Device allowing improved reaction monitoring of gas phase reactions in mass spectrometers using an auto ejection ion trap

Abstract

A collision or reaction device for a mass spectrometer is disclosed comprising a first device arranged and adapted to cause first ions to collide or react with charged particles and/or neutral particles or otherwise dissociate so as to form second ions. A second device is arranged and adapted to apply a broadband excitation with one or more frequency notches to the first device so as to cause the second ions and/or ions derived from the second ions to be substantially ejected from the collision or reaction region. The collision or reaction device further comprises a device arranged and adapted to determine the time when the second ions and/or ions derived from the second ions are substantially ejected from the first device.

Claims

1. A collision or reaction device for a mass spectrometer comprising: a first device arranged and adapted to cause first ions to collide or react with charged particles or neutral particles or otherwise dissociate in a collision or reaction region so as to form second ions; a second device arranged and adapted to apply a broadband excitation with one or more frequency notches to said first device so as to cause said second ions or ions derived from said second ions to be substantially ejected from said collision or reaction region; and a device arranged and adapted to determine when said second ions or ions derived from said second ions are substantially ejected from said first device.

2. A collision or reaction device as claimed in claim 1, wherein said charged particles comprise ions.

3. A collision or reaction device as claimed in claim 2, wherein said collision or reaction device comprises an ion-ion collision or reaction device.

4. A collision or reaction device as claimed in claim 3, wherein said first ions are caused to interact with reagent ions via Electron Transfer Dissociation (ETD) so as to form said second ions.

5. A collision or reaction device as claimed in claim 1, wherein said charged particles comprise electrons.

6. A collision or reaction device as claimed in claim 5, wherein said collision or reaction device comprises an ion-electron collision or reaction device.

7. A collision or reaction device as claimed in claim 1, wherein said collision or reaction device comprises an ion-molecule collision or reaction device.

8. A collision or reaction device as claimed in claim 7, wherein said first ions are caused to interact with gas molecules and fragment via Collision Induced Dissociation (CID) to form said second ions.

9. A collision or reaction device as claimed in claim 7, wherein said first ions are caused to interact with deuterium via Hydrogen-Deuterium exchange (HDx) to form said second ions.

10. A collision or reaction device as claimed in claim 1, wherein said collision or reaction device comprises an ion-metastable collision or reaction device.

11. A collision or reaction device as claimed in claim 1, wherein said collision or reaction device comprises a gas phase collision or reaction device.

12. A collision or reaction device as claimed in claim 1, wherein said collision or reaction device comprises a linear or 2D ion trap.

13. A collision or reaction device as claimed in claim 12, wherein said collision or reaction device comprises a quadrupole rod set ion guide or ion trap.

14. A collision or reaction device as claimed in claim 1, wherein said collision or reaction device comprises a 3D ion trap.

15. A collision or reaction device as claimed in claim 1, further comprising a device for applying a radially dependent trapping potential across at least a portion of said first device.

16. A collision or reaction device as claimed in claim 1, further comprising a device arranged and adapted to maintain an axial DC voltage gradient or to apply one or more transient DC voltages to said first device in order to urge ions in a direction within said first device.

17. A mass spectrometer comprising a collision or reaction device as claimed in claim 1.

18. A method of colliding or reacting ions with a first device, said method comprising: causing first ions to collide or react with charged particles or neutral particles or otherwise dissociate in a collision or reaction region of said first device so as to form second ions; applying a broadband excitation with one or more frequency notches to said first device so as to cause said second ions or ions derived from said second ions to be substantially ejected from said collision or reaction region of said first device; and determining when said second ions or ions derived from said second ions are substantially ejected from said first device.

19. A method of mass spectrometry comprising a method of colliding or reacting ions as claimed in claim 18.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Various embodiments of the present invention will now be described, by way of example only, and with reference to the accompanying drawings in which:

(2) FIG. 1 shows an ion guide, ion trap or collision or reaction device according to an embodiment of the present invention; and

(3) FIG. 2A shows an embodiment wherein different species of analyte ions are arranged to interact with reagent ions, FIG. 2B shows initial first fragment ions being axially ejected at a first time and FIG. 2C shows subsequent second fragment ions which are formed after a longer interaction time than the first fragment ions being axially ejected at a second later time.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

(4) A preferred embodiment of the present invention will now be described.

(5) According to a preferred embodiment a quadrupole rod set ion guide is preferably provided as shown in FIG. 1 comprising four rod electrodes 1. Trap electrodes 2 are preferably provided at an exit region and ions are preferably confined within the ion guide in a radially dependent manner.

(6) A radial dependent barrier (as disclosed, for example, in US 2007/10181804 and GB-467466) is preferably provided by applying appropriate voltages to the trap electrodes 2.

(7) A broadband excitation containing missing frequencies or notches is preferably applied to the electrodes 1 in order to radially excite a plurality ions in a manner such as is disclosed, for example, in U.S. Pat. No. 5,324,939 and WO 2006/054101. The ions which are radially excited are not lost to the rods 1 but instead are preferably axially ejected and are preferably transported to a downstream mass analyser.

(8) In use parent or precursor ions are preferably introduced into the quadrupole ion guide or ion trap and a radially dependent trapping potential is preferably applied or otherwise maintained in order to confine the parent or precursor ions within the ion guide or ion trap. A broadband excitation having frequency components missing in its frequency spectrum which correspond to the secular frequency of the parent or precursor ions is preferably applied to the electrodes 1 of the ion guide. Ions may be pulsed into the device from an upstream mass to charge ratio filter (not shown).

(9) According to a less preferred embodiment the ion guide preferably also contain reagent molecules in the case of an ion-molecule reaction.

(10) According to another embodiment, reagent ions may be introduced and one or more additional frequency notches may be provided in the excitation frequencies applied to the quadrupole ion guide rods so that the reagent ions are not ejected.

(11) FIG. 2A shows a schematic of an ion-ion reaction such as Electron Transfer Dissociation (ETD) according to an embodiment of the present invention. Two parent or precursor ions A,B preferably having similar mass to charge ratios may fragment to give different product or fragment ions D,E and the different reaction times can be measured by measuring the time taken for either of these product or fragment ions to form and preferably be auto-ejected from the ion guide, ion trap or collision or reaction device.

(12) With reference to FIG. 2A two parent or precursor ions A,B preferably having similar mass to charge ratio are shown being introduced into the ion guide, ion trap or collision or reaction device and are preferably trapped on the centre line. Reagent ions C of opposite polarity are also preferably introduced into the ion guide, ion trap or collision or reaction device and preferably interact with the analyte ions A,B. If the reaction time of parent or precursor ions A with reagent ions C is shorter than the reaction time of parent or precursor ions B with reagent ions C then initially parent or precursor ions A will interact with reagent ions C and will fragment to form first fragment ions D.

(13) First fragment ions D are preferably produced and are preferably ejected from the ion guide, ion trap or collision or reaction device before parent or precursor ions B react with the reagent ions C as shown in FIG. 2B.

(14) The time taken for parent or precursor ions A to interact with reagent ions C may be measured by monitoring the appearance time of first product or fragment ions D of the reaction. Similarly, the time taken for parent or precursor ions B to react with reagent ions C and fragment to form second or further fragment ions E may also be determined as shown in FIG. 2C.

(15) Once either precursor ions A,B have reacted with the reagent ions C to form fragment ions D,E, the fragment ions D,E are preferably radially excited and efficiently removed/ejected from the ion guide, ion trap or collision or reaction device. The fragment ions may be analysed by a downstream analyser and the corresponding reaction time(s) may be determined.

(16) When not in use the system preferably operates as normal with no detrimental effects to for example resolution or sensitivity.

(17) According to an embodiment a gas phase Hydrogen-Deuterium exchange (HDx) experiment may be performed wherein the broadband excitation may be applied with missing frequencies corresponding to the mass to charge ratio of the analyte ions. By applying additional missing frequencies the exchange reaction may be forced to continue until a predetermined number of exchanges have occurred. Probing the time taken to reach this number of exchanges preferably yields information about conformations that would otherwise be unavailable. Alternatively, a single frequency or small band of frequencies may be applied to cause ejection of the targeted Hydrogen-Deuterium exchange species.

(18) It is also possible to monitor reaction times in Collision Induced Dissociation (CID) based experiments by appropriate choice of the directions of tickle in devices with radially and directionally dependent barriers.

(19) Alternatively or additionally, the temporal profile may be used as a means of separating a mixture of parent or precursor ions. For example, if more than one parent or precursor exists within an isolation window and they have different reactions times or profiles then this difference may be utilised to separate the parent or precursor ions.

(20) In another mode of operation the reaction products are preferably removed only when multiple or targeted reactions have taken place.

(21) Other ion reactions such as photo-dissociation can also be used for this method.

(22) Other methods of auto-ejection such as RF based instability may also be used.

(23) Other ion traps such as flat traps with quadratic DC wells may also be used.

(24) Although the present invention has been described with reference to preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the scope of the invention as set forth in the accompanying claims.