JP2743034B2 - Mass spectrometry using supplemental AC voltage signals - Google Patents

Abstract

A mass spectrometry method in which one or more high power supplemental AC voltage signals and one or more low power supplemental AC voltage signals are applied to an ion trap (16). The frequency of each supplemental AC voltage is selected to match a resonance frequency of an ion having a desired mass-to-charge ratio. The low power supplemental voltage signals are applied for the purpose of dissociating specific ions (i.e., parent ions) within the trap, and the high power supplemental voltage signals are applied to resonate products of the dissociation process (i.e., daughter ions) so that they can be detected. In one class of embodiments, the high power voltage signals resonate daughter ions out from the trap for detection by an external detector (24). In another class of embodiments, each high power voltage signal resonates the daughter ions only to a degree sufficient for detection by an in-trap detector (which may comprise one or more of the electrodes (11-13) which define the trapping field, or may be mounted integrally with such electrodes).

Description

Description: TECHNICAL FIELD The present invention relates to a method in which a parent ion in an ion trap is dissociated,
The present invention relates to mass spectrometry in which the resulting daughter ions are resonated and detectable. In particular, the present invention is a mass spectrometry in which a supplemental alternating voltage signal is applied to an ion trap such that parent ions in the trap are dissociated and the resulting daughter ions resonate for detection. .

BACKGROUND In conventional mass spectrometry techniques, known as MS / MS, ions having a mass-to-charge ratio within a selected range (known as "parent ions") are sequestered in an ion trap. . The captured parent ions are then allowed to dissociate (eg, by bombardment with background gas molecules in the trap), producing ions known as "daughter ions." Thereafter, daughter ions are emitted from the trap and detected.

For example, U.S. Pat.
No. 4,736,101 discloses an MS / MS method in which ions (with a mass to charge ratio within a given range) are captured in a three-dimensional quadrupole capture field. The capture field is then scanned to cause unwanted parent ions (non-parent ions having the desired mass-to-charge ratio) to be sequentially ejected from the trap. The capture field is then changed again, allowing the daughter ions of interest to be stored. The captured parent ions are then dissociated to produce daughter ions, and the daughter ions are sequentially released from the trap for detection. Unnecessary parent ions are released from the trap prior to dissociation of the parent ions. To do so, US Pat. No. 4,736,101 teaches that the capture field should be scanned by sweeping the amplitude of the fundamental voltage that defines the capture field.

U.S. Pat. No. 4,736,101 also teaches that a supplemental alternating field can be added to the trap during periods when parent ions are dissociating. This is the dissociation process (column 5)
(See lines 43-62) or cause specific ions to be ejected from the trap so that the ejected ions are released during the next ejection and sample ion detection (see column 4, line 60-5, column 6, line 6). The purpose is to prevent detection.

Also, U.S. Pat. No. 4,736,101 teaches that traps may be supplemented during initial ionization to release special ions (especially otherwise abundant ions) that would otherwise interfere with the study of other ions of interest. It also suggests that fields can be added (see column 5, lines 7-12).

However, conventional MS / MS methods provide only a limited range of information for each sample of interest. Conventional MS / M
It is desirable to obtain information on a wider range of samples than can be obtained with the S method. In order to minimize the time required to analyze the sample and maximize information about the sample, such information can also be obtained by selectively resonating the daughter ions of interest for detection. desired. However, until the present invention, it was not known how to achieve all of these objectives simultaneously in a single ion trap.

SUMMARY OF THE INVENTION In the mass spectrometry method of the present invention, at least one high power supplemental AC voltage signal (high power in the sense of a signal amplitude sufficient to resonate the selected ions to an extent that allows detection of the ions). Is applied to the ion trap and at least one low-power supplemental alternating voltage signal whose amplitude is sufficient to induce dissociation of the selected ions, but which permits detection of the selected ions. Up to low power in the sense of insufficient signal amplitude to resonate it). The frequency of each supplemental AC voltage signal is selected to match the resonance frequency of the ion having the desired mass-to-charge ratio. Each of the low power supplemental AC voltage signals is applied for the purpose of dissociating particular ions (ie, parent ions) in the trap, and each of the high power supplemental AC voltage signals is the product of the dissociation process (ie, daughter ions). To resonate so that it can be detected.

In one embodiment, a high power AC voltage signal causes daughter ions to resonate and exit the trap for detection by an external detector. In other embodiments using an in-trap detector, each of the high power alternating voltage signals is an in-trap detector (consisting of, or integral with, one or more electrodes that define the capture field). It is only necessary to resonate the daughter ions to a degree sufficient for the detection in the trap by.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a simplified conceptual diagram of an apparatus useful for implementing a type of preferred embodiment of the present invention.

FIG. 2 is a chart representing the signals generated during operation of the first preferred embodiment of the present invention.

FIG. 3 is a chart representing the signals generated during operation of the second preferred embodiment of the present invention.

FIG. 4 is a chart representing the signals generated during operation of the third preferred embodiment of the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The quadrupole ion trap device shown in FIG. 1 is useful for implementing one of the types of preferred embodiments of the present invention. The device of FIG. 1 includes an annular electrode 11 and end electrodes 12 and 13.
And are included. In the three-dimensional quadrupole capture field, the fundamental voltage generator 14 is switched on and a fundamental high-frequency voltage (comprising a high-frequency component and optionally direct current) is applied between the electrode 11 and the electrodes 12 and 13. Is created in the area 16 surrounded by the electrodes 11 to 13. The ion storage area 16 has a radius r ₀ and a vertical dimension z ₀ . Electrode 1
1, 12, and 13 are commonly grounded through a coupling transformer 32.

By switching on the supplemental AC voltage generator 35, the desired supplemental AC voltage signal can be applied across the end electrodes 12 and 13. The supplemental AC voltage signal can be selected to cause the captured desired ions to resonate at the axial resonance frequency (in a manner described in detail below).

When the filament 17 is heated by the filament power supply 18, this directs the ionized electron beam through the opening in the end electrode 12 to the area 16. The electron beam ionizes the molecules of the sample in the area 16 and the resulting ions can be captured in the area 16 by the quadrupole capture field. The cylindrical gate electrode and lens 19 are controlled by a filament / lens control circuit 21 which gates the electron beam as desired.

In one embodiment, the end electrode 13 includes a perforation 23 that emits ions from the area 16 for detection by an external electron multiplier detector 24. Electric meter 27 receives the current signal collected at the output of detector 24 and converts it to a voltage signal for processing in processor 29. The voltage signals are summed and stored in circuit 28.

In a variant of the device of FIG.
Are omitted and replaced by an ion detector in the trap. Such an in-trap detector can be composed of the electrodes of the trap itself. For example, one or both of the end electrodes can be composed (or partially composed) of a fluorescent material (which emits photons in response to the incidence of ions on one surface of the electrode). In another type of embodiment, the in-trap ion detector is clearly distinguished from the end electrodes, but faces one or both of the end electrodes (the ions that strike the end electrodes face the area 16). (To be detected without significant distortion of the shape of the end electrode surface). One example of this type of trapped ion detector is an electrically insulated conductive pin with its tip positioned flush with the end electrode surface (preferably along the Z axis at the center of end electrode 13). Faraday effect detector mounted (in position). Alternatively, ion detectors that do not require direct impact on the detector to detect ions (examples of this latter type of detector include resonant power absorption detectors and image current detectors). ) Can be used. The output of each in-trap ion detector is provided to processor 29 through appropriate detector electronics.

The control circuit 31 generates control signals for controlling the basic voltage generator 14, the filament / lens control circuit 21, and the supplementary AC voltage generator 35. By circuit 31,
In response to commands received from processor 29, circuits 14, 2
Control signals are sent to 1 and 35, and data is sent to processor 29 in response to a request from processor 29.

A first embodiment of the preferred method of the present invention will now be described with reference to FIG. As shown in FIG. 2, the first step of the method (which proceeds during period A) is to store the parent ions in a trap. This is accomplished by applying a fundamental voltage signal to the trap (by activating the fundamental voltage generator 14 of the apparatus of FIG. 1) to establish a quadrupole capture field and introducing an ionized electron beam into the ion storage area 16. Achieved. Alternatively, the parent ions can be generated externally and injected into the storage area 16.

The basic voltage signal is determined by the capture field (storage area
Within 16) the parent ion (eg, the parent ion resulting from the interaction between the sample molecule and the ionized electron beam) along with daughter ions (generated during period B) having a desired range of mass-to-charge ratios Selected to be stored. Other ions generated in the trap during period A, having a mass to charge ratio outside the desired range, escape from area 16 and during period A, the value of the "ion signal" shown in FIG. As these ions escape, the detector 24 becomes saturated, as indicated by.

Before the end of period A, the ionized electron beam is shut off at the gate.

Thereafter, during the period B, the first supplemental AC voltage signal is output (FIG. 1).
(Such as by activating the supplemental ac voltage generator 35 of the device). The voltage signal has a frequency selected to resonantly excite selected daughter ions, and the resonantly excited daughter ions are detected by a detector within the trap (or a detector mounted outside the trap). Have a sufficiently large amplitude (ie, power) to resonate to a sufficient extent.

While the first supplemental AC voltage is applied to the trap by generator 35, a second supplemental AC voltage is applied to the trap by generator 35 (or a second supplemental AC voltage generator connected to the appropriate electrodes). Applied. The power of the second supplemental AC voltage signal (the applied output voltage) is smaller than the power of the first supplemental AC voltage signal (typically, the power of the second supplementary AC voltage signal is of the order of 100 mV, The power of the first supplemental AC voltage signal is on the order of 1V). The second supplemental AC voltage signal comprises a frequency that is selected to induce the dissociation of a particular parent ion (to produce daughter ions), but whose amplitude (ie, power) is significantly more than this power. Must have a small amplitude such that the ions are not resonated to the extent that they are excited and detected from the trap. (In embodiments using the in-trap ion detector, the second supplemental AC voltage signal is selected Should have enough power to induce the dissociation of the parent ion
The power must be small enough that the trajectory of a significant number of ions excited by this power is not large enough to be detected in the trap. Next (again, during period B), the frequency of the second supplemental AC voltage signal is changed to induce dissociation of another parent ion. Each daughter ion generated during this frequency scan, which happens to comprise a resonance frequency that matches the frequency of the first supplemental signal, is resonated from the trap for detection (or consists of a trap electrode or Or, it is resonated enough to be detected by an in-trap detection device attached together with the trap electrode).
Thus, for example, the "ion signal" shown within period B of FIG. 2 is detected (having a common resonance frequency) resulting from the sequential dissociation of four different types of parent ions.
There are four peaks, each representing a daughter ion.

An alternative method of inducing the dissociation of several different parent ions is to keep the frequency of the second supplemental AC voltage signal fixed and maintain the parameters of the capture field (ie, the frequency or amplitude of the AC component of the fundamental RF voltage, Alternatively, one or more amplitudes of the DC component of the basic high-frequency voltage are changed. By changing the trapping field in this manner, the frequency of each parent ion (the frequency at which each parent ion moves in the trapping field) is changed, and the frequency of another parent ion is changed to the frequency of the second supplementary AC voltage signal. Matching occurs. Changing the capture field in this manner also changes the frequency of each daughter ion, and thus the frequency of the first supplemental AC voltage signal (at any point in time the first supplemental AC voltage signal causes the daughter ion of interest to resonate. Each) must be changed.

During the period immediately following period B, all voltage signal sources are closed. Now (ie, during period C of FIG. 2), the method of the present invention can be repeated.

In a variation of the method of FIG. 2, the first or second supplemental AC voltage signal (or both) has two or more different frequency components within a selected frequency range. Each such frequency component must have a frequency and amplitude characteristic of the type described above in connection with FIG.

Next, a second preferred embodiment will be described with reference to FIG. As shown in FIG. 3, the first step in this embodiment (which occurs during period A) is to store the parent ions in the trap. This is the generator of the device of FIG.
This is achieved by applying a fundamental voltage signal to the trap (by activating 14) to establish a quadrupole capture field and introducing an ionized electron beam into the ion storage area 16. An alternative is to define the quadrupole capture field and store the externally generated parent ions in the storage area.
Inject into 16.

The basic voltage signal is determined by the capture field (period A
The daughter ions (produced in the trap after) are stored together with the parent ions (within area 16) with a mass-to-charge ratio that is all within the desired range. (Including ions resulting from interaction with the electron beam during period A)
Since other ions have mass-to-charge ratios outside the desired range, the detector 24 will saturate as it escapes during period A as indicated by the value of the "ion signal" in FIG. Escape from 16.

Before the end of period A, the ionized electron beam is closed at the gate.

Thereafter, during period B, a first supplemental AC voltage signal is provided to the trap (such as by activating the activation generator 35 of the apparatus of FIG. 1). This voltage signal has a frequency (f _P1 ) that is selected to induce the dissociation of the first parent ion (P1), but a significant number of the ions to be excited are excited and detected from within or outside trap detection. It has such a small amplitude (ie, power) that it does not resonate enough to be detected.

Next (again, during period B), the first supplemental AC voltage signal is stopped and a "daughter" supplemental AC voltage signal is applied to the trap to allow the daughter of the first parent ion from the trap to be detected. Resonate (or resonate enough that the daughter of the first parent ion is detected by the in-trap detector). Thus, for example, the portion of the "ion signal" shown within period B of FIG. 3 has a peak representing the detected daughter ions resulting from the dissociation of the first parent ion during the application of the first correction signal.

Rather than a single daughter supplemental AC voltage signal (as shown during period B in FIG. 3), a set of two or more daughter supplemental AC voltage signals may be applied during period B. Each signal in the set should comprise a frequency that is selected to resonate another daughter of the first parent ion for detection (either by an in-trap detector or an off-trap detector). The same set of daughter supplemental AC voltage signals are applied for periods C, D and E
It can also be applied to the trap during (discussed below).

Generally, the frequency of each daughter ion is different from the frequency of the parent ion. Thus, in one type of embodiment, the frequency of each daughter supplemental AC voltage signal is such that the low power supplemental AC voltage signal applied to dissociate the parent of the daughter ion resonated by the daughter supplemental AC voltage signal (ie, The "first" supplemental AC voltage signal referred to above, or the "second", "third", and "second" discussed with reference to periods "C", "D", and "E" of FIG. 4) Supplementary AC voltage signal).

However, following the application of the low power supplemental AC voltage signal and prior to the application of the daughter supplemental AC voltage signal, the parameters of the capture field (ie, the frequency or amplitude of the AC component of the fundamental RF voltage, or the DC frequency of the fundamental RF voltage) Altering one or more of the component amplitudes) is also within the scope of the invention. By changing the trapping field in this manner, the frequency of each daughter ion (the frequency at which each daughter ion moves in the trapping field) is changed, and the frequency of each daughter ion is changed to the frequency of the low power supplemental AC voltage signal. Can be matched. In this latter case, both the daughter supplemental AC voltage signal and the low power supplemental AC voltage signal can have the same frequency (although these two supplemental AC voltage signals are fed to a "separate" acquisition field). .

Performing only the steps described with reference to periods A and B of FIG. 3 is within the scope of the present invention. Alternatively, additional steps described with reference to periods C, D, E, and F may be performed.

During time period C (shown in FIG. 3), a second supplemental AC voltage signal is applied to the trap (such as by activating generator 35 of the apparatus of FIG. 1). This voltage signal is
Having a different frequency (f _p2 ) selected to induce the dissociation of the second parent ion (P2), this voltage signal excites a significant number of ions and is detected from in-trap or out-of-trap detection. It has such a small amplitude that it does not resonate to a sufficient degree.

Next (and also during period C), the second supplemental AC voltage signal is stopped, and the daughter supplemental AC voltage signal (or a set of daughter supplementary AC voltage signals) is again applied to the trap and the second parental AC voltage signal is applied to the trap. The ions are resonated for detection by the detector inside or outside the trap. FIG. 3 reflects the possibility that such daughter ions of interest were not generated at all in response to the second supplemental signal. Thus, the ion signal portion shown in the period C of FIG.
There is no peak representing the detected daughter ion produced by dissociation of the parent ion.

During period D, a third supplemental AC voltage signal is applied to the trap (such as by activating generator 35 of the apparatus of FIG. 1). This voltage signal is the third parent ion (P3)
_Has another frequency (f _p3 ) selected to induce the dissociation of the ions, but not so much that a significant number of ions are excited and resonated enough to be detected inside or outside the trap It has an amplitude (ie, power).

Next (and also during period D), the third supplemental AC voltage signal is stopped, and the daughter supplemental AC voltage signal (or a set of daughter supplementary AC voltage signals) is again applied to the trap and the third parent AC voltage signal is applied to the trap. The ions are resonated for detection by the detector inside or outside the trap. The "ion signal" portion shown within period D of FIG. 3 has a peak representing the detected daughter ions that result from the dissociation of the third parent ion during the application of the third supplemental signal.

Next, during period E, a fourth daughter supplemental AC voltage signal is applied to the trap (such as by activating generator 35 of the apparatus of FIG. 1). This voltage signal has another frequency ( _fp4 ) selected to induce the dissociation of the fourth parent ion (P4), but to the extent that a significant number of ions are excited and detected. It has such a small amplitude that it cannot be resonated.

Next (and also during period E), the fourth supplemental AC voltage signal is stopped, and the daughter supplemental AC voltage signal (or a set of daughter supplementary AC voltage signals) is again applied to the trap, causing the fourth supplemental AC voltage signal to reappear in the trap. The daughter ions of the fourth daughter ion are resonated for detection (or resonated to a degree sufficient for detection by the detector in the trap). FIG. 3 shows that the daughter ion is the fourth.
It reflects that nothing is generated in response to the supplementary signal. Thus, there is no peak representing the detected daughter ions in the ion signal portion shown within the period E in FIG.

During the period immediately following period E, all supplemental AC voltage signals are stopped. Here, the method of the present invention is repeated (ie, during period F of FIG. 3).

In a variation of the method of FIG. 3, all or some of the supplemental AC voltage has two or more different frequency components within a selected frequency range. Each such frequency component must have the frequency and amplitude characteristics described above with reference to FIG.

Next, a third preferred embodiment of the method of the present invention will be described with reference to FIG. As shown in FIG.
The first step in this embodiment is to store the parent ions in the trap. This causes the basic voltage signal to be generated (by activating generator 14 of the apparatus of FIG. 1).
This is accomplished by applying a trap to establish a quadrupole capture field and introducing an ionized electron beam into the storage area 16. Alternatively, the quadrupole capture field is established and externally generated parent ions are introduced into the storage area 16.

The fundamental voltage signal is such that daughter ions (generated in the trap by interaction with the electron beam during period A) together with parent ions (all produced in the trap during the period A) have a mass-to-charge ratio all within the desired range due to the capture field. (In storage area 16). Other ions having a mass-to-charge ratio outside the desired range (including ions arising from interaction with the electron beam during period A) will cause detector 24 to escape during period A during escape. 3 (saturated as indicated by the value of the "ion signal" of 3).

Before the end of period A, the ionized electron beam is shut off at the gate.

Thereafter, during period B, a first supplemental AC voltage signal is applied to the trap (such as by activating the activation generator 35 of the apparatus of FIG. 1). This voltage signal is (molecular weight
A first ion having a frequency (f _P1-N ) selected to resonantly excite the first parent ion (with _P1-N ) and the first ion is detected (by an external detector or a detector in the trap) It has enough power (i.e., sufficient amplitude) to resonate to an extent that it can be obtained.

The method of FIG. 4 is particularly useful for analyzing “neutral loss” daughter ions. Neutral loss daughter ions consist of two components of the parent ion: a charge of 0 (neutral) and a molecular weight N.
(N is sometimes referred to herein as the “neutral mass lost”) and a daughter molecule (eg, a water molecule);
And the dissociation of P into a neutral loss daughter molecule having a molecular weight of PN with P as the parent ion molecular weight. Thus, during period B of the method of FIG. 4, the first supplemental signal has the same nature as the neutral loss daughter ions generated later during the application of the second supplemental signal (having frequency f _P1 ). Ions having a mass to charge ratio are resonated.

Next (and also during period B), the first supplemental AC voltage signal is stopped and a second supplemental AC voltage signal is applied to the trap. The second supplemental AC voltage signal has a frequency selected to induce dissociation of the first parent ion having a molecular weight of P1. The power of the second supplementary AC voltage signal is smaller than the power of the first supplementary AC voltage signal (typically, the power of the second supplementary AC voltage signal is about 100 mV, Is about 1V). The power of the second supplemental AC voltage signal is small enough not to resonate to the extent that a significant number of ions are excited and detected by the signal.

Next (and also during period B), a third supplemental AC voltage signal is applied to the trap. The third supplemental AC voltage signal has a frequency (f _P1-N ) and a neutral loss daughter having a molecular weight P 1 -N (produced early during application of the second supplemental AC voltage signal during period B). It has sufficient amplitude to resonate the ions to a sufficient extent for detection inside or outside the trap.

The ion signal portion existing during the period B in FIG.
And two peaks occurring during the application of the third supplemental voltage signal. The second peak cannot be confidently interpreted as representing a neutral loss daughter ion resulting from the dissociation of the first parent ion, while the second peak is generated during the application of the second supplemental signal. Can be interpreted without any ambiguity as being representative of the neutrally lost daughter ion.

Next, during period C, fourth, fifth, and sixth supplemental AC voltage signals are sequentially applied to the trap, thereby resulting from dissociation of the second parent ion (having a molecular weight of P2) ( Enables the detection of neutrally lost daughter ions (with a molecular weight of P2-N). The fourth and sixth supplemental voltage signals have a frequency (f _P2-N ) selected to resonately excite the second ion (having a molecular weight of _{P 2 -N} ) to detect the second ion (external detection). Has enough power to resonate to the extent that it is detected (by a detector or detector in the trap).

After the application of the fourth supplemental voltage signal, this signal is stopped,
A fifth supplemental AC voltage signal is applied to the trap. The fifth supplemental AC voltage signal has a frequency selected to induce dissociation of a second parent ion having a molecular weight of P2. The power of the fifth supplemental AC voltage signal is smaller than that of the fourth and sixth supplementary voltage signals (typically, about 100 mV), and a remarkable number of ions are excited and detected by the fifth supplementary voltage signal. It is small enough not to resonate to a degree.

Next (and also during period C), a sixth supplemental AC voltage signal is applied to the trap. The sixth supplementary AC voltage signal is
Resonance to the extent that frequency (f _P2-N ) and neutral loss daughter ions having a molecular weight of P 2 -N (produced early during application of the fourth supplemental AC voltage signal during period C) are detected. And an amplitude sufficient to cause

FIG. 4 reflects the possibility that such neutral daughter ions are not generated at all in response to the fifth supplemental signal. Thus, in the portion of the ion signal that occurs during the application of the sixth supplementary signal (within period C in FIG. 4), the ion signal has a peak representing the sample ions detected during the application of the fourth supplementary signal. , There is no peak representing the detected neutral loss daughter ions created for the dissociation of the second parent ion during the application of the fifth supplemental signal.

Finally, during period D, seventh, eighth, and ninth supplemental AC voltage signals are sequentially applied to the trap, resulting from the dissociation of the third parent ion (with a molecular weight of P3) (P3− N
Enables the detection of neutrally lost daughter ions). The seventh and ninth supplementary voltage signals are the third ions (P3-N
Having a frequency (f _P3-N ) selected to resonately excite the third ion to such an extent that the third ion is detected (by an external detector or a detector in the trap). Each has enough power.

After application of the seventh supplemental voltage signal, this signal is stopped,
An eighth supplemental AC voltage signal is applied to the trap. The eighth supplemental AC voltage signal has a frequency selected to induce the dissociation of a third parent ion having a molecular weight of P3. The power of the eighth supplementary AC voltage signal is smaller than the power of the seventh and ninth supplementary voltage signals (typically about 100 mV), and a remarkable number of ions are excited and detected by the eighth supplementary voltage signal. It is small enough not to resonate to a degree.

Next (and also during period D), a ninth supplemental AC voltage signal is applied to the trap. The ninth supplemental AC voltage signal has a frequency (f _P3-N ) and a molecular weight of P3-N such that neutrally lost daughter ions (generated during the application of the seventh supplemental voltage signal) are detected. And an amplitude sufficient to resonate.

The portion of the ion signal that occurs during the application of the ninth supplemental signal (period D in FIG. 4) does not have a peak representing the ions detected during the application of the seventh supplementary signal, but does In between have peaks representing the detected neutral loss daughter ions produced by the dissociation of the third parent ion.

In one variation of the method of FIG. 4, only the operations described with reference to periods A and B are performed to detect neutrally lost daughter ions for only one parent ion. FIG.
In another variation of the method, an additional series of operations (including steps corresponding to those described with reference to periods B, C, or D) is performed (as in the embodiment of FIG. 4). N) Neutral loss daughter ions are detected for more than just three parent ions.

Generally, the frequency of each neutral loss daughter ion is different from the frequency of the parent ion of each neutral loss daughter ion. Thus, in one type of embodiment, the frequency of each high power supplemental AC voltage signal applied during one of the periods "B", "C", or "D" in FIG. Is different from the frequency of the small-power supplemental AC voltage signal applied in the same period of time. However, following the application of each low power supplemental AC voltage signal, and prior to the application of the next high power supplemental AC voltage signal, the parameters of the capture field (ie, the frequency or amplitude of the AC component of the basic high frequency voltage, or the basic Changing one or more of the amplitudes of the DC component of the high frequency voltage) is also within the scope of the embodiment of FIG. By changing the capture field in this manner, the frequency of each neutral loss daughter ion (the frequency at which each neutral loss daughter ion moves in the capture field) is changed, and the frequency of each neutral loss daughter ion is reduced. True match to the frequency of the power supplemental AC voltage signal. In this latter case, both the high power supplemental AC voltage signal and the low power supplemental AC voltage signal are applied (although these two supplemental AC voltage signals are applied to a "separate" acquisition field).
Can have the same frequency.

In another type of embodiment of the present invention, granddaughter ions (in addition to daughter ions) are generated in zone 16 and subsequently detected (not daughter ions). For example, during phase B of the method of FIG. 4, the second (low power) supplemental AC voltage signal comprises an early part and a late part. That is, the early portion has a frequency selected to induce generation of daughter ions (by dissociating the parent ion) and the late portion has the frequency selected to induce generation of granddaughter ions (by dissociating the daughter ion). Having a selected frequency. In this example, the first (high power) supplemental AC voltage signal applied during period B is selected to match the resonant frequency of the granddaughter ions (as opposed to the daughter ions).

For another example, during step B of the method of FIG.
The first (low power) supplemental AC voltage signal comprises an early portion followed by a late portion. That is, the early portion has a frequency selected to induce the production of daughter ions (by dissociating the first parent ion) and the late portion induces the production of granddaughter ions (by dissociating the daughter ions). Have a frequency that is selected to be In this example, the second (high power) supplemental AC voltage signal applied during period B is selected to match the resonant frequency of the granddaughter ions (as opposed to the daughter ions).

In the claims, the phrase "daughter ion" refers to the first
It is intended to refer to daughter ions of a generation, granddaughter ions (the next generation of daughter ions), and daughter ions of the succeeding (third generation or successor) generation.

In a variation of the embodiment of the present invention described with reference to FIG. 3, at least one of the "daughter" supplemental AC voltage signals (or a set of "daughter" supplemental AC voltage signals) is the first, second, and second Once immediately before one of the third or fourth (low power) supplemental AC voltage signals and immediately after the same one of the first, second, third or fourth (low power) supplementary AC voltage signals Again, it is applied twice. The purpose of each such "preliminary" application is to resonate ions having the same mass-to-charge ratio as daughter ions during the application immediately following the low power supplemental AC voltage signal (see FIG. 4). (As in the embodiment of the invention described above).

It will be apparent to those skilled in the art that various other modifications and variations of the method described for the present invention can be made without departing from the scope and spirit of the invention. Although the invention has been described with respect to particular preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments.

Claims (23)

(57) [Claims] (A) setting a capture field capable of capturing parent and daughter ions within a capture area bounded by a set of electrodes; (b) applying a low power supplemental AC voltage signal to said electrodes; First
C. Causing the dissociation of the captured parent ions of the first and second low power supplemental AC voltages to have a first frequency that matches the resonance frequency of the first captured parent ions; An AC voltage signal is applied to the electrode,
Causing the first daughter ion to resonate to an extent sufficient to permit detection of the daughter ion and wherein the high power supplemental ac voltage signal has a second frequency that matches the resonance frequency of the first daughter ion; Causing the first daughter ion to have a first resonance frequency within the trapped field; and (d) applying a second low power supplemental AC voltage signal to the electrode to dissociate a second trapped parent ion. To thereby induce a second daughter ion to produce the second daughter ion.
The low-power supplemental AC voltage signal has a third frequency that matches the resonance frequency of the second supplementary parent ion; and (e) the second daughter ion is detected to a degree sufficient to enable detection of the second daughter ion. (F) changing the trapping field to a second trapping field before or during step (c), wherein the first daughter ion has a second resonance frequency, before or during step (c); A mass spectrometric method comprising: setting a second resonance frequency to be equal to the second frequency. 2. The method of claim 1, wherein said first frequency is different from said second frequency. 3. The method of claim 1, wherein step (f) is performed after step (b), wherein the first frequency is equal to the second frequency. 4. The high power supplemental AC voltage signal causes the first daughter ions to resonately emanate from the trapping area, and the emitted first daughter ions are detected at a detector located outside the trapping area. The method of claim 1, further comprising detecting. 5. The method of claim 1 wherein said high power supplemental AC voltage signal resonates said first daughter ions to an extent sufficient for in-trap detection by an in-trap detector. 6. A capture field that can capture parent and daughter ions in a capture area bounded by a set of electrodes; and b) applying a low power supplemental AC voltage signal to the electrodes; First
C. Causing the dissociation of the captured parent ions of the first and second low power supplemental AC voltages to have a first frequency that matches the resonance frequency of the first captured parent ions; An AC voltage signal is applied to the electrode,
Causing the first daughter ion to resonate to an extent sufficient to permit detection of the daughter ion and wherein the high power supplemental ac voltage signal has a second frequency that matches the resonance frequency of the first daughter ion; And the high-power supplemental AC voltage signal is sufficiently high for in-trap detection by an in-trap detector consisting of at least one of the electrodes or integrally attached to at least one of the electrodes. Mass spectrometry comprising: causing the first daughter ions to resonate; and (d) detecting the first daughter ions at the at least one electrode while the first daughter ions remain in the trap. 7. The capture field is a three-dimensional quadrupole capture field, and step (a) includes applying a fundamental voltage signal having a radio frequency component to the electrode.
the method of. 8. Set up a capture field capable of capturing parent and daughter ions within a capture area bounded by a set of electrodes; and (b) applying a low power supplemental AC voltage signal to said electrodes; First
C. Causing the dissociation of the captured parent ions of the first and second low power supplemental AC voltages to have a first frequency that matches the resonance frequency of the first captured parent ions; An AC voltage signal is applied to the electrode,
The first to an extent sufficient to enable detection of daughter ions.
Causing the daughter ions to resonate, wherein the high power supplemental AC voltage signal has a second frequency that matches the resonance frequency of the first daughter ions and steps (b) and (c) are performed simultaneously. Analysis method. 9. The step (e) of applying a second high power supplemental AC voltage signal to the electrode, and filtering the second daughter ion to an extent sufficient to enable detection of the second daughter ion. 2. The method of claim 1, including causing to resonate and causing the second high power supplemental AC voltage signal to have a fourth frequency that matches a resonance frequency of the second daughter ion. 10. The apparatus of claim 10, wherein the second frequency is equal to the fourth frequency.
The method of claim 9. 11. The step (c) is performed after the step (b), and prior to the step (b), applying a second high power supplemental AC voltage signal having a frequency equal to the second frequency to the electrode. 3. The method of claim 1, further comprising causing the ions having a mass-to-charge ratio that matches the mass-to-charge ratio of the first daughter ion to resonately eject. 12. Prior to step (b), applying a third high power supplemental alternating voltage signal having a frequency equal to said second frequency to said electrode to match the mass to charge ratio of said first daughter ion. And a fourth high power supplemental AC voltage signal having a frequency equal to the third frequency is applied to the electrode, the ions having a mass-to-charge ratio of
The method of claim 1, further comprising resonantly ejecting ions having a mass-to-charge ratio that matches the mass-to-charge ratio of the daughter ions. 13. A three-dimensional quadrupole capture field capable of capturing parent and daughter ions in a capture area bounded by a set of electrodes, wherein the parent ions are captured in the capture area. (B) then applying a low power supplemental AC voltage signal to the electrode to induce dissociation of a first ion of the parent ion to produce a first daughter ion, wherein the low power supplemental AC voltage signal is Applying a high power supplemental AC voltage signal to the electrode while performing steps (c) and (b), wherein the first frequency matches the resonance frequency of the first ion of the parent ion; Causing the first daughter ion to resonate to an extent sufficient to permit detection of the daughter ion, wherein the high power supplemental AC voltage signal has a second frequency that matches the resonance frequency of the first daughter ion. And the low-power supplemental AC voltage signal is 100 mV A mass fractionation method having a level of power, the method comprising causing the high power supplemental AC voltage signal to have a level of 1V power. (A) setting a three-dimensional quadrupole capture field capable of capturing parent and daughter ions in a capture area bounded by a set of electrodes, capturing the parent ions in the capture area; (B) then applying a low power supplemental AC voltage signal to the electrode to induce dissociation of a first ion of the parent ion to produce a first daughter ion, wherein the low power supplemental AC voltage signal is Applying a high power supplemental AC voltage signal to the electrode while performing steps (c) and (b), wherein the first frequency matches the resonance frequency of the first ion of the parent ion; Causing the first daughter ion to resonate to an extent sufficient to permit detection of the daughter ion, wherein the high power supplemental AC voltage signal has a second frequency that matches the resonance frequency of the first daughter ion After (d) and (b) stages Changing the frequency of the low power supplemental AC voltage signal to induce dissociation of different ions of the parent ion; and performing the steps (e) and (d) while continuing the high power supplemental AC voltage signal. Mass spectrometry comprising applying to the electrodes by resonating the daughter ions to an extent sufficient to allow detection of the daughter ions generated during step (d). (A) setting a three-dimensional quadrupole capture field capable of capturing parent and daughter ions in a capture area bounded by a set of electrodes, capturing the parent ions in the capture area; (B) then applying a low power supplemental AC voltage signal to the electrode to induce dissociation of a first ion of the parent ion to produce a first daughter ion, wherein the low power supplemental AC voltage signal is Applying a high power supplemental AC voltage signal to the electrode while performing steps (c) and (b), wherein the first frequency matches the resonance frequency of the first ion of the parent ion; Causing the first daughter ion to resonate to an extent sufficient to permit detection of the daughter ion, wherein the high power supplemental AC voltage signal has a second frequency that matches the resonance frequency of the first daughter ion So that
The first ion of the parent ion is the first ion in the capture field.
Having a resonance frequency, changing the capture field to a second capture field,
The second ion of the parent ion has the first resonance frequency and the continuous application of the low power supplemental AC voltage signal to the electrode triggers dissociation of the second ion of the parent ion to produce the second ion of the parent ion. Generating a second daughter ion having a second resonance frequency in the capture field; changing the frequency of the high power supplemental AC voltage signal to match the second resonance frequency; Mass spectrometry comprising resonating the second daughter ion to an extent sufficient to enable detection of the second daughter ion. (A) setting a three-dimensional quadrupole capture field capable of capturing parent and daughter ions in a capture area bounded by a set of electrodes, capturing the parent ions in the capture area; (B) then applying a low power supplemental AC voltage signal to the electrode to induce dissociation of a first ion of the parent ion to produce a first daughter ion, wherein the low power supplemental AC voltage signal is Having a first frequency that matches the resonance frequency of the first ion of the parent ion; (c) applying a high power supplemental AC voltage signal to the electrode after performing step (b); Causing the daughter ions to resonate to an extent sufficient to allow detection of the daughter ions, such that the high power supplemental AC voltage signal has a second frequency that matches the resonance frequency of the daughter ions, If the AC voltage signal is Has a force, mass spectrometry method of high power supplemental AC voltage signal consists of a power of 1V levels. 17. A three-dimensional quadrupole capture field capable of capturing parent and daughter ions in a capture area bounded by a set of electrodes, wherein the parent ions are captured in the capture area. (B) after step (a), applying a high power supplemental ac voltage signal to the electrode to cause a first ion having a first mass-to-charge ratio to be sufficient to allow detection of the first ion; (C) after step (b), applying a low power supplemental AC voltage signal to the electrode to generate a first daughter ion;
The low-power supplemental AC voltage signal has a first frequency that matches the resonance frequency of the first parent ion to cause dissociation of the parent ion and the daughter ion has a first frequency within the capture field. A first daughter ion having a resonance frequency;
(D) applying a second high power supplemental AC voltage signal to the electrode after performing steps (c) and (d) to provide a mass to charge ratio sufficient to allow detection of the first daughter ion. (E) (b) causing the first daughter ion to resonate to some extent and causing the second high power supplemental AC voltage signal to have a second frequency that matches the resonance frequency of the first daughter ion; After step (c) but before step (c), changing the capture field to a second capture field so that the daughter ions have a second resonance frequency equal to the second frequency. Mass spectrometry method. 18. The method of claim 17, wherein said first parent ion has a molecular weight of P1, and said first ion and said daughter ion have a molecular weight of P1-N with N as the neutral loss mass. 19. The method according to claim 19, wherein the first frequency is different from the second frequency.
The method of claim 17. 20. During step (a), a second parent ion is also captured in the capture area, and (f) after step (e), applying a third high power supplemental AC voltage signal to the electrode. Causing the second ions to resonate to an extent sufficient to allow detection of a second ion having a second mass-to-charge ratio; (g) after step (f), a second low power A supplemental ac voltage signal is applied to the electrode to induce dissociation of the second parent ion to generate a second daughter ion, wherein the second low power supplemental ac voltage signal is applied to the second parent ion. (H) having a third frequency matched to the resonance frequency and the first daughter ion having the second mass-to-charge ratio, and after performing steps (h) and (g), a fourth high power supplemental AC voltage A signal is applied to the electrode and the second daughter ion is applied to an extent sufficient to permit detection of the second daughter ion. The so as to resonate, the method of the fourth high power supplemental AC voltage signal consists to have a fourth frequency matching a resonant frequency of the second daughter ions claim 17. 21. The first parent ion has a molecular weight of P1, the first ion and the first daughter ion have a molecular weight of P1-N with N as a neutral loss mass, and the second parent ion 21. The method of claim 20, wherein has a molecular weight of P2 and the second ion and the second daughter ion have a molecular weight of P2-N. 22. The method of claim 17, wherein said low power supplemental AC voltage signal has a power of the 100 mV level and said high power supplemental AC voltage signal has a power of the 1V level. 23. (f) After step (e), a low power supplemental AC voltage signal is applied to the electrode to induce dissociation of the captured parent ions, wherein the low power supplemental AC voltage signal is (G) after step (f), applying a high power supplemental AC voltage signal to the electrodes to allow detection of the daughter ions. 18. The method of claim 17, further comprising: causing the daughter ions to resonate to some extent, such that the high power supplemental AC voltage signal has a frequency that matches a resonance frequency of the daughter ions.