Automatic gain control in mass spectrometry using a jet disrupter electrode in an electrodynamic ion funnel

Abstract

We report on the use of a jet disrupter electrode in an electrodynamic ion funnel as an electronic valve to regulate the intensity of the ion beam transmitted through the interface of a mass spectrometer in order to perform automatic gain control (AGC). The ion flux is determined by either directly detecting the ion current on the conductance limiting orifice of the ion funnel or using a short mass spectrometry acquisition. Based upon the ion flux intensity, the voltage of the jet disrupter is adjusted to alter the transmission efficiency of the ion funnel to provide a desired ion population to the mass analyzer. Ion beam regulation by an ion funnel is shown to provide control to within a few percent of a targeted ion intensity or abundance. The utility of ion funnel AGC was evaluated using a protein tryptic digest analyzed with liquid chromatography Fourier transform ion cyclotron resonance (LC-FTICR) mass spectrometry. The ion population in the ICR cell was accurately controlled to selected levels, which improved data quality and provided better mass measurement accuracy. M ass spectrometry (MS) has become a vital tool in biological research. This information-rich detection method can produce sensitive, qualitative, and quantitative measurements, and provides the basis for characterizing proteins, identifying novel biomarkers, and studying protein interactions within biological networks and pathways. Many challenges in protein analysis stem from sample complexity, e.g., a typical mammalian cell can have protein abundances ranging from less than a few hundred to tens of millions of copies [1]. A focus in MS research continues to be the development of techniques to better handle the broad range of relative abundances from a single sample. Developments have included chemical methods [2][3][4], coupling MS to separation techniques [5,6], and improvements in instrumentation [7][8][9]. An example of the latter is automatic gain control (AGC) [8 -11], first developed by the Finnigan Corporation (now Thermo Electron Corporation) [9]. AGC provides automated regulation to a dynamic ion flux transmitted from the source of the instrument (common in liquid chromatography {LC} coupled MS experiments), resulting in a more constant ion population in the mass analyzer. AGC accomplishes this regulation by monitoring the ion production from the ion source (typically with a pre-scan) and providing on-the-fly adjustments of the ion accumulation time of an ion trap.The regulation or control of the ion population is important to the operation of most mass spectrometers, and particularly those based upon ion trapping where performance is degraded by excessive space charge. For example, a key source of mass error in Fourier transform ion cyclotron resonance (FTICR) MS comes from the effect of excessive space charge [12][13][14]. Linear and 3-D ion traps also experience detrimental effects from excessive space charge. These space charge effects lead to shifts in secular frequencies, changes in optimal excitation amplitude, and plasma e...

Experimental evidence for space-charge effects between ions of the same mass-to-charge in Fourier-transform ion cyclotron resonance mass spectrometry

“…Although this method of adjusting the ion population resembles automatic gain control (AGC) [25,26], it has some significant differences from other experimental methods that are used to select ion number. For example, the shape of the ion cloud may be influenced by the hexapole accumulation [17,27,28], and so we have compared these two ways of altering ion population to ensure that the frequency dependence is the same.…”

Sub part-per-million mass accuracy by using stepwise-external calibration in fourier transform ion cyclotron resonance mass spectrometry

“…Examples of high mass accuracy by FTICR-MS can be found in the literatures [26,28,44,51,54], but these are often obtained using experimental conditions that are not optimal for high abundance dynamic range or high sensitivity. To advance the application of FT-ICR mass spectrometry for high-throughput proteomics, it is important to define procedures that achieve high mass accuracy on a routine basis.…”

“…However, Smith and coworkers demonstrated that mass accuracy using AGC depends strongly on the selected abundance level of the ion population. The mass accuracy obtained with a high ion population in the analyzer cell is not as good as for a low population [44,51]. The mass confidence levels using AGC reported by the Gygi and Smith groups are ϳ5 ppm for external calibration experiments [18,46,51].…”

“…The mass accuracy obtained with a high ion population in the analyzer cell is not as good as for a low population [44,51]. The mass confidence levels using AGC reported by the Gygi and Smith groups are ϳ5 ppm for external calibration experiments [18,46,51]. While AGC improves mass accuracy for ESI-FTICR experiments, the implementation is not suitable for pulsed ion sources.…”

Theoretical and experimental evaluation of the low m/z transmission of an electrodynamic ion funnel

“…For example, a disk electrode "jet disrupter" was placed in the entrance region of the ion funnel to disperse the gas jet exiting the heated inlet capillary, thereby reducing the gas load to the following stage and prohibiting neutrals from entering the mass spectrometer [12]. The jet disrupter has also been used as an "ion valve" to regulate the intensity of the ion beam for use with automated gain control to improve mass measurement accuracy [13]. In addition, a controllable m/z filter was created at the exit of the ion funnel that removes lower mass chemical background species in some applications, and reducing down-stream space charge effects in ion trapping devices [14].…”