Glucose response of dissolved-core alginate microspheres: towards a continuous glucose biosensor

Microparticle optical sensors hold potential as implantable smart materials for in vivo analysis. In this work, the reversible response of dissolved-core alginate microspheres containing a homogeneous fluorescence resonance energy transfer (FRET)-based competitive binding assay for glucose was evaluated. The layer-by-layer self assembly technique was used to deposit multilayered nanofilm coatings on the alginate microspheres containing the assay, thereby stabilizing the sensor system when the alginate was de-crosslinked. The response to glucose was then determined in DI water and simulated interstitial fluid (SIF) using a flow cell to establish controlled, dynamic flow conditions for demonstrating reversibility. The glucose sensitivity under dynamic conditions was estimated to be 0.52%/mM glucose in DI water and 0.6%/mM glucose in simulated interstitial fluid; in both cases, the analytical response range was 0-30 mM glucose, covering both physiological (normoglycemia) and pathophysiological range (hyperglycemia and hypoglycemia). The sensor demonstrated a repeatable and reproducible response when tested over a period of one month, under dynamic flow conditions. Finally, in vitro cytotoxicity assays performed with L929 mouse fibroblast cell lines suggested that the dissolved-core alginate microsphere sensor system with nanofilm coating has sufficient biocompatibility for use as implantable glucose biosensors.