Critical Role of Voltage Application Points in “Analog” and “Digital” Electrospray Ionization Mass Spectrometry

In electrospray ionization (ESI) mass spectrometry (MS), an electric DC potential is often applied to a metal capillary used to infuse a liquid sample. However, in some cases, especially when employing nanoelectrospray ionization (nanoESI), it is convenient to use a nonconducting capillary for sample delivery and spraying. In these cases, the potentials can be applied, for example, using a metal union placed in the proximity of the capillary outlet or to an electrode located in the sample reservoir near the capillary inlet. The optimum potential values, which warrant high MS signals, are different in these two operational conditions. A higher potential needs to be applied when the electrode is placed further away from the capillary outlet. Moreover, sample conductivity has a strong influence on the optimum potential values. Lower potentials must be used with highly conductive electrolytes. Thus, DC voltage scans are required to determine the optimum potentials. Applying electric potential to the electrode located in the sample reservoir, rather than metal union, significantly decreases the appearance of oxidized analyte peaks. We also show that a single-polarity square AC waveform can be applied to the union or sample reservoir electrode, and if its frequency is sufficiently high, it has a similar effect as decreasing DC voltage, allowing for digital control of electrospray with square waves (by varying duty cycle). Interestingly, the liquid meniscus oscillation frequency is independent of the AC signal frequency if the frequency is sufficiently high. Applying the AC signal in certain conditions stabilizes the electrospray plume. These observations reveal the resemblance of the ESI sample line to an <i>RC</i> circuit.