JP2001526447A - Ion analysis in devices including time-of-flight mass spectrometers and linear ion traps - Google Patents

Abstract

(57) Abstract A method for analyzing ions is performed in a mass spectrometer device including an ion source, a linear RF quadrupole, and a time-of-flight mass spectrometer. Ions are generated from the ion source and sent to a linear RF quadrupole. To retain ions within the linear RF quadrupole, a voltage is applied across the linear RF quadrupole and the linear RF quad operates as an ion trap. The ions of interest are selected within the linear RF quadrupole and unwanted ions are rejected. The selected ions are then excited and bombarded with a neutral gas, causing collision-induced dissociation of the selected ions, thus forming fragment ions for analysis in a time-of-flight mass spectrometer. The voltage at one end of the linear RF quadrupole is then adjusted to pass the selected ions and fragment ions through a time-of-flight mass spectrometer. Thereby, spectra of the selected ions and fragment ions can be obtained from the time-of-flight mass spectrometer.

Description

DETAILED DESCRIPTION OF THE INVENTION

FIELD OF THE INVENTION The present invention relates to mass spectrometers, and more particularly, to ion analysis in devices including time-of-flight mass spectrometers.

[0002] Very many types of spectrometer in the field of background mass spectrometry invention have been developed and are combined more various analyzer elements. One well-known analyzer is the quadrupole mass spectrometer, which has two or more mass spectrometer quadrupole stages to provide MS / MS (two-stage tandem mass spectrometry) capability. It has been known. It is also known to combine a quadrupole stage with a time-of-flight mass spectrometer (TOF-MS), as described in detail below. TOF-MS has a high scanning speed, and there is no limitation on the mass range.
Further, the use of a reflectron has the advantage that the resolution is 10,000 or more. However, TOF-MS usually does not provide MS / MS capability. 3D ion trap mass spectrometers can perform MS / MS analysis with relatively simple equipment, but generally operate at lower resolution than Reflectron TOF-MS. The ion trap mass spectrometer cannot increase the resolution unless the scanning speed is made very slow. Furthermore, it is difficult to send ions from an external source into a 3D ion trap, and the mass range is limited.

One proposal by one of the inventors of the present invention is disclosed in US Pat. No. 5,179,278.
Issue. This patent describes the use of an RF multipole ion guide as an interface between an ion source and an ion trap. The aim is to improve the duty cycle of the ion trap mass spectrometer. But MS
There is no special teaching about using the multipole device itself in full trapping mode to provide / MS capability. Rather, what is taught is to apply a selected voltage across the space in the multipole device to reflect ions from the second end, the outflow end, to the first end, the inflow end. To achieve trapping by causing the second end to reflect back toward the outflow end.
For this reason, the ions are retained in the space for a long time, which is enough time for the ion trap type analyzer to analyze the ion sample previously given.

[0004] US Patent No. 5,652,427 describes the use of an RF multipole that includes a number of independent stages with different degrees of vacuum. However, this configuration is merely intended to transfer ions from the high pressure source to the mass spectrometer. Without teaching about trapping ions in any multipole stage, M
There is no teaching about S / MS capabilities.

[0005] US Pat. No. 5,420,425 (Bier et al., Assigned to Finnigan Corporation) relates to an ion trap mass spectrometer for analyzing ions. This mass spectrometer has electrodes shaped to increase the volume occupied by ions. A quadrupole electric field is provided to trap ions that are within a predetermined mass-to-charge ratio range, and then those ions of a particular mass of the trapped ions become unstable and become instable relative to the central axis of the trap chamber. The electric field is changed so as to leave the chamber at right angles. Ions leaving the analyzer are detected, providing a signal indicative of the mass-to-charge ratio of the ions. This patent teaches how to initially introduce ions within a predetermined mass-to-charge ratio range into the chamber, and then change the electric field to select only some ions for later processing. The quadrupole electric field is then adjusted to trap product ions of the residual ions. The residual ions then dissociate, that is, react with the neutral gas to form the product ions described above. The quadrupole field is then changed again to remove ions whose mass-to-charge ratio is within the desired range for detection. It should be noted that ions are not detected with time-of-flight (TOF) instruments. Since Finnigan's device uses radial injection, it will create an ion stream with a wide spatial and velocity distribution. It is difficult to handle such a beam and introduce it into a TOF-MS analyzer.

[0006] Some researchers have shown that a linear RF quadrupole operating at moderately high pressures can be used to interface an electrospray source with a TOF-MS (eg, May 12-16, 1996). See Chernushevich et al. At the 44th ASMS Conference on Mass Spectrometry and Related Topics in Portland, Oregon, USA. Some researchers have used hexapole and octopole ion guides instead of quadrupoles. In hexapole and octopole fields, ions of different m / z usually do not have a well-defined kinetic frequency, and thus have the great advantage of using quadrupoles, that is, resonant excitation of selected ions, Injection is not possible.

[0007] It is also known to use a 3D ion trap as an interface between the ion source and the TOF-MS (SM Michael et al .; "Review of Scientific Instruments") , Vol. 63 (19
1992), pp. 4277-4284: and Purves and Li
); Journal of Microcolumn Separations, Vol. 7, 1995, No. 6, p. 603). 3D ion traps can be equipped with MS / MS capabilities (Qian and Lubman; Rapid Communications in Mass Spectrometry, Vol. 10, (1996), p. 1079). The use of a three-dimensional ion trap has many disadvantages. First, the ion implantation efficiency is at most one-tenth that of a two-dimensional quadrupole. Second, in a three-dimensional trap, the ion storage volume is small, so even if there is no space charge problem, only a relatively small number of ions can be stored, thus limiting the dynamic range of concentration in a three-dimensional trap. .

[0008] A related technique using a TOF mass spectrometer in addition to two independent multipoles has been proposed (HR Morris et al .; "Rapid Communications in Mass Spectrometry", ed. 10 (1996), 88
9 pages). Here, the selection of ions at a given m / z is performed by a first quadrupole mass filter as before. The selected ions are then passed through a hexapole to which only RF has been applied and dissociated by collision with a neutral gas. The resulting ions are then passed through a TOF-MS to obtain a product ion spectrum. Furthermore, a system with a first mass analysis quadrupole and a quadrupole to which only a second RF is applied has been described (Chevchenko; "Rapid Communications in Mass Spectrometry", 11 (1997), pp. 1015 to 1024). Both of these two systems are relatively complex and expensive, and have a multi-stage configuration that tends to reduce sensitivity.

Finally, a more recent proposal is a paper entitled "A New Technique for the Decomposition of Selected Ions in Molecular Ion Reactors Combined with True Time-of-Flight Mass Spectrometry" (A. Dodonov, et al.) "Rapid Communications in Mass Spectrometry", Vol. 11, (1997), pp. 1649-1656). This paper shows, in effect, limited experimental results performed on preselected ions. That is, experiments have been performed with only one compound.
There is no special teaching about using the device to perform the selection step. Two modes of ion dissociation are disclosed. In the first mode, the movement of the parent and fragment ions is chosen to be stable, and the RF field forces these ions to oscillate about the quadrupole axis. At the same time, a DC voltage is applied along the axis of the device to accelerate the ions, and this DC field strength controls the collision induced fragmentation of the ions. For this purpose, the quadrupole is 1 mbar (
It is filled with a gas having a pressure of about 100 Pa). No selection of the mass-charge ratio is made,
All ions present are accelerated by the DC field. Fragment ions with larger or smaller m / z than the mass-to-charge ratio of the parent ion can be transported to the TOF mass analyzer for analysis. Note that the applied electric field may accelerate the fragment ions and cause further fragmentation, but this fragmentation can be controlled to some extent by controlling the electric field strength. Nevertheless, the applied axial electric field does not discriminate between different types of ions.

In a second mode, an RF field chosen to have an amplitude and frequency with a mash parameter q = 0.9, such that the desired ion is near the limit of stable ion motion. The ions are fragmented by confining the ions within the quadrupole. This increases the velocity of the parent ion, thus causing collision "heating" and fragmentation of the parent ion. Thus, only precursors, ie, ions having a mass-to-charge ratio greater than the m / z ratio of the parent ion, are stable in the quadrupole, and only these ions are transported to the detector, ie, TOF-MS. Ions whose m / z ratio is smaller than the mass-to-charge ratio of the parent ion are rejected due to the instability of the motion of such ions. For multiply charged ions, this is not a severe limitation, since some of the fragment ions have less charge and therefore have a higher mass-to-charge ratio, but for monovalent ions no fragments are detected. Will.

A disadvantage of both models is that all ions in the quadrupole are simultaneously excited and dissociated. If two compounds are present, they both fragment, and it is generally not possible to know which fragment originated from which precursor.

SUMMARY OF THE INVENTION The present invention has realized a relatively simple device that can obtain the capabilities of a tandem mass spectrometer by combining a linear quadrupole, or other multipole, with TOF-MS. The quadrupole, or other multipole, operates as an ion trap, and the ions are selected by resonant ejection of ions of a different mass than the ions or otherwise. The isolated ions are then excited in a quadrupole or other multipole and subjected to collision-induced dissociation or fragmentation.

According to the present invention, there is provided an ion analysis method in a mass spectrometer device including an ion source, a linear RF quadrupole and a time-of-flight mass spectrometer, comprising: (1) extracting ions from the ion source; Generating and sending the ions to a linear RF quadrupole; (2) applying a voltage across the linear RF quadrupole to operate the linear RF quadrupole as an ion trap; (3) linear RF quadrupole. Selecting the ions of interest in the quadrupole and eliminating unwanted ions; (4) exciting the ions and colliding the ions with a neutral gas to cause collision-induced dissociation of the ions, and thus the time of flight Forming fragment ions for analysis in a mass spectrometer; (5) adjusting the voltage at one end of the linear RF quadrupole to pass selected ions and fragment ions through a time-of-flight mass spectrometer Including; obtaining a spectrum at and (6) time-of-flight mass spectrometer of the selected and fragment ions; to process.

Preferably, a quadrupole device is used as the device that inherently has a well-defined stabilization parameter and excitation frequency for a particular ion. x direction and y
The directional motions are separated and both can be excited with good selectivity. However, for some applications, it may be desirable or possible to use other 2D multipole formats, such as a hexapole or octupole. When operating such a device at low RF voltage,
Ion movements are described in "Advanced Studies in Chemical Physics", Vol. 82 (
(1992), pp. 1-176, frequency is close to a well-defined harmonic motion (as described by Gerlich). It should also be noted that a linear RF quadrupole or multipole may include only one quadrupole or multipole, or may include two sets of quadrupole or multipole rods in tandem. is there.

Another aspect of the present invention is a method for performing MS ⁿ (n-stage tandem mass spectrometry) using a linear R
The F quadrupole can be used to perform multiple mass spectrometry steps. That is, the method comprises, after step (4), isolating and exciting one or more fragment ions within the linear RF quadrupole, causing collision-induced dissociation of the one or more fragment ions and further fragmentation Additional steps can be included to form the formed ions. Further, the method can include multiple isolation-excitation cycles of one or more fragment ions within a linear RF quadrupole, wherein each cycle includes at least one of the fragment ions formed in the previous cycle. This includes isolating and exciting the above to form further fragmented ions. In each cycle, the fragment ions and the selected ions are all excited and can cause collision-induced dissociation.

The selected ions and / or fragment ions are: (i) excitation of the selected ions by resonance excitation at a particular secular frequency; and (ii) collision-induced dissociation of the selected ions. Excitation by applying one of broadband excitation waveforms.

[0017] Yet another aspect of the invention is an apparatus incorporating one or more linear RF quadrupoles, or other multipoles, and a time-of-flight mass spectrometer and adapted to perform the method of the invention. I will provide a.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS To better understand the present invention and to show more clearly how it can be put into practice, reference is made to the accompanying drawings, by way of example.

Referring to FIG. 1, an electrospray source is shown at 2. Of course, any suitable ion source can be used, such as EI (electron ionization), CI (chemical ionization), laser desorption, and the like. Ions from electrospray source 2 pass through orifice 4. Nitrogen gas, which may be heated to promote the evaporation of the solvent, is supplied as shown. The ions are then applied to maintain the desired low pressure.
It is sent to a chamber 5 connected to a rotary pump. The skimmer 6 then provides an orifice through which the desired ions are sent to the first RF quadrupole 8. This quadrupole 8 connects the usual connections for RF and DC voltage supply in a known manner,
Includes a set of equipped quadrupole rods. The quadrupole 8 operates in a mode where only RF is applied to pass ions of a wide range of mass-to-charge ratios. For simplicity, electrical connection details and power supplies have been omitted.

Although the entrance lens 10 separates the first quadrupole 8 from the second RF quadrupole 12,
Although the two chambers can be used at different pressures, the lens 10 is not separating the two chambers because the two quadrupoles 8,12 are substantially in a single chamber. Please be careful. The second RF quadrupole 12 also operates in a mode where only RF is applied. As shown at 11 in FIG. 11, a connection to a turbo pump is provided to keep the pressure at, for example, about 1-10 mTorr (about 0.133-1.33 Pa). As shown, the first quadrupole 8 is shorter than the second quadrupole 12. For example, the length of the first quadrupole 8 is 5 cm, and the length of the second quadrupole 12 is 2 cm.
It can be 0 cm. That is, the quadrupoles need not be the same length.

An injection aperture 14 is provided at an injection portion of the second quadrupole 12, and subsequently, the ion beam is controlled to convert the ion beam into a source region 18 of a time-of-flight mass spectrometer (TOF-MS) 20. There is a series of rear lenses or electrodes 16 to ensure that

Here, the time-of-flight mass spectrometer 20 is shown in a direction perpendicular to the axes of the quadrupoles 8 and 12. Obviously, it is equally possible to arrange the TOF-MS 20 on the same axis with respect to the quadrupoles 8 and 12. A connection 22 is provided in a known manner so that the TOF-MS can be pumped to the desired degree of vacuum.

In use, if the voltages at the entrance and exit of the quadrupoles 8, 12 are set to allow the ions to pass continuously, the TOF-MS 20 is operated conventionally to provide an electrospray source. A mass spectrum of the ions from 2 is obtained. Electrodes in the source region 18 of the TOF-MS 20, in a known manner, to collect the ions and provide an ion pulse traveling through the TOF-MS, the time of flight of the ions being measured to provide a spectrum of these ions Is activated.

Here, according to the present invention, a blocking voltage can be applied to one or both of the entrance and exit of the first and second quadrupoles 8 and 12. This blocking voltage works to trap ions within each quadrupole. Unwanted ions of the trapped ions can then be rejected by resonant excitation at the secular frequency of the ions. In addition, it traps ions with only one m / z value, and
Isolation can also be achieved by using a filtered noise field known as the T waveform to eliminate all other ions. The SWIFT waveform is essentially
This is a noise waveform having a notch or gap at a frequency corresponding to the secular frequency of the ion of interest. The isolated ions can then be excited and dissociated by collision with a neutral gas. There are numerous ways to cause excitation, collision, and fragmentation. Next, by lowering the trapping voltage applied to the electrode 14 between the second quadrupole 12 and the TOF-MS 20, the generated ion fragments are subjected to TOF-MS.
It can be driven, or transported, into the MS 20. The ion is TOF-MS
Entering the source region of 20, a fragment ion mass spectrum is obtained.

The ions have an energy close to the thermal energy that they can have, and the second quadrupole 1
2 can enter the source region 18 of the TOF-MS. Alternatively, ions were described by B. Thomson et al. At the 44th ASMS Conference on Mass Spectrometry and Related Topics, May 12-16, 1996, in Portland, Oregon. 2nd RF quadrupole 1
By setting an appropriate axial electric field at 2, it is also possible to accelerate toward the source region 18. The transfer of TOF-MS to the source region usually takes about several tens of milliseconds for thermal ions, but the acceleration of ions to TOF-MS has the advantage that the transfer time can be reduced to about 1 millisecond.

For example, in ICP-MS (Inductively Coupled Plasma Mass Spectrometry), high intensity Ar ⁺ ions can cause problems and render the detector virtually useless. To overcome this, an ion sample from the ion source 2 can be passed through the first quadrupole 8. In the first quadrupole 8, a voltage can be applied to the skimmer 6 and lens 10, the electric field applied at the resonance frequency of the Ar ⁺ ions is effectively excluded Ar ⁺ ions from the ion sample. Next, the voltage applied to the lens 10 is adjusted to adjust the second quadrupole 1.
2 can advance the ion sample. In the second quadrupole 12, the noise field or SWI filtered to further isolate the ions of interest
An FT waveform can be provided. Then, the voltages of the aperture 14 and the lens 16 are adjusted to move the desired ions to the TOF-MS 20.

[Brief description of the drawings]

FIG. 1 is a schematic diagram showing a preferred embodiment of the present invention.

[Explanation of symbols]

 2 Electrospray source 4 Orifice 5 Chamber 6 Skimmer 8,12 RF quadrupole 10 Incident lens 14 Exit aperture 16 Back lens 18 Source area 20 Time-of-flight mass analyzer

──────────────────────────────────────────────────続 き Continuation of front page (81) Designated country EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE ), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, SD, SZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CU, CZ, DE, DK, EE, ES, FI, GB, GE, GH, GM, HR, HU, ID, IL, IS, JP, KE, KG, KP , KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, UA, UG, US, UZ, VN, YU, ZW (72) Inventor Campbell, Jennifer M. USA 02143 Summerville Francesca Street 37 Apartment 1 (72) Inventors Collings, Bruce A. Canada V5A2S7 British Columbia Burnaby Bainbridge Avenue 2709 F-term (Reference) 5C038 JJ02 JJ06 JJ07 JJ11

Claims (15)

[Claims] 1. A method for analyzing ions in a mass spectrometer device including an ion source, a linear RF quadrupole and a time-of-flight mass spectrometer, the method comprising: (1) generating ions from the ion source; To the linear RF quadrupole; (2) applying a voltage across the linear RF quadrupole to operate the linear RF quadrupole as an ion trap; Selecting at the linear RF quadrupole to eliminate unwanted ions; (4) exciting the selected ions and causing the ions to collide with a neutral gas to cause collision-induced dissociation of the ions; Forming fragment ions for analysis in the time-of-flight mass spectrometer; (5) adjusting the voltage at one end of the linear RF quadrupole to obtain the selected ions and the fragment ions; Passing the fragment ions through the time-of-flight mass spectrometer; and (6) obtaining spectra of the selected ions and the fragment ions in the time-of-flight mass spectrometer. . 2. The step (3) comprises: (i) eliminating ions having a predetermined secular frequency by exciting at the secular frequency; and (ii) only one m / z.
2. The method of claim 1 including applying a filtered noise electric field to reject ions other than desired ions having a value. 3. After step (4), exciting one or more of the fragment ions in the linear RF quadrupole to cause collision-induced dissociation of the one or more fragment ions. 3. The method of claim 1 further comprising the additional step of forming fragmented ions. 4. The method of claim 1, wherein the one or more fragment ions in the linear RF quadrupole include multiple excitation cycles, each cycle exciting one or more of the fragment ions formed in the previous cycle. 4. The method of claim 3, further comprising forming fragmented ions. 5. The method of claim 4, wherein in each of said cycles, all of said fragment ions and said selected ions are excited to cause collision-induced dissociation. 6. The method of claim 6, wherein the selected ions are: (i) excite the selected ions by resonance excitation at a particular secular frequency; and (ii) cause collision-induced dissociation of the selected ions. 2. The method of claim 1, including applying a broadband excitation waveform to cause the excitation to occur. 7. One or more of said selected ions and said fragment ions: (i) exciting said selected ions and said fragment ions by resonance excitation at a particular secular frequency; and (ii) 6. The method of claim 5 including exciting with one of: applying a broadband excitation waveform to cause collision-induced dissociation of the selected ions and the fragment ions. 8. A method for analyzing ions in a mass spectrometer device including an ion source, a linear RF multipole, and a time-of-flight mass spectrometer, the method comprising: (1) generating ions from the ion source; (2) applying a voltage to both ends of the linear RF multipole to operate the linear RF multipole as an ion trap; (3) ions of interest in the linear RF multipole (4) exciting the selected ions and causing the ions to collide with a neutral gas to cause collision-induced dissociation of the ions, and thus the time-of-flight mass Forming fragment ions for analysis in an analyzer; (5) adjusting the voltage at one end of the linear RF multipole to adjust the selected ions and the fragment ions; Passing the fragment ions through the time-of-flight mass spectrometer; and (6) obtaining spectra of the selected ions and the fragment ions in the time-of-flight mass spectrometer. . 9. The step (3) comprises: (i) eliminating ions having a predetermined secular frequency by exciting at the secular frequency; and (ii) only one m / z.
9. The method of claim 8, comprising applying a filtered noise electric field to reject ions other than desired ions having a value. 10. After the step (4), exciting one or more of the fragment ions in the linear RF multipole to cause collision-induced dissociation of the one or more fragment ions; 10. The method according to claim 8, further comprising the additional step of forming fragmented ions. 11. The method according to claim 11, wherein the linear RF multipole includes multiple excitation cycles of one or more of the fragment ions, each cycle exciting one or more of the fragment ions formed in the previous cycle. The method of claim 10, comprising forming fragmented ions. 12. The method of claim 11, wherein in each of said cycles, all of said fragment ions and said selected ions are excited to cause collision-induced dissociation. 13. The selected ions are: (i) excite the selected ions by resonance excitation at a specific secular frequency; and (ii) cause collision-induced dissociation of the selected ions. 9. The method of claim 8, including applying a broadband excitation waveform for exciting by one of the following: 14. One or more of said selected ions and said fragment ions: (i) exciting said selected ions and said fragment ions by resonance excitation at a particular secular frequency; and 13. The method of claim 12, comprising: exciting with one of: ii) applying a broadband excitation waveform to cause collision-induced dissociation of the selected ions and the fragment ions. 15. The method of claim 8, comprising performing the method using one of a hexapole and an octupole as the linear RF multipole.