Advancement of Atmospheric-Vacuum Interfaces for Mass Spectrometers with a Focus on Increasing Gas Throughput for Improving Sensitivity

Abstract

Ion sampling from an electrospray ionization (ESI) source was improved by increasing gas conductance of the MS inlet by 4.3-fold. Converting the gas throughput (<i>Q</i>) into sensitivity improvement was dependent on ion desolvation and handling of the gas load. Desolvation was addressed by using a novel slot shaped inlet that exhibited desolvation properties identical to the 0.58 mm i.d capillary. An assay tailored for “small molecules” at high chromatographic flow rate (500 μL/min) yielded a compound dependent 6.5 to 14-fold signal gain while analysis at nano chromatographic flow rate (300 nL/min) showed 2 to 3.5-fold improvement for doubly charged peptides. Improvement exceeding the <i>Q</i> (4.3-fold) at high chromatographic flow rate was explained by superior sampling of the spatially dispersed ion spray when using the slot shaped capillary. Sensitivity improvement across a wide range of chromatographic flow rate confirmed no compromise in ion desolvation with the increase in <i>Q</i>. Another improvement included less overflow of gas into the mass analyzer from the foreline region owing to the slot shape of the capillary. By doubling the roughing pump capacity and operating the electrodynamic ion funnel (EDIF) at ∼4 Torr, a single pumping stage was sufficient to handle the gas load. The transport of solvent clusters from the LC effluent into the mass analyzer was prevented by a “wavy shaped” transfer quadrupole and was compared with a benchmark approach that delivered ions orthogonally into a differentially pumped dual EDIF at comparable gas <i>Q</i>