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

Abstract

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.

Glucose Response of Near-Infrared Alginate-Based Microsphere Sensors Under Dynamic Reversible Conditions

“…As seen in Figure 6, the sensor response was observed to reach steady state in approximately 2 min (worst-case response time), which matches observations for visible dye systems in our previous work. 21,33 In our previous work with visible dye sensors, we had illustrated that when glucose was added to the microsphere suspension (not exposed to glucose previously), the response time was slightly faster compared with during subsequent additions of glucose concentrations. The increase in response time in subsequent steps is due to the basal level of glucose now already present in the microsphere suspension.…”

Polysaccharides as a source of advanced materials: Cellulose hollow microspheres for drug delivery in cancer therapy

“…Specifically, hollow polymeric spheres have spurred increasing interest due to their potential applications such as drug delivery systems [2], artificial cells [3], biosensors [4], and catalytic systems [5]. The use of spheres as potential carrier for anticancer drug delivery has attracted much attention due to their wide applications [6].…”

Reagentless fluorescent biosensors based on proteins for continuous monitoring systems

“…It has been reported that apoGOx tryptophan fluorescence is slightly modified after binding to glucose and this can be used for glucose sensing [53]; however, our results did not agree with this finding. Procedures for reporting the binding event include the strategies previously indicated, for example competitive binding assays with dextran and FRET [52,54], furnishing analytical figures of merit similar to those previously described; it has recently been demonstrated that binding could also be detected by using the NIR fluorescence of carbon nanotubes [55]. More indepth studies of apoenzymes are needed to properly evaluate their ability as optical biosensors.…”

“…Again, many of the studies involving apoenzymes refer to glucose, mainly apoGOx (obtained after FAD removal by chemical procedures). Compared with ConA, apoGOx seems to be more stable to agglutination [52], and in comparison with GBP, chemical fluorophore attachment can be used for inducing reporting ability. It has been reported that apoGOx tryptophan fluorescence is slightly modified after binding to glucose and this can be used for glucose sensing [53]; however, our results did not agree with this finding.…”