|Publication number||USRE40632 E1|
|Application number||US 11/073,394|
|Publication date||Feb 3, 2009|
|Filing date||Mar 4, 2005|
|Priority date||Dec 3, 1999|
|Also published as||CA2327135A1, CA2327135C, DE60045470D1, EP1109198A2, EP1109198A3, EP1109198B1, EP2302660A1, US6528784|
|Publication number||073394, 11073394, US RE40632 E1, US RE40632E1, US-E1-RE40632, USRE40632 E1, USRE40632E1|
|Inventors||Keqi Tang, Jean-Jacques Dunyach, Alan E. Schoen|
|Original Assignee||Thermo Finnigan Llc.|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (65), Non-Patent Citations (99), Referenced by (8), Classifications (16), Legal Events (4)|
|External Links: USPTO, USPTO Assignment, Espacenet|
Notice: More than one reissue application has been filed for the reissue of U.S. Pat. No. 6,528,784; the reissue applications are application Ser. No. 11/073,394 (the present application filed on Mar. 4, 2005 ), and application Ser. No. 12/330,902, filed Dec. 9, 2008, which is a continuation of the present reissue application Ser. No. 11/073,394.
This application is a continuation-in-part-of- and claims priority to pending application Ser. No. 09/454,273 filed Dec. 3, 1999 now abandoned.
This invention relates generally to mass spectrometry, and more particularly to mass spectrometers employing atmospheric pressure ion sources such as electrospray or atmospheric pressure chemical ionization. More particularly, the invention relates to the use of two consecutive ion guides between the ion source and the mass analyzer to dissociate adduct ions, thus increasing the ion current for the analytically useful molecular species.
Generally, the interface between the atmospheric pressure ion source and the mass analyzer includes a capillary tube or other restrictive aperture which determines ion and gas throughput between the atmospheric pressure ionization region and a lower pressure region. The ions are drawn through the capillary or other restrictive aperture and directed to a downstream conical skimmer with a small aperture through which the sample ions flow. A tube lens or other electrostatic or electrodynamic focusing element may be associated with the capillary to force ions to the center of the jet stream leaving the capillary to thereby increase the ion transmission through the aperture of the skimmer. Reference is made to U.S. Pat. No. 5,157,260 which describes the operation of an atmospheric pressure ionization source, capillary lens and conical skimmer. One or more vacuum stages are interposed between the skimmer and the mass analyzer which is operated at vacuum pressures in the free molecular flow region.
The prior art interface vacuum stages have included ion guides to transfer the ions through the stages of decreasing pressure into the mass analyzer. In many prior art systems, the ions are guided by electrostatic lenses. In other systems, the ions are guided by electrodynamic multipole ion guides.
The use of an r.f.-only octopole ion guide for focusing and guiding ion beams has been described by Teloy and Gerlich (Chem. Phys., Vol. 4, p. 417, 1974) and Jarrold et. al. (Mol. Phys., Vol. 39, p. 787, 1980).
The dissociation of mass-selected ions in an r.f.-only quadrupole by collision with a target gas at low translational energies (Elab<about 100 eV) has been described by R. A. Yost and C. G. Enke et. al. (Anal. Chem., Vol. 51, p. 1251a, 1979), and Dawson et. al. (Int. J. Mass Spec. Ion Proc., Vol. 42, p. 195, 1982).
McIver et. al. described the use of an r.f.-only quadrupole ion guide for guiding a beam of mass-selected ions into a Fourier-transform ion cyclotron resonance mass analyzer (Int. J. Mass Spec. Ion Proc., Vol. 64, p. 67, 1985).
Szabo described the theory of operation for multipole ion guides with various electrode structures (Int. J. Mass Spec. Ion Proc., Vol. 73, pp. 197-312, 1986).
Efficient transport of ions through vacuum chambers by multipole ion guides has been described by Smith et. al. (Anal. Chem., Vol. 60, pp. 436-441, 1988).
Beu et. al. described the use of three quadrupole ion guides to transport ions from an atmospheric pressure ionization source through three vacuum pumping stages into a Fourier-transform ion cyclotron resonance mass analyzer (J. Am. Soc. Mass Spec., Vol. 4, pp. 557-565, 1993).
U.S. Pat. No. 4,963,736 describes the use of a multipole ion guide in the first pumping stage of a two-stage system. Operation of the multipole ion guide in certain length-times-pressure regimes is claimed for the purposes of enhancing ion signal.
U.S. Pat. Nos. 5,179,278 and 5,811,800 describe the temporary storage of ions in an r.f. multipole rod system for subsequent analysis in an rs.f. quadrupole ion trap mass spectrometer. This is done for the purpose of matching the time scales of compounds eluting from chromatographic or electrophoretic separation devices to the time scale of mass spectrometric analyses performed by an r.f. quadrupole ion trap.
U.S. Pat. No. 5,432,343 describes an ion focusing lensing system for interfacing an atmospheric pressure ionization source to a mass spectrometer. It describes the use of an electrostatic lens in a transition flow pressure region of the interface, claiming benefit of independent adjustment of operating voltages controlling the collisionally induced dissociation and declustering processes. Enhancement of ion beam transmission into the mass analyzer is also claimed.
U.S. Pat. No. 5,652,427 describes in one embodiment a system in which a multipole ion guide extends between two vacuum stages and in another embodiment a system which includes a multipole in each of two adjacent stages. Improved performance and lower cost are claimed.
U.S. Pat. No. 5,852,294 describes the construction of a miniature multipole ion guide assembly.
A goal to be achieved in all single or multiple interface vacuum chambers is to transport as many protonated molecular cations or molecular anions as possible from the atmospheric pressure ionization source to the mass analyzer. However, many solvent adduct ions which are formed in the high pressure region travel through the interface vacuum chambers into the analyzer. The process of solvent adduction in the mass spectrometer system is generally considered to be a non-covalent association between sample ions of interest and neutral solvent molecules. Thus, in the case of introduction of an analyte into an electrospray or atmospheric pressure chemical ionization source, the ion current produced from that analyte may be divided between the protonated molecular cation or molecular anion and one or more solvent adduct species. Specific detection is usually accomplished by monitoring the ion signal, or derivative of that signal, for one specific mass. In the case where solvent adducts are formed, the limit of detection or limit of quantitation for the analyte is reduced.
Experimental evidence indicates that these adduct ions are predominantly formed in the high pressure regions of the system ranging from the API source region through the interface vacuum regions. The degree of adduction varies directly with the pressures in these regions. The formation of adduct ions significantly reduces the abundance of sample analyte ions. Furthermore, the adduct ions which enter into the mass analyzer complicates the mass spectrum and make the identification of mass peaks more difficult.
It is an object of the present invention to provide a mass spectrometer system employing an ion source with multiple ion guides configured and operated to convert adduct ions into sample ions and a method of operating multiple ion guides to convert adduct ions into sample ions to thereby increase the analyte ions current and sensitivity of the mass spectrometer system.
In accordance with the invention, there is provided a mass spectrometer including a mass analyzer disposed in a high vacuum chamber for analyzing ions formed in an ionization source which includes first and second evacuated interface chambers immediately preceding the mass analyzer chamber, with the first interface chamber being at a higher pressure than the second interface chamber, and including a first ion guide for guiding ions from the ion source into said second interface chamber which includes a second multipole ion guide for guiding the ions from the first interface chamber into the high vacuum analyzer chamber for analysis. Both r.f. and DC potentials are applied to the said first and second ion guides to ensure ion focusing and transmission through related vacuum chamber. A first ion lens is disposed at the input of the first interface chamber for directing ions into the first multipole ion guide, an interchamber ion lens is disposed between the first and second interface chambers for directing ions into said second multipole ion guide, and an ion lens or a lens stack is disposed between the second interface chamber and the analyzer chamber for directing ions into said analyzer for analysis. These ion lenses also serve as gas conductance restrictors between said interface chambers.
A DC voltage source is connected to provide a potential difference between the first lens and the first multipole ion guide or between interchamber lens and the second multipole ion guide or both which defines the ion's translational kinetic energy as it enters the second multipole ion guide. The ion's translational kinetic energy is chosen such that at the vacuum pressure of the second interface chamber adduct ions are converted into sample ions by collision induced dissociation without fragmentation of sample ions whereby the sample ion current entering the analyzer is increased, thereby increasing the sensitivity of the mass spectrometer system.
There is provided a method of mass analyzing ions produced in an atmospheric pressure ionization source in which adduct ions formed in the mass spectrometer system are dissociated prior to analysis to increase the analyte ion current to the mass analyzer and the sensitivity of the mass spectrometer system.
There is provided a method of operating a mass spectrometer system in which an analyzer in a vacuum chamber analyzes ions formed in an atmospheric pressure ionization source. The system includes first and second multipole ion guides disposed in serial first and second evacuated chambers immediately preceding the analyzer. The method comprises applying a DC voltage between the ion lens preceding either the first or the second multipole ion guide to provide translational kinetic energy to the adduct ions sufficient to dissociate any adduct ions at the pressure of the second chamber without fragmenting the sample ions whereby to increase the sample ion current directed into the analyzer and the sensitivity of the mass spectrometer system.
The foregoing and other objects of the invention will be more clearly understood from the following description when read in conjunction with the accompanying drawings in which:
The atmospheric pressure ion source may be an electrospray ion source or atmospheric pressure chemical ionization source. With either ion source, sample liquid is introduced into the chamber 11, which is at a atmospheric pressure, and ionized. The ions are drawn through a capillary 22, which may be heated, into chamber 13. The end of the capillary is opposite a conical skimmer 24 which includes a central orifice or aperture 26. The skimmer separates the low pressure stage 13 from the lower pressure stage 16. A portion of the ion and gas flow is skimmed from the free jet expansion leaving the capillary and enters the second lower pressure stage. The ions which travel through the skimmer are guided into the mass analyzer by first and second multipole ion guides 27 and 28. In one example, the ion guides are square quadrupoles. The guide 27 is 1.25 inches long and the guide 28 is 3.37 inches with the rods separated by 0.118 inches (3 mm). The ion guides are mounted coaxially using polycarbonate holders (not shown). The quadrupole ion guides are operated by applying AC voltages 31 and 32 to the poles which guide ions as is well known. Ions which enter the second and third stages drift under the influence of DC voltage 33 applied between the skimmer lens 24 and lens 18, by DC voltage 34 applied between the lens 18 and the lens 36, and by DC offset voltages applied to ion guides 27 and 28.
As discussed above, solvent adduct ions are formed in the high pressure regions ranging from the atmospheric pressure region to the quadrupole ion guide stages or regions. The degree of adduction is believed to vary directly with the pressure in these regions. The formation of adduct ions can significantly reduce the abundance of sample analyte ions which reach the analyzer. Consequently, effective conversion of the adduct ions into protonated molecular cations or molecular anions ions can greatly enhance the sample ion current and the sensitivity of the mass spectrometer system.
We have discovered that the solvent adduct ions can be dissociated and converted into sample ions in the second ion guide 28 by applying a small DC offset voltage between the ion guide 28 and the lens 18 to increase the energy of the solvent adduct ions. An additional 10 volts DC offset applied to the second ion guide (usually used with a standard 5 V DC offset) is sufficient to convert the solvent adducts into the protonated molecular cation or molecular anion for all compounds tested. In addition, this offset voltage is insufficient to cause fragmentation of the analyte ions at the pressure of the second stage.
Both pumping efficiency and solvent adduction were evaluated. The pumping requirement and vacuum condition on the double ion guide system were compared to a standard TSQ 7000 system sold by ThermoQuest Corporation under the same gas load conditions. Several different compounds including a) acetaminophen; b) Alprazolam; c) codeine-d3; d) ibuprofen were used to investigate the degree of solvent adduction, conversion to protonated molecular cation or molecular anion, and fragmentation of the protonated molecular cation or molecular anion. The solvent used in the experiment was 50:50 acetonitrile:water+5mM ammonium acetate adjusted to a pH of 4.5. Table 1 lists the main experimental conditions, compound, molecular weight and type of solvent adduction investigated.
The DC offset required for high efficiency solvent adduct ion conversion at different vacuum conditions in both first chamber and second chamber was also investigated. The following tables summarize one set of tests in which the ratio of the acetonitrile adduct to the protonated molecular cation of codeine-d3 was investigated at different pressures and different DC offset voltages on the second ion guide.
DC offset on second ion guide (volts)
First ion guide pressure (mTorr)
Second ion guide pressure (mTorr)
Ratio of acetonitrile adduct ion to
protonated molecular ion
DC offset on second ion guide (volts)
First ion guide pressure (mTorr)
Second ion guide pressure (mTorr)
Ratio of acetonitrile adduct ion to
protonated molecular ion
DC offset on second ion guide (volts)
First ion guide pressure (mTorr)
Second ion guide pressure (mTorr)
Ratio of acetonitrile adduct ion to
protonated molecular ion
The bold data in Table 2 indicates the range of pressure and offset voltages at which the most efficient conversion of solvent adduct to protonated molecular cation is achieved. According to these results, the operating pressure for the ion guides should be:
First Ion Guide: below 500 mTorr
Second Ion Guide: below 1 mTorr and above 0.1 mTorr
Although the offset voltage which provides the translational kinetic energy to the adduct ions has been described as applied between the interstage lens and the second multipole guide, it is apparent that the translational kinetic energy can be provided by applying the DC offset voltage between the skimmer lens and the first multipole stage or by applying voltages simultaneously between each lens and its respective multipole ion guide. The operating pressure will be the same as above.
The DC offset voltage range for efficient solvent adduction conversion should be ±10 to ±30 Volts, although ±10 V is preferable.
The preferred pressure range is less than 250 mTorr for the first stage and 0.7 mTorr for the second stage, and the most preferred pressure range is less than 175 mTorr for the first stage, and 0.5 mTorr for the second stage.
The present invention can be used for other types of mass analyzers such as quadrupole mass analyzers of the type described in U.S. Pat. No. 4,540,884 and U.S. Pat. No. RE 34,000.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US1969399||Mar 3, 1930||Aug 7, 1934||Television Lab Inc||Electron multiplier|
|US3555273||Jul 18, 1968||Jan 12, 1971||Varian Associates||Mass filter apparatus having an electric field the equipotentials of which are three dimensionally hyperbolic|
|US4023398||Mar 3, 1975||May 17, 1977||John Barry French||Apparatus for analyzing trace components|
|US4121099||Apr 25, 1977||Oct 17, 1978||The Governing Council Of The University Of Toronto||Method and apparatus for focussing and declustering trace ions|
|US4137750||Apr 25, 1977||Feb 6, 1979||The Governing Council Of The University Of Toronto||Method and apparatus for analyzing trace components using a gas curtain|
|US4148196||Apr 25, 1977||Apr 10, 1979||Sciex Inc.||Multiple stage cryogenic pump and method of pumping|
|US4328420||Jul 28, 1980||May 4, 1982||French John B||Tandem mass spectrometer with open structure AC-only rod sections, and method of operating a mass spectrometer system|
|US4423324||Jul 23, 1979||Dec 27, 1983||Finnigan Corporation||Apparatus for detecting negative ions|
|US4535236||Feb 23, 1984||Aug 13, 1985||Vg Instruments Group Limited||Apparatus for and method of operating quadrupole mass spectrometers in the total pressure mode|
|US4540884||Dec 29, 1982||Sep 10, 1985||Finnigan Corporation||Method of mass analyzing a sample by use of a quadrupole ion trap|
|US4755670||Oct 1, 1986||Jul 5, 1988||Finnigan Corporation||Fourtier transform quadrupole mass spectrometer and method|
|US4791292||Apr 24, 1986||Dec 13, 1988||The Dow Chemical Company||Capillary membrane interface for a mass spectrometer|
|US4842701||Apr 6, 1987||Jun 27, 1989||Battelle Memorial Institute||Combined electrophoretic-separation and electrospray method and system|
|US4963736||Nov 15, 1989||Oct 16, 1990||Mds Health Group Limited||Mass spectrometer and method and improved ion transmission|
|US4977320||Jan 22, 1990||Dec 11, 1990||The Rockefeller University||Electrospray ionization mass spectrometer with new features|
|US5026987||May 23, 1990||Jun 25, 1991||Purdue Research Foundation||Mass spectrometer with in-line collision surface means|
|US5049739||Dec 1, 1989||Sep 17, 1991||Hitachi, Ltd.||Plasma ion source mass spectrometer for trace elements|
|US5089703||May 16, 1991||Feb 18, 1992||Finnigan Corporation||Method and apparatus for mass analysis in a multipole mass spectrometer|
|US5107109||Mar 7, 1986||Apr 21, 1992||Finnigan Corporation||Method of increasing the dynamic range and sensitivity of a quadrupole ion trap mass spectrometer|
|US5157260||May 17, 1991||Oct 20, 1992||Finnian Corporation||Method and apparatus for focusing ions in viscous flow jet expansion region of an electrospray apparatus|
|US5162650||Jan 25, 1991||Nov 10, 1992||Finnigan Corporation||Method and apparatus for multi-stage particle separation with gas addition for a mass spectrometer|
|US5179278||Aug 23, 1991||Jan 12, 1993||Mds Health Group Limited||Multipole inlet system for ion traps|
|US5182451||Mar 12, 1992||Jan 26, 1993||Finnigan Corporation||Method of operating an ion trap mass spectrometer in a high resolution mode|
|US5206506||Feb 12, 1991||Apr 27, 1993||Kirchner Nicholas J||Ion processing: control and analysis|
|US5298743||Sep 10, 1992||Mar 29, 1994||Hitachi, Ltd.||Mass spectrometry and mass spectrometer|
|US5304798||Apr 10, 1992||Apr 19, 1994||Millipore Corporation||Housing for converting an electrospray to an ion stream|
|US5412208||Jan 13, 1994||May 2, 1995||Mds Health Group Limited||Ion spray with intersecting flow|
|US5420425||May 27, 1994||May 30, 1995||Finnigan Corporation||Ion trap mass spectrometer system and method|
|US5432343||Jun 3, 1993||Jul 11, 1995||Gulcicek; Erol E.||Ion focusing lensing system for a mass spectrometer interfaced to an atmospheric pressure ion source|
|US5538897||Mar 14, 1994||Jul 23, 1996||University Of Washington||Use of mass spectrometry fragmentation patterns of peptides to identify amino acid sequences in databases|
|US5572022||Mar 3, 1995||Nov 5, 1996||Finnigan Corporation||Method and apparatus of increasing dynamic range and sensitivity of a mass spectrometer|
|US5596192||Apr 15, 1996||Jan 21, 1997||Shimadzu Corporation||Mass spectrometric apparatus for use with a liquid chromatograph|
|US5652427||May 14, 1996||Jul 29, 1997||Analytica Of Branford||Multipole ion guide for mass spectrometry|
|US5670378||Feb 23, 1995||Sep 23, 1997||The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration||Method for trace oxygen detection|
|US5739530||May 31, 1996||Apr 14, 1998||Bruker-Franzen Analytik Gmbh||Method and device for the introduction of ions into quadrupole ion traps|
|US5744798||Apr 18, 1997||Apr 28, 1998||Hitachi, Ltd.||Mass spectrometry and mass spectrometer|
|US5747799||May 30, 1996||May 5, 1998||Bruker-Franzen Analytik Gmbh||Method and device for the introduction of ions into the gas stream of an aperture to a mass spectrometer|
|US5750993||May 9, 1996||May 12, 1998||Finnigan Corporation||Method of reducing noise in an ion trap mass spectrometer coupled to an atmospheric pressure ionization source|
|US5756996||Jul 5, 1996||May 26, 1998||Finnigan Corporation||Ion source assembly for an ion trap mass spectrometer and method|
|US5767512||Jan 5, 1996||Jun 16, 1998||Battelle Memorial Institute||Method for reduction of selected ion intensities in confined ion beams|
|US5811800||Sep 13, 1996||Sep 22, 1998||Bruker-Franzen Analytik Gmbh||Temporary storage of ions for mass spectrometric analyses|
|US5847386||Feb 6, 1997||Dec 8, 1998||Mds Inc.||Spectrometer with axial field|
|US5852294||Jul 3, 1997||Dec 22, 1998||Analytica Of Branford, Inc.||Multiple rod construction for ion guides and mass spectrometers|
|US6015972||May 27, 1998||Jan 18, 2000||Mds Inc.||Boundary activated dissociation in rod-type mass spectrometer|
|US6017693||Mar 14, 1994||Jan 25, 2000||University Of Washington||Identification of nucleotides, amino acids, or carbohydrates by mass spectrometry|
|US6107623||Aug 21, 1998||Aug 22, 2000||Micromass Limited||Methods and apparatus for tandem mass spectrometry|
|US6124591||Oct 12, 1999||Sep 26, 2000||Finnigan Corporation||Method of ion fragmentation in a quadrupole ion trap|
|US6259091||Jun 15, 1998||Jul 10, 2001||Battelle Memorial Institute||Apparatus for reduction of selected ion intensities in confined ion beams|
|US6331702||Jan 25, 1999||Dec 18, 2001||University Of Manitoba||Spectrometer provided with pulsed ion source and transmission device to damp ion motion and method of use|
|US6680475||Nov 21, 2001||Jan 20, 2004||University Of Manitoba||Spectrometer provided with pulsed ion source and transmission device to damp ion motion and method of use|
|US6700120||Nov 30, 2000||Mar 2, 2004||Mds Inc.||Method for improving signal-to-noise ratios for atmospheric pressure ionization mass spectrometry|
|US6753523||Sep 6, 2002||Jun 22, 2004||Analytica Of Branford, Inc.||Mass spectrometry with multipole ion guides|
|US6987264||Jun 16, 2004||Jan 17, 2006||Analytica Of Branford, Inc.||Mass spectrometry with multipole ion guides|
|US20040144916||Jan 15, 2004||Jul 29, 2004||University Of Manitoba||Spectrometer provided with pulsed ion source and transmission device to damp ion motion and method of use|
|USRE34000||Mar 27, 1990||Jul 21, 1992||Finnigan Corporation||Method of operating ion trap detector in MS/MS mode|
|CA585694A||Oct 27, 1959||Martin Van Antwerpen||Slitting machine|
|EP0023826A1||Aug 1, 1980||Feb 11, 1981||Canadian Patents and Development Limited||Tandem quadrupole mass spectrometer system|
|EP0023826B1||Aug 1, 1980||Mar 7, 1984||Canadian Patents and Development Limited||Tandem quadrupole mass spectrometer system|
|EP0113207A2||Dec 7, 1983||Jul 11, 1984||Finnigan Corporation||Method of mass analyzing a sample by use of a quadrupole ion trap|
|EP0373835B1||Dec 8, 1989||Apr 17, 2002||MDS Inc.||Mass spectrometer and method with improved ion transmission|
|EP0813228A1||May 30, 1997||Dec 17, 1997||Micromass Limited||Plasma mass spectrometer|
|EP0898297A2||Aug 20, 1998||Feb 24, 1999||Micromass Limited||Methods and apparatus for tandem mass spectrometry|
|JPH04171650A||Title not available|
|JPH10269985A||Title not available|
|WO1998006481A1||Aug 11, 1997||Feb 19, 1998||Analytica Of Branford, Inc.||Multipole ion guide ion trap mass spectrometry|
|1||A. Dodonov et al., abstract for A new technique for decomposition of selected ions in molecule ion reactor coupled with ortho-time-of-flight mass spectrometry, Rapid Commun. Mass Spectrom., vol. 11, 1649-59 (1997).|
|2||A.N. Krutchinsky et al., Orthogonal Injection of Matrix-assisted Laser Desorption/Ionization Ions into a Time-of-flight Spectrometer Through a Collisional Damping Interface, Rapid Commun. Mass Spectrom., vol. 12, pp. 508-518 (1998).|
|3||Alexander Loboda et al., abstract for Novel Linac II electrode geometry for creating an axial field in a multipole ion guide, Eur. J. Mass Spectrom., vol. 6, pp. 531-536 (2000).|
|4||Alexander Loboda et al., Novel LINAC II electrode geometry to create an axial field in a multipole ion guide, available at http://www.physics.umanitoba.ca/~ens/ASMS2000Loboda.pdf (visited on Jun. 29, 2005).|
|5||Alexander Loboda et al., Poster, Novel LINAC II electrode geometry to create an axial field in a multipole ion guide, available at http://www.physics.umanitoba.ca/~ens/ASMS2000LobodaPoster.pdf (visited on Jun. 29, 2005).|
|6||Amos Bairoch & Brigitte Boeckmann, The SWISS-PROT protein sequence data bank, recent developments, Nucleic Acids Research, vol. 21, No. 13, pp. 3093-3096 (1993).|
|7||Andrew N. Krutchinsky et al., Rapidly Switchable Matrix-Assisted Laser Desorption/Ionization and Electrospray Quadrupole-Time-of-Flight Mass Spectrometry for Protein Identification, J. Am. Soc. Mass Spectrom., vol. 11, pp. 493-504 (2000).|
|8||Beaugrand et al., Ion Confinement in the Collision Cell of a Multiquadrupole Mass Spectrometer: Access to Chemical Equilibrium and Determination of Kinetic and Thermodynamic Parameters of an Ion-Molecule Reaction, Am. Chem. Soc., vol. 61, pp. 1447-1453 (1989).|
|9||Bodo Hattendorf & Detlef Günther, Characteristics and capabilities of an ICP-MS with a dynamic reaction cell for dry aerosols and laser ablation, J. Anal. At Spectrom., vol. 15, pp. 1125-1131 (2000).|
|10||Byungchul Cha et al., An Interface with a Linear Quadrupole Ion Guide for an Electrospray-Ion Trap Mass Spectrometer System, Anal. Chem., vol. 72, pp. 5647-5654 (2000).|
|11||C.A. Boitnott, J.R.B. Slayback & U. Steiner, Optimization of Instrument Parameters for Collision Activated Decomposition (CAD) Experiments for a Triple Stage Quadrupole (TSQ(TM))GC/MS/MS/DS, Finnigan MAT, Finnigan Topic 8160 (1981).|
|12||Charles A. Boitnott, Urs Steiner & John R.B. Slayback, Optimization of Instrument Parameters for Collision Activated Decomposition (CAD)Experiments for a Finnigan Triple Stage Quadrupole GC/MS/MS/DS, Pittsburgh Conference Abstracts (1981).|
|13||Charles J. Barinaga & David W. Koppenaal, Ion-trap Mass Spectrometry with an Inductively Coupled Plasma Source, Rapid Communications in Mass Spectrometry, vol. 8, pp. 71-76 (1994).|
|14||Christian Burks et al., GenBank: Current Status and Future Directions, in Methods in Enzymology, vol. 183 (Molecular Evolution: Computer Analysis of Protein and Nucleic Acid Sequences), pp. 3-22 (Russell F. Doolittle ed. 1990).|
|15||D. Gerlich & M. Wirth, Low Energy Crossed-Beam Study of the Reaction N+=02->NO++0, in Symposium on Atomic and Surface Physics, pp. 366-371 (F. Howorka ed., 1986).|
|16||D. Gerlich, Dynamics of ion-molecule collisions at very low energies: Molecular beams, crossed and merged with guided ion beams, in XII International Symposium on Molecular Beams, pp. 37-40 (V. Aquilanti ed., 1989).|
|17||D.A. Church, Storage-Ring Ion Trap Derived from the Linear Quadrupole Radio-Frequency Mass Filter, J. Appl. Phys., vol. 40, No. 8, pp. 3127-3134 (1969).|
|18||D.J. Douglas & J.B. French, Collisional Focusing Effects in Radio Frequency Quadrupoles, J. Am. Soc. Mass Spectrom., vol. 3, pp. 398-408 (1992).|
|19||D.J. Douglas, Mechanism of Collision-Induced Dissociation of Polyatomic Ions Studied by Triple Quadrupole Mass Spectrometry, J. Phys. Chem., vol. 86, pp. 185-191 (1982).|
|20||D.J. Douglas, Some Current Perspectives on ICP-MS, Canadian J. Spectroscopy, vol. 34, pp. 38-49 (1989).|
|21||D.K. Bedford & D. Smith, Variable-Temperature Selected Ion Flow Tube Studies of the Reactions of Ar+, Ar2+ and ArHn+ (n=1-3)Ions with H2, HD and D2 at 300 K and 80 K, Int'l. J. Mass Spectrom. & Ion Processes, vol. 98, 179-190 (1990).|
|22||David W. Koppenaal et al., Performance of an Inductively Coupled Plasma Source Ion Trap Mass Spectrometer, J. Analytical Atomic Spectrometry, vol. 9, pp. 1053-1058 (1994).|
|23||Dieter Gerlich, Inhomogeneous RF Fields: A Versatile Tool for the Study of Processes with Slow Ions, in State-Selected and State-to-State Ion-Molecule Reaction Dynamics, Part 1: Experiment, vol. 82, pp. 1-176 (Cheuk-Yiu Ng & Michael Baer eds., 1992).|
|24||Donald F. Hunt et al., Protein sequencing by tandem mass spectrometry, Proc. Nat'l Acad. Sci. USA, vol. 83, pp. 6233-6237 (1986).|
|25||E. Poussel et al., Dissociation of Analyte Oxide Ions in Inductively Coupled Plasma Mass Spectrometry, J. Analytical Atomic Spectrometry, vol. 9, pp. 61-66 (1994).|
|26||F.L. King & W.W. Harrison, Collision-Induced Dissociation of Polyatomic Ions in Glow Discharge Mass Spectrometry, Int'l J. Mass Spectrom. & Ion Processes, vol. 89, pp. 171-185 (1989).|
|27||F.L. King et al., Study of Molecular Interferences in Glow Discharge Mass Spectrometry, J. Analytical At. Spectrom., vol. 3, pp. 883-886 (1988).|
|28||G.C. Eiden et al., Plasma Source Ion Trap Mass Spectrometry: Enhanced Abundance Sensitivity by Resonant Ejection of Atomic Ions, J. Am. Soc. Mass Spectrom., vol. 7, 1161-1171 (1996).|
|29||G.G. Dolnikowski et al., Ion-Trapping Tecnique for Ion/Molecule Reaction Studies in the Center Quadrupole of a Triple Quadrupole Mass Spectrometer, Int'l J. Mass Spectrom. & Ion Processes, vol. 82, pp. 1-15 (1988).|
|30||G.W. Goodrich & W.C. Wiley, Continuous Channel Electron Multiplier, 33 Rev. Sci. Instrum., vol. 33, pp. 761-762 (1962).|
|31||Gökhan Baykut et al., Matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry with pulsed in-source collision gas and in-source ion accumulation, Rapid Commun. Mass Spectrom., vol. 14, pp. 1238-1247 (2000).|
|32||Gregory C. Eiden et al., Selective Removal of Plasma Matrix Ions in Plasma Source Mass Spectrometry, J. Analytical At. Spectrom., vol. 11, pp. 317-322 (1996).|
|33||H.I. Kenttämaa et al., Scanning a Triple Quadrupole Mass Spectrometer for Doubly Charged Ions, Organic Mass Spectrometry, vol. 18, No. 12, pp. 561-566 (1983).|
|34||Honway Louie & Susan Yoke-Peng Soo, Use of Nitrogen and Hydrogen in Inductively Coupled Plasma Mass Spectrometry, J. Analytical Atomic Spectrometry, vol. 7, pp. 557-564 (1992).|
|35||Index of the Protein Sequence Database of the International Association of Protein Sequence Databanks(PIR-International), Protein Seq. Data Anal., vol. 5, Nos. 2-4, pp. 65-192 (1993).|
|36||Ivan Haller et al., Collision Induced Decomposition of Peptides: Choice of Collision Parameters, J. Am. Soc. Mass Spectrom., vol. 7, pp. 677-681 (1996).|
|37||J. Batey & S. Nelms, Performance Characteristics of a Multipole Collision Cell ICP-MS. (1999).|
|38||J. Batey, "Pittcon 2000."|
|39||J. Scott Anderson & David A. Laude, Experimental methods to alleviate ion coupling effects in matrix-assisted laser desorption ionization Fourier transform ion cyclotron resonance mass spectrometry, Int'l . J. Mass Spectrometry & Ion Processes, vol. 157/158, pp. 163-174 (1996).|
|40||J.A. Buckley et al., TAGA 6000-A New Triple Quadrupole MS/MS System for the Rapid Ultrasensitive Screening for Trace Contaminants, Abstracts, 1981 Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy, No. 783.|
|41||J.F. Mahoney et al., Improving the Detection Sensitivity for High Mass Ions, Proc. 36th ASMS Conference on Mass Spectrometry and Allied Topics, 1988.|
|42||J.H. Batey, An Overview of Collision Cells and Allied Technology for Attenuating Molecular Ion Interferences(1999) VG Elemental, Issue 1.|
|43||Jeffrey S. Crain et al., Matrix interferences in inductively coupled plasma-mass spectrometry: some effects of skimmer orifice diameter and ion lens voltages, Spectrochimica Acta, vol. 43B, Nos. 9-11, pp. 1355-1364 (1988).|
|44||Jimmy K. Eng, Ashley L. McCormack, & John R. Yates, III, An Approach to Correlate Tandem Mass Spectral Data of Peptides with Amino Acid Sequences in a Protein Database, J. Am. Soc. Mass Spectrom., vol. 5, pp. 976-989 (1994).|
|45||John Latino et al., Advantages of Dynamic Bandpass Tuning in Dynamic Reaction Cell ICP-MS, Application Note (2001).|
|46||John T. Rowan & R.S. Houk, Attenuation of Polyatomic Ion Interferences in Inductively Coupled Plasma Mass Spectrometry by Gas-Phase Collisions, Applied Spectroscopy, vol. 43, No. 6, pp. 976-980 (1989).|
|47||Jonathan H. Batey & John M. Tedder, The Study of Ion-Molecule Reactions in Gas Phase using a Triple Quadrupole Mass Spectrometer. Part 1 . The Reactions of CH3+, CD3+, and C2H5+ with Simple Olefins, J. Chem. Soc. Perkin Trans. II, pp. 1263-1267 (1983).|
|48||José A. Olivares et al., On-Line Mass Spectrometric Detection for Capillary Zone Electrophoresis, Anal. Chem., vol. 59, No. 8, pp. 1230-1232 (1987).|
|49||Jun Qin & Brian T. Chait, Identification and Characterization of Posttranslational Modifications of Proteins by MALDI Ion Trap Mass Spectrometry, Anal. Chem., vol. 69, No. 19, pp. 4002-4009 (1997).|
|50||Jun Qin & Brian T. Chait, Matrix-Assisted Laser Desorption Ion Trap Mass Spectrometry: Efficient Isolation and Effective Fragmentation of Peptide Ions, Anal. Chem., vol. 68, No. 13, pp. 2108-2112 (1996).|
|51||Jun Qin & Brian T. Chait, Matrix-Assisted Laser Desorption Ion Trap Mass Spectrometry: Efficient Trapping and Ejection of Ions, Anal. Chem., vol. 68, No. 13, pp. 2102-2107 (1996).|
|52||Jun Qin et al., A Practical Ion Trap Mass Spectrometer for the Analysis of Peptides by Matrix-Assisted Laser Desorption/Ionization, Anal. Chem., vol. 68, No. 10, pp. 1784-1791 (1996).|
|53||K. Birkinshaw et al., The focusing of an ion beam from a quadrupole mass filter using an electrostatic octopole lens, J. Phys. E: Sci. Instrum., vol. 11, pp. 1037-1040 (1978).|
|54||Karen R. Jonscher & John R. Yates III, Matrix-assisted Laser Desorption Ionization/Quadrupole Ion Trap Mass Spectrometry of Peptides, J. Biological Chem., vol. 272, No. 3, pp. 1735-1741 (1997).|
|55||Karen R. Jonscher & John R. Yates III, Mixture Analysis Using a Quadrupole Mass Filter/Quadrupole Ion Trap Mass Spectrometer, Anal. Chem., vol. 68, pp. 659-667 (1996).|
|56||Karen R. Jonscher & John R. Yates, III, The Whys and Wherefores of Quadrupole Ion Trap Mass Spectrometry, with version available at http://www.abrf.org/ABRFNews/1996/September1996/sep96iontrap.html (last revised Sep. 30, 1996).|
|57||Karen R. Jonscher et al., Matrix-assisted Laser Desorption of Peptides and Proteins on a Quadrupole Ion Trap Mass Spectrometer, Rapid Communications in Mass Spectrometry, vol. 7, pp. 20-26 (1993).|
|58||Kenneth Neubauer & Uwe Völlkopf, The Benefits of a Dynamic Reaction Cell to Remove Carbon- and Chloride-Based Spectral Interferences by ICP-MS, Atomic Spectroscopy, vol. 20(2), pp. 64-66 (1999).|
|59||Kenneth R. Neubauer & Ruth E. Wolf, Determination of arsenic in chloride matrices, ICP Mass Spectrometry: Application Note (2000).|
|60||Kent M. Ervin & P.B. Armentrout, Translational energy dependence of Ar++XY->ArX++Y(XY=H2D2HD)from thermal to 30 eV c.m., J. Chem Phys., vol. 83, pp. 166-189 (1985).|
|61||Linda A. Powell & G.M. Hieftje, Computer Indentification of Infrared Spectra by Correlation-Based File Searching, Analytica Chimica Acta, vol. 100, pp. 313-327 (1978).|
|62||Luke Hanley & Scott L. Anderson, Chemistry and Cooling of Transition Metal Cluster Ions, Chem. Phys. Lett., vol. 122, pp. 410-414 (1985).|
|63||Luke Hanley, Stephen A. Ruatta, & Scott L. Anderson, Collision-induced dissociation of aluminum cluster ions: Fragmentation patterns, bond energies, and structures for Al2+-Al7+ (1987).|
|64||M. Barber et al., Fast atom bombardment of solids as an ion source in mass spectrometry, Nature, vol. 293, pp. 270-275 (1981).|
|65||Mark Johnston, Energy Filtering in Triple Quadrupole MS/MS, Application Report, No. 203 (1984).|
|66||P. Kofel et al., A Novel Quadrupole, Quistor, Quadrupole Tandem Mass Spectrometer, Organic Mass Spectrometry, vol. 26, pp. 463-467 (1991).|
|67||P.H. Dawson & D.J. Douglas, Quantitative Studies of the Kinetics of Ion Dissociation and Ion Molecule Declustering Using a Triple Quadrupole, Proc. 29th Ann. Conf. on Mass Spectrometry (1981).|
|68||P.H. Dawson & N.R. Whetten, Mass Spectroscopy Using RF Quadrupole Fields, in Advances in Electronics and Electron Physics, vol. 27, pp. 59-185 (L. Marton ed., 1969).|
|69||P.H. Dawson et al., The Use of Triple Quadrupoles for Sequential Mass Spectrometry: 1-The Instrument Parameters, Organic Mass Spectrometry, vol. 17, No. 5, pp. 205-211 (1982).|
|70||P.H. Dawson et al., The Use of Triple Quadrupoles for Sequential Mass Spectrometry: 2-A Detailed Case Study, Organic Mass Spectrom., vol. 17, No. 5, pp. 212-219 (1982).|
|71||P.H. Hemberger et al., Laser photodissociation probe for ion tomography studies in a quadrupole ion-trap mass spectrometer, Chem. Phys. Lett., vol. 191, No. 5, pp. 405-410 (1992).|
|72||Patricia Kahn & Graham Cameron, EMBL Data Library, in Methods in Enzymology, vol. 183 (Molecular Evolution: Computer Analysis of Protein and Nucleic Acid Sequences), vol. 183, pp. 23-31 (Russell F. Doolittle ed. 1990).|
|73||Patrick R. Griffin et al., Analysis of Proteins by Mass Spectrometry, in Techniques in Protein Chemistry III, pp. 467-476 (1992).|
|74||Patrick R. Griffin et al., Structural analysis of proteins by capillary HPLC electrospray tandem mass spectrometry, Int'l J. Mass Spectrometry & Ion Processes, vol. 111, pp. 131-149 (1991).|
|75||Quadrupole Mass Spectrometry and Its Applications (Peter H. Dawson ed., 1976) (excerpts).|
|76||R. Gradewald, Das Verhalten geladener Teilchen in elektrischen Vierpolfeldern, Ann. Physik, vol. 20, pp. 1-13 (1967) (English translation enclosed).|
|77||R. Kostianen, Characterization of Trichotecenes by Tandem Mass Spectrometry Using Reactive Collisions with Ammonia, Biomedical & Environmental Mass Spectrometry, vol. 16, pp. 197-200 (1988).|
|78||R.S. Houk, Mass Spectrometry of Inductively Coupled Plasmas, Analytical Chem., vol. 58, No. 1, pp. 97-105 A (1986).|
|79||Raymond E. March, An Introduction to Quadrupole Ion Trap Mass Spectrometry, J. Mass Spectrometry, vol. 32, pp. 351-369 (1997).|
|80||Recent developments in ICP-MS, "Bmass 2000", 1999 VGE Issue 1.|
|81||S. Mills, "WPC2000", Sep. 99, VGE Issue 1.|
|82||S.A. Jarvis et al., Spectrometer, Proc. 45thASMS Conf. on Mass Spectrometry and Allied Topics, p. 1193 (1997).|
|83||S.A. Lammert, Toroidal RF Ion Trap Mass Analyzer(revised 2001), at http:/www.orml.gov/sci/casd/lammert/sal_research_toroid.html (visited on Nov. 4, 2004).|
|84||Scott A. McLuckey et al., Radio-Frequency Glow Discharge Ion Trap Mass Spectrometry, Anal. Chem., vol. 64, pp. 1616-1609 (1992).|
|85||Scott A. McLuckey et al., Tandem Mass Spectrometry of Small, Multiply Charged Oligonucleotides, J. Am. Soc. Mass Spectrom., vol. 3, pp. 60-70 (1992).|
|86||Scott L. Anderson & Luke Hanley, Metal Cluster Ion Chemistry, SPIE, vol. 669 (Laser Applications in Chemistry), pp. 133-136 (1986).|
|87||Steven F. Durrant, Alternatives to all-argon plasmas in inductively coupled plasma mass spectrometry (ICP-MS)an overview, Fresenius J. Anal. Chem., vol. 347, pp. 389-392 (1993).|
|88||Stu Borman, Combinatorial Synthesis Hits the Spot, Chem. & Eng'g News, vol. 78, No. 27, pp. 25-27 (Jul. 3, 2000).|
|89||Swapan K. Chowdhury et al., An Electrospray-ionization Mass Spectrometer with New Features, Rapid Communications in Mass Spectrometry, vol. 4, No. 3, pp. 81-87 (1990).|
|90||V.J. Caldecourt, D. Zakett & J.C. Tou, An Atmospheric-Pressure Ionization Mass Spectrometer/Mass Spectrometer, Int'l J. Mass Spectrometry & Ion Physics, vol. 49, pp. 233-251 (1983).|
|91||Victor V. Laiko et al., Atmospheric Pressure MALDI/Ion Trap Mass Spectrometry, Anal. Chem., vol. 72, pp. 5239-5243 (2000).|
|92||Vladimir I. Baranov & Scott D. Tanner, A dynamic reaction cell for inductively coupled plasma mass spectrometry(ICP-DRC-MS): Part 1. The rf-field energy contribution in thermodynamics of ion-molecule reactions, J. Anal. At. Spectrom., vol. 14, 1133-1142 (1999).|
|93||Vladimir M. Doroshenko & Robert J. Cotter, Injection of Externally Generated Ions into an Increasing Trapping Field of a Quadrupole Ion Trap Mass Spectrometer, J. Mass Spectrom., vol. 31, pp. 602-615 (1997).|
|94||W. Frobin, Ch. Schlier, K. Strein, & E. Teloy, Ion-molecule reactions of N+ with CO: Integral reactive cross sections in the collision energy range 0.2-13 eV (1977).|
|95||William J. Henzel et al., Identifying proteins from two-dimensional gels by molecular mass searching of peptide fragments in protein sequence databases, Proc. Nat'l Acad. Sci. USA, vol. 90, pp. 5011-5015 (1993).|
|96||William McFadden, Techniques of Combined Gas Chromatography Mass Spectrometry: Applications in Organic Analysis, pp. 51-52 (1973).|
|97||Winona C. Barker et al., Protein Sequence Database, in Methods in Enzymology, vol. 183 (Molecular Evolution: Computer Analysis of Protein and Nucleic Acid Sequences) pp. 31-49 (Russell F. Doolittle ed. 1990).|
|98||Yu-Luan Chen et al., Collision Cross Sections of Myoglobin and Cytochrome c Ions with Ne, Ar, and Kr, J. Am. Soc. Mass Spectron, vol. 8, pp. 681-687 (1997).|
|99||Zoe Grosser et al., Current Measurement Capabilities for Endocrine Disrupting Compounds, Proc. 16thAnnual Waste Testing & Quality Assurance Symposium (2000).|
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|U.S. Classification||250/282, 250/281, 250/288|
|International Classification||H01J49/06, H01J49/26, G01N27/62, H01J49/42, H01J49/04, B01D59/44, H01J49/00|
|Cooperative Classification||H01J49/044, H01J49/067, H01J49/063|
|European Classification||H01J49/04L3, H01J49/06L, H01J49/06G1|
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