DE10340849B4 - Use of a quadrupole rod set and an ion detector of a mass spectrometer - Google Patents

Abstract

use a quadrupole rod set (6, 6 ') and an ion detector (7) a mass spectrometer in two modes of operation, where the quadrupole rod set (6, 6 ') in the first operating mode as a mass filter for selective Passing ions according to their mass-to-charge ratio the ion detector (7) is operated, characterized in that the Quadrupole rod set (6, 6 ') in the second mode of operation as a Flight time range is operated, with toning in this second mode of operation pulsed into the quadrupole rod set (6, 6 ') are introduced and the ion detector (7) determines the time of flight of the ions through the time-of-flight range.

Description

The The present invention relates to a use of a quadrupole rod set and an ion detector of a mass spectrometer.

It are quadrupole rod sets known having two pairs of parallel bars. Two paired diametrically opposed bars are electrically connected to each other and to the same phase of an RF power supply connected. The RF power supply is set up so that the RF voltage applied to a pair of diametrically opposed rods results in a phase difference from 180 ° in Reference to the other rod pair has.

Of the Quadrupole rod set can be operated as a mass filter to Let through ions with specific mass-to-charge ratios and others Toning down ions, by a DC potential difference between adjacent pairs of rods is maintained. If a DC potential difference between the pairs of rods, certain ions remain in the quadrupole rod set and are from one end of the quadrupole rod set let others through. However, other ions become unstable and therefore not let through by the quadrupole set of rods. The between the bars sustained DC potential difference, for example be set up so that ions, their mass-charge ratios outside of a narrow range, are destabilized and not let through. The DC potential difference can also be increased or be scanned, so eventually only ions with a specific mass-to-charge ratio in remain stable to the quadrupole rod set while other ions are filtered out become. Another increase the DC voltage can cause that all ions are destabilized, so that no ions are transmitted. Accordingly allows a suitable selection of the applied to the quadrupole rod set RF and DC voltages that only ions with selected mass-to-charge ratios to be let through while all other ions are eliminated.

The Quadrupole rod set mass filter allows ions with a specific Mass-to-charge ratio efficient through. However, when ions have a range of mass-to-charge ratios need to be recorded have to the applied to the quadrupole rod set RF and DC voltages be scanned to successively pass ions that are specific Mass-to-charge ratio exhibit. this leads to to that the duty cycle for letting ions with a specific mass-to-charge ratio decrease, when the range of mass-to-charge ratios to be recorded increases. If the mass range to be scanned is for example 500 mass units and the Mass peak width at the base is a mass unit, is the time which is used to pass through ions that are within one Mass to charge ratio unit the same mass-to-charge ratio , 1/1000 of the total scan time, and the duty cycle drops, therefore to 0.1%. This is to be compared with a duty cycle of 100%, when the quadrupole rod set mass filter for passing ions is used with a single mass to charge ratio.

A further restriction when using a quadrupole rod set mass filter / mass analyzer for recording ions having a range of mass-to-charge ratios is the time to record a complete mass spectrum is required. Ions transmitted by a quadrupole mass filter, typically have a relatively low Energy, for example only a few eV. Therefore, the ions usually need one relatively long Period to get over the length to move the quadrupole rod set. The time depends on the length of the quadrupole rod set and the energy of the ions. The quadrupole rod set mass filter can therefore not be scanned at a faster rate than the time that they need, to get over the length of the quadrupole rod set, because otherwise the ions move not enough Time is allowed to pass. For example, the Ions between 0.1 ms and 1 ms need to get over the Length of the Quadrupole set of rods to move. Therefore, the quadrupole rod set mass filter not be scanned much faster than 1 ms per mass unit, because otherwise the ions are not allowed enough time to to be let through. Accordingly, the minimum time is which is required to scan 500 mass units, typically between 0.1 and 0.5 seconds.

It is based on the above considerations it can be seen that the Quadrupole rod set mass filter is suitable for applications where it is not necessary ions with a single mass-to-charge ratio or record a limited range of mass-to-charge ratios and to quantify. A quadrupole rod set mass filter is not particularly for applications suitable, where it is necessary, ions with a relatively broad Range of mass-to-charge ratios record with high sensitivity and relatively high speed.

A Time of Flight mass analyzer is another known mass analyzer. A flight time Mas senanalysator has a drift or flight range and a detector for fast ions. Provision is made for ions entering the drift or flight area to have constant energy and therefore to be separated as they move through the drift or flight area according to their mass-to-charge ratio. A fast analog-to-digital converter ("ADC") or a time-to-digital converter ("TDC") can be used to record the arrival times of the ions at the ion detector. The arrival times allow the mass-to-charge ratios of the ions to be calculated because the mass-to-charge ratio of an ion squared is the time of flight of the ion proportional to the entrance of the drift region to the ion detector.

One Time of flight mass spectrometer can be for each leaving the ion source Ion impulse a complete Record mass spectrum. If the ion source is a pulsed Ion source in the manner of a laser ablation ion source or a Matrix Assisted Laser desorption and ionization ion source ("MALDI ion source"), the duty cycle for recording the complete mass spectrum 100%. If the ion source is continuous and, for example an electrospray or Electron impact ion source is, the duty cycle becomes determined by the means by which the continuous ion beam is sampled and ion packets into the drift or flight range of the time of flight mass analyzer be injected.

Cross acceleration Time of Flight Mass Spectrometer typically achieve a sample duty cycle in the range of 5-25%. By combined use of a non-mass selective ion trap with a lateral acceleration time of flight mass spectrometer, the duty cycle for ions with a specific narrow range of mass-to-charge ratios increased to about 100%, while the duty cycle for ions, the outside this range of mass-to-charge ratios decreases to 0%.

One Time of flight mass spectrometer is for recording ions with a narrow range of mass-to-charge ratios, for example ions with a range of only one or two mass-to-charge ratio units, not ideal. The duty cycle and the transmission of a time-of-flight mass spectrometer required are to ions with a narrow scatter of only one or two Mass to charge ratio units do not match those of a quadrupole rod set mass filter in a comparable situation. Furthermore, the linear Dynamic range typically in a conventional time-of-flight mass spectrometer ion detection systems used are inferior to those used in a mass spectrometer using a quadrupole rod set mass analyzer having. This is because ions in a time-of-flight mass spectrometer recorded in very short bursts be while Ions in a mass spectrometer having a quadrupole mass analyzer be recorded continuously.

Although Time of flight mass spectrometer for Applications are required in which it is necessary to have a complete mass spectrum fast and with high sensitivity are time of flight mass spectrometers not especially for Applications. in which it is necessary ions with mass-to-charge ratios record and quantify themselves by only a few mass-to-charge ratio units differ.

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. The use of a quadrupole rod set as flight time range of a time-of-flight mass spectrometer is not disclosed.

The US Pat. No. 6,093,929 A refers to a mass spectrometer which fragments fragment ions and thus generates daughter ions and subsequently analyzes these daughter ions. A first quadrupole rod set acts as an internal guide for transmitting exit ions through an aperture. A second quadrupole rod set acts as a mass filter, which transmits only exit ions with a certain mass-to-charge ratio. The transmitted exit ions are then fragmented within a third quadrupole rod set. A fourth quadrupole rod set acts as a mass filter, which transmits only daughter ions with a certain mass-to-charge ratio. Each of the quadrupole rod sets has a specific, well-defined function. None of these quadrupole rod sets are designed to operate in two different modes of operation.

The publication EP 0 237 259 A2 discloses a similar arrangement.

The WO 01/78106 A2 discloses a mass spectrometer having a fragmentation section comprising a delay stage, an ion trap stage, and an axial acceleration stage. The ion trap is connected to a gas inlet system and is differentially pumped with the adjacent delay stage and the acceleration stage and is thus designed as a collision cell.

It is desired to provide an improved mass spectrometer.

According to the invention is a Use of a quadrupole rod set and an ion detector of a mass spectrometer having the features of claim 1.

Advantageously, a mass spectrometer is provided which comprises:
a multi-mode quadrupole rod set and
an ion detector,
wherein in a first mode of operation the quadrupole rod set acts as a mass filter and wherein in a second mode of operation the quadrupole rod set forms a time-of-flight range of a time-of-flight mass analyzer.

in the first mode of operation will be ions within a first range lying mass-charge ratios preferably transmitted by the quadrupole rod set and ions with outside of the first range of mass-to-charge ratios preferably significantly attenuated by the quadrupole rod set. Exchange or RF voltages are applied to the bars of the quadrupole rod set, and a DC potential difference is between adjacent bars maintained when the quadrupole rod set is in the first operating mode.

in the In the second operating mode, ions are pulsed into the time-of-flight range brought in. Ions are transmitted by the quadrupole rod set without to be mass filtered considerably, and they become correspondingly their mass-to-charge ratio separated in time. The ion detector determines the time of flight of the ions by the time-of-flight area. AC or RF voltages are connected to the Bars of the Quadrupole rod set applied, and all rods of the quadrupole rod set be in the second mode of operation at substantially the same DC potential held.

In the first and / or second mode of operation, the quadrupole rod set is preferably maintained at a pressure selected from the following group: (i) greater than or equal to 1 × 10 ^-7 mbar, (ii) greater than or equal to 5 × 10 ^{. 7} mbar, (iii) greater than or equal to 1 × 10 ^-6 mbar, (iv) greater than or equal to 5 × 10 ^-6 mbar, (v) greater than or equal to 1 × 10 ^-5 mbar and (vi) greater than or equal to 5 × 10 ^-5 mbar.

In the first and / or second mode of operation, the quadrupole rod set is preferably maintained at a pressure selected from the following group: (i) less than or equal to 1 × 10 ^-4 mbar, (ii) less than or equal to 5 × 10 ^{. 5} mbar, (iii) less than or equal to 1 × 10 ^-5 mbar, (iv) less than or equal to 5 × 10 ^-6 mbar, (v) less than or equal to 1 × 10 ^-6 mbar, (vi) less than or equal to 5 × 10 ^-7 mbar and (vii) less than or equal to 1 × 10 ^-7 mbar.

In the first and / or second mode of operation, the quadrupole rod set is preferably maintained at a pressure selected from the following group: (i) between 1 × 10 ^-7 and 1 × 10 ^-4 mbar, (ii) between 1 × 10 ^-7 and 5 × 10 ^-5 mbar, (iii) is between 1 x 10 ^-7 and 1 x 10 ^-5 mbar, (iv) between 1 × 10 ^-7 and 5 × 10 ^-6 mbar, (v) between 1 x 10 ^-7 and 1 x 10 ^-6 mbar, (vi) is between 1 × 10 ^-7 and 5 × 10 ^-7 mbar, (vii) between 5 × 10 ^-7 and 1 x 10 ^-4 mbar, (viii) between 5 × 10 ^-7 and 5 × 10 ^-5 mbar, (ix) between 5 × 10 ^-7 and 1 × 10 ^-5 mbar, (x) between 5 × 10 ^-7 and 5 × 10 ^-6 mbar, (xi) between 5 x 10 ^-7 and 1 x 10 ^-6 mbar, (xii) between 1 x 10 ^-6 and 1 x 10 ^-4 mbar, (xiii) between 1 x 10 ^-6 and 5 x 10 ^-5 mbar, (xiv ) between 1 × 10 ^-6 and 1 × 10 ^-5 mbar, (xv) between 1 × 10 ^-6 and 5 × 10 ^-6 mbar, (xvi) between 5 × 10 ^-6 and 1 × 10 ^-4 mbar, ( xvii) between 5 × 10 ^-6 and 5 × 10 ^-5 mbar, (xviii) between 5 × 10 ^-6 and 1 × 10 ^-5 mbar, (xix) between 1 × 10 ^-5 and 1 × 10 ^-4 mbar, (xx) between 1 × 10 ^-5 and 5 × 10 ^-5 mbar and (xxi) between 5 × 10 ^-5 and 1 × 10 ^-4 mbar.

The Mass spectrometer preferably has a collision cell and a another quadrupole rod set, which is located upstream of the collision cell is on. The multi-mode quadrupole rod set is preferably downstream of Collision cell arranged.

In In an MS mode of operation, the additional quadrupole rod set acts as one Mass filter for mass filtering of output ions. parent ions are cooled by collisions within the collision cell, and Exit ions preferably exit the collision cell substantially not pulsed out. The multi-mode quadrupole rod set is preferably in a operated in the third mode of operation to allow passage of initial ions, without significantly mass filtering the output ions.

In an MS / MS mode of operation, the additional quadrupole rod set acts as a mass filter for mass filtering of parent ions. Preferably, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or 100% of the exit ions entering or entering the collision cell enter the collision cell or within this to form Frag mentionen fragmented. The fragment ions are cooled by collisions within the collision cell and preferably exit the collision cell substantially non-pulsed. The multi-mode quadrupole rod set is operated in the first mode of operation to mass-filter fragment ions. The multi-mode quadrupole rod set can be scanned. to act as a mass analyzer.

In In an MS-TOF mode of operation, the additional quadrupole set of rods acts as one Inside guide to Passage of exit ions, without the exit ions in considerable Mass filter mass. The Exit ions are collided within the collision cell chilled and / or captured, and they can be removed from the collision cell pulsed. The multi-mode quadrupole rod set is preferably operated in the second mode of operation, so that output ions when separated by the multi-mode quadrupole rod set running time range are running.

In In an MS / MS TOF operating mode, the additional quadrupole rod set acts as a mass filter for mass filtering of output ions. At least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or 100% of the Be collision cell entering or located therein Ausgangssionen preferably upon entering the collision cell or within fragmented by this to form fragment ions. The fragmentions become within the collision cell cooled by collisions and / or captured and preferably pulsed out of the collision cell. The multi-mode quadrupole rod set is operated in the second mode of operation, so that fragment ions are separated in time when they pass through the from the multi-mode quadrupole rod set running time range are running.

The Collision cell may be a segmented rod set or a stacked one Ring set having a number of electrodes in which openings which allow ions to pass through in use.

One axial DC voltage gradient may be along during use at least a portion of the length the collision cell are maintained. In an operating mode becomes in use along an axial DC voltage difference maintained at least a first portion of the collision cell and selected from the following group: (i) 0.1-50 V, (ii) 50-100 V, (iii) 100-200 V, (iv) 200-500 V, (v) 500-1000 V, (vi) 1000-2000 V, (vii) 2000-3000 V, (viii) 3000-4000 V, (ix) 4000-5000 V, (x) 5000-6000 V, (xi) 6000-7000 V, (xii) 7000-8000 V, (xiii) 8000-9000 V, (xiv) 9000-10000 V and (xv)> 10 kV. In an operating mode, an axial DC voltage gradient is used in use maintained along at least a first portion of the collision cell and selected from the following group: (i) 0.1-5 V / mm, (ii) 5-10 V / mm, (iii) 10-20 V / mm, (iv) 20-30 V / mm, (v) 30-40 V / mm, (vi) 40-50 V / mm, (vii) 50-60 V / mm, (viii) 60-70 V / mm, (ix) 70-80 V / mm, (x) 80-90 V / mm, (xi) 90-100 V / mm, (xii) 100-150 V / mm, (xiii) 150-200 V / mm, (xiv) 200-250 V / mm, (xv) 250-300 V / mm, (xvi) 300-350 V / mm, (xvii) 350-400 V / mm, (xviii) 400-450 V / mm, (xix) 450-500 V / mm and (xx)> 500 V / mm. The first section is within a range which is at 0-10%, 10-20%, 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90% or 90-100% the length the collision cell, measured from an ion input of the collision cell to an ion exit of the collision cell. The first Section may preferably be in the farthest 10%, 20%, 30%, 40% or 50% of the collision cell.

The Collision cell preferably consists of 10-20 electrodes, 20-30 electrodes, 30-40 Electrodes, 40-50 Electrodes, 50-60 Electrodes, 60-70 electrodes, 70-80 Electrodes, 80-90 Electrodes, 90-100 Electrodes, 100-110 Electrodes, 110-120 electrodes, 120-130 Electrodes, 130-140 Electrodes, 140-150 Electrodes and> 150 Electrodes.

The collision cell in use is preferably maintained at a pressure selected from the following group: (i)> 1.0 × 10 ^-3 mbar, (ii)> 5.0 × 10 ^-3 mbar, (iii)> 1.0 x 10 ^-2 mbar, (iv) 10 ^-3 - 10 ^-2 mbar and (v) 10 ^-4 - 10 ^-1 mbar.

In In an operating mode, ions are trapped in the collision cell, but not to a considerable extent fragmented in it. In another mode of operation, ions become trapped in the collision cell and to a considerable extent in it fragmented. In another mode of operation, ions are within the collision cell captured and progressing to an output the collision cell moves. Ions can be inside the collision cell near stored or captured at their exit. In an operating mode ions are within the collision cell in an ion trapping region, close up located at the exit of the collision cell, cooled by collisions.

According to a preferred embodiment, the collision cell-forming electrodes may be maintained at different DC potentials such that at least a first and a second longitudinally-accelerating electric field region of different levels are provided to accelerate ions out of the collision cell. Prior to accelerating ions out of the collision cell, the pressure within the collision cell can be reduced. The ratio between the axial electric field strength in the The second-stage electric longitudinal acceleration field region and the axial electric field intensity in the first-stage electric longitudinal acceleration field region are preferably ≥ 2, ≥ 3, ≥ 4, ≥ 5, ≥ 6, ≥ 7, ≥ 8, ≥ 9 or ≥ 10. A ratio of about 8 is particularly preferred.

The Collision cell may further comprise one or more grid electrodes, the electrodes forming between the collision cell are arranged, wherein one or more DC voltages to the one or more Grid electrodes are applied to the electric longitudinal acceleration field area the first and / or the second stage.

A or more transient DC voltages or one or more Transient DC voltage waveforms may be initially at a first axial Position and then at a second and then at a third different axial position along the collision cell.

A or more transient DC voltages or one or more Transient DC voltage waveforms may vary from one end to the other Move the collision cell to another end of the collision cell, so that ions are forced along the collision cell. The one or more transient DC voltages can a potential hill or potential wall, a potential well, several potential mounds or Potential ramparts, several Potential wells, a combination of a potential hill or a potential wall and a potential well or a combination from several potential hills or potential walls and generate several potential wells. One or more, Transient DC voltage waveforms preferably include one Repeating waveform in the manner of a square wave.

According to one less preferred embodiment For example, the collision cell may have a quadrupole rod set. A however, such arrangement does not facilitate the provision of axial electric fields.

The Mass spectrometer preferably further has an upstream of the another quadrupole rod set arranged AC or RF ion guide on. The AC or RF ion guide preferably has one Number of electrodes on. additionally or alternatively, the mass spectrometer may be an AC voltage or RF ion guide, the upstream of the multi-mode quadrupole rod set is arranged, wherein the AC or RF ion guide a Number of electrodes. The AC or RF ion guide can a quadrupole, hexapole, octapole or multipole rod set of higher order exhibit. Alternatively, the AC or RF ion guide may have a have segmented rod set. More preferably, the AC voltage or RF ion guide an ion tunnel ion guide include a number of electrodes in which openings from which ions are allowed to pass.

Of the AC or RF ion guide Preferably, an AC or RF voltage is supplied, the Frequency selected from the following group: (i) <100 kHz, (ii) 100-200 kHz, (iii) 200-300 kHz, (iv) 300-400 kHz, (v) 400-500 kHz, (vi) 0.5-1.0 MHz, (vii) 1.0-1.5 MHz, (viii) 1.5-2.0 MHz, (ix) 2.0-2.5 MHz, (x) 2.5-3.0 MHz, (xi) 3.0-3.5 MHz, (xii) 3.5-4.0 MHz, (xiii) 4.0-4.5 MHz, (xiv) 4.5-5.0 MHz, (xv) 5.0-5.5 MHz, (xvi) 5.5-6.0 MHz, (xvii) 6.0-6.5 MHz, (xviii) 6.5-7.0 MHz, (xix) 7.0-7.5 MHz, (xx) 7.5-8.0 MHz, (xxi) 8.0-8.5 MHz, (xxii) 8.5-9.0 MHz, (xxiii) 9.0-9.5 MHz, (xxiv) 9.5-10.0 MHz and (xxv)> 10.0 MHz.

Of the AC or RF ion guide Preferably, an AC or RF voltage is supplied, the Amplitude selected from the following group: (i) <50V from peak to peak, (ii) 50-100 V from tip to tip, (iii) 100-150 V peak to peak, (iv) 150-200 V from tip to tip, (v) 200-250 V from tip to tip, (vi) 250-300 V peak to peak, (vii) 300-350 V from tip to tip, (viii) 350-400 V peak to peak, (ix) 400-450 V from tip to tip, (x) 450-500 V from tip to tip and (xi)> 500 V from tip to tip.

In An operating mode can do this be worried that home versions captured in the AC or RF ion guide or otherwise accumulated while other ions in the collision cell cooled by collisions and / or become fragmented and / or during ions from that in the second Operating mode operating multi-mode quadrupole ion trap transmitted become. In an operating mode, ions are pulsed from the AC or DC RF ion guide away.

One or several transient DC potentials or one or several DC potential waveforms can be applied to the electrodes of the AC or RF ion guide applied become. The one or more transient DC potentials or the one or more DC potential waveforms press Preferably ions from a range of AC or RF ion guide to another area of the AC or RF ion guide.

According to one less preferred embodiment For example, an ion trap may be placed between the collision cell and the multi-mode quadrupole rod set become. Another drift or Time of flight range can be downstream of the multi-mode quadrupole rod set to be ordered. A reflectron may additionally / alternatively downstream of the Multi-mode quadrupole rod set to be ordered.

Advantageously, a method for mass spectrometry is provided which has the following steps:
Providing a multi-mode quadrupole rod set and an ion detector,
Operating the quadrupole rod set in a first mode of operation in which the quadrupole rod set acts as a mass filter, and
Operating the quadrupole rod set in a second mode of operation in which the quadrupole rod set forms a time-of-flight range of a time-of-flight mass analyzer.

advantageously, a mass spectrometer is provided which is a first multi-mode AC voltage or RF ion guide wherein, in a first operating mode, the first AC voltage or RF ion guide as an ion guide acts and wherein in a second operating mode the first AC voltage or RF ion guide forms a flight time range.

in the In the first mode of operation, ions are preferably removed from the first AC voltage source. or RF ion guide let through, without being mass filtered to any significant extent. Ions are preferably within the first AC or RF ion guide not to a considerable extent fragmented. Ions are preferably derived from the first AC voltage or RF ion guide essentially continuously transmitted.

In In the second mode of operation, ions are pulsed into the time-of-flight range brought in. Ions are preferably derived from the first AC voltage or RF ion guide let through, without being mass-filtered to a considerable extent, and separated according to their mass-to-charge ratio.

It For example, an ion detector may be provided in which the ion detector the time of flight of the ions is determined by the time-of-flight range.

A second AC or RF ion guide may preferably be downstream of the first Multi-mode AC or RF ion guide, being transmitted by the first multi-mode AC or RF ion guide Receive ions from the second AC voltage or RF ion guide become. The second AC or RF ion guide can have a segmented rod set. Alternatively, the second AC or RF ion guide an ion tunnel ion guide lock in, which has a number of electrodes with openings, of which Ions are allowed to pass through during use.

at The use of one or more transient DC voltages or one or more transient DC voltage waveforms first a first axial position and then at a second and then at a third different axial position along the second AC or RF ion guide provided.

A or more transient DC voltages or one or more Transient DC voltage waveforms may be in use from one end of the second AC or RF ion guide move to another end of the second AC or RF ion guide, such that ions are forced along the second AC or RF ion guide. The one or more transient DC voltages may be one potential hill or potential wall, a potential well, several potential mounds or Potential barriers, several potential wells, a combination of a potential hill or a potential wall and a potential well or a combination from several potential hills or potential walls and generate several potential wells. The one or more transient DC voltage waveforms applied to the second AC voltage or RF ion guide applied will close a repeating wave form in the manner of a square wave one.

When the first multi-mode AC or RF ion guide is operated in the second mode of operation, ions having in-first-order mass-to-charge ratios are trapped in a first axial trapping region within the second AC or RF ion guide and ions within one second different area mass-to-charge ratios are captured in a second different axial trapping region within the second AC or RF ion guide. Ions having mass-to-charge ratios within a third different range in a third axial capture region within the second AC or RF ion guide are also preferably captured in a third axial capture region within the second AC or RF ion guide, and ions within of a fourth different range mass-to-charge ratios are preferably in a fourth different axial trapping region within the captured second AC or RF ion guide. Similarly, ions having mass-to-charge ratios within a fifth range are preferably trapped in a fifth axial trapping region within the second AC or RF ion guide, and ions having mass-to-charge ratios within a sixth range are preferably trapped in a sixth different axial capture region captured within the second AC or RF ion guide.

In the first and / or second mode of operation, the first AC or RF ion guide is preferably maintained at a pressure selected from the following group: (i) greater than or equal to 1 × 10 ^-7 mbar, (ii) greater than or equal to 5 × 10 ^-7 mbar, (iii) greater than or equal to 1 × 10 ^-6 mbar, (iv) greater than or equal to 5 × 10 ^-6 mbar, (v) greater than or equal to 1 × 10 ^-5 mbar and (vi) greater or equal to 5 × 10 ^-5 mbar. In the first and / or second mode of operation, the first AC or RF ion guide is preferably maintained at a pressure selected from the following group: (i) less than or equal to 1 × 10 ^-4 mbar, (ii) less than or equal to 5 × 10 ^-5 mbar, (iii) less than or equal to 1 × 10 ^-5 mbar, (iv) less than or equal to 5 × 10 ^-6 mbar, (v) less than or equal to 1 × 10 ^-6 mbar, (vi) smaller or equal to 5 × 10 ^-7 mbar and (vii) less than or equal to 1 × 10 ^-7 mbar. In the first and / or second mode of operation, the first AC or RF ion guide is preferably maintained at a pressure selected from the following group: (i) between 1 × 10 ^-7 and 1 × 10 ^-4 mbar, (ii ) between 1 × 10 ^-7 and 5 × 10 ^-5 mbar, (iii) between 1 × 10 ^-7 and 1 × 10 ^-5 mbar, (iv) between 1 × 10 ^-7 and 5 × 10 ^-6 mbar, ( v) between 1 × 10 ^-7 and 1 × 10 ^-6 mbar, (vi) between 1 × 10 ^-7 and 5 × 10 ^-7 mbar, (vii) between 5 × 10 ^-7 and 1 × 10 ^-4 mbar, (viii) between 5 × 10 ^-7 and 5 × 10 ^-5 mbar, (ix) between 5 × 10 ^-7 and 1 × 10 ^-5 mbar, (x) between 5 × 10 ^-7 and 5 × 10 ^-6 mbar , (xi) between 5 x 10 ^-7 and 1 x 10 ^-6 mbar, (xii) between 1 x 10 ^-6 and 1 x 10 ^-4 mbar, (xiii) between 1 x 10 ^-6 and 5 x 10 ^-5 mbar, (xiv) is between 1 × 10 ^-6 and 1 × 10 ^-5 mbar, (xv) between 1 × 10 ^-6 and 5 × 10 ^-6 mbar, (xvi) between 5 × 10 ^-6 and 1 x 10 ^{- 4} mbar, (xvii) between 5 × 10 ^-6 and 5 × 10 ^-5 mbar, (xviii) between 5 × 10 ^-6 and 1 × 10 ^-5 mbar, (xix) between 1 × 10 ^-5 and 1 × 10 ^-4 mbar, (xx ) between 1 × 10 ^-5 and 5 × 10 ^-5 mbar and (xxi) between 5 × 10 ^-5 and 1 × 10 ^-4 mbar.

According to one another embodiment may the first AC or RF ion guide in the first mode of operation at a pressure selected from the following group: (i) greater or equal to 0.0001 mbar, (ii) greater than or equal to equal to 0.0005 mbar, (iii) greater than 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 0.05 mbar, (vii) larger or equal to 0.1 mbar, (viii) greater or equal to 0.5 mbar, (ix) greater than or equal to 1 mbar, (x) larger or equal to 5 mbar and (xi) greater or equal to 10 mbar. In the first operating mode, the first AC voltage or RF ion guide at a pressure selected from the following group: (i) less than or equal to 10 mbar, (ii) less than or equal to 5 mbar, (iii) less than or equal to 1 mbar, (iv) less than or equal to 0.5 mbar, (v) less than 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) smaller or equal to 0.0005 mbar and (xi) less than or equal to 0.0001 mbar. in the first mode of operation may be the first AC or RF ion guide 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.

The first AC or RF ion guide can be a quadrupole, Hexapole, octapole rod set or a multi-pole rod set higher order. alternative For example, the first AC or RF ion guide has a segmented rod set on. More preferred closes the first AC or RF ion guide includes an ion tunnel ion guide a number of electrodes in which there are openings, of which when using ions are allowed to pass.

in the first mode of operation is preferably the first AC or RF ion guide an AC or RF voltage fed to the a frequency selected from the following group: (i) <100 kHz, (ii) 100-200 kHz, (iii) 200-300 kHz, (iv) 300-400 kHz, (v) 400-500 kHz, (vi) 0.5-1.0 MHz, (vii) 1.0-1.5 MHz, (viii) 1.5-2.0 MHz, (ix) 2.0-2.5 MHz, (x) 2.5-3.0 MHz, (xi) 3.0-3.5 MHz, (xii) 3.5-4.0 MHz, (xiii) 4.0-4.5 MHz, (xiv) 4.5-5.0 MHz, (xv) 5.0-5.5 MHz, (xvi) 5.5-6.0 MHz, (xvii) 6.0-6.5 MHz, (xviii) 6.5-7.0 MHz, (xix) 7.0-7.5 MHz, (xx) 7.5-8.0 MHz, (xxi) 8.0-8.5 MHz, (xxii) 8.5-9.0 MHz, (xxiii) 9.0-9.5 MHz, (xxiv) 9.5-10.0 MHz and (xxv)> 10.0 MHz.

In the second mode of operation, the first AC or RF ion guide is preferably supplied with an AC or RF voltage having a frequency selected from the following group: (i) <100 kHz, (ii) 100-200 kHz, (iii) 200-300 kHz, (iv) 300-400 kHz, (v) 400-500 kHz, (vi) 0.5-1.0 MHz, (vii) 1.0-1.5 MHz, (viii) 1, 5-2.0 MHz, (ix) 2.0-2.5 MHz, (x) 2.5-3.0 MHz, (xi) 3.0-3.5 MHz, (xii) 3.5- 4.0 MHz, (xiii) 4.0-4.5 MHz, (xiv) 4.5-5.0 MHz, (xv) 5.0-5.5 MHz, (xvi) 5.5-6, 0 MHz, (xvii) 6.0-6.5 MHz, (xviii) 6.5-7.0 MHz, (xix) 7.0-7.5 MHz, (xx) 7.5-8.0 MHz , (xxi) 8.0-8.5 MHz, (xxii) 8.5-9.0 MHz, (xxiii) 9.0-9.5 MHz, (xxiv) 9.5-10.0 MHz and ( xxv)> 10.0 MHz.

in the first mode of operation is preferably the first AC or RF ion guide an AC or RF voltage fed to the an amplitude selected from the following group: (i) <50V from peak to peak, (ii) 50-100 V from tip to tip, (iii) 100-150 V peak to peak, (iv) 150-200 V from tip to tip, (v) 200-250 V from tip to tip, (vi) 250-300 V peak to peak, (vii) 300-350 V from tip to tip, (viii) 350-400 V peak to peak, (ix) 400-450 V from tip to tip, (x) 450-500 V from tip to tip and (xi)> 500 V from tip to tip.

in the second mode of operation is preferably the first AC or RF ion guide an AC or RF voltage fed to the an amplitude selected from the following group: (i) <50V from peak to peak, (ii) 50-100 V from tip to tip, (iii) 100-150 V peak to peak, (iv) 150-200 V from tip to tip, (v) 200-250 V from tip to tip, (vi) 250-300 V peak to peak, (vii) 300-350 V from tip to tip, (viii) 350-400 V peak to peak, (ix) 400-450 V from tip to tip, (x) 450-500 V from tip to tip and (xi)> 500 V from tip to tip.

The A mass spectrometer preferably further comprises an electrospray ion source ("ESI ion source"), an atmospheric pressure ion source with chemical ionization ("APCI ion source"), an atmospheric pressure photoionization ("APPI") ion source, a matrix assisted laser desorption ionization ion source ("MALDI ion source"), a laser desorption ionization ion source ("LDI ion source"), an inductively coupled Plasma ion source ("ICP ion source"), an electron impact ion source ("EI ion source"), an ion source with chemical ionization ("CI ion source"), an ion source with fast atom bombardment ("FAB ion source") and a liquid secondary ion mass spectrometry ion source ("LSIMS ion source"). The ion source can be pulsed or continuous.

Advantageously, a method for mass spectrometry is provided which has the following steps:
Providing a multi-mode AC or RF ion guide,
Operating the AC or RF ion guide in a first mode of operation, wherein the AC or RF ion guide acts as an inner guide, and
Operating the AC or RF ion guide in a second mode of operation, wherein the AC or RF ion guide forms a time-of-flight region.

advantageously, a mass spectrometer with a collision cell is provided, wherein the collision cell has a number of electrodes, wherein in an operating mode, an electric longitudinal acceleration field region of a first stage and an axial field area of a second different Stage are provided to accelerate ions out of the collision cell.

The relationship between the axial electric field strength in the longitudinal electric field force region the second stage and the axial electric field strength in the longitudinal electric field acceleration The first level is selected from the following group: (i) ≥2, (ii) ≥3, (iii) ≥4, (iv) ≥5, (v) ≥6, (vi) ≥7, (vii) ≥ 8, (viii) ≥ 9 and (ix) ≥ 10. A ratio of about 8 is particularly preferred.

In front accelerating out ions from the collision cell, the Pressure within the collision cell can be reduced.

Advantageously, a method for mass spectrometry is provided which has the following steps:
Providing a collision cell with a number of electrodes,
Providing a longitudinal electrical acceleration field of a first stage at a first region of the collision cell and
Providing an axial field of a second different stage at a second different area of the collision cell,
wherein the axial fields of the first and second stages are provided to accelerate ions out of the collision cell.

According to certain embodiments of the present invention, the multi-mode quadrupole rod set may receive ions continuously or in pulses. An AC or RF ion guide may be placed between the ion source and the quadrupole rod set to either pass ions continuously into the quadrupole rod set or pulsed ions into the quadrupole rod set. In one mode of operation, the quadrupole rod set is used as a quadrupole mass filter with the AC or RF ion guide between the ion source and the quadrupole rod set is set to pass ions continuously. In this mode of operation, the quadrupole rod set is operated with both AC / RF voltages and DC voltages applied to the rods so that the ions are radially confined by the AC electric field / RF field and by a DC potential difference between the rods is maintained, mass filtered. An ion detector preferably records the ion signal continuously.

In another mode of operation is the quadrupole rod set as a Time of flight or drift range for use in Time of Flight mass analysis used. In this operating mode, the AC voltage or RF ion guide established between the ion source and the quadrupole rod set be used to accumulate ions and release them in discrete pulses. The quadrupole rod set is fitted with AC voltages / RF voltages applied to the rods operated so that the ions are locked radially and axially drift in the quadrupole rod set. The bars are all on essentially kept the same DC potential. An ion detector preferably records both the intensity of the ion signal and the time released by the AC or RF ion guide Need ions, to arrive at the ion detector.

In the operating mode in which the quadrupole rod set has a time-of-flight range The quadrupole rod set may be used as a drift region be because the alternating electric fields / rf fields within of the set of rods have only radial components. The alternating fields / HF fields effect the radial confinement of the ions, and they exert no axial force the ions out. In the process disturb the square radial electric fields are not the function device providing a drift or time-of-flight range should.

At The AC / RF voltages applied to the quadrupole rod set may become too light electrical fringing fields at the entrance and at the exit of the quadrupole rod set to lead. These border fields can be distorted, and they can have a non-axial component of the electric field, the a minor one disorder the drift speeds are reflected in the quadrupole rod set or could evoke from this moving ions. If, however, a pulsed ion source close is arranged to the input of the quadrupole rod set and the acceleration the ions into the quadrupole rod set with the AC voltage or RF power supply for The bars is synchronized, can take care of it be that the Ions enter the quadrupole rod set when the AC / RF voltage goes through zero. The right synchronization of the ion acceleration into the quadrupole rod set using the alternating voltage / rf voltage helps to ensure that the axial component of the edge field at the entrance of the quadrupole rod set is both constant and a minimum perturbation of the ions during the Occurrence of them in the quadrupole rod set causes.

The Synchronizing the exit time of the ions from the quadrupole rod set with the time at which the applied AC voltage / RF voltage passes through Zero is not possible because the ions correspond to their mass-to-charge ratios be separated and the set of staff at significantly different times leave when the quadrupole rod set as a drift or time-of-flight range acts. However, the ion detector can be in close proximity to the output of the quadrupole rod set, so that one through the axial component of the fringing field caused either minor disturbance minimal or negligible is. By placing the ion detector near the output of the quadrupole rod set is the distance, over the ions move after leaving the quadrupole rod set, compared with the length of the quadrupole rod set itself small. Therefore, the time that the Ions need to from the quadrupole rod set to the ion detector to run, and thus the disorder the temporal separation of the ions relatively insignificant. If necessary, can a disorder be further reduced by the ions from the quadrupole rod set and accelerated into the ion detector.

In the preferred embodiment, the mass spectrometer may include more than one quadrupole rod set and / or other additional analyzers. For example, the mass spectrometer may include a collision cell and at least one multi-mode quadrupole rod set that operates as a mass filter in a first mode and operates as a drift or time-of-flight region in a second mode. In the preferred embodiment, the mass spectrometer may comprise an ion source, an AC / RF ion guide, a preferred dual-function or multi-mode quadrupole rod set, a collision cell, a dual-function or multi-mode quadrupole rod set, and an ion detector arranged in series , The AC / RF ion guide may have a multipole rod set. The preferred multi-mode quadrupole rod set may act as a drift or time-of-flight region in one mode of operation and as a mass filter in another mode of operation. Therefore, the preferred mass spectrometer is capable of performing all the functions of a conventional triple quadrupole mass spectrometer, but it has an advantageous ability to use Mas To record spectra for ions with a wide range of mass-to-charge ratios and also fragment ion spectra resulting from the fragmentation of parent ions with a high sensitivity and a faster rate than in conventional arrangements.

According to the preferred Embodiment is the AC or RF ion guide between the ion source and preferably the preferred quadrupole rod set, so that ions accumulated in an area of the AC or RF ion guide can and can then released as a discrete ion packet into a quadrupole rod set can be. The AC voltage or RF ion guide For example, a segmented rod set or a stacked Have ring set, and it allows preferably, that ions are linear downstream for subsequent mass analysis be accelerated when the mass spectrometer in a time of flight mode is operated.

Various embodiments The present invention will now be described by way of example only to the following drawing, wherein:

1A shows a preferred mass spectrometer operating in an MS mode of operation, 1B shows a preferred mass spectrometer operating in an MS / MS mode of operation, 1C shows a preferred mass spectrometer operating in an MS-TOF mode of operation and 1D shows a preferred mass spectrometer operating in an MS / MS TOF mode of operation,

2A a schematic view of the cross section - through a preferred collision cell shows 2 B shows the potential profile along the collision cell in an ion collection-without-fragmentation mode, 2C shows the potential profile along the collision cell in an ion accumulation and fragmentation mode, 2D shows the potential profile along the collision cell at a time when the ions are moved to an area near the exit of the collision cell, 2E shows the potential profile along the collision cell at a time when the ions are trapped in an area near the exit of the collision cell and cooled by collisions, and 2F shows the potential profile along the collision cell at a time when the ions from the collision cell are accelerated or pulsed removed,

3A Showing ions with different initial positions in the exit region of a collision cell, 3B shows the ions in an axial acceleration field of a first stage, 3C the ions, having exited the collision cell and entered a field-free time-of-flight region, 3D showing the ions towards the output of the field-free region, 3E Shows ions that initially run in opposite directions, and 3F initially in opposite directions running ions and a spatial focusing of second order shows and

4A a schematic view of a cross section through a mass spectrometer according to a less preferred embodiment shows and 4B shows the potential profile at a time along the mass spectrometer when the multi-mode quadrupole rod set is operating in a time-of-flight mode of operation.

A preferred embodiment of the present invention will now be described with reference to FIGS 1A - 1D described. The mass spectrometer 1 preferably has at least one multi-mode quadrupole rod set 6 . 6 ' . 6 '' which functions in (or provides) an operating mode as a drift or flight range for use in Time of Flight mass analysis and which functions or operates in a mode of operation other than a quadrupole mass filter. The 1A - 1D show the components of a preferred triple quadrupole mass spectrometer 1 which is used in several different operating modes.

The mass spectrometer 1 preferably comprises an ion source 2 , an AC or RF ion guide 3 , a first quadrupole rod set 4 . 4 ' For example, which may be operated in either a mass filter mode of operation or an ion guide mode of operation (RF only), an RF collision cell 5 . 5 ' , a multi-mode quadrupole rod set 6 . 6 ' according to the preferred embodiment, which may be operated in either an ion guide, mass filter, or time-of-flight mode of operation, and an ion detector 7 , The AC or RF ion guide 3 For example, a quadrupole rod set or an ion tunnel ion guide may have a number of electrodes with openings of substantially similar size, from which ions are transmitted in use.

1A shows the preferred mass spectrometer 1 when used in an MS mode. Ions from the ion source 2 enter the AC or RF ion guide 3 or are received in it, and they become the first quadrupole rod set 4 passed through, which is operated as a mass filter. The first quadrupole rod set 4 points to the rods of the quadrupole rod set 4 applied RF potentials, and it is a DC potential between adjacent bars maintained the difference, so that by the first quadrupole rod set 4 passing through ions of mass filtering.

Accordingly, from the first quadrupole rod set 4 only ions with certain desired mass-to-charge ratios to the RF collision cell 5 passed downstream of the first quadrupole rod set 4 is arranged. A collision gas at a pressure of for example> 10 ^-3 mbar is preferably in the collision cell 5 exists or is initiated in this. It is ensured that exit ions with a certain mass-to-charge ratio with sufficiently low energies into the collision cell 5 penetrate and the collision cell 5 go through so that the ions within the collision cell 5 are cooled by collisions without being significantly fragmented. The output ions are then from the collision cell 5 to the preferred multi-mode quadrupole rod set 6 '' which is operated in an RF-only mode (ie, an ion guide mode) such that the quadrupole rod set 6 '' acts as an RF ion guide and ions within the ion guide 6 ' locked radially. The ions pass through the quadrupole ion guide 6 '' and then from the ion detector 7 detected downstream of the quadrupole rod set 6 ' is arranged. In this mode of operation, the multi-mode quadrupole rod set acts 6 '' neither as a mass filter nor as a time-of-flight range because ions are not mass-filtered and are not pulsed out of the collision cell 5 into the quadrupole rod set 6 '' be transferred.

In 1B is the preferred mass spectrometer 1 when used in MS / MS mass analysis mode. Ions from the ion source 2 be from the AC or RF ion guide 3 passed through and run to the first quadrupole rod set 4 operated as a mass filter. Neighboring rods of the first quadrupole rod set 4 opposite phases are fed to an AC or RF voltage, and a DC potential is maintained between adjacent bars so that the quadrupole rod set 4 Ion filters according to their mass-to-charge ratios.

Ions having a specific mass to charge ratio or a specific range of mass to charge ratios are derived from the quadrupole mass filter 4 to the collision cell 5 continue to run while other ions from the quadrupole mass filter 4 be significantly weakened. The collision cell 5 is preferably maintained at a DC potential, so that in the collision cell 5 entering ions are relatively energetic.

Within the RF collision cell 5 is a gas provided so that at least some of the in the RF collision cell 5 penetrating exit ions are collided with the gas molecules and fragment to produce fragment ions. The fragment ions and any non-fragmented parent ions are then from the collision cell 5 to the preferred multi-mode quadrupole rod set 6 pass through. The multi-mode quadrupole rod set 6 is operated in a mass filter operating mode. Accordingly, RF voltages are applied to the rods of the quadrupole rod set 6 applied, and a DC potential difference is between Benach disclosed rods of the quadrupole rod set 6 maintained so that the quadrupole rod set 6 the fragment ions are selectively mass filtered according to their mass-to-charge ratio and selected fragment ions to the ion detector 7 keep running.

1C shows the preferred mass spectrometer 1 when used in an MS-TOF mode of operation. In this mode, ions are preferably in the AC or RF ion guide 3 accumulated, preferably next to the ion source 2 is arranged. The ions are then preferably periodically from the AC or RF ion guide 3 leak and from the first quadrupole rod set 4 ' which is preferably operated in a RF-only or ion-guide mode. RF potentials are applied to the rods of the first quadrupole rod set 4 ' applied, and all the rods are held at substantially the same DC potential, so that the first quadrupole rod set 4 ' Ions, without essentially subjecting them to mass filtering, to the collision cell 5 ' passes. That of the first quadrupole ion guide 4 ' Passed ions are then in the collision cell 5 ' accumulated or captured where they are cooled by collisions. The ions are pulsed out of the collision cell 5 ' removed, and it is ensured that they are in the second quadrupole rod set 6 ' that is set up to operate in a time-of-flight mode of operation. RF voltages are applied to the rods of the preferred multi-mode quadrupole rod set 6 ' filed, and the rods of the quadrupole rod set 6 ' are all held at substantially the same DC potential, so that the quadrupole rod set 6 ' locks the ions radially, but does not subject the passing ions to any significant mass filtering. Inside the quadrupole rod set 6 ' Essentially, no axial electric field is provided and the quadrupole rod set 6 ' therefore acts as a drift or lugzeitbereich, which allows ions from the collision cell 5 ' pulsed into the quadrupole rod set 6 ' have been introduced, according to their mass-charge ratios are separated in time. In front Preferably, the time at which the ions are pulsed from the RF collision cell 5 ' removed and into the quadrupole rod set 6 ' to be initiated, substantially synchronized with time, to which the quadrupole rod set 6 ' applied RF potentials through 0V run.

The pulsed from the collision cell 5 ' ions removed are in the quadrupole rod set 6 ' separated in time, with ions having relatively low mass-to-charge ratios the end of within the quadrupole rod set 6 ' reached time range before ions with higher mass-to-charge ratios. Those from the quadrupole rod set 6 ' leaking ions then run to the ion detector 7 which is preferably near the exit of the quadrupole rod set 6 ' is arranged. The ions can be from the output of the quadrupole rod set 6 ' to the ion detector 7 be accelerated. In the time-of-flight mode of operation described above, ions may preferably be in the AC or RF ion guide 3 upstream of the first quadrupole rod set 4 ' while previously received ions are either collisions within the collision cell 5 ' be cooled and / or mass analyzed by passing the ions through from the quadrupole ion guide 6 ' be formed flying time range.

1D shows the preferred mass spectrometer when used in an MS / MS TOF mode of operation. Exit ions from the ion source 2 are preferably in the AC or RF ion guide 3 accumulated and then preferably periodically from the AC or RF ion guide 3 released or pulsed out of it and then to the first quadrupole rod set 4 transfer. The first quadrupole rod set 4 is operated as a mass filter so as to selectively pass through source ions having a specific mass to charge ratio or to starting ions having a specific range of mass to charge ratios. The first quadrupole rod set 4 transmitted desired exit ions are then preferably in the collision cell 5 ' accumulated. The collision cell 5 ' is preferably maintained at a DC potential such that ions are caused to travel by a number of relatively high energy collisions with within the collision cell 5 ' fragment existing gas molecules. The fragment ions generated by these collisions are then preferably collisions within the collision cell 5 ' cooled. The resulting fragment ions are then pulsed out of the collision cell 5 ' removed and run to the preferred quadrupole rod set 6 ' operated in a time-of-flight mode and therefore together with the ion detector 7 Is part of a time-of-flight mass analyzer. Output ions can continue in the AC or RF ion guide 3 next to the ion source 2 accumulated while other output ions, previously from the AC or RF ion guide 3 were released, either in the collision cell 5 ' fragmented and / or cooled, and / or during fragment ions pulsed from the collision cell 5 ' are removed and mass analyzed by the Time of Flight mass analyzer selected from the preferred multi-mode quadrupole rod set 6 ' and the ion detector 7 consists.

In another embodiment, the resolution of the mass spectrometer may be further enhanced in operation in a time-of-flight mode by extending the overall ionic flight path by adding additional drift or flight ranges in addition to the preferred multi-mode quadrupole rod set 6 ' to be provided. These further drift or flight regions may be, for example, downstream of the multi-mode quadrupole rod set 6 ' to be provided. Additionally, or alternatively, a reflectron may be provided through which the ions can travel after having passed within the multi-mode quadrupole rod set 6 ' have left drift or flight time range formed. The use of a reflectron has the beneficial effect of supporting the maintenance of time focusing of the ions.

The operation of the multi-mode quadrupole rod set 6 ' in connection with the ion detector 7 as a time-of-flight mass analyzer depends on the energy width of the ions pulsed out of the collision cell 5 ' are removed and preferably accelerated to the drift or time-of-flight range within the multi-mode quadrupole rod set 6 ' is provided. It is preferable to control the energy width of the ions by cooling them in the collision cell 5 ' minimize before the ions are pulsed out of the collision cell 5 ' removed and introduced into the drift or flight time range. It is preferably allowed that the ions make numerous collisions with a buffer gas in the collision cell 5 ' so that they are cooled to substantially the same temperature as the buffer gas. For example, if the buffer gas is maintained at ambient temperature, the ions are cooled to an average energy of about 0.03 eV. The temperature of the buffer gas can be further reduced, and it is therefore possible that the collisions cool the ions even to an even lower average energy, and therefore even further reduce the energy width of the ions.

The 2A - 2F show the structure of the collision cell 5 . 5 ' and the potential profile along the collision cell 5 . 5 ' according to a preferred Embodiment during various stages of ion accumulation, collision cooling, fragmentation and release. The collision cell 5 . 5 ' preferably contains a gas at a pressure in the range of 10 ^-3 - 10 ^-2 mbar, so that many ion-gas molecule collisions occur when the ions 8th through the collision cell 5 . 5 ' to run.

2A shows a cross section through a preferred collision cell 5 . 5 ' , preferably a ring-stack collision cell 5 . 5 ' which has a number of electrodes with openings from which ions are transmitted. 2 B shows the potential profile along the collision cell 5 . 5 ' if the collision cell 5 . 5 ' for accumulating ions 8th used without significant fragmentation. The stacked rings of the collision cell 5 . 5 ' are preferably kept at such potentials that the ions 8th in a relatively flat potential well, preferably within a central region of the collision cell 5 . 5 ' to be caught. In the 2 B For example, the illustrated embodiment may be used to generate output ions within the collision cell 5 ' before the parent ions pulsed in the above with respect to 1C described MS TOF operating mode in the preferred quadrupole rod set 6 ' be introduced.

2C shows the potential profile along the preferred collision cell 5 . 5 ' in a mode where the collision cell 5 . 5 ' both for accumulating and fragmenting ions 8th is used. In this mode, the stacked rings or electrodes are preferably held at such potentials that in the collision cell 5 . 5 ' incoming ions 8th through a relatively steep potential well into a region of the collision cell 5 . 5 ' be accelerated. The voltage gradient across the collision cell 5 . 5 ' helps with the ions 8th to accelerate to cause high-energy collisions with the collision gas. These collisions cause at least some of those in the collision cell 5 . 5 ' penetrating exit ions 8th within the collision cell 5 . 5 ' fragmenting.

2D shows the potential profile along the collision cell 5 . 5 ' when ions reach an area near the exit of the collision cell 5 . 5 ' to be moved. The ions 8th may have been fragmented before this stage, or this may not be the case. The to the electrodes of the collision cell 5 . 5 ' applied axial DC potentials can be progressively changed so that the bottom of the potential well progressively closer to the output of the collision cell 5 . 5 ' is moved.

2E shows the potential profile along the preferred collision cell 5 . 5 ' if initial or fragment ions 8th in an area near the exit of the collision cell 5 . 5 ' are enclosed and cooled by a buffer gas by collisions. The applied to the electrodes potentials are preferably changed so that a relatively narrow and / or steep potential well in the vicinity of the output of the collision cell 5 . 5 ' is provided. The potentials applied to the electrodes are preferably changed so that the ions 8th do not absorb significant amounts of kinetic energy. As soon as the ions 8th are trapped in the potential well, they can be cooled by the buffer gas by collisions until their range of kinetic energies has been sufficiently reduced. As soon as the ions 8th Preferably, they can be cooled from the collision cell 5 . 5 ' be ejected.

2F shows the potential profile along the collision cell 5 ' at a time, to the ions 8th from the collision cell 5 ' ejected or pulsed and into the preferred multi-mode quadrupole rod set 6 ' initiated in a time-of-flight mode of operation. For introducing the ions 8th into the multi-mode quadrupole rod set 6 ' become the cells of the collision cell 5 ' at the end of the collision cell 5 ' applied potentials preferably progressively lowered. The output of the collision cell 5 ' is preferably maintained at a DC potential greater than or equal to the DC potential at which the preferred multi-mode quadrupole rod set 6 ' is held. According to a preferred embodiment, the pressure of the collision cell 5 ' also diminished before the ions 8th from the collision cell 5 ' accelerated or pulsed removed and into the preferred multi-mode quadrupole rod set 6 ' be introduced.

In the preferred embodiment, a two-stage axial acceleration field is used to generate ions 8th from the collision cell 5 ' and in the preferred multi-mode quadrupole rod set 6 ' to accelerate. To generate an axial acceleration field of the first stage, those to the electrodes of the collision cell 5 ' in an area to the end of the collision cell 5 ' applied potentials preferably for example over a first length 9 of the collision cell 5 ' from a DC potential V ₁ > 0 V, for example, 0 V lowered. A second-stage acceleration field is preferably generated substantially simultaneously by applying the DC potentials of the electrodes in the rearmost portion of the collision cell 5 ' be lowered from V ₁ to V ₂ , whereby preferably along a second rear piece 10 the collision cell 5 ' V ₂ <0 V is.

In one embodiment, the length of the multi-mode quadrupole rod set is 6 ' 250 mm, has the acceleration field range 9 the first stage has a length of 10 mm and has the acceleration field area 10 the second stage has a length of 5 mm. Preferably, the potentials V ₁ and V ₂ are selected so that the electric field strength of the second stage 10 is about eight times larger than the field strength of the first stage 9 so that a spatial focusing condition and first order velocity focusing condition is satisfied, as will be described in more detail below. According to the preferred embodiment, the first stage acceleration field may be applied by applying voltages V ₁ and 0 V to electrodes of the collision cell 5 ' 15 mm upstream or 5 mm upstream of the collision cell exit 5 ' be set up. The second stage acceleration field may be generated by simultaneously applying a voltage V ₂ to the end electrode of the collision cell 5 ' be set up.

If V ₁ is 250V and V _{2 is} -1000V, the first stage acceleration field strength is 25V / mm and the second stage acceleration field strength is 200V / mm. For ions with a mass-to-charge ratio of 500 and an average energy of 0.03 eV, the turnaround time, described in more detail below, is approximately 23 ns. The time of flight of the ions to the ion detector 7 is about 13.7 μs, and a mass resolution of about 300 can be expected.

Alternatively, if V _{1 is increased} to 1000 V and V _{2 is} increased proportionally to -4000 V, the first acceleration field strength is 100 V / mm and the second acceleration field strength is 800 V / mm. According to this embodiment, the inversion time is reduced from 23 ns to about 6 ns.

The time of flight of ions with a mass to charge ratio of 500 up to the ion detector 7 is also reduced to about 6.6 μs, and an improved mass resolution of about 500 can be expected.

The above embodiment will be described with respect to a two-stage acceleration field with well-defined limits. This can be done by using grid electrodes in the preferred collision cell 5 . 5 ' be achieved with a stacked ring set. However, in some circumstances this may be less desirable because the grid electrodes interfere with the operation of the collision cell 5 when used in an ion guide mode. In embodiments where there are no grid electrodes in the collision cell 5 . 5 ' are included, the axial DC electric fields along the central axis of the collision cell 5 ' weaker and therefore less well-defined than the DC fields between adjacent electrodes of the collision cell 5 ' , Larger potentials V ₁ and V ₂ can therefore be applied, so that the DC field along the central axis is as expected. Therefore, larger potentials V ₁ and V _{2 can be} applied so that the DC field along the central axis is as required.

Ions with the same mass-to-charge ratio from a position near the output of the collision cell 5 ' can go out, the ion detector 7 in front of ions farther from the exit of the collision cell 5 ' out. On the other hand, if the ions are accelerated by an electric field, it follows that ions coming from the ion detector 7 lie next, assume a smaller electrical potential difference than those emanating from a point from the output of the collision cell 5 ' further away. Accordingly, the ions closest to the exit at the time they left the acceleration field and in the field-free region are within the preferred quadrupole rod set 6 less energy than those that go farther from the exit. Therefore, the ions coming from a point near the output of the collision cell 5 ' go out early, but they move slower than those ions from a position that comes from the exit of the collision cell 5 ' further away. The faster ions therefore catch up with and overtake the slower ions that emanate from a point closer to the exit. The point where the faster ions are just catching up with the slower ions is the position of the first-order spatial focussing.

3A shows three ions 11 at three different starting positions within the collision cell 5 ' are at rest. In 3B a voltage V _{1 is} applied to generate the first acceleration field. The ions 11 become the output of the collision cell 5 ' accelerate and run through the first field area 9 to a second field area 10 which is generated by a voltage V ₂ . The ions 11 continue in the second field area 10 accelerates until it reaches the second field area 10 leave and in with the preferred quadrupole rod set 6 ' penetrate drift area provided. The drift region is at a constant DC potential. 3C shows the three ions 11 shortly after entering the drift area. The three ions are still spatially separated, but the ions in the back area move faster because they have been accelerated by a larger potential difference. 3D shows the same three ions 11 when they are the output of the time-of-flight range of the ion detector 7 approach. The faster ions have almost overtaken the slower ions in front of them. At the time, to which the ions 11 the ion detector 7 The faster ions have just caught up with the slower ions, leaving all three ions 11 the ion detector 7 reach at substantially the same time. By using two axial electric accelerator field areas 9 . 10 becomes in the construction of the collision cell 5 ' provides a greater degree of freedom and allows second order spatial focusing to be achieved. If two axial electric acceleration fields are used, there are an infinite number of solutions to the conditions required for second order spatial focusing.

Although second-order spatial focusing can be achieved, there may still be a small spread in ion arrival times due to a difference in initial ion velocities. This is in the 3E and 3F shown. In 3E become two ions 12 considered. The two ions 12 have the same initial position just before the application of the first electric acceleration field, but they have equal and opposite speeds. An ion moves directly to the exit of the collision cell 5 ' and to the ion detector 7 while the other ion to the entrance of the collision cell 5 ' running. In 3F suddenly the first axial electric acceleration field was applied. The ion leading to the exit of the collision cell 5 ' moves, now starts to ion detector 7 to be accelerated. The ion that is initially to the entrance of the collision cell 5 ' moves, decelerates until its movement stops, and then it starts to exit the collision cell 5 ' to be accelerated back. By the time this ion returns to its starting point, it has the same velocity it originally had, but now it moves in the opposite direction, that is, to the exit of the collision cell 5 ' out. From that time on, it closely follows the movement of the first ion, but reduces it by a turnaround time required to reverse and return to its initial position. Two ions 12 come to times separated by the reversal time at the ion detector 7 at. The use of two axial electric acceleration fields allows greater freedom for minimizing the turnaround time while still maintaining second order spatial focussing.

According to an alternative embodiment, ions may be stored and cooled in a separate segmented ring ion trap located between the exit of the collision cell 5 . 5 ' and the input of the preferred multi-mode quadrupole rod set 6 . 6 ' is arranged. The separated ion trap may be used as an internal guide when the mass spectrometer is used in an operating mode and may be used to detect the ions 8th to store, cool and accelerate when using the mass spectrometer 1 is used in a different operating mode.

According to a less preferred embodiment, the mass spectrometer 1' a single multi-mode quadrupole rod set 6 . 6 which acts either as a mass filter in a first mode of operation or as a drift or time-of-flight range in a second mode of operation.

4A shows the mass spectrometer 1' according to the less preferred embodiment, which is an ion source 2 , an AC or RF ion guide 3 , a multi-mode quadrupole rod set 6 . 6 ' and an ion detector 7 having. The AC or RF ion guide 3 preferably comprises an inner guide with stacked rings or an ion tunnel ion guide. In a first. Operating mode run ions 8th straight through the AC or RF ion guide 3 and are used by the multi-mode quadrupole rod set 6 which is operated in a mass filter mode to provide output ions having a desired mass-to-charge ratio selective to the ion detector 7 transferred to. In another mode of operation, ions become 8th in the AC or RF ion guide 3 captured and stored and from the AC or RF ion guide 3 ejected or pulsed away and into the multi-mode quadrupole rod set 6 ' introduced operating in a time-of-flight mode. An interior guide 3 with stacked rings allows the ions 8th for the subsequent time of flight mass analysis axially from the inner guide 3 be accelerated out. In time-of-flight mode, RF voltages are applied to the rods of the quadrupole rod set 6 ' applied, and the rods are all held at substantially the same DC potential, so that the quadrupole rod set 6 ' acts as a drift or time-of-flight region of a Time of Flight mass analyzer.

4B shows the potential profile along the AC or RF ion guide 3 , the multi-mode quadrupole rod set 6 ' and the area between the output of the multi-mode quadrupole rod set 6 ' and the ion detector 7 at a time when the mass spectrometer 1' works in a time of flight mode. ions 8th previously by applying DC potentials to the electrodes of the AC or RF ion guide 3 are captured therein, preferably using a two-stage axial acceleration field from the AC or RF ion guide 3 into the multi-mode quadrupole rod set 6 ' out accelerated. The last electrode of the AC or RF ion guide 3 is preferably maintained substantially at a potential V ₂ which is the potential similar to that of the multi-mode quadrupole rod set 6 ' held within the multi-mode quadrupole rod set 6 ' there is essentially no axial electric field. Therefore, the multi-mode quadrupole rod set works 6 ' as a drift or time-of-flight area in which the ions 8th be separated according to their mass-charge ratios. The ion detector 7 is preferably near the exit of the multi-mode quadrupole rod set 6 ' arranged and can be kept at a potential V ₃ , so that the ions 8th from the output of the multi-mode quadrupole rod set 6 ' into the ion detector 7 be accelerated.

According to further embodiments not shown, other ion optical devices may be interposed between the output of the multi-mode quadrupole rod set 6 . 6 ' and the ion detector 7 to be ordered. For example, one or more RF collision cells, further multipole rod sets or ion traps may be provided.

According to a further embodiment not shown, a first multi-mode AC or RF ion guide may be provided, which according to a first operating mode can be operated over a wide pressure range, for example up to about 10 mbar. The first AC or RF ion guide may comprise, for example, a multipole rod set or, more generally, an ion tunnel ion guide. In a second mode of operation, the first AC or RF ion guide is maintained at a pressure <10 ^-3 mbar and operated as a time-of-flight region, for example a region where ions are separated according to their mass-to-charge ratio. In the first mode of operation, ions may be continuously transmitted through the first multi-mode AC or RF ion guide while in the second mode of operation ions are preferably pulsed into the first AC or RF ion guide. The first multi-mode AC or RF ion guide is preferably provided upstream of a second AC or RF ion guide. When the first multi-mode AC or RF ion guide is operated in the second mode of operation, ions are dispersed in time as they travel through the time-of-flight range. Ions with relatively small mass-to-charge ratios reach the output of the AC or RF ion guide from ions of relatively large mass-to-charge ratios. In accordance with the preferred embodiment, transient or continuous DC voltages are applied to the electrodes of the second AC or RF ion guide to produce a number of axial capture regions, which are then propagated along the second AC or RF ion guide from the input of the second AC or RF Ion guide to the output of the second AC or RF ion guide to be moved. When an axial capture region is moved along the second AC or RF ion guide, a new axial capture region is preferably created toward or substantially at the entrance of the second AC or RF ion guide. Accordingly, ions transmitted by the multi-mode AC or RF ion guide are effectively fractionated from the plurality of axial capture regions generated in and moved along the length of the second AC or RF ion guide. Ions are received and trapped in the second AC or RF ion guide so that ions of relatively low mass-to-charge ratios are held in axial trapping regions for at least a period of time relatively close to the output of the second AC or RF ion guide; while ions having relatively high mass-to-charge ratios are held in axial trapping regions at least for a period of time relatively close to the input of the second AC or RF ion guide. Preferably, at any given time, two, three, four, five, six, seven, eight, nine, ten, or more than ten axial capture regions may be provided along the second AC or RF ion guide, and ions exiting the time-of-flight region may enter therein axial capture areas are received.

Claims (23)

Use of a quadrupole rod set ( 6 . 6 ' ) and an ion detector ( 7 ) of a mass spectrometer in two operating modes, wherein the quadrupole rod set ( 6 . 6 ' ) in the first mode of operation as a mass filter for selectively passing ions according to their mass-to-charge ratio to the ion detector ( 7 ), characterized in that the quadrupole rod set ( 6 . 6 ' ) is operated in the second operating mode as a time-of-flight range, wherein cloning in this second operating mode is pulsed into the quadrupole rod set ( 6 . 6 ' ) and the ion detector ( 7 ) determines the time of flight of the ions through the time-of-flight range. Use according to claim 1, wherein in the first operating mode AC voltages or RF voltages are applied to the rods of the quadrupole rod set ( 6 . 6 ' ) are applied and a DC potential difference between adjacent bars is maintained. Use according to claim 1 or 2, wherein in the second mode of operation AC or RF voltages are applied to the rods of the quadrupole rod set ( 6 . 6 ' ) and all rods of the quadrupole rod set ( 6 . 6 ' ) are kept at the same DC potential. Use according to any one of the preceding claims, wherein the mass spectrometer further comprises: a collision cell ( 5 . 5 ' ) and another quadrupole rod set ( 4 . 4 ' ) upstream of the collision cell ( 5 . 5 ' ), wherein the quadrupole rod set ( 6 . 6 ' ) downstream of the collision cell ( 5 . 5 ' ) is arranged. Use according to claim 4, wherein the further quadrupole rod set ( 4 . 4 ' ) acts as a mass filter for mass filtering of output ions. Use according to claim 4 or 5, wherein exit ions within the collision cell ( 5 . 5 ' ) are cooled by collisions. Use according to claim 4, 5 or 6, wherein in the first mode of operation output ions are not pulsed out of the collision cell ( 5 . 5 ' ) exit. Use according to any one of the preceding claims, wherein the quadrupole rod set ( 6 . 6 ' ) is scanned in the first mode of operation so that it acts as a mass analyzer. Use according to claim 4, wherein the further quadrupole rod set ( 4 . 4 ' ) acts as an inner guide to transmit output ions. Use according to claim 9, wherein exit ions within the collision cell ( 5 . 5 ' ) are cooled and / or trapped by collisions. Use according to one of claims 9 or 10, wherein in the second mode of operation output ions are pulsed from the collision cell into the quadrupole rod set ( 6 . 6 ' ). Use according to any one of claims 4 to 11, wherein the collision cell ( 5 . 5 ' ) has a segmented set of rods. Use according to any one of claims 4 to 11, wherein the collision cell ( 5 . 5 ' ) has a stacked ring set with a number of electrodes in which openings are located. Use according to any one of claims 4 to 13, wherein an axial DC voltage gradient along at least one. Section of the Length of Collision cell is maintained. Use according to claim 4, wherein in the second operating mode the collision cell ( 5 . 5 ' ) are maintained at different DC potentials such that at least a first and a second longitudinally-accelerating electric field region of different levels are provided to detect ions from the collision cell (12). 5 . 5 ' ) accelerate out. Use according to claim 15, wherein prior to accelerating out ions from the collision cell ( 5 . 5 ' ) the pressure within the collision cell ( 5 . 5 ' ) is reduced. Use according to one of claims 15 or 16, wherein the collision cell ( 5 . 5 ' ) further comprises one or more grid electrodes arranged between the cells of collision ( 5 . 5 ' ) are arranged, wherein one or more DC voltages are applied to the one or more grid electrodes to provide the electrical longitudinal acceleration field region of the first and / or the second stage. Use according to claim 4, wherein the collision cell ( 5 . 5 ' ) has a quadrupole rod set. Use according to one of claims 4 to 18, wherein an ion trap between the collision cell ( 5 . 5 ' ) and the quadrupole rod set ( 6 . 6 ' ) is arranged. Use according to one of claims 1 to 19, characterized in that instead of the quadrupole rod set ( 6 . 6 ' ) a hexapole, octapole or multipole rod set of higher order is used. Use according to any one of the preceding claims, wherein the mass spectrometer further comprises an ion source ( 2 ) selected from the group consisting of: (i) an electrospray ion source ("ESI ion source"), (ii) an atmospheric pressure ion source with chemical ionization ("APCI ion source"), (iii) an atmospheric pressure A photoionization ion source ("APPI ion source"), (iv) a matrix assisted laser desorption ionization ion source ("MALDI ion source"), (v) a laser desorption ionization ion source ("LDI ion source"), (vi) an inductively coupled plasma source. Ion source ("ICP ion source"), (vii) an electron impact ion source ("EI ion source"), (viii) a chemical ionization ion source ("CI ion source"), (ix) a fast atom bombardment ion source (" FAB ion source ") and (x) a liquid secondary ion mass spectrometry ion source (" LSIMS ion source "). Use according to any one of claims 1 to 20, wherein the mass spectrometer further has a ge Pulse has ion source. Use according to any one of claims 1 to 20, wherein the mass spectrometer further comprises a continuous ion source.