Synthesis and characterization of novel photocrosslinkable poly(2-oxazoline)-based hydrogel systems for the application as biosensor matrix

The main work of this thesis is focused on the synthesis and characterization of novel photocrosslinkable and thermoresponsive hydrogel systems for the application as biosensor matrix. Poly(2-oxazoline)s are very attractive polymers for this application, as they exhibit a lower critical solution temperature (LCST) in aqueous media, with the possibility of tuning this LCST by copolymerization of monomers with different hydrophobic side chains.
For this purpose, an optimized synthesis route of a novel benzophenone-2-oxazoline-based photocrosslinker (BPOxa) photocrosslinker was developed and this monomer was copolymerized with various 2-alkyl-2-oxazolines (2-ethyl-, 2-n-propyl- and 2-isopropyl-2-oxazoline), to study the impact on the cloud point of the resulting thermoresponsive BPOxa copolymer systems. Here it was found that the large hydrophobic benzophenone moieties cause a significant decrease of the cloud point temperature compared to the corresponding 2-alkyl-2-oxazoline homopolymers. Poly(2-oxazoline)-based hydrogel layers were fabricated from these polymers by photocrosslinking with UV light at wavelength of 365 nm. The fabricated layers were characterized by surface plasmon resonance and optical waveguide mode spectroscopy (SPR/OWS) with respect to their swelling properties in aqueous media, showing that an increasing irradiation dose leads to a decrease in swelling ratio as a direct consequence of the higher crosslinking density in the respective hydrogel network. In addition, phase transition temperature and swelling ratio were studied for polymer networks of varying monomer composition, which was found to correlate to their cloud point in aqueous media.
Another major application target of this thesis is the development of a multifunctional sensor matrix in SPR-based biosensors. For this purpose, an azido-2-oxazoline derivative (AzOxa) was developed, which can serve as a post-modification unit for the incorporation of analyte-specific ligands or as a conjugation site for antifouling motives to improve protein binding resistance of the polymer network. First, the impact of the novel azido-2-oxazoline comonomer on the cloud point of poly(2-ethyl-2-oxazoline) and poly(2-isopropyl-2-oxazoline) derivatives was studied. A linear decrease of the cloud point temperature for an increasing AzOxa content was found, which is contrary to the expected trend for increased polarity of polymers with higher amounts of the more polar azide group (compared to plain alkyl substituents), but apparently, a higher tendency for chain aggregation is introduced with the N3 groups. Additionally, different alkyne-modified antifouling motives (e.g. sulfo- and carboxybetains, oligoethylene glycol and oligoethylene glycol-sulfobetaine) were developed and incorporated into the AzOxa copolymer backbone by copper(I) catalyzed azide-alkyne cycloaddition reaction (CuAAC). The conjugated hydrogels were characterized by SPR/OWS, with respect to their swelling behavior in aqueous solution. It was found that the swelling ratio (SR) of the prepared hydrogel layers is strongly influenced by the nature of the alkyne conjugate, as the SR increases from the non-modified polymer to the oligoethylene glycol and the zwitterionic systems. The results are explained by the increasing hydrophilic character of the modified polymers in correlation to their cloud point in aqueous media.
In addition, this work includes the synthesis and characterization of photocrosslinkable and thermoresponsive poly(N-isopropylacrylamide)-based and photocrosslinkable dextran-based hydrogel systems (in analogy to previous publications). Resulting applications are highlighted by the joint publications that emerged from the collaboration with Jakub Dostalek and Wolfgang Knoll in the context of the Austrian Institute of Technology (AIT) partner group.