Probe electrospray ionization (PESI) is an electrospray-based atmospheric-pressure surface sampling and ionization technique for mass spectrometry that uses a solid needle instead of a capillary. While ionization occurs in a fashion similar to that involved in electrospray ionization, the novel aspect of PESI is discontinuous sampling. The needle is driven up and down along the vertical axis to the apex of the ion-sampling orifice. At the highest position, the liquid trapped at the needle tip is electrosprayed. PESI is applicable to analyze the biological samples, imaging, real-time reaction monitoring, etc. The most unique feature of PESI is the sequential and exhaustive ionization of the analytes that cannot be accomplished by the capillary-based electrospray.