Dry eye disease (DED) affects millions of individuals in the United States and worldwide, and the incidence is increasing with an aging population. There is widespread agreement that the measurement of total tear osmolarity is the most reliable test, but this procedure provides only the total ionic strength and does not provide the concentration of each ionic species in tears. Here, we describe an approach to determine the individual ion concentrations in tears using modern silicone hydrogel (SiHG) contact lenses. We made pH (or H3O+, hydronium cation,/OH-, hydroxyl ion) and chloride ion (two of the important electrolytes in tear fluid) sensitive SiHG contact lenses. We attached hydrophobic C18 chains to water-soluble fluorescent probes for pH and chloride. The resulting hydrophobic ion sensitive fluorophores (H-ISF) bind strongly to SiHG lenses and could not be washed out with aqueous solutions. Both H-ISFs provide measurements which are independent of total intensity by use of wavelength-ratiometric measurements for pH or lifetime-based sensing for chloride. Our approach can be extended to fabricate a contact lens which provides measurements of the six dominant ionic species in tears. This capability will be valuable for research into the biochemical processes causing DED, which may improve the ability to diagnose the various types of DED.
Keywords: Chloride ion; Contact lens; Dry eye disease; Electrolytes; Fluorescence sensors; Hydrogels; Hydronium ion; Silicone hydrogels.
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