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

Abstract

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 Q 1/2 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.

Bipolar Electrospray from Electrodeless Emitters for ESI without Electrochemical Reactions in the Sprayer

“…This contributed to the absence of a plateau in spray current, i.e., the spray current continued to rise with the increment of voltage even in the steady cone-jet mode. This trend was similar to our previous result for a high-pressure offline nanoESI with an inserted platinum electrode . Another measurement using a different solvent (0.1% formic acid in 75% v/v ethanol) is shown in Figure S4.…”

“…30 The hyphenation of the high-pressure source to the AP-MS followed the indirect coupling method described in our previous report. 33 In brief, the transmission of ions was via a transport tube of 0.5 mm i.d. The electric conductivity here was ∼1 S/m, and the electrospray current was ∼200 nA.…”

A Subtle Change in Nanoflow Rate Alters the Ionization Response As Revealed by Scanning Voltage ESI-MS

“…Previously we reported a new paradigm of generating nanoESI from large-bore capillaries with a well-controlled flow rate that is insensitive to the inner diameter of the capillary. , The concept is based on the well-established spray current–flow rate relationship for steady cone-jet mode under an electric-discharge-free condition. The new ion source employed a high-pressure ESI technique which was developed previously in our laboratory to handle pure water, superheated solutions for high-throughput proteomics, and direct hyphenation with high-temperature liquid chromatography. , Common micropipette tips could be conveniently employed as the emitter for the direct detection of proteins from high-salt buffers without clogging and with minimal interaction with the capillary surface .…”

“…The validity of the scaling law in the nanoflow regime was verified in our previous publications (see combined data set in Figure S2). , The radius of the initial droplet R o is related to the flow rate by R o ∼ false( ϵ o ϵ r Q / K false) 1 / 3 where ϵ o is the vacuum permittivity. It is noted that eq and eq assume a much smaller jet diameter relative to the nozzle diameter; thus it may not apply to the fine capillary-based nanoESI.…”

“…The validity of the scaling law in the nanoflow regime was verified in our previous publications (see combined data set in Figure S2). 16,17 The radius of the initial droplet R o is related to the flow rate by 22…”