DE10336500B4 - Method for mass spectrometry - Google Patents

Abstract

Method for mass spectrometry, which comprises the following steps:
Providing a first quadrupole ion trap (T1) having a first lower mass cutoff threshold, a second quadrupole ionic trap (T2) having a second lower mass cutoff threshold, the second lower mass cutoff limit being lower than the first lower mass cutoffline such that at least some mass fractionated ions Charge ratios below the first lower mass cutoff limit, which are not trapped in the first ion trap (T1), are trapped in the second quadrupole ion trap (T2), another ion trap (T0) formed from the second quadrupole ion trap (T2) ejected ions, and a time-of-flight mass analyzer (2, 3) receiving ions ejected from the further ion trap (T0),
mass-selective ejection or scanning of a pulse of ions from the second quadrupole ion trap (T2), wherein the further ion trap (T0) receives the pulse of ions and wherein the ratio between the maximum mass-to-charge ratio of the ions in the pulse of ions and the minimum mass-to-charge ratio of ions in the pulse of ions ≤ 4.0 ...

Description

The The present invention relates to a method for mass spectrometry.

Known 3D (Paul) quadrupole ion trap mass spectrometers have a circular central Ring electrode and two end cap electrodes. These known 3D (Paul) quadrupole ion trap mass spectrometer typically have, compared to other types of mass spectrometers, such as magnetic sector and time of flight mass spectrometers, a relatively low resolution and a relatively low mass accuracy, if the full Mass area is scanned. However, 3D quadrupole ion traps have both MS as well as in MS / MS operating mode a relatively high sensitivity on. There is a particular problem with 3D quadrupole ion traps in that she the disadvantage of a relatively limited Have a mass range and a low cut-off of the Mass to charge ratio below which ions are not stored within the quadrupole ion trap can be. In an MS / MS operating mode can only about a ratio of 3: 1 between the starting mass and the fragment mass and recorded.

Cross acceleration Time of Flight Mass Spectrometer have in contrast Both MS and MS / MS modes offer higher resolution capabilities and higher mass metering accuracy.

typically, become lateral acceleration time-of-flight mass spectrometers with ion sources coupled, which provide a continuous ion beam. Segments of this continuous ion beam then become the subsequent mass analysis extracted in the transverse direction. However, about 75% of the ions do not for the Mass analysis are extracted and lost accordingly.

In the EP 1 367 631 A2 For example, a dual ion trapping mass spectrometer is shown in which an RF potential applied to the first ion trap is decreased over time so that ions are forced out of the trap at a certain potential, regardless of their mass. Heavier ions leave the trap in front of lighter ions. The ions are then trapped in the second ion trap.

The WO 01/15201 A2 discloses a method for fragmentation and analysis of ions using multiple ion traps. Multiple ion traps are provided to provide opportunities for intermediate storage of ions or fragment ions from a mixture of exit ions in a first ion trap. The parent ions may, for example, be fragmented and / or selectively or non-selectively converted to the next and then once more to the last ion trap. Finally, the last ion trap contains the ions to be analyzed which consist of a selection or the entirety of the parent ions or fragment ions thereof. The contents of the last ion trap, ie the ions to be analyzed, are then fed to a mass analyzer.

In both cases For example, the volume of ions to be analyzed is determined by the mass range limitation of predetermined first ion trap.

It is therefore desirable the mass range limitation to address that in conventional Quadrupole ion traps always occur, and the duty cycle of a Increase lateral acceleration time-of-flight mass analyzer when MS and MS / MS experiments performed become.

Advantageously, a mass spectrometer is provided which comprises:
a first ion trap and a second ion trap, wherein the first ion trap is configured to have a first lower mass cut limit in use, and wherein the second ion trap is configured to have a second lower mass cut limit in use; lower mass cut limit is lower than the first lower mass cut limit so that at least some ions having mass to charge ratios below the first lower mass cut limit not captured in the first ion trap are trapped in the second ion trap.

The Combination of two or more ion traps in series, the different lower mass cutoffs advantageously increases the overall ion capture volume or the total ion capture capacity and thus the dynamic range of the ion capture system.

One Mass spectrometers according to the preferred embodiment is able to execute both MS and MS / MS operating modes, and it has an ion source, a series of coupled quadrupole ion traps and a lateral acceleration time-of-flight mass analyzer. The Combination of multiple quadrupole ion traps and the lateral acceleration time of flight mass analyzer provides, compared to other known arrangements, a mass spectrometer with an increased mass range (especially in MS / MS), an increased sensitivity, a increased Massenmeßgenauigkeit and an elevated one Mass resolution.

According to a less preferred embodiment Thus, fragment ions outside the first ion trap can be generated by surface-induced dissociation (SID), collision-induced dissociation (CID), or post-source decomposition (PSD) and then transferred to the first ion trap.

According to the preferred Embodiment can a collision cooling with a bath gas in one or more of the ion traps and / or in the transmission area (in the transmission areas) between the ion traps are used. Collision cooling is reduced advantageously both the kinetic energy of the ions and the kinetic energy width of the ions. The collision cooling causes also improving trapping efficiency within the ion trap, while the ions for the subsequent mass analysis in a time-of-flight mass analyzer, preferably a lateral acceleration time-of-flight mass analyzer, which may optionally have a reflectron, be prepared.

The first ion trap preferably has a quadrupole ion trap. According to the one embodiment includes the first ion trap has a 3D (Paul) quadrupole ion trap with one Ring electrode and two end cap electrodes, wherein the ring electrode and the end cap electrodes have a hyperbolic surface.

According to one another embodiment the first ion trap one or more cylindrical ring electrodes and two substantially planar end cap electrodes.

According to one another embodiment the first ion trap one, two, three or more than three ring electrodes and two substantially planar end cap electrodes.

A the end cap electrode may include a sample or target plate. The sample or target plate can be a substrate with several in have sample areas arranged in a microtitration format, for example, the distance between the samples is approximately or exactly 18 mm, 9 mm, 4.5 mm, 2.25 mm or 1.125 mm. To to or at least 48, 96, 384, 1536 or 6144 samples can be so Be set up on the sample or target plate can be received. One Laser beam or an electron beam is preferably used in the Use directed to the sample or target plate.

A the end cap electrodes of the first ion trap may be a net or have a grid.

The first ion trap can be a 2D (linear) quadrupole ion trap with several Stick electrodes and two end electrodes have.

According to others less preferred embodiments For example, the first ion trap may have a segmented ring set with several Electrodes containing openings of which ions are transmitted or have a Penning ion trap.

Preferably, a first AC or RF voltage having a first amplitude is applied to the first ion trap. The first amplitude is preferably selected from the following group: (i) 0-250 V _pp , (ii) 250-500 V _pp , (iii) 500-750 V _pp , (iv) 750-1000 V _pp , (v) 1000-1250V _pp , (vi) 1250-1500V _pp , (vii) 1500-1750V _pp , (viii) 1750-2000V _pp , (ix) 2000-2250V _pp , (x) 2250-2500V _pp , (xi) 2500-2750V _pp , (xii) 2750-3000V _pp , (xiii) 3000-3250V _pp , (xiv) 3250-3500V _pp , (xv) 3500-3750V _pp , (xvi) 3750 -4000V _pp , (xvii) 4000-4250V _pp , (xviii) 4250-4500V _pp , (xix) 4500-4750V _pp , (xx) 4750-5000V _pp , (xxi) 5000-5250V _pp , (xxii) 5250-5500V _pp , (xxiii) 5500-5750V _pp , (xxiv) 5750-6000V _pp , (xxv) 6000-6250V _pp , (xxvi) 6250-6500V _pp , (xxvii) 6500 6750V _pp , (xxviii) 6750-7000V _pp , (xxix) 7000-7250V _pp , (xxx) 7250-7500V _pp , (xxxi) 7500-7750V _pp , (xxxii) 7750-8000V _pp , ( xxxiii) 8000-8250 V _pp , (xxxiv) 8250-8500 V _pp , (xxxv) 8500-8750 V _pp , (xxxvi) 8750-9000 V _pp , (xxxvii) 9000-9250 V _pp , (xxxviii) 9250-9500 V _pp , (xxxix) 9500-9750 V _pp , (xl) 9750-10000 V _pp and (xli)> 10000 V _pp .

The first alternating or HF voltage preferably has an inside frequency range selected from the following group: (i) <100 kHz, (ii) 100-200 kHz, (iii) 200-400 kHz, (iv) 400-600 kHz, (v) 600-800 kHz, (vi) 800-1000 kHz, (vii) 1.0-1.2 MHz, (viii) 1.2-1.4 MHz, (ix) 1.4-1.6 MHz, (x) 1.6-1.8 MHz, (xi) 1.8-2.0 MHz and (xii)> 2.0 MHz.

The second ion trap closes preferably a quadrupole ion trap one.

The second ion trap can be a 3D (Paul) quadrupole ion trap with a Ring electrode and two end cap electrodes, wherein the ring electrode and the end cap electrodes are hyperbolic surface exhibit. Alternatively, the second ion trap may be a cylindrical one Ring electrode and two substantially planar Endkappenelektroden exhibit.

The second ion trap may be one, two, three or more than three ring electrodes and two substantially planar end cap electrodes. A or more of the end cap electrodes of the second ion trap may be Mesh or grid.

According to one another embodiment may the second ion trap has a 2D (linear) quadrupole ion trap include several stick electrodes and two end electrodes.

According to less preferred embodiments the second ion trap may have a segmented ring set with several Electrodes containing openings which pass ions through, or a Penning ion trap lock in.

Preferably, a second AC or RF voltage having a second amplitude is applied to the second ion trap. The second amplitude is preferably selected from the following group: (i) 0-250 V _pp , (ii) 250-500 V _pp , (iii) 500-750 V _pp , (iv) 750-1000 V _pp , (v) 1000-1250V _pp , (vi) 1250-1500V _pp , (vii) 1500-1750V _pp , (viii) 1750-2000V _pp , (ix) 2000-2250V _pp , (x) 2250-2500V _pp , (xi) 2500-2750V _pp , (xii) 2750-3000V _pp , (xiii) 3000-3250V _pp , (xiv) 3250-3500V _pp , (xv) 3500-3750V _pp , (xvi) 3750 -4000V _pp , (xvii) 4000-4250V _pp , (xviii) 4250-4500V _pp , (xix) 4500-4750V _pp , (xx) 4750-5000V _pp , (xxi) 5000-5250V _pp , (xxii) 5250-5500V _pp , (xxiii) 5500-5750V _pp , (xxiv) 5750-6000V _pp , (xxv) 6000-6250V _pp , (xxvi) 6250-6500V _pp , (xxvii) 6500 6750V _pp , (xxviii) 6750-7000V _pp , (xxix) 7000-7250V _pp , (xxx) 7250-7500V _pp , (xxxi) 7500-7750V _pp , (xxxii) 7750-8000V _pp , ( xxxiii) 8000-8250 V _pp , (xxxiv) 8250-8500 V _pp , (xxxv) 8500-8750 V _pp , (xxxvi) 8750-9000 V _pp , (xxxvii) 9000-925 0 V _pp , (xxxviii) 9250-9500 V _pp , (xxxix) 9500-9750 V _pp , (xl) 9750-10000 V _pp and (xli)> 10000 V _pp .

The second AC or RF voltage preferably has an inside frequency range selected from the following group: (i) <100 kHz, (ii) 100-200 kHz, (iii) 200-400 kHz, (iv) 400-600 kHz, (v) 600-800 kHz, (vi) 800-1000 kHz, (vii) 1.0-1.2 MHz, (viii) 1.2-1.4 MHz, (ix) 1.4-1.6 MHz, (x) 1.6-1.8 MHz, (xi) 1.8-2.0 MHz and (xii)> 2.0 MHz.

The Amplitude of an applied to the first ion trap change or HF voltage is preferably greater than the amplitude of an alternating current applied to the second ion trap or RF voltage.

The amplitude of an AC or RF voltage applied to the first ion trap is preferably at least x V _pp greater than the amplitude of an AC or RF voltage applied to the second ion trap, where x is selected from the following group: (i) 5, (ii) 10, (iii) 20, (iv) 30, (v) 40, (vi) 50, (vii) 60, (viii) 70, (ix) 80, (x) 90, (xi) 100, (xii) 110, (xiii) 120, (xiv) 130, (xv) 140, (xvi) 150, (xvii) 160, (xviii) 170, (xix) 180, (xx) 190, (xxi) 200, (xxii) 250, (xxiii) 300, (xxiv) 350, (xxv) 400, (xxvi) 450, (xxvii) 500, (xxviii) 550, (xxix) 600, (xxx) 650, (xxxi) 700, (xxxii) 750, (xxxiii) 800, (xxxiv) 850, (xxxv) 900, (xxxvi) 950 and (xxxvii) 1000.

The first ion trap and / or the second ion trap are preferably on a pressure selected from the following group: (i) greater than or equal to equal to 0.0001 mbar, (ii) greater than or equal to 0.0005 mbar, (iii) larger or equal to 0.001 mbar, (iv) greater or equal to 0.005 mbar, (v) greater or less equal to 0.01 mbar, (vi) greater than or equal to equal to 0.05 mbar, (vii) larger or equal to 0.1 mbar, (viii) greater or equal to 0.5 mbar, (ix) greater or equal to 1 mbar, (x) larger or equal to 5 mbar and (xi) greater than or equal to 10 mbar.

The first ion trap and / or the second ion trap are preferably on a pressure selected from the following group: (i) smaller or equal to 10 mbar, (ii) less than or equal to 5 mbar, (iii) smaller or equal to 1 mbar, (iv) less than or equal to 0.5 mbar, (v) smaller or equal to 0.1 mbar, (vi) less than or equal to 0.05 mbar, (vii) less than or equal to 0.01 mbar, (viii) less than or equal to 0.005 mbar, (ix) less than or equal to 0.001 mbar, (x) less than or equal to 0.0005 mbar and (xi) less than or equal to 0.0001 mbar.

The first ion trap and / or the second ion trap are preferably on a pressure selected from the following group: (i) between 0.0001 and 10 mbar, (ii) between 0.0001 and 1 mbar, (iii) between 0.0001 and 0.1 mbar, (iv) between 0.0001 and 0.01 mbar, (v) between 0.0001 and 0.001 mbar, (vi) between 0.001 and 10 mbar, (vii) between 0.001 and 1 mbar, (viii) between 0.001 and 0.1 mbar, (ix) between 0.001 and 0.01 mbar, (x) between 0.01 and 10 mbar, (xi) between 0.01 and 1 mbar, (xii) between 0.01 and 0.1 mbar, (xiii) between 0.1 and 10 mbar, (xiv) between 0.1 and 1 mbar and (xv) between 1 and 10 mbar.

According to others embodiments can more Ion traps provided in series with the first and second ion traps become. Accordingly, a third ion trap is provided which is arranged that in use they have a third lower mass cut limit wherein the third lower mass cut limit is lower is as the second lower Massenabschneidegreze, so that at least some ions with mass-to-charge ratios below the first and second mass cut limits, the not be trapped in the first and second ion traps, be trapped in the third ion trap.

A third alternating or HF voltage having a third amplitude may be applied to the third ion trap. The third amplitude is preferably selected from the following group: (i) 0-250 V _pp , (ii) 250-500 V _pp , (iii) 500-750 V _pp , (iv) 750-1000 V _pp , (v) 1000-1250 V _pp, (vi) 1250-1500 V _pp, (vii) 1500-1750 V _pp, (viii) 1750-2000 V _pp, (ix) 2000-2250 V _pp , (x) 2250-2500 V _pp , (xi) 2500-2750 V _pp , (xii) 2750-3000 V _pp , (xiii) 3000-3250 V _pp , (xiv) 3250-3500 V _pp , (xv ) 3500-3750 V _pp , (xvi) 3750-4000 V _pp , (xvii) 4000-4250 V _pp , (xxiii) 4250-4500 V _pp , (xix) 4500-4750 V _pp , (xx) 4750-5000 V _pp , (xxi) 5000-5250 V _pp , (xxii) 5250-5500 V _pp , (xxiii) 5500-5750 V _pp , (xxiv) 5750-6000 V _pp , (xxv) 6000-6250 V _pp , (xxvi) 6250-6500 V _pp , (xxvii) 6500-6750 V _pp , (xxviii) 6750-7000 V _pp , (xxix) 7000-7250 V _pp , (xxx) 7250-7500 V _pp , (xxxi) 7500-7750 V _pp , (xxxii) 7750-8000 V _pp , (xxxiii) 8000-8250 V _pp , (xxxiv) 8250-8500 V _pp , (xxxv) 8500-8750 V _pp , (xxxvi) 8750-9000 V _pp , (xxxvii) 9000 -9250 V _pp , (xxxviii) 9250-9500 V _pp , (xxxix) 9500-9750 V _pp , (xl) 9750-10000 V _pp and (xli)> 10000 V _pp .

The third AC or RF voltage preferably has a frequency, which is in a range selected from the following group: (i) <100 kHz, (ii) 100-200 kHz, (iii) 200-400 kHz, (iv) 400-600 kHz, (v) 600-800 kHz, (vi) 800-1000 kHz, (vii) 1.0-1.2 MHz, (viii) 1.2-1.4 MHz, (ix) 1.4-1.6 MHz, (x) 1.6-1.8 MHz, (xi) 1.8-2.0 MHz and (xii)> 2.0 MHz.

The Amplitude of an applied to the second ion trap change or HF voltage is preferably greater than the third amplitude.

It For example, a fourth ion trap may be provided, preferably is set up so that when using a fourth lower Massenabschneidegrenze, wherein the fourth lower Massenabschneidegreze is lower than the third lower Massenabschneidegrenze, so that at least some ions with mass-to-charge ratios below the first, the second and the third mass cut limit, which are not in the first, second and third ion traps are captured, be trapped in the fourth ion trap.

Preferably, a fourth AC or RF voltage having a fourth amplitude is applied to the fourth ion trap. The fourth amplitude is preferably selected from the following group: (i) 0-250 V _pp , (ii) 250-500 V _pp , (iii) 500-750 V _pp , (iv) 750-1000 V _pp , (v) 1000-1250V _pp , (vi) 1250-1500V _pp , (vii) 1500-1750V _pp , (viii) 1750-2000V _pp , (ix) 2000-2250V _pp , (x) 2250-2500V _pp , (xi) 2500-2750V _pp , (xii) 2750-3000V _pp , (xiii) 3000-3250V _pp , (xiv) 3250-3500V _pp , (xv) 3500-3750V _pp , (xvi) 3750 -4000V _pp , (xvii) 4000-4250V _pp , (xviii) 4250-4500V _pp , (xix) 4500-4750V _pp , (xx) 4750-5000V _pp , (xxi) 5000-5250V _pp , (xxii) 5250-5500V _pp , (xxiii) 5500-5750V _pp , (xxiv) 5750-6000V _pp , (xxv) 6000 -6250V _pp , (xxvi) 6250-6500V _pp , (xxvii) 6500 6750V _pp , (xxviii) 6750-7000V _pp , (xxix) 7000-7250V _pp , (xxx) 7250-7500V _pp , (xxxi) 7500-7750V _pp , (xxxii) 7750-8000V _pp , ( xxxiii) 8000-8250 V _pp , (xxxiv) 8250-8500 V _pp , (xxxv) 8500-8750 V _pp , (xxxvi) 8750-9000 V _pp , (xxxvii) 9000-92 50 V _pp , (xxxviii) 9250-9500 V _pp , (xxxix) 9500-9750 V _pp , (xl) 9750-10000 V _pp and (xli)> 10000 V _pp .

The fourth AC or RF voltage preferably has an inside frequency range selected from the following group: (i) <100 kHz, (ii) 100-200 kHz, (iii) 200-400 kHz, (iv) 400-600 kHz, (v) 600-800 kHz, (vi) 800-1000 kHz, (vii) 1.0-1.2 MHz, (viii) 1.2-1.4 MHz, (ix) 1.4-1.6 MHz, (x) 1.6-1.8 MHz, (xi) 1.8-2.0 MHz and (xii)> 2.0 MHz.

The third amplitude is preferably greater than the fourth amplitude.

According to others embodiments can five, six, seven, eight, nine, ten or more than ten ion traps in series be provided.

It is preferably a continuous or pulsed ion source provided. The ion source may include: an electrospray ion source, a chemical atmospheric pressure ionization ion source ("APCI ion source"), an atmospheric pressure MALDI ion source, an electron ionization ion source ("EI ion source"), an ion source with chemical ionization ("CI ion source"), a field desorption ionization ion source ("FI ion source"), a matrix assisted laser desorption ionization ion source ("MALDI ion source"), a laser desorption ionization ion source ("LDI ion source"), a laser desorption / ionization on silicon ion source ("DIOS ion source"), a surface-enhanced laser desorption ionization ion source ("SELDI ion source") or an ion source with fast atom bombardment ("FAB ion source").

One Ion detector can be downstream the second ion trap can be arranged. The ion detector can an electron multiplier, a photomultiplier or a channeltron.

It can be a time-of-flight mass analyzer in the manner of an axial time-of-flight mass analyzer or more preferably, a lateral acceleration time-of-flight mass analyzer to be provided.

In addition to first, second and optionally third, fourth, etc. ion traps is preferably provided a further ion trap. The further ion trap includes preferably a quadrupole ion trap.

The further ion trap may include a 3D (Paul) quadrupole ion trap with a ring electrode and two end cap electrodes, wherein the ring electrode and the end cap electrodes have a hyperbolic surface.

The Another ion trap can be one or more cylindrical ring electrodes and two substantially planar end cap electrodes.

alternative the further ion trap can be one, two, three or more than three Ring electrodes and two substantially planar end cap electrodes exhibit.

According to one embodiment can one or more of the end cap electrodes of the further ion trap have a net or a grid.

According to one another embodiment may the further ion trap has a 2D (linear) quadrupole ion trap include several stick electrodes and two end electrodes.

According to less preferred embodiments the further ion trap may have a segmented ring set with several Electrodes containing openings which pass ions through, or a Penning ion trap lock in.

ions are preferably in a non-mass selective mode or non-scanning mode pulsed extracted from the other ion trap. For example, you can Ions by applying a DC extraction pulse to the End cap electrodes of the other ion trap pulsed from the other Ion trap can be removed. A DC voltage can also or alternatively to the ring electrode (the ring electrodes) of the other Ion trap can be applied, so that a more linear axial electrical Gleichfeldgradient is provided.

additional Ion traps can for storing output ions in MS / MS modes of operation become. The mass spectrometer can therefore continue a first additional Have ion trap. The first additional ion trap preferably closes a quadrupole ion trap. The first additional ion trap can be a 3D (Paul) quadrupole ion trap with a ring electrode and two end cap electrodes, wherein the ring electrode and the end cap electrodes are hyperbolic surface exhibit.

alternative may be the first additional Ion trap one or more cylindrical ring electrodes and two have substantially planar Endkappenelektroden.

The first additional Ion trap can be one, two, three or more than three ring electrodes and two substantially planar end cap electrodes. One or more end cap electrodes of the first additional ones Ion trap can have a net or a grid.

The first additional Ion trap can be a 2D (linear) quadrupole ion trap with multiple stick electrodes and include two end electrodes. Alternatively, the first additional Ion trap a segmented ring set with multiple electrodes, in which are openings of which ions are transmitted, or include a Penning ion trap.

It may preferably be a second additional ion trap for storage from source versions in MS / MS modes of operation. The second additional Ion trap may include a quadrupole ion trap. The second additional ion trap can be a 3D (Paul) quadrupole ion trap with a ring electrode and two end cap electrodes, the ring electrode and the end caps electrodes have a hyperbolic surface.

The second additional Ion trap can be one or more cylindrical ring electrodes and have two substantially planar Endkappenelektroden. alternative may be the second additional Ion trap one, two, three or more than three ring electrodes and have two substantially planar Endkappenelektroden. A or a plurality of end cap electrodes of the second additional ion trap may be one Mesh or grid.

The second additional Ion trap can be a 2D (linear) quadrupole ion trap with multiple stick electrodes and include two end electrodes. Alternatively, the second additional Ion trap a segmented ring set with multiple electrodes, in which are openings of which ions are transmitted, or include a Penning ion trap.

According to another aspect of the present invention, there is provided a method of mass spectrometry comprising the steps of:
Providing a first ion trap having a first lower mass cut-off limit,
Providing a second ion trap having a second lower mass cutoff limit, the second lower mass cutoff limit being less than the first lower mass cutoff limit,
Trapping some ions in the first ion trap and
Trapping at least some ions in the second ion trap whose mass to charge ratios are less than the first lower mass cutoff and which are not trapped in the first ion trap.

If according to the different ones Embodiments provided in the present application, a quadrupole ion trap with multiple internal electrodes (or ring electrodes) (which are easier to make are used as electrodes with a hyperbolic surface) can, the quadrupole field by applying various alternating or RF voltage amplitudes be generated with the same phase to each inner electrode. The Inner electrodes should preferably be around the center of the ion trap be symmetrical. However, it is by selecting a particular opening or a certain inner radius for the ring electrodes possible, a electrical alternating or RF field which approximates a quadrupole field, with the same amplitude and phase of the AC or RF voltage applied to each ring electrode and wherein the opposite phase to the end cap electrodes is created.

If an ion trap, for example, with flat or thin cylindrical Pulsed electrodes should remove ions from the ion trap (for example the ions are pulsed into an axial or lateral acceleration time-of-flight mass analyzer should contribute) those applied to the electrodes in such an ion extraction mode DC voltages are set up so that essentially one linear electric field is generated. This can be in terms of the ion transfer efficiency is advantageous be. Furthermore, after the pulsed extraction a certain Degree of a spatial Flight time focusing occur.

Advantageously, a mass spectrometer is provided which comprises:
a quadrupole ion trap,
another ion trap configured to receive ions ejected from the quadrupole ion trap, and
a time-of-flight mass analyzer configured to receive ions ejected from the further ion trap,
wherein the further ion trap in a first mode of operation receives a pulse of ions mass selectively ejected from or extracted from the quadrupole ion trap, the ratio between the maximum mass to charge ratio of the ions in the ion pulse and the minimum Mass-to-charge ratio of the ions in which the ion pulse is a maximum x, where x ≤ 4.0, and wherein the ions received by the quadrupole ion trap within the other ion trap are cooled by collisions.

Preferably x is selected from the following group: (i) 3.9, (ii) 3.8, (iii) 3.7, (iv) 3.6, (v) 3.5, (vi) 3.4, (vii) 3.3, (viii) 3.2, (ix) 3.1, (x) 3.0, (xi) 2.9, (xii) 2.8, (xiii) 2.7, (xiv) 2.6, (xv) 2.5, (xvi) 2,4, (xvii) 2,3, (xviii) 2,2, (xix) 2,1, (xx) 2,0, (xxi) 1,9, (xxii) 1,8, (xxiii) 1.7, (xxiv) 1.6, (xxv) 1.5, (xxvi) 1.4, (xxvii) 1.3, (xxviii) 1.2 and (xxix) 1,1.

According to one first mode of operation, the further ion trap is preferably on a pressure selected from the following group: (i) greater than or equal to equal to 0.0001 mbar, (ii) greater than or equal to 0.0005 mbar, (iii) larger or equal to 0.001 mbar, (iv) greater or equal to 0.005 mbar, (v) greater or less equal to 0.01 mbar, (vi) greater than or equal to equal to 0.05 mbar, (vii) larger or equal to 0.1 mbar, (viii) greater or equal to 0.5 mbar, (ix) greater or equal to 1 mbar, (x) larger or equal to 5 mbar and (xi) greater than or equal to 10 mbar.

According to one first mode of operation, the further ion trap is preferably on one selected from the following group: (i) smaller or equal to 10 mbar, (ii) less than or equal to 5 mbar, (iii) smaller or equal to 1 mbar, (iv) less than or equal to 0.5 mbar, (v) smaller or equal to 0.1 mbar, (vi) less than or equal to 0.05 mbar, (vii) less than or equal to 0.01 mbar, (viii) less than or equal to 0.005 mbar, (ix) less than or equal to 0.001 mbar, (x) less than or equal to 0.0005 mbar and (xi) less than or equal to 0.0001 mbar.

According to one first mode of operation, the further ion trap is preferably on a pressure selected from the following group: (i) between 0.0001 and 10 mbar, (ii) between 0.0001 and 1 mbar, (iii) between 0.0001 and 0.1 mbar, (iv) between 0.0001 and 0.01 mbar, (v) between 0.0001 and 0.001 mbar, (vi) between 0.001 and 10 mbar, (vii) between 0.001 and 1 mbar, (viii) between 0.001 and 0.1 mbar, (ix) between 0.001 and 0.01 mbar, (x) between 0.01 and 10 mbar, (xi) between 0.01 and 1 mbar, (xii) between 0.01 and 0.1 mbar, (xiii) between 0.1 and 10 mbar, (xiv) between 0.1 and 1 mbar and (xv) between 1 and 10 mbar.

In a second mode of operation, ions are preferably pulsed out of the further ion trap or ejected in a non-mass selective or non-scanning manner such that ions are not resonantly excited from the further ion trap and therefore not in an essentially excited state from the further ion Ion trap are ejected. In the second mode of operation, ions may be pulsed out of the further ion trap by ejection of one or more DC extraction pulses to the further ion trap. The one or more extraction DC voltages may also be applied to one or more end electrodes or end cap electrodes of the further ion trap and / or to one or more central or ring electrodes of the white ones are applied to the lower ion trap. In the second operating mode, alternating or HF voltages are preferably not applied to a considerable extent to the electrodes of the further ion trap.

According to a second mode of operation, the further ion trap is preferably maintained at a lower pressure than in the case where it is operated in the first mode of operation. The further ion trap is preferably maintained at a pressure selected from the following group when operating in the second mode of operation: (i) <5 × 10 ^-2 mbar, (ii) <10 ^-2 mbar, (iii) <5 × 10 ^-3 mbar, (iv) <10 ^-3 mbar, (v) <5 × 10 ^-4 mbar, (vi) <10 ^-4 mbar, (vii) <5 × 10 ^-5 mbar, (viii) <10 ^{- 5} mbar, (ix) <5 x 10 ^-6 mbar and (x) <10 ^-6 mbar.

In the first mode of operation, a pulse of ions ejected from the quadrupole ion trap and received by the further ion trap preferably has a first energy range ΔE ₁ , wherein in the second mode of operation ions ejected from the further ion trap preferably have a second energy range ΔE ₂ , where ΔE ₂ <ΔE ₁ is. ΔE ₁ / ΔE ₂ is preferably at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100. ΔE ₁ is preferably at least 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 eV, and ΔE ₂ preferably takes a maximum of 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.09, 0.08, 0.07, 0.06, 0.05, 0.04, 0.03, 0, 02 or 0.01 eV.

According to the invention is a Method for mass spectrometry according to claim 1 provided.

Advantageously, a method for mass spectrometry is provided which has the following steps:
Storing output ions having a first mass-to-charge ratio in a first ion trap,
Storing at least some other parent ions having mass-to-charge ratios different from the first mass-to-charge ratio in one or more additional ion traps,
Fragmenting the parent ions having the first mass-to-charge ratio in the first ion trap to form fragment ions;
Trapping some of the fragment ions in the first ion trap with a first lower mass cutoff and
Trapping other fragment ions in a second ion trap having a second lower mass cut-off limit, the second lower mass cut-off limit being lower than the first lower mass cut-off limit.

Advantageously, a method for mass spectrometry is provided which has the following steps:
Storing output ions having a first mass-to-charge ratio in a first ion trap,
Storing at least some other parent ions having mass-to-charge ratios different from the first mass-to-charge ratio in one or more additional ion traps,
Fragmenting the parent ions having the first mass-to-charge ratio in a first ion trap to form fragment ions;
Trapping some of the fragment ions in the first ion trap with a first lower mass cutoff and
Trapping other fragment ions in a second ion trap having a second lower mass cut-off limit, the second lower mass cut-off limit being lower than the first lower mass cut-off limit.

Advantageously, a method for mass spectrometry is provided which has the following steps:
Storing output ions having a first mass-to-charge ratio in an ion trap,
Storing at least some other parent ions having mass-to-charge ratios different from the first mass-to-charge ratio in one or more additional ion traps,
Fragmenting the parent ions with the first mass to charge ratio to form fragment ions
Trapping some of the fragment ions in a first ion trap having a first lower mass cutoff and
Trapping other fragment ions in a second ion trap having a second lower mass cut-off limit, the second lower mass cut-off limit being lower than the first lower mass cut-off limit.

The Ion trap can be like the first ion trap.

fragment ions are preferably within the first and / or the second ion trap cooled by collisions. Some fragment ions are preferably obtained by scanning from the first and / or taken from the second ion trap or mass selectively ejected therefrom, while others Fragment ions within the first and / or second ion trap being held.

In a first mode of operation at least some fragment ions by scanning from the first Ion trap and / or the second ion trap taken or mass selective ejected from it have been received in another ion trap and cooled by collisions become.

An impulse from the further ion trap in egg Preferably, ions ejected or pulsed therefrom in the second mode of operation are received by a Time of Flight mass analyzer, such as an axial or lateral acceleration time of flight mass analyzer.

Advantageously, a mass spectrometer is provided, which has the following:
a first ion trap storing, in use, first ions to first mass-to-charge ratio ion distributions,
one or more additional ion traps which, in use, store at least some other exit ions having mass to charge ratios other than the first mass to charge ratio, and
a second ion trap,
wherein, in use, the first mass-to-charge ratio parent ions are fragmented in the first ion trap to form fragment ions, and wherein some of the fragment ions in the first ion trap are trapped with a first lower mass cut-off and others of the fragment ions in the second Trapped ion trap with a second lower Massenabschneidegre-ze, wherein the second lower Massenabschneidegreze is lower than the first lower Massenabschneidegre-ze.

Advantageously, a mass spectrometer is provided which comprises:
an ion trap storing, in use, first ions to first ion charge ratio output ions,
one or more additional ion traps in which, in use, at least some other exit ions having mass to charge ratios other than the first mass to charge ratio are stored,
a first ion trap and
a second ion trap,
wherein, in use, the first mass-to-charge ratio parent ions are fragmented in the first ion trap to form fragment ions, and wherein some of the fragment ions in the first ion trap are trapped with a first lower mass cut-off and others of the fragment ions in the second Trapped ion trap with a second lower Massenabschneidegre-ze, wherein the second lower Massenabschneidegreze is lower than the first lower Massenabschneidegre-ze.

Advantageously, a mass spectrometer is provided which comprises:
an ion trap storing, in use, first ions to first ion charge ratio output ions,
one or more additional ion traps in which, in use, at least some other exit ions having mass to charge ratios other than the first mass to charge ratio are stored,
a first ion trap and
a second ion trap,
wherein, in use, the source ions are fragmented at the first mass to charge ratio to form fragment ions, and wherein some of the fragment ions in the first ion trap are trapped with a first lower mass cut limit and others of the fragment ions in the second ion trap with a second mass trap lower mass cutoff limit, the second lower mass cutoff limit being lower than the first lower mass cutoff limit.

Advantageously, a mass spectrometer is provided which comprises:
a first ion trap having an ion trap ion source with one or more central electrodes, a first end cap electrode and a second end cap electrode,
wherein a sample or target plate forms at least a portion of the first endcap electrode of the first ion trap.

The Ion trap ion source may be an ion source of a matrix assisted laser desorption ionization ion trap ("MALDI ion source"), an ion source a laser desorption ionization ion trap ("LDI ion source"), an ion source of a laser desorption / ionization on silicon ion trap ("DIOS ion source"), an ion source a surface-enhanced laser desorption ionization ion trap ("SELDI ion source") and an ion trap ion source with fast atom bombardment ("FAB ion source").

Advantageously, a method for mass spectrometry is provided which has the following steps:
Providing a first ion trap, the first ion trap having an ion trap ion source with one or more central electrodes, a first end cap electrode and a second end cap electrode, a sample or target plate forming at least a portion of the first end cap electrode,
Establishing that a laser beam or electron beam hits the sample or target plate and ionizing samples or targets on the sample or target plate.

Various embodiments The present invention will now be described by way of example only to the attached drawing. Show it:

1 an ion trap system according to a Embodiment comprising two ion traps arranged in series with different lower mass cutoff boundaries, so that ions not trapped in the first ion trap are trapped in the second ion trap,

2 a Mathieu stability diagram for a quadrupole ion trap,

3 an ion trap system according to the preferred embodiment having a further ion trap for aiding the coupling of the ion trap system to a lateral acceleration time of flight mass analyzer;

4 a table showing the various stages which, according to one embodiment of the present invention, can be carried out in the mass analysis of ions whose mass-to-charge ratios are within the range of 100-3000 mass-to-charge ratio units,

5 a less preferred embodiment in which a single mass-selective ion trap is coupled via a further ion trap to a cross-acceleration time-of-flight mass analyzer,

6 an ion trap system according to the preferred embodiment for performing MS / MS experiments, wherein additional ion storage traps are provided for storing output ions, and

7 an ion trap ion source according to an embodiment, wherein a microtitration sample plate or other target plate forms part of an end cap of an ion trap.

A preferred embodiment of the present invention will now be described with reference to 1 described. 1 Figure 4 shows an embodiment in which two ion traps T1, T2, for example, 3D (Paul) quadrupole ion traps, are arranged in series to provide an ion capture system with an improved overall mass range. The ion capture system is adapted to receive ions from an ion source 1 to recieve. However, the ions are not necessarily generated outside the first ion trap T1 and may be generated or formed within the first ion trap T1 according to another embodiment described in more detail below.

If ions are generated outside of the first ion trap T1, they are preferably made using inhomogeneous RF blocking fields from the ion source 1 transferred to the first ion trap T1. For example, an RF ion guide may be provided, and an axial DC electrical gradient and / or DC currents or DC current waveforms (in which axial trapping regions are moved along an ion guide) may be applied to the RF ion guide to introduce ions into the first Ion trap T1 to urge. Ions can also be similarly transferred from one ion trap to the other.

ions can less preferred using DC focusing lenses or an ion guide, at the one central guidewire with a radial confining DC field or RF field with or without collision gas is transferred to the first ion trap T1 or between ion traps become.

In another embodiment, ions may be axial or radial from one or more continuous or pulsed ion sources 1 are introduced into the first ion trap T1 and / or the second ion trap T2. According to another embodiment, ions may be switched from a continuous ion source and temporarily stored in a transfer region before being transferred to the first ion trap T1.

The RF power supply for Each ion trap T1, T2 may be under a single RF generator Using different resistors derived to give different amplitudes for each ion trap T1, T2 produce.

wobei V_rf die Amplitude (von 0 bis zur Spitze) der an die zentrale Ringelektrode angelegten HF-Spannung (oder der zwischen die Ringelektrode und die Endkappenelektroden angelegten Spannung) ist, r₀ der eingeschriebene Radius der zentralen Ringelektrode ist, ω die Winkelfrequenz der angelegten HF-Spannung ist, U_dc die zwischen die Ringelektrode und die Endkappenelektroden angelegte Gleichspannung ist und m/z das Masse-Ladungs-Verhältnis eines Ions innerhalb der 3D-Quadrupol-Ionenfalle ist.Ions with certain mass-to-charge ratios are under operating conditions that take the form of an in 2 Mathieu stability diagram summarized and can be expressed by the Mathieu coordinates a _z and q _z , stable. The hatched area off 2 represents ions that are stable both radially and axially. The Mathieu coordinates a _z and q _z are:

where V _{rf is} the amplitude (from 0 to the peak) of the RF voltage applied to the central ring electrode (or the voltage applied between the ring electrode and the end cap electrodes), r _{0 is} the inscribed radius of the central ring electrode, ω is the angular frequency of the applied HF voltage is, U _dc between the ring electrode and the And m / z is the mass-to-charge ratio of an ion within the 3D quadrupole ion trap.

It is known that 3D (Paul) quadrupole ion traps do not store ions below a certain mass-to-charge ratio known as the lower mass cut-off limit ("LMCO"). If the central ring electrode is kept at the same DC voltage as the end cap electrodes (so if U _dc is set to zero volts and therefore a _z = 0), there is a maximum q _z value at which punctures become axially unstable. This maximum q _z value is q = 0.908 _{z_max.} With this setting of q _z , LMCO can be calculated as follows:

As can be understood by considering the above equation, the LMCO value can be decreased either by decreasing V _rf or by increasing r ₀ or ω. Conversely, the LMCO value is increased by increasing V _rf .

According to the preferred embodiment, to overcome the mass range limitation inherent in a quadrupole ion trap, two (or more) ion traps T1, T2, such as 3D quadrupole ion traps, are provided in series with a first ion trap T1, preferably for receiving ions from an ion source 1 is set up. Some ions of interest whose mass-to-charge ratios are below the LMCO value of the first ion trap T1 become axially unstable within the first ion trap T1. These ions are ejected axially from the first ion trap T1, but the ions of interest are preferably not lost because they are trapped in the second ion trap T2, which is preferably downstream of the first ion trap T1. The second ion trap T2 is preferably configured to have a lower LMCO value than the first ion trap T1. Ions whose mass-to-charge ratios are lower than the LMCO value of the second ion trap T2 are either not ions of interest, or alternatively other additional ion traps (not shown) with increasingly smaller LMCO values in series with the first ion trap T1 and the second ion trap T2 to capture these ions and to further increase the mass range of the overall ion capture system.

ions, their mass-charge ratios below the LMCO value of the first ion trap T1 are preferably by applying a small dc field (or alternating field) to the Transmit end caps of the first ion trap T1 in the axial direction. Ions, their mass-to-charge ratio is below the LMCO value of the first ion trap T1, are preferably in the second ion trap T2 downstream of the first ion trap T1 whose LMCO value is lower than the LMCO value of the first ion trap T1. The trapped and analyzed ions can either be positively or negatively charged.

According to the in 1 The illustrated embodiment is an ion detector 2 downstream of the first ion trap T1 and the second ion trap T2. According to further embodiments (not shown), three, four, five, six, seven, eight, nine, ten or more than ten ion traps may be provided in series to provide an ion trapping system having a still further improved overall mass range. As will be understood, in these embodiments, the ion traps may progressively have lower LMCO values.

A particularly preferred feature of the preferred embodiment is that the amplitude of the AC or RF voltage V _{rf applied to} , for example, the ring electrode (or less preferably between the ring electrode and the end cap electrodes) of the first ion trap T1 may be significantly higher as the voltage that could otherwise be applied in a conventional manner to a quadrupole ion trap in a comparable situation. Although increasing the amplitude of the AC or RF voltage applied to the electrode of the first ion trap T1 increases the LMCO value of the first ion trap T1, ions of mass-to-charge ratios of interest go below the LMCO value of the first ion trap T1 are not lost because they are trapped in the second ion trap T2 downstream of the first ion trap T1.

As can be seen by the following equation for the depth D _{z of} the axial pseudopotential well, increasing the amplitude V _rf of the AC or RF voltage applied to the ring electrode of the first ion trap T1 has the advantage that the depth of the axial pseudopotential well inside the first ion trap T1 is increased. Accordingly, ions having higher mass-to-charge ratios and / or larger kinetic energy ions are advantageously trapped more efficiently in the first ion trap T1. Ions having larger kinetic energies are more effectively trapped in the first ion trap T1 because ions (in first approximation) must have greater kinetic energy than the depth of the axial pseudopotential well to escape from the trap state in the ion trap. The depth of the axial pseudopotential well is given by the following equation:

It is clear from the above equation that by increasing the amplitude of the applied AC or RF voltage V _rf, the depth of the axial pseudopotential well is increased. Similarly, the depth of the axial well can be increased by reducing the frequency of the applied AC or RF voltage or by decreasing the radius r _{0 of} the central ring electrode.

3 shows a particularly preferred embodiment for performing MS experiments, wherein an ion capture system with two ion traps T1, T2 is coupled via a further ion trap T0 to a lateral acceleration time-of-flight mass analyzer. The further ion trap T0 may include a 3D quadrupole ion trap, but in other embodiments may also include other forms of ion traps.

For effectively transferring all output ions stored in the first ion trap T1 and the second ion trap T2 into a lateral acceleration time-of-flight mass analyzer, it is desirable to limit the mass range of the ions transmitted to the time-of-flight mass analyzer at each time so that the ions emitted in each individual ion pulse from Time of flight mass analyzer ions have a limited range of mass-to-charge ratios. As will be explained in more detail below, it is desirable to set the range of mass-to-charge ratios in the extraction region 3 limit the ions received by the Time of Flight mass analyzer so that all ions received by the mass analyzer are still in the extraction range at that time 3 are present, to which an electrostatic pulse to electrodes in the extraction area 3 is applied to ions pulsed from the extraction area 3 and to lead into the drift or flight area of the time of flight mass analyzer. If the ions pulsed in a time-of-flight mass analyzer have a wide range of mass-to-charge ratios, the ions will be slightly time dispersed in accordance with their mass-to-charge ratios because the ions have passed substantially through a brief drift or flight region. around the extraction area 3 to reach. Accordingly, some ions are beyond the end of the extraction region 3 while other ions are the extraction area 3 have not yet reached, when ions are pulsed removed from the extraction area and introduced into the drift or flight area of the time-of-flight mass analyzer. Accordingly, when ions having a relatively high range of mass-to-charge ratios are pulsed introduced into the time of flight mass analyzer, the duty cycle is reduced because some of these ions are not orthogonally accelerated into the drift or flight range of the Time of Flight mass analyzer. The further ion trap T0 is provided to address this problem and will be described in more detail below.

Ions are also preferably ejected and led out of the first ion trap T1 and the second ion trap T2 by mass-selective instability. In the process the amplitude of the voltage applied to the ring electrodes AC or RF voltage is ramped and ions are pushed with low mass to charge ratios above a q _z value from 0.908. An alternative method of mass selection is resonant excitation, where either a specific secular frequency or a broad band of secular frequencies are applied to axially eject or trap ion groups with particular mass-to-charge ratios. A supplemental RF electric dipole field may be applied to the end cap electrodes and used in conjunction with a mass selective instability scan.

Ions that have been mass selectively ejected from the first ion trap T1 and the second ion trap T2 are relatively energetic, and these ions are then preferentially trapped within the further ion trap T0 and cooled (ie, thermalized) by collisions. Once the ions have been cooled by collisions, the RF voltage applied to the further ion trap T0 is preferably switched off or otherwise significantly reduced. The pressure of the collision cooling gas can also be significantly reduced at the same time. For example, it may be permitted to reduce the pressure within the further ion trap T0 from, for example, 10 ^-3 mbar to <10 ^-4 mbar. If the further ion trap T0 is a quadrupole ion trap, an axial dc field can be applied to one or more of the end cap electrodes and / or ring electrodes of the further ion trap T0 so that ions are pulsed out of the further ion trap T0. The axial dc field is used to move ions from the further ion trap T0 into the extraction region 3 to accelerate and transmit, for example, the lateral acceleration time-of-flight mass analyzer.

The width or distribution of the ion energies in the axial direction of the in the extraction area 3 The time of flight mass analyzer entering ions depends on their thermal energy after collision cooling, for example with helium gas at room temperature in the other ion trap T0 from. Ions that have been thermalized have an energy of about 0.05 eV. After applying of an electrostatic extraction pulse of about 100V to the end cap electrodes, the ions of the further ion trap T0 accept differential kinetic energies which depend on their location within the further ion trap T0 when the extraction pulse is applied. Pulsed ions extracted from the further ion trap T0 therefore have an average kinetic energy of, for example, 50 eV and an energy width of ± 5 eV.

Without a collision cooling of the ions in the further ion trap T0 would be the ion energy width of ions ejected from the first and second ion traps considerably larger and she could have a negative effect on the time of flight mass analyzer, the tried a mass analysis of the ions. By reducing the energy width on some eV is guaranteed that the time-of-flight mass analyzer is not negatively affected.

After the ions reach the extraction area 3 of the lateral acceleration time-of-flight mass analyzer, an electrostatic cross pulse is preferably applied to the extraction area 3 applied to accelerate ions into the drift or flight range of the Time of Flight mass analyzer. The time-of-flight mass analyzer may have a reflectron. The above method of collision cooling ions with the further ion trap T0 and transferring ions from the further ion trap T0 to the extraction region 3 in a pulsed, non-mass selective manner has the important advantage of minimizing the energy width of the ions exiting the further ion trap T0. This effects optimizing the sensitivity and resolution of the lateral acceleration Time of Flight mass analyzer. Scanning a quadrupole ion trap, such as the first ion trap T1 and / or the second ion trap T2, for mass selective ejection of ions causes these ions to be driven or excited to an unstable state. Therefore, by avoiding the mass selective scanning of the ions from the further ion trap T0, once they have been collisionally cooled in the further ion trap T0, they remain in a relatively non-energetic state, which is advantageous when the ions are transferred to a Time of Flight mass analyzer , Another important advantage of in 3 illustrated embodiment is that ions mass selective from the first and / or the second ion trap T1, T2 can be ejected into the further ion trap T0 such that the ions in the further ion trap T0, which are then forwarded to the time-of-flight mass analyzer, a have limited range of mass-to-charge ratios, which is desirable to optimize the duty cycle of the Time of Flight mass analyzer.

In spite of of the above can according to a less preferred embodiment the AC or RF voltage applied to the further ion trap T0 nonetheless, and ions could become less preferably axially from the further ion trap T0, either by resonant expel (where an oscillating AC voltage between the end cap electrodes applied) or by mass selective ejection (where the RF voltage elevated or the RF frequency is reduced or a DC voltage between some or all of the ring electrodes and the end cap electrodes axially) from the further ion trap T0 into the lateral acceleration time-of-flight mass analyzer pushed out become. The mass-selective ejection of ions from the other Ion trap T0 is less preferred because the ion energy width increases, which is generally undesirable if a time-of-flight mass analyzer is used. Although the increased energy width disadvantageous can be, the other ion trap T0 can emit ions that have a limited range of mass-to-charge ratios, thereby the duty cycle time of flight mass analyzer is improved. Such an arrangement can have some advantages over usual Arrangements, however, is compared to the use of DC extraction techniques less preferred for the reasons given above.

By the time the extraction pulse of the lateral acceleration Time of Flight mass analyzer is activated, it is desirable that the lowest ratio ions received by the further ion trap T0 not quite reach the end of the extraction range 3 while the ions with the highest mass-to-charge ratio are just in the extraction range 3 occurred. Design constraints and other considerations significantly limit the physical position or length of the extraction region 3 , and this significantly limits the mass range of ions which can be accelerated at a duty cycle of nearly 100 in a pulse in the transverse direction. To address this problem, the AC or DC and / or DC voltage of the penultimate ion trap (ie the second ion trap T2 in the case of in 3 1) are preferably controlled such that only ions whose mass-to-charge ratios within a partial range or fraction of the total range of mass-to-charge ratios of the ions stored in the (second) ion trap T2 are transferred to the last ion trap (ie the further ion trap T0) is transferred axially. Therefore, ions are preferably emitted in a mass-selective manner from the (second) ion trap T2 into the further ion trap T0, so that all ions which are subsequently pulsed out of the further ion trap T0 are ejected within the extraction zone Reich 3 of the time of flight mass analyzer are accelerated substantially in the transverse direction.

After this a mass of ions mass analyzed by the lateral acceleration time-of-flight mass analyzer may be another subarea or fraction of the one in the second ion trap T2 stored ions in the other ion trap T0 transferred be cooled by collisions before being forwarded to the time of flight mass analyzer. A partial area or a fraction of that in the first ion trap T1 stored ions can also be transferred to the second ion trap T2 be forwarded to the other ion trap T0 or to the process of mass selective ejection of some ions from the to repeat the second ion trap T2. This process can be some Repeat times until all ions in the first ion trap T1 and the second ion trap T2 via the further ion trap T0 transferred in a number of stages in the time of flight mass analyzer have been. The further ion trap T0 can be regarded as forming a collision cooling stage, which reduces the energy width of the ions, thereby allowing that the time-of-flight mass analyzer works more effectively.

It can therefore be assumed that the in 3 embodiment shown, at least two ion traps T1, T2 used to increase the total mass range of the ions stored in the ion trapping T1, T2, by ensuring that the LMCO value of the second ion trap T2 is lower than the LMCO value of the first ion trap T1. In the 3 The illustrated embodiment also preferably optimizes the mass-to-charge ratio range of the ions transferred to the lateral acceleration time-of-flight mass analyzer through the use of another ion trap T0. In the further ion trap T0, a collision cooling of ions is also effected, whereby the energy width of the ions is reduced.

Now, an MS operation mode will be referred to 3 described in further detail. The ion source 1 For example, according to one embodiment, it may comprise a MALDI ion source, which typically generates ions with mass-to-charge ratios in the range of 30-3000, for example. Especially interesting ions have mass-to-charge ratios in the range of 100-3000, so that ions with mass-to-charge ratios in the range of 30-100 may not be of particular interest and have been lost. The ions from the ion source 1 are preferably transferred to the first ion trap T1, and the ions are preferably cooled within the first ion trap T1 by collisions.

For example, the LMCO value of the first ion trap T1 may be set to m / z 300 so that ions having relatively high mass-to-charge ratios of, for example, up to m / z 3000 are trapped more efficiently within the first ion trap T1 than would otherwise be the case This would be because a higher AC or RF amplitude V _{rf can be applied} to the ring electrode (s) (or less preferably between the ring electrode (s) and the end cap electrodes) of the first ion trap T1. Preferably, the end cap electrode (the end cap electrodes) of the first ion trap T1 are grounded. The higher AC or RF voltage amplitude applied to the ring electrode (s) of the first ion trap T1 results in providing a greater depth of the axial pseudopotential well within the first ion trap T1, thereby capturing ions having a high mass-to-charge ratio and energetic ions is improved.

It can provide a slight DC bias to the end cap electrodes the first ion trap T1 are applied so that ions with mass-to-charge ratios below the LMCO value the first ion trap T1 (ie with m / z <300), which within the first Ion trap T1 are axially unstable, in the direction of the second ion trap T2 are ejected axially from the first ion trap T1. The one low Having a mass-to-charge ratio Ions ejected from the first ion trap T1 are transferred while they preferably experience another collision cooling, and in the second Trapped ion trap T2, preferably downstream of the first ion trap T1 is located.

Of the LMCO value for the second ion trap T2 is preferably at a lower one Value is set as the LMCO value of the first ion trap T1. For example For example, the LMCO value of the second ion trap T2 may be set to m / z 100 (compared with m / z 300 for the first ion trap T1). Trapped in the first ion trap T1 Ions therefore have mass-to-charge ratios within the range m / z 300-3000 on, and within the second ion trap T2 trapped ions have mass-to-charge ratios within the range of m / z 100-300 on.

sein.If the distance from the origin of the further ion trap T0 to the beginning of the orthogonal extraction region 3 of the time-of-flight mass analyzer is 100 mm and the distance from the origin of the further ion trap T0 to the end of the orthogonal extraction range 3 Is 141.4 mm, the maximum mass-to-charge ratio divided by the minimum mass-to-charge ratio of ions in an ion packet received by the time-of-flight mass analyzer should be less than for efficient ion transfer

be.

According to one embodiment, ions are preferably transferred in two (or more) separate stages from the second ion trap T2 into the further ion trap T0. For example, ions with mass-to-charge ratios in the range of m / z 100-200 can be transmitted from the second ion trap T2 in a first stage and ions with mass-to-charge ratios in the range m / z 200-300 in a second stage from the second ion trap T2 are transmitted. After these two stages, the second ion trap T2 is essentially emptied of ions. Ions from the first ion trap T1 can then reach the extraction region via the second ion trap T2 and via the further ion trap T0 3 of the time of flight mass analyzer. For example, ions with mass-to-charge ratios in the range m / z 300-600 can be carried out of the first ion trap T1 in a stage followed by ions with mass-to-charge ratios in the range m / z 600-1200 in the next stage, which are followed by ions with mass-to-charge ratios in the range of m / z 1200-2400, which are finally followed by ions with mass-to-charge ratios in the range of m / z 2400-3000 in a final stage. It will be understood that at each stage in which ions are transferred, the ratio between the maximum mass-to-charge ratio and the minimum mass-to-charge ratio preferably does not exceed 2. According to this particular example, ions are transmitted in six discrete steps into the time-of-flight mass analyzer and a total of six orthogonal extraction pulses are required to mass-analyze ions effectively over the entire desired m / z range of 100-3000.

It will be understood that because the first ion trap T1 and the second ion trap T2 are preferably operated in mass-selective (ie, scanning) modes of operation, the order in which ions are transmitted may be changed as long as those in the extraction region 3 of the time-of-flight mass analyzer in each individual pulse, preferably have a limited range of mass-to-charge ratios. In one embodiment, the ratio between the maximum mass-to-charge ratio and the minimum mass-to-charge ratio is less than or equal to 4, more preferably less than or equal to 3, and even more preferably less than or equal to 2.

In order to remove ions pulsed from the further ion trap T0, the cooling gas is preferably removed from the further ion trap T0 or allowed to disperse therefrom, so that the pressure within the further ion trap T0 decreases, for example, to <10 ^-4 mbar. The AC or RF voltage applied to the further ion trap T0 is also preferably switched off, and one or more DC extraction pulses are preferably applied to the end cap electrodes of the further ion trap T0 to deliver ions from the further ion trap T0 into the extraction region 3 of the transversal acceleration time-of-flight mass analyzer.

4 shows in more detail how the in 3 shown arrangement of ion traps can be operated to perform a typical MS experiment. The first ion trap T1, the second ion trap T2 and the further ion trap T0 are preferably similar 3D (Paul) quadrupole ion traps. The frequency of all three ion traps T1, T2, T0 applied RF voltage is preferably 0.8 MHz (5.0 rad / us), and the radius of the central annular electrode r ₀ of each ion trap T1, T2, T0 is preferably 0.707 cm , U _dc is preferably 0 V for all ion traps T1, T2, T0, and the ion traps T1, T2, T0 are preferably supplied with helium gas at a pressure of, for example, 0.001 mbar. As will be understood from the following description, in a case where the low and high RF voltages in FIG 4 are shown as equal in one stage of operation during this particular stage is not scanned.

In a first stage S1 become ions with mass-to-charge ratios in the range 300-3000 in the first ion trap T1 stored at which an RF voltage of 913.8 V to the ring electrode (ring electrodes) of the first ion trap T1 is created. Ions with mass-to-charge ratios in the range 100-300 are stored in the second ion trap T2, at which an RF voltage of 304.6 V to the ring electrode (the ring electrodes) of the second Ion trap T2 is applied. The further ion trap T0 preferably contains initially no ions.

In the next Stage S2 is the amplitude of the ring electrode (the ring electrodes) the second ion trap T2 applied RF voltage of 304.6 V to 609.2 V scanned, which leads to that ions with mass-to-charge ratios in the range of 100-200 out the second ion trap T2 are ejected and in the further Transmitted ion trap T0 in which they are cooled by collisions.

In the next stage S3, the cooling gas is allowed to disperse within the further ion trap T0, and the pressure within the further ion trap T0 is effectively dropped by switching off a valve pump which supplies cooling gas to the further ion trap T0. The to the ring electrode (The ring electrodes) of the further ion trap T0 applied 304.6 V RF voltage is turned off, and ions are pulsed from the other ion trap T0 in the lateral acceleration range 3 led the time of flight mass analyzer. The cooling gas is then reintroduced into the further ion trap T0, and an RF voltage of 609.2 V is applied to the ring electrode (ring electrodes) of the further ion trap T0, so that the further ion trap T0 is optimized to be at the next stage Receive ions with mass-to-charge ratios above 200 mass-to-charge ratio units.

In a fourth stage S4 is applied to the second ion trap RF voltage is scanned from 609.2 V to 913.8 V, which causes the remaining ions with mass-to-charge ratios within the range of 200-300 ejected from the second ion trap T2 and transferred into the further ion trap T0, where they cooled by collisions become.

In a fifth stage S5, the cooling gas is allowed to disperse within the further ion trap T0 and the pressure within the further ion trap T0 is allowed to drop by switching off a valve pump which supplies cooling gas to the further ion trap T0. The RF voltage of 609.2 V applied to the ring electrode (ring electrodes) of the further ion trap T0 is turned off and ions are pulsed out of the further ion trap T0 into the lateral acceleration region 3 led the time of flight mass analyzer. The cooling gas is then reintroduced into the further ion trap T0, and an RF voltage of 913.8 V is applied to the ring electrode (ring electrodes) of the further ion trap T0, so that the further ion trap T0 is optimized to be at the next stage Receive ions with mass-to-charge ratios above 300 mass-to-charge ratio units.

In of a sixth stage S6 is applied to the first ion trap T1 Scanned RF voltage from 913.8 V to 1827.6 V, which causes the ions with mass-to-charge ratios within the range of 300-600 Mass to charge ratio units ejected from the first ion trap T1 and into the second ion trap T2 be transferred.

In the next seventh stage S7, the amplitude of the to the ring electrode (the Ring electrodes) of the second ion trap T2 applied RF voltage scanned from 913.8 V to 1827.6 V, resulting in the ions having mass-to-charge ratios in the range of 300-600 ejected from the second ion trap T2 and into the further ion trap T0 be transferred where they are cooled by collisions.

In an eighth stage S8, the cooling gas is allowed to disperse within the further ion trap T0 and the pressure within the further ion trap T0 is dropped by switching off a valve pump which supplies cooling gas to the further ion trap T0. The RF voltage of 913.8 V applied to the ring electrode (ring electrodes) of the further ion trap T0 is turned off, and ions are pulsed from the other ion trap T0 into the lateral acceleration region 3 led the time of flight mass analyzer. The cooling gas is then reintroduced into the further ion trap T0, and an RF voltage of 1827.6 V is applied to the ring electrode (ring electrodes) of the further ion trap T0, so that the further ion trap T0 is optimized to be at the next stage Receive ions with mass-to-charge ratios above 600 mass-to-charge ratio units.

In of a ninth stage S9 is applied to the first ion trap T1 HF voltage from 1827.6 V to 3655.2 V scanned, which causes the ions with mass-to-charge ratios within the range of 600-1200 Mass to charge ratio units ejected from the first ion trap T1 and into the second ion trap T2 be transferred.

In the next The tenth step S10 is the amplitude of the ring electrode (the Ring electrodes) of the second ion trap T2 applied RF voltage scanned from 1827.6 V to 3655.2 V, resulting in the ions with mass-to-charge ratios in the range of 600-1200 ejected from the second ion trap T2 and into the further ion trap T0 be transferred where they are cooled by collisions.

In an eleventh stage S11, the cooling gas is allowed to disperse within the further ion trap T0 and the pressure within the further ion trap T0 is allowed to drop by switching off a valve pump which supplies cooling gas to the further ion trap T0. The RF voltage of 1827.6 V applied to the ring electrode (ring electrodes) of the further ion trap T0 is turned off and ions are pulsed out of the further ion trap T0 into the lateral acceleration region 3 led the time of flight mass analyzer. The cooling gas is then reintroduced into the further ion trap T0, and an RF voltage of 3655.2 V is applied to the ring electrode (ring electrodes) of the further ion trap T0, so that the further ion trap T0 is optimized to be at the next stage Receive ions with mass-to-charge ratios above 1200 mass-to-charge ratio units.

In a twelfth stage S12, the RF voltage applied to the first ion trap T1 is scanned from 3655.2 V to 7310.5 V, which causes the ions with mass-to-charge ratios in within the range of 1200-2400 mass-to-charge ratio units are ejected from the first ion trap T1 and transferred to the second ion trap T2.

In the next The thirteenth stage S13 is the amplitude of the ring electrode (the ring electrodes) of the second ion trap T2 applied RF voltage Scanned from 3655.2 V to 7310.5 V, which causes the ions with mass-to-charge ratios in the range of 1200-2400 ejected from the second ion trap T2 and into the further ion trap T0 be transferred where they cooled by collisions become.

In a fourteenth stage S14, the cooling gas is allowed to disperse within the further ion trap T0 and the pressure within the further ion trap T0 is dropped by switching off a valve pump which supplies cooling gas to the further ion trap T0. The 3655.2 V RF voltage applied to the ring electrode (s) of the further ion trap T0 is turned off and ions are pulsed out of the further ion trap T0 into the lateral acceleration region 3 led the time of flight mass analyzer. The cooling gas is then reintroduced into the further ion trap T0, and an RF voltage of 7310.5 V is applied to the ring electrode (ring electrodes) of the further ion trap T0, so that the further ion trap T0 is optimized to be at the next stage Receive ions with mass-to-charge ratios above 2400 mass-to-charge ratio units.

In a fifteenth Stage S15 becomes the RF voltage applied to the first ion trap T1 scanned from 7310.5 V to 9138.1 V, which causes the ions to have mass-to-charge ratios within the range of 2400-3000 Mass to charge ratio units ejected from the first ion trap T1 and into the second ion trap T2 be transferred whereby the first ion trap T1 is emptied of ions.

In the next Sixteenth stage S16 is the amplitude of the ring electrode (the ring electrodes) of the second ion trap T2 applied RF voltage Scanned from 7310.5 V to 9138.1 V, which causes the ions with mass-to-charge ratios in the range of 2400-3000 ejected from the second ion trap T2 and into the further ion trap T0 be transferred whereby the second ion trap is emptied. The ions are preferably cooled within the other ion trap T0 by collisions.

In a last seventeenth stage S17, the cooling gas is allowed to disperse within the further ion trap T0 and the pressure within the further ion trap T0 is dropped by switching off a valve pump which supplies cooling gas to the further ion trap T0. The RF voltage of 7310.5 V applied to the ring electrode (ring electrodes) of the further ion trap T0 is turned off, and ions are pulsed out of the further ion trap T0 into the lateral acceleration region 3 led the time of flight mass analyzer. The cooling gas may then be reintroduced into the further ion trap T0, and an RF voltage may be applied to the ring electrode (ring electrodes) of the further ion trap T0 prepared for the next cycle.

In order to remove ions pulsed from the further ion trap T0 and into the extraction area 3 of a Time of Flight mass analyzer, a DC voltage preferably in the range of 10-500 V may be applied to the end cap electrodes of the further ion trap. T0 be applied to accelerate ions from the other ion trap T0 out. The DC voltage may be applied, for example, for a minimum of 1 μs, and the DC extraction voltage according to other embodiments at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75 , 80, 85, 90, 95 or 100 μs.

In an above regarding 4 ions are removed by scanning either from the first ion trap T1 or from the second ion trap T2 ten times per cycle. Each scan of the RF voltage applied to the ion trap is preferably 50 ms. The stage of collision cooling and pulsed extraction occurs in the other ion trap T0 in relation to 4 example described six times per cycle. The ions are preferably cooled in the further ion trap T0 for at least 30 ms by collisions. As soon as the ions in the further ion trap T0 have been cooled by collisions, the HF voltage applied to the further ion trap T0 is preferably switched off, ions are pulsed out of the further ion trap T0, the HF voltage is applied again and a gas is re-introduced into the further ion trap T0 is initiated. This process takes about 50 ms. The total cycle time is preferably about 1.1 seconds. The calculation of the cycle time does not include the time needed to ionize the ions and transfer them into the first ion trap T1. The ion source is preferably pulsed and may be pulsed for example 10-100 times per second.

Referring again to 3 It should be noted that an MS / MS mode of operation may also be practiced, in which the first ion trap T1 is controlled to selectively capture output ions having a particular mass-to-charge ratio of interest, while all other output ions are preferably derived from the first embodiment th ion trap T1 are ejected.

The retained within the first ion trap T1 parent ions are then preferably fragmented in the first ion trap T1 by collisions, for example by the q _z value of the first ion trap is set to about 0.3 T1, thereby causing the parent ions are energetic enough so that they fragment upon colliding with the background gas within the first ion trap T1. Preferably, resonance excitation is applied to specific output ions, thereby causing repeated higher energy collisions, for example, with helium gas within the first ion trap T1, such that the parent ions gain sufficient internal energy to cause collision-induced dissociation (CID). The fragment ions with q _z > 0.908 are axially unstable within the first ion trap T1 and emerge from the first ion trap T1 along the z-axis and are preferably captured within the second ion trap T2. Therefore, fragment ions can be trapped in both the first ion trap T1 and the second ion trap T2, and the fragment ions can be efficiently transmitted to the mass analyzer via the second ion trap T2 and the further ion trap T0 similarly to the MS mode of operation has been described.

According to a in 5 In the less preferred embodiment illustrated, a single, for example, mass-selective ion trap T1 may be coupled to a transverse acceleration time-of-flight mass analyzer via a further ion trap T0. Such an arrangement allows a limited mass range of ions to be cooled by collisions and then transmitted to the time-of-flight mass analyzer so that the ions received by the time-of-flight mass analyzer in a pulse are all accelerated substantially transversely into the drift region. In the 5 However, the illustrated embodiment does not offer the advantage of an improved mass range capture system that requires two or more ion traps T1, T2 with different LMCO values.

Although in the 3 and 5 In embodiments shown to be able to perform MS / MS experiments, other output ions than those initially captured in the first ion trap T1 can be effectively lost. To significantly increase the scanning efficiency of the parent ions, another is in 6 shown preferred embodiment in which additional ion traps TA, TB are provided to store output ions ejected from the first ion trap T1, which are not subject of the present MS / MS analysis. A second additional ion trap TB may preferably be configured to have a lower LMCO value than the first additional ion trap TA, thus providing an improved ion capture system for storing exit ions that are not yet subject to the present mass analysis.

As soon as an MS / MS experiment has been performed is, can the next interesting initial ions from the first additional Ion trap TA and / or the second additional ion trap TB in the first ion trap T1 transmitted in which the parent ions are then fragmented become.

According to one alternative embodiment can all within the first and second additional ion traps TA and TB trapped ions, for example, in a non-mass selective manner, in the first Transfer ion trap T1 back be, and it can then the next interesting exit ions selectively in the first ion trap T1 are detained while all other parent ions are mass selective from the first ion trap T1 pushed out and into one or more of the additional ion traps TA, TB to be led back. Additional additional Ion traps (not shown) can be provided the capture efficiency of those waiting for further MS / MS analysis To improve parent ions.

For example, ions can be generated by a MALDI ion source 1 and typically have mass-to-charge ratios in the range of m / z 30-3000. The from the ion source 1 emitted ions can be transferred into the first ion trap T1 and cooled there by collisions, although according to other embodiments, ions can be generated within the first ion trap T1.

One MS spectrum may have been previously recorded, and it may, for example be desired an MS / MS mass spectrum of the parent ions with a given Mass-to-charge ratio of For example, to obtain 1500. Exit versions with of 1500 different Mass-to-charge ratios can ejected from the first ion trap T1 and first in the first additional Ion trap TA are transferred. This can be done, for example, by applying a sweep frequency to the End cap electrodes of the first ion trap T1 can be achieved, whereby a resonant excitation (axial modulation with an additional oscillating potential) of all ions except the desired one Output ions is effected. The applied to the first ion trap T1 RF voltage can also be temporary be reduced to increase the LMCO value.

According to one another embodiment can all ions within the first ion trap T1 in the first additional one Transfer ion trap TA and the interesting source ions with mass-to-charge ratios from 1500 can then using similar ones Processes such as those described above from the first additional Ion trap TA are transferred back into the first ion trap T1.

parent ions with mass-to-charge ratios below the LMCO value of the first additional ion trap TA, in a second (or even more) additional ion trap TB captured which are preferably in series with the first additional Ion trap TA is provided and the preferred in use a lower LMCO value as the first additional Ion trap TA has.

After ions have been at a mass to charge ratio of 1500 isolated in the first ion trap T1 and is preferably at a different location (ie, in additional ion traps TA, TB) have been stored, the q _z value for the first ion trap T1 can be applied to 0.3 (for m / z of 1500) to cause sufficient excitation to cause fragmentation of the parent ions without axial or radial ejection. The LMCO value of the first ion trap T1 can be set to m / z 500. The LMCO value for the second ion trap T2 downstream of the first ion trap T1 can be set to m / z 100, ie to a lower value than the LMCO value of the first ion trap T1. A background collision gas is preferentially maintained in or introduced into the first ion trap T1, and preferably a resonant excitation function is applied to the end cap electrodes of the first ion trap T1 to increase the kinetic and internal energies of the source ions so that they may be excited Colliding with gas molecules within the first ion trap T1 fragment.

fragment ions with mass-to-charge ratios in the m / z range of for example, 100-1500 can through such a collision activation can be generated. fragment ions with mass-to-charge ratios below m / z 500 become axially unstable in the first ion trap T1 and preferably ejected axially from the first ion trap T1, so that they are trapped in the second ion trap T2.

Fragment ions are now effectively extracted from the first ion trap T1 and the second ion trap T2 and in a number of discrete steps in a manner similar to that described above 4 described MS operating mode transferred to the mass analyzer. In a first stage, ions in the m / z range of 100-200 may be transferred from the second ion trap T2 to the further ion trap T0 where they are cooled by collisions before being forwarded to the time-of-flight mass analyzer. In a second stage, ions in the 200/400 m / z range can be transferred from the second ion trap T2 to the further ion trap T0, where they are cooled by collisions before being forwarded to the time of flight mass analyzer. In a third stage, ions in the m / z range of 400-500 can be transferred from the second ion trap T2 to the further ion trap T0, where they are cooled by collisions before being forwarded to the time-of-flight mass analyzer.

The three stages described above cause the second Ion trap T2 is emptied of all fragment ions. fragment ions with mass-to-charge ratios in the m / z range of 500-1000 can then over the second ion trap T2 and over the further ion trap T0 transferred from the first ion trap T1 in the time-of-flight mass analyzer become. Below you can Fragment ions having mass-to-charge ratios in the range of 1000-2000 mass-to-charge ratio units over the second ion trap T2 and the further ion trap T0 from the first Ion trap T1 are transferred to the time-of-flight mass analyzer.

After this all MS / MS data has been acquired from a particular output version others can MS / MS acquisitions on some, or preferably all, remaining ones Executed versions which are now in the first and the second additional Ion trap TA and TB have been stored. advantageously, no parent ions are lost, and it may be for all parent ions of interest complete MS / MS data be recorded.

According to one less preferred and not explained embodiment can the first additional Ion trap TA and the second additional Ion trap TB between the first ion trap T1 and the second Be arranged ion trap T2, or they can be downstream of the first ion trap T1 and / or the second ion trap T2 are located.

Now, a particularly preferred ion trap system and a particularly preferred ion trap ion source will be referred to 7 described. To reduce potential transmission losses between ion traps and increase the homogeneity of the electric field when pulsing ions into the lateral acceleration time of flight mass analyzer, the electrodes of the various ion traps may be in the form of a plurality of cylindrical thin rings 10A . 10B . 10C being constructed. According to the in 7 illustrated embodiment, each ion trap on three such thin rings. Neighboring ion traps may continue through common end cap electrodes 11 be separated, the highly permeable grid 12 to reduce the field penetration. Alternatively, some or all of the grated end cap electrodes may be used 11 are replaced by circular plate electrodes having relatively small openings which, according to one embodiment, can form differential pumping openings between vacuum stages.

Ions may be from a sample or target plate within or near the first ion trap T1 by a laser 14 , a laser beam 15 generated, generated. The shooting of the laser 14 can with the phase of the ring electrodes 10A the first ion trap T1 applied RF voltage are synchronized so that on or at the sample or target plate 13 generated ions fly immediately into or within the first ion trap T1. The electric field applied to the first ion trap T1, therefore, preferably effectively extracts ions at the moment they are generated, preferably to preclude or minimize the risk of the ions becoming the sample or target plate 13 be reflected back, which could otherwise cause the ions to be lost. The angle θ between the sample or target plate 13 and the ionizing pulsed laser beam 15 (or less preferably an electron beam) may be 90 °, in which case the pulsed laser beam 15 (or electron beam) through the extraction area 13 of the lateral acceleration time-of-flight mass analyzer. It is also possible to use smaller angles than 90 °, and they are for example in the in 7 illustrated specific embodiment illustrated. In another embodiment, a mirror or other reflective element may be provided between the ion trap ion source and the mass analyzer. The mirror may, for example, be oriented at 45 °. A laser beam can be directed at the mirror and then at the target or sample plate 13 be reflected. Preferably, ions generated by the ion trap ion source may be transmitted by a small aperture provided in the mirror or other reflective element.

According to the preferred embodiment, to the ring electrodes 10A . 10B . 10C the first, the second and the further ion trap T1, T2, T0 applied RF voltages with a frequency of 800 kHz. The amplitudes of the RF voltages applied to each of the first, second and further ion traps T1, T2, T0 may differ. The DC voltage applied to all ion traps T1, T2, T0 is preferably set to zero. The first, second and further ion traps T1, T2, T0 are preferably supplied with helium gas, and they are preferably maintained at a pressure of 10 ^-3 mbar. Before ions extracted from the other ion trap T0 and in the lateral acceleration range 3 of the time-of-flight mass analyzer, the pressure in the further ion trap T0 can be reduced to <10 ^-4 mbar. If, according to one embodiment, the pressure in the further ion trap T0 is reduced, the pressure in the first and / or the second ion trap T1, T2 can also be reduced to a pressure similar to that of the further ion trap T0.

To hold an ion trap at a pressure such that collision cooling of ions occurs or collision activation occurs for MS / MS experiments, helium gas can be introduced into the ion trap to increase the pressure in the ion trap to about 10 ^-3 mbar. The helium or other gas may be introduced using a solenoid-operated needle valve or a pulsed supersonic valve (available, for example, from RM Jordan Inc.). The pulsed supersonic valve can be operated to provide 50 μs gas pulses at a repetition rate of 10 Hz. Once the collision or cooling gas has been introduced into an ion trap, it can be expected that the gas will remain within the ion trap for about 10 milliseconds before it is dispersed or pumped out of the ion trap by the vacuum pump. The exact time that it can be assumed that the collision gas will effectively remain within the ion trap depends on the geometry of the ion trap and the vacuum chamber as well as the capacity of the vacuum pumps.

In all the embodiments described above, between the first ion trap T1 and / or the second ion trap T2 and / or between the second ion trap T2 and the further ion trap T0 and / or between the further ion trap T0 and the mass analyzer, for example the time-of-flight mass analyzer, differential pumping systems are used. According to an embodiment, the further ion trap T0 may be provided downstream of the first ion trap T1 and the second ion trap T2 in a vacuum chamber different from those of the first ion trap T1 and the second ion trap T2. Providing the further ion trap T0 in a separate vacuum stage allows the pressure of the gas in the further ion trap T0 to be more easily between 10 ^-3 mbar (for collision cooling) and <10 ^-4 mbar (for the pulsed extraction of ions). can be changed, while the first ion trap T1 and the second ion trap T2, for example, can be kept constant at about, for example, 10 ^-3 mbar. According to a less preferred embodiment, the valves that are the first ions trap T1 and the second ion trap T2, turn off when the valve supplying the other ion trap T0 gas is turned off.

According to the in 7 As shown and described, the lattice-shaped end cap electrode between the second ion trap T2 and the further ion trap T0 can be replaced by a pump provided with a differential pumping opening.

The referring to 7 The illustrated and described embodiment in which ions are generated directly within an ion trap is particularly advantageous compared to conventional arrangements in which ions are generated outside of an ion trap. If an ion pulse is accelerated with a dc field from a point outside an ion trap, ions with different mass-to-charge ratios will have different times of flight into the ion trap. The timing of the RF voltage applied to the ion trap must therefore be carefully optimized, or the voltage must even be turned off until all desired ions are within the ion trap, because otherwise they can be reflected back and lost. The acceptance, and therefore the successful trapping, of ions in a conventional ion trap depends on the position, kinetic energy, and mass-to-charge ratio of the ions, which are pulsed at the time to the ion trap to which the RF voltage is applied Ion trap is applied. Therefore, ions generated outside the ion trap usually have a significant variation in their position, resulting in a detrimental effect on the acceptance of ions within the ion trap.

In addition to The constraints given by the trapping potential also limit geometrical constraints Constraints the acceptance of ions in a conventional Ion trap. For example, you can some ions with a low mass to charge ratio too the time in the ion trap and through the cap electrode of the Outgoing of the ion trap must be passed, to the one effective RF capture voltage is applied to the ion trap while others Ions with a relatively high Mass-to-charge ratio the ion trap maybe at the time not yet reached, to which an effective RF capture voltage is applied to the ion trap. Conventional ion trap arrangements can therefore discriminating according to the mass-to-charge ratio Have effects. The ion trap ion source according to the preferred embodiment preferably does not have these problems and therefore stops significantly improved ion trap and ion source system.

Claims (5)

A method of mass spectrometry, comprising the steps of: providing a first quadrupole ion trap (T1) having a first lower mass cutoff, a second quadrupole ion trap (T2) having a second lower mass cutoff, the second lower mass cutoff being lower than the first lower mass cutoff Mass cutoff so that at least some ions with mass-to-charge ratios below the first lower mass cutoff boundary that are not captured in the first ion trap (T1) are captured in the second quadrupole ion trap (T2), another ion trap (T0), receives the ions ejected from the second quadrupole ion trap (T2) and a time of flight mass analyzer ( 2 . 3 receiving ions ejected from the further ion trap (T0), mass selective ejection or scanning of a pulse of ions from the second quadrupole ion trap (T2), wherein the further ion trap (T0) receives the pulse of ions and wherein Ratio between the maximum mass-to-charge ratio of the ions in the pulse of ions and the minimum mass-to-charge ratio of the ions in the pulse of ions ≤ 4.0, collision cooling the ions received from the second quadrupole ion trap (T2) within the further ion trap (T0), non-mass-selective transfer of the collision-cooled ions from the further ion trap (T0) into the time-of-flight mass analyzer ( 2 . 3 ) and analyzing the ions in the Time of Flight mass analyzer ( 2 . 3 ). The method of claim 1, wherein the collision-cooled ions by applying one or more DC extraction pulses Pulsed to the other ion trap (T0) are taken from this. The method of claim 2, wherein one or more Extraction DC voltages to one or more end or end cap electrodes the other ion trap (T0) are applied. The method of claim 2 or 3, wherein one or several extraction DC voltages to one or more central Electrodes or ring electrodes of the other ion trap (T0) applied become. The method of any one of claims 1 to 4, wherein the further ion trap (T0) is at a lower pressure for non-mass selective transfer of the collision cooled ions to the time-of-flight mass analyzer than for receiving the pulse of ions from the second quadrupole ion trap (T2) is held.