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

Abstract

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: 110) and identified based on their CCS, accurate mass (R: 550k), and tandem MS using IRMPD in the ICR cell.

Recommendations for reporting ion mobility Mass Spectrometry measurements

“…The report should include the V ramp range, ramp time ( t ramp ), and pressures in the entrance and exit (P1 and P2) (Hernandez et al, ). In the case of nonlinear scan operation of the TIMS device, the V ramp ( t ) profile should be reported (Silveira et al, ; Benigni et al, ).…”

Coupling trapped ion mobility spectrometry to mass spectrometry: trapped ion mobility spectrometry–time‐of‐flight mass spectrometry versus trapped ion mobility spectrometry–Fourier transform ion cyclotron resonance mass spectrometry

“…TIMS separation was performed using nitrogen as a bath gas at ca 300 K, P 1 = 2.2 and P 2 = 0.9 mbar, and a constant RF (2200 kHz and 140–160 Vpp). A nonlinear stepping scan function was used, with a gate width of 3 ms. The TIMS cell was operated using a fill/trap/elute/quench sequence of 9/3/9/3 ms, using an average of 1000 IMS scans per mass spectrum and a voltage difference across the Δ E gradient of 5.0 V. The ramp voltage gradient was stepped by 0.25 V/frame with a Δ V ramp range of −160 to −60 V, for a total of 400 steps.…”

“…TIMS separation was performed using nitrogen as a bath gas at ca 300 K, P 1 = 2.2 and P 2 = 0.9 mbar, and a constant RF (2200 kHz and 140-160 Vpp). A nonlinear stepping scan function was used, 40…”

“…With the advent of high-resolution mobility analyzers (R >80), there is a natural push for their integration to high-resolution mass analyzers for the analysis of complex mixtures. 21,[24][25][26][27][28][29][30][31][32] Our team has pioneered the integration of TIMS with FT-ICR MS since 2015, 33 and several reports have shown the unique advantages of TIMS with FT-ICR MS. [34][35][36][37][38][39][40] In the work presented here, we evaluated the performance of a TIMS analyzer when coupled to TOF MS and FT-ICR MS for the analysis of a complex mixture standard (i.e., Suwannee River Fulvic Acid Standard). The goal was to study the reproducibility of TIMS across platforms, applicability range, and potential challenges during routine analysis.…”

Recommendations for Reporting Ion Mobility Mass Spectrometry Measurements

“…The report should include the V ramp range, ramp time (t ramp ), and pressures in the entrance and exit (P1 and P2) (Hernandez et al, 2014). In the case of nonlinear scan operation of the TIMS device, the V ramp (t) profile should be reported (Silveira et al, 2016a;Benigni et al, 2018).…”