Nanoelectrospray ionization (nanoESI or NSI) is a form of ESI that employs low flow rates of 10–1,000 nL/min. In comparison, conventional ESI employs flow rates from 1 μL/min to 1 mL/min. Due to the high volume of liquid exiting the emitter during ESI, a drying gas, thermal heating, or both are often required to expedite desolvation and droplet shrinkage. However, NSI generally does not require a drying gas or thermal heating and is typically preferred for peptides and proteins. Further, compared with ESI or H-ESI, NSI tolerates a wider range of liquid compositions, including pure water.

As you lower the flow rate during NSI, a smaller volume of mobile phase passes through the emitter, producing smaller aerosol droplets. This makes NSI more effective than conventional ESI or H-ESI at concentrating the analyte at the emitter tip. This produces significant increases in sensitivity as demonstrated by the signal response of the MS.