Piezo-electric vibration on an in-source surface ionization structure to aid secondary droplet reduction

Abstract

An ion source is disclosed comprising a nebulizer and a target. The nebulizer is arranged and adapted to emit, in use, a stream of analyte droplets which are caused to impact upon the target and to ionize analyte to form a plurality of analyte ions. The target is vibrated by a piezo-electric vibration device to reduce the size of resultant secondary droplets.

Claims

1. An ion source comprising: one or more nebulisers and one or more targets; and a vibration device arranged and adapted to cause said one or more targets to vibrate; wherein said one or more nebulisers are arranged and adapted to emit, in use, a stream predominantly of droplets which are caused to impact upon said one or more targets and to ionise said droplets to form a plurality of ions wherein said vibration device is arranged and adapted to vibrate said one or more targets at a frequency f selected from the group consisting of: (i) <1 kHz; (ii) 1-2 kHz; (iii) 2-3 kHz; (iv) 3-4 kHz; (v) 4-5 kHz; (vi) 5-6 kHz; (vii) 6-7 kHz; (viii) 7-8 kHz; (ix) 8-9 kHz; (x) 9-10 kHz; (xi) 10-11 kHz; (xii) 11-12 kHz; (xiii) 12-13 kHz; (xiv) 13-14 kHz; (xv) 14-15 kHz; (xvi) 15-16 kHz; (xvii) 16-17 kHz; (xviii) 17-18 kHz; and (xix) 18-19 kHz.

2. An ion source as claimed in claim 1, wherein said vibration device is arranged and adapted to cause said one or more targets to vibrate in order to reduce the size of resultant secondary droplets through surface disruption.

3. An ion source as claimed in claim 1, wherein said vibration device comprises a piezo-electric vibration source.

4. An ion source as claimed in claim 1, wherein said droplets comprise analyte droplets and said plurality of ions comprise analyte ions.

5. An ion source as claimed in claim 1, wherein said droplets comprise reagent droplets and said plurality of ions comprise reagent ions.

6. An ion source as claimed in claim 1, wherein an analyte liquid is supplied to said one or more targets and is ionised to form a plurality of analyte ions or a reagent liquid is supplied to said one or more targets and is ionised to form reagent ions which transfer charge to neutral analyte atoms or molecules to form analyte ions or which enhance the formation of analyte ions; wherein: said one or more targets comprise one or more apertures and wherein said analyte liquid or said reagent liquid is supplied directly to said one or more targets and emerges from said one or more apertures.

7. An ion source as claimed in claim 1, wherein said one or more targets are coated with one or more liquid, solid or gelatinous analytes and wherein said one or more analytes are ionised to form a plurality of analyte ions.

8. An ion source as claimed in claim 1, wherein said one or more targets are formed from one or more analytes and wherein said one or more analytes are ionised to form a plurality of analyte ions.

9. An ion source as claimed in claim 1, wherein said ion source comprises an Atmospheric Pressure Ionisation (API) ion source.

10. An ion source as claimed in claim 1, wherein said one or more nebulisers are arranged and adapted such that the majority of the mass or matter emitted by said one or more nebulisers is in the form of droplets not vapour; wherein: at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the mass or matter emitted by said one or more nebulisers is in the form of droplets.

11. An ion source as claimed in claim 1, wherein said one or more nebulisers are arranged and adapted to emit a stream of droplets wherein the Sauter mean diameter of said droplets is in a range: (i) <5 m; (ii) 5-10 m; (iii) 10-15 m; (iv) 15-20 m; (v) 20-25 m; or (vi) >25 m.

12. An ion source as claimed in claim 1, wherein said stream of droplets emitted from said one or more nebulisers forms a stream of secondary droplets after impacting said one or more targets; wherein: said stream of droplets or said stream of secondary droplets traverse a flow region with a Reynolds number (Re) in the range: (i) <2000; (ii) 2000-2500; (iii) 2500-3000; (iv) 3000-3500; (v) 3500-4000; or (vi) >4000.

13. An ion source as claimed in claim 1, wherein at the point of said droplets impacting said one or more targets said droplets have one or more of the following: a Weber number (We) selected from the group consisting of: (i) <50; (ii) 50-100; (iii) 100-150; (iv) 150-200; (v) 200-250; (vi) 250-300; (vii) 300-350; (viii) 350-400; (ix) 400-450; (x) 450-500; (xi) 500-550; (xii) 550-600; (xiii) 600-650; (xiv) 650-700; (xv) 700-750; (xvi) 750-800; (xvii) 800-850; (xviii) 850-900; (xix) 900-950; (xx) 950-1000; and (xxi) >1000; and a Stokes number (S.sub.k) in the range: (i) 1-5; (ii) 5-10; (iii) 10-15; (iv) 15-20; (v) 20-25; (vi) 25-30; (vii) 30-35; (viii) 35-40; (ix) 40-45; (x) 45-50; and (xi) >50.

14. An ion source as claimed in claim 1, wherein the mean axial impact velocity of said droplets upon said one or more targets is selected from the group consisting of: (i) <20 m/s; (ii) 20-30 m/s; (iii) 30-40 m/s; (iv) 40-50 m/s; (v) 50-60 m/s; (vi) 60-70 m/s; (vii) 70-80 m/s; (viii) 80-90 m/s; (ix) 90-100 m/s; (x) 100-110 m/s; (xi) 110-120 m/s; (xii) 120-130 m/s; (xiii) 130-140 m/s; (xiv) 140-150 m/s; and (xv) >150 m/s; or said one or more targets are arranged <20 mm, <19 mm, <18 mm, <17 mm, <16 mm, <15 mm, <14 mm, <13 mm, <12 mm, <11 mm, <10 mm, <9 mm, <8 mm, <7 mm, <6 mm, <5 mm, <4 mm, <3 mm or <2 mm from the exit of said one or more nebulisers.

15. An ion source as claimed in claim 1, wherein said one or more nebulisers are arranged and adapted to nebulise one or more eluents emitted by one or more devices over a period of time; wherein: said one or more devices comprise one or more liquid chromatography separation devices.

16. An ion source as claimed in claim 1, wherein said one or more nebulisers comprise: one or more rotating disc nebulisers; or a first capillary tube having an exit which emits, in use, said stream of droplets.

17. An ion source as claimed in claim 16, further comprising one or more heaters which are arranged and adapted to supply one or more heated streams of gas to the exit of said one or more nebulisers; wherein either: (i) said one or more heaters surround said first capillary tube and are arranged and adapted to supply a heated stream of gas to the exit of said first capillary tube; or (ii) said one or more heaters comprise one or more infra-red heaters; or (iii) said one or more heaters comprise one or more combustion heaters.

18. An ion source as claimed in claim 1, further comprising one or more heating devices arranged and adapted to directly or indirectly heat said one or more targets; wherein: said one or more heating devices comprise one or more lasers arranged and adapted to emit one or more laser beams which impinge upon said one or more targets in order to heat said one or more targets.

19. An ion source as claimed in claim 1, wherein in a mode of operation said one or more targets are maintained at: a positive potential and wherein said droplets impacting upon said one or more targets form a plurality of positively charged ions; or a negative potential and wherein said droplets impacting upon said one or more targets form a plurality of negatively charged ions.

20. An ion source as claimed in claim 1, further comprising a device arranged and adapted to apply a sinusoidal or non-sinusoidal AC or RF voltage to said one or more targets.

21. An ion source as claimed in claim 1, wherein said one or more targets are arranged or otherwise positioned so as to deflect said stream of droplets or said plurality of ions towards an ion inlet device of a mass spectrometer.

22. An ion source as claimed in claim 1, wherein said one or more targets are positioned upstream of an ion inlet device of a mass spectrometer so that ions are deflected towards the direction of said ion inlet device.

23. An ion source as claimed in claim 1, wherein said one or more targets comprise a stainless steel target, a metal, gold, a non-metallic substance, a semiconductor, a metal or other substance with a carbide coating, an insulator or a ceramic.

24. An ion source as claimed in claim 1, wherein said one or more targets comprise a plurality of target elements so that droplets from said one or more nebulisers cascade upon a plurality of target elements or wherein said target is arranged to have multiple impact points so that droplets are ionised by multiple glancing deflections.

25. An ion source as claimed in claim 1, wherein said one or more targets are shaped or have an aerodynamic profile so that gas flowing past said one or more targets is directed or deflected towards, parallel to, orthogonal to or away from an ion inlet device of a mass spectrometer; wherein: at least some or a majority of said plurality of ions are arranged so as to become entrained, in use, in said gas flowing past said one or more targets.

26. An ion source as claimed in claim 1, wherein in a mode of operation droplets from one or more reference or calibrant nebulisers are directed onto said one or more targets.

27. An ion source as claimed in claim 1, wherein in a mode of operation droplets from one or more analyte nebulisers are directed onto said one or more targets.

28. A mass spectrometer comprising an ion source as claimed in claim 1.

29. A method of ionising a sample comprising: causing a stream predominantly of droplets to impact upon one or more targets to ionise said droplets to form a plurality of analyte ions; and vibrating said one or more targets at a frequency f selected from the group consisting of: (i) <1 kHz; (ii) 1-2 kHz; (iii) 2-3 kHz; (iv) 3-4 kHz; (v) 4-5 kHz; (vi) 5-6 kHz; (vii) 6-7 kHz; (viii) 7-8 kHz; (ix) 8-9 kHz; (x) 9-10 kHz; (xi) 10-11 kHz; (xii) 11-12 kHz; (xiii) 12-13 kHz; (xiv) 13-14 kHz; (xv) 14-15 kHz; (xvi) 15-16 kHz; (xvii) 16-17 kHz; (xviii) 17-18 kHz; and (xix) 18-19 kHz.

30. A method of mass spectrometry comprising a method of ionising ions as claimed in claim 29.

31. A mass spectrometer comprising: an ion source including: a target; a vibration device arranged and adapted to cause said target to vibrate; and a nebuliser configured to emit, in use, a stream formed predominantly of droplets which are caused to impact upon the target and to ionise the droplets to form a plurality of ions; wherein said vibration device is arranged and adapted to vibrate said target at a frequency f selected from the group consisting of: (i) <1 kHz; (ii) 1-2 kHz; (iii) 2-3 kHz; (iv) 3-4 kHz; (v) 4-5 kHz; (vi) 5-6 kHz; (vii) 6-7 kHz; (viii) 7-8 kHz; (ix) 8-9 kHz; (x) 9-10 kHz; (xi) 10-11 kHz; (xii) 11-12 kHz; (xiii) 12-13 kHz; (xiv) 13-14 kHz; (xv) 14-15 kHz; (xvi) 15-16 kHz; (xvii) 16-17 kHz; (xviii) 17-18 kHz; and (xix) 18-19 kHz.

32. An ion source comprising: a target; a vibration device arranged and adapted to cause said target to vibrate; and a nebuliser configured to emit, in use, a stream formed predominantly of droplets which are caused to impact upon the target and to ionise the droplets to form a plurality of ions; wherein said vibration device is arranged and adapted to vibrate said target at a frequency f selected from the group consisting of: (i) <1 kHz; (ii) 1-2 kHz; (iii) 2-3 kHz; (iv) 3-4 kHz; (v) 4-5 kHz; (vi) 5-6 kHz; (vii) 6-7 kHz; (viii) 7-8 kHz; (ix) 8-9 kHz; (x) 9-10 kHz; (xi) 10-11 kHz; (xii) 11-12 kHz; (xiii) 12-13 kHz; (xiv) 13-14 kHz; (xv) 14-15 kHz; (xvi) 15-16 kHz; (xvii) 16-17 kHz; (xviii) 17-18 kHz; and (xix) 18-19 kHz.

33. A method of mass spectrometry comprising: ionising a sample by generating a stream predominantly foillied of droplets and ionising the droplets to form a plurality of ions by impacting the droplets upon one or more targets; and vibrating said one or more targets at a frequency f selected from the group consisting of: (i) <1 kHz; (ii) 1-2 kHz; (iii) 2-3 kHz; (iv) 3-4 kHz; (v) 4-5 kHz; (vi) 5-6 kHz; (vii) 6-7 kHz; (viii) 7-8 kHz; (ix) 8-9 kHz; (x) 9-10 kHz; (xi) 10-11 kHz; (xii) 11-12 kHz; (xiii) 12-13 kHz; (xiv) 13-14 kHz; (xv) 14-15 kHz; (xvi) 15-16 kHz; (xvii) 16-17 kHz; (xviii) 17-18 kHz; and (xix) 18-19 kHz.

34. A method of ionising a sample comprising generating a stream predominantly formed of droplets and ionising the droplets to form a plurality of ions by impacting the droplets upon one or more targets and vibrating said one or more targets at a frequency f selected from the group consisting of: (i) <1 kHz; (ii) 1-2 kHz; (iii) 2-3 kHz; (iv) 3-4 kHz; (v) 4-5 kHz; (vi) 5-6 kHz; (vii) 6-7 kHz; (viii) 7-8 kHz; (ix) 8-9 kHz; (x) 9-10 kHz; (xi) 10-11 kHz; (xii) 11-12 kHz; (xiii) 12-13 kHz; (xiv) 13-14 kHz; (xv) 14-15 kHz; (xvi) 15-16 kHz; (xvii) 16-17 kHz; (xviii) 17-18 kHz; and (xix) 18-19 kHz.

35. A desolvation device comprising: one or more nebulisers and one or more targets; a vibration device arranged and adapted to cause said one or more targets to vibrate; wherein said one or more nebulisers are arranged and adapted to emit, in use, a stream predominantly of droplets which are caused to impact upon said one or more targets and to cause said droplets to form desolvated gas phase molecules or secondary droplets; wherein said vibration device is arranged and adapted to vibrate said one or more targets at a frequency f selected from the group consisting of: (i) <1 kHz; (ii) 1-2 kHz; (iii) 2-3 kHz; (iv) 3-4 kHz; (v) 4-5 kHz; (vi) 5-6 kHz; (vii) 6-7 kHz; (viii) 7-8 kHz; (ix) 8-9 kHz; (x) 9-10 kHz; (xi) 10-11 kHz; (xii) 11-12 kHz; (xiii) 12-13 kHz; (xiv) 13-14 kHz; (xv) 14-15 kHz; (xvi) 15-16 kHz; (xvii) 16-17 kHz; (xviii) 17-18 kHz; and (xix) 18-19 kHz.

36. A method of desolvation comprising: causing a stream predominantly of droplets to impact upon one or more targets and to cause said droplets to form desolvated gas phase molecules or secondary droplets; and vibrating said one or more targets at a frequency f selected from the group consisting of: (i) <1 kHz; (ii) 1-2 kHz; (iii) 2-3 kHz; (iv) 3-4 kHz; (v) 4-5 kHz; (vi) 5-6 kHz; (vii) 6-7 kHz; (viii) 7-8 kHz; (ix) 8-9 kHz; (x) 9-10 kHz; (xi) 10-11 kHz; (xii) 11-12 kHz; (xiii) 12-13 kHz; (xiv) 13-14 kHz; (xv) 14-15 kHz; (xvi) 15-16 kHz; (xvii) 16-17 kHz; (xviii) 17-18 kHz; and (xix) 18-19 kHz.

37. The method as claimed in claim 34, wherein generating a stream including droplets comprises generating a stream of droplets having a Sauter mean diameter in a range: (i) <5 m; (ii) 5-10 m; (iii) 10-15 m; (iv) 15-20 m; (v) 20-25 m; or (vi) >25 m.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Various embodiments of the present invention together with other arrangements given for illustrative purposes only will now be described, by way of example only, and with reference to the accompanying drawings in which:

(2) FIG. 1 shows an impactor spray API ion source according to a preferred embodiment of the present invention;

(3) FIG. 2A shows a plan view of a target and a first vacuum stage of a mass spectrometer according to a preferred embodiment of the present invention with the nebuliser omitted and FIG. 2B shows a side view of the nebuliser or sprayer tip, target and first vacuum stage of a mass spectrometer according to a preferred embodiment of the present invention;

(4) FIG. 3 shows a conventional APCI ion source with a corona discharge pin;

(5) FIG. 4 shows the relative intensities of five test analytes measured using a conventional Electrospray ion source, a conventional APCI ion source and an impactor ion source according to the preferred embodiment;

(6) FIG. 5 shows the effect of target potential on ion signal according to a preferred embodiment of the present invention;

(7) FIG. 6A shows a mass spectrum obtained from an impactor spray ion source according to a preferred embodiment of the present invention with a target potential of 2.2 kV, FIG. 6B shows a mass spectrum obtained from an impactor spray source according to an embodiment of the present invention with a target potential of 0V and FIG. 6C shows a mass spectrum obtained with a conventional Electrospray ion source with an optimized capillary potential of 4 kV;

(8) FIG. 7 shows a known Surface Activated Chemical Ionisation ion source;

(9) FIG. 8 shows a comparison of the relative intensities obtained with a conventional SACI ion source and an impactor ion source spray according to a preferred embodiment;

(10) FIG. 9 shows data obtained from a Phase Doppler Anemometry analysis of the droplets emitted from a preferred nebuliser; and

(11) FIG. 10 shows a comparison of the radial distribution of the data rate for a pneumatic nebuliser according to an embodiment of the present invention and from a heated nebuliser such as used in a SACI ion source.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

(12) FIG. 1 shows a schematic of the general layout of an impactor spray API ion source according to an embodiment of the present invention. A flow of liquid containing analyte is arranged to enter a nebuliser or sprayer 1 and is delivered to the sprayer tip 2 via a liquid capillary tube 3. The liquid capillary tube 3 is preferably surrounded by a second capillary 4 which preferably includes a gas inlet 5 to deliver a stream of high velocity gas to the exit of the liquid capillary tube 3. According to an embodiment the inner diameter of the liquid capillary tube 3 is 130 m and the outer diameter of the liquid capillary tube 3 is 270 m. The inner diameter of the second (gas) capillary tube 4 is preferably 330 m. This arrangement produces a nebulised spray which contains droplets with a typical diameter of 10-20 m and which have velocities greater than 100 m/s at a close distance from the sprayer tip.

(13) The resulting droplets are preferably heated by an additional flow of gas that enters a concentric heater 6 via a second gas inlet 7. The nebuliser or sprayer 1 may be hinged to the right hand side of the ion inlet cone 8 of a mass spectrometer so that it can swing to vary the horizontal distance between the sprayer tip and an ion inlet orifice 9. The probe may also configured such that the vertical distance between the sprayer tip and the ion inlet orifice 9 can also be varied. A target 10 which preferably has a similar dimension to that of the liquid capillary tube 3 is placed between the sprayer tip and the ion inlet orifice 9. The target 10 can preferably be manipulated in the x and y directions (in the horizontal plane) via a micro adjuster stage and is preferably held at a potential of 0-5 kV relative to a source enclosure 11 and the ion inlet orifice 9. The ion inlet cone 8 is surrounded by a metal cone gas housing 12 that is preferably flushed with a low flow of nitrogen gas that enters via a gas inlet 13. All gasses that enter the source enclosure preferably leave via a source enclosure exhaust 14 or the ion inlet orifice 9 which is pumped by the first vacuum stage 15 of the mass spectrometer. As will be described in more detail below, the target 10 is preferably vibrated by a piezo-electric vibration source.

(14) FIG. 2A shows a schematic plan view of an embodiment of the present invention with the nebuliser or sprayer 1 omitted. A target 10 is located adjacent the first vacuum stage 15 of the mass spectrometer. According to an embodiment the target 10 may comprise a 0.8 mm diameter stainless steel pin which preferably incorporates a straight taper section over a distance of 5 mm. The pin is preferably positioned at a horizontal distance X.sub.1 of 5 mm from the ion inlet orifice 9. The pin 10 is preferably positioned such that the point of impact between the probe axis and the target 10 is on the side of the taper cone that faces the ion inlet orifice 9 as shown in FIG. 2B. This position results in an optimized glancing angle of incidence shown as an arrowed line 16 in the end view schematic of FIG. 2B. FIG. 2B also shows the relative vertical positions of the nebuliser or probe 2 and target 10 according to the preferred embodiment i.e. Z.sub.1=9 mm and Z.sub.2=1.5 mm. The nebuliser or sprayer 2 is preferably maintained at 0V, the target 10 is preferably held at 2.2 kV, the ion inlet cone is preferably held at 100 V, the cone gas housing is preferably held at 100 V and the heater assembly and source enclosure are preferably held at ground potential. The nitrogen nebuliser gas is preferably pressurized to 7 bar, the nitrogen heater gas flow is preferably pressurized to deliver 1200 L/hr and the nitrogen cone gas flow is preferably pressurized to deliver 150 L/hr.

(15) A series of tests were conducted to test the relative sensitivities of the preferred impactor spray source, a conventional ESI ion source and a conventional APCI ion source.

(16) The conventional ESI ion source was constructed by removing the target 10 and applying a potential of 2.5 kV directly to the sprayer tip. All other potentials and gas flows were maintained as above.

(17) The APCI ion source was constructed by replacing the nebuliser or sprayer 2 with a conventional heated nebuliser probe 17 as shown in FIG. 3 as used in commercial APCI ion sources and adding a corona discharge pin 18. The tip of the corona discharge pin 18 was located at a distance X=7 mm and Z=5.5 mm as shown in FIG. 3. The APCI ion source probe was operated at 550 C., the heater gas was unheated at a flow rate of 500 L/hr and the corona discharge pin 18 was set at a current of 5 A. All other settings were as described above.

(18) A test solution was prepared consisting of 70/30 acetonitrile/water and containing sulphadimethoxine (10 pg/L), verapamil (10 pg/L), erythromycin (10 pg/L), cholesterol (10 ng/L) and cyclosporin (100 pg/L). The test solution was infused at a flow rate of 15 L/min into a carrier liquid flow of 0.6 mL/min of 70/30 acetonitrile/water which was then sampled by the three different API ion sources.

(19) FIG. 4 shows the relative signal intensities obtained for the five test analytes with a conventional Electrospray ion source, a conventional APCI ion source and an impactor ion source according to the preferred embodiment. For each analyte the signal intensity was monitored for the protonated molecule ([M+H].sup.+). However, owing to signal saturation with the preferred impactor spray, the cholesterol signal was measured on the carbon-13 isotope of the [M+H].sup.+ ion. From this figure, it is clear that although the APCI ion source has some advantages over ESI ion sources (e.g. for non-polar analytes such as cholesterol), ESI is generally the more sensitive of these two techniques. It is also clear that the preferred impactor spray source gives rise to significantly greater signal intensities than either the ESI or APCI ion source for all compound types.

(20) In API ion sources that utilize the SACI ionization technique, a broad area target is maintained at an elevated potential to optimize ion signal. FIG. 5 shows the effect of varying the target potential on the resulting ion signal for the preferred impactor spray source where the same test mixture was analysed with a target potential of 2.2 kV followed by a target potential of 0 kV. In contrast to SACI, it is apparent that an elevated target potential, although advantageous, is not essential to the ionization process. By contrast, a broad area SACI source would lose >90% of the ion signal under the same experimental conditions (data not shown).

(21) Although not essential, an elevated target potential is nonetheless advantageous and has the result of improving the qualitative aspects of mass spectral data. To illustrate this, FIG. 6A shows a mass spectrum obtained from an impactor ion source according to the preferred embodiment with a target potential of 2.2 kV, FIG. 6B shows a mass spectrum obtained from an impactor ion source according to an embodiment with a target potential of 0V and FIG. 6C shows a mass spectrum obtained with a conventional electrospray source with an optimized capillary potential of 4 kV. The mass spectra shown in FIGS. 6A and 6B which were obtained using an ion source according to the preferred embodiment are shown to produce more analyte ions than ESI but significantly an elevated target potential also reduces the susceptibility to ion adduct formation ([M+Na].sup.+ and [M+K].sup.+) such that the protonated molecule ([M+H].sup.+) is the base peak only for the mass spectrum shown in FIG. 6A.

(22) An experiment was conducted to compare the sensitivity of the impactor ion source according to the preferred embodiment with a SACI-type ionization source. FIG. 7 shows a schematic of the SACI ion source which was used. The SACI ion source was constructed by replacing the impactor pin target 10 with a 0.15 mm thick rectangular tin sheet 19 which measured approximately 30 mm15 mm. The sheet target 19 was angled at approximately 30 to horizontal and was positioned such that the point of intersection between the nebuliser or probe 2 axis and the target 19 was at X=4 mm and Z=4 mm. The SACI ion source was optimised at a nebuliser or sprayer potential of 0 V and a target potential of 1 kV. All other gas flows and voltages were as described for the preferred impactor spray source.

(23) FIG. 8 compares the relative signal intensities obtained with a SACI ion source and an impactor ion source according to the preferred embodiment. It is observed that the preferred impactor spray ion source is typically between 5-10 more sensitive than the broad area SACI ion source.

(24) Further embodiments are contemplated wherein the performance of the preferred impactor ion source may be further improved by positioning a central wire in the bore of the liquid capillary tube 3. Video photography has shown that the central wire focuses the droplet stream such that the target may be placed at the focal point to further increase the droplet flux density. The position of the focal point is comparable to the sprayer tip/target distance used in the preferred embodiment (1-2 mm).

(25) As described above a SACI ion source converts a liquid stream into a vapour stream that then impinges on a broad area target. Experiments on SACI (Cristoni et al., J. Mass Spectrom., 2005, 40, 1550) have shown that ionisation occurs as a result of the interaction of neutral analyte molecules in the gas phase with the proton rich surface of the broad area target. Furthermore, there is a linear relationship between ionisation efficiency and target area within the range 1-4 cm.sup.2.

(26) In contrast to SACI, the preferred ion source uses a streamlined target to intercept a high velocity stream of liquid droplets which results in a secondary stream consisting of secondary droplets, gas phase neutrals and ions.

(27) A pneumatic nebuliser according to an embodiment of the present invention was investigated further. The nebuliser comprised an inner liquid capillary with an internal diameter of 127 m and an outer diameter of 230 m. The inner liquid capillary was surrounded by a gas capillary with an internal diameter of 330 m that was pressurised to 7 bar.

(28) FIG. 9 shows typical data obtained from a Phase Doppler Anemometry (PDA) analysis of the preferred nebuliser for a 1 mL/min liquid flow consisting of 90% water/10% methanol and a nitrogen nebuliser gas.

(29) The PDA sampling point was scanned radially across the spray (probe axis=0) at an axial distance of 5 mm from the spray point i.e. equivalent to the typical nebuliser/target distance according to the preferred embodiment. FIG. 9 shows that the nebuliser typically produces liquid droplets with a Sauter mean diameter (d.sub.32) in the range 13-20 m with mean axial velocities in excess of 100 ms.sup.1.

(30) FIG. 9 also shows that the very high velocity droplets are well collimated and are typically confined within a radius of 1 mm from the probe axis.

(31) The upper trace of FIG. 10 shows the radial distribution of the data rate N/T (number of validated samples per unit time) for the preferred pneumatic nebuliser and experimental conditions as described above. This logrithmic plot demonstrates that the spray is well collimated with greater than two thirds of the total droplet mass being confined to a radius of 1 mm from the probe axis. The lower trace of FIG. 10 shows the equivalent N/T distribution from a heated nebuliser such as used in a conventional SACI source. The heated nebuliser consists of a pneumatic nebuliser which sprays into a 90 mm long cylindrical tube with a 4 mm diameter bore (tube temperature=600 C.). The N/T data for this nebuliser was obtained at an axial distance of 7 mm from the exit end of the heated tube. It is important to note that the N/Ts for the few detected droplets from the heated nebuliser (d.sub.32 was typically 14 m, data not shown) are typically three orders of magnitude lower than those obtained from the pneumatic nebuliser according to the preferred embodiment. This is a due to the fact that the overwhelming mass of the liquid is vaporised in the SACI-type heated nebuliser resulting in a stream of vapour that contains a very low number density of surviving droplets.

(32) Accordingly, a known SACI ion source should be construed as comprising a nebuliser which emits a stream predominantly of vapour and hence a SACI ion source should be understood as not falling within the scope of the present invention.

(33) Referring to the data presented in FIGS. 9 and 10 it can be assumed that the physical model of the ion source according to the preferred embodiment is dominated by the impact of high velocity liquid droplets on a target that is indirectly heated by the source heater. Such impact effects give rise to the formation of secondary droplets, where the nature of the droplet breakup is determined by the Weber number W.sub.e which is given by the following:
W.sub.e=U.sup.2d/(1)
wherein is the droplet density, U is the droplet velocity, d is the droplet diameter and is the droplet surface tension.

(34) If it is assumed that the water droplets are at 40 C., the nitrogen gas environment is at 100 C., d=18 m and U=50 ms.sup.1 then a value of W.sub.e=640 is obtained for the droplets according to the preferred embodiment. It has been shown (in the literature) that the number of reatomised water droplets increases linearly with W.sub.e in the range 50-750 for impact on a heated steel target for temperatures between 260-400 C. At W.sub.e=750, a single droplet typically gave rise to 40 secondary droplets.

(35) It is apparent, therefore, that the impactor target leads to significant droplet breakup to produce a secondary stream that consists of charged droplets, neutrals, ions and clusters.

(36) The impact efficiency of the system will be largely governed by the Stokes number S.sub.k where:
S.sub.k=d.sup.2U/18a(2)
wherein is the droplet density, d is the droplet diameter, U is the droplet velocity, is the gas viscosity and a is the characteristic dimension of the target.

(37) Impact efficiency increases with increasing S.sub.k and thus favours large droplets with high velocity and a small target diameter. Thus for the preferred impactor spray conditions described above, it may be expected that S.sub.k has a typical value of 30.

(38) For S.sub.k1 droplets are highly likely to deviate from the flow streamlines and impact upon the target. In contrast, if the target dimension is increased by an order of magnitude and the velocity is decreased by an order of magnitude (i.e. similar conditions to SACI), then the value of S.sub.k drops to 0.3 at which point the droplets are more likely to follow the gas flow around the target. The impact efficiency is also known to increase with reducing Reynolds numbers which will further favour the streamlined nature of the impactor spray target according to the preferred embodiment.

(39) The shape of the secondary stream will be governed by the gas flow dynamics and, in particular, the Reynolds number (R.sub.e) which is given by:
R.sub.e=vL/(3)
wherein is the gas density, v is the gas velocity, is the gas viscosity and L is the significant dimension of the target.

(40) With a 1 mm diameter impactor target, a gas velocity of 50 ms.sup.1 and nitrogen gas at 100 C. then a value of R.sub.e=3000 is obtained.

(41) Reynolds numbers in the range 2000-3000 generally correspond to the transition region from laminar to turbulent flow. Therefore, it can be expected that the wake from the target contains some turbulence and eddy features, However, severe turbulence that could hinder the sampling of ions or droplets at the ion inlet cone is not expected.

(42) The preferred ion source can be tuned by swinging the nebuliser to move the impact zone from one side of the rod-like target to the other. This results in changes to the wake which can be visually observed by strong illumination of the secondary droplet stream. Other embodiments are therefore also contemplated wherein similar source optimisation could be achieved with a centralised impact zone and a non-symmetric target cross section e.g. (the profile of) an aircraft wing.

(43) According to a particularly preferred embodiment the surface ionization impactor bar or target as described above which is preferably used to ionise compounds with similar results to an API/ESI or APCI ion source may be further enhanced by utilising a piezoelectric vibration device to vibrate the bar or target. Vibration of the bar or target upon which the surface ionization occurs aids in the reduction of the size of the secondary droplets, increasing the evaporation rate of the solvent and thereby aids signal response.

(44) According to a preferred embodiment an impactor bar or target is located within an API/ESI source enclosure. In this configuration the capillary is preferably grounded and potentials are preferably applied to the impactor bar or target and to the sample cone inlet structure. Experiments have shown that this API source configuration provides the conditions for compound ionisation coverage that is encompassed by both API/ESI and APCI techniques. The integration an impactor spray with API/ESI introduces the potential for the simultaneous generation of non-polar, highly polar, singularly charged and/or multiply charged gas phase ions for introduction into the mass spectrometer for analysis. The ionization processes and flow dynamics may, however, be different which can result in the formation of larger sized droplets. The use of piezoelectric vibration applied to the impactor bar or target is particularly advantageous in that it aids in the reduction of resultant secondary droplets.

(45) It will be understood by those skilled in the art that the mechanisms of droplet production in pneumatically assisted nebulisation are non-trivial and it cannot be approximated by a particular model for which the boundary conditions are known. There is no single process that is believed to be solely responsible for droplet production and the initial spray produced is rapidly modified by secondary fragmentation and by recombination and coalescence. The use of piezoelectric vibration applied to the impactor bar or target preferably aids in the reduction of the resultant secondary droplets through surface disruption.

(46) The preferred embodiment described above has particular applicability to MS source technology and may be utilised within MS API source assemblies and other ion sources.

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