Abstract: The detection of biological samples requires the adaptation of nanoelectrospray ionization mass spectrometry (nESI-MS) to hasher conditions, such as high concentrations nonvolatile buffers and sub-micrometer scale capillary tips. The two above-mentioned requirements would pose a considerable challenge, clogging, to nESI-MS. Herein, to mitigate the clogging problem, an induced alternative voltage was applied on the nanoemitters, which had inner diameter of less than 1 μm, with the infusion of a high-concentration salt solution, to induce electrospray ionization. The tips lifetime of the modified nESI was found to be 1～2 orders of magnitude longer than that of conventional nESI. The much longer spray time could be attributed to the re-dissolution effect of salt crystals owing to the periodic change in the electric field direction. Meanwhile, the signal of the modified nESI remained stable and sensitive even after a long run (～10 min) for analysis of high-concentration salt solutions. Finally, the mimic extracellular fluid and intracellular fluid were both evaluated, and the result indicated that the application of an induced alternating current voltage can be a widely applicable method to delay clogging during biological sample analysis.