Activity vs Concentration

Ion-selective electrodes respond to the electrochemical activity of an ion, not its total analytical concentration. In very dilute, simple solutions these two quantities are essentially the same. In more complex samples — with multiple dissolved salts, high total ionic content, or competing ions — they can differ substantially, and the difference matters for accurate quantitation.

This distinction is not a measurement limitation to be apologised for. In clinical and biological applications, ionic activity is actually the quantity of physiological interest: it is what governs enzyme kinetics, membrane transport, and receptor activation. For these applications, an ISE measurement is more directly meaningful than a total concentration measurement would be.

For most analytical laboratory applications, however, the goal is total concentration, and a correction is required.

Ions in solution are not isolated particles. They carry electrical charges and therefore exert forces on each other over short distances. In a concentrated solution, a given ion is surrounded by a cloud of oppositely charged ions that partially screen and constrain it, reducing its ability to participate in electrochemical reactions. The ion is present in full concentration, but its effective “thermodynamic availability” is reduced.

This effect is quantified by the activity coefficient γ (gamma), a dimensionless factor that is always between 0 and 1 (in practical aqueous solutions):

In a perfectly dilute solution, γ = 1 and activity equals concentration exactly. As the ionic strength of the solution increases, γ decreases and the measured activity falls progressively below the true concentration.

Because the Nernst equation relates electrode potential to activity, not concentration, an ISE calibrated against standards in pure water will give systematically low concentration readings when used with samples that have higher ionic strength — even if the target ion concentration is identical.

Consider two water samples that both contain exactly 10 ppm of nitrate but have different overall dissolved salt contents. Their millivolt readings on a nitrate ISE will differ — not because the nitrate concentrations differ, but because the activity coefficients differ. Without correction, one sample will appear to have a higher nitrate concentration than the other, even though they are identical.

More concretely: if you calibrate using standards prepared in deionised water, then measure a sample with moderate ionic strength, the electrode will give a reading that is systematically lowerthan the true concentration. The higher the sample’s ionic strength, the larger this systematic underestimate.

ISAB is a highly concentrated solution of an inert electrolyte (one that does not interfere with the target ion’s electrode). It is added in a fixed proportion to all standards and samples. The goal is for the added ionic strength to be so much larger than any variation in the samples’ own ionic strength that those variations become negligible.

When every solution in the run has the same ionic strength (dominated by the ISAB), every solution also has the same activity coefficient γ. The proportionality between millivolts and concentration then holds regardless of sample matrix — and the electrode effectively calibrates in concentration units.

A secondary — but practically important — benefit of ISAB is its effect on the liquid junction potential of the reference electrode.

At the porous frit (junction) of a reference electrode, the reference filling solution makes ionic contact with the sample. When the sample and reference filling solution have very different ionic strengths or compositions, the ions at the interface diffuse at different rates. Faster-moving ions cross the junction boundary more quickly, creating a small but non-zero charge separation — the liquid junction potential. If this potential changes between measurements (because samples have different matrices), it introduces a systematic offset that is impossible to distinguish from a genuine change in the target ion concentration.

ISAB reduces this problem by ensuring all solutions in a run have similar ionic strength, making the junction potential essentially constant.