Abstract
BACKGROUND: Continuous glucose monitoring is crucial to developing a successful artificial pancreas. However, biofouling and host response make in vivo sensor performance difficult to predict. We investigated changes in glucose diffusivity and sensor response of optical enzymatic glucose sensors due to biological exposure. METHOD: Three hydrogel materials, poly(2-hydroxyethyl methacrylate) (pHEMA), poly(acrylamide) (pAM), and poly(2-hydroxyethyl methacrylate)-co-poly(acrylamide) (p(HEMA-co-AM)), were tested for glucose diffusivity before and after exposure to serum or implantation in rats for 1 month. Luminescent sensors based on these materials were measured to compare the response to glucose before and after serum exposure. RESULTS: Glucose diffusivity through the pHEMA [(8.1 ± 0.38) × 10(-8) cm(2)/s] slabs was much lower than diffusivity through pAM [(2.7 ± 0.15) × 10(-6) cm(2)/s] and p(HEMA-co-AM) [(2.5 ± 0.08) × 10(-6)]. As expected from these differences, sensor response was highly dependent on material type. The pHEMA sensors had a maximum sensitivity of 2.5%/(mg/dl) and an analytical range of 4.2-356 mg/dl, while the p(HEMA-co-AM) sensors had a higher sensitivity [14.9%/(mg/dl)] and a narrower analytical range (17.6-70.5 mg/dl). After serum exposure, the pHEMA sensors were unaffected, whereas the p(HEMA-co-AM) sensors exhibited significantly decreased sensitivity and increased analytical range. CONCLUSIONS: Decreases in glucose diffusivity in the polymers resulting from in vitro serum exposure and residence in vivo were shown to be similar, suggesting that serum incubation was a reasonable approximation of in vivo fouling. While biofouling is expected to affect the response of flux-based sensors, we have shown that this depended on the type of sensor and matrix used. Therefore, proper design and materials selection may minimize response alterations occurring upon implantation.