Monika Bach

Optical sensors with molecularly imprinted nanospheres: a promising approach for robust and label-free detection of small molecules

Molecularly imprinted nanospheres obtained by miniemulsion polymerization have been applied as the sensitive layer for label-free direct optical sensing of small molecules. Using these particles as the sensitive layer allowed for improving response times in comparison to sensors using MIP layers. As a model compound, well-characterized nanospheres imprinted against l-Boc-phenylalanine anilide (l-BFA) were chosen. For immobilization, a simple concept based on electrostatic adsorption was used, showing its applicability to different types of surfaces, leading to a good surface coverage. The sensor showed short response times, good selectivity, and high reversibility with a limit of detection down to 60xa0μM and a limit of quantitation of 94xa0μM. Furthermore, reproducibility, selectivity, and long-term stability of the sensitive layers were tested. The best results were achieved with an adsorption on aminopropylsilane layers, showing a chip-to-chip reproducibility of 22%. Furthermore, the sensors showed no loss in signal after a storage time of 1xa0year.

Desmosine-Inspired Cross-Linkers for Hyaluronan Hydrogels

We designed bioinspired cross-linkers based on desmosine, the cross-linker in natural elastin, to prepare hydrogels with thiolated hyaluronic acid. These short, rigid cross-linkers are based on pyridinium salts (as in desmosine) and can connect two polymer backbones. Generally, the obtained semi-synthetic hydrogels are form-stable, can withstand repeated stress, have a large linear-elastic range, and show strain stiffening behavior typical for biopolymer networks. In addition, it is possible to introduce a positive charge to the core of the cross-linker without affecting the gelation efficiency, or consequently the network connectivity. However, the mechanical properties strongly depend on the charge of the cross-linker. The properties of the presented hydrogels can thus be tuned in a range important for engineering of soft tissues by controlling the cross-linking density and the charge of the cross-linker.

Side chain thiol-functionalized poly(ethylene glycol) by post-polymerization modification of hydroxyl groups: synthesis, crosslinking and inkjet printing

Polymers with a poly(ethylene glycol) backbone and mercaptomethyl side chains were synthesized by post-polymerization modification of hydroxymethyl side chains in three steps. As the starting point of the synthetic route, linear copolymers of ethylene oxide and glycidol with molar contents of glycidol repeating units of approximately 20, 40, 60, 80 and 100% were used. The polymer-bound hydroxyl groups were converted to thiol groups in three steps, comprising tosylation, introduction of a triphenylmethyl protected thiol and thiol deprotection by acid treatment. The degree of thiol-functionalization was controlled by the degree of functionalization of the starting material. The degree of conversion of hydroxyl groups to thiol groups determined by 1H NMR spectroscopy was quantitative for copolymers with approximately 20 and 40% glycidol repeating units and 92, 81 and 87% for copolymers with approximately 60, 80 and 100% glycidol repeating units, respectively. Exemplarily, poly(glycidylthiol) obtained by conversion of poly(glycidol) was crosslinked with poly(ethylene glycol) diacrylate (PEG-DA) to yield hydrogels which supported adhesion and proliferation of human fibroblasts 48 h after cell seeding. Spatially defined and surface attached gel structures were fabricated by subsequent inkjet printing of poly(glycidylthiol) and PEG-DA solutions onto acrylated glass slides.

Active Ester Containing Surfmer for One-Stage Polymer Nanoparticle Surface Functionalization in Mini-Emulsion Polymerization

Functional surface active monomers (surfmers) are molecules that combine the functionalities of surface activity, polymerizability, and reactive groups. This study presents an improved pathway for the synthesis of the active ester containing surfmer p-(11-acrylamido)undecanoyloxyphenyl dimethylsulfonium methyl sulfate (AUPDS). Further, the preparation of poly(methyl methacrylate) and polystyrene nanoparticles (NPs) by mini-emulsion polymerization using AUPDS is investigated, leading to NPs with active ester groups on their surface. By systematically varying reaction parameters and reagent concentrations, it was found that AUPDS feed concentrations between 2–4 mol% yielded narrowly distributed and stable spherical particles with average sizes between 83 and 134 nm for non-cross-linked NPs, and up to 163 nm for cross-linked NPs. By basic hydrolysis of the active ester groups in aqueous dispersion, the positive ζ-potential (ZP) was converted into a negative ZP and charge quantities determined by polyelectrolyte titrations before and after hydrolysis were in the same range, indicating that the active ester groups were indeed accessible in aqueous suspension. Increasing cross-linker amounts over 10 mol% also led to a decrease of ZP of NPs, probably due to internalization of the AUPDS during polymerization. In conclusion, by using optimized reaction conditions, it is possible to prepare active ester functionalized NPs in one stage using AUPDS as a surfmer in mini-emulsion polymerization.

Chitosan nanoparticles via high-pressure homogenization-assisted miniemulsion crosslinking for mixed-matrix membrane adsorbers

Glutaraldehyde-crosslinked chitosan nanoparticles (Chi-NPs) were prepared reproducibly via miniemulsion crosslinking for effective adsorption of the active pharmaceutical ingredient (API) Diclofenac (DCL). Three different molecular weights (MWs) of highly deacetylated (>90%) chitosans (low, medium and high MW) were used to vary the disperse phase viscosity. Particle formation was evaluated ranging from one to seven homogenization cycles at 40u202fMPa. Particles were prepared successfully with the low and medium MW chitosan in the range of 125u202fnm-250u202fnm (z-average). In HPLC assisted, static adsorption experiments, all particles showed a rapid sorption rate (<2u202fmin) with an adsorption capacity of up to 256.2u202fmgu202fg-1 DCL. Modelling of adsorption isotherms resulted in a qmax 358.3u202fmgu202fg-1 for Langmuir and 502.5u202fmgu202fg-1 for Sips, respectively. Membrane adsorbers were prepared by processing Chi-NPs into porous polyether sulfone microfiltration membranes via a casting and phase inversion process, resulting in an adsorption capacity of up to 3.6u202fmgu202fm-2 DCL in dynamic adsorption experiments.