Glucose-Responsive Polymeric Hydrogel Materials: From a Novel Technique for the Measurement of Glucose Binding toward Swelling Pressure Sensor Applications

Abstract

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.

Smart Hydrogels for Advanced Drug Delivery Systems

“…Examples of GRHs are glucose oxidase-loaded, lectin-loaded hydrogels, and hydrogels with phenylboronic acid moieties. However, these smart hydrogels can also be used to send therapeutic to tissues such as bone that have been damaged by diabetes [ 86 ]. Diabetes as a metabolic disease cause a pathological high-glucose microenvironment in tissues, which would significantly accelerate the progress of the preexist inflammation and prevent local tissue regeneration [ 87 ].…”

Hydrogel‐based composites: Unlimited platforms for biosensors and diagnostics

“…Although enzymes are highly selective receptors for certain biomarkers, the risk of protein denaturation has limited their service life. [ 250 ] Therefore, enzyme‐free glucose detection methods are well needed. [ 59 ] Many noble NSs such as AuNSs, [ 251,252 ] PtNSs, [ 253–256 ] and PdNSs [ 224,257–260 ] have been found to exhibit enzyme‐like catalytic activities.…”

Bottom-Up Engineering of Responsive Hydrogel Materials for Molecular Detection and Biosensing

“…When glucose is present, the total proportion of anionic boronate esters increases within the hydrogel (as K tet ≫ K trig ), increasing the gel’s hydro­philicity which can lead to swelling in chemically cross-linked hydrogels . The degree of swelling is correlated to the pressure the gel exerts, and can be used to quantify glucose content when the hydrogel is incorporated into pressure sensors . By changing the ionic nature of a polymer hydrogel, changes in the gel’s electric field can be exploited for glucose sensing using miniature electronic devices as well.…”