A Polarity-Sensitive Far-Red Fluorescent Probe for Glucose Sensing through Skin

The field of glucose biosensors for diabetes management has been of great interest over the past 60 years. Continuous glucose monitoring (CGM) is important to continuously track the glucose level to provide better management of the disease. Concanavalin A (ConA) can reversibly bind to glucose and mannose molecules and form a glucose biosensor via competitive binding. Here, we developed a glucose biosensor using ConA and a fluorescent probe, which generated a fluorescent intensity change based on solvatochromism, the reversible change in the emission spectrum dependent on the polarity of the solvent. The direction in which the wavelength shifts as the solvent polarity increases can be defined as positive (red-shift), negative (blue-shift), or a combination of the two, referred to as reverse. To translate this biosensor to a subcutaneously implanted format, Cyanine 5.5 (Cy5.5)-labeled small mannose molecules were used, which allows for the far-red excitation wavelength range to increase the skin penetration depth of the light source and returned emission. Three Cy5.5-labeled small mannose molecules were synthesized and compared when used as the competing ligand in the competitive binding biosensor. We explored the polarity-sensitive nature of the competing ligands and examined the biosensor’s glucose response. Cy5.5-mannotetraose performed best as a biosensor, allowing for the detection of glucose from 25 to 400 mg/dL. Thus, this assay is responsive to glucose within the physiologic range when its concentration is increased to levels needed for an implantable design. The biosensor response is not statistically different when placed under different skin pigmentations when comparing the percent increase in fluorescence intensity. This shows the ability of the biosensor to produce a repeatable signal across the physiologic range for subcutaneous glucose monitoring under various skin tones.