Apparatus and method for analyzing samples in a dual ion...

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

Reexamination Certificate

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C250S287000, C250S288000

Reexamination Certificate

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06627883

ABSTRACT:

TECHNICAL FIELD OF THE INVENTION
The present invention relates generally to an apparatus and method for a dual ion trap mass spectrometer. More specifically, an apparatus is described which, using a dual ion trap system, analyzes parent ion masses, by temporarily trapping ions generated by an ion source in a first ion trap and gating the sample ions into an analytical multipole for selection. Once selected, the ions of interest are then transported into a second ion trap, which is preferably a collision chamber, to undergo fragmentation. The fragmented ions are then forced out of the collision chamber for mass analysis in, for example, a time-of-flight mass spectrometer.
BACKGROUND OF THE PRESENT INVENTION
The present invention relates to a dual ion trap apparatus for use in a mass spectrometer, and a method for its use in mass analysis of sample ions. The apparatus and method for analyzing sample ions described herein are enhancements of the techniques that are referred to in the literature relating to mass spectrometry. Mass spectrometry is a systematic method that involves the analysis of gas-phase ions produced from a particular sample. The produced ions are then separated according to their mass-to-charge ratio. This separation process is similar to the dispersion of light through a prism according to the wavelength. Since the behavior of charged particles in electric and magnetic field is known, the sample ions' trajectories can be measured, and the ions' respective mass can be determined. For example, a magnetic sector analyzer subjects ions to a magnetic field which disperses the ions according to their mass-to-charge ratio.
Mass spectrometry plays an important role in determining the molecular weight of sample chemical compounds. Analyzing samples using mass spectrometry consists of three steps—formation of gas phase ions from sample material, separation and analysis of ions according to ion mass, and detection of the ions. There are several methods in which mass spectrometry can be performed.
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 bio-molecules, 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 action 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).
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 Symposium on Mass Spectrometry in the Health and Life Sciences, San Francisco, Aug. 25-29, 1998) and by Standing et al. at elevated pressures (Time of Flight Mass Spectrometry of Biomolecules with Orthogonal Injection+Collisional Cooling, poster #1272, 4
th
International Symposium on Mass Spectrometry in the Health and Life Sciences, San Francisco, Aug. 25-29, 1998; and Orthogonal Injection TOFMS
Anal Chem.
71(13), 452A (1999)). The benefit of adapting ion sources in this manner is that the ion optics and mass spectral results are largely independent of the ion production method used.
An elevated pressure ion source always has an ion production region (wherein ions are produced) and an ion transfer region (wherein ions are transferred through differential pumping stages and into the mass analyzer). The ion production region is at an elevated pressure—most often atmospheric pressure—with respect to the analyzer. The ion production r

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