Fourier transform ion cyclotron resonance mass spectrometry at the true cyclotron frequency

Abstract

Ion cyclotron resonance (ICR) cells provide stability and coherence of ion oscillations in crossed electric and magnetic fields over extended periods of time. Using the Fourier transform enables precise measurements of ion oscillation frequencies. These precisely measured frequencies are converted into highly accurate mass-to-charge ratios of the analyte ions by calibration procedures. In terms of resolution and mass accuracy, Fourier transform ICR mass spectrometry (FT-ICR MS) offers the highest performance of any MS technology. This is reflected in its wide range of applications. However, in the most challenging MS application, for example, imaging, enhancements in the mass accuracy of fluctuating ion fluxes are required to continue advancing the field. One approach is to shift the ion signal power into the peak corresponding to the true cyclotron frequency instead of the reduced cyclotron frequency peak. The benefits of measuring the true cyclotron frequency include increased tolerance to electric fields within the ICR cell, which enhances frequency measurement precision. As a result, many attempts to implement this mode of FT-ICR MS operation have occurred. Examples of true cyclotron frequency measurements include detection of magnetron inter-harmonics of the reduced cyclotron frequency (i.e., the sidebands), trapping fieldfree (i.e., screened) ICR cells, and hyperbolic ICR cells with quadrupolar ion detection. More recently, ICR cells with spatially distributed ion clouds have demonstrated attractive performance characteristics for true cyclotron frequency ion detection. Here, we review the corresponding developments in FT-ICR MS over the past 40 years.

Super-resolution mass spectrometry enables rapid, accurate, and highly-multiplexed proteomics at the MS2-level

“…18 Finally, the described application of LSF in TMTc/TMTproC quantitative proteomics is a welcome addition to the arsenal of LSF-enabled strategies, such as targeted drug monitoring in mass spectrometry imaging. 39 The described approach is compatible with any high-field Orbitrap-quadrupole instrument like the Q Exactive HF or the Exploris. The LSF algorithm applied here and other SR algorithms, such as the filter-diagonalization method, 40,41 phase-constrained spectral decomposition method, 42 and compressed sensing, are starting to confirm the initially high expectations toward the SRMS.…”

Enhancing the Throughput of FT Mass Spectrometry Imaging Using Joint Compressed Sensing and Subspace Modeling

“…Here, the basis transients determine the reconstructed mass resolution, which is the same as long transient data (e.g., high-resolution mass spectra), thus achieving the target mass resolution with a minimal loss of spectral fidelity (Figure C). More details on subspace model can be found in the Supporting Information (SI) and ref . While effective with spatially fully sampled data, the original pixel-by-pixel subspace fitting is not applicable to spatial sparse sampling.…”

“…12 Targeted least-squares fitting for selected m/z features (cyclotron frequencies) has been used to achieve spectral super-resolution compared to conventional Fourier transform analyses from transients acquired at reduced durations. 13 A phase spectrum deconvolution method was proposed to enhance the resolution several times higher than standard FT. 14 Hence, transients with the reduced duration can be collected for improved throughput without sacrificing the mass resolution. Subspace imaging has recently been adapted to accelerate FT-ICR MSI by enabling efficient reconstruction of high-resolution mass spectra from short transients (short-time acquisition) in an untargeted and data-driven fashion.…”

“…Absorption mode FT has been applied to MSI to achieve improved mass resolution over standard FT on the same data . Targeted least-squares fitting for selected m / z features (cyclotron frequencies) has been used to achieve spectral super-resolution compared to conventional Fourier transform analyses from transients acquired at reduced durations . A phase spectrum deconvolution method was proposed to enhance the resolution several times higher than standard FT .…”

Super-Resolution Mass Spectrometry Enables Rapid, Accurate, and Highly Multiplexed Proteomics at the MS2 Level

“…18 The described application of LSF in TMTc/TMTproC quantitative proteomics is a welcome addition to the arsenal of LSF-enabled strategies, such as targeted drug monitoring in mass spectrometry imaging. 43 The described approach is compatible with other Orbitrap instruments as well, e.g., Q Exactive HF and Exploris. The LSF algorithm applied here and other SR algorithms, such as the filter-diagonalization method, 44,45 phase-constrained spectral decomposition method, 46 and compressed sensing, are starting to confirm the initially high expectations toward the SRMS.…”