Multipole ion guide

Radiant energy – Ionic separation or analysis – Cyclically varying ion selecting field means

Reexamination Certificate

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C250S288000

Reexamination Certificate

active

06797948

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates generally to methods and devices for the transportation of ions through one or more pumping stages of a mass spectrometer. More specifically, an apparatus is described which facilitates the separation of neutral gas molecules from ions and passes the ions through one or more pumping stages or regions of a mass spectrometer. Further, the present invention may be used in an apparatus for selecting and/or transporting ions and charged droplets generated from an API source (e.g., Electrospray or Atmosphere Pressure Chemical Ionization, etc.) through a differential pumping region or regions for analysis in a mass spectrometer.
BACKGROUND OF THE PRESENT INVENTION
The present invention relates to multipole ion guides for use in mass spectrometry. The apparatus and methods for ionization described herein are enhancements of the techniques that are referred to in the literature relating to mass spectrometry.
Mass spectrometry plays an important role in the analysis of chemical compounds. Specifically, mass spectrometers are useful in determining the molecular weight of sample compounds. Analyzing samples using mass spectrometry consists of three steps—formation of gas phase ions from sample material, mass analysis of the ions to separate the ions from one another according to ion mass, and detection of the ions. Several methods exist in the field of mass spectrometry to perform each of these three functions. The certain combination of means used in a particular spectrometer determines that spectrometer's characteristics.
Mass analysis, for example, can be performed through magnetic (B) or electrostatic (E) analysis. Ions passing through a magnetic or electrostatic field follow a curved path. The path's curvature in a magnetic field indicates the momentum-to-charge ratio of the ion. In an electrostatic field, the curvature of the path will be indicative of the energy-to-charge ratio of the ion. Using magnetic and electrostatic analyzers consecutively determines the momentum-to-charge and energy-to-charge ratios of the ions, and the mass of the ion will thereby be determined. Other mass analyzers are the quadrupole (Q), the ion cyclotron resonance (ICR), the time-of-flight (TOF), and the quadrupole ion trap analyzers. The analyzer, which accepts ions from the ion guide described here, may be any of a variety of these.
Before mass analysis can begin, however, gas phase ions must be formed from sample material. If the sample material is sufficiently volatile, ions may be formed by electron ionization (EI) or chemical ionization (CI) of the gas phase sample molecules. For solid samples (e.g. semiconductors, or crystallized materials), ions can be formed by desorption and ionization of sample molecules by bombardment with high energy particles. Secondary ion mass spectrometry (SIMS), for example, uses keV ions to desorb and ionize sample material. In the SIMS process a large amount of energy is deposited in the analyte molecules. As a result, fragile molecules will be fragmented. This fragmentation is undesirable in that information regarding the original composition of the sample—e.g., the molecular weight of sample molecules—will be lost.
For more labile, fragile molecules, other ionization methods now exist. The plasma desorption (PD) technique was introduced by Macfarlane et al. in 1974 (Macfarlane, R. D.; Skowronski, R. P.; Torgerson, D. F.,
Biochem. Biophys. Res Commoun.
60 (1974) 616). Macfarlane et al. discovered that the impact of high energy (MeV) ions on a surface, like SIMS would cause desorption and ionization of small analyte molecules, however, unlike SIMS, the PD process results also in the desorption of larger, more labile species e.g., insulin and other protein molecules.
Lasers have been used in a similar manner to induce desorption of biological or other labile molecules. See, for example, VanBreeman, R. B.: Snow, M.: Cotter, R. J.,
Int. J. Mass Spectrom. Ion Phys.
49 (1983) 35; Tabet, J. C.; Cotter, R. J.,
Anal. Chem.
56 (1984) 1662; or Olthoff, J. K.; Lys, I.: Demirev, P.: Cotter, R.;
J., Anal. Instrument.
16 (1987) 93. Cotter et al. modified a CVC 2000 time-of-flight mass spectrometer for infrared laser desorption of involatile biomolecules, using a Tachisto (Needham, Mass.) model 215G pulsed carbon dioxide laser. The plasma or laser desorption and ionization of labile molecules relies on the deposition of little or no energy in the analyte molecules of interest. The use of lasers to desorb and ionize labile molecules intact was enhanced by the introduction of matrix assisted laser desorption ionization (MALDI) (Tanaka, K.; Waki, H.; Ido, Y.; Akita, S.; Yoshida, Y.; Yoshica, T.,
Rapid Commun. Mass Spectrom.
2 (1988) 151 and Karas, M.; Hillenkamp, F.,
Anal. Chem.
60 (1988) 2299). In the MALDI process, an analyte is dissolved in a solid, organic matrix. Laser light of a wavelength that is absorbed by the solid matrix but not by the analyte is used to excite the sample. Thus, the matrix is excited directly by the laser, and the excited matrix sublimes into the gas phase carrying with it the analyte molecules. The analyte molecules are then ionized by proton, electron, or cation transfer from the matrix molecules to the analyte molecules. This process, MALDI, is typically used in conjunction with time-of-flight mass spectrometry (TOFMS) and can be used to measure the molecular weights of proteins in excess of 100,000 daltons.
Atmospheric pressure ionization (API) includes a number of methods. Typically, analyte ions are produced from liquid solution at atmospheric pressure. One of the more widely used methods, known as electrospray ionization (ESI), was first suggested by Dole et al. (M. Dole, L. L. Mack, R. L. Hines, R. C. Mobley, L. D. Ferguson, M. B. Alice,
J. Chem. Phys.
49, 2240, 1968). In the electrospray technique, analyte is dissolved in a liquid solution and sprayed from a needle. The spray is induced by the application of a potential difference between the needle and a counter electrode. The spray results in the formation of fine, charged droplets of solution containing analyte molecules. In the gas phase, the solvent evaporates leaving behind charged, gas phase, analyte ions. Very large ions can be formed in this way. Ions as large as 1 MDa have been detected by ESI in conjunction with mass spectrometry (ESMS).
For example,
FIG. 1
depicts a conventional mass spectrometer using an ESI ion source. Ions are produced from sample material in an ionization chamber
104
. Sample solution enters the ionization chamber through a spray needle
105
, at the end of which the solution is formed into a spray of fine droplets
111
. The spray is formed as a result of an electrostatic field applied between the spray needle
105
and a sampling orifice
107
. The sampling orifice may be an aperture, capillary, or other similar inlet leading into the vacuum chambers (
101
,
102
&
103
) of the mass spectrometer. Electrosprayed droplets evaporate while in the ionization chamber thereby producing gas phase analyte ions. In addition, heated drying gas may be used to assist the evaporation of the droplets. Some of the analyte ions are carried with the gas from the ionization chamber
104
through the sampling orifice
107
and into the vacuum system (comprising vacuum chambers
101
,
102
&
103
) of the mass spectrometer. With the assistance of electrostatic lenses and/or prior art RF driven ion guides
109
, ions pass through a differential pumping system (which includes vacuum chambers
101
,
102
&
103
and lens/skimmer
108
) before entering the high vacuum region
1
wherein the mass analyzer (not shown) resides. Once in the mass analyzer, the ions are mass analyzed to produce a mass spectrum.
Many other ion production methods might be used at atmospheric or elevated pressure. For example, MALDI has recently been adapted by Victor Laiko and Alma Burlingame to work at atmospheric pressure (Atmospheric Pressure Matrix Assisted Laser Desorption Ionization, poster #1121, 4
th
International Sym

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