1. Field of the Invention
The present invention relates to a mass spectrometer and a method of mass spectrometry.
2. Discussion of the Prior Art
Quadrupole rod sets are known which comprise two pairs of parallel rods. Each pair of diametrically opposed rods are electrically connected to each other and to the same phase of an RF voltage supply. The RF voltage supply is arranged such that the RF voltage applied to one pair of diametrically opposed rods has a 180xc2x0 phase difference with respect to the other pair of rods.
The quadrupole rod set can be operated as a mass filter to transmit ions having specific mass to charge ratios and to attenuate other ions by maintaining a DC potential difference between adjacent pairs of rods. When a DC potential difference is maintained between the pairs of rods certain ions will remain stable in the quadrupole rod set and will be transmitted from one end of the quadrupole rod set to the other. However, other ions will become unstable and hence will not be transmitted by the quadrupole rod set. The DC potential difference maintained between the rods may be arranged, for example, such that ions with mass to charge ratios outside of a narrow range are destabilised and are not transmitted. The DC potential difference can also be increased or scanned so that eventually only ions having a specific mass to charge ratio will be stable in the quadrupole rod set whilst other ions have been filtered out. A further increase in the DC voltage may result in all of the ions being destabilised such that no ions are transmitted. Accordingly, appropriate selection of the RF and DC voltages applied to the quadrupole rod set allows ions of only selected mass to charge ratios to be transmitted whilst all other ions are discarded.
The quadrupole rod set mass filter efficiently transmits ions having a specific mass to charge ratio. However, when ions having a range of mass to charge ratios are required to be recorded the RF and DC voltages applied to the quadrupole rod set must be scanned so as to successively transmit ions of one mass to charge ratio at a time. This results in the duty cycle for transmitting ions of any specific mass to charge ratio decreasing as the range of mass to charge ratios to be recorded increases. For example, if the mass range to be scanned is 500 mass units and the mass peak width at base is one mass unit, then the time spent transmitting ions having the same mass to charge ratio to within one mass to charge ratio unit is 1/1000 of the total scan time and hence the duty cycle drops to 0.1%. This is to be compared with a duty cycle of 100% when the quadrupole rod set mass filter is used to transmit ions having a single mass to charge ratio.
A further limitation of using a quadrupole rod set mass filter/mass analyser to record ions having a range of mass to charge ratios is the time taken to acquire a complete mass spectrum. Ions transmitted through a quadrupole mass filter typically have a relatively low energy, e.g. only a few eV. Therefore, the ions tend to take a relatively long period of time to travel the length of the quadrupole rod set. The length of time is dependent upon the length of the quadrupole rod set and the energy of the ions. The quadrupole rod set mass filter cannot therefore be scanned at a rate faster than the time taken for ions to travel the length of the quadrupole rod set otherwise the ions will not be allowed adequate time to be transmitted. For examples the ions may require between 0.1 ms and 1 ms to travel the length of the quadrupole rod set. Therefore, the quadrupole rod set mass filter cannot be scanned much faster than 1 ms per mass unit otherwise ions will no longer have adequate time to be transmitted. Accordingly, the minimum time required to scan 500 mass units is typically between 0.1 and 0.5 seconds.
It is apparent from the above considerations that the quadrupole rod set mass filter is suited to applications in which it is only required to record and quantify ions having a single or limited range of mass to charge ratios. A quadrupole rod set mass filter is not particularly suited to applications where it is required to record ions having a relatively wide range of mass to charge ratios with high sensitivity and at relatively high speed.
A Time of Flight mass analyser is another known mass analyser. A Time of Flight mass analyser comprises a drift or flight region and a fast ion detector. Ions entering the drift or flight region are arranged to have a constant energy and therefore separate as they travel through the drift or flight region according to their mass to charge ratio. A fast Analogue to Digital Converter (xe2x80x9cADCxe2x80x9d) or a Time to Digital Converter (xe2x80x9cTDCxe2x80x9d) may be used to record the arrival times of the ions at the ion detector. The arrival times enable the mass to charge ratios of the ions to be calculated since the mass to charge of an ion is proportional to the square of the flight time of the ion from the entrance of the drift region to the ion detector.
A Time of Flight mass spectrometer may record a full mass spectrum for each pulse of ions leaving the ion source. If the ion source is a pulsed ion source, such as a Laser Ablation or a Matrix Assisted Laser Desorption and Ionisation (xe2x80x9cMALDIxe2x80x9d) ion source, then the duty cycle for recording the full mass spectrum can be 100%. If the ion source is continuous, such as an Electrospray or Electron Impact ion source, then the duty cycle is determined by the means by which the continuous beam of ions is sampled and packets of ions are injected into the drift or flight region of the Time of Flight mass analyser.
Orthogonal acceleration Time of Flight mass spectrometers typically achieve a sampling duty cycle in the range of 5-25%. The combination of a non-mass selective ion trap used in conjunction with an orthogonal acceleration Time of Flight mass spectrometer may increase the duty cycle to around 100% for ions having a specific narrow range of mass to charge ratios, whilst the duty cycle for ions outside of that range of mass to charge ratios will fall to 0%.
A Time of Flight mass spectrometer is not ideal for recording ions having a narrow range of mass to charge ratios e.g. ions having a range of only one or two mass to charge ratio units. The duty cycle and transmission of a Time of Flight mass spectrometer required to record ions having a narrow spread of only one or two mass to charge ratio units does not match that of a quadrupole rod set mass filter in a comparable situation. Furthermore, the linear dynamic range of the ion detection systems typically used in a conventional Time of Flight mass spectrometer is inferior to that used in a mass spectrometer incorporating a quadrupole rod set mass analyser. This is due to the fact that ions are recorded in very short bursts in a Time of Flight mass spectrometer whereas ions are recorded continuously in a mass spectrometer incorporating a quadrupole mass analyser.
Although Time of Flight mass spectrometers are suited to applications where it is required to acquire a full mass spectrum quickly and with high sensitivity, Time of Flight mass spectrometers are not particularly suited to applications where it is required to record and quantify ions having mass to charge ratios which differ by a few mass to charge ratio units.
It is desired to provide an improved mass spectrometer.
According to an aspect of the present invention there is provided a mass spectrometer comprising:
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 region of a Time of Flight mass analyser.
In the first mode of operation ions having mass to charge ratios within a first range are preferably transmitted by the quadrupole rod set and ions having mass to charge ratios outside of the first range are preferably substantially attenuated by the quadrupole rod set. AC or RF voltages are applied to the rods of the quadrupole rod set and a DC potential difference is maintained between adjacent rods when the quadrupole rod set is in the first mode of operation.
In the second mode of operation ions are pulsed into the time of flight region. Ions are transmitted through the quadrupole rod set without being substantially mass filtered and become temporally separated according to their mass to charge ratio. The ion detector determines the time of flight of the ions through the time of flight region. AC or RF voltages are applied to the rods of the quadrupole rod set and all the rods of the quadrupole rod set are maintained at substantially the same DC potential in the second mode of operation.
In the first and/or the second mode of operation the quadrupole rod set is preferably maintained at a pressure selected from the group consisting of: (i) greater than or equal to 1xc3x9710xe2x88x927 mbar; (ii) greater than or equal to 5xc3x9710xe2x88x927 mbar; (iii) greater than or equal to 1xc3x9710xe2x88x926 mbar; (iv) greater than or equal to 5xc3x9710xe2x88x926 mbar; (v) greater than or equal to 1xc3x9710xe2x88x925 mbar; and (vi) greater than or equal to 5xc3x9710xe2x88x925 mbar.
In the first and/or the second mode of operation the quadrupole rod set is preferably maintained at a pressure selected from the group consisting of: (i) less than or equal to 1xc3x9710xe2x88x924 mbar; (ii) less than or equal to 5xc3x9710xe2x88x925 mbar; (iii) less than or equal to 1xc3x9710xe2x88x925 mbar; (iv) less than or equal to 5xc3x9710xe2x88x926 mbar; (v) less than or equal to 1xc3x9710xe2x88x926 mbar; (vi) less than or equal to 5xc3x9710xe2x88x927 mbar; and (vii) less than or equal to 1xc3x9710xe2x88x927 mbar.
In the first and/or the second mode of operation the quadrupole rod set is preferably maintained at a pressure selected from the group consisting of: (i) between 1xc3x9710xe2x88x927 and 1xc3x9710xe2x88x924 mbar; (ii) between 1xc3x9710xe2x88x927 and 5xc3x9710xe2x88x925 mbar; (iii) between 1xc3x9710xe2x88x927 and 1xc3x9710xe2x88x925 mbar; (iv) between 1xc3x9710xe2x88x927 and 5xc3x9710xe2x88x926 mbar; (v) between 1xc3x9710xe2x88x927 and 1xc3x9710xe2x88x926 mbar; (vi) between 1xc3x9710xe2x88x927 and 5xc3x9710xe2x88x927 mbar; (vii) between 5xc3x9710xe2x88x927 and 1xc3x9710xe2x88x924 mbar; (viii) between 5xc3x97107 and 5xc3x9710xe2x88x925 mbar; (ix) between 5xc3x9710xe2x88x927 and 1xc3x9710xe2x88x925 mbar; (x) between 5xc3x9710xe2x88x927 and 5xc3x9710xe2x88x926 mbar; (xi) between 5xc3x9710xe2x88x927 and 1xc3x9710xe2x88x926 mbar; (xii) between 1xc3x9710xe2x88x926 mbar and 1xc3x9710xe2x88x924 mbar; (xiii) between 1xc3x9710xe2x88x926 and 5xc3x9710xe2x88x925 mbar; (xiv) between 1xc3x9710xe2x88x926 and 1xc3x9710xe2x88x925 mbar; (xv) between 1xc3x9710xe2x88x926 and 5xc3x9710xe2x88x926 mbar; (xvi) between 5xc3x9710xe2x88x926 mbar and 1xc3x9710xe2x88x924 mbar; (xvii) between 5xc3x9710xe2x88x926 and 5xc3x9710xe2x88x925 mbar; (xviii) between 5xc3x9710xe2x88x926 and 1xc3x9710xe2x88x925 mbar; (xix) between 1xc3x9710xe2x88x925 mbar and 1xc3x9710xe2x88x924 mbar; (xx) between 1xc3x9710xe2x88x925 and 5xc3x9710xe2x88x925 mbar; and (xxi) between 5xc3x9710xe2x88x925 and 1xc3x9710xe2x88x924 mbar.
The mass spectrometer preferably further comprises a collision cell and a further quadrupole rod set arranged upstream of the collision cell. The multi-mode quadrupole rod set is preferably arranged downstream of the collision cell.
In a MS mode of operation the further quadrupole rod set acts as a mass filter to mass filter parent ions. Parent ions are collisionally cooled within the collision cell, and parent ions preferably exit the collision cell in a substantially non-pulsed manner. The multi-mode quadrupole rod set is preferably operated in a third mode of operation so as to transmit parent ions without substantially mass filtering the parent ions.
In a MS/MS mode of operation the further quadrupole rod set acts as a mass filter to mass filter parent ions. At least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or 100% of parent ions entering or within the collision cell are preferably fragmented upon entering or within the collision cell to form fragment ions. Fragment ions are collisionally cooled within the collision cell, and preferably exit the collision cell in a substantially non-pulsed manner. The multi-mode quadrupole rod set is operated in the first mode of operation so as to mass filter fragment ions. The multi-mode quadrupole rod set may be scanned so as to act as a mass analyser.
In a MS-TOF mode of operation the further quadrupole rod set acts as an ion guide to transmit parent ions without substantially mass filtering the parent ions. The parent ions are collisionally cooled and/or trapped within the collision cell and may be pulsed out of the collision cell. The multi-mode quadrupole rod set is preferably operated in the second mode of operation so that parent ions become temporally separated as they pass through the time of flight region formed by the multi-mode quadrupole rod set.
In a MS/MS-TOF mode of operation the further quadrupole rod set acts as a mass filter to mass filter parent ions. At least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or 100% of parent ions entering or within the collision cell are preferably fragmented upon entering or within the collision cell to form fragment ions. The fragment ions are collisionally cooled and/or trapped within the collision cell and are 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 become temporally separated as they pass through the time of flight region formed by the multi-mode quadrupole rod set.
The collision cell may comprise a segmented rod set or a stacked ring set comprising a plurality of electrodes having apertures wherein ions are transmitted, in use, through the apertures.
An axial DC voltage gradient may be maintained in use along at least a portion of the length of the collision cell. In a mode of operation an axial DC voltage difference is maintained, in use, along at least a first portion of the collision cell and is selected from the group consisting of: (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)  greater than 10 kV. In a mode of operation an axial DC voltage gradient is maintained, in use, along at least a first portion of the collision cell selected from the group consisting of: (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)  greater than 500 V/mm. The first portion is preferably located within a region located 0-10%, 10-20%, 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90%, or 90-100% of the length of the collision cell measured from an ion entrance of the collision cell to an ion exit of the collision cell. The first portion may preferably be located in the rearmost 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 or  greater than 150 electrodes.
The collision cell is preferably maintained, in use, at a pressure selected from the group consisting of: (i)  greater than 1.0xc3x9710xe2x88x923 mbar; (ii)  greater than 5.0xc3x9710xe2x88x923 mbar; (iii)  greater than 1.0xc3x9710xe2x88x922 mbar; (iv) 10xe2x88x923xe2x88x9210xe2x88x922 mbar; and (v) 10xe2x88x924xe2x88x9210xe2x88x921 mbar.
In a mode of operation ions are trapped but are not substantially fragmented within the collision cell. In another mode of operation ions are trapped and are substantially fragmented within the collision cell. In a further mode of operation ions are trapped within the collision cell and are progressively moved towards an exit of the collision cell. Ions may be stored or trapped within the collision cell near the exit of the collision cell. In a mode of operation ions are collisionally cooled within the collision cell in an ion trapping region located near the exit of the collision cell.
According to a preferred embodiment electrodes forming the collision cell may be maintained at different DC potentials so that at least a first and a second different stage axial acceleration electric field region 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 may be reduced. The ratio of the axial electric field strength in the second stage axial acceleration electric field region to the axial electric field strength in the first stage axial acceleration electric field region is preferably xe2x89xa72, xe2x89xa73, xe2x89xa74, xe2x89xa75, xe2x89xa76, xe2x89xa77, xe2x89xa78, xe2x89xa79 or xe2x89xa710. A ratio of approximately 8 is particularly preferred.
The collision cell may further comprise one or more grid electrodes arranged between electrodes forming the collision cell, wherein one or more DC voltages are applied to the one or more grid electrodes in order to provide the first and/or the second stage axial acceleration electric field regions.
One or more transient DC voltages or one or more transient DC voltage waveforms may be initially provided at a first axial position and may then subsequently provided at second, then third different axial positions along the collision cell.
One or more transient DC voltages or one or more transient DC voltage waveforms may move from one end of the collision cell to another end of the collision cell so that ions are urged along the collision cell. The one or tore transient DC voltages may create a potential hill or barrier, a potential well, multiple potential hills or barriers, multiple potential wells, a combination of a potential hill or barrier and a potential well, or a combination of multiple potential hills or barriers and multiple potential wells. The one or more transient DC voltage waveforms preferably comprise a repeating waveform such as a square wave.
According to a less preferred embodiment the collision cell may comprise a quadrupole rod set. However, such an arrangement does not easily facilitate the provision of axial electric fields.
The mass spectrometer preferably further comprises an AC or RF ion guide arranged upstream of the further quadrupole rod set. The AC or RF ion guide preferably comprises a plurality of electrodes. Additionally or alternatively, the sass spectrometer may comprise an AC or RF ion guide arranged upstream of the multi-mode quadrupole rod set wherein the AC or RF ion guide comprises a plurality of electrodes. The AC or RF ion guide may comprise a quadrupole, hexapole, octapole or higher order multipole rod set. Alternatively, the AC or RF ion guide may comprise a segmented rod set. More preferably, the AC or RF ion guide may comprise an ion tunnel ion guide comprising a plurality of electrodes having apertures through which ions are transmitted.
The AC or RF ion guide is preferably supplied with an AC or RF voltage having a frequency selected from the group consisting of; (i)  less than 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)  greater than 10.0 MHz.
The AC or RF ion guide is preferably supplied with an AC or RF voltage having an amplitude selected from the group consisting of: (i)  less than 50V peak to peak; (ii) 50-100V peak to peak; (iii) 100-150V peak to peak; (iv) 150-200V peak to peak; (v) 200-250V peak to peak; (vi) 250-300V peak to peak; (vii) 300-350V peak to peak; (viii) 350-400V peak to peak; (ix) 400-450V peak to peak; (x) 450-500V peak to peak; and (xi)  greater than 500V peak to peak.
In a mode of operation parent ions may be arranged to be trapped, stored or otherwise accumulated in the AC or RF ion guide whilst other ions are being collisionally cooled and/or fragmented in the collision cell and/or whilst ions are being transmitted through the multi-mode quadrupole ion trap operating in the second mode of operation. In one mode of operation ions are pulsed out of the AC or RF ion guide.
One or more transient DC potentials or one or more DC potential waveforms may be applied to the electrodes of the AC or RF ion guide. The one or more transient DC potentials or the one or more DC potential waveforms preferably urge ions from one region of the AC or RF ion guide to another region of the AC or RF ion guide.
According to a less preferred embodiment an ion trap may be arranged between the collision cell and the multi-mode quadrupole rod set. A further drift or time of flight region may also be arranged downstream of the multi-mode quadrupole rod set. A reflectron may additionally/alternatively be arranged downstream of the multi-mode quadrupole rod set.
According to another aspect of the present invention there is provided a method of mass spectrometry comprising:
providing a multi-mode quadrupole rod set and an ion detector;
operating the quadrupole rod set in a first mode of operation wherein the quadrupole rod set acts as a mass filter; and
operating the quadrupole rod set in a second mode of operation wherein the quadrupole rod set forms a time of flight region of a Time of Flight mass analyser.
According to another aspect of the present invention there is provided a mass spectrometer comprising a first multi-mode AC or RF ion guide wherein in a first mode of operation the first AC or RF ion guide acts as an ion guide and wherein in a second mode of operation the first AC or RF ion guide forms a time of flight region.
In the first mode of operation ions are preferably transmitted through the first AC or RF ion guide without being substantially mass filtered. Ions are preferably not substantially fragmented within the first AC or RF ion guide. Ions are preferably substantially continuously transmitted through the first AC or RF ion guide.
In the second mode of operation ions are pulsed into the time of flight region. Ions are preferably transmitted through the first AC or RF ion guide without being substantially mass filtered and become temporally separated according to their mass to charge ratio.
An ion detector may be provided wherein the ion detector determines the time of flight of the ions through the time of flight region.
A second AC or RF ion guide may be provided, preferably downstream of the first multi-mode AC or RF ion guide, wherein ions transmitted through the first multi-mode AC or RF ion guide are received by the second AC or RF ion guide. The second AC or RF ion guide may comprise a segmented rod set. Alternatively, the second AC or RF ion guide may comprise an ion tunnel ion guide comprising a plurality of electrodes having apertures through which ions are transmitted in use.
In use one or more transient DC voltages or one or more transient DC voltage waveforms are initially provided at a first axial position and are then subsequently provided at second, then third different axial positions along the second AC or RF ion guide.
One or more transient DC voltages or one or more transient DC voltage waveforms may move in use from one end of the second AC or RF ion guide to another end of the second AC or RF ion guide so that ions are urged along the second AC or RF ion guide. The one or more transient DC voltages may create a potential hill or barrier, a potential well, multiple potential hills or barriers, multiple potential wells, a combination of a potential hill or barrier and a potential well, or a combination of multiple potential hills or barriers and multiple potential wells. The one or more transient DC voltage waveforms applied to the second AC or RF ion guide preferably comprise a repeating waveform such as a square wave.
When the first multi-mode AC or RF ion guide is operated in the second mode of operation ions having mass to charge ratios within a first range are preferably trapped in a first axial trapping region within the second AC or RF ion guide and ions having mass to charge ratios within a second different range are preferably trapped 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 are likewise preferably trapped in a third axial trapping region within the second AC or RF ion guide and ions having mass to charge ratios within a fourth different range are preferably trapped in a fourth different axial trapping region within the 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 different range are preferably trapped in a sixth different axial trapping region 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 group consisting of: (i) greater than or equal to 1xc3x9710xe2x88x927 mbar; (ii) greater than or equal to 5xc3x9710xe2x88x927 mbar; (iii) greater than or equal to 1xc3x9710xe2x88x926 mbar; (iv) greater than or equal to 5xc3x9710xe2x88x926 mbar; (v) greater than or equal to 1xc3x9710xe2x88x925 mbar; and (vi) greater than or equal to 5xc3x9710xe2x88x925 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 group consisting of: (i) less than or equal to 1xc3x9710xe2x88x924 mbar; (ii) less than or equal to 5xc3x9710xe2x88x925 mbar; (iii) less than or equal to 1xc3x9710xe2x88x925 mbar; (iv) less than or equal to 5xc3x9710xe2x88x926 mbar; (v) less than or equal to 1xc3x9710xe2x88x926 mbar; (vi) less than or equal to 5xc3x9710xe2x88x927 mbar; and (vii) less than or equal to 1xc3x9710xe2x88x927 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 group consisting of: (i) between 1xc3x9710xe2x88x927 and 1xc3x9710xe2x88x924 mbar; (ii) between 1xc3x9710xe2x88x927 and 5xc3x9710xe2x88x925 mbar; (iii) between 1xc3x9710xe2x88x927 and 1xc3x9710xe2x88x925 mbar; (iv) between 1xc3x9710xe2x88x927 and 5xc3x9710xe2x88x926 mbar; (v) between 1xc3x9710xe2x88x927 and 1xc3x9710xe2x88x926 mbar; (vi) between 1xc3x9710xe2x88x927 and 5xc3x9710xe2x88x927 mbar; (vii) between 5xc3x9710xe2x88x927 and 1xc3x9710xe2x88x924 mbar; (viii) between 5xc3x9710xe2x88x927 and 5xc3x9710xe2x88x925 mbar; (ix) between 5xc3x9710xe2x88x927 and 1xc3x9710xe2x88x925 mbar; (x) between 5xc3x9710xe2x88x927 and 5xc3x9710xe2x88x926 mbar; (xi) between 5xc3x9710xe2x88x927 and 1xc3x9710xe2x88x925 mbar; (xii) between 1xc3x9710xe2x88x926 mbar and 1xc3x9710xe2x88x924 mbar; (xiii) between 1xc3x9710xe2x88x926 and 5xc3x9710xe2x88x925 mbar; (xiv) between 1xc3x9710xe2x88x926 and 1xc3x9710xe2x88x925 mbar; (xv) between 1xc3x9710xe2x88x926 and 5xc3x9710xe2x88x926 mbar; (xvi) between 5xc3x9710xe2x88x926 mbar and 1xc3x9710xe2x88x924 mbar; (xvii) between 5xc3x9710xe2x88x926 and 5xc3x97105 mbar; (xviii) between 5xc3x9710xe2x88x926 and 1xc3x9710xe2x88x925 mbar; (xix) between 1xc3x9710xe2x88x925 mbar and 1xc3x9710xe2x88x924 mbar; (xx) between 1xc3x9710xe2x88x925 and 5xc3x9710xe2x88x925 mbar; and (xxi) between 5xc3x9710xe2x88x925 and 1xc3x9710xe2x88x924 mbar.
According to another embodiment in the first mode of operation the first AC or RF ion guide may be maintained at a pressure selected from the group consisting of: (i) greater than or equal to 0.0001 mbar; (ii) greater than or equal to 0.0005 mbar; (iii) greater than or equal to 0.001 mbar; (iv) greater than or equal to 0.005 mbar; (v) greater than or equal to 0.01 mbar; (vi) greater than or equal to 0.05 mbar; (vii) greater than or equal to 0.1 mbar; (viii) greater than or equal to 0.5 mbar; (ix) greater than or equal to 1 mbar; (x) greater than or equal to 5 mbar; and (xi) greater than or equal to 10 mbar. In the first mode of operation the first AC or RF ion guide may be maintained at a pressure selected from the group consisting of: (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) less than or equal to 0.0005 mbar; and (xi) less than or equal to 0.0001 mbar. In the first mode of operation the first AC or RF ion guide may be maintained at a pressure selected from the group consisting of: (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 may comprise a quadrupole, hexapole, octapole or higher order multipole rod set. Alternatively, the first AC or RF ion guide comprises a segmented rod set. More preferably, the first AC or RF ion guide comprise an ion tunnel ion guide comprising a plurality of electrodes having apertures through which ions are transmitted in use.
In the first 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 group consisting of: (i)  less than 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)  greater than 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 group consisting of: (i)  less than 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)  greater than 10.0 MHz.
In the first mode of operation the first AC or RF ion guide is preferably supplied with an AC or RF voltage having an amplitude selected from the group consisting of; (i)  less than 50V peak to peak; (ii) 50-100V peak to peak; (iii) 100-150V peak to peak; (iv) 150-200V peak to peak; (v) 200-250V peak to peak; (vi) 250-300V peak to peak; (vii) 300-350V peak to peak; (viii) 350-400V peak to peak; (ix) 400-450V peak to peak; (x) 450-500V peak to peak; and (xi)  greater than 500V peak to peak.
In the second mode of operation the first AC or PR ion guide is preferably supplied with an AC or RF voltage having an amplitude selected from the group consisting of: (i)  less than 50V peak to peak; (ii) 50-100V peak to peak; (iii) 100-150V peak to peak; (iv) 150-200V peak to peak; (v) 200-250V peak to peak; (vi) 250-300V peak to peak; (vii) 300-350V peak to peak; (viii) 350-400V peak to peak; (ix) 400-450V peak to peak; (x) 450-500V peak to peak; and (xi)  greater than 500V peak to peak.
The mass spectrometer preferably further comprises an Electrospray (xe2x80x9cESIxe2x80x9d) ion source, an Atmospheric Pressure Chemical Ionisation (xe2x80x9cAPCIxe2x80x9d) ion source, an Atmospheric Pressure Photo Ionisation (xe2x80x9cAPPIxe2x80x9d) ion source, a Matrix Assisted Laser Desorption Ionisation (xe2x80x9cMALDIxe2x80x9d) ion source, a Laser Desorption Ionisation (xe2x80x9cLDIxe2x80x9d) ion source, an Inductively Coupled Plasma (xe2x80x9cICPxe2x80x9d) ion source, an Electron Impact (xe2x80x9cEIxe2x80x9d) ion source, a Chemical Ionisation (xe2x80x9cCIxe2x80x9d) ion source, a Fast Atom Bombardment (xe2x80x9cFABxe2x80x9d) ion source or a Liquid Secondary Ions Mass Spectrometry (xe2x80x9cLSIMSxe2x80x9d) ion source. The ion source may be pulsed or continuous.
According to another aspect of the present invention there is provided a method of mass spectrometry comprising:
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 ion 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.
According to another aspect of the present invention there is provided a mass spectrometer comprising a collision cell, the collision cell comprising a plurality of electrodes wherein in a mode of operation a first stage axial acceleration electric field region and a second different stage axial field region are provided to accelerate ions out of the collision cell.
The ratio of the axial electric field strength in the second stage axial acceleration electric field region to the electric field strength in the first stage axial acceleration electric field region is selected from the group consisting of: (i) xe2x89xa72; (ii) xe2x89xa73; (iii) xe2x89xa74; (iv) xe2x89xa75; (v) xe2x89xa76; (vi) xe2x89xa77; (vii) xe2x89xa78; (viii) xe2x89xa79; and (ix)  greater than 10. A ratio of about 8 is particularly preferred.
Prior to accelerating ions out of the collision cell the pressure within the collision cell may be reduced.
According to another aspect of the present invention there is provided a method of mass spectrometry comprising:
providing a collision cell comprising a plurality of electrodes;
providing a first stage axial acceleration electric field across a first region of the collision cell; and
providing a second different stage axial field across a second different region of the collision cell;
wherein the first and second stage axial fields are provided to accelerate ions out of the collision cell.
In 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 arranged between the ion source and the quadrupole rod set to either transmit ions continuously or to pulse ions into the quadrupole rod set. In one mode of operation the quadrupole rod set is employed as a quadrupole mass filter with the AC or RF ion guide between the ion source and quadrupole rod set arranged to continuously transmit ions. In this mode of operation the quadrupole rod set is operated with both AC/RF and DC voltages being applied to the rods such that ions are radially confined by the AC/RF electric fields and are mass filtered due to a DC potential difference being maintained between the rods. An ion detector preferably continuously records the ion signal.
In another mode of operation the quadrupole rod set is employed as a time of flight or drift region for use in time of flight mass analysis. In this mode of operation the AC or RF ion guide between the ion source and the quadrupole rod set may be arranged to accumulate ions and release them in discrete pulses. The quadrupole rod set is operated with AC/RF voltages applied to the rods such that the ions are radially confined and drift axially in the quadrupole rod set. The rods are all maintained at substantially the same DC potential. An ion detector preferably records both the ion signal intensity and the time taken for ions released from the AC or RF ion guide to arrive at the ion detector.
In the mode of operation wherein the quadrupole rod set provides a time of flight region, the quadrupole rod set may be used as a drift region because the AC/RF electric fields within the rod set only have radial components. The AC/RF fields act to confine the ions radially and do not exert any axial force on the ions. As such, the quadratic radial electric fields do not interfere with the function of the device which is to provide a drift or time of flight region.
AC/RF voltages applied to the quadrupole rod set may give rise to slight fringe electric fields at the entrance and exit of the quadrupole rod set. These fringe fields may be distorted and may contain a non-linear axial electric field component which could cause a small degree of disruption to the drift velocities of the ions travelling into or out of the quadrupole rod set. However, if a pulsed source of ions is arranged in close proximity to the entrance of the quadrupole rod set and the acceleration of the ions into the quadrupole rod set is synchronised with the AC/RF voltage supply to the rods, then it can be arranged for the ions to enter the quadrupole rod set when the AC/RF voltage is passing through zero. Correct synchronisation of ion acceleration into the quadrupole rod set with the AC/RF voltage will help to ensure that the axial component of the fringe field at the entrance to the quadrupole rod set is both constant and has minimal disruption to the ions during ion entry into the quadrupole rod set.
Synchronising the time of exit of the ions from the quadrupole rod set with the time that the applied AC/RF voltage passes through zero is not possible since when the quadrupole rod set acts as a drift or time of flight region the ions separate according to their mass to charge ratios and exit the rod set at substantially different times. However, the ion detector may be arranged in close proximity to the exit of the quadrupole rod set such that any minor distortion caused by the axial component of the fringe field will be either minimal or negligible. By arranging the ion detector close to the exit of the quadrupole rod set the distance the ions travel after leaving the quadrupole rod set is small in comparison to the length of the quadrupole rod set itself. As such, the time taken for ions to travel from the quadrupole rod set to the ion detector, and hence the distortion in the ions temporal separation is relatively insignificant. If necessary, any distortion may be yet further reduced by accelerating the ions out of the quadrupole rod set and in to the ion detector.
In the preferred embodiment the mass spectrometer may comprise more than one quadrupole rod set and/or other additional analysers. For example, the mass spectrometer may comprise a collision cell and at least one multi-mode quadrupole rod set which in a first mode operates as a mass filter and in a second mode operates as a drift or time of flight region. 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 comprise a multipole rod set. The preferred multi-mode quadrupole rod set may function as a drift or time of flight region in one mode of operation and as a mass filter in another mode of operation. As such the preferred mass spectrometer is capable of performing all the functions of a conventional triple quadrupole mass spectrometer but advantageously has the capability of recording mass spectra for ions having a wide range of mass to charge ratios and also fragment ion spectra resulting from fragmentation of parent ions with high sensitivity and at a faster rate compared with conventional arrangements.
In the preferred embodiment the AC or RF ion guide between the ion source and preferred quadrupole rod set is preferably segmented so that ions may be accumulated in one region of the AC or RF ion guide and may then be released into a quadrupole rod set as a discrete packet of ions. The AC or RF ion guide may comprise, for example, a segmented rod set or stacked ring set and preferably allows ions to be linearly accelerated for subsequent mass analysis downstream when the mass spectrometer is operated in a time of flight mode.