| dc.description.abstract | Continuous glucose monitors (CGMs) that permit real-time tracking of glucose levels have the potential to vastly improve diabetes management. The membrane used to construct an optical glucose sensor must address challenges related to assay retention, glucose diffusivity, and minimizing the foreign body reaction (FBR). In this work, thermosensitive, double network (DN) hydrogel membranes based on N-isopropyl-acrylamide (NIPAAm) were designed. With a tuned volume phase transition temperature (VPTT), membranes are expected to “self-clean” via cyclical deswelling/reswelling with body temperature fluctuations.
In a first study, the membrane mesh size was reduced with a comb architecture, towards eventual formation of a biosensor with a förster resonance energy transfer (FRET)-based glucose sensing assay. A tightly cross-linked first network was comprised of NIPAAm copolymerized with negatively charged 2-acrylamido-2-methylpropane sulfonic acid (AMPS), and a loosely cross-linked second network was formed from NIPAAm copolymerized with N-vinylpyrrolidone (NVP). Combs of varying charges, lengths, and concentrations were introduced to the first network. Able to achieve the targeted mesh size (~1-3 nm), negatively charged combs were the most effective in reducing mesh size, attributed to electrostatic repulsive forces.
In a second study, a membrane was customized to directly embed a phosphorescence sensing assay based on an oxygen-sensitive metalloporphyrin (HULK) and glucose oxidase (GOx). The membrane’s first network was prepared from NIPAAm and cationic (3-acrylamidopropyl)trimethylammonium chloride (APTAC). The second network was formed with NIPAAm copolymerized with acrylamide (AAm). Anionic HULK was retained via electrostatic attractive forces while the GOx was covalently bonded via a glutaraldehyde linker. A membrane achieved the desired increase in phosphorescence lifetime with increasing glucose concentrations from 50 to 200 mg/dL. A lack of sensitivity at higher glucose levels was attributed to membrane oxygen depletion.
In a final study, to improve the glucose sensitivity of the phosphorescence assay at higher glucose levels, a membrane with improved oxygen permeability was prepared by incorporation of silicone microdroplets. A ultrasonicate processor was used to disperse the silicone phase during formation of the first network and the second network was comprised of P(NIPAAm-co-AAm). With the optimal concentration of silicone microdroplets, glucose sensitivity was observed for concentrations from 100 to 300 mg/dL. | |
