Radiant energy – Ionic separation or analysis – Cyclically varying ion selecting field means
Reexamination Certificate
2000-10-18
2003-05-27
Berman, Jack (Department: 2881)
Radiant energy
Ionic separation or analysis
Cyclically varying ion selecting field means
C250S282000
Reexamination Certificate
active
06570153
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates generally to apparatus and methods for performing mass spectrometric analyses of material samples and, in particular, to tandem mass spectrometers and mass spectrometric methods for detecting molecular ions and fragments of molecular ions.
Mass spectrometry is an analytical methodology used for qualitative and quantitative chemical analysis of materials and mixtures of materials. In mass spectrometry, a sample of a material to be analyzed called an analyte is broken into electrically charged particles of its constituent parts in an ion source. Once produced, the analyte particles are separated by the spectrometer based on their respective mass-to-charge ratios. The separated particles are then detected and a mass spectrum of the material is produced. The mass spectrum is analogous to a fingerprint of the sample material being analyzed. The mass spectrum provides information about the masses and, in some cases, quantities of the various analyte particles that make up the sample and to some extent molecular structure. In particular, mass spectrometry can be used to determine the molecular weights of molecules and molecular fragments of an analyte. Additionally, mass spectrometry is used to identify molecular structure and components that form the structure within the analyte based on the fragmentation pattern when the bonds of the molecules are dissociated. Mass spectrometry has proven to be a very powerful analytical tool in material science, chemistry and biology along with a number of other related fields.
For structure determination of large biomolecules, a technique called tandem mass spectrometry (often referred to as tandem MS or MS/MS) is particularly important and such an instrument was disclosed by R. A. Yost, et al., (1978) J. Am. Chem. Soc., page 2274. A conventional tandem mass spectrometer requires two mass analyzers in series. In a tandem mass spectrometer, certain molecular ions, or so-called parent ions or precursors created from a sample, are selected by the first mass analyzer. The precursors are sent into a collision cell which contains an inert gas (helium, nitrogen, argon or xenon, etc) of pressure in the range of about 10
−1
to 10
−3
torr. In the collision cell, precursors undergo collision with the inert gas and become fragmented based on collisional induced dissociation (CID). The fragment ions, or so-called daughter ions, are then analyzed by the second mass analyzer. Tandem MS provides structural information of the biomolecules by establishing relationship between the precursor ions and their fragmentation products. Tandem mass spectrometry in combination with fragmentation based on collisional induced dissociation has been successful for sequencing peptides, proteins, DNA's, RNA's and other biomolecules. Another proven application of tandem MS is in the study of drug metabolism pharmacokinetics (DMPK). A discussion of this technique can be found in a publication of Fernandez-Metzler, et al.,
Drug Metab. Dispo
. (1999) 27:32. In such application, quantitation of the sample with high sensitivity and high dynamic range is achieved because most chemical interferences are eliminated by the first precursor selection.
Conventional tandem mass spectrometers have been developed using a combination of the same type of mass analyzers, such as tandem quadrupole MS developed by Morrison, et al.,
Proc
. 34
th
Annual Conf. Mass Spectrom. Allied Topics
, 1986, page 222, tandem magnetic field MS published by McLafferty (ed.) in “Tandem Mass Spectrometry,” Wiley, New York (1983) and tandem time-of-flight MS (TOFMS) disclosed in U.S. Pat. Nos. 5,032,722 and 5,202,563. Other tandem mass spectrometers involve two different types of mass analyzers (hybrid tandem MS). Such instruments include, for instance, combinations of magnet field MS with TOFMS by Strobel, et al.,
J. Am. Soc. Mass Spectrom
. (1991), 2:91-94, quadrupole MS with TOFMS (Q-TOF) by Glish, et al.,
Anal. Instrum
. (1987), 16:191-206, and ion trap with TOFMS by Michael, et al.,
Anal. Chem
. (1993) 65:2614-2620.
It should be noted that, in the prior art as mentioned above, a minimum number of two mass analyzers are required to perform tandem mass spectrometry operation. In some cases, more than two mass analyzers are needed. Discussions about the fundamental aspects of tandem mass spectrometry can also be found in more detail in McLafferty (1981)
Science
214:280-287 and Kondrat and Cooks (1978)
Anal. Chem
. 50:81A-92A.
A molecule collision cell is an important part of a tandem mass spectrometer. In collisional induced dissociation (CID), a radio frequency (RF) multipole ion guide is often used as a collision cell. When molecular ions or precursors are sent into a RF multipole field, these ions are forced to oscillation due to alternated potential field inside the multipole. At the same time, the molecular ions or precursors collide with the background gas (normally a neutral inert gas), a portion of the translation energy of the ions converts into activation energy that is sufficiently high enough and certain molecular bonds are broken. In tandem MS, the multipole ion guide is placed between two mass spectrometers. The major functions of a collision cell are generation of desirable fragments from the complex molecular ions or precursors as well as to confine both the parent ions and their fragment daughters.
2. Brief Description of Related Art
U.S. Pat. No. 4,234,791 (Enke, et al.) discloses a tandem quadrupole mass spectrometer for selected ion fragmentation studies and low energy collision induced dissociator therefor.
U.S. Pat. No. 6,011,259 (Whitehouse, et al.) discusses multipole ion guide ion trap mass spectrometry with MS/MS
N
analysis.
SUMMARY OF THE INVENTION
One embodiment of the present invention is a mass spectrometry apparatus comprising a single quadrupole mass analyzer having a first end opposite a second end. A source of charged particles is adjacent the first end of the quadrupole mass analyzer and a gate for controlling passage of charged particles is present between the source of charged particles and the first end. The apparatus further comprises a first element between the gate and the first end, a second element adjacent the second end, and a detector for detecting charged particles, or fragments thereof, exiting the quadrupole mass analyzer.
Another embodiment of the present invention is a mass spectrometry apparatus comprising a single quadrupole mass analyzer having a first end opposite a second end. An ion source is adjacent the first end of the quadrupole mass analyzer and an ion gate is present between the ion source and the first end. The apparatus further comprises a first element between the ion gate and the first end, a second element adjacent the second end, and an ion detector for detecting ions, or fragments thereof, exiting the quadrupole mass analyzer.
Another embodiment of the present invention is a mass spectrometry apparatus comprising a single quadrupole mass analyzer having a first end opposite a second end, an ion source adjacent the first end, and an ion gate between the ion source and the first end. A first ion detector is adjacent the ion gate and offset with respect to the optical axis of the quadrupole mass analyzer. A second ion detector is adjacent the second end. An ion deflector lies between the ion source and the first end. The apparatus further comprises an element adapted to generate an oscillating field and two electrodes adjacent opposite ends of the element. Each of the electrodes is independently connected to a source of electrical activation.
Another embodiment of the present invention is a mass spectrometry apparatus comprising a single quadrupole mass analyzer having a first end opposite a second end. An ion source and a first set of electrodes are adjacent the first end. The electrodes are disposed with respect to each other to form a space therebetween. Each of the electrodes is independently adapted to receive a voltage. A second set of
Li Gangqiang
Yin Hongfeng
Agilent Technologie,s Inc.
Berman Jack
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