Methods for compressing an ion beam

Abstract

Methods of mass spectrometry or ion mobility spectrometry, including: Accumulation of ions in an ion capture volume (4); Release of ions from the ion capture volume (4) into an ion separation region (2) having a longitudinal axis, wherein the ions leave the ion capture volume (4) distributed over an initial width in a first direction orthogonal to the longitudinal axis; Transfer of the ions along the longitudinal axis of the ion separation region (2) such that the ions separate along the longitudinal axis according to a physicochemical property; Compression of the width in the first direction over which the ions are distributed as the ions separate along the longitudinal axis, so that the ions are distributed over a width in the first direction that is smaller than the original width; and Transmission of the compressed ion beam through an outlet opening (6), wherein the original width of the ion beam in the first direction is greater than the width of the outlet opening (6) in the first direction, and wherein the ion beam is compressed in the first direction such that when the ions reach the outlet opening (6), the ion beam has a width in the first direction that is less than or equal to the width of the outlet opening (6) in the first direction; wherein the ions leave the ion capture volume (4) directly into a region where the ions are compressed in the first direction, so that the ions begin to be compressed in the first direction immediately after exiting the ion capture volume (4).

Description

AREA OF INVENTION

[0001] The present invention relates to a method of mass spectrometry or ion mobility spectrometry in which an ion beam is compressed in width. BACKGROUND

[0002] Space charge effects can limit the performance of ion mobility spectrometers and mass spectrometers in a variety of ways. One of the most common limitations is the ability to accumulate large ion populations in an ion trap before ejection or release of the ions into a downstream analyzer. Space charge effects in ion traps can be limited by making the ion trap relatively large to provide a relatively large ion capture volume. However, to simultaneously eject ions from such an ion trap, the ions must be ejected in a relatively wide packet or pulse. This ion packet must then be bundled in width to be guided through the relatively narrow differential pump orifices located between regions of differing pressures.However, this bundling compresses and concentrates the ion packet, thus leading again to the problem of space charge effects.

[0003] Document WO 2013 / 067366 A2 discloses a method and an apparatus for improving ion mobility spectrometry by using an ion gate based on a local RF field barrier. Document WO 2013 / 027054 A2 relates to an ion trap with a spatially extended ion capture area. Document US 7,723,679 B2 relates to a coaxial hybrid ion trap. It is desirable to provide an improved method of mass spectrometry or ion mobility spectrometry and an improved mass spectrometer or ion mobility spectrometer. SUMMARY

[0004] According to the invention, methods of mass spectrometry or ion mobility spectrometry and mass spectrometers or ion mobility spectrometers with the features of the independent claims are provided; dependent claims relate to preferred embodiments.

[0005] In a first aspect, the present invention provides a method of mass spectrometry or ion mobility spectrometry, comprising: Accumulation of ions in an ion capture volume; Release of ions from the ion capture volume into an ion separation region having a longitudinal axis, wherein the ions leave the ion capture volume distributed over an initial width in a first direction orthogonal to the longitudinal axis; Transfer of ions along a longitudinal axis of the ion separation region, such that the ions separate along the longitudinal axis according to a physicochemical property; Compression of the width in the first direction over which the ions are distributed as the ions separate along the longitudinal axis, such that the ions are distributed over a width in the first direction that is less than or equal to the original width; and Transmission of the compressed ion beam through an ion receiving aperture, wherein the initial width of the ion beam in the first direction is greater than the width of the aperture in the first direction, and wherein the ion beam is compressed in the first direction such that when the ions reach the aperture, the ion beam has a width in the first direction that is less than or equal to the width of the outlet aperture in the first direction.

[0006] By compressing the ion beam, the ions can be focused to be directed through a relatively small ion receiving aperture. This compression increases the charge density of the ions at points along the longitudinal axis, thus resulting in such compression. However, separating the ions according to their physicochemical properties along the longitudinal axis reduces the charge density of the ions at any given point along the longitudinal axis and thus at least partially counteracts the effect of the ion beam compression. The present invention therefore makes it possible to focus ions without increasing the charge density and thus the space charge effects to undesirable levels.

[0007] Ion funnel arrays are known for compressing ion clouds into a focused beam. However, it has not yet been recognized that ions from large ion capture volumes can be focused while space charge effects can be attenuated by separating the ions before or during compression.

[0008] It is known to use a relatively wide ion mobility separator to separate ions according to their ion mobility. It is also known to funnel the ions downwards into a narrower ion beam after separation, in order to transfer the separated ions into a relatively narrow, downstream device. However, the step of separating the ions to determine their ion mobility and the step of funneling the ions downwards have always been considered isolated and independent steps. It was not recognized in the prior art that ion separation can be used during the compression of an ion beam to avoid negative space charge effects that occur during compression.

[0009] It is understood that the term "ion beam" used here can refer to an essentially continuous stream of ions that have been separated according to their physicochemical properties, or to one or more groups of ions that have been separated from other ions along their path through the separation area.

[0010] The separated ions can leave the ion separation area at different exit times, and the exit times must not be used when determining the values ​​of a physicochemical property of the ions.

[0011] In a second aspect, the present invention provides a method of mass spectrometry or ion mobility spectrometry, comprising: Accumulation of ions in an ion capture volume; Release of ions from the ion capture volume into an ion separation region having a longitudinal axis, wherein the ions leave the ion capture volume distributed over an initial width in a first direction orthogonal to the longitudinal axis; Transfer of ions along a longitudinal axis of the ion separation region, such that the ions separate along the longitudinal axis according to a physicochemical property; and Compression of the width in the first direction over which the ions are distributed while the ions are separating along the longitudinal axis, or after the ions have been separated along the longitudinal axis, so that the ions are distributed over a width in the first direction that is less than or equal to the original width; wherein the separated ions leave the ion separation area at different exit times and wherein the exit times may not be used in determining the values ​​of a physicochemical property of the ions.

[0012] As described above, it is known to use a relatively wide ion mobility separator to separate ions according to their ion mobility. It is also known to funnel the ions downwards into a narrower ion beam after separation, in order to transfer the separated ions into a relatively narrow, downstream device. However, the ion separation step is performed to determine the ion mobility of the ions. It has not been recognized in the prior art that ion separation can be used during the compression of an ion beam to avoid negative space charge effects that occur during compression. Accordingly, it is neither known nor obvious to separate ions and compress the ion beam in a context where ion separation is not used to determine the ion mobility of the ions.

[0013] The following characteristics are described with reference to both the first and the second aspect.

[0014] Ions can be passed through the ion separation section with different transit or drift times, and the transit or drift times must not be used when determining the values ​​of a physicochemical property of the ions.

[0015] The exit times, transit times or drift times must not be used to determine the ion mobility of the separated ions.

[0016] In an unclaimed example, the compression can begin in the ion separation region at a distance of x cm from the point where ions are released from the ion capture volume, where x is selected from the group consisting of: ≤ 100; ≤ 90; ≤ 80; ≤ 70; ≤ 60; ≤ 50; ≤ 40; ≤ 30; ≤ 20; ≤ 10; ≤ 5; ≤ 4; ≤ 3; ≤ 2; and ≤ 1.

[0017] The ions leave the ion capture volume directly into a region where the ions are compressed in the first direction, so that the ions are compressed in the first direction immediately after exiting the ion capture volume.

[0018] As explained above, prior art has not recognized the possibility of using ion separation during the compression of an ion beam to avoid adverse space charge effects that occur during compression. Accordingly, it is not known to compress an ion beam released from a relatively wide ion capture volume while the ions are separating, such that the compression begins at or relatively close to the point where the ions are released from the ion capture volume.

[0019] The ions can be supplied to the separation zone as a packet or ion pulse. Within the separation zone, the ions can separate into a more continuous ion beam.

[0020] The ion beam can be compressed to gradually narrow the widths in the first direction as the ions move along the longitudinal axis of the separation area.

[0021] The ion beam can be continuously and gradually compressed in the first direction over y% of the length of the ion separation region, where y is selected from the group consisting of: > 5%; > 10%; > 15%; > 20%; > 25%; > 30%; > 35%; > 40%; > 50%; > 55%; > 60%; > 65%; > 70%; > 75%; > 80%; > 85%; > 90%; and > 95%.

[0022] To eliminate any doubt, the length of the ion separation zone runs in the direction along the longitudinal axis.

[0023] The method can include the accumulation of ions in the ion capture volume and the subsequent release, pulsing, or ejection of the ions from the ion capture volume into the separation area.

[0024] The ions are distributed across their original width at the moment they are released or pulsed from the capture area.

[0025] The process can involve the accumulation of successive ions in the capture region from an upstream ion source, after the previously captured ions have been released or ejected from the ion capture region and while they are being separated in the separation region.

[0026] The process can repeatedly perform a large number of process cycles, with each process cycle comprising the accumulation of ions in the ion capture area and the subsequent pulsing of the ions into the separation area.

[0027] The ions can separate along the longitudinal axis according to an ion mobility or a mass-charge ratio.

[0028] The separation zone can be filled with gas.

[0029] The physicochemical property according to which the ions are separated in the ion separation region can be the ion mobility due to a gas present in the separation region. Alternatively, the physicochemical property can be a mass-to-charge ratio.

[0030] The method can involve pushing ions away from the ion capture volume along the longitudinal axis of the separation region.

[0031] One or more static and / or time-varying electric fields can be used to drive the ions along the longitudinal axis. For example, a DC voltage gradient can be applied along the longitudinal axis of the separation zone. Alternatively or additionally, a DC potential barrier can be moved along the longitudinal axis of the separation zone to guide ions along this barrier and toward the opening. This can be achieved by successively applying one or more voltages to successive electrodes arranged along the longitudinal axis of the separation zone. The DC barrier can be moved repeatedly along the separation zone.

[0032] Ions can be compressed in the first direction by RF and / or DC potential barriers.

[0033] An RF and / or DC field can be arranged along the longitudinal axis of the separation zone to compress the ion beam in the first direction, and a characteristic of the field can vary with distance along the longitudinal axis to produce varying degrees of compression of the ion beam along the longitudinal axis. This characteristic can be, for example, the amplitude of the RF and / or DC field or the frequency of the voltage used to generate the RF field.

[0034] The method of the first aspect can further comprise the transmission of the compressed ion beam through an ion receiving aperture, wherein the initial width of the ion beam in the first direction is greater than the width of the aperture in the first direction, and wherein the ion beam is compressed in the first direction such that, when the ions reach the aperture, the ion beam has a width in the first direction that is less than or equal to the width of the outlet aperture in the first direction.

[0035] The ion uptake aperture described with respect to both the first and second aspects of the invention can be an opening in a wall or electrode, for example, an opening in a wall between two vacuum chambers of a spectrometer. The physical boundaries of the opening can thus determine the width and size of the ion uptake aperture. Alternatively, the ion uptake aperture can be defined by a downstream component, wherein the region of the ion uptake aperture corresponds to the region over which ions can be taken up by the component. The width and size of the ion uptake aperture can thus be defined by the physical dimensions of an input to the component and / or by the potentials applied to the component.

[0036] The opening can be a differential pump opening formed in a wall separating two areas which are held at different pressures.

[0037] The opening can be provided in a wall and a plurality of electrodes can be arranged on the wall radially outside the opening in at least the first direction, the method comprising applying direct current and / or alternating current voltages to the electrodes to compress the ions in the first direction.

[0038] The procedure may involve applying RF potentials to the electrodes to repel ions and prevent them from coming into contact with the wall.

[0039] The electrodes can comprise a variety of closed-loop electrodes arranged concentrically around and radially outside the opening.

[0040] The electrodes can be ring-shaped, round, or have another shape. Closed-loop electrodes can have the same shape as the circumference of the opening.

[0041] The method may involve applying different direct current voltages to different electrodes to form a direct current voltage gradient that compresses the ion beam in the first direction; and / or it may involve successively applying one or more direct current voltages to successive electrodes in a direction from the radially outermost electrode to the radially innermost electrode, such that a direct current potential barrier runs radially inward toward the opening and radially compresses the ion beam.

[0042] The DC potential barrier can be designed so that it repeatedly moves from the outermost electrode to the innermost electrode.

[0043] The ions can leave the ion capture area, which is distributed over an original width in a second direction orthogonal to the longitudinal axis and to the first direction; and wherein the method comprises compressing the width in the second direction over which the ions are distributed while the ions are separating along the longitudinal axis, or after the ions have been separated along the longitudinal axis, such that the ions are distributed over a width in the second direction which is less than or equal to the original width in the second direction.

[0044] The compressed ion beam can then be passed through the opening.

[0045] The ions can be compressed in the second direction in a manner corresponding to the compression in the first direction. The features corresponding to those described here with regard to the compression of the ions in the first direction can be applied to the step of compressing the ions in the second direction. It is also taken into account that ions can be compressed simultaneously in all radial directions relative to the longitudinal axis.

[0046] The capture volume and / or ion separation region can confine ions in a volume that does not have a circular, toroidal, or cylindrical cross-section.

[0047] Compression can occur in a linear direction.

[0048] The ions can be passed directly from the ion separation region into a downstream opening or device, and the ion separation region and the downstream opening or device can have the same cross-sectional shape.

[0049] The cross-sectional shape can be the shape in the plane perpendicular to the longitudinal axis.

[0050] The procedure may include the detection or analysis of ions that pass through the opening, for example, the mass analysis of such ions.

[0051] The compressed ion beam can be subjected to ion analysis and / or further processing; for example, it can be directed onto a surface to perform surface-induced dissociation (SID) of the ions, or it can be directed into a reaction chamber so that the ions react with other ions or molecules, or a laser can be directed at the ions.

[0052] It is taken into account that the procedure of the second aspect is not limited to the fact that it includes the feature that the exit times are not used in determining the values ​​of a physicochemical property of the ions.

[0053] Accordingly, a third aspect of the present invention provides a method of mass spectrometry or ion mobility spectrometry, comprising: Accumulation of ions in an ion capture volume; Release of ions from the ion capture volume into an ion separation region having a longitudinal axis, wherein the ions leave the ion capture region which is distributed over an initial width in a first direction orthogonal to the longitudinal axis; Transfer of ions along a longitudinal axis of the ion separation region, such that the ions separate along the longitudinal axis according to a physicochemical property; and Compression of the width in the first direction over which the ions are distributed while the ions are separating along the longitudinal axis, or after the ions have been separated along the longitudinal axis, such that the ions are distributed over a width in the first direction that is less than or equal to the original width.

[0054] The present invention also provides a spectrometer that is arranged and configured to perform any of the process steps described herein.

[0055] Accordingly, the first aspect of the present invention provides a mass spectrometer or an ion mobility spectrometer comprising the following: an ion source; an ion capture volume; an ion separation region having a longitudinal axis; wherein the ion capture volume is configured such that the ions exiting the ion capture volume are distributed over an initial width in a first direction orthogonal to the longitudinal axis; and a controller configured to control the spectrometer to: to transfer ions along the longitudinal axis of the ion separation region, so that the ions separate along the longitudinal axis according to a physicochemical property; and to compress the width in the first direction over which the ions are distributed, while the ions separate along the longitudinal axis, so that the ions are distributed over a width in the first direction that is less than or equal to the original width; and to transmit the compressed ion beam through an ion receiving aperture, wherein the original width of the ion beam in the first direction is greater than the width of the aperture in the first direction, and wherein the ion beam is compressed in the first direction such that when the ions reach the aperture, the ion beam has a width in the first direction that is less than or equal to the width of the outlet aperture in the first direction.

[0056] The second aspect of the present invention provides a mass spectrometer or an ion mobility spectrometer comprising the following: an ion source; an ion capture volume; an ion separation region having a longitudinal axis; wherein the ion capture volume is configured such that the ions exiting the ion capture volume are distributed over an initial width in a first direction orthogonal to the longitudinal axis; and a controller configured to control the spectrometer to: to transfer ions along the longitudinal axis of the ion separation region, so that the ions separate along the longitudinal axis according to a physicochemical property; and to compress the width in the first direction over which the ions are distributed while the ions separate along the longitudinal axis, or after the ions have been separated along the longitudinal axis, so that the ions are distributed over a width in the first direction that is less than or equal to the original width. wherein the separated ions leave the ion separation area at different exit times, and wherein the spectrometer does not determine the values ​​of a physicochemical property of the ions from the exit times.

[0057] The third aspect of the present invention provides a mass spectrometer or an ion mobility spectrometer comprising the following: an ion source; an ion capture volume; an ion separation region having a longitudinal axis; wherein the ion capture volume is configured such that the ions exiting the ion capture volume are distributed over an initial width in a first direction orthogonal to the longitudinal axis; and a controller configured to control the spectrometer to: to transfer ions along the longitudinal axis of the ion separation region, so that the ions separate along the longitudinal axis according to a physicochemical property; and to compress the width in the first direction over which the ions are distributed while the ions separate along the longitudinal axis, or after the ions have been separated along the longitudinal axis, so that the ions are distributed over a width in the first direction that is less than or equal to the original width.

[0058] The mass spectrometer may include the following: (a) an ion source selected from the group consisting of: (i) an electrospray ionization (“ESI”) ion source; (ii) an atmospheric pressure photo-ionization (“APPI”) ion source; (iii) an atmospheric pressure chemical ionization (“APCI”) ion source; (iv) a matrix-assisted laser desorption ionization (“MALDI”) ion source; (v) a laser desorption ionization (“LDI”) ion source; (vi) an atmospheric pressure ionization (“API”) ion source; (vii) a silicon desorption / ionization (“DIOS”) ion source; (viii) an electron impact (“EI”) ion source; (ix) a chemical ionization (“CI”) ion source; (ix) a field ionization (“Fl”) ion source; (xi) a field desorption (“FD”) ion source; (xii) an inductively coupled plasma (“ICP”) ion source;) a fast atom bombardment (“FAB”) ion source; (xiv) a liquid secondary ion mass spectrometry (“LSI MS”) ion source;(xv) a desorption electrospray ionization (“DESl”) ion source; (xvi) a nickel-63 radioactive ion source; (xvii) a matrix-assisted atmospheric pressure laser desorption ionization ion source; (xviii) a thermospray ion source; (xix) an atmospheric sampling glow discharge ionization (“ASGDI”) ion source; (xx) a glow discharge ion source; (xxi) an impactor ion source; (xxii) a direct analysis in real time (“DART”) ion source; (xxiii) a laser spray ionization (“LSI”) ion source; (xxiv) a sonic spray ionization (“SSI”) ion source; (xxv) a matrix-assisted inlet ionization (“MAII”) ion source; (xxvi) a solvent-assisted inlet ionization (“SAII”) ion source; (xxvii) a desorption electrospray ionization (“DESI”) ion source; and (xxviii) a laser ablation electrospray ionization (“LAESI”) ion source; and / or; (b one or more continuous or pulsed ion sources; and / or (c) one or more ion guides; and / or (d) one or more ion mobility separation devices and / or one or more field asymmetric ion mobility spectrometer devices; and / or (e) one or more ion traps or one or more ion containment areas; and / or (f) one or more collision, fragmentation, or reaction cells selected from the group consisting of: (i) a collision-induced dissociation (“CID”) fragmentation device; (ii) a surface-induced dissociation (“SID”) fragmentation device; (iii) an electron transfer dissociation (“ETD”) fragmentation device; (iv) an electron capture dissociation (“ECD”) fragmentation device; (v) an electron impact or collision dissociation fragmentation device; (vi) a photo-induced dissociation (“PID”) fragmentation device; (vii) a laser-induced dissociation fragmentation device; (viii) an infrared radiation-induced dissociation device; (ix) an ultraviolet radiation-induced dissociation device; (x) a nozzle-skimmer interface fragmentation device; (xi) an in-source fragmentation device; (xii) an in-source impact-induced dissociation fragmentation device;(xiii) a thermal or temperature source fragmentation device; (xiv) an electric field-induced fragmentation device; (xv) a magnetic field-induced fragmentation device; (xvi) an enzyme digestion or enzyme degradation fragmentation device; (xvii) an ion-ion reaction fragmentation device; (xviii) an ion-molecule reaction fragmentation device; (xix) an ion-atom reaction fragmentation device; (xx) an ion-metastable ion reaction fragmentation device; (xxi) an ion-metastable molecule reaction fragmentation device; (xxii) an ion-metastable atom reaction fragmentation device; (xxiii) an ion-ion reaction device for reacting ions to form adducts or productions; (xxiv) an ion-molecule reaction device for reacting ions to form adducts or productions;(xxv) an ion-atom reaction device for reacting ions to form adducts or productions; (xxvi) an ion-metastable ion reaction device for reacting ions to form adducts or productions; (xxvii) an ion-metastable molecular reaction device for reacting ions to form adducts or productions; (xxviii) an ion-metastable atom reaction device for reacting ions to form adducts or productions; and (xxix) an electron ionization dissociation ("EID") fragmentation device; and / or; (g) a mass analyzer selected from the group consisting of: (i) a quadrupole mass analyzer; (ii) a two-dimensional or linear quadrupole mass analyzer; (iii) a Paul or three-dimensional quadrupole mass analyzer; (iv) a Penning trap mass analyzer; (v) an ion trap mass analyzer; (vi) a magnetic sector mass analyzer; (vii) an ion cyclotron resonance (“ICR”) mass analyzer; (viii) a Fourier transform ion cyclotron resonance (“FTICR”) mass analyzer; (ix) an electrostatic mass analyzer configured to generate an electrostatic field with a quadrologarithmic potential distribution; (x) an electrostatic Fourier transform mass analyzer; (xi) a Fourier transform mass analyzer; (xii) a time-of-flight mass analyzer; (xiii) an orthogonal acceleration time-of-flight mass analyzer; and (xiv) a linear acceleration time-of-flight mass analyzer; and / or (h) one or more energy analyzers or electrostatic energy analyzers; and / or (i) one or more ion detectors; and / or (j) one or more mass filters selected from the group consisting of: (i) a quadrupole mass filter; (ii) a two-dimensional or linear quadrupole ion trap; (iii) a Paul or three-dimensional quadrupole ion trap; (iv) a Penning ion trap; (v) an ion trap; (vi) a magnetic sector mass filter; (vii) a time-of-flight mass filter; and (viii) a Wien filter; and / or (k) a device or ion gate for pulsing ions; and / or (l) a device for converting a substantially continuous ion beam into a pulsed ion beam.

[0059] The mass spectrometer may also include the following: (i) a C-trap and a mass analyzer comprising an outer tubular electrode and a coaxial inner spindle-shaped electrode forming an electrostatic field with a quadrologarithmic potential distribution, wherein in a first operating mode ions are transferred to the C-trap and then injected into the mass analyzer, and wherein in a second operating mode ions are transferred to the C-trap and then transferred to a collision cell or electron transfer dissociation device, fragmenting at least some ions into fragment ions, and wherein the fragment ions are then transferred to the C-trap before being injected into the mass analyzer; and / or (ii) a ring-stack ion guide comprising multiple electrodes, each having an opening through which ions pass during use, wherein the distance between the electrodes increases along the ion path, and wherein the openings in the electrodes in an upstream section of the ion guide have a first diameter, and wherein the openings in the electrodes in a downstream section of the ion guide have a second diameter which is smaller than the first diameter, and wherein opposite phases of an alternating or RF voltage are applied to successive electrodes during use.

[0060] The mass spectrometer may further include a device configured and designed to supply an alternating or RF voltage to the electrodes. The alternating or RF voltage optionally has an amplitude selected from the group consisting of: (i) about < 50 V peak-to-peak; (ii) about 50–100 V peak-to-peak; (iii) about 100–150 V peak-to-peak; (iv) about 150–200 V peak-to-peak; (v) about 200–250 V peak-to-peak; (vi) about 250–300 V peak-to-peak; (vii) about 300–350 V peak-to-peak; (viii) about 350–400 V peak-to-peak; (ix) approximately 400-450 V peak-to-peak; (x) approximately 450-500 V peak-to-peak and (xi) approximately > 500 V peak-to-peak.

[0061] The alternating or RF voltage can have a frequency selected from the group consisting of: (i) < about 100 kHz; (ii) about 100-200 kHz; (iii) about 200-300 kHz; (iv) about 300-400 kHz; (v) about 400-500 kHz; (vi) about 0.5-1.0 MHz; (vii) about 1.0-1.5 MHz; (viii) about 1.5-2.0 MHz; (ix) about 2.0-2.5 MHz; (x) about 2.5-3.0 MHz; (xi) about 3.0-3.5 MHz; (xii) about 3.5-4.0 MHz; (xiii) about 4.0-4.5 MHz; (xiv) about 4.5-5.0 MHz; (xv) approximately 5.0-5.5 MHz; (xvi) approximately 5.5-6.0 MHz; (xvii) approximately 6.0-6.5 MHz; (xviii) approximately 6.5-7.0 MHz; (xix) approximately 7.0-7.5 MHz; (xx) approximately 7.5-8.0 MHz; (xxi) approximately 8.0-8.5 MHz; (xxii) approximately 8.5-9.0 MHz; (xxiii) approximately 9.0-9.5 MHz; (xxiv) approximately 9.5-10.0 MHz and (xxv) > approximately 10.0 MHz.

[0062] The mass spectrometer may include a chromatography or other separation device located upstream of an ion source. The chromatography separation device may be a liquid chromatography or gas chromatography device. The separation device may include: (i) a capillary electrophoresis (“CE”) separation device, (ii) a capillary electrochromatography (“CEC”) separation device, (iii) a separation device with an essentially rigid ceramic-based multilayer microfluidic substrate (“ceramic tile”), or (iv) a supercritical fluid chromatography separation device.

[0063] The ion guidance can be maintained at a pressure selected from the group consisting of: (i) < about 0.0001 mbar, (ii) about 0.0001-0.001 mbar; (iii) about 0.001-0.01 mbar; (iv) about 0.01-0.1 mbar; (v) about 0.1-1 mbar; (vi) about 1-10 mbar; (vii) about 10-100 mbar; (viii) about 100-1000 mbar and (ix) > about 1000 mbar.

[0064] The analytes can be subjected to electron transfer dissociation (ETD) fragmentation in an electron transfer dissociation fragmentation device. The analytes can be caused to interact with ETD reagents within an ion guide or fragmentation device.

[0065] Optionally, to effect electron transfer dissociation, either: (a) analyte ions are fragmented or caused to dissociate and form product or fragment ions after interacting with reagent ions; and / or (b) electrons are transferred from one or more reagent anions or negatively charged ions to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions; and / or (c) analyte ions are fragmented or caused to dissociate and form product or fragment ions after interacting with neutral reagent gas molecules or atoms or a non-ionic reagent gas;and / or (d) electrons are transferred from one or more neutral nonionic or uncharged starting gases or vapors to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions; and / or (e) electrons are transferred from one or more neutral nonionic or uncharged superbase reagent gases or vapors to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions;and / or (f) electrons are transferred from one or more neutral, non-ionic or uncharged alkali metal gases or vapors to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions;and / or (g) electrons are transferred from one or more neutral, nonionic or uncharged gases, vapors or atoms to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions, wherein the one or more neutral, nonionic or uncharged gases, vapors or atoms are selected from the group consisting of: (i) sodium vapor or atoms, (ii) lithium vapor or atoms, (iii) potassium vapor or atoms, (iv) rubidium vapor or atoms, (v) cesium vapor or atoms, (vi) francium vapor or atoms, (vii) C60 vapor or atoms and (viii) magnesium vapor or atoms.;

[0066] The multiply charged analyte cations or positively charged ions can include peptides, polypeptides, proteins, or biomolecules.

[0067] Optionally, to effect electron transfer dissociation: (a) the reagent anions or negatively charged ions are derived from a polyaromatic hydrocarbon or a substituted polyaromatic hydrocarbon and / or (b) the reagent anions or negatively charged ions are derived from the group consisting of: (i) anthracene; (ii) 9,10-diphenylanthracene; (iii) naphthalene; (iv) fluorine; (v) phenanthrene; (vi) pyrene; (vii) fluoranthene; (viii) chrysene; (ix) triphenylene; (x) perylene; (xi) acridine; (xii) 2,2'-dipyridyl; (xiii) 2,2'-biquinoline; (xiv) 9-anthracenecarbonitrile; (xv) dibenzothiophene; (xvi) 1,10'-phenanthroline; (xvii) 9'-Anthracenecarbonitrile and (xviii) anthraquinone and / or (c) contain the reagents or negatively charged ions azobenzene anions or azobenzene radical anions.

[0068] The process of electron transfer dissociation fragmentation can involve the interaction of analyte ions with reagents, where the reagents include dicyanobenzene, 4-nitrotoluene, or azulene.

[0069] The method disclosed here enables the use of an extended capture region to accommodate a large ion population, thus reducing space charge effects within the capture region. Ions from this capture region then enter a mobility separator, which compresses the separating ion bunches into smaller volumes with lower ion populations suitable for passage through a differential pump orifice. The process of ion mobility separation in a direction other than the compression direction facilitates the compression of ions into smaller volumes than would otherwise be possible for the entire population contained within the original capture region, due to space charge effects.

[0070] The methods disclosed here support the overcoming of limitations caused by space charge effects in ion mobility spectrometers and mass spectrometers, which is an increasingly important issue with brighter ion sources. BRIEF DESCRIPTION OF THE DRAWINGS

[0071] Various embodiments of the invention are now described by way of example with reference to the accompanying drawings, wherein: Fig. Figure 1A shows a schematic representation of an ion mobility spectrometer according to an embodiment of the present invention and Fig. Figures 1B-1D show different representations of the charge density of the ions along the ion mobility spectrometer at different time points; and Fig. Figure 2 shows a schematic representation of another embodiment, wherein ions are compressed radially inwards as they move along the separation area of ​​the ion mobility spectrometer. DETAILED DESCRIPTION

[0072] Fig. Figure 1A shows a schematic representation of an ion mobility spectrometer (IMS) device according to a preferred embodiment of the present invention. The IMS device has an ion mobility separation region 2, which is arranged between an ion capture region 4 and an outlet opening 6. The ion capture region 4 can be elongated in a first direction that is orthogonal to the longitudinal axis of the region 2, so that a relatively large ion volume can be captured in the elongated capture region 4. The ion trap 4 can be extended in the first direction so that ions are captured over a length in the first direction that is longer than the length of the outlet opening 6 in the first direction.

[0073] During operation, ions accumulate in the ion capture area 4 until the desired number of ions is captured. The ions are then pulsed from the ion capture area 4 into the separation area 2. The ions move along the longitudinal axis of the separation area 2 towards the outlet port 6. As the ions move through the separation area 2, they separate according to their ion mobility and then exit the IMS device through the outlet port 6. The separation area 2 is filled with gas, and the ions separate according to their ion mobility as they pass through the gas. Therefore, the ions pass through the outlet ports 6 in a sequence from high to low ion mobility and can be detected or transferred to a downstream analyzer, such as a mass analyzer.As the ions are transferred through the separation region 2, various ions from an ion source located upstream of the device are accumulated in the ion capture region 4. These ions remain trapped in the ion capture region until they are ready to be pulsed into the separation region 2 in a subsequent packet.

[0074] The Chevrons 8 in Fig. Figure 1A represents the movement of the ions from the ion capture area 4 to the outlet opening 6. As the ions are transferred from the ion capture area 4 to the outlet opening 6, the ions are compressed in the first direction from a beam with a width equal to the width of the ion capture area 4 to a beam with a width equal to or less than the width of the outlet opening 6. This is described in Fig. 1A is represented by the converging dashed lines. If the ions are compressed in the first direction to be transferred through the relatively narrow outlet openings 6, an increase in space charge effects would be expected, as with conventional arrangements. However, since the ions are separated along the separation region 2 during compression, the amount of charge at any point along the longitudinal axis is reduced, thus compensating for the increased charge density caused by compression of the ions in the first direction. Therefore, space charge effects do not become problematic, even if the ions have been compressed in the first direction to exit the narrow outlet opening 6.

[0075] Fig. Figure 1B shows the charge quantity in the IMS device as a function of the length along the device at time T=0, when the ions are stored in the capture region 4 before being pulsed into the separation region 2. The tip 10 represents the ion charge in the capture region 4.

[0076] Fig. Figure 1C shows the charge quantity in the IMS device as a function of its length along the device at a subsequent time T=1, when ions released from the capture region 4 have separated along the longitudinal axis. The ions have separated into five distinct groups according to their ion mobility, with the groups represented by the five peaks spaced along the longitudinal axis downstream of the peak 10. These ions continue along the device until they exit the outlet 6. As the ions separate in the separation region 2, additional ions are accumulated in the ion capture region 4 from an ion source located upstream of the IMS device. This is represented by the peak 10 in Fig. 1C illustrates.

[0077] Fig. Figure 1D shows the charge quantity in the IMS device as a function of the length along the device at time T=2, which is later than T=1. At time T=2, the charge is induced by the two points on the far right. Fig. The ions shown in 1C exit the outlet opening 6. The remaining three ion groups, represented by the remaining three peaks located downstream of peak 10, have further separated along the longitudinal axis of the separation region 2. The leftmost peak 10 is, in relation to Fig. 1C increases in amplitude, indicating that ion capture area 4 has been filled with more ions.

[0078] Fig. Figures 1B to 1D illustrate the principle that the charge density at any point along the longitudinal axis of the separation region 2 is reduced by separating the ions along this axis. This charge reduction is used to compensate for the increase in charge density caused by the compression of the ions in the first direction. This technique makes it possible to use ion capture regions 4 with a width significantly larger than the width of the outlet aperture 6, without subjecting the ions to excessive space charge effects during their concentration towards the outlet aperture 6. Thus, a larger number of ions can be pulsed into the separation region 2 simultaneously. Because this technique allows the ions to be compressed without excessive space charge effects, the outlet aperture 6 can remain relatively small.This can be useful, for example, if the outlet opening 6 forms a differential pump opening between two areas with different pressures. Since the opening 6 can remain small, the velocity at which gas flows between the two areas separated by the opening is relatively low, and thus pumps with relatively low power can be used to remove the gas from these areas.

[0079] Fig. Figure 2 shows a schematic representation of an end view of an embodiment of the present invention, which operates in the same manner as above with reference to Fig. 1 described. In this embodiment, the ion capture region 4 pulses a substantially circular ion beam along the longitudinal axis of the separation region 2 towards the outlet opening 6, wherein the outlet opening 6 has a smaller diameter than the ion beam at the time the ion beam is pulsed out of the ion capture region 4. The outlet opening 6 is provided in a wall of the device and has a plurality of ring electrodes arranged concentrically around the outlet opening 6. Electrical potentials are applied to the ring electrodes to provide a force on the ions that compresses the ion beam radially in a direction towards the central axis of the opening 6.

[0080] Direct current voltages can be applied to the ring electrodes, for example, to create a direct current voltage gradient that drives ions radially inward toward the center of the outlet opening 6. Alternatively, a direct current voltage can be applied successively to the ring electrodes in one direction, from the outermost to the innermost ring electrode. This creates a potential barrier that moves radially inward toward the rear of the outlet opening 6, driving the ions radially inward. The moving potential can be applied in such a way that it repeatedly moves from the outermost to the innermost electrode.If the radial driving force is provided by a static DC gradient or by a moving potential, an RF potential can be applied to the wall or RF potentials can be applied to the ring electrodes to drive ions approaching the wall in a direction away from the wall along the longitudinal axis. This prevents ions from acting on the wall or the ring electrodes, instead allowing them to be transferred through the outlet opening 6.

[0081] The embodiment from Fig. 2 works in the same way as the one with reference to Fig. As described in section 1, ions are pulsed out of the ion capture area 4 and separate along the longitudinal axis according to their ion mobility. The voltages applied to the ring electrodes cause the compression of the ion beam in the first direction (i.e., in the radial direction).

[0082] In all embodiments of the present invention, the ions can be forced along the longitudinal axis of the separation region 2 towards the outlet opening 6. One or more static electric fields and / or time-varying electric fields can be used to separate the ions along the longitudinal axis. This can be achieved, for example, by applying a DC voltage gradient along the longitudinal axis of the separation region 2. Alternatively or additionally, a DC potential barrier can be guided along the longitudinal axis of the separation region 2 to direct ions along it and towards the outlet opening 6. This can be achieved by successively applying one or more voltages to successive electrodes arranged along the longitudinal axis of the separation region 2.

[0083] Linear and / or nonlinear electric fields can be used to separate ions along the longitudinal axis.

[0084] Although the present invention has been described with reference to embodiments, those skilled in the art will recognize that various changes in form and details are possible without departing from the scope of the invention as set out in the attached claims.

[0085] Although, for example, the ions have been described as being separated along the longitudinal axis according to their ion mobility, they can instead be separated according to a different physicochemical property, such as mass-charge ratio.

[0086] It should be noted that the outlet opening 6 can be circular, but it can also have a different, non-circular shape. For example, the opening 6 can be significantly larger in one dimension than in another; it can be, for instance, slit-shaped, oval, or rectangular. The larger dimension can be in the direction of ion compression or in another direction.

[0087] The ion separation area 2 can have a curved or circular cross-section through the longitudinal axis, as in the embodiment shown in Fig. 2. Alternatively, the cross-section can be non-circular. For example, the separation area 2 can have a larger dimension in one direction orthogonal to the longitudinal axis compared to another direction. One direction can also be orthogonal to the other direction. The cross-sectional shape can be, for example, oval or rectangular.

[0088] Both the outlet opening 6 and the cross-sectional shape of the separating region 2 can be larger in one dimension than in another, as described above. In such embodiments, the larger dimension of the separating region can correspond to the larger dimension of the outlet opening (i.e., be parallel).

[0089] Ions can be compressed in the first direction by applying RF and / or DC current voltages to the electrodes of the device.

Claims

[1] Methods of mass spectrometry or ion mobility spectrometry, comprising: Accumulation of ions in an ion capture volume (4); Release of ions from the ion capture volume (4) into an ion separation region (2) having a longitudinal axis, wherein the ions leave the ion capture volume (4) distributed over an initial width in a first direction orthogonal to the longitudinal axis; Transfer of the ions along the longitudinal axis of the ion separation region (2) such that the ions separate along the longitudinal axis according to a physicochemical property; Compression of the width in the first direction over which the ions are distributed as the ions separate along the longitudinal axis, so that the ions are distributed over a width in the first direction that is smaller than the original width; and Transmission of the compressed ion beam through an outlet opening (6), wherein the original width of the ion beam in the first direction is greater than the width of the outlet opening (6) in the first direction, and wherein the ion beam is compressed in the first direction such that when the ions reach the outlet opening (6), the ion beam has a width in the first direction that is less than or equal to the width of the outlet opening (6) in the first direction; wherein the ions leave the ion capture volume (4) directly into a region where the ions are compressed in the first direction, so that the ions begin to be compressed in the first direction immediately after exiting the ion capture volume (4). [2] Method according to claim 1, wherein the separated ions leave the ion separation area (2) at different exit times, and wherein the exit times are not used in determining the values ​​of a physicochemical property of the ions. [3] Methods of mass spectrometry or ion mobility spectrometry, comprising: Accumulation of ions in an ion capture volume (4); Release of ions from the ion capture volume (4) into an ion separation region (2) having a longitudinal axis, wherein the ions leave the ion capture volume (4) distributed over an initial width in a first direction orthogonal to the longitudinal axis; Transfer of the ions along the longitudinal axis of the ion separation region (2) such that the ions separate along the longitudinal axis according to a physicochemical property; and Compression of the width in the first direction over which the ions are distributed, while the ions separate along the longitudinal axis, so that the ions are distributed over a width in the first direction that is smaller than the original width; wherein the separated ions leave the ion separation region (2) at different exit times, and wherein the exit times are not used in determining the values ​​of a physicochemical property of the ions; and wherein the ions leave the ion capture volume (4) directly into a region where the ions are compressed in the first direction, so that the ions begin to be compressed in the first direction immediately after exiting the ion capture volume (4). [4] Method according to claim 2 or 3, wherein the exit times are not used to determine the ion mobility of the separated ions. [5] Method according to one of the preceding claims, wherein the ions are separated along the longitudinal axis according to an ion mobility or a mass-charge ratio. [6] Method according to any of the preceding claims, comprising the pushing of ions along the longitudinal axis of the ion separation region (2) away from the ion capture volume (4). [7] Method according to any of the preceding claims, wherein ions are compressed in the first direction by RF and / or DC potential barriers. [8] Method according to any of the preceding claims, insofar as dependent on claim 3, further comprising the transmission of the compressed ion beam through an outlet opening (6), wherein the original width of the ion beam in the first direction is greater than the width of the outlet opening (6) in the first direction, and wherein the ion beam is compressed in the first direction such that when the ions reach the outlet opening (6), the ion beam has a width in the first direction which is less than or equal to the width of the outlet opening (6) in the first direction. [9] Method according to claim 1, 2 or 8, wherein the outlet opening (6) is a differential pump opening formed in a wall separating two areas which are held at different pressures. [10] Method according to claim 1, 2, 8 or 9, wherein the outlet opening (6) is provided in a wall and a plurality of electrodes are arranged on the wall radially outside of the outlet opening (6) in at least the first direction, wherein the method comprises applying direct current and / or alternating current voltages to the electrodes to compress the ions in the first direction. [11] Method according to claim 10, comprising the application of RF potentials to the electrodes to repel ions and prevent them from coming into contact with the wall. [12] Method according to claim 10 or 11, wherein the electrodes comprise a plurality of closed-loop electrodes arranged concentrically around and radially outside the outlet opening (6). [13] A method according to claim 10, 11 or 12, comprising applying different direct current voltages to different electrodes to form a direct current voltage gradient that compresses the ion beam in the first direction; and / or which includes the successive application of one or more direct current voltages to successive electrodes in a direction from the radially outermost electrode to the radially innermost electrode, such that a direct current potential barrier extends radially inwards towards the outlet opening (6) and radially compresses the ion beam. [14] A method according to any of the preceding claims, wherein the ions leave the ion capture volume (4) which is distributed over an original width in a second direction which is orthogonal to the longitudinal axis and to the first direction; and wherein the method comprises compressing the width in the second direction over which the ions are distributed while the ions separate along the longitudinal axis, such that the ions are distributed over a width in the second direction which is smaller than the original width in the second direction. [15] Method according to any of the preceding claims, wherein the ion capture volume (4) and / or the ion separation region (2) confines ions in a volume which does not have a circular, toroidal or cylindrical cross-section. [16] Mass spectrometer or ion mobility spectrometer, comprising: an ion source; a ion capture volume (4); an ion separation region (2) having a longitudinal axis; wherein the ion capture volume (4) is configured such that the ions exiting the ion capture volume (4) are distributed over an initial width in a first direction orthogonal to the longitudinal axis; and a controller configured to control the spectrometer to: to transfer ions along the longitudinal axis of the ion separation region (2) such that the ions separate along the longitudinal axis according to a physicochemical property; and to compress the width in the first direction over which the ions are distributed, while the ions separate along the longitudinal axis, so that the ions are distributed over a width in the first direction that is smaller than the original width; and to transmit the compressed ion beam through an outlet opening (6), wherein the original width of the ion beam in the first direction is greater than the width of the outlet opening (6) in the first direction, and wherein the ion beam is compressed in the first direction such that when the ions reach the outlet opening (6), the ion beam has a width in the first direction that is less than or equal to the width of the outlet opening (6) in the first direction; wherein the ions leave the ion capture volume (4) directly into a region where the ions are compressed in the first direction, so that the ions begin to be compressed in the first direction immediately after exiting the ion capture volume (4). [17] Mass spectrometer or ion mobility spectrometer, comprising: an ion source; a ion capture volume (4); an ion separation region (2) having a longitudinal axis; wherein the ion capture volume (4) is configured such that the ions exiting the ion capture volume (4) are distributed over an initial width in a first direction orthogonal to the longitudinal axis; and a controller configured to control the spectrometer to: to transfer ions along the longitudinal axis of the ion separation region (2) such that the ions separate along the longitudinal axis according to a physicochemical property; and to compress the width in the first direction over which the ions are distributed, while the ions separate along the longitudinal axis, so that the ions are distributed over a width in the first direction that is smaller than the original width; wherein the separated ions leave the ion separation region (2) at different exit times and wherein the spectrometer does not determine the values ​​of a physicochemical property of the ions from the exit times; and wherein the ions leave the ion capture volume (4) directly into a region where the ions are compressed in the first direction, so that the ions begin to be compressed in the first direction immediately after exiting the ion capture volume (4).

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