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Title: High Performance Ion Mobility Spectrometry Using Hourglass Electrodynamic Funnel And Internal Ion Funnel

Abstract

A method and apparatus enabling increased sensitivity in ion mobility spectrometry/mass spectrometry instruments which substantially reduces or eliminates the loss of ions in ion mobility spectrometer drift tubes utilizing a device for transmitting ions from an ion source which allows the transmission of ions without significant delay to an hourglass electrodynamic ion funnel at the entrance to the drift tube and/or an internal ion funnel at the exit of the drift tube. An hourglass electrodynamic funnel is formed of at least an entry element, a center element, and an exit element, wherein the aperture of the center element is smaller than the aperture of the entry element and the aperture of the exit elements. Ions generated in a relatively high pressure region by an ion source at the exterior of the hourglass electrodynamic funnel are transmitted to a relatively low pressure region at the entrance of the hourglass funnel through a conductance limiting orifice. Alternating and direct electrical potentials are applied to the elements of the hourglass electrodynamic funnel thereby drawing ions into and through the hourglass electrodynamic funnel thereby introducing relatively large quantities of ions into the drift tube while maintaining the gas pressure and composition at the interiormore » of the drift tube as distinct from those at the entrance of the electrodynamic funnel and allowing a positive gas pressure to be maintained within the drift tube, if desired. An internal ion funnel is provided within the drift tube and is positioned at the exit of said drift tube. The advantage of the internal ion funnel is that ions that are dispersed away from the exit aperture within the drift tube, such as those that are typically lost in conventional drift tubes to any subsequent analysis or measurement, are instead directed through the exit of the drift tube, vastly increasing the amount of ions exiting the drift tube.« less

Inventors:
 [1];  [1];  [1]
  1. (Richland, WA)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
OSTI Identifier:
880598
Patent Number(s):
US 6967325
Application Number:
10/933661
Assignee:
Battelle Memorial Institute (Richland, WA) PNNL
DOE Contract Number:
AC06-76RL01830
Resource Type:
Patent
Country of Publication:
United States
Language:
English

Citation Formats

Smith, Richard D., Tang, Keqi, and Shvartsburg, Alexandre A. High Performance Ion Mobility Spectrometry Using Hourglass Electrodynamic Funnel And Internal Ion Funnel. United States: N. p., 2005. Web.
Smith, Richard D., Tang, Keqi, & Shvartsburg, Alexandre A. High Performance Ion Mobility Spectrometry Using Hourglass Electrodynamic Funnel And Internal Ion Funnel. United States.
Smith, Richard D., Tang, Keqi, and Shvartsburg, Alexandre A. Tue . "High Performance Ion Mobility Spectrometry Using Hourglass Electrodynamic Funnel And Internal Ion Funnel". United States. doi:. https://www.osti.gov/servlets/purl/880598.
@article{osti_880598,
title = {High Performance Ion Mobility Spectrometry Using Hourglass Electrodynamic Funnel And Internal Ion Funnel},
author = {Smith, Richard D. and Tang, Keqi and Shvartsburg, Alexandre A.},
abstractNote = {A method and apparatus enabling increased sensitivity in ion mobility spectrometry/mass spectrometry instruments which substantially reduces or eliminates the loss of ions in ion mobility spectrometer drift tubes utilizing a device for transmitting ions from an ion source which allows the transmission of ions without significant delay to an hourglass electrodynamic ion funnel at the entrance to the drift tube and/or an internal ion funnel at the exit of the drift tube. An hourglass electrodynamic funnel is formed of at least an entry element, a center element, and an exit element, wherein the aperture of the center element is smaller than the aperture of the entry element and the aperture of the exit elements. Ions generated in a relatively high pressure region by an ion source at the exterior of the hourglass electrodynamic funnel are transmitted to a relatively low pressure region at the entrance of the hourglass funnel through a conductance limiting orifice. Alternating and direct electrical potentials are applied to the elements of the hourglass electrodynamic funnel thereby drawing ions into and through the hourglass electrodynamic funnel thereby introducing relatively large quantities of ions into the drift tube while maintaining the gas pressure and composition at the interior of the drift tube as distinct from those at the entrance of the electrodynamic funnel and allowing a positive gas pressure to be maintained within the drift tube, if desired. An internal ion funnel is provided within the drift tube and is positioned at the exit of said drift tube. The advantage of the internal ion funnel is that ions that are dispersed away from the exit aperture within the drift tube, such as those that are typically lost in conventional drift tubes to any subsequent analysis or measurement, are instead directed through the exit of the drift tube, vastly increasing the amount of ions exiting the drift tube.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Nov 22 00:00:00 EST 2005},
month = {Tue Nov 22 00:00:00 EST 2005}
}

Patent:

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  • A method and apparatus enabling increased sensitivity in ion mobility spectrometry/mass spectrometry instruments which substantially reduces or eliminates the loss of ions in ion mobility spectrometer drift tubes utilizing an hourglass electrodynamic ion funnel at the entrance to the drift tube and/or an internal ion funnel at the exit of the drift tube. An hourglass electrodynamic funnel is formed of at least an entry element, a center element, and an exit element, wherein the aperture of the center element is smaller than the aperture of the entry element and the aperture of the exit elements. Ions generated in a relativelymore » high pressure region by an ion source at the exterior of the hourglass electrodynamic funnel are transmitted to a relatively low pressure region at the entrance of the hourglass funnel through a conductance limiting orifice. Alternating and direct electrical potentials are applied to the elements of the hourglass electrodynamic funnel thereby drawing ions into and through the hourglass electrodynamic funnel thereby introducing relatively large quantities of ions into the drift tube while maintaining the gas pressure and composition at the interior of the drift tube as distinct from those at the entrance of the electrodynamic funnel and allowing a positive gas pressure to be maintained within the drift tube, if desired. An internal ion funnel is provided within the drift tube and is positioned at the exit of said drift tube. The advantage of the internal ion funnel is that ions that are dispersed away from the exit aperture within the drift tube, such as those that are typically lost in conventional drift tubes to any subsequent analysis or measurement, are instead directed through the exit of the drift tube, vastly increasing the amount of ions exiting the drift tube.« less
  • The utility of ion mobility spectrometry (IMS) for separation of mixtures and structural characterization of ions has been demonstrated extensively, including in the biological and nanoscience contexts. A major attraction of IMS is its speed, several orders of magnitude above that of condensed-phase separations. Nonetheless, IMS combined with mass spectrometry (MS) has remained a niche technique, substantially due to limited sensitivity resulting from ion losses at the IMS-MS junction. We have developed a new electrospray ionization (ESI)-IMS-QToF MS instrument that incorporates electrodynamic ion funnels at both front ESI-IMS and back IMS-QToF interfaces. The front funnel is of the novel ''hourglass''more » design that efficiently accumulates ions and pulses them into the IMS drift tubes. Even for drift tubes of two meter length, ion transmission through IMS and on to QToF is essentially lossless across the range of ion masses relevant to most applications. The RF ion focusing at IMS terminus does not degrade IMS resolving power, which exceeds 100 (for singly-charged ions) and is close to the theoretical limit. The overall sensitivity of present ESI-IMS-MS system is shown to be comparable to that of commercial ESI-MS, which should make IMS-MS suitable for analyses of complex mixtures with ultra-high sensitivity and exceptional throughput.« less
  • The ability of ion mobility spectrometry coupled with mass spectrometry (IMS-MS) to characterize biological mixtures has been illustrated over the past eight years. However, the challenges posed by the extreme complexity of many biological samples have demonstrated the need for higher resolution IMS-MS measurements. We have developed a higher resolution ESI-IMS-TOF MS by utilizing high pressure electrodynamic ion funnels at both ends of the IMS drift cell and operating the drift cell at an elevated pressure compared to a previous design. The ESI-IMS-TOF MS instrument consists of an ESI source, an hourglass ion funnel used for ion accumulation/injection into anmore » 88 cm drift cell followed by a 10 cm ion funnel and a commercial orthogonal time-of-flight mass spectrometer providing high mass measurement accuracy. It was found that the rear (exit) ion funnel could be effectively operated as an extension of the drift cell when the DC fields were matched, allowing the instrument to have an effective drift region of 98 cm. Two differentially pumped quadrupole regions were used to couple the IMS and TOF MS to focus and minimize the ion transient time between the stages. The resolution of the instrument was evaluated at pressures ranging from 4 to12 Torr and ion mobility drift voltages of 16 V/cm (4 Torr) to 43 V/cm (12 Torr). An increase in resolution from 55 to 80 was observed from 4 to 12 Torr nitrogen drift gas with no loss in sensitivity. Given the increased usage of ion funnels prior to ion mobility separations, additional attention was directed towards the influence of drift gas on the observed ion populations trapped and transmitted using an electrodynamic ion funnel. The choice of drift gas was shown to influence the degree of ion heating and relative trapping efficiency within the ion funnel.« less
  • Selected reaction monitoring-mass spectrometry (SRM-MS) is playing an increasing role in quantitative proteomics and biomarker discovery studies as a method for high throughput candidate quantification and verification. While SRM-MS offers advantages in sensitivity and quantification compared to other MS-based techniques, current SRM technologies are still challenged by detection and quantification of low-abundance proteins (e.g., present at ~10 ng/mL or lower levels in blood plasma). Here we report enhanced detection sensitivity and reproducibility for SRM-based targeted proteomics by coupling a dual electrodynamic ion funnel interface to a commercial triple quadrupole mass spectrometer. Due to the increased efficiency in ion transmission, significantmore » enhancements in overall signal intensities and improved limits of detection were observed with the new interface compared to the original (capillary/skimmer) interface for SRM measurements of tryptic peptides from proteins spiked into non-depleted mouse plasma over a range of concentrations. Overall, average SRM peak intensities were increased by ~70-fold. The average level of detection for peptides also improved by ~14-fold, with notably improved reproducibility of peptide measurements as indicated by the reduced coefficients of variance. The ability to detect proteins ranging from 40 to 80 ng/mL within mouse plasma was demonstrated for all spiked proteins without the application of front-end immunoaffinity depletion and fractionation. This significant improvement in detection sensitivity for low-abundance proteins in complex matrices is expected to enhance a broad range of SRM-MS applications in addition to targeted protein and metabolite validation.« less
  • 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 populationmore » to the mass analyzer. Ion beam regulation by an ion funnel is shown to provide an unbiased 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 a variety of different levels, which improved data quality and provided better mass measurement accuracy.« less