Multi-dimensional ion separation

Abstract

A sub-ambient gas pressure ion separation device is disclosed comprising: an ion entrance aperture having an axis therethrough that extends in a first direction, and an ion exit aperture; wherein the entrance aperture and exit aperture are spatially separated from each other in the first direction and in a second, orthogonal direction; and means for urging ions in said second direction as the ions travel in the first direction, said means for causing ions to separate in said second direction according to a physicochemical property such that ions having a first value, or first range of values, of the physicochemical property exit the device through the exit aperture and other ions having a different value, or different range of values, of said physicochemical property do not exit the device through the exit aperture.

Claims

1. An ion separation device configured to operate at sub-ambient gas pressure comprising: an ion entrance aperture having an axis therethrough that extends in a first direction, and an ion exit aperture; wherein the entrance aperture and exit aperture are spatially separated from each other in the first direction and in a second, orthogonal direction; means for urging ions through the device in said first direction; and means for urging ions in said second direction for causing ions to separate in said second direction according to a first physicochemical property such that ions having a first value, or first range of values, of the physicochemical property exit the device through the exit aperture and other ions having a different value, or different range of values, of said physicochemical property do not exit the device through the exit aperture.

2. The device of claim 1, wherein said sub-ambient gas pressure is a pressure lower than atmospheric pressure and is also selected from the group consisting of: 10.sup.4 mbar; 510.sup.4 mbar; 10.sup.3 mbar; 510.sup.3 mbar; 10.sup.2 mbar; between 10.sup.4 mbar and 10.sup.1 mbar; between 10.sup.4 mbar and 10.sup.2 mbar; 10.sup.1 mbar; 510.sup.2 mbar; 10.sup.2 mbar; 510.sup.3 mbar; and 10.sup.3 mbar.

3. The device of claim 1, wherein the device is configured such that there is substantially no gas flow through the device; and/or such that ions are not driven through the device by a gas flow.

4. The device of claim 1, comprising one or more RF voltage supply arranged and configured so as to apply RF voltages to the device so as to confine ions within the device in at least one dimension.

5. The device of claim 1, wherein ions having different first physicochemical property values are driven in the second direction at different rates.

6. The device of claim 1, wherein different ions are caused to travel in said first and/or second directions at different rates such that said ions having said first physicochemical property value(s) arrive at and pass through the exit aperture, whereas ions having said different physicochemical property value(s) do not arrive at the exit aperture.

7. The device of claim 1, comprising means for confining ions in said device in a third direction that is orthogonal to said first and second directions by applying RF and/or DC voltages to said device.

8. The device of claim 1, wherein the entrance aperture is spaced from the exit aperture in the first direction, in the second direction and in a third direction that is orthogonal to both said first and second directions; wherein the device comprises means for urging ions within the device in the third direction; and (i) wherein, in use, said means for urging ions in the third direction causes ions to separate in said third direction according to a second, different physicochemical property such that ions having a first value, or first range of values, of the second physicochemical property exit the device through the exit aperture and other ions having a different value, or different range of values, of said second physicochemical property do not exit the device through the exit aperture; or (ii) wherein, in use, said means for urging ions in the second and third directions both cause ions to separate according to the same, first physicochemical property but at different rates and such that ions having a first value, or first range of values, of the first physicochemical property exit the device through the exit aperture and other ions having a different value, or different range of values, of said first physicochemical property do not exit the device through the exit aperture.

9. The device of claim 8, further comprising means for urging ions through the device in said first direction, wherein said means for urging ions in said first direction, said means for urging ions in said second direction and said means for urging ions in said third direction either: (i) cause ions having a first combination of values for said first and second physicochemical properties to exit the device through the exit aperture and other ions having a second, different combination of values for said first and second physicochemical properties not to exit the device through the exit aperture; or (ii) cause ions having a first value or first range of values of the first physicochemical property to exit the device through the exit aperture and other ions having a different value or different range of values of said first physicochemical property not to exit the device through the exit aperture.

10. The device of claim 8, wherein different types of ions are caused to travel in said first and/or second and/or third directions at different rates such that some of said ions arrive at and pass through the exit aperture, whereas other, different types of ions do not arrive at the exit orifice.

11. The device of claim 1, wherein the device is configured such that ions are simultaneously separated in the first and second directions, or in the second and third directions, or in all of the first, second and third direction.

12. The device of claim 1, wherein the exit aperture is arranged in a wall of the device such that ions that are not transmitted through the exit aperture collide with said wall.

13. The device of claim 1, comprising control means for varying the force with which ions are urged in the first and/or second and/or third directions with time such that ions having different values of said first and/or second physicochemical property exit a given exit aperture at different times.

14. The device of claim 1, wherein said device comprises a further exit aperture that is coaxial with the entrance aperture for allowing ions to pass from the entrance aperture to the further exit aperture in a substantially straight line.

15. The device of claim 1, wherein the device comprises multiple exit apertures that are spaced apart from the entrance aperture in the first direction, and: i) wherein the multiple exit apertures are spaced apart from the entrance aperture by different distances in the second direction: and/or ii) wherein the multiple exit apertures are spaced apart from the entrance aperture by different distances in the third direction orthogonal to said first and second directions; and/or iii) wherein at least one of the multiple exit apertures is spaced apart from the entrance aperture in the second direction and at least one other of the multiple exit apertures is spaced apart from the entrance aperture in the third direction.

16. The device of claim 15, comprising control means for varying the force with which ions are urged in the first and/or second and/or third directions with time such that ions having the same value of said first and/or second physicochemical property exit different exit apertures at different times.

17. The device of claim 1, wherein said first physicochemical property is ion mobility and ions separate in the first and/or second and/or third direction according to their ion mobility; or wherein the ions are separated in the first and/or second and/or third directions according to different separation techniques, said different separation techniques optionally being selected from the list consisting of: low electric field ion mobility separation; high electric field ion mobility separation; differential mobility separation; and ion mobility separation by driving the ions through a gas using a potential barrier.

18. The device of claim 1, comprising means for driving ions in the first direction by travelling one or more DC voltage in the first direction.

19. An ion mobility spectrometer or a mass spectrometer comprising a device as claimed in claim 1.

20. A method of separating ions at sub-ambient gas pressure using an ion separation device configured to operate at sub-ambient gas pressure including an ion entrance aperture having an axis therethrough that extends in a first direction, and an ion exit aperture; wherein the entrance aperture and exit aperture are spatially separated from each other in the first direction and in a second, orthogonal direction, said method comprising urging ions in said first direction, and urging ions in said second direction as the ions travel in the first direction such that ions separate in said second direction according to a physicochemical property and so that ions having a first value, or first range of values, of the physicochemical property exit the device through the exit aperture and other ions having a different value, or different range of values, of said physicochemical property do not exit the device through the exit aperture.

21. A method of ion mobility spectrometry or mass spectrometry comprising a method as claimed in claim 20.

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 a separation device according to a first embodiment of the present invention operating in a first mode;

(3) FIGS. 2A and 2B shows the separation device of FIG. 1 operating in a second mode; and

(4) FIG. 3 shows a separation device according to a second embodiment of the present invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENT

(5) FIG. 1 shows a schematic of a separation device according to a preferred embodiment of the present invention. The separation device comprises an ion entrance aperture 2 in the wall 4 of one side of the device, and first and second ion exit apertures 6,8 in the wall 10 on the opposite side of the device. The ion entrance aperture 2 and the first exit aperture 6 are arranged so as to be coaxial, such that ions may pass in a straight line from the ion entrance aperture 2 to the first ion exit aperture 6.

(6) In the first mode of operation shown in FIG. 1, ions pass through the device in a first direction from the ion entrance aperture 2 to the first exit aperture 6. This is illustrated by arrow 12 in FIG. 1. The ions are desirably not separated according to a physicochemical property as they pass from the entrance aperture 2 to the first exit aperture 6. This mode offers an off or bypass state of the separation device. Ions may or may not be driven through the device in the first direction in this mode. Such a driving force is illustrated by arrow 14 in FIG. 1.

(7) However, less preferably, the ions may be separated in the first mode according to a physicochemical property as they pass through the device in the first direction from the ion entrance aperture 2 to the first exit aperture 6. The ions may separate axially along the axis through the entrance aperture 2 and the first exit aperture 6 according to said physicochemical property. The duration of time between any given ion entering the device through the entrance aperture 2 and exiting the device through the first exit aperture 6 may be used to determine the physicochemical property of that ion. Ions may be driven along the axis extending between the entrance aperture 2 and the first exit aperture 6 in this mode. By way of example, in the first mode the device may pulse one or more packets of ions into the entrance aperture 2. The ions in each packet may then separate according to their ion mobility through a gas that is present in the device between the entrance aperture 2 and first exit aperture 6. The ions may be driven through the gas by applying electrical potentials to the device, such as by applying a static voltage gradient between the entrance aperture 2 and the first exit aperture 6.

(8) FIG. 2A shows the device of FIG. 1 when being operated in a second mode of operation. According to this mode of operation a separation force 16 is applied to the ions in a second direction that extends in a direction from the first exit aperture 6 to the second exit aperture 8, as the ions pass through the device in the first direction (i.e. pass from the entrance aperture 2 towards the exit apertures 6,8). This causes the ions to separate in the second direction according to a physicochemical property as they pass through the device. Preferentially, the driving force is simultaneously applied so as to drive the ions in the first direction.

(9) Ions are transmitted from the entrance aperture 2 in the first side 4 of the device to the second side 10 of the device. Ions which have been driven by said separation force 16 in the second direction to the location of the second exit aperture 8 at the time that these ions reach the second side 10 of the device are able to leave the device through the second exit aperture 8. These ions are illustrated by arrow 18 in FIG. 2A. Other ions are not able to leave the device. These ions are illustrated by arrows 20 and 22 in FIG. 2A. Accordingly, the type of ions that exit the device through the second exit aperture 8 will depend upon the magnitude of the separation force 16 applied in the second direction. As the driving force 14 in the first direction is also preferentially applied in the second mode, then the type of ions that exit the second exit aperture 8 will also depend upon the magnitude or nature of the driving force 14. It is therefore possible to determine said physicochemical property of ions exiting the second exit aperture 8 from the magnitude of the separation force 16 in the second direction and from the driving force 14.

(10) FIG. 2B is a plan view of the embodiment shown in FIG. 2A and illustrates the criteria for transmission of an ion species from the entrance aperture 2 to the second exit aperture 8. It can be assumed that it takes an ion species a time t.sub.1 to be transmitted in the first direction from the entrance aperture 2 to the plate 10 containing the second exit aperture 8, under the influence of the driving force 14 in the first direction. It can also be assumed that it takes an ion species a time t.sub.2 to be transmitted from the entrance aperture 2 to the second exit aperture 8 in the second direction, under the influence of the separation force 16 in the second direction. For an ion species to be transmitted from the entrance aperture 2 to the exit aperture 8 then t.sub.1 and t.sub.2 must be equivalent, as shown by the central ion path 18 in FIG. 2B. If the time t.sub.1 is not equivalent to time t.sub.2 then the ions cannot exit the exit aperture 8, as shown by the leftmost 20 and rightmost 22 ion paths in FIG. 2B.

(11) The magnitude of the driving force 14 in the first direction and/or separation force 16 in the second direction may be varied with time in order to cause ions having different values of said physicochemical property to exit the device through the second exit aperture 8 at different times. The driving force 14 and/or separation force 16 may be scanned with time and the physicochemical property value of the ions detected as exiting the device through the second exit aperture 8 at any given time may be determined from the driving force 14 and/or separation force 16 present at the time that these ions are transmitted through the device.

(12) FIG. 3 shows another embodiment of the present invention that is the same as that of FIGS. 1 and 2, except that a third exit aperture 30 is provided in the second side 10 of the device. The device of FIG. 3 may be operated in the same modes as described above in relation to FIGS. 1 and 2. More specifically, the ions may be transmitted in the first direction from the entrance aperture 2 to the first exit aperture 6. Alternatively, a first separation force 16 may be applied in the second direction so as to cause ions to exit the device through the second exit aperture 8, as described above in relation to FIGS. 2A and 2B. The device of FIG. 3 may be operated in a third mode in which said first separation force 16 is applied in the second direction and a second separation force 28 is also applied in a third direction that extends in a direction from said second exit aperture 8 to said third exit aperture 30. This second separation force 28 causes the ions to separate in the third direction according to a physicochemical property as they pass through the device. Optionally, the driving force 14 of the first mode is simultaneously applied.

(13) Ions are transmitted from the entrance aperture 2 in the first side 4 of the device to the second side 10 of the device. Ions which have been driven by said driving force 14 and said first and second separation forces 16,28 to the location of the third exit aperture 30 at the time that these ions reach the second side 10 of the device are able to leave the device through the third exit aperture 30. Other ions are not able to leave the device. Accordingly, the type of ions that exit the device through the third exit aperture 30 will depend upon the magnitude and nature of the driving force 14 and the first and second separation forces 16,28. It is therefore possible to determine said physicochemical property of ions exiting the third exit aperture 30 from the driving force 14, first separation force 16 and second separation force 28.

(14) According to this embodiment, in order for an ion to be transmitted from the entrance aperture 2 to the third exit aperture 30, the time it takes for the ion to be transmitted from the entrance aperture 2 to the third exit aperture 30 in the third direction under the influence of the second separation force 28 in the third direction must be equivalent to t.sub.1 and t.sub.2 described above in relation to FIG. 2B.

(15) The first separation force 16 and the second separation force 28 optionally separate the ions according to different physicochemical properties, or may separate the ions at different rates according to the same physicochemical property. For example, the first separation force 16 may separate the ions according to low electric field ion mobility and the second separation force 28 may separate the ions according to high electric field ion mobility. The driving force 14 may also separate the ions according to the same physicochemical property as one or both of the separation forces 16,28, or by a different physicochemical property. However, it is preferred that the driving force 14 does not separate the ions. For example, the driving force 14 may be generated by a gas flow or a DC potential that moves along the device in the first direction so as to drive the ions in the first direction.

(16) The magnitude (or other property) of the driving force 14 in the first direction and/or first separation force 16 in the second direction and/or second separation force 28 in the third direction may be varied with time in order to cause ions having different values of said physicochemical property (or physicochemical properties) to exit the device through the third exit aperture 30 at different times. The driving force 14 and/or first separation force 16 and/or second separation force 28 may be scanned with time and the physicochemical property value (or values of the different physicochemical properties) of the ions detected as exiting the device through the third exit aperture 30 at any given time may be determined from the driving force 14 and/or first separation force 16 and/or second separation force 28 present at the time that these ions are transmitted through the device.

(17) In any of the above embodiments, the driving force 14 and/or first separation force 16 and/or second separation force 28 may be varied in time so as to provide sequential selection of ion species exiting the device, for example, for full spectrum analysis or to synchronise with subsequent analytical analyses.

(18) In any of the above embodiments, the driving force 14 may or may not cause the ions to disperse or separate according to any physicochemical property. For example, the driving force may be provided by a gas flow in the first direction or by travelling a potential barrier (e.g. DC barrier) along the device in the first direction that urges the ions through the device in the first direction. Such techniques may be used so as not to encourage dispersion of the ions in the first direction. Alternatively, the ions can be caused to disperse in the first direction, for example, by applying a DC potential gradient in the first direction.

(19) In any of the above embodiments, the physicochemical property that the ions are separated by may be ion mobility. The driving force 14 and/or first separation force 16 and/or second separation force 28 may provide ion mobility separation. For example, the driving force 14 and/or first separation force 16 and/or second separation force 28 may provide low electric field ion mobility separation, high electric field ion mobility separation, differential mobility separation (DMS), or ion mobility separation by driving the ions through a gas using a potential barrier (e.g. DC barrier) that is travelled along the device. As described above in relation to the third mode of operation, different separation techniques may be used to separate the ions in the second and third directions (and less preferably the first direction).

(20) In any of the above embodiments, the physicochemical property by which ions are separated (in one or more of the directions) may be mass to charge ratio. The driving force 14 and/or first separation force 16 and/or second separation force 28 may provide separation according to mass to charge ratio.

(21) Desirably, the driving force 14 and/or first separation force 16 and/or second separation force 28 separate ions according to different physicochemical properties.

(22) The driving force 14 and/or first separation force 16 and/or second separation force 28 may be provided by time and/or spatially varying electric fields.

(23) The driving force 14 and/or first separation force 16 and/or second separation force 28 may result in different functional dependencies of a physicochemical property in both space and/or time.

(24) For example, as described above in relation to FIG. 2B, the condition for ion transmission is that the transit times in the first and second directions must be equivalent for transmission through the second exit orifice 8. In the simplest case, the force 14 in the first direction will be non-separative and the transit time will be a constant, A, for all species, i.e. t.sub.1=A. If the separative force 16 in the second direction is, for example, low field drift tube ion mobility then t.sub.2=L/(KE), where L is the distance between the entrance aperture 2 and second exit aperture 8 in the second direction, E is the electric field strength in the second direction and K is the mobility value of the ion. Consequently, for transmission, an ion species must have a mobility, K=L/(AE). Operating with different values of A or E will transmit different ion species through the second exit aperture 8.

(25) In more selective modes of operation, for example, the force 14 in the first direction will also be separative, such that t.sub.1 is a function of a physicochemical property, P. Then t.sub.1=fn(P) and for transmission of ion species i, its mobility K.sub.i must equal L/(fn(P.sub.i).E). The ions can be separated in the two directions by different physicochemical properties or they can be separated by the same property but with different temporal and/or spatial functional dependence as a consequence of the nature of the applied separation forces. For example, ions may be separated in one direction by low field drift tube ion mobility in which the separation time t1/K, whereas ions may be separated in another direction by travelling wave ion mobility separation in which the separation time t1/K.sup.2. The device may be constructed from RF ion guides or surfaces to ensure minimal ion losses in dimensions where ion separation is not occurring. For example, in the arrangements shown in FIGS. 1 and 2 electrodes may be arranged above and below the device and RF voltages may be applied to such electrodes so as to confine ions within the device in a direction between the top and bottom of the device.

(26) Preferably, the device is operated at sub-atmospheric pressure.

(27) The device can be arranged such that the driving and separating force(s) can be in any combination of orthogonal directions within the device.

(28) Ion delivery into the device may be continuous or discontinuous, for example by trapping and then releasing ions into the device.

(29) In less desired methods, initially no driving force is employed in the first direction and ions are injected in a pulsed packet through the entrance aperture and their distance of penetration into the device in said first direction prior to cooling is dependent on a physicochemical property, thereby providing spatially separated ion species. Subsequently, the driving force in the first direction may be activated, in conjunction with one or both of the orthogonal separating forces in the second and/or third directions so as to cause the spatially separated ions to be ejected from the device. Alternatively, the driving force could be continually operated but at a sufficiently low magnitude such that when ion separation is occurring in the first direction the driving force urges ions through the device in the first direction in a transit time that is longer than the time required for the spatial separation in the first direction to establish.

(30) In less preferred methods, initially no driving force is employed in the first direction and ions are injected in a pulsed packet through the entrance aperture with sufficiently high energy to induce ion fragmentation and the distance of penetration into the device in said first direction prior to cooling is dependent on physicochemical properties of the precursor and fragment ions, thereby providing spatially separated ion species. Subsequently, the driving force in the first direction could be activated, in conjunction with one or both of the orthogonal separating forces so as to cause the spatially separated ions to be ejected from the device. Alternatively, the driving force could be continually operated but at a sufficiently low magnitude such that when ion separation in the first direction is occurring the driving force urges ions through the device in the first direction in a transit time that is longer than the time required for the spatial separation in the first direction to establish. This mode of operation provides separation both in time or position-of-birth of fragment ions and their mobility.

(31) 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.

(32) For example, although the various driving and separation forces have been described as being applied in orthogonal directions, these forces may be applied at other angles to each other.