Generation of Ions from Aqueous Taylor Cones near the Minimum Flow Rate: “True Nanoelectrospray” without Narrow Capillary

Generating ultrafine charged droplets using electrospray is crucial for attaining high ionization efficiency for mass spectrometry. The size of the precursor charged droplets depends on the spray flow rate, and conventional wisdom holds that an electrospray of a nL/min flow rate (nanoelectrospray) is only possible using narrow capillaries with an inner diameter of ∼1 μm or smaller. Here, the electrospray of aqueous solutions with high electric conductivities generated from a large off-line capillary of 0.4 mm i.d. has been performed using a high-pressure ion source. The electric discharge is avoided by operating the ion source at 2.5 bar gauge pressure. The highly stable Taylor cone can be tuned to a near-hydrostatic state that exhibits the "true nanoelectrospray" properties, i.e., high salt tolerance and minimal ion suppression. The Q1/2 scaling law describing the electrospray current I and flow rate Q is found to be valid down to the nanoflow regime under a condition that is free of electric discharge. For a given solution, the flow rate and the size of the initial droplets and ionization species can be controlled with the spray current as the indicator for the instantaneous flow rate without changing the emitter capillary of different sizes. In regard to the application, the nanoelectrospray with a large micropipette tip is easy to use, free of clogging when dealing with viscous and high-salt buffer solutions, and with reduced surface interaction with the emitter inner surface. An acquisition of very clean mass spectra of proteins from concentrated solutions of nonvolatile salts such as phosphate-buffered saline is demonstrated.