Time-base modulation for the correction of cyclotron frequency shifts observed in long-lived transients from fourier-transform ion-cyclotron-resonance mass spectrometry of electrosprayed biopolymers

The occurrence of small shifts in the cyclotron frequency during the acquisition of very long transients (in excess of 80 s) has been observed to be a limiting factor for ultrahigh‐resolution mass measurements of protein ions performed with electrospray‐ionization Fourier‐transform ion‐cyclotron‐resonance mass spectrometry. Resolution measurements were restricted to values less than 106 because of the frequency shifts. Measurements of the frequency shifts, performed by sequentially transforming small segments of the transient, allowed the shift to be characterized and fitted to a 4th‐order equation. The sampling rate of the acquired transient was then modulated (at a rate equal to the reciprocal of the rate for the frequency shift) to allow ultrahigh resolution, greater than 2 × 106, and improved mass measurement and precision to be achieved for a small protein.