Radiant energy – Ionic separation or analysis – Cyclically varying ion selecting field means
Reexamination Certificate
2002-01-30
2004-03-23
Lee, John R. (Department: 2881)
Radiant energy
Ionic separation or analysis
Cyclically varying ion selecting field means
Reexamination Certificate
active
06710336
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates generally to mass spectrometers, and more particularly the invention relates to ion traps for ion isolation and collision induced dissociation (CID) in mass spectrometers.
Mass spectrometers are well-known scientific instruments for analyzing chemical structures. A mass spectrometer includes an ion source, an ion filter, and an ion detector. Gas at low pressure is introduced into the ion source which ionizes the gas. Ions are then selected by the ion filter and passed to the ion detector. The ion filter selects ions having a particular m/e ratio which may be varied to analyze the gas.
U.S. Pat. No. 4,736,101 describes a quadrupole technique called MS/MS which includes the steps of forming and storing ions having a range of masses in an ion trap, mass selecting among them to select an ion of particular mass to be studied (parent ion), dissociating the parent ion by collisions, and analyzing or separating and ejecting the fragments (daughter ions) to obtain a mass spectrum of the daughter ions. To isolate an ion for purposes of MS/MS, a method of scanning or ramping up an RF trapping field voltage according to known equations ejects ions having atomic mass up to the m/e of the ion of interest. Then, the RF trapping field voltage is lowered and the ions remaining are dissociated by collision. Finally, the RF trapping voltage is scanned up again and a mass spectrogram of the ejected daughter ions is obtained. One technique of obtaining CID to obtain daughter ions is to employ a second fixed frequency generator connected to the endplates of the quadrupole ion trap which frequency is at the calculated secular frequency of the retained ion being investigated. The secular frequency is the frequency in which the ion is periodically, physically moving within the RF trapping field.
FIG. 1
illustrates a quadrupole ion trap as described in U.S. Pat. No. 5,198,665. The quadrupole ion trap
1
employs a ring electrode
2
of hyperbolic configuration which is connected to a radio frequency trapping field generator
7
. A digital to analog converter (DAC)
10
is connected to the RF trapping field generator
7
for controlling the amplitude of the output voltage
11
. Hyperbolic end caps
3
and
3
′ are connected to coil
4
of a coupling transformer
8
having a center tap
9
connected to ground. The transformer
8
secondary winding is connected to a fixed frequency generator
5
and to a fixed broadband spectrum generator
6
. Controller
12
is connected to digital to analog converter (DAC)
10
via connector
18
and the three generators
5
,
6
and
7
via connectors
13
,
14
and
19
respectively, to manage the timing of the quadrupole ion trap sequences.
As described above, MS/MS procedures require two steps including (1) precursor mass isolation, and (2) collision induced dissociation or CID. Mass isolation is accomplished by the method illustrated in the waveforms of
FIG. 2
, which are described in detail in U.S. Pat. No. 5,198,665, supra, with the addition of a notched waveform as shown in
FIG. 3
that is applied during the ionization step and for a short “cool time” after the end of ionization. Undesired ion masses are energized by the waveform and removed from the ion trap. However, the notch (i.e., a frequency range) in which there are no frequencies of significant intensity, does not energize the ions of interest which remain in the ion trap. After the unenergized ion is mass isolated, the RF trapping field is lowered to allow the trapping of product ions formed from CID, and a waveform is applied at the secular frequency of the ion to effect CID.
There are many ways of optimizing and phasing multifrequency notched waveforms that are known in the art. U.S. Pat. No. 5,324,939 requires calculation of the entire waveform. U.S. Pat. No. 5,449,905 calculates the frequencies within the notch of the waveform and are then subtracted from a waveform containing no notches. U.S. Pat. No. 5,134,286 filters a base broadband noise waveform to remove a selected range of frequencies. In all of these prior art methods multiple discrete frequencies have to be calculated and summed with the appropriate phasing and amplitude to produce the final waveform. Further, the intensity of each frequency component to be summed must be calculated at each data point comprising the waveform. For example, a multifrequency waveform having a frequency range from 5 kHz to 500 kHz requires 5,000 data points clocked out at 2.5 mHz. This represents 5 points per cycle at 500 kHz, which is sufficient to meet the Nyquist requirement to prevent frequency aliasing. A total of 990 frequencies, spaced 500 Hz apart, can be in this waveform. If an intensity at each data point must be calculated for each frequency component, then a total of 4,950,000 intensities must be calculated and appropriately summed to produce the final waveform. Each calculation is of the form of a trigonometric function, which converges slowly when digitally calculated.
SUMMARY OF THE INVENTION
The present invention provides an improved quadrupole ion trap in a mass spectrometer by including a library of optimized notched waveforms stored in computer memory which can be selectively accessed and applied to isolate desired ions for analysis. The library can include second waveforms for use in CID after the precursor mass is isolated.
The secular frequency of a particular ion can be adjusted to match the central frequency of a pre-calculated waveform by adjusting a trapping parameter, such as RF voltage amplitude.
Thus the apparatus and method in accordance with the invention can present the required conditions to isolate a specified ion mass and then cause CID without the need to recalculate the waveforms needed to effect ion mass isolation and CID.
The invention and objects and features thereof will be more readily apparent from the following detailed description and appended claims when taken with the drawings.
REFERENCES:
patent: 4736101 (1988-04-01), Syka et al.
patent: 5134286 (1992-07-01), Kelley
patent: 5198665 (1993-03-01), Wells
patent: 5302826 (1994-04-01), Wells
patent: 5324939 (1994-06-01), Louris et al.
patent: 5448061 (1995-09-01), Wells
patent: 5449905 (1995-09-01), Hoekman et al.
patent: 5521380 (1996-05-01), Wells et al.
patent: 5640011 (1997-06-01), Wells
patent: 5696376 (1997-12-01), Doroshenko et al.
patent: 5793038 (1998-08-01), Buttrill, Jr.
patent: 0 575 778 (1993-12-01), None
Shenheng G et al., entitled “Storged Waveform Inverse Fourier Transform (SWIFT) Ion Excitation in Trapped-Ion Mass Spectrometry: Theory and Applications” published by International Journal of Mass Specrometry and IOn Processes, 157/158 (1996). 5-37.
Article by Raymond March, entitled “An Introduction to Quadrupole Ion Trap Mass Spectrometry”, published by Journal of Mass Spectrometry, vol. 32, pp. 351-369 (1997).
Berkowitz Edward H.
Fishman Bella
Kalivoda Christopher M.
Lee John R.
Varian Inc.
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