How space charge screws with your spectrum. Prof. Peter B. O’Connor Coulombic effects in the FTICR mass spectrometer or…

What is “space charge” 2 For two charges: For many charges:

The two major ‘demons’ in an FTICR 3 Space charge: I. J. Amster, Fourier Transform Mass Spectrometry. J. Mass Spectrom. 1996,

The two major ‘demons’ in an FTICR 4 Magnetron expansion: I. J. Amster, Fourier Transform Mass Spectrometry. J. Mass Spectrom. 1996,

The two major ‘demons’ in an FTICR 5 Magnetron expansion: I. J. Amster, Fourier Transform Mass Spectrometry. J. Mass Spectrom. 1996,

First: Global frequency shifts 6 T. J. Francl, M. G. Sherman, R. L. Hunter, M. H. Locke, W. D. Bowers, R. T. McIver, Int. J. Mass Spec. 1983, M. L. Easterling, T. H. Mize, I. J. Amster, Routine part-per-million mass accuracy for high- mass ions: Space-charge effects in MALDI FT-ICR. Anal. Chem. 1999, ppm shift With this linear correction term, +/- 5 ppm mass accuracy was routinely achieved Often this linear correction is insufficient due to the inability to account for low intensity ‘chemical noise’ ions

Second: Local frequency shifts 7 1.D. K. Williams, A. L. Kovach, D. C. Muddiman, K. W. Hanck, Utilizing Artificial Neural Networks in MATLAB to Achieve Parts-Per-Billion Mass Measurement Accuracy with a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer. J. Am. Soc. Mass Spectrom. 2009, , DOI: /j.jasms K. Williams, A. M. Hawkridge, D. C. Muddiman, Sub parts-per- million mass measurement accuracy of intact proteins and product ions achieved using a dual electrospray ionization quadrupole Fourier transform ion cyclotron resonance mass spectrometer. J. Am. Soc. Mass Spectrom. 2007, , DOI: /j.jasms D. K. Williams, D. C. Muddiman, Parts-per-billion mass measurement accuracy achieved through the combination of multiple linear regression and automatic gain control in a Fourier transform ion cyclotron resonance mass spectrometer. Anal. Chem. 2007, , DOI: /ac D. K. Williams, M. A. Chadwick, T. I. Williams, D. C. Muddiman, Calibration laws based on multiple linear regression applied to matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry. J. Mass Spectrom. 2008, , DOI: /jms C. Masselon, A. V. Tolmachev, G. A. Anderson, R. Harkewicz, R. D. Smith, Mass measurement errors caused by "local" frequency perturbations in FTICR mass spectrometry. J. Am. Soc. Mass Spectrom. 2002, See also recent results by RD Smith group and DC Muddiman groups on multiple linear regression and neural network approaches toward solving this problem.

Third/fourth: Peak Coalescence 8 Y. Naito, M. Inoue, Int. J. Mass Spectrom. Ion Processes 1996,

Third/fourth: Peak shape distortion 9 S. Guan, M. C. Wahl, A. G. Marshall, Elimination of frequency drift from FTICR mass spectra by digital quadrature heterodyning: ultrahigh mass resolving power for laser-desorbed molecules. Anal. Chem. 1993, As the space charge causes expansion of the ion cloud, the net space charge term decreases in magnitude, so the frequency increases, causing a frequency shift. The shift is not usually as smooth and predictable as shown here. Most of the frequency shift occurs at the beginning of the transient. Apodization “smooths out” this frequency shift, so that you can’t tell if/when it is occurring.

Third/fourth: Peak shape distortion – extreme case 10 Ideal Low space charge High space charge SLCC or “nipple” SLCC eliminates signal coherence in, typically, 10’s of milliseconds. SLCC or “nipple” occurs at the point where magnetron expansion (from space charge) causes the magnetron radius to equal the cyclotron radius. At this point, the ion packets experience high velocity “coulombic” collisions at the center of the cell – causing scattering and rapid dephasing of the ion cloud. K. Aizikov, R. Mathur, P. B. O'Connor, The Spontaneous Loss of Coherence Catastrophe in Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2009,

Fifth: Resolution decrease 11 If frequencies are shifting (due to space charge), the ion packet is dephasing – shortening the transient. Shorter transients result in lower resolution. I. J. Amster, Fourier Transform Mass Spectrometry. J. Mass Spectrom. 1996,

How do you combat space charge? 12 Keep the ion population low Stabilize the number of ions from scan to scan - Automatic Gain Control Explore advanced calibration functions Don’t apodize in day-to-day operation – don’t fool yourself High magnetic field (all space-charge related problems are worse with lower magnetic field instruments) Don’t excite all ions to the same orbital radius (sacrifice ion abundance accuracy for resolution and mass accuracy)