürsten mit Polymer-Prodrugs betrachtet, wodurch eine neue Materialklasse entsteht, die als „Polymerbürsten-Prodrugs“ bezeichnet wird. Hierfür wurden zwei monomere Prodrugs auf Basis der Antibiotika Chloramphenicol und Sulfanilamid synthetisiert. Diese enthalten entweder eine Ester- oder eine Iminbindung als hydrolysierbare Verknüpfung und wurden anschließend zur Herstellung entsprechender Polymerbürsten verwendet. Die resultierenden Materialien wurden umfassend charakterisiert und hinsichtlich ihrer Fähigkeit untersucht, unter physiologischen Bedingungen durch hydrolytische Spaltung der Bindungen das jeweilige Antibiotikum freizusetzen. Eine verlängerte Wirkstofffreisetzung konnte ausschließlich für das hydrolytisch labile Imin-System beobachtet werden. Dabei wurden Wirkstoffkonzentrationen erreicht, die ausreichten, um drei planktonische Stämme von Staphylococcus aureus zu inaktivieren. Der zweite Teil der Arbeit legt die Grundlage für neuartige Zellkulturplattformen auf Basis hybrider Systeme, die aus mit Polymerbürsten modifizierten Lipidmembranen bestehen. Durch die Übertragung der oberflächeninitiierten Bürstensynthese mittels reversibler Additions-Fragmentierungs-Kettenübertragungspolymerisation (RAFT) auf einen neu entwickelten UV-induzierten Ansatz konnten Polymerbürsten für die Untersuchung der Zelladhäsion auf diesen Oberflächen hergestellt werden. Es zeigte sich, dass sich die Antifouling-Eigenschaften der modifizierten Membranen gezielt über die Länge der Ethylenglykol-Seitenketten einstellen lassen, wodurch Zelladhäsion entweder ermöglicht oder verhindert werden kann. Darüber hinaus eröffnet die Kettenverlängerung der Polymerbürsten mit einem zweiten Block aus funktionalisierbarem Glycidylmethacrylat die Möglichkeit, spezifische biochemische Motive einzuführen und so zelluläre Reaktionen gezielt zu untersuchen. Insgesamt bietet die entwickelte Plattform neue Möglichkeiten, das Zellverhalten an Polymerbürsten-Grenzflächen detailliert zu analysieren.Source Type:Doctoral Thesis14 13 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Open Access , Entwicklung, Charakterisierung und Prüfung von neuartigen Polystyrol-Rezepturen mit reduziertem Brandverhalten(2025-11-28)Polystyrene and styrene copolymers belong to the group of easily flammable standard plastics. [1] Currently, a polybrominated SBS copolymer is used as a flame retardant for flame-retardant styrene polymers in applications within the construction and building sector. [2] Brominated compounds exhibit high persistence in the environment, which means they degrade slowly and can remain in ecosystems for long periods. Another risk arises under thermal stress, as these compounds release gaseous hydrogen bromide (HBr), which is highly reactive and strongly corrosive to metals. Inhalation of HBr can cause severe burns to the respiratory tract. Due to these material properties, there is currently significant interest in developing alternative flame-retardant systems with improved risk profiles. In this context, halogen-free flame retardant combinations could potentially be attractive candidates. The aim of this study was therefore to develop, characterize, and test novel halogen-free phosphorus- and sulfur-containing flame-retardant formulations (P-S flame retardant systems) for foamed polystyrene. Additionally, the developed formulations were to be comparatively evaluated with regard to their flame-retardant efficiency. Various methods were used in this process, including a newly developed screening test for polystyrene foams, the standardized fire test DIN 4102 (B2) [3] for applications in construction and building, as well as the quantitative Limiting Oxygen Index (LOI). Testing the fire behavior of various phosphorus-organic flame retardants in polystyrene foams according to DIN 4102 (B2) revealed that the variation in the number of oxygen atoms directly bonded to the phosphorus atom in the flame retardant had no measurable impact on its efficiency—provided the co-flame retardant was a di- or oligosulfide. Rather, the decisive factor for effective fire protection in polystyrene was the phosphorus content (as a percentage) in the flame retardant. Further investigations using thermogravimetric analysis (TGA), gel permeation chromatography (GPC), scanning electron microscopy combined with energy-dispersive X-ray spectroscopy (SEM-EDX), and thermogravimetric analysis combined with mass spectrometry (TGA-MS) provided insights into the mechanism of action of the P-S flame retardant system in both the solid and gas phases. TGA investigations combined with GPC showed a significant influence of poly(tert-butylphenol) disulfide (FR-S1) on the thermal stability of polystyrene. In TGA experiments, the presence of the sulfur-containing co-flame retardant FR-S1 led to a significantly accelerated degradation of the polystyrene molecular weight under heat input compared to both reference polystyrene alone and polystyrene in combination with FR P1. Fire tests according to DIN 4102 (B2) showed increased burning drips in foams containing FR-S1, which also indicates a reduction in polymer viscosity due to molecular weight degradation. SEM-EDX investigations revealed an accumulation of phosphorus and oxygen on the surface of the burned polystyrene foam bodies. Gas phase analysis using TGA-MS detected sulfur indicators such as hydrogen sulfide and dihydrogen sulfide as potential thermal degradation products. This suggests at least partial gas-phase activity of the co-flame retardant FR-S1. The cooperative effect of the phosphorus- and sulfur-containing flame retardants was then specifically used to synthesize tailor-made flame retardants from elemental sulfur and various organic comonomers. Initially synthesized highly sulfur-rich flame retardants did not show sufficient flame-retardant efficiency in polystyrene on their own. As a result, styrene copolymers were subsequently synthesized that covalently incorporated both sulfur and phosphorus functionalities into the polymer. Foam bodies made from these terpolymers (CP3–CP7) exhibited self-extinguishing behavior in initial fire tests according to DIN 4102 (B2) and passed the test. However, this positive characteristic was compromised by undesirable burning drips.Source Type:Doctoral Thesis3 6 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Open Access , Spectroscopic investigations of light-emitting thin-film materials with intrinsic or induced supramolecular chirality(2025-12-05)In this cumulative doctoral thesis, polymer-based film blends with large circular dichroism (CD) and large circularly polarized luminescence (CPL) are investigated using advanced steady-state and time-resolved optical spectroscopy and microscopy methods to understand their structure and dynamics upon photoexcitation. These systems include polymer thin films consisting of intrinsically chiral polyfluorene derivatives, films with induced circular dichroism consisting of achiral polyfluorene derivatives and helicene-like chiral inducers as well as an organic host material which could be used together with these chiral polymer emitters. First, a comprehensive picture of the photoinduced dynamics of the chiral helicene-like molecule (+)-/(−)-2,2’-dimethoxy-5,5’,6,6’-tetrahydro-1,1’-bidibenzo-[c,h]acridine and its methylene-bridged analogue (+)-/(−)-bis-5,5’,6,6’-tetrahydro-dibenzo[c,h]acridino[1,1’,2,2’-d,f]-[1,3]dioxepine is obtained. After photoexcitation, the depopulation of the S1 state is fast (< 50 ps) for both systems. The quantum yield for internal conversion (IC) is about 80%, resulting in the formation of hot ground state molecules (S0∗). Triplet formation via intersystem crossing (ISC) is responsible for the remaining 20%. The bridged system exhibits a reduced Stokes shift and a slightly slower S1 decay. This effect is likely due to its more rigid structure. A characteristic excited-state absorption band at 575 nm is assigned to the T1 state which decays on a time scale of more than 500 ps. Very efficient chiral induction by these two additives is found in their blends with achiral poly-[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-(benzo-[2,1,3]thiadiazol-4,8-diyl)] (F8BT), reaching CD signals with peak signals of up to 9000 mdeg. The less rigid structure of the unbridged derivative might be responsible for the significantly better chiral induction, possibly because of better adaptation to the F8BT scaffold during the formation of the supramolecular structure. Using a newly developed setup for the detection of transient circularly polarized luminescence (TrCPL) with a time resolution of 28 ps, a static mechanism for the generation of the CPL is confirmed. When studying enantiomer mixtures of a given chiral additive as inducing agent for F8BT, it is found that the ”sergeant and soldiers” concept and “majority rules” do not apply, as demonstrated by CD and CPL microscopy images of the different thin film blends. In addition, cholesteric thin films of the intrinsically chiral polymer {9,9-bis[(3S)-3,7-dimethyloctyl]fluorenyl-2,7-diyl}-alt-benzo[2,1,3]thiadiazol-4,8-diyl} (c PFBT) are produced which also reach large CD values of up to 10000 mdeg. These are characterized in the UV−Vis range upon photoexcitation using a newly developed setup for broadband transient circular dichroism (TrCD) spectroscopy. The ultrafast chiral response of the c-PFBT copolymer thin film was of supramolecular origin. TrCD signals only monitor the recovery of the ground state S0 without contributions from excited-state CD signals, which makes their interpretation easier than for the transient absorption (TA) response. The relaxation processes are assigned to mainly diffusive S1−S1 singlet–singlet annihilation (SSA) and a minor channel for Förster resonance energy transfer (FRET). In addition, charge pair formation is observed with a total quantum yield of 15%. The fluorescing polymer films may be applied as materials for OLEDs which emit circularly polarized light, so-called CP-OLEDs. Such devices require host materials for the transfer of electrical charges to the emitter. Understanding the photophysical processes in such a host material, namely 1,3-bis(N-carbazolyl)benzene (mCP), is therefore important. Thus, mCP is investigated in tetrahydrofuran (THF) solution and in poly(methyl methacrylate) (PMMA) film blends at different dopant concentrations. Time-correlated single photon counting (TCSPC) provides a monoexponential decay with lifetimes in the range of 6–7 ns for “isolated” mCP in solution and in the mCP:PMMA thin film with a mass ratio of 2:98. With increasing dopant concentration in the mCP:PMMA blends and also for the neat mCP thin film, the mCP emission is strongly quenched. Neat mCP films and films with high mCP content show three different bands, which are assigned to monomer, aggregate and excimer emission. At higher mCP concentration, an S1−S0 homo-FRET mechanism becomes operative. This way, the excitation energy is transferred via other mCP molecules to an energetically lower trap site, which can be either an mCP aggregate or excimer. For the neat mCP thin film, the average relaxation lifetimes for the monomer, aggregate and excimer bands are 0.92, 3.84 and 7.22 ns respectively. Complementary transient absorption measurements show that at high initial exciton number densities, triplet formation, which has a quantum yield of 20% in THF, is outperformed by SSA.Source Type:Doctoral Thesis4 7 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Open Access , Entwicklung und Untersuchung pyrotechnischer Verzögerungspellets unter Berücksichtigung der Green Chemistry(2026-05-05)Due to the toxic and carcinogenic properties of substances used in pyrotechnic delay compositions, the aim of this work was the production and investigation of alternative pyrotechnic delay mixtures. The development process was accom-panied by the “rules of green chemistry”. The oxidizing agents CaO2, Li2O2, SrO2, KClO4, LiClO4 and SiO2 and the reducing agents Al, CaSi2, Fe, Mg, Mn, Si, pSi, Ti and Zr were used as alternative substances. The delay compositions were produced as pellets and then loaded into tubes for further investigation. In addition, the use of solvents was avoided and dry binders (HPMC, MgSt, PEG1, PEG2 and PVP) were used as adhesion promoters between the parti-cles. Furthermore, selected mixtures were subjected to an ageing simulation over 11 days at 80 °C with ambient air humidity. The delay pellets achieved combustion rates ranging from 1,1 mm s-1 to 91,4 mm s-1. The combustion rate depended on the particle size of the oxidizing agents, the pellet diameter, the binder type and content, the fuel content, the tube material and if the pellets were post pressed into the delay tubes. It was also found that the addition of binders lowers the ignition temperature of mixtures with peroxides. No reduction in the ignition temperature was determined for the perchlorates. In addition, the mechanical stability of the pellets depended on the binder content, binder type and the actual components (oxidizing agent and reducing agent). Furthermore, Raman spectroscopic investigations were carried out to examine the reaction products for residual oxidants, to characterize the two silicon powders and to investigate aging processes. No residues of oxidizing agents could be detected in the reaction products, the two silicon powders were classified as crystalline and non-porous (also using BET and grain size analysis) and indications of ag-ing processes could be detected but not fully assigned. Using DSC analyses, the earlier ignition of the peroxide mixtures with the binders could be attributed to the combustion/decomposition of the binders. Most of the mixtures were classified as impact- and friction-sensitive, but unwanted ignition with the bind-ers HPMC, PEG1, PEG2 and PVP occurred during pellet production. Even if the mixtures are classified as “gasless”, a pressure increase of up to 13 bar can be expected during the combustion of SrO2/Al/MgSt pellets. However, this de-pends on the binder content. Finally, the investigation of the aged pellets SrO2/Al/MgSt and CaO2/pSi/MgSt led to the conclusion that both mixtures are stable in the long term and can therefore be regarded as possible substitution candidates for use in delay elements.Source Type:Doctoral Thesis2 5 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Open Access , Design, Synthesis, and Biological Evaluation of a Modular Polymer-based Platform for Antimicrobial Photodynamic Therapy(2025-12-01)The emergence of antibiotic-resistant bacteria, particularly in respiratory infections, presents an urgent need for alternative therapeutic approaches. This thesis describes the development of polymer-based antimicrobial photodynamic therapy systems designed specifically for treating Pseudomonas aeruginosa respiratory infections. Two complementary synthetic strategies were employed to create functional polymeric materials incorporating photosensitizers and other active ingredients (biofilm-disrupting agents). The first approach involved post-polymerization modification of active ester polymers, enabling controlled incorporation of both ruthenium complexes and phenalenone derivatives as photosensitizers. The second strategy utilized direct free radical polymerization of photosensitizer-containing monomers alongside functional comonomers. Both approaches successfully yielded water-soluble polymers intended for nebulization-based delivery. Compared to free photosensitizers, these polymer-based systems offer advantages including enhanced local drug concentration through multivalent presentation and improved solubility, addressing key limitations of conventional photosensitizers. Comprehensive biological evaluation highlighted various properties of the polymers designed with identification of structure-activity relationships. Some of these materials can effectively inactivate and/or eliminate both planktonic bacteria and biofilms upon visible light illumination, with activity maintained in physiologically relevant conditions. Notably, certain polymers also showed enhanced efficacy in high-salt environments representative for respiratory infections such as cystic fibrosis. The materials exhibited excellent biocompatibility with human bronchial epithelial cells and maintained their structural integrity and antimicrobial activity through nebulization, supporting their potential for therapeutic applications. This work establishes a promising platform for treating respiratory infections through controlled, light-activated antimicrobial activity, offering advantages over conventional antibiotic treatments while maintaining compatibility with clinical delivery methods.Source Type:Doctoral Thesis2 6 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Open Access , Morphological design and structure evaluation of poly(divinylbenzene) -based particles(2025-07-25)This thesis focuses on advancing the synthesis of polydivinylbenzene (PDVB) microparticles via precipitation polymerization and swelling techniques, aiming to tailor their morphological features for enhanced applications, particularly in size exclusion chromatography (SEC). The first part focuses on the synthesis of core-shell particles via precipitation polymerization, consisting of a non-porous core and a porous shell, intended as column material for SEC. Monodisperse, non-porous core particles were reliably produced using cost-efficient standard laboratory equipment in place of specialized devices. Next to shell growth, it could be shown that low-molecular-weight porogens common for suspension polymerization do not yield pores suitable for SEC in precipitation polymerization under the tested conditions. This could be explained by the lack of confined space during particle formation in precipitation polymerization. The synthesized particles proved effective for hydrodynamic chromatography (HDC) and can be used as size standards for analytical applications like particle size analyzers. The second part presents an approach to PDVB particle synthesis by combining precipitation polymerization with a template-swelling technique. Three distinct strategies involving different polystyrene templates were explored, resulting in particles with intricate morphologies, including surface grooves and hollow cores. SEM analysis revealed the impact of template architecture on the particle morphology. The resulting particles with adjustable void sizes hold promise for various applications, like catalysis and delivery systems. This work provides a proof of concept, and future research may further extend control over the nanoarchitecture and explore other templating methods. The third part explores an alternative route to create a porous shell on a highly crosslinked PDVB core particle, utilizing the template swelling method with macromolecular porogen aiming at pore sizes larger than 10 nm. The two-step swelling method sought to integrate the PS porogen into the precursor particle shells and subsequently remove it to leave behind the desired porous structure. However, despite successful incorporation of the PS template during the initial swelling stage, the subsequent removal of the porogen did not lead to the expected porous structure. Excessive, unintended crosslinking, possibly due to chain transfer reactions or residual double bonds in the PDVB system, appears to have hindered the removal of the PS template. While the procedure still seems promising, further research needs to be done to lower the crosslinking degree of the precursor particle shell. The findings contribute to the ongoing efforts to enhance the versatility of PDVB particles for diverse applications, like for example for HDC chromatography or in the biomedical field, emphasizing the importance of combining and tailoring synthesis methods to achieve specific morphological features. Parts of this thesis were performed in collaboration with PSS GmbH, Mainz and LiNaCon Dr. Ingo Lieberwirth, Mainz.Source Type:Doctoral Thesis1 12 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Open Access , Development of Novel pH-Sensitive Dyes for Early Stage Wound Infection Detection and Monitoring(2025)Early-stage wound infections are challenging to detect; however, a timely diagnosis significantly improves healing outcomes and reduces the risk of scarring or systemic complications. Healthy skin is mildly acidic (average pH ~4.7), while chronic or infected wounds remain alkaline (7.15–8.9) and gradually return to acidic during healing. Real-time monitoring of wound pH has emerged as a valuable tool for tracking the progression of healing, providing an early warning of potential bacterial infection, and reducing unnecessary antibiotic therapy. pH-sensitive dyes that undergo visible color changes within carrier materials present a simpler and cost-effective approach for wound pH monitoring. Current pH indicators, however, suffer from low photostability and dye leaching, limiting their practical use. This work presents the design, synthesis, and functional evaluation of carborhodol dyes, developed as photostable alternatives to conventional pH indicators, optimized for the physiological pH range. Nine novel carborhodols were synthesized from their respective carbopyronine precursors through hydrolytic deamination, with structural modifications designed to enhance photostability, solubility, and bioconjugation potential. The dyes exhibit distinct pH-dependent optical properties, with pKa values in the physiologically relevant range (5–7). Deprotonation leads to increases in absorption, quantum yield, and fluorescence lifetime, enabling sensitive detection of pH changes by both colorimetric and fluorogenic modes. Compared to the standard indicator fluorescein and the common biological label Cy5, carborhodols display superior photostability, addressing a key limitation of existing probes. Additionally, the basic forms exhibit pronounced positive solvatochromism, indicating their utility as polarity-sensitive probes. To demonstrate practical applications, the dyes were incorporated into polymer-based systems. Encapsulation in PEG-b-PLA vesicles resulted in an increase in fluorescence intensity with rising pH levels, whereas covalent grafting to chitosan films yielded hydrogel dressings capable of reversible, real-time pH monitoring within the wound-relevant range. These hybrid materials combine high stability and biocompatibility, with pH-dependent color changes visible to the naked eye under ambient light, and fluorescence turn-on readily detectable by the eye under UV illumination, showing the successful translation of molecular dye properties into functional biomedical platforms, and highlighting their promise for smart wound dressings and related diagnostic devices.Source Type:Doctoral Thesis3 10 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Open Access , Rapid Detection and Photodynamic Eradication of Bacteria: A Dual approach to Combat Multidrug-Resistant Bacterial Infections(2025)Antimicrobial resistance (AMR) represents a growing global health threat, driven in part by the overuse of broad-spectrum antibiotics and the limited effectiveness of conventional diagnostics and therapeutic approaches. This Thesis addresses a dual strategy to address these challenges: (i) rapid, enzyme-responsive diagnostics to enable early detection and mitigate antibiotic misuse, and (ii) targeted antimicrobial photodynamic therapy (aPDT) to enhance treatment efficacy. For bacterial detection, the strategy of autonomously reporting chitosan-based sensors was further developed, focusing on E. coli detection using β-glucuronidase as a biomarker. A paper-based carrier for chitosan hydrogels was integrated with smartphone-assisted RGB analysis, enabling visible, low-cost, and user-friendly point-of-care diagnostics. The system relies on color intensity changes of a released reporter dye, modulated by enzyme concentrations corresponding to bacterial load. To improve β-glucuronidase sensitivity and facilitate scalable fabrication, enzyme-responsive chitosan-based electrospun nanofibers were investigated. At a fixed enzyme concentration, these nanofibers exhibited a 3.4-fold increase in the initial enzymatic hydrolysis rate compared to the hydrogel system and achieved a limit of detection of 4.7 nM after 60 min, in contrast to 16 nM for the hydrogel system. The enhanced sensitivity of the nanofiber platform was further validated through in vitro experiments using pathogenic E. coli, demonstrating its potential utility in real biological samples. For bacterial eradication, a Ru(II)-based photosensitizer (Ru(phen)₃) encapsulated in polymeric nanocarriers was evaluated against P. aeruginosa in its planktonic form, in biofilms and in artificial sputum medium (ASM), which simulates the Cystic Fibrosis (CF) lung environment. Ru(phen)3-loaded vesicles exhibited a greater photodynamic inactivation of planktonic P. aeruginosa compared to Ru(phen)3-loaded micelles, attributed to the higher loading capacity of Ru(phen)3. The biological complexity of ASM significantly influenced aPDT efficacy, with Ru(phen)₃-loaded vesicles showing reduced activity compared to the neat Ru(phen)₃ at similar overall Ru(phen)3 concentrations. In biofilm eradication assay, a 4.8 log reduction was achieved with neat Ru(phen)3 while Ru(phen)3-loaded vesicles resulted in 2 log reduction after 120 min of irradiation. Notably, prolonged pre-incubation times appeared to facilitate deeper photosensitizer penetration into biofilms, thereby improving aPDT outcomes. This approach was further applied to multidrug-resistant (MDR) isolates of P. aeruginosa and S. aureus from CF patients, as well as pathogenic E. coli. The results underscore the therapeutic potential and versatility of Ru(phen)3-loaded vesicles in treating MDR infections, particularly those associated with CF pathology. Overall, this Thesis contributes to the development of effective, enzyme-responsive diagnostic tools and optimized aPDT treatment strategies for combating bacterial infections to fight AMR.Source Type:Doctoral Thesis7 9 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Open Access , Surface-Assisted Flowing Atmospheric-Pressure Afterglow Mass Spectrometry (SA-FAPA-MS)(2025)Analytical chemistry plays a crucial role in ensuring the safety, quality, and authenticity of products and processes, e.g. in the food and beverage industry, pharmaceutical production, but also in forensics, diagnostics, and environmental sciences. One of its most powerful tools is mass spectrometry (MS) which allows scientists to selectively detect substances even at lowest amounts. Conventional MS techniques usually require extensive and complex sample preparation and additional separation procedures which make them time-consuming, resource-intensive and therefore costly. A novel approach known as ambient desorption/ionization MS (ADI-MS), offers a faster and more sustainable alternative by allowing direct analysis of samples in their original state. This dissertation presents the development, optimization, and application of a specific ADI-MS technique termed surface-assisted flowing atmospheric-pressure afterglow MS (SA FAPA MS). This method is based on a plasma-based ionization source in combination with functionalized sample carrier surfaces and enables rapid, preparation-free detection of small molecules in matrix-containing samples, e.g. in beverages, pharmaceutical products or even body fluids. One core goal was to improve the quantitative capabilities of SA FAPA MS as ADI MS in general faces challenges regarding signal stability and overall reproducibility. A key finding was that the choice of the sampling surface dramatically influences performance. Among the surfaces tested, cyano- and dimethyl-functionalized thin-layer chromatography (TLC) plates performed better than conventional supports such as glass or metal mesh. These surfaces enabled higher ion yields, better signal stability, and broader dynamic ranges, ultimately leading to detection limits down to the femtomole (fmol) range. The method was successfully applied to accurately quantify model substances in beverages and electronic cigarette liquids even when matrix effects were expected. Precision and accuracy were further improved by isotopically labeled standards. Further, the semi-quantitative detection of benzocaine in human saliva demonstrated the potential for biomonitoring and diagnostic applications. For the applications above, SA FAPA MS proves to be a fast, sensitive, and sustainable alternative to conventional MS methods. Minimal sample pre-treatment requirements, versatility, and high throughput make it very attractive for use in quality control, toxicology, diagnostics, and environmental monitoring where accurate results are required as quickly as possible.Source Type:Doctoral Thesis4 5 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Open Access , Investigation of 2D and 3D Polymeric Cell Culture Platforms to Study the Response of Cells to Bacterial Signalling Molecules(2025)The investigation of the response of the immune system, which is influenced by the communication between cells of the same as well as different species (interkingdom signalling), is a crucial part in biomedical research. Especially the sensing of signalling molecules that are produced by bacteria can induce a response of eukaryotic cells present in the immune system. For the studies of cellular response in vitro, the extracellular matrix (ECM), which surrounds the cells in their natural environment, needs to be simulated. The creation of an artificial three-dimensional (3D) environment is essential and affects the cell adhesion, proliferation as well as migration. Thereby, the cell detachment and separation can be induced. In this Thesis, different approaches to generate suitable cell culture platforms were explored and their suitability for future work in cell communication investigated. In particular, polymer brushes as well as lipid bilayers were examined as approaches to spatially and temporally control selective cell attachment and detachment. Furthermore, hydrogel-based scaffolds were prepared and investigated regarding their suitability to create viable environments for cell encapsulation. Thermoresponsive poly(di(ethylene glycol) methyl ether methacrylate) (PDEGMA) brushes were successfully used for selective separation of human umbilical vein endothelial cells (HUVEC) from a coculture with macrophages without the use of additional compounds, such as releasing agents or antibodies. The decrease of the temperature below the transition temperature of 35 °C for (5 ± 1) nm thin PDEGMA brushes, resulted in a change of the chain conformation and thus cause a desorption of cell adhesion proteins. HUVECs and macrophages attached and spread in a coculture on (5 ± 1) nm thin PDEGMA brushes at 37 °C. In contrast to macrophages HUVECs, which possess a lower adhesion strength, detached from the brushˈ surface after decreasing the temperature to 22 °C. HUVECs could be reseeded on a new surface with a yield of 71 % and a purity of almost 100 %. Square-shaped, patterned polymeric lipid bilayers that were modified with PDEGMA and poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) brushes with brush thicknesses of 26 nm and 20 nm, respectively, were investigated in terms of selective cell attachment. Mouse fibroblasts (NIH 3T3) cells were able to attach and spread on polymeric lipid bilayer. In contrast, polymer brushes possess cell repulsive properties, so that the cells are only able to attach on bare glass squares. The use of patterned polymeric lipid bilayers, which are modified with polymer brushes, allows a selective cell attachment. The adhesion and spreading of cells inside different hydrogels with various geometries were investigated. The encapsulation of NIH 3T3 cells and pancreatic tumor cells (PaTu 8988t) inside chitosan microbeads cross-linked with glycerol phosphate disodium salt (CS + GP) as well as inside alginate — fibrin microbeads were not successful due to the too harsh conditions of the gelling bath and the lack of cell adhesion properties, respectively. However, a hydrogel consisting of alginate dialdehyde (ADA) with a degree of oxidation of 30 % and gelatine modified with carbohydrazide (GelCHD) in a ratio of 1 : 3 were shown to be useful, afford attachment, spreading, and proliferation of encapsulated cells. Finally, the response of encapsulated NIH 3T3 cells, in the above-mentioned hydrogel, to the signalling molecule N-(3-oxododecanoyl)-L-homoserine lactone (HSL) was examined. A pronounced decrease of the cellsˈ viability from 90 % to 71 % and an increase in the intracellular Ca2+ concentration was detected after treatment with HSL, confirming a response of the cells on the signal molecules. Overall, the results reported in this Thesis highlight the potential of polymer brushes, lipid bilayers as well as hydrogel scaffolds for the encapsulation of cells and the investigation of cellular communication processes.Source Type:Doctoral Thesis1 8
