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Accurate drift time determination by traveling wave ion mobility spectrometry: The concept of the diffusion calibration Christopher Kune, Johann Far, and Edwin De Pauw Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.6b03215 • Publication Date (Web): 02 Nov 2016 Downloaded from http://pubs.acs.org on November 4, 2016
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Analytical Chemistry
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Accurate drift time determination by traveling wave ion mobility spectrometry: The concept of the diffusion calibration
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Christopher Kune†, Johann Far† and Edwin De Pauw†
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†
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11, B-4000, Liege, Belgium
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Keywords:
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Ion mobility mass spectrometry, arrival time distribution, data processing, peak deconvolution, Gaussian function, full width at half maximum, peak width, diffusion, conformers.
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Laboratory of Mass Spectrometry, University of Liege, Quartier Agora, Allée du six Aout
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Abstract
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Ion mobility spectrometry (IMS) is a gas phase separation technique which relies on
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differences in collision cross section (CCS) of ions. Ionic clouds of unresolved conformers
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overlap if the CCS difference is below the instrumental resolution expressed as CCS/ΔCCS.
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The experimental arrival time distribution (ATD) peak is then a superimposition of the
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various contributions weighted by their relative intensities. This paper introduces a strategy
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for accurate drift time determination using traveling wave ion mobility spectrometry
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(TWIMS) of poorly resolved or unresolved conformers. This method implements through a
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calibration procedure the link between the peak full width at half maximum (FWHM) and the
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drift time of model compounds for wide range of settings for wave heights and velocities.
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We modified a Gaussian equation which achieves the deconvolution of ATD peaks where the
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FWHM is fixed according to our calibration procedure. The new fitting Gaussian equation
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only depends on two parameters: The apex of the peak (A) and the mean drift time value
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(µ). The standard deviation parameter (correlated to FWHM) becomes a function of the drift
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time. This correlation function between µ and FWHM is obtained using the TWIMS
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calibration procedure which determines the maximum instrumental ion beam diffusion
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under limited and controlled space charge effect using ionic compounds which are detected
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as single conformers in the gas phase. This deconvolution process has been used to highlight
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the presence of poorly resolved conformers of crown ether complexes and peptides leading
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to more accurate CCS determinations in better agreement with quantum chemistry
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predictions.
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Introduction
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The physicochemical properties of molecules strongly depend on their structure (e.g. acidity,
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peptide activity, molecular recognition, specific reactivity...). Therefore, getting information
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on the structure is an important figure of merit not only in specialized structural elucidation
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techniques but also in analytical methods1. Mass spectrometry (MS), especially with exact
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mass determination and tandem MS, is used for identifying compounds as a function of the
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mass to charge (m/z) ratio, which is largely used to obtain connectivity information allowing
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molecular identification2. However, three-dimensional information of large systems is not
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directly attainable without additional strategies (e.g. hydrogen-deuterium exchange or cross-
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linking).
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The three-dimensional structure of a compound is frequently elucidated using a set of
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independent methods, such as nuclear magnetic resonance spectroscopy (NMR)3 or
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spectroscopic methods (e.g. Infrared spectroscopy, X-ray crystallography and other
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spectroscopic methods) which need large amounts of high purity samples. Nowadays, with
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the development of ion mobility spectrometry (IMS) hyphenated with mass spectrometry
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and computational chemistry support, information about three-dimensional structures can
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be estimated4–6 retaining the advantages of an MS analysis, e.g. low time consumption for
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data acquisition, applicable for low concentration and moderately purified samples.
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Analytical Chemistry
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Ion Mobility Spectrometry is a separation technique which allows temporal or physical
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separations of ions mainly depending on their three-dimensional structure (described as
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Collision Cross Section or CCS). Kanu and coworkers7 described several ion mobility
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spectrometers using mass spectrometry detection including Drift Time Ion Mobility
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Spectrometry (DTIMS)8 and Traveling Wave Ion Mobility Mass Spectrometry (TWIMS)9. In
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DTIMS devices, ions are moving at a characteristic stationary velocity in a low pressure tube
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owing to a constant drag force with the buffer gas and the applied low electric field in the
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drift tube7. Each ion can be described by the time it needs to reach the mass detector, called
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“drift time”. Direct CCS measurements is allowed with DTIMS using the Mason-Schamp
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equation (eq 1)10–12, where K is the measured mobility at standard conditions (273.15 K and
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101.325 Pa), v is the velocity, E is the electric field, q is the charge of the ion, N is the density
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number of the drift gas, m is the mass of the ion, M is the mass of the drift gas, kb is the
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Boltzmann constant, T is the gas temperature and Ω is the collision cross section in the CGS
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system of units.
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=
=
+
Ω
(1)
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According to Giles and coworkers9, the principle of temporal separation in TWIMS is similar
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to the DTIMS devices except for the electric field being neither uniform nor time
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independent. The experimental TWIMS setup allows the formation of an oscillating electric
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field which moves through the TWIMS device as waves. Wave height (V), wave velocity (m/s)
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and gas pressure are the main settings affecting the drift time of ions. The ion motions that
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occur in TWIMS do not allow a direct determination of CCS values due to non-constant
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stationary velocities of ions. However, calibration procedures for CCS determinations using
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TWIMS are available and have been reported in literature13–17. Structural elucidation by IMS
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is often performed comparing experimental and theoretical CCS values obtained after
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structure optimization using computational chemistry strategies (e.g. molecular mechanics,
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Density Functional Theory…) and CCS calculations (e.g. MOBCAL18,19 or IMoS20–22) agreeing
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within around 1 to 5% (typically
