Radiant energy – Ionic separation or analysis – Cyclically varying ion selecting field means
Reexamination Certificate
2000-06-02
2003-01-28
Anderson, Bruce (Department: 2881)
Radiant energy
Ionic separation or analysis
Cyclically varying ion selecting field means
C250S282000, C250S287000, C250S288000, C250S42300F
Reexamination Certificate
active
06512226
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to a mass spectrometer, and more particularly relates to collision-induced dissociation (CID) in a tandem mass spectrometer or in an ion guide.
BACKGROUND OF THE INVENTION
Radio frequency (RF) only multipole spectrometers, more particularly quadrupole spectrometers, are widely applied in mass spectrometry and nuclear physics, due to their ability to transport ions with minimal losses. During such transportation of the ions, the initial ion positions and velocities change, but the total phase space volume occupied by the ion beam remains constant (see Dawson, Quadrupole mass spectrometry and its applications). However, if a buffer gas is introduced into the ion guide, a dissipative process occurs, due to ion molecule collisions, and this enables an ion beam to be focused onto the quadrupole axis after the initial velocities have been damped.
Collisional quadrupole or other multipole devices have been used as an ion guide providing an interface between an ion source and a mass spectrometer, or alternatively as a collision cell for collision-induced dissociation (CID) experiments. As a straightforward interface, collisional damping reduces the space and velocity distributions of the ions leaving the ion source, thus improving the beam quality. For CID experiments, primary ions having relatively large velocities enter the multipole and collide with buffer gas molecules, so collision-induced dissociation takes place. The multipole helps to keep both primary ions and fragment ions, resulting from the collision-induced dissociation, close to the axis and to deliver them to the exit for further analysis. Collisions inside the multipole spectrometer again act to reduce the space and velocity distribution of the ion beam.
Ion motion in a perfect quadrupole field is governed by Mathieu's equation (See Dawson as cited above); ions oscillate around the quadrupole axis at an appropriate fundamental frequency which is determined by their m/z and quadrupole parameters, and is independent of ion position and velocity. If the frequency of any periodic forces acting on ions coincides with the ion fundamental frequency, then resonance excitation takes place. Similar resonance excitation is widely applied in quadrupole ion trap or in ion cyclotron resonance mass spectrometers (R. E. March, R. J. Hughes, Quadrupole storage mass spectrometry, 1989, John Wiley & Sons).
These properties of spectrometers have been employed in many ways. Thus, in U.S. provisional patent application No. 60/046,926 filed May 16, 1997, there is disclosed a high pressure MS-MS system. This was intended to provide improvements to a conventional triple quadrupole mass spectrometer arrangement, employing two precision quadrupole mass spectrometers separated by an RP-only quadrupole which is operated as a gas collision cell. The first mass spectrometer is used to select a specific ion mass-to-charge ratio (m/z), and to transmit the selected ions into the RF-only quadrupole or collision cell. In the RF-only quadrupole collision cell, some or all of the parent ions are fragmented by collisions with the background gas, commonly argon or nitrogen, at a pressure of up to several millitorr. The fragment ions, along with any unfragmented parent ions are then transmitted into the second precision-quadrupole which is operated in a mass resolving mode. Usually, the mass resolving mode of this second spectrometer is set to scan over a specified mass range, or else to transmit selected ion fragments by peak hopping, i.e. by being rapidly adjusted to select specific ion m/z ratios in sequence. The ions transmitted through this spectrometer are detected by an ion detector. A problem with this conventional arrangement is that the two mass resolving quadrupoles are required to operate in the high vacuum region (less than 10
−5
torr), while the intermediate collision cell operates at a pressure up to several millitorr. That earlier invention was intended to simplify the apparatus and eliminate the necessity for separate RF-only and resolving spectrometers at the input to the apparatus. Instead, a single quadrupole is provided, operating in the RF-mode to act as a high pass filter. Additionally, this quadrupole is provided with an AC field, which can be identified as a “filtered noise field”, which contains a notch in the frequency range corresponding to the mass of an ion of interest. This notch can be moved, to select and separate desired ions.
Other older proposals can be found, for example, in U.S. Pat. No. 5,420,425 (Bier et al. and assigned to Finnigan Corporation). This relates to an ion trap mass spectrometer, for analyzing ions. It has electrodes shaped to promote an enlarged ion occupied volume. A quadrupole field is provided to trap ions within a predetermined range of mass to charge ratios. Then, the quadrupole field is changed so that trapped ions with specific masses become unstable and leave the trapping chamber in a direction orthogonal to the central axis of the chamber. The ions leaving the spectrometer are detected, to provide a signal indicative of their mass-to-rations. One method that is taught in this patent is to first introduce ions within a predetermined range of mass-to-charge ratios into the chamber and subsequently change the field to select just some ions for further manipulation. The quadrupole field is then adjusted so as to be capable of trapping product ions of the remaining ions, and the remaining ions are then dissociated or reacted with a neutral gas to form those product ions. Subsequently, the quadrupole field is changed again, to remove, for detection, ions whose mass-to-charge ratios lie within the desired range, which ions are then detected.
The first technique taught above is complex, and requires a number of separate quadrupoles or the like, and the ability to move the ions sequentially through the different quadrupole sections. The technique taught in the Finnigan patent is complex and requires a number of steps. Also, it is concerned with ion traps and not a flow quadrupole. Accordingly, it is desirable to provide one technique which, in one device, readily enables ions of a selected mass-to-charge ratio to be subject to collision-induced-dissociation (CID) or fragmentation, so that the fragments can be transported further for subsequent analysis. It is desirable to provide this in a single device, since movement of ions from one device to another inevitably leads to some losses. Similarly, the techniques of the Finnigan patent work with pulse ion sources, but attempts to use them for continuous ion flow, for instance from an electrospray ion source, will lead to inefficiencies. In this field, spectrometers are frequently used to analyze small samples, and often, high efficiency is required, if any reliable reading or measurement is to be obtained.
A further proposal is found is published European patent application 0529885, to the assignee of the present invention. This discloses a multipole inlet system for ion traps. They both suggest the possibility of ejecting unwanted ions by resonant ejection, and also exciting ions by excitation at their lowest or other resonant frequencies sufficiently to cause collision-induced dissociation.
SUMMARY OF THE PRESENT INVENTION
In accordance with a first aspect of the present invention, there is provided a method of analyzing a substance, the method comprising the steps of:
(1) ionizing the substance to generate a stream of ions;
(2) supplying the stream of ions to a quadrupole ion guide;
(3) providing a buffer gas in the ion guide;
(4) applying a radio frequency field by the quadrupole ion guide to maintain desired ions in a stable trajectory through the ion guide;
(5) in addition to the radio frequency field applied in step (4), applying a periodic change to the ion guide to cause resonance excitation of ions having a selected m/z ratio whereby the selected ions acquire increased kinetic energies resulting in enhanced collision-induced dissociation with the buffer gas;
(6) applying at least one additi
Ens Werner
Krouttchinskikh Andrei
Loboda Alexandre V.
Spicer Victor
Standing Kenneth
Anderson Bruce
Devinsky Paul
McDermott & Will & Emery
University of Manitoba
Wells Nikita
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