Increasing Analytical Separation and Duty Cycle with Nonlinear Analytical Mobility Scan Functions in TIMS-FT-ICR MS

In this work, nonlinear, stepping analytical mobility scan functions are implemented to increase the analytical separation and duty cycle during tandem Trapped Ion Mobility Spectrometry and FT-ICR MS operation. The differences between linear and stepping scan functions are described based on length of analysis, mobility scan rate, signal-to-noise, and mobility resolving power. Results showed that for the linear mobility scan function only a small fraction of the scan is sampled, resulting in the lowest duty cycle 0.5% and longest experiment times. Implementing nonlinear targeted scan functions for analysis of known mobilities resulted in increased duty cycle (0.85%) and resolving powers (R up to 300) with a 6-fold reduction in time from 30 to 5 min. For broad range characterization, a nonlinear mobility stepping scan function provided the best sensitivity, resolving power, duty cycle (4%), and points per peak. The applicability of nonlinear mobility scan functions for the analysis of complex mixtures is illustrated for the case of a direct infusion of a MCF-7 breast cancer cell digest, where isobaric peptides (e.g., DFTPAELR and TTILQSTGK) were separated in the mobility domain (R_IMS: 110) and identified based on their CCS, accurate mass (R_MS: 550k), and tandem MS using IRMPD in the ICR cell.