Patent Grant
8779353
This application is in the field of mass spectrometry and, more specifically, relates to ion guides to be used advantageously at interfaces between a high-pressure region and a low-pressure region. Mass spectrometers can be used to determine the molecular weight of gaseous compounds. The analysis of samples by mass spectrometry consists of three main steps, formation of gas phase ions from sample material, mass analysis of the ions to separate the ions from one another according to ion mass to charge ratio m/z, and detection of the ions. A variety of well-known means and methods exist in the field of mass spectrometry to perform each of these three functions. The particular combination of the means and methods used in a given mass spectrometer determine the characteristics of that instrument.
Before mass analysis can begin, gas phase ions must be formed from a sample material. If the sample material is sufficiently volatile, ions may be formed by electron ionization (EI) or chemical ionization (CI) of the gas phase sample molecules, for instance.
Atmospheric Pressure Ionization (API) includes a number of ion production means and methods. Typically, analyte ions are produced from liquid solution at atmospheric pressure. In one of the more widely used methods known as electrospray ionization (ESI), analyte is dissolved in a liquid solution and sprayed from a needle. The spray is induced by the application of a potential difference between the needle and a counter electrode. The spray results in the formation of fine, charged droplets of solution containing analyte molecules. In the gas phase, the solvent evaporates leaving behind charged gaseous analyte ions.
In addition to ESI, other ion production methods may be used at atmospheric or elevated pressure. For example, matrix-assisted laser desorption/ionization (MALDI) has been adapted to work at atmospheric pressure. The benefit of adapting ion sources in this manner generally is that the ion optics (that is, the electrode structure and operation) in the mass analyzer and mass spectral results obtained are largely independent of the ion production method used.
In hybrid analytical instruments, such as liquid chromatography/mass spectrometry (LC/MS) instruments, where two analytical techniques are coupled and the liquid output of one serves as the analytical input of the other, it is preferred to generate ions in an ion source which is maintained at (or near) atmospheric pressure.
Elevated pressure (that is, elevated relative to the pressure of the mass analyzer) and atmospheric pressure ion sources always have an ion production region wherein ions are produced, and an ion transfer region wherein ions are transferred through differential pumping stages into the mass analyzer. Generally, mass analyzers operate in a vacuum between 10−2 and 10−8 Pascal depending on the type of mass analyzer used. When using, for example, an ESI or elevated pressure MALDI source, ions are formed and initially reside in a high pressure region of “carrier” gas. In order for the gas phase ions to enter the mass analyzer, the ions must be separated from the carrier gas and transported through the single or multiple vacuum stages.
The use of multipole ion guides has been shown to be an effective means of transporting ions through a vacuum system, see for example U.S. Pat. No. 4,963,736 to Douglas et al. Under the generic name of “ion guide” different electrical devices are used, such as quadrupole, hexapole or octopole rod systems, but also stacked ring electrodes (see, for instance, U.S. Pat. No. 6,891,153 B2 to Bateman et al.). The function of the ion guides is to confine and transfer the ion beam throughout the intermediate vacuum stages via a radio frequency (RF) field generated by the guide itself. The normal operating pressure of such ion guides ranges from about 100 to 10,000 Pascal. A novel way of micro-engineering stacked ring ion guides has been presented recently by Syms et al. (U.S. Pat. No. 7,960,693 B2).
One of the principal differences between multipole rod ion guides and stacked ring electrode ion guides is the manner of electrical wiring, or in other words the electrical contacting. Rod ion guides conventionally comprise an even number of elongated pole rods arranged around a longitudinal axis under rotational symmetry. The wiring is (or in other words, the electrical contacts are arranged) normally such that two opposing rods receive the same phase of a radio frequency potential whereas other pairs of opposing rods receive different phases of the same RF potential. In other words, the pole rods receive different phases of an RF potential in a “cross-wise” manner.
On the other hand, stacked ring ion guides are wired such that, along the row of rings, adjacent rings receive alternating phases (normally, 180 degrees out of phase) of an RF potential. In other words, the stacked ring electrodes receive different phases of an RF potential in an “axially alternating” manner. As a result, stacked ring ion guides generally have a narrow range of effective geometries. That is, the thickness of the rings and the gap between the rings must be relatively small compared to the size of the inner aperture of the ring. Otherwise, ions may get trapped in pseudopotential “wells” in the ion guide and therefore not be efficiently transmitted.
Another means for guiding ions at “near atmospheric” pressures (that is, pressures between about 10 and 105 Pascal) is disclosed by Smith et al. (U.S. Pat. No. 6,107,628 A). One embodiment consists of a row of rings the inner apertures of which gradually decrease along the row. Thus the aggregate of the apertures form a “funnel” shape, otherwise known as an ion funnel. The ion funnel has an entry corresponding with the largest aperture, and an exit corresponding with the smallest aperture. The row of rings is wired in the axially alternating manner as mentioned before. Further, a direct current (DC) electrical gradient is created using a power supply and a resistor chain to supply the desired and sufficient voltage to each ring to create a driving force for ions to be transported through the funnel. Additional driving forces may be necessary with ion funnels since the pseudopotentials created therein, due to the tapering aperture of the rings, could otherwise be ion repulsive along the axis.
Generally, the ion funnel has the advantage, when properly operated, that it can efficiently transmit ions through a relatively high pressure region (that is, larger than about 10 Pascal) of a vacuum system, whereas multipole ion guides perform poorly at such pressures. However, the ion funnel generally performs poorly at lower pressures where multipole ion guides transmit ions efficiently.
The other side of the inlet capillary 10 is opposite a stacked ring ion funnel 16 as known, for example, from the aforementioned disclosure by Smith et al. The ion funnel 16 is connected to an RF+DC voltage generation network 12, 14 which supplies RF voltages to the individual rings with axially alternating phase so that pseudopotentials necessary for radial confinement can be created. The separate electrodes of the stacked ring ion funnel 16 can also be supplied with a DC potential gradient along the axis in order to provide additional driving force acting on the ions to drive them through the funnel 16. With the largest aperture ring electrode facing the outlet of the inlet capillary 10 and the smallest aperture ring electrode facing an insulated orifice plate 50 at the interface to the next differential pumping chamber 32, which allows the generation of a potential drop along the ion pathway, the stacked ring ion funnel 16 has a large acceptance profile for ions passing the inlet capillary 10 and, along its axis by means of its tapering aperture, promotes radial focusing so that, upon exiting the funnel 16, the outer dimension of the ion stream is small enough to pass the insulated orifice plate 50 without much ion loss.
The vacuum chambers 32, 34 downstream of the vacuum chamber 30 with the ion funnel 16 may then each have a quadrupole rod ion guide 42, 44 as known from the aforementioned disclosure of Douglas et al., for instance, as well as further insulated orifice plates 52 and 54 at the downstream interfaces, respectively. Due to the radial focusing of the ions in the ion funnel 16 the rod ion guides 42, 44 are well suited to transfer the ions further without significant ion loss. The last vacuum chamber 36 in this example then has a quadrupole rod mass filter 46 as is well known in the art. By applying appropriate RF and DC voltages to the pole rods of the mass filter 46 a window of mass to charge ratios m/z can be set, or a range of corresponding windows can be scanned through, to allow ions having the respective mass to charge ratio m/z to pass the mass filter 46 and reach the ion detector 48 where they can be measured as a function of the voltage conditions applied.
Recently, Kim et al. (U.S. Pat. No. 7,851,752 B2 which is incorporated by reference in its entirety in the present disclosure) proposed a new ion guide design which encompasses the features of a cross-wise wiring and an axially alternating wiring at the same time. The design includes segmenting each ring (or electrode) in a conventional stacked ring ion guide design into a number of electrically conductive regions separated from each other by insulating regions, and supplying the electrically conductive regions of each electrode, as known from multipole rod ion guides, in a cross-wise manner while also, as known from stacked ring ion guides, providing axially alternating phase differences between electrically conductive regions of adjacent electrodes in the row, which are aligned with each other. Thereby, in particular, the presence of undesired trapping pseudopotential wells between adjacent electrodes in the stack is supposed to be overcome. However, the assembly of Kim's ion guide turns out to be rather cumbersome as it is suggested to provide ring-shaped electrically insulating supports to which metal foils are bonded in the areas designated for the electrically conductive regions. All these electrically conductive regions then have to be wired according to the desired electrical circuitry. This procedure is rather time consuming as every single electrode in the stack has to be machined individually.
In view of the above a need exists to provide an ion guide that includes the favorable combined wiring in an axially alternating as well as a cross-wise manner while, in particular, being easier to fabricate and assemble.
In accordance with the principles of the invention, a radio frequency ion guide comprises a plurality of electrodes, each of which has at least one row of elements protruding from a holder, each of the protruding elements, at a distal end, having an electrically conductive aperture contour forming portion. Upon assembly of the electrodes, the rows of protruding elements cooperate to form a row of substantially plane segmented aperture members, each of the segmented aperture members having a plurality of insulating gaps located between cooperating protruding elements, and a central aperture defined by cooperating aperture contour forming portions. The disclosed radio frequency ion guide design greatly simplifies the manufacturing process, reducing cost, and improving robustness and reliability of the ion guide itself.
In various embodiments, a dimension of the aperture contour forming portion generally changes along the at least one row of protruding elements in each of the plurality of electrodes, such that, when the rows of protruding elements of different electrodes cooperate, a dimension of the central aperture generally decreases along the row of segmented aperture members to form an ion funnel.
In various embodiments, the electrodes at one of their respective ends comprise attachment plates, via which they are coupled to a support plate.
In further embodiments, the holder comprises a plurality of pumping apertures in each of the plurality of electrodes. The holder may take the form of a back plate.
In some embodiments, each row of protruding elements comprises a first protruding element, a last protruding element, and a group of intermediate protruding elements, wherein in each of the plurality of electrodes the holder and at least the group of intermediate protruding elements are machined integrally from a single piece of conductive material. Apart from simplifying the electrical wiring, an integral design also allows for the parts of the electrode to be simultaneously heated. Heating may prevent durable deposition of substances which could promote undesirable electrostatic charging or deleterious outgassing. Furthermore, modern machining techniques allow for the features of the electrodes to be machined in one clamping of the workpiece, so that geometrical tolerances among the different features of an electrode can be kept at a minimum.
In some embodiments, the first protruding element and the last protruding element are attached to the holder in an insulating manner and separately supplied with RF and DC potentials.
Preferably, the plurality of protruding elements are arranged in two parallel rows on the holder in each of the plurality of electrodes, wherein one row is shifted spatially in an axial direction, such that the protruding elements in one row are located, in particular centrally, across a space between two protruding elements in the other row.
In various embodiments, the protruding elements of each segmented aperture member cooperate to form opposing pairs, the opposing pairs being configured to receive different phases of a radio frequency potential.
In further embodiments, the protruding elements of the segmented aperture members are substantially aligned along a common axis along the row, each protruding element in one segmented aperture member receiving a different phase of radio frequency potential than the protruding elements in adjacent segmented aperture members aligned therewith.
Favorably, all electrodes are identical and assembled around a common longitudinal axis under rotational symmetry.
In a second aspect, the invention relates to an apparatus for performing mass spectrometry, comprising an ion source, a mass analyzer, and an ion guide as herein before specified. The ion guide has an inlet end coupled to the ion source and an outlet end coupled to the mass analyzer, and is configured for guiding ions from the ion source to the mass analyzer. The ion source is maintained at a pressure higher than the mass analyzer. If the ion guide is configured as an ion funnel, the large aperture end advantageously faces the ion source and the small aperture end faces the mass analyzer.
In a third aspect, the invention relates to an electrode for an ion guide, comprising a plurality of protruding elements extending in at least two adjacent rows from a holder, each of the rows having a first protruding element, a last protruding element, and a group of intermediate protruding elements. Each of the protruding elements, at a distal end, has an electrically conductive aperture contour forming portion, and the holder and at least the group of intermediate protruding elements are machined integrally from a single piece of conductive material, such as metal.
In various embodiments, the first protruding element, the last protruding element, and the group of intermediate protruding elements in each row together with the holder are machined integrally from a single piece of conductive material.
In some embodiments, however, the first protruding element and the last protruding element are attached to the holder in an insulating manner.
In further embodiments, the protruding elements have the shape of fins, and the aperture contour forming portion is a recessed outer contour portion at a distal end of the fins.
Preferably, the holder is a back plate. The back plate may comprise a plurality of pumping apertures.
In various embodiments, the plurality of protruding elements is surface treated to provide chemical resistance.
Other aspects and features of the invention would be apparent from the detailed description, which is made with reference to the following drawings. It should be appreciated that the detailed description and the drawings (often schematically) provides various non-limiting examples of various embodiments of the invention, which is defined by the appended claims.
Embodiments of the invention provide an ion funnel that transfers ions from an ion source to a mass analyzer. An embodiment is illustrated in
As shown in the example of
In the particular example of
As illustrated in
From the illustration of
The four electrodes are preferably machined with the identical shape of features, that is, identical back plates, fins and cuts. The four identical electrodes are assembled with respect to the features of an adjacent electrode, such that together the fins of the assembled electrodes form plane segmented aperture members with an aperture for ion transfer, wherein each successive aperture member, in the axial direction of the ion guide, has a smaller aperture in this embodiment. However, it is also conceivable to configure the electrodes such that, upon assembly, an “ion tunnel” with substantially constant inner aperture is created.
For the funnel design, it goes without saying that it is not strictly mandatory for each segmented aperture member to have an individual central aperture compared to adjacent segmented aperture members. Designs are also possible, and may result in the same beneficial ion transport and confinement properties, where a certain number of adjacent aperture members, such as two adjacent aperture members, has the same central aperture size, as long as there is an overall gradient of central aperture size along the row of aperture members from the ion source end to the mass analyzer end. Such designs are also envisaged to be encompassed in the scope of the invention.
When assembled, the electrodes are electrically insulated from each other. The electrodes are coupled to power sources in pairs. In the specific example shown in
It is to be noted here that the number, design and arrangement of the optional pumping openings 215 is shown in
It should be appreciated that the embodiment of an ion guide shown in
In one example, the ion guide is placed immediately upstream of the inlet of a mass analyzer, but other architectures can be used. For example, in some embodiments there are more than one stage between the ion source and the mass analyzer as exemplified in
In the embodiments described above, no DC bias voltage is applied to the ion guide. Therefore, the entire electrode can be made integrated with the protruding elements, such as the fins, and the holder, such as the back plate, being machined from a conductive material. However in other embodiments of the present invention the electrodes could be constructed with insulating material in order to sustain a DC gradient (in volts/cm) between the entrance and exit of the ion guide.
While in
As can be understood from the above description, opposite phase RF voltages are applied to adjacent electrodes to thereby produce the confinement field. In the example of
Another embodiment of an ion guide is illustrated in
In
From the illustration of
The four electrodes 500 are preferably machined with the identical shape of features, that is, identical bars 505, sickles 510 and recesses 525. As before, the four identical electrodes 500 are assembled with respect to the features of an adjacent electrode, such that together the sickles 510 of the assembled electrodes form plane segmented aperture members (formed by the coplanar sickle “blades”) with an aperture for ion transfer, wherein each successive aperture member, in an axial direction, has a smaller aperture in this example.
In the embodiments described above, the aperture contour forming portions all have recessed (or in other words concave) characteristics. However, this not mandatory.
The inlet capillary 10 is encased by a gas flow guiding cylinder 20 that allows for a better channeling of gas flows in the first vacuum chamber 30. A channeled gas flow may entrain ions and thereby provide a driving force for driving the ions through the funnel architecture, in particular when no DC potential gradient is established between the large aperture end and the small aperture end of the funnel.
Opposite the exit of the inlet capillary 10 is the ion funnel assembled according to embodiments of the invention. The ion funnel may have a quadrupolar design and therefore contains four electrodes of which two are designated with 24 and 26 in the planar view of
One advantage of the hybrid wiring of the ion guide according to embodiments of the invention is that another multipole ion guide (in
As can be appreciated from the above description, embodiments of the invention enable a rather easy manufacturing, since the four electrodes are identical. The device can also be miniaturized and the electrical connection can be made easy, since the number of connections merely corresponds to the polarity of the ion guide, such as four for a quadrupolar ion guide, six for a hexapolar ion guide, etc., rather than individual connection to each ring electrode as is known from the prior art. The construction of the ion guide provides flexibility in the design of the radio frequency field, by simply shaping the features of the protruding elements, that is, thickness, spacing, and recess or bulge size. Also, since all of the protruding elements are attached, or made integral, to the holder, the precise spacing and positioning of the plane segmented aperture members is assured. Further, this design needs no DC field along the ion beam axis inside the ion guide. Axial ion propagation may be facilitated, for example, by a gas flow from the high pressure region at the upstream side, for example facing the ion source, to the low pressure region at the downstream side, for example facing the mass analyzer. The gaps between the segments of the plane segmented aperture members allow for electrical insulation among the different assembled electrodes.
In the embodiments described above, a quadrupolar ion guide is described, which is constructed by machining from a single block of material an electrode integrated with the feature, that is, fins in this example, that, together with complementary fins of complementary electrodes, co-define the radio frequency field and shape the central aperture of the ion guide. This construction is simple and inexpensive; however, it should be appreciated that the electrodes need not be machined integrated with the protruding elements, and that the protruding elements can be manufactured separately and then attached to a holder of the electrode. Also, while the assembly shown here comprises four electrodes, the ion guide according to embodiments of the invention can be made with more electrodes, for instance, six for a hexapole, eight for an octopole, etc. Moreover, while in the described embodiments the holder and protruding elements are machined from a single block of electrically conductive material, such as metal, they may also instead be machined from a single piece of insulating material which is then coated with a conductive material, favorably only at the aperture contour forming portions where the RF fields need to be created.
It should be understood that processes and techniques described herein are not inherently related to any particular apparatus and may be implemented by any suitable combination of components. Further, various types of general purpose devices may be used in accordance with the teachings described herein. It may also prove advantageous to construct specialized apparatus to perform the method steps described herein.
The present invention has been described in relation to particular examples, which are intended in all respects to be illustrative rather than restrictive. Those skilled in the art will appreciate that many different combinations of hardware, software, and firmware will be suitable for practicing the present invention. Moreover, other implementations of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.
| Number | Name | Date | Kind |
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| 20050189486 | Fuhrer et al. | Sep 2005 | A1 |
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| Number | Date | Country |
|---|---|---|
| 2370686 | Jul 2002 | GB |
| 2428514 | Jan 2007 | GB |
| 2451239 | Jan 2009 | GB |
| Number | Date | Country | |
|---|---|---|---|
| 20130175441 A1 | Jul 2013 | US |
