Probe-Substrate Distance Control in Desorption Electrospray Ionization

We introduce probe-substrate distance (D_ps)-control to desorption electrospray ionization (DESI) and report a systematic investigation of key experimental parameters. Examination of voltage, flow rate, and nebulizing gas pressure suggests as D_ps decreases, the distance-dependent spray current increases, until a critical point. At the critical point the relationship inverts, and the spray current decreases as the probe moves closer to the surface due to constriction of solution flow by the nebulizing gas. D_ps control was used to explore the use of spray current as a signal for feedback positioning, while mass spectrometry imaging was performed simultaneously. Further development of this technique is expected to find application in study of structure-function relationships for clinical diagnostics, biological investigation, and materials characterization. Graphical abstract ᅟ.