Mass resolution and mass accuracy: how much is enough?

Abstract

Accurate mass measurement requires the highest possible mass resolution, to ensure that only a single elemental composition contributes to the mass spectral peak in question. Although mass resolution is conventionally defined as the closest distinguishable separation between two peaks of equal height and width, the required mass resolving power can be ∼10× higher for equal width peaks whose peak height ratio is 100 : 1. Ergo, minimum resolving power requires specification of maximum dynamic range, and is thus 10-100× higher than the conventional definition. Mass resolving power also depends on mass-to-charge ratio. Mass accuracy depends on mass spectral signal-to-noise ratio and digital resolution. Finally, the reliability of elemental composition assignment can be improved by resolution of isotopic fine structure. Thus, the answer to the question of "how much is enough mass resolving power" requires that one first specify S/N ratio, dynamic range, digital resolution, mass-to-charge ratio, and (if available) isotopic fine structure. The highest available broadband mass resolving power and mass accuracy is from Fourier transform ion cyclotron resonance mass spectrometry. Over the past five years, FT-ICR MS mass accuracy has improved by about an order of magnitude, based on higher magnetic field strength, conditional averaging of time-domain transients, better mass calibration (spectral segmentation; inclusion of a space charge term); radially dispersed excitation; phase correction to yield absorption-mode display; and new ICR cell segmentation designs.

Keywords: FTMS; Fourier transform; ion cyclotron resonance; isotopic fine structure.

Fig. 1. Seven-section¹⁵⁾ (top) and dynamically harmonized¹⁶⁾ (bottom) ICR cells.

Fig. 2. Discrete mass spectrum. A: peak amplitude. ∆m_50%: peak full width at half-maximum peak height. σ: standard deviation of baseline noise. Predicted mass measurement precision is given by Eq. (1) (see the text). (Reproduced, with permission, from ref. .)

Fig. 3. Barely resolved pairs of Lorentzian magnitude-mode spectral peaks of equal width. Peak height ratio is 1 : 1 (top) and 100 : 1 (bottom). Note that the resolving power required to distinguish the peaks is ∼10 times higher for the 100 : 1 pair.

Fig. 4. Atomic mass defects for selected isotopes of some common chemical elements. (Reproduced, with permission, from ref. .)

Fig. 5. (+) ESI 9.4 T FT-ICR mass spectra of a Russian bitumen. Bottom: Broadband (+) ESI 9.4 T FT-ICR mass spectrum (black) with a 4 Mword 10 MHz SWIFT excitation waveform overlaid (red). Middle: Mass scale-expanded segment for SWIFT-isolated ions, including assignment of two monoisotopic molecular formulas. Top: Mass scale-expanded segments for ions 1 or 2 Da higher in mass than the assigned monoisotopic ions. Appearance of the ¹⁸O and ³⁴S isotopologues serves to validate the monoisotopic compositional assignments. Also note the detection of isotopologues containing ²H, ¹³C, or ¹⁵N.

Fig. 6. Magnitude (top) and absorption (bottom) (+) ESI 9.4 T FT-ICR mass spectral segments for a North American petroleum crude oil. Note the absorption-mode resolution of three pairs of peaks (compositions differing by C₃ vs. SH₄, 0.0034 Da and H₄N₂S₂ vs. C₄O₃, 0.0032 Da) that are unresolved in magnitude-mode display.