EP0575777A2 - Verfahren zur Verwendung eines Massenspektrometers - Google Patents

Verfahren zur Verwendung eines Massenspektrometers Download PDF

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Publication number
EP0575777A2
EP0575777A2 EP93108670A EP93108670A EP0575777A2 EP 0575777 A2 EP0575777 A2 EP 0575777A2 EP 93108670 A EP93108670 A EP 93108670A EP 93108670 A EP93108670 A EP 93108670A EP 0575777 A2 EP0575777 A2 EP 0575777A2
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EP
European Patent Office
Prior art keywords
trap
ions
ion trap
supplemental
sample
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Application number
EP93108670A
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English (en)
French (fr)
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EP0575777A3 (de
EP0575777B1 (de
Inventor
Gregory J. Wells
Mingda Wang
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Varian Medical Systems Inc
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Varian Associates Inc
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Priority to EP98103434A priority Critical patent/EP0852390B1/de
Priority to EP97104015A priority patent/EP0786796B1/de
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Publication of EP0575777A3 publication Critical patent/EP0575777A3/en
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    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/14—Ion sources; Ion guns using particle bombardment, e.g. ionisation chambers
    • H01J49/145—Ion sources; Ion guns using particle bombardment, e.g. ionisation chambers using chemical ionisation
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/004—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn
    • H01J49/0045—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn characterised by the fragmentation or other specific reaction
    • H01J49/005—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn characterised by the fragmentation or other specific reaction by collision with gas, e.g. by introducing gas or by accelerating ions with an electric field
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/26—Mass spectrometers or separator tubes
    • H01J49/34—Dynamic spectrometers
    • H01J49/42—Stability-of-path spectrometers, e.g. monopole, quadrupole, multipole, farvitrons
    • H01J49/4205—Device types
    • H01J49/424—Three-dimensional ion traps, i.e. comprising end-cap and ring electrodes
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/26—Mass spectrometers or separator tubes
    • H01J49/34—Dynamic spectrometers
    • H01J49/42—Stability-of-path spectrometers, e.g. monopole, quadrupole, multipole, farvitrons
    • H01J49/426—Methods for controlling ions
    • H01J49/427—Ejection and selection methods

Definitions

  • the present invention relates to methods of using ion trap mass spectrometers ("ion traps”) by applying supplemental voltages to the trap, and is particularly related to methods of operating ion traps in the chemical ionization mode, and for conducting multiple mass spectroscopy experiments ("MS n ").
  • ion traps mass spectrometers
  • the quadrupole ion trap is a well-known device for performing mass spectroscopy.
  • a ion trap comprises a ring electrode and two coaxial end cap electrodes defining an inner trapping volume.
  • Each of the electrodes preferably has a hyperbolic surface, so that when appropriate AC and DC voltages (conventionally designated “V” and “U”, respectively) are placed on the electrodes, a quadrupole trapping field is created. This may be simply done by applying a fixed frequency (conventionally designated "f") AC voltage between the ring electrode and the end caps. The use of an additional DC voltage is optional.
  • an ion trap is operated by introducing sample molecules into the ion trap where they are ionized.
  • ions may be stably contained within the trap for relatively long periods of time. Under certain trapping conditions, a large range of masses may be simultaneously held within the trap.
  • Various means are known for detecting ions that have been so trapped.
  • One known method is to scan one or more of the trapping parameters so that ions become sequentially unstable and leave the trap where they may be detected using an electron multiplier or equivalent detector.
  • Another method is to use a resonance ejection technique whereby ions of consecutive masses can be sequentially scanned out of the trap and detected.
  • ⁇ is equal to 2 ⁇ f.
  • the equations set forth actually relate to stability in the direction of the z axis, i.e. , the direction of the axis of the electrodes. Ions will become unstable in this direction before becoming unstable in the r direction, i.e. , a direction radial to the axis. Thus, it is normal to limit consideration of stability to z direction stability.
  • the differential in stability results in the fact that unstable ions will leave the trap in the z direction, i.e. , axially.
  • the DC voltage, U is set at 0.
  • U the DC voltage
  • a z 0 for all mass values.
  • the value of q z will be inversely proportional to the mass of the particle, i.e., the larger the value of the mass the lower the value of q z .
  • V the higher the value of q z .
  • EI electron impact ionization
  • Chemical ionization involves the use of a reagent gas which is ionized, usually by EI within the trap, and allowed to react with sample molecules to form sample ions.
  • Commonly used reagent gases include methane, isobutane, and ammonia. Chemical ionization is considered to be a "softer" ionization technique. With many samples CI produces fewer ion fragments than the EI technique, thereby simplifying mass analysis.
  • Chemical ionization is a well known technique that is routinely used not only with quadrupole ion traps, but also with most other conventional types of mass spectrometers such as quadrupole mass filters, etc.
  • photoionization is a well known technique that, similar to electron impact ionization, will affect all molecules contained in the trap.
  • ion trap mass spectrometer systems in use today include a gas chromatograph ("GC") as a sample separation and introduction device.
  • GC gas chromatograph
  • sample which elutes from the GC continuously flows into the mass spectrometer, which is set up to perform periodic mass analyses.
  • Such analyses may, typically, be performed at a frequency of about one scan per second. This frequency is acceptable since peaks typically elute from a modern high resolution GC over a period of several seconds to many tens of seconds.
  • a continuous flow of reagent gas is maintained. As a practical matter it is undesirable to interrupt the flow of sample gas from the GC to the ion trap.
  • the trap when operating using the RF only method, which is preferred in the '367 patent and which is the method used in all known commercial embodiments of the ion trap, the trap inherently traps all masses above a cut-off mass which is set by the value of the RF trapping voltage.
  • V When V is set low enough the trap inherently has a poor efficiency in trapping high mass ions due to space charge effects.
  • a theoretical way of loocking at this is that the volume of the interior of the ion trap which stores ions of a particular mass is proportional to the value of V and is inversely proportionally to the mass.
  • V a smaller volume of the ion trap is available to store high mass ions than low mass ones.
  • the volume is quite small the number of ions than can be stored is reduced due to space charge effects.
  • Some reagent molecules form a variety of ions having different masses. Ionization at RF voltages substantially below that necessary to trap the lowest mass reagent ion, which is necessary to remove most of the high mass sample ions, will reduce the number of reagent ions that are trapped, as well as the high mass sample ions. This effect is related to mass so that the higher mass reagent ions will be disproportionately lost from the trap.
  • the method of the lowering the trapping voltage is not applicable, however, to solving this problem since it would not eliminate low mass reagent ions from the trap.
  • One solution used to solve this problem is to raise the RF trapping voltage so as not to store the low mass reagent ions.
  • this has the undesired effect of changing the trapping conditions from those which are normally used. For example, when the trapping voltage is set to store ions of mass 20 and above, the average ionizing energy of electron entering the trap is 70 eV. Raising the trapping voltage to store only ions of mass 45 and above, so as to eliminate methane reagent ions at mass 43, would double the average electron energy. Such an increase would change the mass spectrum of many compounds and would reduce the trapping efficiency for the sample ions.
  • product ions In a CI process it is desirable to optimize the number of product ions that undergo mass analysis. If there are too few product ions, the mass analysis will be noisy, and if there are too many product ions resolution and linearity will be lost.
  • the formation of product ions is a function of the number of reagent ions present in the trap, the number of sample molecules in the trap, the reaction rate between the reagent ions and the sample ions, and the reaction time during which reagent ions are allowed to react with sample molecules.
  • This prescan is a complete CI scan cycle in which the ionization and reaction times are fixed at values smaller than those that would be used in a normal analytical scan, and in which the product ions are scanned out of the trap faster than in a normal analytical scan.
  • the resulting product ions that are ejected from the trap during the prescan are not mass resolved and the ion signal is only integrated to give a total product ion signal.
  • the prescan the total number of product ions in the trap are measured and the parameters, i.e. , the ionization time and/or the reaction time for the subsequent mass analysis scan are adjusted.
  • the patent covers a two-step process consisting of first conducting a "prescan" of the contents of the ion trap to obtain a gross determination of the number of product ions in the trap, followed by a mass analysis scan of the type taught in the '367 patent, with the parameters of mass analysis scan being adjusted based on the data collected during the prescan.
  • the disadvantage of the prior art method of extending the dynamic range by using a prescan to estimate the sample amounts in the trap is that it requires additional time to perform the prescan, and thus fewer analytical scans can be performed in the same time period. Not only does each of the prescan consume time, but each produces data which has no independent value apart from its use in adjusting the parameters for the mass analysis scan.
  • MS n experiments There is a demand to employ the ion trap mass spectrometer in conducting so-called MS n experiments.
  • MS n experiments a single ion species is isolated in the trap and is dissociated into fragments.
  • the fragments created directly from the sample species are known in the art as daughter ions, and the sample is referred to as the parent ion.
  • the daughter ions may also be fragmented to create granddaughter ions, etc.
  • the value of n refers to the number of ion generations that are formed; thus, is an MS2 or MS/MS experiment, only daughter ions are formed and analyzed.
  • the ions oscillate within the trap they collide with molecules of the damping gas in the trap and undergo collision induced dissociation thereby forming daughter ions.
  • the ions can similarly be fragmented.
  • the difficulty with the method of the '101 patent is that the precise resonant frequency of the ions of interest cannot be determined a priori but must be determined a posteriori .
  • the resonant frequency of an ion also referred to as its secular frequency, varies with the ion mass-to-charge ratio, the number of ions in the trap, hardware variances and other parameters which cannot be precisely determined in a simple way.
  • the precise resonant frequency must of an in species be determined empirically. While empirical determination can be performed without great difficulty when a static sample is introduced into the trap, it is quite difficult to accomplish when a dynamic sample, such as the output of a GC, is used.
  • One prior art approach to overcoming the foregoing problem in determining the precise resonant frequency of a sample ion of interest is to use a broadband excitation centered around the calculated frequency.
  • a broadband excitation may have a bandwidth of about 10 KHz.
  • Another method is to conduct a frequency prescan, i.e. , sweep the supplemental field across a frequency range in the area of interest and observe the resonant frequency empirically.
  • a frequency prescan i.e.
  • Another object of the present invention is to provide a method for conducting electron impact ionization experiments in an ion trap in the presence of a reagent gas, whereby reagent ions formed in the trap are eliminated from the trap before they are able to react with sample molecules.
  • Yet another object of the present invention related to a method of optimizing the experimental parameters utilized in an ion trap in order to operate within dynamic range of the trap.
  • Still another object of the present invention is to provide a simple, yet highly effective, method for conducting MS n experiments in an ion trap that does not require the empirical determination of the resonant frequency of the sample species isolated in the trap.
  • Yet another object of the present invention is to provide an alternate method of scanning a trap to obtain a mass spectrum of its contents.
  • the invention comprises adjusting the trapping field parameters of an ion trap mass spectrometer so that ions having mass-to-charge ratios within a desired range will be stably trapped, introducing sample and reagent gas into the trap, ionizing the contents of the trap, and eliminating sample ions from the trap by applying a supplemental AC voltage to the trap which cause the sample ions, but not the reagent ions, to be ejected from the trap.
  • the supplemental AC voltage may either be a broadband voltage having frequency components corresponding to the resonant frequencies of the higher mass sample ions, or a low-frequency voltage having a magnitude selected to cause only masses above a selected cut-off mass to be ejected from the trap.
  • a supplemental AC field is used to eliminate reagent ions, but not sample ions, formed in the ion trap during electron ionization of the contents of the trap, by resonant ejection so that EI experiments may be conducted in the presence of a reagent gas flow, without the need to readjust the trapping field.
  • mass spectral data associated with the largest peak measured during one scan of the ion trap is used to adjust, if necessary, experimental parameters utilized during the subsequent scan so that the trap is operated within its dynamic range.
  • a low frequency supplemental dipole voltage is applied to the trap and is used to cause fragmentation of the ions within the trap, and may be used to scan the contents of the trap.
  • FIG. 1 is a plot of the stability diagram associated with an ion trap.
  • FIG. 2 is a partially schematic view of apparatus used to practice the method of the present inventions.
  • FIG. 3 is a grah showing the control of the supplemental broadband AC field in relation to the gating of the electron beam used for electron impact ionization in accordance with the present invention.
  • FIGS. 4A - 4G are mass spectra of various samples comparing the present invention with the method of the prior art.
  • FIG. 5 shows an alternate arrangement of the apparatus of FIG. 2 for use in practicing the present invention.
  • FIGS 6A - 6E are mass spectra of various samples showing how the application of a supplemental low frequency field may be used to cause fragmentation of a parent ion within an ion trap.
  • FIGS. 7A - 7C are mass spectra showing how the application of a supplemental low frequency field may be used to eliminate high mass ions from an ion trap.
  • FIGS. 8A - 8C are mass spectra showing how the application of a supplemental low frequency field may be used in conducting chemical ionization experiments.
  • Ion trap 10 shown schematically in cross-section, comprises a ring electrode 20 coaxially aligned with upper and lower end cap electrodes 20 and 35, respectively.
  • the trap electrodes have hyperbolic inner surfaces, although other shapes, for example, electrodes having a cross-sections forming an arc of a circle, may also be used to create trapping fields.
  • the design and construction of ion trap mass spectrometers is well-known to those skilled in the art and need not be described in detail.
  • a commercial model ion trap of the type described herein is sold by the assignee hereof under the model designation Saturn.
  • Sample gas for example from a gas chromatograph 40, is introduced into the ion trap 10. Since GC's typically operate at atmospheric pressure while ion traps operate at greatly reduced pressures, pressure reducing means (not shown) are required. Such pressure reducing means are conventional and well known to those skilled in the art. While the present invention is described using a GC as a sample source, the source of the sample is not considered a part of the invention and there is no intent to limit the invention to use with gas chromatographs. Other sample sources, such as, for example, liquid chromatographs with specialized interfaces, may also be used.
  • Sample and reagent gas that is introduced into the interior of ion trap 10 may be ionized by electron bombardment as follows.
  • a beam of electrons such as from a thermionic filament 60 powered by filament power supply 65, is controlled by a gate electrode 70.
  • the center of upper end cap electrode 30 is perforated (not shown) to allow the electron beam generated by filament 60 and gate electrode 70 to enter the interior of the trap.
  • the electron beam collides with sample and reagent molecules within the trap thereby ionizing them.
  • Electron impact ionization of sample and reagent gases is also a well-known process that need not be described in greater detail.
  • a trapping field is created by the application of an AC voltage having a desired frequency and amplitude to stably trap ions within a desired range of mass-to-charge ratios.
  • RF generator 80 is used to create this field, and is applied to the ring electrode. While it is well known that one may also apply a DC voltage to modify the trapping field and to work at a different portion of the stability diagram of FIG. 1, as a practical matter, commercially available ion traps all operate using an AC trapping field only.
  • a variety of methods are known for determining the mass-to-charge ratios of the ions which are trapped in the ion trap to thereby obtain a mass spectrum of the sample.
  • One known method is to scan the trap so that ions of sequential mass-to-charge ratio are ejected in order.
  • a first known method of scanning the trap is to scan one of the trapping parameters, such as the magnitude of the AC voltage, so that ions sequentially become unstable and leave the trap where they are detected using, for example, electron multiplier means 90.
  • a supplemental AC dipole voltage applied across end caps 30 and 35 of ion trap 10.
  • a voltage may be created by a supplemental waveform generator 100, coupled to the end caps electrodes by transformer 110.
  • the supplemental AC field is used to resonantly eject ions in the trap.
  • Each ion in the trap has a resonant frequency which is a function of its mass-to-charge ratio and of the trapping field parameters.
  • Ions ejected in this manner can also be detected by electron multiplier 90 or an equivalent detector.
  • the contents of the trap can be scanned in sequential order by either scanning the frequency of the supplemental RF field or by scanning one of the trapping parameters such as the magnitude of V, the AC trapping voltage. As a practical matter, scanning the magnitude of the AC voltage is preferred.
  • supplemental RF generator 100 which may also be used for scanning the trap as described above, is capable of generating a broadband RF field which is used to resonantly eject sample ions created by EI during the time that the reagent gas is being ionized.
  • FIG. 3(a) shows the gating of the electron beam used to ionize the reagent gas. Beginning at t1 and ending at t2, electron gate 70 is turned on to allow the electron beam to enter the trap to form reagent ions from the neutral reagent gas. As shown in FIG.
  • supplemental waveform generator 100 applies a broadband signal to the end caps of the trap, 30, 35, for a period of time that begins at t1 and ends at t3. As shown, the broadband excitation exceeds the gate time. Alternately, the supplemental broadband signal could be applied starting at a time later than t1, or even later than t2, i.e. , after the electron ionization is complete. Likewise, the supplemental signal could also start at a time prior to t1. The important aspect being that the supplemental field for elimination of unwanted sample ions be kept "on" for a period of time extending after the end of the period during which ions are created.
  • the broadband AC voltage applied to the end caps can either be out of phase (dipole excitation) or in phase (quadrupole excitation).
  • An alternative method of obtaining quadrupole excitation is the application of the supplemental waveform to the ring electrode as shown in FIG. 5, rather than to the end caps.
  • the supplemental waveform contains a range of frequencies of sufficient amplitude to eject unwanted sample ions of mass greater than the highest mass reagent ion, by means of resonant power absorption by the trapped ions.
  • Each of the sample ions is in resonance with a frequency component of the supplementary waveform. Accordingly, they absorb power from the supplementary field and leave the trapping field. After the supplemental field has ejected the unwanted ions it is turned off and the CI reagent ions react with the sample molecules to produce CI sample ions. These ions are then scanned from the trap for detection in a conventional manner as described above.
  • the supplemental waveform described above is broadband and has a first frequency component corresponding to the lowest mass to be ejected and a last frequency corresponding to the highest mass to be ejected. Between the first and last frequencies are a series of discrete frequency components which may be spaced evenly or unevenly, and which may have phases that are either random or with a fixed functional relationship.
  • the amplitudes of the frequency components can either be uniform or thy can be tailored to a functional form so as to compensate for frequency dependencies of the hardware or to compensate for the distribution of q values due to the distribution of the masses that are stored in the trap.
  • the broadband waveform has a sufficient number of frequency components so that any ion with a resonant frequency between the first and last components of the waveform will be resonantly ejected by this supplemental field.
  • all sample ions formed during EI will be eliminated from the trap before the mass ananlysis scan and there will be no gaps in the mass range that is affected.
  • the reagent gases that are used in CI experiments are all low in molecular weight such that the reagent ions formed during EI of the contents of the trap will, in almost all cases, be lower in mass-to-charge ratio than the sample ions.
  • a specific frequency may be added to the broadband excitation to cause that specific mass to be ejected along with others.
  • the advantage of the invention over prior art is the ability to remove unwanted sample ions formed by EI during the ionization of the CI reagent gas.
  • the ability to reject these ions will allow longer ionization times and greater emission currents to be used, thus increasing the sensitivity of CI.
  • FIG. 4A shows the residual EI spectrum of a sample of tetrachloroethane using the scan conditions that are used in the prior art method.
  • FIG. 4B shows the elimination of the sample ions formed during the ionization step using the broadband waveform.
  • FIG. 4C shows the residual EI spectrum of a sample of trichloroethane and PFTBA with methane reagent gas present in the trap using the prior art method.
  • FIG. 4D shows the elimination of the sample ions formed during the ionization step using the broadband waveform of the present invention. It can be seen that the reagent ions at mass 43 are still present even though the sample ions that are just above them in mass are removed.
  • FIG. 4E shows the spectrum under the same conditions as in FIG.
  • FIG. 4F shows a spectrum of hexachlorobenzene using the prior art method. A mixture of EI ion fragments are observed at mass 282, 284, 286, 288 and 290. In addition, ions due to the protonated sample (from CI) are observed at mass 283, 285, 287, 289 and 291.
  • FIG. 4G shows the spectrum using the method described herein. It can be seen that the unwanted ions from the EI process are almost completely removed.
  • data obtain from one scan are used, if necessary, to adjust the parameters of the subsequent scan to ensure that the trap is operated within its dynamic range.
  • the amplitude of the most intense ion of a scan (the base peak) is used to adjust the ionization and/or reaction time for the next scan.
  • the magnitude of the base peak is used to adjust the ionization and reaction times for the subsequent scan so as to maintain a substantially constant number of ions of the base peak. Since most of the charge ejected from the trap during the scan is due to the base peak, it is a good representation of the total amount of charge from the sample in the trap. By keeping the total sample charge nearly constant in the trap the dynamic range of the sample can be increased.
  • the mass spectral information from one scan it is possible to adjust the parameters of the subsequent mass analysis scan to focus, for example, on only particular sample ions of interest, i.e., to optimize for a particular species.
  • both the reaction time and the ionization time are changed in a set ratio. This makes it easier to normalize the results from one scan to the next.
  • An advantage of this inventive method is the reduction in the scan time for large dynamic range samples. This is accomplished by using the intensity of the base peak from the previous scan as a measure of the amount of sample in the trap; thus eliminating the need for a time-consuming prescan as is used in the prior art.
  • a broadband supplemental field can also be used to eliminate reagent ions from the trap when conducting an EI experiment.
  • the user of an ion trap may wish to conduct both EI and CI experiments on the same sample stream. Under such circumstances, it is undesirable to stop the flow of reagent gas into the trap while conducting EI, yet the presence of reagent ions is likely to cause confused analytic data.
  • a supplemental RF broadband excitation any reagent ions formed during electron impact ionization of the sample can be resonantly ejected from the trap as soon as they are created.
  • the same timing sequence shown in FIG. 3 can be used to practice this aspect of the invention.
  • the broadband RF excitation may be constructed in accordance with any of the above-described alternatives, except that the frequency range should be tailored to eliminate only the low mass reagent ions.
  • Waveform generator 100 of FIG. 2 can also be used to apply a low frequency non-resonant field to perform CI experiments, to conduct MS n , experiments and to scan the contents of the trap to obtain a mass spectrum
  • a low frequency supplemental voltage from waveform generator 100 is applied as a dipole field across end caps 30, 35 of ion trap 10.
  • the frequency of the dipole field is unrelated to the resonant frequencies of any of the ions (whether sample or reagent ions) stored in the trap.
  • the waveform shape is preferably a square wave, but may be almost any shape including sine, sawtooth, triangular waveforms.
  • the frequency of the supplemental voltage is relatively low, such as between 100 Hz and several thousand Hz. Experiments suggest that the present invention would work at frequencies below about 10,000 Hz, which is about the beginning of the range of resonant frequencies of sample ions. Preferably, however, the frequency should be in the range of hundreds of Hz.
  • the supplemental squarewave dipole field alternately displaces the center of the pseudo-potential well of the trapping field to different locations along the z-axis.
  • trapped ions pick up translational energy from the trapping field and begin to oscillate around the new center.
  • displacement of the center of the oscillations tends to increase the magnitude of the oscillations.
  • the ions lose energy to the background gas, they move towards the new center. If the center of the pseudo-potential field is again moved, such as when the squarewave changes polarity, the process repeats itself. It can be seen that the frequency of the supplemental dipole field should be low so that ions are able to migrate towards the new center before the field is changed.
  • the ions When the center of the pseudo-potential well is moved, as described above, the ions begin oscillating about a new point in space becoming more energetic. The energy added to ions will be sufficient to cause many of then to dissociate due to collisions with the damping gas, thereby forming daughter ions. As the process is repeated, more and more of the ions will dissociate in this manner.
  • Another advantage of this method is that it imparts more energy to the ions than resonance excitation and, thus, in some cases, can result in more extensive ion fragmentation.
  • the method described above does not rely on the resonant frequency of the ions in the ion trap, it operates on all ions in the trap simultaneously.Thus, using this method it is possible to simultaneously create several generations of ion fragments without the need to apply resonant frequencies associated with each of the fragments. If desired, prior to practicing the present invention, an ion species of interest could first be isolated in the trap in accordance with known prior art methods.
  • Mass-to-charge ratio cannot, alone, be used to unambiguously identify a parent ion. However, knowing not only the mass-to-charge ratio of the parent ion, but also the masses of all of the ion fragments can be used to unambiguously identify the parent.
  • a low frequency voltage to the ion trap can be used as a mechanism to cause ions having masses above a certain cutoff mass to be eliminated from the ion trap.
  • the cutoff mass is a function of the magnitude of the supplemental low-frequency voltage.
  • One model of how an ion trap operates is that the ions are, in essence, trapped in a potential well, with the "depth" of the well being a function of, among other things, the mass-to-charge ratio. The higher the mass, the shallower the well. It is believed that the observed phenomenon of elimination of high mass ions by application of a low frequency supplemental field is related to the relatively shallow depth of the potential well associated with high mass ions. In particular, it is believed that the shifting of the center of the pseudo-potential well causes high mass ions to gain sufficient energy to overcome the well barrier and leave the ion trap.
  • This phenomenon can be used to advantage both in chemical ionization experiments and in scanning the ion trap.
  • An alternate method of eliminating the sample ions is to apply a low-frequency supplemental field, as described above, having a magnitude which is sufficient to eliminate all sample ions from the trap, while leaving the reagent ions unaffected.
  • the timing sequence for applying this supplemental low-frequency field may be as depicted in FIG. 3, or any of the alternatives timing sequences described above in connection therewith. In this regard, it is noted that the ionization period of FIG.
  • FIG. 3(a) which may be less than a millisecond in duration, may be shorter in duration than a half-cycle of the low-frequency supplemental voltage.
  • the duration of application of the supplemental voltage as shown in FIG. 3(b), may be much longer in duration, and FIG. 3 is not drawn to scale.
  • a low-frequency supplemental voltage can also be used as a mechanism for scanning the ion trap to obtain a mass spectrum. This can be done by scanning the magnitude of the supplemental low-frequency voltage. If the supplemental voltage is initially low and is ramped-up, masses will be ejected from the trap sequentially in descending order. Alternately, the low-frequency supplemental voltage can be held constant and one of the trapping parameters scanned to obtain the equivalent effect.
  • FIG. 6A is a mass spectrum of 1,1,1-trichloroethane obtained in a conventional manner.
  • the peak at mass 97 corresponds to CH3CCl2+.
  • FIG. 6B is a mass spectrum of 1,1,1-trichloroethane obtained using the same experimental parameters as FIG. 6A, except that a low-frequency supplemental squarewave voltage (100 Hz, 42 volts) was applied for 20 milliseconds. It can be seen from FIG. 6B that the peak intensity at mass 97 has been reduced, and that ions of mass 61 (CH2CCl+) are abundant. As a result of non-resonant excitation, the mass 97 ions absorbed energy and some were dissociated to form the mass 61 ions.
  • FIGS. 6C and 6D show spectra of 1,1,1-trichloroethane obtained using the same parameters used to obtain the results of FIGS. 6A and 6B, except that the frequency of the supplemental squarewave was set at 300 and 600Hz, respectively.
  • the similarity of the spectra of FIGS. 6B, 6C and 6D show that the dissociation is largely independent of the frequency of the supplemental field over a broad range.
  • FIG. 6E shows a mass spectrum of 1,1,1-trichloroethane obtained using the method of the prior art, i.e.
  • a resonant sine wave of 139.6KHz (the z-axis resonant frequency of ion mass 97) was applied for 20ms at a level of 800 mv. It can be seen that the daughter ion yields of both methods were about the same.
  • FIGS. 7A-C show mass spectra of PFTBA under various conditions to demonstrate how the method of the present invention may be used to eliminate high mass ions from the ion trap.
  • FIG. 7A shows a complete mass spectra including both the parent and fragment ions.
  • FIG. 7B shows that all ions with mass above 131 were eliminated from the trap when the voltage of the supplemental squarewave was raised to 20v.
  • FIG. 7C shows that raising the voltage to 33v causes all ions with mass greater than 100 to be eliminated from the trap.
  • FIGS. 8A-C show the application to chemical ionization experiments of the ability to eliminate high mass ions from the ion trap by using a low frequency supplemental field.
  • FIGS. 8A-C show the same CI experiments of FIGS. 4B, 4D and 4G, respectively.
  • a low frequency supplemental waveform was used. It can be seen that the results are substantially the same by either method.
  • the FIG. 8A results were obtained using a supplemental field having a frequency of 600 Hz; the FIG. 8B results were obtained using a supplemental field having frequency of 300 Hz; and the FIG. 8C results were obtained using a supplemental field having frequency of 400 Hz.
  • the magnitude of the supplemental voltage was between 20 and 40 v.

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  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • Plasma & Fusion (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electron Tubes For Measurement (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
EP19930108670 1992-05-29 1993-05-28 Verfahren zur Verwendung eines Massenspektrometers Expired - Lifetime EP0575777B1 (de)

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EP98103434A EP0852390B1 (de) 1992-05-29 1993-05-28 Verfahren zum Betreiben eines Ionenfallen-Massenspektrometers
EP97104015A EP0786796B1 (de) 1992-05-29 1993-05-28 Verfahren zum Betrieb von Ionenfallenmassenspektrometern

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0608885A1 (de) * 1993-01-27 1994-08-03 Varian Associates, Inc. Ionenfalle Massenspektrometer
GB2291534A (en) * 1994-07-19 1996-01-24 Bruker Franzen Analytik Gmbh Collisionally induced decomposition of ions in nonlinear ion traps
EP0746873A1 (de) * 1994-01-11 1996-12-11 Varian Associates, Inc. Verfahren zur isolierung einer quadrupolionenfalle
EP0793256A1 (de) * 1996-03-01 1997-09-03 Varian Associates, Inc. Verfahren zur Massenabtastung mittels eines Ionenfallenmassenspektrometers
EP1009015A2 (de) * 1994-01-10 2000-06-14 Varian Associates, Inc. Raumladungskontrollverfahren für hohe Ionenisolierung in einem Ionenfallenmassenspektrometer mittels dynamish anpassbarer Probenaufnahme
US6410913B1 (en) * 1999-07-14 2002-06-25 Bruker Daltonik Gmbh Fragmentation in quadrupole ion trap mass spectrometers
WO2015003819A1 (de) * 2013-07-10 2015-01-15 Carl Zeiss Smt Gmbh Massenspektrometer, dessen verwendung, sowie verfahren zur massenspektrometrischen untersuchung eines gasgemisches

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4384542B2 (ja) 2004-05-24 2009-12-16 株式会社日立ハイテクノロジーズ 質量分析装置
DE102005061425B4 (de) * 2005-12-22 2009-06-10 Bruker Daltonik Gmbh Rückgesteuerte Fragmentierung in Ionenfallen-Massenspektrometern
JP4996962B2 (ja) 2007-04-04 2012-08-08 株式会社日立ハイテクノロジーズ 質量分析装置
US10985002B2 (en) * 2019-06-11 2021-04-20 Perkinelmer Health Sciences, Inc. Ionization sources and methods and systems using them

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EP0202943A2 (de) * 1985-05-24 1986-11-26 Finnigan Corporation Steuerungsverfahren für eine Ionenfalle
EP0215615A2 (de) * 1985-09-06 1987-03-25 Finnigan Corporation Betriebsverfahren einer Quadrupolionenfalle
EP0336990A1 (de) * 1988-04-13 1989-10-18 Bruker Franzen Analytik GmbH Methode zur Massenanalyse einer Probe mittels eines Quistors und zur Durchführung dieses Verfahrens entwickelter Quistor
EP0362432A1 (de) * 1988-10-07 1990-04-11 Bruker Franzen Analytik GmbH Methode zur Massenanalyse einer Probe
WO1993005533A1 (en) * 1991-08-30 1993-03-18 Teledyne Mec Mass spectrometry method using supplemental ac voltage signals

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EP0202943A2 (de) * 1985-05-24 1986-11-26 Finnigan Corporation Steuerungsverfahren für eine Ionenfalle
EP0215615A2 (de) * 1985-09-06 1987-03-25 Finnigan Corporation Betriebsverfahren einer Quadrupolionenfalle
EP0336990A1 (de) * 1988-04-13 1989-10-18 Bruker Franzen Analytik GmbH Methode zur Massenanalyse einer Probe mittels eines Quistors und zur Durchführung dieses Verfahrens entwickelter Quistor
EP0362432A1 (de) * 1988-10-07 1990-04-11 Bruker Franzen Analytik GmbH Methode zur Massenanalyse einer Probe
WO1993005533A1 (en) * 1991-08-30 1993-03-18 Teledyne Mec Mass spectrometry method using supplemental ac voltage signals

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0608885A1 (de) * 1993-01-27 1994-08-03 Varian Associates, Inc. Ionenfalle Massenspektrometer
EP1009015A3 (de) * 1994-01-10 2006-01-25 Varian Associates, Inc. Raumladungskontrollverfahren für hohe Ionenisolierung in einem Ionenfallenmassenspektrometer mittels dynamisch anpassbarer Probenaufnahme
EP1009015A2 (de) * 1994-01-10 2000-06-14 Varian Associates, Inc. Raumladungskontrollverfahren für hohe Ionenisolierung in einem Ionenfallenmassenspektrometer mittels dynamish anpassbarer Probenaufnahme
EP0746873A1 (de) * 1994-01-11 1996-12-11 Varian Associates, Inc. Verfahren zur isolierung einer quadrupolionenfalle
EP0746873A4 (de) * 1994-01-11 1997-08-27 Varian Associates Verfahren zur isolierung einer quadrupolionenfalle
GB2291534A (en) * 1994-07-19 1996-01-24 Bruker Franzen Analytik Gmbh Collisionally induced decomposition of ions in nonlinear ion traps
US5528031A (en) * 1994-07-19 1996-06-18 Bruker-Franzen Analytik Gmbh Collisionally induced decomposition of ions in nonlinear ion traps
GB2291534B (en) * 1994-07-19 1998-02-18 Bruker Franzen Analytik Gmbh Collisionally induced decomposition of ions in nonlinear ion traps
EP0793256A1 (de) * 1996-03-01 1997-09-03 Varian Associates, Inc. Verfahren zur Massenabtastung mittels eines Ionenfallenmassenspektrometers
US6410913B1 (en) * 1999-07-14 2002-06-25 Bruker Daltonik Gmbh Fragmentation in quadrupole ion trap mass spectrometers
WO2015003819A1 (de) * 2013-07-10 2015-01-15 Carl Zeiss Smt Gmbh Massenspektrometer, dessen verwendung, sowie verfahren zur massenspektrometrischen untersuchung eines gasgemisches
KR20160030186A (ko) * 2013-07-10 2016-03-16 칼 짜이스 에스엠티 게엠베하 질량 분석계, 그의 사용 및 혼합 가스의 질량 분석 검사를 위한 방법
EP3020063A1 (de) * 2013-07-10 2016-05-18 Carl Zeiss SMT GmbH Massenspektrometer, dessen verwendung, sowie verfahren zur massenspektrometrischen untersuchung eines gasgemisches
TWI579888B (zh) * 2013-07-10 2017-04-21 卡爾蔡司Ｓｍｔ有限公司 質譜儀、其使用方法、及氣體混合物的質譜分析方法
US10304672B2 (en) 2013-07-10 2019-05-28 Carl Zeiss Smt Gmbh Mass spectrometer, use thereof, and method for the mass spectrometric examination of a gas mixture
KR102219556B1 (ko) 2013-07-10 2021-02-24 칼 짜이스 에스엠티 게엠베하 질량 분석계, 그의 사용 및 혼합 가스의 질량 분석 검사를 위한 방법

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DE69333589D1 (de) 2004-09-16
DE69328979T2 (de) 2001-02-15
EP0575777A3 (de) 1994-03-16
JP2004004082A (ja) 2004-01-08
DE69333589T2 (de) 2005-02-03
DE69321165T2 (de) 1999-06-02
DE69328979D1 (de) 2000-08-10
CA2097211A1 (en) 1993-11-30
JP3444429B2 (ja) 2003-09-08
DE69321165D1 (de) 1998-10-29
EP0575777B1 (de) 1998-09-23
JPH0696727A (ja) 1994-04-08

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