Glucose biosensors based on Michael addition crosslinked poly(ethylene glycol) hydrogels with chemo-optical sensing microdomains

Abstract

Continuous glucose monitoring (CGM) devices have the potential to lead to better disease management and improved outcomes in patients with diabetes. Chemo-optical glucose sensors offer a promising, accurate, long-term alternative to the current CGMs that require frequent calibration and replacement. Recently, we have proposed glucose sensor designs using phosphorescence lifetime-based measurement of chemo-optical glucose sensing microdomains embedded within alginate hydrogels. Due to the poor long-term stability of calcium-crosslinked alginate, we propose poly(ethylene glycol) (PEG) hydrogels synthesized via thiol-Michael addition chemistry as an alternative hydrogel carrier. The objective of this study was to evaluate the suitability of Michael addition crosslinked PEG hydrogels compared to calcium crosslinked alginate hydrogels for encapsulating glucose-sensing microdomains. PEG hydrogels crosslinked via thiol–vinyl sulfone addition achieved gelation in under 5 minutes, resulting in an even distribution of sensing microdomains. The shear storage modulus of the PEG hydrogels was tunable from 2.2 ± 0.1 kPa to 9.5 ± 1.8 kPa, which was comparable to the alginate hydrogels (10.5 ± 0.8 kPa), and the inclusion of microdomains did not significantly impact stiffness. The high water content of PEG hydrogels resulted in high glucose permeability that closely corresponded to the glucose permeability of alginate (D = 0.09 and 0.12 cm² s⁻¹, respectively; p = 0.47), but the PEG hydrogels exhibited superior stability. Both PEG and alginate-embedded sensors exhibited a sensing range up to ∼200 mg dL⁻¹ glucose. The lower limits of detection (LOD) for PEG and alginate-based glucose sensors were 19.8 and 20.6 mg dL⁻¹ with a difference of just 4.2% variation. The small difference between PEG and alginate embedded sensors indicates that their sensing properties are primarily determined by the glucose sensing microdomains rather than the hydrogel matrix. Overall, the results of this study indicate that Michael addition-crosslinked PEG hydrogels are a promising platform for encapsulation of chemo-optical glucose sensing microdomains.