A Novel, Nonenzymatic Strategy for Stable, Optical Glucose Detection in Small Volumes of Fluid

The performance of any continuous glucose monitor (CGM) cannot exceed the performance of the underlying glucose sensor. Commercially available CGMs are built around the enzyme glucose oxidase. However, the performance of the enzyme is known to drift over time; accordingly, existing CGMs must be calibrated over periods of hours to days and replaced over periods of weeks. To overcome these fundamental limitations, we have developed a non-enzymatic glucose detection strategy that offers the promise of significantly improved stability and sensitivity. Specifically, we have designed and synthesized a water-soluble, molecular recognition element, which binds glucose with appropriate specificity and selectivity (Kd = 1.9 mM for glucose vs. Kd = 3.3 mM for fructose). The molecular recognition of glucose by our synthetic probes activates interactions between fluorescence-based reporters. Moreover, by coupling the recognition element with a light-harvesting molecular system with high optical cross-section, we are able to amplify optical signals that betray the presence of glucose, making it possible to carry out measurements in volumes as small as picoliters using off-the-shelf LEDs and photodetectors. Our detection platform also offers broad tunability: by altering the molecular recognition element and/or optical reporter we seek to achieve stable, optical detection of other sugars and biomarkers.