GB2443853A

GB2443853A - A mounting arrangement for positioning an ion source

Info

Publication number: GB2443853A
Application number: GB0622744A
Authority: GB
Inventors: Alan Finlay
Original assignee: Microsaic Systems PLC
Current assignee: Microsaic Systems PLC
Priority date: 2006-11-15
Filing date: 2006-11-15
Publication date: 2008-05-21
Anticipated expiration: 2026-11-15
Also published as: GB2443853B; GB0622744D0

Abstract

Ion source mounting arrangement for positioning an ion source relative to a mass spectrometer, the arrangement including a base portion (2) coupled to an arm (3), the base portion being usable to locate the arm relative to the mass spectrometer (1), the arrangement further including a mount (4) configured to receive the ion source, the mount and the arm cooperating to provide for movement of the ion source relative to the mass spectrometer, such movement being useable to ensure that an ion beam generated within the ion source may be introduced into the mass spectrometer. The arrangement may further include a laser for alignment of the ion source.

Description

A mounting arrangement for an ion source.

Field of the Invention

The present invention relates to a mounting arrangement and in particular to a mounting arrangement for use in mass spectrometry. The invention more particularly relates to a mounting arrangement that is useable in a mounting of an atmospheric ion source relative to a mass spectrometer. The teaching of the invention is particularly useful in the mounting of an atmospheric ion source in a fashion such that it may be easily and cheaply mounted on or at the inlet of a mass spectrometer system.

Background

Mass spectrometry (MS) is a powerful analytical technique that is used for the qualitative and quantitative identification of organic molecules, peptides, proteins and nucleic acids. MS offers speed, accuracy and high sensitivity.

Key components of a mass spectrometer are the ion source, ion coupling optics, mass analyser and detector. The ion source transforms analyte molecules into a stream of charged particles, or ions, through a process of electron addition or subtraction. Such a stream may be known as an ion beam. The ions can be steered' or channeled using electric or magnetic fields. Ion coupling optics or lenses collimate the ion flux from the ion source into the mass analyser. The analyser separates ions by their mass to charge ratio. Several different kinds of mass analyser are known in the art, including, but not limited to; magnetic sector, quadrupole, ion trap, time of flight and cycloidal. The ions exit the analyser in order of mass to charge ratio and in so doing produce a mass spectrum which is a unique signature or fingerprint' for the analyte. Ions are directed to a detector where they impact and discharge an ion current which may be counted and amplified by signal electronics before being displayed on a computer screen as a mass spectrum. The detector is normally an electron multiplier. These components together form the analytical sub-system of the mass spectrometer system.

There are many types of ionisation sources that are useful in mass spectrometry (hereinafter referred to as MS). Types of ionisation sources include, but are not limited to, electron impact, chemical ionisation, plasma, fast ion or atom bombardment, field desorption, laser desorption, plasma desorption, inductively coupled plasma, thermospray and electrospray ionisation (ESI). Two of the most widely used ionization sources for gaseous analytes are the electron impact (hereinafter referred to as El) and chemical ionisation (hereinafter referred to as Cl). Some of these sources have been developed that produce similar ions and results under standard atmospheric pressure conditions. Atmospheric pressure ionisation (API) has, therefore, been adopted for use with mass spectrometers. One of the most widely used API sources is the ESI source. ESI sources, however, have the common problem of requiring an external mounting and alignment of the source with the inlet of the mass spectrometer system. In most cases the mounting is an assembly of machined metal and ceramic parts to provide alignment and electrical insulation. Such mounting typically requires accurate alignment between the output of the source and the input to the mass spectrometer. In order to achieve this accurate alignment it is known to use vision inspections system equipment such as cameras and the like to provide a user with the tools to achieve the accurate positioning of the two relative to one another.

Recently, nanospray ionisation sources have been developed which have the advantage of low flow rates (nLlmin), extremely high ionisation efficiency and low sample and solvent usage. Nanospray also has the advantage that very large molecules (e.g. peptides, proteins) may be ionized through the efficient creation and detection of multiply protonated ions. However, nanospray ionisation even more so than electrospray ionization requires very precise alignment of the nanospray capillary with respect to the mass spectrometer inlet in order to create a stable Taylor cone and produce a steady stream of ions. This has led to the development of expensive assemblies of capillary submounts, micropositioners, microscopes and video cameras into which the user may insert a capillary and move it into place while observing the capillary tip on screen for Taylor cone formation. Once the Taylor cone is in place the ion signal may be observed in the mass spectrometer. As mechanical precision is critical to the final performance of the nanospray capillary once alignment is achieved through the alignment process, the parts of the mount are then fixed in place. The mounting mechanisms typically incorporate translational platforms including one or more moveable plates.

Regular maintenance is also needed to avoid burn-out of certain parts with a definite lifetime like capillaries. Also, the spray may deteriorate over time due to wear and tear of the capillary tip, erosion of capillary coatings and slight changes in the electrical field. Over time capillaries are known to clog up, requiring the user to replace the capillary with a fresh one, necessitating repetition of the alignment process. In these circumstances users need to re-align the capillary using the micropositioners and cameras, and re-adjust of other operating parameters like flow rate and applied voltage. The entire capillary replacement and re-alignment process can take some time to replace and re-align the capillary. This downtime' has a substantial impact on productivity of research chemists, and on system availability and overall cost of ownership. In the context of a chromatography run which may take several hours, this leads to the waste of valuable sample and lost productMty. These factors have made nanospray capillaries difficult to use and have limited their uptake by the market.

An alternative approach includes on-chip nanospray ionisation. Nozzles and counter-electrodes may be micromachined on a silicon chip with the advantage the capillary tip is pre-aligned' with the rest of the source. These chips can feature arrays of nozzles, so that if one clogs other nozzles can be used to continue spraying. However, to date this approach has been implemented using large, expensive systems including robots and bolt-on' mountings to get sample into the chip, and to position it with respect to the mass spectrometer inlet.

Another important disadvantage of nanospray ionisation solutions to date has been the need for custom-designed mechanical mountings in order to couple the alignment system to the front of the mass spectrometer inlet. Because each mass spectrometer manufacturer has a proprietary atmospheric pressure inlet, a different mechanical mounting with unique locating features is required. Typically, a different mounting is marketed with each product line.

This introduces cost and complexity into the operation of such mass spectrometer systems in that if a user wishes to use an alternative ion source they are obliged to obtain specific mounting equipment for that ion source.

There are therefore a number of problems associated with known mounting arrangements and there is a need to provide a mounting arrangement that will enable an easy positioning of the exit of the ion source relative to the inlet of the mass spectrometer.

Summary

These and other problems are addressed by a mounting arrangement according to the teaching of the invention. Such a mounting arrangement includes an arm coupled at one end to a base portion, the arm being useable to support an ion source and wherein movement of the mounting arrangement provides for relative positioning of the ion source to a mass spectrometer to allow for an introduction of an ion spray generated by the ion source into the mass spectrometer.

Such a mounting arrangement or system provides for a mechanism in which an ion source may be quickly and cheaply attached to any mass spectrometer using a standard, universal mounting mechanism. The ion source is desirably provided on a mount which is cooperably engageable with the arm. Such a mount is desirably configured to interface with a plurality of different types of ion sources which may be suitably releasably engaged with the mount to facilitate replacement of ion sources where required.

These and other features of the invention will be described with reference to the exemplary embodiments which follow.

Brief Description of The Drawings

Figure 1 is a side view of functional components of a mounting arrangement for an ion source in accordance with the teaching of the present invention.

Figure 2 is a side view of functional components of an alternative mounting arrangement for an ion source mounting device in accordance with the teaching of the present invention.

Figure 3 is a plan view of a further embodiment of a mounting arrangement including an alignment mechanism.

Figure 4 is a side view of an ionisation source mounted relative to a mass spectrometer, the mounting arrangement further including a laser device.

Figure 5 is a plan view of an ion source mounted on a submount.

Figure 6 is a plan view of a mounting arrangement in which more than one laser device is provided.

Detailed Description of the Drawings

The invention will now be described with reference to the exemplary embodiments of Figures 1 to 6. Such exemplary embodiments are provided to assist in an understanding of the teaching of the invention. Therefore while illustrative embodiments of a mounting arrangement will be described-such mounting arrangements are not to be construed as limiting as the invention is only to be limited insofar as is deemed necessary in the light of the appended claims.

A mounting arrangement in accordance with the teaching of the invention is useful in locating an ion source relative to a mass spectrometer. The mounting arrangement includes a mount for the ion source, and a base portion coupled to an arm, the base portion being useable to locate the arm relative to the mass spectrometer with which the mounting arrangement is to be used. The arm and the mount for the ion source are configured to provide for movement of the ion source relative to the mass spectrometer. Such movement can be used to ensure that an ion beam generated within the ion source may be introduced into the mass spectrometer through the entrance aperture to the mass spectrometer. Within the context of the present invention the term uarm should be given its normal dictionary meaning which is a thing resembling a human arm in form or function, a long narrow object. It will be appreciated that while a human arm may require an elbow, such functionality is optional in the context of the present invention.

The base portion typically includes securing means by which the mounting arrangement may be secured to a surface. Typically this is a releasable securement achieved through use of a suction cup or the like.

The arm may be an articulated arm having two or more segments coupled by a joint that facilitates movement of a first segment relative to another segment.

Alternatively the arm could be moveable relative to the base portion, the movement being achieved through a coupling mechanism that allows relative movement of the two. In a further alternative the arm and base portion are fixed relative to one another and the mount on which the ion source is mountable is moveable relative to the arm, such movement achieving relative movement of he source relative to the mass spectrometer.

The achievable movement of the ion source relative to the mass spectrometer is provided by providing the mounting arrangement with at least one degree of freedom. This could be either translational or rotational in nature. The provision of one degree of freedom could allow a user to bring an ion source which is mounted on the arm in and out of cooperation with the entrance to the mass spectrometer. Such an embodiment could for example be where the mount for the ion source is fixed relative to the arm, but the arm is pivotable relative to the base portion. Within this context it will be appreciated that as the base portion is secured to a surface that it is a cooperation of the mount and arm which provides for movement of the ion source relative to the mass spectrometer. This cooperation is to be construed as movement of at least one of the arm or mount relative to the mass spectrometer. In certain embodiments the arm and mount may not move relative to one another to achieve the overall movement relative to the mass spectrometer whereas other embodiments will require movement of one of the arm or mount relative to the other.

While such an arrangement may suit certain configurations of ion sources and mass spectrometers, typically the mounting arrangement will be provided with at least two degrees of freedom. In this way the ion source will be moveable relative to the mass spectrometer in both an X and Y direction-achievable through or in a combination of translational or rotational motion. Desirably a third degree providing for movement in the Z direction is also possible. In this way an ion source mounted to or on the arm may be controllably positioned at a desired location relative to a mass spectrometer. Desirably the available movement is controllable and in this way the mounting arrangement in accordance with the teaching of the invention may be considered as a holonomic system in which the available degrees of freedom are controllable degrees of freedom.

As mentioned above a mounting arrangement in accordance with the teaching of the invention includes a base portion, an arm and a mount for an ion source. The base portion may be provided with securing means such as a universal clamping mechanism and the arm provides a flexible support for a mount that will permit users to couple ion sources such as nanospray capillaries to any mass spectrometers with an atmospheric inlet. Using the teaching of the invention, a capillary, mounted on the end of an articulated arm such as a goose neck' or other similar semi-rigid, articulated flexure, may be positioned relative to the inlet of the mass spectrometer. One end of the mounting arrangement, the base portion which is coupled to the arm, is fixably secured or clamped, for example by means of a Suction cup or other fixture to the mass spectrometer enclosure or other suitable, typically smooth surface and the end of the arm remote from that surface is moveable to correctly orientate the ion source that is mounted thereon relative to the inlet of the mass spectrometer.

Using the invention, a nanospray capillary or other ion source, may be quickly and cheaply attached to any mass spectrometer with an API interface using a standard, universal mounting mechanism. The mounting mechanism may be manufactured at high volumes and at relatively low cost. This opens up the possibility of a universal mounting system which is cheap enough to be sold with every mass spectrometer system.

In a first embodiment shown in Figure 1, there is provided a mounting arrangement or system 100 comprising a articulated arm coupled at a first end to a base portion in the form of a removable clamp 2 configured to mate and firmly connect to a mass spectrometer 1 enclosure surface(s) or other suitable surface(s). The arm in this arrangement is provided in the form of a flexure 3 which terminates at a second end in a mounting feature or mount 4 configured to support an ion source such as an electrospray ionisation source 5, which can be a electrospray capillary or nanospray ionisation chip. The flexure 3 includes a plurality of jointed segments which are moveable in at least two planes-the X and Y direction-to provide for an alignment of the ion source with the mass spectrometer vacuum interface, inlet orifice or inlet capillary for API 6. The joint mechanism useable in coupling adjacent segments may provide for a rotation of a first segment relative to a second.

Using such an arrangement it is possible to secure the arm at a first location and then move the ion source at the end of the arm to a supported position where its outlet is aligned with the inlet to the mass spectrometer. In this way an ion beam generated by the ion source may be introduced into the mass spectrometer for subsequent analysis.

The clamp 2 is representative of a suitable securing or fixing means that is useful in securing the arm to a fixed location. Examples of such means include a suction cup or an assembly of several rubber feet which can be clamped onto either side of the mass spectrometer enclosure and tightened in place by a lead screw or some other tightening mechanism. The suction cup is a normally circular rubber membrane which mates with the surface and forms a vacuum tight seal once the membrane is pulled back from the surface by a wing nut, clasp, lead screw or some pulling mechanism. In effect any fixing means that may allow for a secure coupling of the arm would be suitable. The arm has a portion which is proximal to the fixing means and a portion which is distal to the fixing means, the distal portion being desirably the region where the ion source is located. By securing the arm at one end and having the other end moveable, it is possible to orientate that end relative to the mass spectrometer so as to achieve correct positioning of the ion source relative to the input to the mass spectrometer.

The arm includes, in this arrangement, a semi-rigid flexure 3 providing an articulated support than can be adjusted into any position and orientation but retains its rigidity once adjusted. Examples of this type of arrangement include the goose neck' and angle poise' assemblies of the type typically used in desk lamps. In this way the position of nanospray capillary 5 can be adjusted in front of vacuum inlet 6 until optimum ion transmission and solvent desolvation is achieved. In Figure 2 the semi-rigid flexure is an articulated support similar to an angle poise' lamp which a series or rigid rods or joints 7 connected by a plurality of pivots 8. The source 5 may be moved into the desired location with respect to the inlet 6 by adjusting the rods 7, which are free to move in the pivots 8. Once in the desired location the pivots 8 can be held in place by tightening nuts, wing nuts or fasteners. Alternatively the rigidity of the arm could be integral such that it requires an action to create the movement but in the absence of that action that the position is retained. The arm could be fixed in length or alternatively could include at least one telescopic or otherwise extendible portion such that the distance of the distal end to the proximal end of the arm may be varied.

The mounting feature 4 is typically a simple platform to which an electrospray lonisation source 5 may be mechanically attached by means of some connectors or fastenings 9. The electrospray ionisation source 5 can be a fluidic capillary, a nanospray capillary, a nanospray capillary mounted inside a grooved piece of ceramic, plastic or polymer, or a nanospray ionisation source integrated and micromachined on a chip 10 formed from a suitable semiconductor material-i.e. any source of an ion beam. The electrospray ionisatiori source may be connected to a printed circuit board 7 which may be in turn attached to the mounting feature 4. The connectors 9 or fastenings may be provided on the printed circuit board. Typical components that are commonly used for formation of such an ion source will be well known to the person skilled in the art and will not be detailed here. It is desirable that the ion source provides a collimated exit ion beam, and an example of such an ion source is disclosed in our pending European application, European Patent Application No. 06117211.0 Heretofore the mounting of the ion source has been described with reference to being at one end of the arm. In another arrangement which is not shown, the mount for the ion source could be movevable along the arm, such that it may travel from one end of the arm to another. In this way the arm could be located relative to the mass spectrometer and by moving the mount along the arm, the ion source exit could be aligned with the entrance to the mass spectrometer.

To improve alignment of the outlet of the ion source-which may be a nanospray capillary tip, with the inlet of the mass spectrometer system, a simple laser device 12 may be added to the mounting feature 4. Such an arrangement could be used independently of the type of mounting arrangement heretofore described, i.e. could be coupled to existing mounting arrangements for coupling ion sources to mass spectrometers. Such an arrangement is shown in Figure 4. The laser device 12 could be similar to the Class A' laser pointing devices commonly used for public speaking purposes by presenters, or an inexpensive laser diode and provides a visible beam which is easily observable by a user. These devices can be easily mounted on a PCB using standard surface mount technology and controlled electronically from a PC. In Figure 4, the laser device 12 can be used to determine the orientation, and distance, of the capillary tip 5 from the mass spectrometer vacuum interface 6 and may be used to direct the electrospray 5A, and by implication the beam of ions so generated, efficiently into the mass spectrometer inlet.

The addition of a diffraction grating, aperture or collimation slits 13 in front of the laser, as shown in Figure 5, can provide cross hairs' for ease of aiming of the electrospray.

Furthermore, in Figure 6 we show the use of more than one laser device, pointed in known angles, to cause the laser beams 12A to intersect at a predetermined distance from the nanospray capillary tip. In Figure 6, these intersecting laser beams 1 2A provide the user with a useful, known reference distance when setting up the electrospray ionisation system with respect to the mass spectrometer inlet. Knowing this distance may be important in certain ionisation conditions, for example when ionising large molecules which require more desolvation like proteins. The angle of orientation of the laser beam is either by a predetermined manufacturers' setting or is user variable based on aligning the laser device with alignment features 14 It will be appreciated that what has been described herein are exemplary embodiments of a mounting arrangement which is useful in achieving correct orientation of an ion source relative to a mass spectrometer. By providing a mount for the ion source which cooperates with an arm which is coupled at one end to a fixable base portion and enabling movement of at least one of the arm and/or the base portion it is possible to achieve relative movement of the ion source to the mass spectrometer. Typically the arm is a flexible arm which is fixed at one end, the distance and orientation of the source relative to the inlet of the mass spectrometer may be varied to achieve correct and efficient introduction of a generated ion beam into the mass spectrometer for subsequent analysis. While the invention has been described with reference to preferred embodiments it will be understood that these are provided to assist in an understanding of the teaching of the invention and it is not intended to limit the invention in any way except as may be deemed necessary in the light of the appended claims. Furthermore features described with reference to one figure may be interchanged or replaced with those of another figure without departing from the scope of the invention. Such modifications will be readily apparent to the person skilled in the art and it is not intended to limit the invention to the embodiment presented in any one Figure.

The words comprises/comprising when used in this specification are to specify the presence of stated features, integers, steps or components but does not preclude the presence or addition of one or more other features, integers steps, components or groups thereof.

Claims

Claims.

1. An ion source mounting arrangement for positioning an ion source relative to a mass spectrometer, the arrangement including a base portion coupled to an arm, the base portion being useable to locate the arm relative to the mass spectrometer with which the mounting arrangement is to be used, the mounting arrangement further including a mount configured to receive the ion source, the mount and arm cooperating to provide for movement of the ion source relative to the mass spectrometer, such movement being useable to ensure that an ion beam generated within the ion source may be introduced into the mass spectrometer.

2. The mounting arrangement as claimed in claim 1 wherein the arm and base portion are moveable relative to one another.

3. The mounting arrangement as claimed in claim 1 or 2 wherein the arm and base portion represent two segments of an articulated structure.

4. The mounting arrangement as claimed in any preceding claim wherein the arm is an articulated arm having at least two segments which are moveable relative to one another.

5. The mounting arrangement as claimed in any preceding claim wherein the mount for the ion source is moveable relative to the arm.

6. The mounting arrangement as claimed in claim 5 wherein the mount for the ion source is movable along the arm.

7. The mounting arrangement as claimed in any preceding claim being configured to allow for movement of the ion source relative to the mass spectrometer in at least two directions..

8. The mounting arrangement as claimed in any preceding claim wherein the base portion includes securing means to provide for a securing of the arm relative to the mass spectrometer.

9. The mounting arrangement as claimed in claim 8 wherein the securing is to a surface of the external casing of the mass spectrometer.

10. The mounting arrangement as claimed in claim 8 wherein the securing is to a work surface on which the mass spectrometer is situated.

11.The mounting arrangement as claimed in claim 8 wherein the securing means provides for a releasable securing of the arm.

12. The mounting arrangement as claimed in claim 8 wherein the securing means includes at least one suction cup.

13. The mounting arrangement as claimed in any preceding claim wherein the arm is moveable in the X and Y planes.

14. The mounting arrangement as claimed in any preceding claim wherein the arm is moveable in the X and V and Z planes.

15. The mounting arrangement as claimed in any preceding claim wherein the mount for the ion source provides for a removable securing of the ion source to the mounting arrangement.

16. The mounting arrangement as claimed in any preceding claim wherein the mounting arrangement is configured to support a mounting of a plurality of different types of ion sources.

17. The mounting arrangement as claimed in any preceding claims further including means for aligning the ion source relative to the mass spectrometer.

18. The mounting arrangement as claimed in claim 17 wherein the means for alignment including at least one laser.

19. The mounting arrangement as claimed in claim 18 wherein the at least one laser provides for a determination of at least one of orientation to and distance from the mass spectrometer of the ion source.

20. The mounting arrangement as claimed in claim 17 or 18 wherein the at least one laser enables a user to align the ion source relative to the mass spectrometer to introduce the ion beam into the spectrometer.

21.The mounting arrangement as claimed in any one of claims 18 to 20 further including alignment means, the alignment means being useable with the at least one laser to assist in an alignment of the ion source with the mass spectrometer.

22.The mounting arrangement as claimed in any one of claims 18 to 21 including two lasers, each of the lasers being orientated relative to the other such that their outputs beams intersect, the point of intersection being selectable to indicate a reference distance of the ion source from the mass spectrometer.

23. The mounting arrangement of claim 22 wherein the reference distance generated by the intersection of the two laser beams is changeable depending on the type of ion beam being generated.

24. The mounting arrangement as claimed in any preceding claim wherein the arm is telescopic.

25. The mounting arrangement as claimed in any preceding claim wherein the arm includes a plurality of segments, neighbouring segments being moveable relative to one another.

26.The mounting arrangement as claimed in claim 25 where the arm includes a plurality of joints, the joints interconnecting neighbouring segments and enabling a movement of a first segment relative to a second segment.

27.The mounting arrangement as claimed in claim 26 wherein the joints enable a rotation of a first segment relative to a second segment.

28. The mounting arrangement as claimed in any preceding claim wherein the ion source is an electrospray ion source.

29.The mounting arrangement as claimed in any one of claims 1 to 27 wherein the ion source includes a nanospray capillary.

30.A mounting arrangement for positioning an ion source relative to a mass spectrometer, the mounting arrangement including at least one laser, the laser including means for aligning the ion source relative to the mass spectrometer.

31. The mounting arrangement as claimed in claim 30 wherein the at least one laser provides for a determination of at least one of orientation to and distance from the mass spectrometer of the ion source.

32. The mounting arrangement as claimed in claim 30 or 31 wherein the at least one laser enables a user to align the ion source relative to the mass spectrometer to assist in an introduction of an ion beam generated by the ion source into the spectrometer.

33.The mounting arrangement as claimed in any one of claims 30 to 32 further including alignment means, the alignment means being useable with the at least one laser to assist in an alignment of the ion source with the mass spectrometer.

34.The mounting arrangement as claimed in any one of claims 30 to 33 including two lasers, each of the lasers being orientated relative to the other such that their outputs beams intersect, the point of intersection being selectable to indicate a reference distance of the ion source from the mass spectrometer.

35. A mounting arrangement substantially as hereinbefore described with reference to any one of Figures 1 to 6 of the accompanying drawings.