This work presents new insights into material design and physicochemical interactions that are relevant for the use of glucose-responsive polymeric hydrogels in continuously operating biosensor systems. Investigated hydrogels were based on either acrylamide or N-isopropylacrylamide, covalently cross-linked by N,N'-methylenebis(acrylamide), and 3-acrylamidophenylboronic acid and (N-(3-dimethylaminopropyl)) acrylamide were the comonomers to enable selective glucose binding at a physiological pH. A novel assay for the determination of the amount of bound glucose inside the hydrogel was developed, enabling the direct recording of these receptor effects parallel to the determination of the change of water content, i.e., free swelling. Binding isotherms, affinity constants, and maximum degree of complexation of boronic acid groups with glucose were determined. The affinity toward glucose could be increased 3-fold compared to literature values for phenylboronic acid free in solution by the use of a suitable hydrogel composition. The library of differently composed materials was then evaluated in a pressure sensor setup. Thereby, the long-term use of the hydrogels was established, and the hydrogels could be analyzed for a period of three months without the reduction of the pressure signal sensitivity. Based on all results, a composition that is suitable for efficient glucose recognition was identified, at which up to 25% water was released at 37 °C and pH 7.4 and a change of the glucose concentration from 0 to 10 mM. In the physiologically relevant range (3-10 mM), a linear dependence of the swelling pressure on the glucose concentration was found, allowing an accurate determination of glucose concentration. Overall, the obtained results provide significant progress in efforts to enable glucose detection by a robust sensor setup.
Keywords: binding isotherm; glucose recognition; hydrogels; polyacrylamides; pressure sensor.