Optimizing Salt Lipophilicity for Reference Electrodes Based on Organic Electrolytes

Reference electrodes (REs) based on membranes doped with organic electrolytes offer an attractive route toward versatile, miniaturized, and maintenance-free sensing platforms. Nevertheless, the choice of the reference electrolyte remains a critical design parameter that determines the performance of the corresponding REs. Different ranges of ionic liquid and solid organic salt lipophilicity have previously been explored for RE design, each characterized by different intrinsic limitations. Although the increased partitioning of less lipophilic electrolytes from the reference membrane to the sample establishes stable RE potentials, it also results in rapid electrolyte loss and sample contamination. This might in principle be mitigated with highly lipophilic organic electrolytes, but even minor deviations from the ideal stoichiometric composition of such salts induce parasitic responses of the RE to sample species. To combine the advantages of both characteristics, we investigate here the intermediate electrolyte lipophilicity range that has largely remained underexplored for RE design. Ionic liquids with lipophilicities exceeding that of commercial analogues based on the bis-(trifluoromethanesulfonyl)-imide ([C₁C₁N^-]) anion were prepared via potentiometric titrations by systematically varying the lipophilicity of the tetraalkylammonium used as countercation. The best-performing composition, based on tetrahexylammonium ([THA⁺]-[C₁C₁N^-]), provided reproducible and stable reference electrode potentials in both bulk solutions and under flow conditions, giving a potential variation of only 0.16 mV for solutions bracketing the physiological electrolyte range. This stability was accompanied by dramatically reduced leaching of the salt from the membrane, which was confirmed via quartz crystal microbalance measurements and the absence of chemical poisoning of ion-selective membranes placed in the same solution.