EP1505634A2 - Spectromètre de masse. - Google Patents

Spectromètre de masse. Download PDF

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Publication number
EP1505634A2
EP1505634A2 EP04026519A EP04026519A EP1505634A2 EP 1505634 A2 EP1505634 A2 EP 1505634A2 EP 04026519 A EP04026519 A EP 04026519A EP 04026519 A EP04026519 A EP 04026519A EP 1505634 A2 EP1505634 A2 EP 1505634A2
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EP
European Patent Office
Prior art keywords
fragmentation cell
ions
electrodes
voltage
cell
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Application number
EP04026519A
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German (de)
English (en)
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EP1505634A3 (fr
EP1505634B1 (fr
Inventor
Robert Harold Bateman
Kevin Giles
Steven Pringle
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Micromass UK Ltd
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Micromass UK Ltd
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Priority claimed from GB0120122A external-priority patent/GB0120122D0/en
Priority claimed from GB0206164A external-priority patent/GB0206164D0/en
Application filed by Micromass UK Ltd filed Critical Micromass UK Ltd
Priority claimed from EP02254394.6A external-priority patent/EP1271610B1/fr
Publication of EP1505634A2 publication Critical patent/EP1505634A2/fr
Publication of EP1505634A3 publication Critical patent/EP1505634A3/fr
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Publication of EP1505634B1 publication Critical patent/EP1505634B1/fr
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    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/004—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn
    • H01J49/0045—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn characterised by the fragmentation or other specific reaction
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/06—Electron- or ion-optical arrangements
    • H01J49/062—Ion guides
    • H01J49/065—Ion guides having stacked electrodes, e.g. ring stack, plate stack

Definitions

  • the present invention relates to mass spectrometers.
  • a known fragmentation cell comprises a multipole (e.g. a quadrupole or hexapole) rod set wherein adjacent rods are connected to opposite phases of an RF voltage supply.
  • the quadrupole or hexapole collision cell is housed in a cylindrical housing which is open at an upstream end and at a downstream end to allow ions to enter and exit the collision cell.
  • the housing includes a gas inlet port through which a collision or buffer gas, typically nitrogen or argon, is introduced into the collision cell.
  • the collision cell is maintained at a pressure of 10 -3 -10 -2 mbar.
  • Ions entering the collision cell are arranged to be sufficiently energetic so that when they collide with the collision or buffer gas at least some of the ions will fragment into daughter or fragment ions by means of Collisional Induced Dissociation/Decomposition ("CID"). Ions in the collision cell will also become thermalised after they have undergone a few collisions i.e. their kinetic energy will be considerably reduced, and this leads to greater radial confinement of the ions in the presence of the RF electric field. In order to ensure that ions are sufficiently energetic so as to fragment when entering the collision cell, the collision cell is typically maintained at a DC potential which is offset from that of the ion source by approximately -30V DC or more (for positive ions).
  • ions Once ions have fragmented and have been thermalised within the collision cell, their low kinetic energy is such that they will tend to remain within the collision cell. In practice, ions are observed to exit the collision cell after a relatively long period of time, and this is believed to be due to the effects of diffusion and the repulsive effect of further ions being admitted into the collision cell.
  • ions tend to have a relatively long residence time within the collision cell. This is problematic for certain types of mass spectrometry methods since it is necessary to wait until ions have exited the collision cell before further ions are admitted into it.
  • MS/MS i.e. fragmentation
  • a quadrupole mass filter Q1 (MS1) upstream of a collision cell Q2 is scanned rapidly compared to the typical empty time ( ⁇ 30ms) of ions to exit the collision cell Q2
  • MS1 quadrupole mass filter
  • ⁇ 30ms typical empty time
  • MRM Multiple Reaction Monitoring
  • a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein at least some of the electrodes are connected to both a DC and an AC or RF voltage supply and wherein an axial DC voltage gradient or difference is maintained in use along at least a portion of the length of the fragmentation cell.
  • the preferred collision or fragmentation cell differs from a conventional multipole collision cell in that instead of comprising four or six elongated rod electrodes, the fragmentation cell comprises a number (e.g. typically > 100) of ring, annular or plate like electrodes having apertures, preferably circular, through which ions are transmitted. Furthermore, an axial DC voltage gradient is preferably maintained across at least a portion of the length of the fragmentation cell, preferably the whole length of the fragmentation cell.
  • the fragmentation cell according to the preferred embodiment is capable of being emptied of and filled with ions much faster than a conventional collision cell. Mass spectra obtained using the preferred fragmentation cell exhibit improved resolution and greater sensitivity.
  • the fragmentation cell may comprise 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, 90-100, 100-110, 110-120, 120-130, 130-140, 140-150, or >150 electrodes.
  • the fragmentation cell may have a length ⁇ 5 cm, 5-10 cm, 10-15 cm, 15-20 cm, 20-25 cm, 25-30 cm, or >30 cm.
  • at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of the electrodes are connected to both a DC and an AC or RF voltage supply.
  • an axial DC voltage difference of approximately 3V may be maintained along the whole length of the fragmentation cell (i.e.
  • electrodes at the downstream end of the fragmentation cell are maintained at a DC voltage approximately 3V below electrodes at the upstream end of the fragmentation cell).
  • the axial DC voltage difference maintained along at least a portion, preferably the whole length, of the fragmentation cell is 0.1-0.5 V, 0.5-1.0 V, 1.0-1.5 V, 1.5-2.0 V, 2.0-2.5 V, 2.5-3.0 V, 3.0-3.5 V, 3.5-4.0 V, 4.0-4.5 V, 4.5-5.0 V, 5.0-5.5 V, 5.5-6.0 V, 6.0-6.5 V, 6.5-7.0 V, 7.0-7.5 V, 7.5-8.0 V, 8.0-8.5 V, 8.5-9.0 V, 9.0-9.5 V, 9.5-10.0 V or > 10V.
  • the axial DC voltage gradient maintained along at least a portion of the fragmentation cell, and preferably along the whole length of the collision cell may be 0.01-0.05 V/cm, 0.05-0.10 V/cm, 0.10-0.15 V/cm, 0.15-0.20 V/cm, 0.20-0.25 V/cm, 0.25-0.30 V/cm, 0.30-0.35 V/cm, 0.35-0.40 V/cm, 0.40-0.45 V/cm, 0.45-0.50 V/cm, 0.50-0.60 V/cm, 0.60-0.70 V/cm, 0.70-0.80 V/cm, 0.80-0.90 V/cm, 0.90-1.0 V/cm, 1.0-1.5 V/cm, 1.5-2.0 V/cm, 2.0-2.5 V/cm, 2.5-3.0 V/cm or > 3.0 V/cm.
  • the voltage gradient may be a linear voltage gradient, or the voltage gradient may have a stepped or curved stepped profile similar to that shown in Fig. 4.
  • the term "voltage gradient” should be construed broadly to cover embodiments wherein the DC voltage offset of electrodes along the length of the fragmentation cell relative to the DC potential of the ion source varies at different points along the length of the fragmentation cell. This term should not, however, be construed to include arrangements wherein all the electrodes forming the fragmentation cell are maintained at substantially the same DC potential.
  • the electrodes forming the fragmentation cell are supplied with an AC or RF voltage which can be considered to be superimposed upon the DC potential supplied to the electrodes.
  • adjacent electrodes are connected to opposite phases of an AC or RF supply but according to other less preferred embodiments adjacent electrodes may be connected to different phases of the AC or RF supply i.e. voltage supplies having more than two phases are contemplated.
  • the AC or RF voltage supplied to the electrodes has a sinusoidal waveform (with a frequency 0.1-3.0 MHz, preferably 1.75 MHz), non-sinusoidal waveforms including square waves may be supplied to the electrodes.
  • the fragmentation cell may comprise a plurality of segments.
  • fifteen segments are provided.
  • Each segment comprises a plurality of electrodes, with preferably either eight or ten electrodes per segment.
  • Each electrode has an aperture through which ions are transmitted.
  • the diameter of the apertures of at least 50% of the electrodes forming the fragmentation cell is preferably ⁇ 10 mm, ⁇ 9 mm, ⁇ 8 mm, ⁇ 7 mm, ⁇ 6 mm, ⁇ 5 mm, ⁇ 4 mm, ⁇ 3 mm, ⁇ 2 mm, or ⁇ 1 mm.
  • the thickness of at least 50% of the electrodes forming the fragmentation cell is preferably ⁇ 3 mm, ⁇ 2.5 mm, ⁇ 2.0 mm, ⁇ 1.5 mm, ⁇ 1.0 mm, or ⁇ 0.5 mm.
  • at least 50%, 60%, 70%, 80%, 90% or 95% of the electrodes forming the fragmentation cell have apertures which are substantially the same size or area. All the electrodes in a particular segment are preferably maintained at substantially the same DC potential, but adjacent electrodes in a segment are preferably supplied with different or opposite phases of an AC or RF voltage.
  • ions may be trapped within the fragmentation cell in a mode of operation.
  • Embodiments are contemplated wherein ions may be trapped in a downstream portion of the fragmentation cell whilst ions may be continually admitted into an upstream portion of the fragmentation cell.
  • V-shaped axial DC potential profiles may be used to accelerate and trap ions within the collision cell.
  • the fragmentation cell is preferably maintained, in use, at a pressure > 1.0 x 10 -3 mbar, > 5.0 x 10 -3 mbar, > 1.0 x 10 -2 mbar, 10 -3 -10 -2 mbar, or 10 -4 -10 -1 mbar.
  • the mass spectrometer preferably comprises a continuous ion source, further preferably an atmospheric pressure ion source, although other ion sources are contemplated.
  • Electrospray (“ESI”), Atmospheric Pressure Chemical Ionisation (“APCI”), Atmospheric Pressure Photo Ionisation (“APPI”), Matrix Assisted Laser Desorption Ionisation (“MALDI”), non-matrix assisted Laser Desorption Ionisation, Inductively Coupled Plasma (“ICP”), Electron Impact (“EI”) and Chemical Ionisation (“CI”) ion sources may be provided.
  • the fragmentation cell preferably comprises a housing having an upstream opening for allowing ions to enter the fragmentation cell and a downstream opening for allowing ions to exit the fragmentation cell.
  • a mass spectrometer comprising: an ion source; one or more ion guides; a first quadrupole mass filter; a fragmentation cell for fragmenting ions, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein at least some of the electrodes are connected to both a DC and an AC or RF voltage supply and wherein an axial DC voltage gradient or difference is maintained in use along at least a portion of the length of the fragmentation cell; a second quadrupole mass filter; and a detector.
  • a mass spectrometer comprising: an ion source; one or more ion guides; a quadrupole mass filter; a fragmentation cell for fragmenting ions, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein at least some of the electrodes are connected to both a DC and an AC or RF voltage supply and wherein an axial DC voltage gradient or difference is maintained in use along at least a portion of the length of the fragmentation cell; and a time of flight mass analyser.
  • the fragmentation cell comprises a plurality of segments, each segment comprising a plurality of electrodes having apertures through which ions are transmitted and wherein all the electrodes in a segment are maintained at substantially the same DC potential and wherein adjacent electrodes are supplied with different phases of an AC or RF voltage.
  • the one or more ion guides may comprise one or more AC or RF only ion tunnel ion guides (wherein at least 90% of the electrodes have apertures which are substantially the same size) and/or one or more hexapole ion guides.
  • a mass spectrometer comprising: a first mass filter/analyser; a fragmentation cell for fragmenting ions, the fragmentation cell being arranged downstream of the first mass filter/analyser and comprising at least 20 electrodes having apertures through which ions are transmitted in use, wherein at least 75% of the electrodes are connected to both a DC and an AC or RF voltage supply and wherein a non-zero axial DC voltage gradient or difference is maintained in use along at least 75% of the length of the fragmentation cell; and a second mass filter/analyser arranged downstream of the fragmentation cell.
  • the first mass filter/analyser comprises a quadruople mass filter/analyser and the second mass filter comprises a quadrupole mass filter/analyser or a time of flight mass analyser.
  • a mass spectrometer comprising: a fragmentation cell comprising ⁇ 10 ring or plate electrodes having substantially similar internal apertures between 2-10 mm in diameter arranged in a housing having a buffer gas inlet port, wherein a buffer gas is introduced in use into the fragmentation cell at a pressure of 10 -4 -10 -1 mbar and wherein a DC potential gradient or difference is maintained, in use, along the length of the fragmentation cell.
  • the mass spectrometer further comprises an ion source and ion optics upstream of the fragmentation cell, wherein the ion source and/or the ion optics are maintained at potentials such that at least some of the ions entering the fragmentation cell have, in use, an energy ⁇ 10 eV for a singly charged ion such that they are caused to fragment.
  • a mass spectrometer comprising: an ion source; a fragmentation cell for fragmenting ions, the fragmentation cell comprising at least ten plate-like electrodes arranged substantially perpendicular to the longitudinal axis of the fragmentation cell, each electrode having an aperture therein through which ions are transmitted in use, the fragmentation cell being supplied in use with a collision gas at a pressure ⁇ 10 -3 mbar, wherein adjacent electrodes are connected to different phases of an AC or RF voltage supply and a DC potential gradient ⁇ 0.01 V/cm is maintained over at least 20% of the length of the fragmentation cell; and ion optics arranged between the ion source and the fragmentation cell; wherein in a mode of operation the ion source, ion optics and fragmentation cell are maintained at potentials such that singly charged ions are caused to have an energy ⁇ 10 eV upon entering the fragmentation cell so that at least some of the ions fragment into daughter ions.
  • a mass spectrometer comprising: a collision or fragmentation cell comprising at least three segments, each segment comprising at least four electrodes having substantially similar sized apertures through which ions are transmitted in use; wherein in a mode of operation: electrodes in a first segment are maintained at substantially the same first DC potential but adjacent electrodes are supplied with different phases of an AC or RF voltage supply; electrodes in a second segment are maintained at substantially the same second DC potential but adjacent electrodes are supplied with different phases of an AC or RF voltage supply; electrodes in a third segment are maintained at substantially the same third DC potential but adjacent electrodes are supplied with different phases of an AC or RF voltage supply; wherein the first, second and third DC potentials are all different.
  • a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein at least some of the electrodes are connected to an AC or RF voltage supply.
  • At least some of the electrodes are also connected to a DC voltage supply and wherein an axial DC voltage gradient or difference is maintained in use along at least a portion of the length of the fragmentation cell.
  • a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein in a mode of operation at least a portion of the fragmentation cell is maintained at a DC potential so as to prevent ions from exiting the fragmentation cell.
  • a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein the empty time taken for ions to exit the fragmentation cell is selected from the group comprising: (i) ⁇ 0.5 ms; (ii) ⁇ 1.0 ms; (iii) ⁇ 5 ms; (iv) ⁇ 10 ms; (v) ⁇ 20 ms; (vi) 0.01-0.5 ms; (vii) 0.5-1 ms; (viii) 1-5 ms; (ix) 5-10 ms; and (x) 10-20 ms.
  • a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, and wherein in a mode of operation trapping DC voltages are supplied to some of the electrodes so that ions are confined in two or more axial DC potential wells.
  • a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, and wherein in a mode of operation a V-shaped, sinusoidal, curved, stepped or linear axial DC potential profile is maintained along at least a portion, preferably at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of the length of the fragmentation cell.
  • a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, and wherein in a mode of operation an upstream portion of the fragmentation cell continues to receive ions into the fragmentation cell whilst a downstream portion of the fragmentation cell separated from the upstream portion by a potential barrier stores and periodically releases ions.
  • the upstream portion of the fragmentation cell has a length which is at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the total length of the fragmentation cell.
  • the downstream portion of the fragmentation cell has a length which is less than or equal to 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the total length of the fragmentation cell.
  • the downstream portion of the fragmentation cell is shorter than the upstream portion of the fragmentation cell.
  • a mass spectrometer comprising: a fragmentation cell in which ions are fragmented in use, said fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, and wherein in a mode of operation an AC or RF voltage is applied to at least some of said electrodes and the peak amplitude of said AC or RF voltage is varied.
  • the peak amplitude of the AC or RF voltage is increased in time.
  • the peak amplitude of the AC or RF voltage is ⁇ 200 V Pp , ⁇ 150 V Pp , ⁇ 100 V Pp , or ⁇ 60 V Pp .
  • the peak amplitude of the AC or RF voltage is ⁇ 100 V Pp , ⁇ 150 V Pp , ⁇ 200 V Pp , ⁇ 250 V Pp , or ⁇ 300 V Pp .
  • a method of mass spectrometry comprising: fragmenting ions in a fragmentation cell, the fragmentation cell comprising a plurality of electrodes having apertures through which ions are transmitted in use, wherein at least some of the electrodes are connected to both a DC and an AC or RF voltage supply and wherein an axial DC voltage gradient or difference is maintained in use along at least a portion of the length of the fragmentation cell.
  • the ion tunnel fragmentation cell 1 comprises a reasonably gas tight housing having a relatively small entrance aperture 2 and a relatively small exit aperture 3.
  • the entrance and exit apertures 2,3 are preferably 2.2 mm diameter substantially circular apertures.
  • the plates forming the entrance and/or exit apertures 2,3 may be connected to independent programmable DC voltage supplies (not shown).
  • Each ion tunnel segment 4a;4b;4c comprises two interleaved and electrically isolated sections i.e. an upper and lower section.
  • the ion tunnel segment 4a closest to the entrance aperture 2 preferably comprises ten electrodes (with five electrodes in each section) and the remaining ion tunnel segments 4b,4c preferably each comprise eight electrodes (with four electrodes in each section). All the electrodes are preferably substantially similar in that they have a central substantially circular aperture (preferably 5 mm in diameter) through which ions are transmitted.
  • the entrance and exit apertures 2,3 are preferably smaller (e.g. 2.2 mm in diameter) than the apertures in the electrodes, and this helps to reduce the amount of collision gas leaking out of the fragmentation cell 1 into the vacuum chamber containing the fragmentation cell 1 which is preferably maintained at a lower pressure e.g. 10 -4 mbar or less.
  • All the ion tunnel segments 4a,4b,4c are preferably connected to the same AC or RF voltage supply, but different segments 4a;4b;4c may be provided with different DC voltages.
  • the two sections forming an ion tunnel segment 4a;4b;4c are connected to different, preferably opposite, phases of the AC or RF voltage supply.
  • a single ion tunnel section is shown in greater detail in Figs. 3(a)-(c).
  • the ion tunnel section has four (or five) electrodes 5, each electrode 5 having a 5 mm diameter central aperture 6.
  • the four (or five) electrodes 5 depend or extend from a common bar or spine 7 and are preferably truncated at the opposite end to the bar 7 as shown in Fig. 3(a).
  • Each electrode 5 is typically 0.5 mm thick.
  • Two ion tunnel sections are interlocked or interleaved to provide a total of eight (or ten) electrodes 5 in an ion tunnel segment 4a;4b;4c with a 1 mm inter-electrode spacing once the two sections have been interleaved.
  • All the eight (or ten) electrodes 5 in an ion tunnel segment 4a;4b;4c comprised of two separate sections are preferably maintained at substantially the same DC voltage.
  • Adjacent electrodes in an ion tunnel segment 4a;4b;4c comprised of two interleaved sections are connected to different, preferably opposite, phases of an AC or RF voltage supply i.e. one section of an ion tunnel segment 4a;4b;4c is connected to one phase (RF+) and the other section of the ion tunnel segment 4a;4b;4c is connected to another phase (RF-).
  • Each ion tunnel segment 4a;4b;4c is mounted on a machined PEEK support that acts as the support for the entire assembly.
  • Individual ion tunnel sections are located and fixed to the PEEK support by means of a dowel and a screw. The screw is also used to provide the electrical connection to the ion tunnel section.
  • the PEEK supports are held in the correct orientation by two stainless steel plates attached to the PEEK supports using screws and located correctly using dowels. These plates are electrically isolated and have a voltage applied to them.
  • Collision gas is supplied to the fragmentation cell 1 via a 4.5 mm ID tube.
  • Another tube may be connected to a vacuum gauge allowing the pressure in the fragmentation cell 1 to be monitored.
  • Fig. 1(a) The electrical connections shown in Fig. 1(a) are such that a substantially regular stepped axial accelerating DC electric field is provided along the length of the fragmentation cell 1 using two programmable DC power supplies DC1 and DC2 and a resistor potential divider network of 1 M ⁇ resistors.
  • An AC or RF voltage supply provides phase (RF+) and anti-phase (RF-) voltages at a frequency of preferably 1.75 MHz and is coupled to the ion tunnel sections 4a,4b,4c via capacitors which are preferably identical in value (100pF). According to other embodiments the frequency may be in the range of 0.1-3.0 MHz.
  • Four 10 ⁇ H inductors are provided in the DC supply rails to reduce any RF feedback onto the DC supplies.
  • FIG. 4 shows how, in one embodiment, the axial DC potential varies across a 10 cm central portion of the ion tunnel fragmentation cell 1.
  • the inter-segment voltage step in this particular embodiment is -1V. However, according to more preferred embodiments lower voltage steps of e.g. approximately -0.2V may be used.
  • Fig. 5 shows a potential energy surface across several ion tunnel segments 4b at a central portion of the ion tunnel fragmentation cell 1. As can be seen, the potential energy profile is such that ions will cascade from one ion tunnel segment to the next.
  • Fig. 1(b) shows another embodiment wherein the ion tunnel fragmentation cell 1 also traps, accumulates or otherwise confines ions within the fragmentation cell 1.
  • the DC voltage applied to the final ion tunnel segment 4c i.e. that closest and adjacent to the exit aperture 3 is independently controllable and can in one mode of operation be maintained at a relatively high DC blocking or trapping potential (DC3) which is more positive for positively charged ions (and vice versa for negatively charged ions) than the preceding ion tunnel segment(s) 4b.
  • DC3 DC blocking or trapping potential
  • Other embodiments are also contemplated wherein other ion tunnel segments 4a,4b may alternatively and/or additionally be maintained at a relatively high trapping potential.
  • an AC or RF voltage may or may not be applied to the final ion tunnel segment 4c.
  • the DC voltage supplied to the plates forming the entrance and exit apertures 2,3 is also preferably independently controllable and preferably no AC or RF voltage is supplied to these plates.
  • Embodiments are also contemplated wherein a relatively high DC trapping potential may be applied to the plates forming entrance and/or exit aperture 2,3 in addition to or instead of a trapping potential being supplied to one or more ion tunnel segments such as at least the final ion tunnel segment 4c.
  • the DC trapping potential applied to e.g. the final ion tunnel segment 4c or to the plate forming the exit aperture 3 is preferably momentarily dropped or varied, preferably in a pulsed manner.
  • the DC voltage may be dropped to approximately the same DC voltage as is being applied to neighbouring ion tunnel segment(s) 4b.
  • the voltage may be dropped below that of neighbouring ion tunnel segment(s) so as to help accelerate ions out of the fragmentation cell 1.
  • a V-shaped trapping potential may be applied which is then changed to a linear profile having a negative gradient in order to cause ions to be accelerated out of the fragmentation cell 1.
  • the voltage on the plate forming the exit aperture 3 can also be set to a DC potential such as to cause ions to be accelerated out of the fragmentation cell 1.
  • Fig. 6 shows how the DC potential may vary along a portion of the length of the fragmentation cell 1 when no axial DC field is applied and the fragmentation cell 1 is acting in a trapping or accumulation mode.
  • 0 mm corresponds to the midpoint of the gap between the fourteenth 4b and fifteenth (and final) 4c ion tunnel segments.
  • the blocking potential was set to +5V (for positive ions) and was applied to the last (fifteenth) ion tunnel segment 4c only.
  • the preceding fourteen ion tunnel segments 4a,4b had a potential of -1V applied thereto.
  • the plate forming the entrance aperture 2 was maintained at 0V DC and the plate forming the exit aperture 3 was maintained at -1V.
  • FIG. 7(a) shows a portion of the axial DC potential profile for a fragmentation cell 1 according to one embodiment operated in a "fill" mode of operation
  • Fig. 7(b) shows a corresponding "closed” mode of operation
  • Fig. 7(c) shows a corresponding "empty” mode of operation.
  • the fragmentation cell 1 may be opened, closed and then emptied in a short defined pulse.
  • 0 mm corresponds to the midpoint of the gap between the tenth and eleventh ion tunnel segments 4b.
  • the first nine segments 4a,4b are held at -1V, the tenth and fifteenth segments 4b act as potential barriers and ions are trapped within the eleventh, twelfth, thirteenth and fourteenth segments 4b.
  • the trap segments are held at a higher DC potential (+5V) than the other segments 4b.
  • When closed the potential barriers are held at +5V and when open they are held at -1V or -5V.
  • a relatively long upstream length of the fragmentation cell 1 may be used for trapping and storing ions and a relatively short downstream length may be used to hold and then release ions. By using a relatively short downstream length, the pulse width of the packet of ions released from the fragmentation cell 1 may be constrained. In other embodiments multiple isolated storage regions may be provided.
  • axial DC voltage gradients may additionally be applied along at least a portion of the fragmentation cell 1 so as to enhance the speed of the device.
  • Fig. 8 shows the effect of applying various axial DC voltage differences or gradients along the whole length of the fragmentation cell 1 when performing parent ion scans of reserpine.
  • An upstream quadrupole mass filter Q1 (MS1) was scanned from 600 to 620 amu in a time of 20 ms with an inter-scan delay ("ISD") of 10 ms (during which time the RF voltage applied to the fragmentation cell 1 was momentarily pulsed to zero for 5 ms so as to empty the fragmentation cell 1, and after which the fragmentation cell 1 was allowed to recover for a further 5 ms).
  • ISD inter-scan delay
  • the fragmentation cell 1 was set to operate in a fragmentation mode with the fragmentation cell 1 being held at approx. 35V DC below the DC potential at which the ion source is held so that ions are sufficiently energetic when entering the fragmentation cell 1 that they fragment when they collide with collision gas in the fragmentation cell 1.
  • a downstream quadrupole mass filter Q3 (MS2) was set so as to transmit only daughter ions having a mass to charge ratio of 195.
  • the sample used was 50 pg/ ⁇ l reserpine (having a mass to charge ratio of 609) infused at 5 ⁇ l/min. Results are shown for applied axial DC voltage differences of 0V, 3V, 5V and 10V across the length of the whole fragmentation cell 1.
  • the ordinate axis indicates the intensity of daughter ions (having a mass to charge ratio equal to 195) which were observed.
  • the daughter ions are still produced in the fragmentation cell 1, but once thermalised they will have relatively low axial velocities and the absence of any axial DC voltage difference means that the daughter ions will tend not to exit the fragmentation cell 1 during the 20 ms that the upstream quadrupole mass filter Q1 (MS1) is being scanned.
  • the greatest intensity of daughter ions was observed when an axial DC voltage difference of 3V was maintained along the whole length of the fragmentation cell 1.
  • the recovery time period In order to maintain a reasonable duty cycle at short acquisition (scan or dwell) times, the recovery time period must also be correspondingly short. However, if the time period allowed for recovery is too short (i.e. ⁇ 30 ms) then the conventional collision cell does not have enough time to refill with ions with the result that a decrease in signal intensity is observed.
  • Fig. 9 shows the effect of shortening the dwell time when using the preferred ion tunnel collision cell 1 on the intensity of ions observed with 10 ⁇ l loop injections of reserpine into 200 ⁇ l/min 50% Aqu. MeCN.
  • the interscan delay was set to 10 ms in all cases.
  • the upstream quadrupole Q1 (MS1) was set to transmit ions having a mass to charge ratio of 609 and the downstream quadrupole Q3 (MS2) was fixed to transmit ions having a mass to charge ratio of 195.
  • the fragmentation cell 1 was set to operate in a fragmentation mode (i.e. the fragmentation cell 1 was maintained at a DC bias of 35V relative to the ion source).
  • the fragmentation cell 1 equilibrates within approx. 3 ms and so has no problem operating at inter-scan delays of 10 ms unlike conventional collision cells without axial voltage gradients which can require an inter-scan delay of up to approx. 35 ms for maximum sensitivity.
  • Fig. 10 shows data relating to the fragmentation cell 1 being operated in a non-fragmenting mode without any collision gas being present in the fragmentation cell 1.
  • the DC bias was equal throughout the fragmentation cell 1 and was set to 3V i.e. no axial DC voltage gradient was maintained.
  • the amplitude of the RF voltage supply should be relatively low in order for these ions to be efficiently transmitted, whereas for ions of higher mass to charge ratio (e.g. 1081, 1544 and 2034) the amplitude of the RF voltage supply should be relatively high in order for those ions to be efficiently transmitted.
  • Fig. 12(a) shows the transmission characteristics for ions having a mass to charge ratio of 117
  • Fig. 12(b) for ions having a mass to charge ratio of 609
  • Fig. 12(c) for ions having a mass to charge ratio of 1081
  • Fig. 12(a) shows the transmission characteristics for ions having a mass to charge ratio of 117
  • Fig. 12(b) for ions having a mass to charge ratio of 609
  • Fig. 12(c) for ions having a mass to charge ratio of 1081
  • Fig. 12(a) shows the transmission characteristics for ions having a mass to charge ratio of 117
  • Fig. 12(b) for ions having a mass to charge ratio of 609
  • Fig. 12(c) for ions having a mass to charge ratio of 1081
  • the transmission characteristics show that in order to efficiently transmit ions having relatively low mass to charge ratios (e.g. 117) the amplitude of the RF voltage should be relatively low whereas in order to efficiently transmit ions having relatively high mass to charge ratios (e.g. 2034) the amplitude of the RF voltage should be relatively high. It is apparent therefore than when MS/MS experiments are performed wherein both high and low mass to charge ratio ions must be transmitted, the amplitude of the RF voltage should ideally be set to some intermediate value.
  • the amplitude of the RF voltage is linearly ramped from 50 V pp for ions having a mass to charge ratio of 2 up to 320 V pp for ions having a mass to charge ratio of 1000, and for ions having a mass to charge ratio > 1000 the amplitude of the RF voltage is preferably maintained at 320 V pp .
  • Fig. 13 shows the intensity of daughter ions having a mass to charge ratio of 173 produced by fragmenting a high mass cluster from NaRbCsI (having a mass to charge ratio of 2872) in a daughter ion MS/MS experiment as a function of the amplitude of the applied RF voltage with and without a 3V DC voltage difference being maintained along the length of the fragmentation cell 1.
  • the amplitude of the RF voltage required for maximum transmission is closer to that of the higher mass to charge ratio parent ion than that of the lower mass to charge ratio daughter ion.
  • the application of an axial DC voltage gradient improves the intensity of the signal compared with no axial DC voltage gradient. Similar results were obtained using PPG 3000 and also for lower mass parent ions.
  • One of the reasons for applying a DC voltage gradient across the fragmentation cell 1 is to decrease the transit time of ions travelling through the cell.
  • the transit time was measured using an oscilloscope attached to the detector head amplifier set to trigger off a change in mass program.
  • the time taken for the preferred fragmentation cell 1 to empty as a function of axial DC voltage gradient is shown in Fig. 14.
  • the empty time is reduced from about 150 ms with no applied DC voltage difference to about 400 ⁇ s for a DC voltage difference of 10V across the whole fragmentation cell 1.
  • the pressure in the fragmentation cell was 3 x 10 -3 mbar.
  • a conventional hexapole fragmentation cell typically has a 30 ms empty time. It will therefore be appreciated that by applying an axial DC voltage gradient to an ion tunnel fragmentation cell 1 shorter exit times can be obtained compared with those inherent with using a conventional multipole collision cell.
  • Fig. 15 compares neutral loss spectra obtained using a hexapole fragmentation cell (see Fig. 15(a)) with a fragmentation cell 1 according to the preferred embodiment (see Fig. 15(b)).
  • the sample was S-desmethyl metabolite formed by human liver microsomal incubation of Rabeprazole for 60 minutes. As is apparent, the sensitivity has improved by a factor of approximately x10 when using the fragmentation cell 1 according to the preferred embodiment.
  • Fig. 16 compares parent ion spectra obtained using a conventional hexapole fragmentation cell (see Fig. 16(a)) and a fragmentation cell 1 according to the preferred embodiment (see Fig. 16(b)).
  • the sample was a Sulphone metabolite formed by human liver microsomal incubation of Rabeprazole.
  • the sensitivity has increased by a factor x10 and also the resolution has greatly improved from over 25 amu to unit base resolution.
  • the ion tunnel fragmentation cell 1 according to the preferred embodiment therefore enables more sensitive and higher resolution mass spectra to be obtained.
  • Fig. 17 shows extracted ion chromatograms of Sulphone metabolite formed during microsomal incubation of Rabeprazole for 60 minutes.
  • Fig. 17(a) shows the results obtained with a conventional hexapole fragmentation cell, and
  • Fig. 17(b) shows the results obtained using a fragmentation cell 1 according to the preferred embodiment.

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  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
  • Electron Tubes For Measurement (AREA)
EP04026519A 2001-06-25 2002-06-24 Spectromètre de masse Expired - Lifetime EP1505634B1 (fr)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
GB0115429 2001-06-25
GB0115429A GB0115429D0 (en) 2001-06-25 2001-06-25 Mass spectrometers and methods of mass spectrometry
GB0120096A GB0120096D0 (en) 2001-06-25 2001-08-17 Mass spectrometers and methods of mass spectrometry
GB0120122 2001-08-17
GB0120122A GB0120122D0 (en) 2001-06-25 2001-08-17 Gas collision cell
GB0120096 2001-08-17
GB0206164 2002-03-15
GB0206164A GB0206164D0 (en) 2001-06-25 2002-03-15 Mass spectrometer
EP02254394.6A EP1271610B1 (fr) 2001-06-25 2002-06-24 Spectromètre de masse

Related Parent Applications (2)

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EP02254394.6A Division EP1271610B1 (fr) 2001-06-25 2002-06-24 Spectromètre de masse
EP02254394.6A Division-Into EP1271610B1 (fr) 2001-06-25 2002-06-24 Spectromètre de masse

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EP1505634A2 true EP1505634A2 (fr) 2005-02-09
EP1505634A3 EP1505634A3 (fr) 2006-05-24
EP1505634B1 EP1505634B1 (fr) 2012-08-22

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5206506A (en) * 1991-02-12 1993-04-27 Kirchner Nicholas J Ion processing: control and analysis
US5818055A (en) * 1996-07-12 1998-10-06 Bruker-Franzen Analytik Gmbh Method and device for injection of ions into an ion trap
US6107628A (en) * 1998-06-03 2000-08-22 Battelle Memorial Institute Method and apparatus for directing ions and other charged particles generated at near atmospheric pressures into a region under vacuum

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5206506A (en) * 1991-02-12 1993-04-27 Kirchner Nicholas J Ion processing: control and analysis
US5818055A (en) * 1996-07-12 1998-10-06 Bruker-Franzen Analytik Gmbh Method and device for injection of ions into an ion trap
US6107628A (en) * 1998-06-03 2000-08-22 Battelle Memorial Institute Method and apparatus for directing ions and other charged particles generated at near atmospheric pressures into a region under vacuum

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EP1505634B1 (fr) 2012-08-22
GB0120096D0 (en) 2001-10-10
GB0115429D0 (en) 2001-08-15

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