The hope of achieving high performance identification of ionic species using ion mobility drift tubes coupled with time of flight mass spectrometers has long been held by those skilled in the art. The general concept has been known since at least the publication of the paper entitled “Ion Mobility/Mass Spectrometric Investigation of Electrospray Ions” by R. Guevremont, K. W. M. Siu, and L. Ding in the Proceedings of the 44th ASMS Conference, p. 1090 (1996). This paper, and all other papers and patents identified herein are hereby explicitly incorporated into this disclosure by this reference. The concept was again published in the paper “Combined ion mobility/time-of-flight mass spectrometry study of electrospray-generated ions. Anal. Chem. 69, 3959 (1997). The concept was again described in the patent literature in May of 1999, when U.S. Pat. No. 5,905,258 titled “Hybrid ion mobility and mass spectrometer” issued to David E. Clemmer, et al.
While the general concept of such systems has thus long been recognized, those having skill in the art have also recognized limitations associated with the technique when put into practice. One approach towards achieving the objective of increased sensitivity in ion mobility spectrometry/mass spectrometry (IMS/MS) instruments is described in U.S. Patent Application Pub No. 2001/0032929A1 by Fuhrer et al. wherein improvements in sensitivity are claimed as a result of preserving a narrow spatial distribution of migrating ions through the use of periodic/hyperbolic field focusing. Variations on the general IMS/MS concept are shown in U.S. Pat. No. 6,323,482 filed May 17, 1999, granted Nov. 27, 2001, “Ion mobility and mass spectrometer” which shows the use of collision cell in an IMS/time of flight MS hybrid system and various means to incorporate the collision cell into such instrumentation. Further variations are also shown in U.S. Pat. No. 6,498,342 filed Jul. 13, 2000, granted Dec. 24, 2002 “Ion separation instrument” which introduces the liquid-phase separation (such as liquid chromatography) prior to IMS/time of flight MS or a tandem IMS/time of flight MS system. Finally, U.S. Pat. No. 6,559,441 filed Feb. 12, 2002, granted May 6, 2003 “Ion separation instrument” details various conceivable versions of tandem IMS, e.g. use of different buffer gases and/or different temperatures.
Despite these and other improvements, problems associated with loss of ions in ion mobility spectrometer (IMS) drift tubes have continued to prevent IMS/MS systems from reaching their full potential as analytical instruments. Rather, other systems with much slower separations times, but lower ion losses, such as liquid chromatography mass spectrometry (LC/MS), have prevailed despite the sample analysis “throughput” reductions associated with such systems. The problem of excessive ion losses in IMS/MS systems is well known by those having skill in the art, and has repeatedly been identified in the literature by numerous researchers active in the field. For example, in the paper titled “Gas-phase separations of complex tryptic peptide mixtures” published in Fresenius J. Anal. Chem. 369, 234 (2001), by J. A. Taraszka, A. E. Counterman and D. E. Clemmer, in the sentence bridging pages 242 and 243, the authors described one aspect of the problem thusly: “Currently one stumbling block associated with high-resolution instruments is that most signal (˜99-99.9%) is discarded when the short pulse of ions is introduced into the drift tube.” In the paper titled “Multidimensional separations of complex peptide mixtures: a combined high performance liquid chromatography/ion mobility/time-of-flight mass spectrometry approach” published in Intern. J. Mass Spectrom. 212, 97 (2001), by S. J. Valentine, M. Kulchania, C. A. Srebalus Barnes, and D. E. Clemmer, at the final paragraph on page 108, the authors again recognize difficulties with the technique stating: “It is typical to discard 99-99.9% of the ion signal during the mobility experiment [34]; thus, these experiments are inherently less sensitive than conventional LC-ESI-MS methods.” Yet another paper in the literature identifying the problem is entitled “Coupling ion mobility separations, collisional activation techniques, and multipole stages of MS for analysis of complex peptide mixtures”, Anal. Chem. 74, 992 (2002), by C. S. Hoaglund-Hyzer, Y. J. Lee, A. E. Counterman, and D. E. Clemmer. At page 1005, the authors state: “We also note that although improvements in sensitivity have been demonstrated, the current technologies are still not as sensitive as the well-developed MS/MS strategies; however we believe that much of this difference will be diminished as additional improvements in the instruments are made. Finally, other authors, including Russell and coworkers active in the field at Texas A&M University, have repeatedly pointed out the need for much better IMS/MS sensitivity.
Thus, there remains a need for methods and apparatus that enable increased sensitivity in ion mobility spectrometry/mass spectrometry (IMS/MS) instruments and which substantially reduces the loss of ions in ion mobility spectrometer (IMS) drift tubes.