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.