On an aerodynamic mechanism to enhance ion transmission and sensitivity of FAIMS for nano-electrospray ionization-mass spectrometry.

Simulations show that significant ion losses occur within the commercial electrospray ionization-field asymmetric waveform ion mobility spectrometer (ESI-FAIMS) interface owing to an angular desolvation gas flow and because of the impact of the FAIMS carrier gas onto the inner rf (radio frequency) electrode. The angular desolvation gas flow diverts ions away from the entrance plate orifice while the carrier gas annihilates ions onto the inner rf electrode. A novel ESI-FAIMS interface is described that optimizes FAIMS gas flows resulting in large improvements in transmission. Simulations with the bromochloroacetate anion showed an improvement of ~9-fold to give ~70% overall transmission). Comparable transmission improvements were attained experimentally for six peptides (2+) in the range of m/z 404.2 to 653.4 at a chromatographic flow rate of 300 nL/min. Selected ion chromatograms (SIC) from nano-LC-FAIMS-MS analyses showed 71% (HLVDEPQNLIK, m/z 653.4, 2+) to 95% (LVNELTEFAK, m/z 582.3, 2+) of ion signal compared with ion signal in the SIC from LC-MS analysis. IGSEVYHNLK (580.3, 2+) showed 24% more ion signal compared with LC-MS and is explained by enhanced desolvation in FAIMS. A 3-10 times lower limits of quantitation (LOQ) (<15% RSD) was achieved for chemical noise limited peaks with FAIMS. Peaks limited by ion statistics showed subtle improvement in RSD and yielded comparable LOQ to that attained with nano-LC-MS (without FAIMS). These improvements were obtained using a reduced FAIMS separation gap (from 2.5 to 1.5 mm) that results in a shorter residence time (13.2 ms ± 3.9 ms) and enables the use of a helium free transport gas (100% nitrogen).