HK1193497B

HK1193497B - Atmospheric pressure ion source by interacting high velocity spray with a target

Info

Publication number: HK1193497B
Application number: HK14106891.1A
Authority: HK
Inventors: 斯特万．巴伊奇
Original assignee: 英国质谱公司
Priority date: 2011-04-20
Filing date: 2012-04-20
Publication date: 2017-12-08

Description

Atmospheric pressure ion source interacting with target by high velocity spray

Cross Reference to Related Applications

This application claims priority from U.S. provisional patent application No.61/478,725, filed 2011, 4/25 and uk patent application No.1106694.1, filed 2011, 4/20. The entire contents of these applications are incorporated herein by reference.

Technical Field

The present invention relates to an ion source for a mass spectrometer and a method of ionizing a sample. Preferred embodiments relate to mass spectrometers and methods of mass spectrometry.

Background

Atmospheric pressure ionization ("API") ion sources are commonly used to ionize a liquid stream from an HPLC or UPLC chromatography apparatus prior to analyzing the generated gas phase ions by a mass spectrometer. The two most commonly used techniques include electrospray ionization ("ESI") and atmospheric pressure chemical ionization ("APCI"). ESI is most suitable for medium to high polarity analytes, APCI is most suitable for non-polar analytes. API ion sources combining these two technologies have been proposed and implemented in designs that combine ESI and APCI ionization simultaneously using geometries that ensure that the electric fields generated by each technology are shielded and independent of each other. These so-called "multi-mode" ion sources have the advantage of being able to ionize analyte mixtures containing various polarities in a single chromatographic analysis without the need to switch between different ionization techniques. US-7034291 discloses an ESI/APCI multimode ionization source comprising an ESI ion source and a downstream corona discharge needle, and US-7411186 discloses a multimode ESI/APCI ion source. Known multimode ion sources suffer from mechanical complications.

Other general purpose or multimode ionization sources have been proposed for integrating liquid chromatography into mass spectrometry. One such example is a surface activated chemical ionization ("SACI") ion source that directs a vapor stream from a heated nebulizer (nebuliser) probe toward a large area charged target plate positioned proximate to an ion entrance aperture of a mass spectrometer and 15-20mm from the end of the nebulizer. The ejection point of the SACI ion source is located within the heated atomizer probe such that the typical distance between the ejection point of the SACI ion source and the target plate is 70 mm. This geometry with a relatively large distance between the injector and the target will produce a divergent jet with a divergent reflected flow at the target, which typically results in lower sensitivity when compared to the optimized ESI and APCI sources. US-7368728 discloses a known surface activated chemical ionization ion source.

It is also known to place small targets in the form of beads in close proximity to the atomizing spray point in impactor atomizers used in atomic absorption spectroscopy. Impactor atomizers are disclosed, for example, in anal. chem.1982,54, 1411-. Known impactor atomizers are not used for ionizing samples.

It is desirable to provide an improved ion source for a mass spectrometer.

Disclosure of Invention

According to an aspect of the present invention, there is provided an ion source comprising:

one or more atomizers and one or more targets;

wherein the one or more atomisers are arranged and adapted to emit, in use, a stream of predominantly droplets which are caused to impinge on the one or more targets and ionise the droplets to form a plurality of ions.

The droplet preferably comprises an analyte droplet and the plurality of ions preferably comprises analyte ions.

However, according to another embodiment, the droplet may comprise a reactant droplet and the plurality of ions may comprise reactant ions.

According to a preferred embodiment, the generated reactant ions may react with, interact with or transfer charge to neutral analyte molecules and cause the analyte molecules to be ionized. The reactant ions may also be used to enhance the formation of analyte ions.

According to embodiments, one or more tubes may be arranged and adapted to supply one or more analyte gases or other gases to a region adjacent to the one or more targets.

The reactant ions are preferably arranged to ionize the analyte gas to form a plurality of analyte ions.

The analyte liquid may be supplied to the one or more targets and may be ionized to form a plurality of analyte ions, and/or the reactant liquid may be supplied to the one or more targets and may be ionized to form reactant ions that impart charge to neutral analyte atoms or molecules to form analyte ions and/or the reactant ions enhance the formation of analyte ions.

The one or more targets preferably comprise one or more holes, and wherein the analyte liquid and/or the reagent liquid is supplied directly to the one or more targets and emerges from the one or more holes.

According to an embodiment, the one or more targets may be coated with one or more liquid, solid or gel analytes, and wherein the one or more analytes are ionized to form a plurality of analyte ions.

The one or more targets may be formed from one or more analytes, and wherein the one or more analytes may be ionized to form a plurality of analyte ions.

According to a preferred embodiment, the ion source comprises an atmospheric pressure ionization ("API") ion source.

The one or more atomisers are preferably arranged and adapted such that a substantial portion of the mass or substance emitted by the one or more atomisers is in the form of non-vapour droplets.

Preferably, at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the mass or substance emitted by the one or more atomizers is in droplet form.

The one or more atomizers are preferably arranged and adapted to emit a stream of droplets, wherein the sauter mean diameter ("SMD", d32) of the droplets is in the following range: (i) <5 μm; (ii)5-10 μm; (iii)10-15 μm; (iv)15-20 μm; (v)20-25 μm; or (vi) >25 μm.

The stream of droplets emitted from the one or more atomizers preferably forms secondary droplets after impacting one or more targets.

The stream of droplets and/or the stream of secondary droplets preferably passes through a flow region having a reynolds number (Re) in the range: (i) < 2000; (ii) 2000-; (iii) 2500-; (iv) 3000-3500; (v) 3500-4000; or (vi) > 4000.

According to a preferred embodiment, at substantially the point where the droplets impact the one or more targets, the droplets have a Weber number (We) selected from the group consisting of: (i) < 50; (ii)50-100 parts of; (iii) 100-150; (iv) 150-200; (v) 200-; (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-; (xviii) 850-; (xix) 900-; (xx) 950-; and (xxi) > 1000.

According to a preferred embodiment, at approximately the point where the droplets impact the one or more target materials, the stokes number (Sk) of the droplets is in the following range: (i) 1-5; (ii) 5-10; (iii)10-15 parts of; (iv)15-20 parts of; (v) 20-25; (vi) 25-30; (vii) 30-35; (viii)35-40 parts of; (ix) 40-45; (x)45-50 parts of; and (xi) > 50.

The mean axial impact velocity of the droplets on the one or more targets is preferably 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.

The one or more targets are preferably arranged at <20mm, <19mm, <18mm, <17mm, <16mm, <15mm, <14mm, <13mm, <12mm, <11mm, <10mm, <9mm, <8mm, <7mm, <6mm, <5mm, <4mm, <3mm or <2mm from the outlet of the one or more atomizers.

The one or more nebulisers are preferably arranged and adapted to nebulise the one or more eluents emitted by the one or more devices over a period of time.

The one or more devices preferably comprise one or more liquid chromatography separation devices.

The one or more nebulizers are preferably arranged and adapted to nebulize one or more eluents, wherein the liquid flow rate of the one or more eluents is selected from the group consisting of: (i) <1 μ L/min; (ii)1-10 muL/min; (iii)10-50 μ L/min; (iv)50-100 μ L/min; (v) 100-; (vi) 200-; (vii) 300-; (viii)400-500 μ L/min; (ix) 500-; (x) 600-; (xi) 700-; (xii) 800-; (xiii) 900-; (xiv) 1000-; (xv) 1500-; (xvi) 2000-; and (xvii) >2500 μ L/min.

The one or more atomizers may comprise one or more rotary disc atomizers according to a less preferred embodiment.

The one or more nebulisers preferably comprises a first capillary tube having an outlet which, in use, emits the stream of droplets.

The first capillary is preferably held at the following potential in use: (i) -5 to-4 kV; (ii) -4 to-3 kV; (iii) -3 to-2 kV; (iv) -2 to-1 kV; (v) -1000 to-900V; (vi) -900 to-800V; (vii) 800 to 700V; (viii) -700 to-600V; (ix) -600 to-500V; (x) -500 to-400V; (xi) -400 to-300V; (xii) -300 to-200V; (xiii) -200 to-100V; (xiv) -100 to-90V; (xv) -90 to-80V; (xvi) -80 to-70V; (xvii) -70 to-60V; (xviii) -60 to-50V; (xix) -50 to-40V; (xx) -40 to-30V; (xxi) -30 to-20V; (xxii) -20 to-10V; (xxiii) -10 to 0V; (xxiv) 0-10V; (xxv) 10-20V; (xxvi) 20-30V; (xxvii) 30-40V; (xxviii) 40-50V; (xxix) 50-60V; (xxx) 60-70V; (xxxi) 70-80V; (xxxii) 80-90V; (xxxiii) 90-100V; (xxxiv) 100-200V; (xxxv) 200-300V; (xxxvi) 300-400V; (xxxvii) 400-500V; (xxxviii) 500-600V; (xxxix) 600-700V; (xl) 700-800V; (xli) 800-900V; (xlii) 900-1000V; (xliii)1-2 kV; (xliv)2-3 kV; (xlv)3-4 kV; and (xlvi)4-5 kV.

The first capillary is preferably held, in use, at a potential relative to a potential of a housing surrounding the ion source and/or a potential of an ion inlet arrangement to the first vacuum stage and/or the one or more targets of the mass spectrometer as follows: (i) -5 to-4 kV; (ii) -4 to-3 kV; (iii) -3 to-2 kV; (iv) -2 to-1 kV; (v) -1000 to-900V; (vi) -900 to-800V; (vii) 800 to 700V; (viii) -700 to-600V; (ix) -600 to-500V; (x) -500 to-400V; (xi) -400 to-300V; (xii) -300 to-200V; (xiii) -200 to-100V; (xiv) -100 to-90V; (xv) -90 to-80V; (xvi) -80 to-70V; (xvii) -70 to-60V; (xviii) -60 to-50V; (xix) -50 to-40V; (xx) -40 to-30V; (xxi) -30 to-20V; (xxii) -20 to-10V; (xxiii) -10 to 0V; (xxiv) 0-10V; (xxv) 10-20V; (xxvi) 20-30V; (xxvii) 30-40V; (xxviii) 40-50V; (xxix) 50-60V; (xxx) 60-70V; (xxxi) 70-80V; (xxxii) 80-90V; (xxxiii) 90-100V; (xxxiv) 100-200V; (xxxv) 200-300V; (xxxvi) 300-400V; (xxxvii) 400-500V; (xxxviii) 500-600V; (xxxix) 600-700V; (xl) 700-800V; (xli) 800-900V; (xlii) 900-1000V; (xliii)1-2 kV; (xliv)2-3 kV; (xlv)3-4 kV; and (xlvi)4-5 kV.

According to an embodiment, a wire may be located within a volume surrounded by the first capillary, wherein the wire is arranged and adapted to focus the stream of droplets.

According to a preferred embodiment:

(i) the first capillary being surrounded by a second capillary arranged and adapted to provide a flow of gas to an outlet of the first capillary; or

(ii) A second capillary tube is arranged and adapted to provide a cross-flow stream of gas to the outlet of the first capillary tube.

The second capillary preferably surrounds the first capillary and/or is concentric or non-concentric with the first capillary.

The ends of the first and second capillaries are preferably: (i) flush or parallel to each other; or (ii) are convex, concave, or non-parallel with respect to each other.

The outlet of the first capillary preferably has a diameter D, and the droplet spray is preferably arranged to impinge on an impingement area of the one or more targets.

The impact area preferably has a maximum dimension x, wherein the ratio x/D is in the following range: <2, 2-5, 5-10, 10-15, 15-20, 20-25, 25-30, 30-35, 35-40 or > 40.

The area of the impact region is preferably selected from the group consisting of: (i) <0.01mm 2; (ii)0.01-0.10mm 2; (iii)0.10-0.20mm 2; (iv)0.20-0.30mm 2; (v)0.30-0.40mm 2; (vi)0.40-0.50mm 2; (vii)0.50-0.60mm 2; (viii)0.60-0.70mm 2; (ix)0.70-0.80mm 2; (x)0.80-0.90mm 2; (xi)0.90-1.00mm 2; (xii)1.00-1.10mm 2; (xiii)1.10-1.20mm 2; (xiv)1.20-1.30mm 2; (xv)1.30-1.40mm 2; (xvi)1.40-1.50mm 2; (xvii)1.50-1.60mm 2; (xviii)1.60-1.70mm 2; (xix)1.70-1.80mm 2; (xx)1.80-1.90mm 2; (xxi)1.90-2.00mm 2; (xxii)2.00-2.10mm 2; (xxiii)2.10-2.20mm 2; (xxiv)2.20-2.30mm 2; (xxv)2.30-2.40mm 2; (xxvi)2.40-2.50mm 2; (xxvii)2.50-2.60mm 2; (xxviii)2.60-2.70mm 2; (xxix)2.70-2.80mm 2; (xxx)2.80-2.90mm 2; (xxxi)2.90-3.00mm 2; (xxxii)3.00-3.10mm 2; (xxxiii)3.10-3.20mm 2; (xxxiv)3.20-3.30mm 2; (xxxv)3.30-3.40mm 2; (xxxvi)3.40-3.50mm 2; (xxxvii)3.50-3.60mm 2; (xxxviii)3.60-3.70mm 2; (xxxix)3.70-3.80mm 2; (xl)3.80-3.90mm 2; and (xli)3.90-4.00mm 2.

The ion source preferably further comprises one or more heaters arranged and adapted to supply one or more streams of heated gas to the outlet of the one or more atomisers.

According to an embodiment:

(i) the one or more heaters surround the first capillary tube and are arranged and adapted to supply a flow of heated gas to the outlet of the first capillary tube; and/or

(ii) The one or more heaters comprise one or more infrared heaters; and/or

(iii) The one or more heaters include one or more fired heaters.

The ion source may further comprise one or more heating devices arranged and adapted to directly and/or indirectly heat the one or more targets.

The one or more heating devices may comprise one or more lasers arranged and adapted to emit one or more laser beams that are incident on the one or more targets to heat the one or more targets.

According to an embodiment, the one or more targets are maintained at the following potential in use: (i) -5 to-4 kV; (ii) -4 to-3 kV; (iii) -3 to-2 kV; (iv) -2 to-1 kV; (v) -1000 to-900V; (vi) -900 to-800V; (vii) 800 to 700V; (viii) -700 to-600V; (ix) -600 to-500V; (x) -500 to-400V; (xi) -400 to-300V; (xii) -300 to-200V; (xiii) -200 to-100V; (xiv) -100 to-90V; (xv) -90 to-80V; (xvi) -80 to-70V; (xvii) -70 to-60V; (xviii) -60 to-50V; (xix) -50 to-40V; (xx) -40 to-30V; (xxi) -30 to-20V; (xxii) -20 to-10V; (xxiii) -10 to 0V; (xxiv) 0-10V; (xxv) 10-20V; (xxvi) 20-30V; (xxvii) 30-40V; (xxviii) 40-50V; (xxix) 50-60V; (xxx) 60-70V; (xxxi) 70-80V; (xxxii) 80-90V; (xxxiii) 90-100V; (xxxiv) 100-200V; (xxxv) 200-300V; (xxxvi) 300-400V; (xxxvii) 400-500V; (xxxviii) 500-600V; (xxxix) 600-700V; (xl) 700-800V; (xli) 800-900V; (xlii) 900-1000V; (xliii)1-2 kV; (xliv)2-3 kV; (xlv)3-4 kV; and (xlvi)4-5 kV.

According to an embodiment, the one or more targets are held at, in use, the following potentials relative to a potential of a housing surrounding the ion source and/or a potential of an ion inlet arrangement to a first vacuum stage and/or the one or more nebulisers of a mass spectrometer: (i) -5 to-4 kV; (ii) -4 to-3 kV; (iii) -3 to-2 kV; (iv) -2 to-1 kV; (v) -1000 to-900V; (vi) -900 to-800V; (vii) 800 to 700V; (viii) -700 to-600V; (ix) -600 to-500V; (x) -500 to-400V; (xi) -400 to-300V; (xii) -300 to-200V; (xiii) -200 to-100V; (xiv) -100 to-90V; (xv) -90 to-80V; (xvi) -80 to-70V; (xvii) -70 to-60V; (xviii) -60 to-50V; (xix) -50 to-40V; (xx) -40 to-30V; (xxi) -30 to-20V; (xxii) -20 to-10V; (xxiii) -10 to 0V; (xxiv) 0-10V; (xxv) 10-20V; (xxvi) 20-30V; (xxvii) 30-40V; (xxviii) 40-50V; (xxix) 50-60V; (xxx) 60-70V; (xxxi) 70-80V; (xxxii) 80-90V; (xxxiii) 90-100V; (xxxiv) 100-200V; (xxxv) 200-300V; (xxxvi) 300-400V; (xxxvii) 400-500V; (xxxviii) 500-600V; (xxxix) 600-700V; (xl) 700-800V; (xli) 800-900V; (xlii) 900-1000V; (xliii)1-2 kV; (xliv)2-3 kV; (xlv)3-4 kV; and (xlvi)4-5 kV.

According to a preferred embodiment, in the operational mode, the one or more targets are kept at a positive potential and wherein the droplets impinging on the one or more targets form a plurality of positively charged ions.

According to a preferred embodiment, in the operational mode, the one or more targets are kept at a negative potential and wherein the droplets impinging on the one or more targets form a plurality of negatively charged ions.

The ion source may further comprise means arranged and adapted to apply a sinusoidal or non-sinusoidal AC or RF voltage to said one or more targets.

The one or more targets are preferably arranged or otherwise positioned to deflect the stream of droplets and/or the plurality of ions towards an ion inlet arrangement of a mass spectrometer.

The one or more targets are preferably positioned upstream of an ion inlet arrangement of a mass spectrometer such that ions are deflected in a direction towards the ion inlet arrangement.

The one or more targets may include stainless steel targets, metals, gold, non-metallic substances, semiconductors, metals or other substances with carbide coatings, insulators, or ceramics.

The one or more targets may comprise a plurality of target elements such that droplets from the one or more atomisers fall onto the plurality of target elements, and/or wherein the target is arranged with a plurality of impact points such that the droplets are ionised by multiple grazing deflection (glancing deflection).

The one or more targets may be shaped or have an aerodynamic profile such that gas flowing through the one or more targets is directed or deflected towards, parallel to, orthogonal to or away from an ion inlet arrangement of a mass spectrometer.

At least some or a majority of the plurality of ions may be arranged to be entrained, in use, into the gas flowing through the one or more targets.

According to an embodiment, in an operation mode droplets from one or more reference or calibration atomizers are directed onto the one or more targets.

According to an embodiment, in an operational mode droplets from one or more analyte atomizers are directed onto the one or more targets.

According to another aspect of the present invention there is provided a mass spectrometer comprising an ion source as described above.

The mass spectrometer preferably further comprises an ion inlet arrangement to the first vacuum stage of the mass spectrometer.

The ion inlet means preferably comprises an ion aperture, ion inlet cone, ion inlet capillary, ion inlet heated capillary, ion channel, ion mobility spectrometer or separator, differential ion mobility spectrometer, Field Asymmetric Ion Mobility Spectrometer (FAIMS) device or other ion inlet.

The one or more targets are preferably positioned at a first distance X1 from the ion inlet arrangement in a first direction and at a second distance Z1 from the ion inlet arrangement in a second direction, wherein the second direction is orthogonal to the first direction, and wherein:

(i) x1 is selected from the group consisting of: (i)0-1 mm; (ii)1-2 mm; (iii)2-3 mm; (iv)3-4 mm; (v)4-5 mm; (vi)5-6 mm; (vii)6-7 mm; (viii)7-8 mm; (ix)8-9 mm; (x)9-10 mm; and (xi) >10 mm; and/or

(ii) Z1 is selected from the group consisting of: (i)0-1 mm; (ii)1-2 mm; (iii)2-3 mm; (iv)3-4 mm; (v)4-5 mm; (vi)5-6 mm; (vii)6-7 mm; (viii)7-8 mm; (ix)8-9 mm; (x)9-10 mm; and (xi) >10 mm.

The one or more targets are preferably positioned to deflect the stream of droplets and/or the plurality of ions towards the ion inlet arrangement.

The one or more targets are preferably positioned upstream of the ion inlet arrangement.

The one or more targets preferably comprise: (i) one or more rods; or (ii) one or more needles having a conical portion.

The stream of droplets is preferably arranged to impinge on the conical portion of the one or more stems or the one or more needles in the following manner: (i) directly impinging on the centerline of the one or more rods or needles; or (ii) impinges on a side of the conical portion of the one or more rods or the one or more needles facing or away from the ion inlet aperture.

The mass spectrometer may further comprise a housing surrounding the one or more nebulisers, the one or more targets and the ion inlet arrangement.

The mass spectrometer may further comprise one or more deflection or push electrodes to which one or more DC voltages or DC voltage pulses are applied, in use, to deflect or push ions towards an ion inlet arrangement of the mass spectrometer.

According to an aspect of the present invention, there is provided a method of ionising a sample, comprising:

impinging a stream of predominantly droplets on one or more targets to ionize the droplets, thereby forming a plurality of analyte ions.

According to one aspect of the present invention there is provided a method of mass spectrometry comprising a method of ionising ions as described above.

According to one aspect of the present invention, there is provided a mass spectrometer comprising:

an ion source, comprising:

a target material; and

an atomiser configured to emit, in use, a stream formed primarily of droplets which are caused to impinge on the target and ionise the droplets to form a plurality of ions.

a target material; and

According to an aspect of the present invention, there is provided a method of mass spectrometry comprising:

the sample is ionized by generating a stream formed primarily of droplets, and ionizing the droplets by impinging the droplets on one or more targets to form a plurality of ions.

According to one aspect of the invention, there is provided a method of ionising a sample, the method comprising generating a stream formed predominantly of droplets, and ionising the droplets to form a plurality of ions by impinging the droplets on one or more targets.

According to one aspect of the present invention, there is provided a desolvation device comprising:

one or more atomizers and one or more targets;

wherein the one or more atomisers are arranged and adapted to emit, in use, a stream of predominantly droplets which are caused to impinge on the one or more targets and cause the droplets to form desolvated gas phase molecules and/or secondary droplets.

According to one aspect of the present invention, there is provided a desolvation method comprising:

impinging a stream of predominantly droplets on one or more targets and causing the droplets to form desolvated vapor-phase molecules and/or secondary droplets.

It will be appreciated that the invention extends beyond ion sources or methods of ionising samples to include apparatus and methods for at least partially desolvating or further desolvating a stream of droplets. The resulting gas phase molecules and/or secondary droplets may be sequentially ionized by a separate ion source.

a nebulizer comprising a first capillary and having an outlet which, in use, emits a stream of analyte droplets; and

a target arranged at a distance of <10mm from the outlet of the atomizer;

the mass spectrometer is characterized in that the mass spectrometer further comprises:

a liquid chromatography separation device arranged and adapted to emit an eluent over a period of time; and

an ion source arranged and adapted to ionize the eluent, the ion source comprising a nebulizer, and wherein, in use, a stream of analyte droplets is caused to impinge on the target and ionize the analyte to form a plurality of analyte ions.

In contrast, the target of the SACI ion source is arranged downstream of the ion inlet aperture of the mass spectrometer, towards which the ions are reflected back.

According to another aspect of the present invention, there is provided a method of mass spectrometry comprising:

providing a nebulizer comprising a first capillary and having an outlet which, in use, emits a stream of analyte droplets; and

positioning the target <10mm from the exit of the atomizer;

the method of mass spectrometry is characterized in that the method further comprises:

providing a liquid chromatography separation device that emits an eluent over a period of time; and is

The eluent is ionized by impinging a stream of analyte droplets on the target material and forming the analyte into a plurality of analyte ions.

As described above, the spray spot of the SACI ion source is within the heated atomizer probe such that the typical distance between the spray spot and the target plate is about 70 mm. By contrast, with the preferred impactor ion source, the spray point is located at the tip of the inner capillary, and the distance between the spray point and the target may be <10 mm.

Those skilled in the art will appreciate that SACI ion sources emit a vapor stream with a relatively low impingement velocity of the vapor on the target and about 4 m/s. In contrast, the impactor ion source according to the preferred embodiment does not emit a vapor stream, but rather a stream of high density droplets. Furthermore, the impact velocity of the droplet stream on the target is relatively high and is about 100 m/s.

It will therefore be apparent that the ion source according to the present invention is distinct from known SACI ion sources.

According to a preferred embodiment, the liquid flow is converted into an atomized spray, preferably by a concentric flow of high velocity gas, without the need for resorting to high potential differences at the tip of the atomizer or nebulizer. A micro-target having a size or impact area comparable to the droplet stream is preferably positioned in close proximity to the nebulizer tip (e.g. <5 mm) to define the impact area and partially deflect the spray towards the ion inlet aperture of the mass spectrometer. The ions and charged droplets produced are sampled by a first vacuum stage of the mass spectrometer.

According to a preferred embodiment, the target preferably comprises a stainless steel target. However, other embodiments are contemplated wherein the target may include other metallic (e.g., gold) and non-metallic substances. For example, embodiments are contemplated wherein the target comprises a semiconductor, a metal or other substance with a carbide coating, an insulator, or a ceramic.

According to another embodiment, the target may comprise a plurality of plates or target elements, such that droplets from the atomizer fall onto the plurality of target plates or target elements. According to this embodiment, there are preferably multiple impact points, and the droplets are ionized by multiple glancing deflections.

From the perspective of the API source, the close-coupled impactor, which also serves as a charged ionization surface, provides the basis for a sensitive multimode ionization source. The spray tip and micro-target are preferably configured in close proximity to a glancing impact geometry, which results in increased spray flux and significantly less beam divergence or reflection divergence at the target as compared to known large area SACI ion sources. The preferred embodiments thus provide a high sensitivity API source.

Preferred embodiments include multimode ion sources that can advantageously and efficiently ionize both high and low polarity analytes without the need to switch hardware or adjust parameters.

The droplets impacting the one or more targets are preferably unchanged.

It is clear that the ion source and the method of ionizing ions according to the present invention are particularly advantageous compared to known SACI ion sources.

Drawings

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

FIG. 1 illustrates an impactor spray API ion source according to a preferred embodiment of the invention;

figure 2A shows a plan view of a target and a first vacuum stage of a mass spectrometer omitting a nebulizer according to a preferred embodiment of the invention, and figure 2B shows a side view of a nebulizer or nebulizer tip, a target and a first vacuum stage of a mass spectrometer according to a preferred embodiment of the invention;

FIG. 3 illustrates a conventional APCI ion source with corona discharge needles;

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 a preferred embodiment;

FIG. 5 illustrates the effect of target potential on ion signal according to a preferred embodiment of the present invention;

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

FIG. 7 illustrates a known surface-activated chemical ionization ion source;

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;

FIG. 9 shows data obtained from phase Doppler velocimetry analysis of droplets emitted by a preferred nebulizer; and

fig. 10 shows a comparison of radial profiles of data rates for a pneumatic nebulizer according to an embodiment of the invention and from a heated nebulizer such as used in a SACI ion source.

Detailed Description

Fig. 1 shows a schematic diagram of the general arrangement of an impactor spray API ion source according to a preferred embodiment of the invention. The analyte-containing liquid stream is arranged to enter the nebulizer or atomizer 1 and is transported to the nebulizer tip 2 through a liquid capillary 3. The liquid capillary 3 is preferably surrounded by a second capillary 4, the second capillary 4 preferably comprising a gas inlet 5 to deliver a high-velocity gas flow to the outlet of the liquid capillary 3. According to the embodiment, the inner diameter of the liquid capillary 3 is 130 μm and the outer diameter of the liquid capillary 3 is 270 μm. The inner diameter of the second (gas) capillary 4 is preferably 330 μm. This arrangement produces an atomized spray containing droplets typically 10-20 μm in diameter and having a velocity greater than 100m/s at a close distance from the nebulizer tip.

The droplets produced are preferably heated by an additional gas flow entering the concentric heater 6 through the second gas inlet 7. The nebulizer or atomizer 1 may be hingedly connected to the right hand side of the ion inlet cone 8 of the mass spectrometer so that the nebulizer or atomizer 1 can be rocked to change the horizontal distance between the nebulizer tip and the ion inlet aperture 9. The probe may also be configured such that the vertical distance between the nebulizer tip and the ion inlet aperture 9 may also be varied. The target 10 is preferably of similar dimensions to the liquid capillary 3, the target 10 being placed between the nebulizer tip and the ion inlet aperture 9. The target 10 may preferably be operated in the x and y directions (in the horizontal plane) by a micro-actuator stage and is preferably maintained at a potential of 0-5kV with respect to the source housing 11 and the ion inlet aperture 9. The ion inlet cone 8 is surrounded by a metal cone gas housing 12, the metal cone gas housing 12 preferably being flooded with a low nitrogen gas flow entering through the gas inlet 13. All gas entering the source housing preferably exits through the source housing exhaust 14 or is drawn by the first vacuum stage 15 of the mass spectrometer to exit through the ion inlet aperture 9.

Fig. 2A shows a schematic plan view of an embodiment of the invention omitting the atomizer or nebulizer 1. The target 10 is positioned adjacent to a first vacuum stage 15 of the mass spectrometer. According to an embodiment, the target 10 may comprise a 0.8mm diameter stainless steel needle, preferably comprising a straight cone over a distance of more than 5 mm. The needle is preferably positioned at a horizontal distance X from the ion inlet aperture 9₁Is 5 mm. The needle 10 is preferably positioned such that the probe axis is in contact with the target 10On the side of the cone facing the ion inlet aperture 9, as shown in figure 2B. This position results in an optimized grazing angle of incidence, as shown by the arrowed line 16 in the top view schematic of fig. 2B. FIG. 2B also shows the relative vertical positions of the atomizer or probe 2 and the target 10, i.e., Z, according to a preferred embodiment₁=9mm，Z₂=1.5 mm. The atomizer or nebulizer 2 is preferably kept at 0V, the target 10 at 2.2kV, the ion inlet cone at 100V, the cone gas housing at 100V, and the heater assembly and source housing at ground potential. The nitrogen atomizer gas is preferably pressurized to 7bar, the nitrogen heater gas stream is preferably pressurized to deliver 1200L/hr, and the nitrogen cone gas stream is preferably pressurized to deliver 150L/hr.

A series of tests were conducted to test the relative sensitivity of the preferred impactor spray source, the conventional ESI ion source and the conventional APCI ion source.

A conventional ESI ion source was constructed by removing the target 10 and applying a 2.5kV potential directly to the nebulizer tip. All other potentials and gas flows were maintained as described above.

The APCI ion source was constructed by replacing the atomizer or nebulizer 2 with a conventional heated atomizer probe 17 as shown in fig. 3 and adding a corona discharge needle 18 as used in commercial APCI ion sources. As shown in fig. 3, the tip of the corona discharge needle 18 is positioned at distances X =7mm and Z =5.5 mm. The APCI ion source probe was operated at 550 deg.C with the heater gas at a flow rate of 500L/hr and unheated, and the corona discharge needle 18 was set at a current of 5 μ A. All other settings are as described above.

Test solutions were prepared consisting of 70/30 acetonitrile/water and included sulfadimethoxine (10 pg/μ L), verapamil (10 pg/μ L), erythromycin (10 pg/μ L), cholesterol (10 ng/μ L), and cyclosporin (100 pg/μ L). The test solution was injected into a 0.6mL/min stream of carrier liquid of 70/30 acetonitrile/water at a flow rate of 15 μ L/min, and then sampled by three different API ion sources.

Fig. 4 shows the relative signal intensities obtained for five test analytes using a conventional electrospray ion source, a conventional APCI ion source, and an impactor ion source according to the preferred embodiment. For each analyte, signal intensity was monitored for protonated molecules ([ M + H ] +). However, since signal saturation of the impactor spray is preferred, the cholesterol signal is measured on the carbon-13 isotope of the [ M + H ] + ion. It is clear from the figure that although APCI ion sources have certain advantages over ESI ion sources (e.g., for non-polar analytes such as cholesterol), ESI is generally more sensitive in both techniques. It is also apparent that the preferred impactor spray sources produce significantly greater signal sensitivity for all compound types than either ESI or APCI ion sources.

In an API ion source utilizing SACI ionization techniques, a large area target is maintained at an elevated potential to optimize ion signal. Fig. 5 shows the effect of varying target potential on the generated ion signal for a preferred impactor spray source, where the same test mixture was analyzed using a target potential of 0kV followed by a target potential of 2.2 kV. In contrast to SACI, it is clear that an elevated target potential, although advantageous, is not necessary for the ionization process. In contrast, a large area SACI source will lose > 90% of the ion signal under the same experimental conditions (data not shown).

Although not necessary, elevated target potentials are still advantageous and have the result of improving the qualitative aspects of the mass spectral data. To illustrate this, fig. 6A shows a mass spectrum obtained from an impactor ion source according to a preferred embodiment using a target potential of 2.2kV, fig. 6B shows a mass spectrum obtained from an impactor ion source according to an embodiment using a target potential of 0V, and fig. 6C shows a mass spectrum obtained from a conventional electrospray source using an optimized capillary potential of 4 kV. The mass spectra shown in fig. 6A and 6B obtained using an ion source according to a preferred embodiment are shown to produce more analyte ions than ESI, but the significantly elevated target potential also reduces the sensitivity of ion adduction to form ([ M + Na ] + and [ M + K ] +) so that the protonated molecules ([ M + H ] +) are only fundamental peaks for the mass spectrum shown in fig. 6A.

An experiment was performed to compare the sensitivity of an impactor ion source according to the preferred embodiment with the sensitivity of an SACI type ionization source. Fig. 7 shows a schematic of a SACI ion source being used. The SACI ion source was constructed by replacing the impactor needle target 10 with a 0.15mm thick rectangular tin plate 19 measured approximately 30mm x 15 mm. The sheet-like target 19 is angled at about 30 ° with respect to the horizontal and is positioned such that the intersection between the atomizer or nebulizer 2 axis and the target 19 is at X =4mm and Z =4 mm. The SACI ion source is optimized at 0V nebulizer or atomizer potential and 1kV target potential. All other gas flows and voltages are as described above for the preferred impactor spray source.

Figure 8 compares the relative signal intensities obtained with the SACI ion source and the impactor ion source according to the preferred embodiment. It was observed that the preferred impactor spray ion source was typically x5 to 10 times more sensitive than the large area SACI ion source.

Other embodiments are contemplated in which the performance of the preferred impactor ion source may be further improved by positioning the center wire in the bore of the liquid capillary 3. Video photography shows that the center wire will focus the droplet stream so that the target can be placed at the focal point to further increase the droplet flux density. The position of the focal spot is comparable to the nebulizer tip/target distance (1-2 mm) used in the preferred embodiment.

As described above, the SACI ion source converts a liquid flow into a vapor flow, which then impinges on a large area target. Experiments on SACI (Cristoni et al, j. mass spectra, 2005,40, 1550) have shown that ionization occurs due to interaction of neutral analyte molecules in the gas phase with the abundant proton surface of large area targets. Furthermore, there is a linear relationship between ionization efficiency and target area in the range of 1-4cm 2.

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

A pneumatic atomizer according to an embodiment of the present invention was further studied. The atomizer comprised an inner liquid capillary having an inner diameter of 127 μm and an outer diameter of 230 μm. The inner liquid capillary was surrounded by a gas capillary with an inner diameter of 330 μm pressurized to 7 bar.

Figure 9 shows typical data obtained from phase doppler velocimetry ("PDA") analysis of a preferred nebulizer for a 1ml/min liquid flow consisting of 90% water/10% methanol and nitrogen atomisation gas.

The PDA sampling points were scanned radially (probe axis = 0) along the spray at an axial distance of 5mm from the spray point (i.e. equal to the typical atomizer/target distance according to the preferred embodiment). Figure 9 shows that the atomiser typically produces a liquid having a sauter mean diameter (d 32) in the range 13-20 μm and having a mean axial velocity in excess of 100 ms-1.

Figure 9 also shows that very high velocity droplets are well collimated and are typically confined to within a 1mm radius from the probe axis.

The upper trace of fig. 10 shows the radial distribution of data rate N/T (number of valid samples per unit time) for the preferred pneumatic nebulizer and test conditions described above. The logarithmic plot demonstrates that the spray collimation is good, being two thirds greater than the total droplet mass defined within a radius of 1mm from the probe axis. The lower trace of fig. 10 shows the equivalent N/T distribution from a heated atomizer such as used in conventional SACI sources. The heated atomizer consisted of a pneumatic atomizer spraying into a 90mm long cylindrical tube with a 4mm diameter hole (temperature of tube =600 ℃). The N/T data for this atomizer was obtained at an axial distance of 7mm from the outlet end of the heated tube. It is important to note that the N/T for fewer detected droplets from the heated nebulizer (d 32 is typically 14 μm, data not shown) is typically three orders of magnitude less than that obtained from the pneumatic nebulizer according to the preferred embodiment. This is because a significant portion of the mass of the liquid is evaporated in a heated atomizer of the SACI type, resulting in a vapor stream containing a very low density of residual droplets.

Accordingly, it is known that SACI ion sources should be understood to include atomizers that emit a predominantly vapor flow, and thus the SACI ion source should be understood not to fall within the scope of the present invention.

Referring to the data presented in fig. 9 and 10, it can be considered that the physical model of the ion source according to the preferred embodiment is dominated by the impact of high velocity droplets on the target that is not directly heated by the source heater. This impact causes the formation of secondary droplets, where the characteristics of droplet breakup are determined by the weber number We given as follows:

We=ρU2d/σ (1)

where ρ is the droplet density, U is the droplet velocity, d is the droplet diameter, and σ is the droplet surface tension.

If the water droplet is considered to be at 40 ℃, the nitrogen environment at 100 ℃, d =18 μm and U =50ms "1, the droplet according to the preferred embodiment obtains a value of We = 640. It has been shown (in the literature) that for temperatures between 260-400 ℃, the number of re-atomized water droplets increases linearly with We in the range of 50-750 ℃ for impingement on a heated steel target. We =750, a single droplet typically results in the generation of 40 secondary droplets.

Thus, it is clear that the impactor target causes significant droplet breakup to produce a secondary stream consisting of charged droplets, neutrals, ions and clusters.

The impact efficiency of the system will be largely governed by the stokes number Sk, where:

Sk=ρd2U/18μa (2)

where ρ is the droplet density, d is the droplet diameter, U is the droplet velocity, μ is the gas viscosity, and a is the characteristic size of the target.

The impact efficiency increases with increasing Sk, thus favoring high speed large droplets and small target diameters. Thus, for the preferred impactor spray conditions described above, it is desirable for Sk to have a typical value of 30.

For Sk > >1, the droplets are likely to deviate from the streamlines and impinge on the target. Conversely, if the target size increases by an order of magnitude and the velocity decreases by an order of magnitude (i.e., similar conditions to SACI), the value of Sk drops to 0.3, at which point the droplets are more likely to follow the gas flow around the target. It is also known that the impact efficiency increases with decreasing reynolds number, which will further contribute to the streamlined character of the impactor spray target according to the preferred embodiment.

The shape of the secondary flow will be controlled by gas flow dynamics, and in particular by the reynolds number (Re), expressed as:

Re=ρvL/μ (3)

where ρ is the gas density, v is the gas velocity, μ is the gas viscosity, and L is an important dimension of the target.

With a 1mm diameter impactor target, a gas velocity of 50ms "1 and nitrogen at 100 ℃, a value of Re =3000 will be obtained.

Reynolds numbers in the range 2000-. Therefore, it is desirable that the wake from the target contain certain turbulence and eddy current characteristics. However, severe turbulence is undesirable which would prevent sampling of ions or droplets at the ion entrance cone.

The preferred ion source is adjusted by rocking the atomizer to move the impact region from one side of the rod-shaped target to the other. This results in a change to a wake which can be visually observed by intense illumination of the secondary droplet stream. Other embodiments are therefore also contemplated in which similar source optimization can be achieved with a centered impingement area and an asymmetric target cross-section (e.g., (the profile of) an airfoil).

While the present invention has been particularly shown and described with reference to preferred embodiments, it will be apparent to one skilled in the art that various changes in form and detail may be made therein without departing from the scope of the invention as defined by the appended claims.

Claims

1. An ion source, comprising:

one or more atomizers and one or more targets;

wherein the one or more atomizers are arranged and adapted to atomize over a period of time the one or more eluents emitted by the one or more liquid chromatography separation devices;

wherein the liquid flow rate of the one or more eluents is selected from the group consisting of: 1-10 muL/min; (ii)10-50 μ L/min; (iii)50-100 μ L/min; (iv) 100-; (v) 200-; (vi) 300-; (vii)400-500 μ L/min; (viii) 500-; (ix) 600-; (x) 700-; (xi) 800-; (xii) 900-; (xiii) 1000-; (xiv) 1500-; (xv) 2000-; and (xvi) >2500 μ L/min;

wherein the one or more atomisers are arranged and adapted to emit, in use, a stream of droplets which are caused to impinge on the one or more targets and ionise the droplets to form a plurality of ions;

wherein the average axial impact velocity of the droplets on the one or more targets is not less than 20 m/s;

wherein the one or more targets are arranged <10mm from the outlet of the one or more atomizers; and is

Wherein the one or more targets comprise: (i) one or more rods; or (ii) one or more needles having a conical portion.

2. An ion source as claimed in claim 1, wherein said droplet comprises an analyte droplet and said plurality of ions comprises analyte ions.

3. The ion source of claim 1, wherein the droplet comprises a reactant droplet and the plurality of ions comprises reactant ions.

4. An ion source as claimed in claim 3, further comprising one or more tubes arranged and adapted to supply one or more analyte or other gases to a region adjacent said one or more targets.

5. An ion source as claimed in claim 4, wherein said reagent ions are arranged to ionize said analyte gas to form a plurality of analyte ions.

6. An ion source as claimed in any preceding claim, wherein analyte liquid is supplied to said one or more targets and ionised to form a plurality of analyte ions, and/or reactant liquid is supplied to said one or more targets and ionised to form reactant ions which transfer charge to neutral analyte atoms or molecules to form analyte ions and/or which enhance formation of analyte ions.

7. An ion source as claimed in claim 6, wherein said one or more targets comprise one or more apertures, and wherein said analyte liquid and/or said reactant liquid is supplied directly to said one or more targets and emerges from said one or more apertures.

8. An ion source as claimed in claim 3, wherein said one or more targets are coated with one or more liquid, solid or gel 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 3, 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.

10. The ion source of claim 1, wherein the ion source comprises an atmospheric pressure ionization ("API") ion source.

11. An ion source according to claim 1 wherein the one or more nebulisers are arranged and adapted such that a substantial portion of the mass or substance emitted by the one or more nebulisers is in the form of non-vapour droplets.

12. The ion source of claim 11, wherein at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the mass or substance emitted by the one or more nebulisers is in droplet form.

13. 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 ("SMD", d32) of said droplets is in the following range: (i) <5 μm; (ii)5-10 μm; (iii)10-15 μm; (iv)15-20 μm; (v)20-25 μm; or (vi) >25 μm.

14. The ion source of claim 1, wherein said stream of droplets emitted from said one or more atomizers forms a secondary stream of droplets after impacting one or more targets.

15. An ion source as claimed in claim 14, wherein said stream of droplets and/or said stream of secondary droplets passes through a flow region having a reynolds number (Re) in the range: (i) < 2000; (ii) 2000-; (iii) 2500-; (iv) 3000-3500; (v) 3500-4000; or (vi) > 4000.

16. The ion source of claim 1, wherein at a point where said droplets impact said one or more targets, said droplets have a Weber number (We) selected from the group consisting of: (i) < 50; (ii)50-100 parts of; (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-; (xviii) 850-; (xix) 900-; (xx) 950-; and (xxi) > 1000.

17. The ion source of claim 1, wherein the droplets impact the one or more targets when the droplets impact the one or more targetsAt a point, the Stokes number (S) of the droplet_k) In the following ranges: (i) 1-5; (ii) 5-10; (iii)10-15 parts of; (iv)15-20 parts of; (v) 20-25; (vi) 25-30; (vii) 30-35; (viii)35-40 parts of; (ix) 40-45; (x)45-50 parts of; and (xi)>50。

18. The ion source of claim 1, wherein the mean axial impact velocity of the droplets on the one or more targets is selected from the group consisting of: (i)20-30 m/s; (ii)30-40 m/s; (iii)40-50 m/s; (iv)50-60 m/s; (v)60-70 m/s; (vi)70-80 m/s; (vii)80-90 m/s; (viii)90-100 m/s; (ix)100-110 m/s; (x)110-120 m/s; (xi)120-130 m/s; (xii)130-140 m/s; (xiii)140-150 m/s; and (xiv) >150 m/s.

19. The ion source of claim 1, wherein the one or more targets are disposed <9mm, <8mm, <7mm, <6mm, <5mm, <4mm, <3mm, or <2mm from an outlet of the one or more atomizers.

20. An ion source as claimed in claim 1, wherein said one or more nebulisers comprises a first capillary having an outlet which, in use, emits said stream of droplets.

21. An ion source as claimed in claim 20, wherein said first capillary is held, in use, at a potential: (i) -5 to-4 kV; (ii) -4 to-3 kV; (iii) -3 to-2 kV; (iv) -2 to-1 kV; (v) -1000 to-900V; (vi) -900 to-800V; (vii) 800 to 700V; (viii) -700 to-600V; (ix) -600 to-500V; (x) -500 to-400V; (xi) -400 to-300V; (xii) -300 to-200V; (xiii) -200 to-100V; (xiv) -100 to-90V; (xv) -90 to-80V; (xvi) -80 to-70V; (xvii) -70 to-60V; (xviii) -60 to-50V; (xix) -50 to-40V; (xx) -40 to-30V; (xxi) -30 to-20V; (xxii) -20 to-10V; (xxiii) -10 to 0V; (xxiv) 0-10V; (xxv) 10-20V; (xxvi) 20-30V; (xxvii) 30-40V; (xxviii) 40-50V; (xxix) 50-60V; (xxx) 60-70V; (xxxi) 70-80V; (xxxii) 80-90V; (xxxiii) 90-100V; (xxxiv) 100-200V; (xxxv) 200-300V; (xxxvi) 300-400V; (xxxvii) 400-500V; (xxxviii) 500-600V; (xxxix) 600-700V; (xl) 700-800V; (xli) 800-900V; (xlii) 900-1000V; (xliii)1-2 kV; (xliv)2-3 kV; (xlv)3-4 kV; and (xlvi)4-5 kV.

22. An ion source as claimed in claim 20, wherein the first capillary is held, in use, at a potential relative to a potential of a housing surrounding the ion source and/or a potential of an ion inlet arrangement to a first vacuum stage and/or the one or more targets of a mass spectrometer as follows: (i) -5 to-4 kV; (ii) -4 to-3 kV; (iii) -3 to-2 kV; (iv) -2 to-1 kV; (v) -1000 to-900V; (vi) -900 to-800V; (vii) 800 to 700V; (viii) -700 to-600V; (ix) -600 to-500V; (x) -500 to-400V; (xi) -400 to-300V; (xii) -300 to-200V; (xiii) -200 to-100V; (xiv) -100 to-90V; (xv) -90 to-80V; (xvi) -80 to-70V; (xvii) -70 to-60V; (xviii) -60 to-50V; (xix) -50 to-40V; (xx) -40 to-30V; (xxi) -30 to-20V; (xxii) -20 to-10V; (xxiii) -10 to 0V; (xxiv) 0-10V; (xxv) 10-20V; (xxvi) 20-30V; (xxvii) 30-40V; (xxviii) 40-50V; (xxix) 50-60V; (xxx) 60-70V; (xxxi) 70-80V; (xxxii) 80-90V; (xxxiii) 90-100V; (xxxiv) 100-200V; (xxxv) 200-300V; (xxxvi) 300-400V; (xxxvii) 400-500V; (xxxviii) 500-600V; (xxxix) 600-700V; (xl) 700-800V; (xli) 800-900V; (xlii) 900-1000V; (xliii)1-2 kV; (xliv)2-3 kV; (xlv)3-4 kV; and (xlvi)4-5 kV.

23. The ion source of claim 20, further comprising a wire located within a volume surrounded by said first capillary, wherein said wire is arranged and adapted to focus said stream of droplets.

24. The ion source of claim 20,

25. An ion source according to claim 24 wherein the second capillary surrounds and/or is concentric or non-concentric with the first capillary.

26. The ion source of claim 24 wherein the ends of the first and second capillaries are: (i) flush or parallel to each other; or (ii) are convex, concave, or non-parallel with respect to each other.

27. An ion source as claimed in claim 20, wherein the outlet of said first capillary has a diameter D, said droplet spray being arranged to impinge on an impingement region of said one or more targets.

28. The ion source of claim 27 wherein the impact region has a maximum dimension x, wherein the ratio x/D ≦ 30.

29. The ion source of claim 27 wherein the area of the impact region is selected from the group consisting of: (i)<0.01mm²；(ii)0.01-0.10mm²；(iii)0.10-0.20mm²；(iv)0.20-0.30mm²；(v)0.30-0.40mm²；(vi)0.40-0.50mm²；(vii)0.50-0.60mm²；(viii)0.60-0.70mm²；(ix)0.70-0.80mm²；(x)0.80-0.90mm²；(xi)0.90-1.00mm²；(xii)1.00-1.10mm²；(xiii)1.10-1.20mm²；(xiv)1.20-1.30mm²；(xv)1.30-1.40mm²；(xvi)1.40-1.50mm²；(xvii)1.50-1.60mm²；(xviii)1.60-1.70mm²；(xix)1.70-1.80mm²；(xx)1.80-1.90mm²；(xxi)1.90-2.00mm²；(xxii)2.00-2.10mm²；(xxiii)2.10-2.20mm²；(xxiv)2.20-2.30mm²；(xxv)2.30-2.40mm²；(xxvi)2.40-2.50mm²；(xxvii)2.50-2.60mm²；(xxviii)2.60-2.70mm²；(xxix)2.70-2.80mm²；(xxx)2.80-2.90mm²；(xxxi)2.90-3.00mm²；(xxxii)3.00-3.10mm²；(xxxiii)3.10-3.20mm²；(xxxiv)3.20-3.30mm²；(xxxv)3.30-3.40mm²；(xxxvi)3.40-3.50mm²；(xxxvii)3.50-3.60mm²；(xxxviii)3.60-3.70mm²；(xxxix)3.70-3.80mm²；(xl)3.80-3.90mm²(ii) a And (xli)3.90-4.00mm²。

30. An ion source as claimed in claim 20, further comprising one or more heaters arranged and adapted to supply one or more streams of heated gas to the outlet of said one or more nebulisers.

31. The ion source of claim 30, wherein:

(ii) The one or more heaters comprise one or more infrared heaters; and/or

(iii) The one or more heaters include one or more fired heaters.

32. The ion source of claim 1, further comprising one or more heating devices arranged and adapted to directly and/or indirectly heat the one or more targets.

33. An ion source as claimed in claim 32, wherein said one or more heating means comprises one or more lasers arranged and adapted to emit one or more laser beams which are incident on said one or more targets to heat said one or more targets.

34. An ion source as claimed in claim 1, wherein said one or more targets are held, in use, at potentials which are: (i) -5 to-4 kV; (ii) -4 to-3 kV; (iii) -3 to-2 kV; (iv) -2 to-1 kV; (v) -1000 to-900V; (vi) -900 to-800V; (vii) 800 to 700V; (viii) -700 to-600V; (ix) -600 to-500V; (x) -500 to-400V; (xi) -400 to-300V; (xii) -300 to-200V; (xiii) -200 to-100V; (xiv) -100 to-90V; (xv) -90 to-80V; (xvi) -80 to-70V; (xvii) -70 to-60V; (xviii) -60 to-50V; (xix) -50 to-40V; (xx) -40 to-30V; (xxi) -30 to-20V; (xxii) -20 to-10V; (xxiii) -10 to 0V; (xxiv) 0-10V; (xxv) 10-20V; (xxvi) 20-30V; (xxvii) 30-40V; (xxviii) 40-50V; (xxix) 50-60V; (xxx) 60-70V; (xxxi) 70-80V; (xxxii) 80-90V; (xxxiii) 90-100V; (xxxiv) 100-200V; (xxxv) 200-300V; (xxxvi) 300-400V; (xxxvii) 400-500V; (xxxviii) 500-600V; (xxxix) 600-700V; (xl) 700-800V; (xli) 800-900V; (xlii) 900-1000V; (xliii)1-2 kV; (xliv)2-3 kV; (xlv)3-4 kV; and (xlvi)4-5 kV.

35. An ion source as claimed in claim 1, wherein the one or more targets are held at potentials, in use, relative to a potential of a housing surrounding the ion source and/or a potential of an ion inlet arrangement to a first vacuum stage and/or the one or more nebulisers of a mass spectrometer, as follows: (i) -5 to-4 kV; (ii) -4 to-3 kV; (iii) -3 to-2 kV; (iv) -2 to-1 kV; (v) -1000 to-900V; (vi) -900 to-800V; (vii) 800 to 700V; (viii) -700 to-600V; (ix) -600 to-500V; (x) -500 to-400V; (xi) -400 to-300V; (xii) -300 to-200V; (xiii) -200 to-100V; (xiv) -100 to-90V; (xv) -90 to-80V; (xvi) -80 to-70V; (xvii) -70 to-60V; (xviii) -60 to-50V; (xix) -50 to-40V; (xx) -40 to-30V; (xxi) -30 to-20V; (xxii) -20 to-10V; (xxiii) -10 to 0V; (xxiv) 0-10V; (xxv) 10-20V; (xxvi) 20-30V; (xxvii) 30-40V; (xxviii) 40-50V; (xxix) 50-60V; (xxx) 60-70V; (xxxi) 70-80V; (xxxii) 80-90V; (xxxiii) 90-100V; (xxxiv) 100-200V; (xxxv) 200-300V; (xxxvi) 300-400V; (xxxvii) 400-500V; (xxxviii) 500-600V; (xxxix) 600-700V; (xl) 700-800V; (xli) 800-900V; (xlii) 900-1000V; (xliii)1-2 kV; (xliv)2-3 kV; (xlv)3-4 kV; and (xlvi)4-5 kV.

36. The ion source of claim 1, wherein in an operational mode, the one or more targets are held at a positive potential, and wherein the droplets impinging on the one or more targets form a plurality of positively charged ions.

37. The ion source of claim 1, wherein in an operational mode, the one or more targets are held at a negative potential, and wherein the droplets impinging on the one or more targets form a plurality of negatively charged ions.

38. The ion source of claim 1 further comprising means arranged and adapted to apply a sinusoidal or non-sinusoidal AC or RF voltage to the one or more targets.

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

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

41. The ion source of 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.

42. An ion source as claimed in claim 1, wherein said one or more targets comprise a plurality of target elements such that droplets from said one or more nebulisers land on the plurality of target elements, and/or wherein said target is arranged to have a plurality of impact points such that said droplets are ionised by a plurality of glancing deflections.

43. An ion source as claimed in claim 1, wherein said one or more targets are shaped such that gas flowing through said one or more targets is directed or deflected towards, parallel to, orthogonal to or away from an ion inlet arrangement of a mass spectrometer.

44. An ion source as claimed in claim 43, wherein at least some or a majority of said plurality of ions are arranged to be entrained, in use, into said gas flowing past said one or more targets.

45. An ion source as claimed in claim 1 wherein, in an operational mode, droplets from one or more reference or calibration nebulisers are directed onto said one or more targets.

46. An ion source as claimed in claim 1, wherein in an operational mode droplets from one or more analyte nebulisers are directed onto said one or more targets.

47. A mass spectrometer comprising an ion source according to any preceding claim.

48. A mass spectrometer as claimed in claim 47, further comprising an ion inlet arrangement to a first vacuum stage of said mass spectrometer.

49. A mass spectrometer of claim 48, wherein the ion inlet device comprises an ion aperture, an ion inlet cone, an ion inlet capillary, an ion inlet heated capillary, an ion channel, an ion mobility spectrometer or separator, a differential ion mobility spectrometer, a Field Asymmetric Ion Mobility Spectrometer (FAIMS) device, or other ion inlet.

50. A mass spectrometer of claim 48, wherein the one or more targets are positioned at a first distance X from the ion inlet arrangement in a first direction₁At and along a second direction a second distance Z from said ion inlet arrangement₁Wherein the second direction is orthogonal to the first direction, and wherein:

(i)X₁selected from the group consisting of: (i)0-1 mm; (ii)1-2 mm; (iii)2-3 mm; (iv)3-4 mm; (v)4-5 mm; (vi)5-6 mm; (vii)6-7 mm; (viii)7-8 mm; (ix)8-9 mm; (x)9-10 mm; and (xi)>10 mm; and/or

(ii)Z₁Selected from the group consisting of: (i)0-1 mm; (ii)1-2 mm; (iii)2-3 mm; (iv)3-4 mm; (v)4-5 mm; (vi)5-6 mm; (vii)6-7 mm; (viii)7-8 mm; (ix)8-9 mm; (x)9-10 mm; and (xi)>10mm。

51. A mass spectrometer of claim 48, wherein said one or more targets are positioned to deflect said stream of droplets and/or said plurality of ions towards said ion inlet arrangement.

52. A mass spectrometer of claim 48, wherein the one or more targets are positioned upstream of the ion inlet arrangement.

53. A mass spectrometer according to claim 48, wherein the stream of droplets is arranged to impinge on the conical portion of the one or more rods or the one or more needles in a manner that: (i) directly impinging on the centerline of the one or more rods or needles; or (ii) impinges on a side of the conical portion of the one or more stems or the one or more needles facing or away from an ion inlet aperture of the ion inlet device.

54. The mass spectrometer of claim 48, further comprising a housing surrounding the one or more nebulizers, the one or more targets, and the ion inlet device.

55. A mass spectrometer as claimed in claim 47, further comprising one or more deflecting or pushing electrodes, wherein in use one or more DC voltages or DC voltage pulses are applied to said one or more deflecting or pushing electrodes to deflect or push ions towards an ion inlet arrangement of said mass spectrometer.

56. A method of ionizing a sample, comprising:

nebulizing over a period of time one or more eluents emitted by one or more liquid chromatography separation devices;

impinging a stream of droplets on one or more targets to ionize the droplets, thereby forming a plurality of analyte ions;

wherein the stream is emitted by the one or more atomizers, and wherein the one or more targets are arranged <10mm from the outlet of the one or more atomizers; and is

57. A method of mass spectrometry comprising a method of ionising a sample according to claim 56.