Subnanomolar Detection Limit of Stripping Voltammetric Ca²⁺-Selective Electrode: Effects of Analyte Charge and Sample Contamination

Ultrasensitive ion-selective electrode measurements based on stripping voltammetry are an emerging sensor technology with low- and subnanomolar detection limits. Here, we report on stripping voltammetry of down to 0.1 nM Ca²⁺ by using a thin-polymer-coated electrode and demonstrate the advantageous effects of the divalent charge on sensitivity. A simple theory predicts that the maximum concentration of an analyte ion preconcentrated in the thin membrane depends exponentially on the charge and that the current response based on exhaustive ion stripping from the thin membrane is proportional to the square of the charge. The theoretical predictions are quantitatively confirmed by using a thin ionophore-doped polymer membrane spin-coated on a conducting-polymer-modified electrode. The potentiostatic transfer of hydrophilic Ca²⁺ from an aqueous sample into the hydrophobic double-polymer membrane is facilitated by an ionophore with high Ca²⁺ affinity and selectivity. The resultant concentration of the Ca²⁺–ionophore complex in the ∼1 μm-thick membrane can be at least 5 × 10⁶ times higher than the aqueous Ca²⁺ concentration. The stripping voltammetric current response to the divalent ion is enhanced to achieve a subnanomolar detection limit under the condition where a low-nanomolar detection limit is expected for a monovalent ion. Significantly, charge-dependent sensitivity is attractive for the ultrasensitive detection of multivalent ions with environmental and biomedical importance such as heavy metal ions and polyionic drugs. Importantly, this stripping voltammetric approach enables the absolute determination of subnanomolar Ca²⁺ contamination in ultrapure water containing 10 mM supporting electrolytes, i.e., an 8 orders of magnitude higher background concentration