Limitations of current fluorescent glucose sensing assays based on competitive binding
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Competitive binding assays based on the protein Concanavalin A (ConA) have been proposed as potential sensors for continuous glucose monitoring applications. However, ConA-based assays in the literature have primarily displayed a lack of sensitivity or a lack of repeatability in their glucose response. This work explores this apparent trade-off by separating the measured glucose response into the recognition and fluorescence transduction mechanisms. The recognition responses are modeled for typical competing ligands/assays used in the literature, and they are combined with an optimized fluorescence approach to yield expected fluorescent glucose responses. Because aggregation is known to increase the apparent affinity between multivalent ligands and multivalent receptors, preliminary models are generated for assays that were initially optimized with multivalent ligands but increase in affinity over time. These models accurately predict the low sensitivity for monovalent ligands and the lack of repeatability in the responses with multivalent ligands as seen in the literature. This subsequently explains the aforementioned trade-off no matter the optical approach. 2013 Copyright SPIE.
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Optical Diagnostics and Sensing XIII: Toward Point-of-Care Diagnostics