Improving the Quadrupole to Ion Mobility Region in a Digital Quadrupole/Ion Mobility/Orbitrap Mass Spectrometer.

A quadrupole/drift tube ion mobility/Orbitrap instrument requires pumping from atmosphere to 10^-5 Torr in the quadrupole analyzer region, back to 1 Torr for the drift tube, and a return to 10^-5 Torr for the Orbitrap high vacuum region. The Orbitrap high vacuum region contains the transfer multipole, C-trap, and HCD cell. Insufficient pumping between the drift tube and quadrupole leads to helium in the quadrupole analyzer chamber which compromises performance. Additional vacuum regions were added between the drift tube and the analyzer chamber to maintain the analyzer pressure below 5.5 × 10^-5 Torr with the drift tube pressurized to 1.5 Torr of He. In this configuration, the isolation of a single charge state of C-reactive protein (m/z 5,000) was demonstrated. Fourier transform ion mobility spectra were acquired with the quadrupole in full scan mode and in the isolation mode. Ion optic voltages were optimized for both helium and nitrogen bath gases in the drift tube so that minimal ion heating was observed entering the drift tube. These instrument modifications enable improved ion transfer efficiency, allowing for better ion isolation by the digital quadrupole ion mobility separation of large protein complexes, as illustrated by the 23+ and 24+ charge states of C-reactive protein.